Malignancy in non-HIV infected patients with cryptococcal meningitis: a retrospective study

Malignancy in non-HIV infected patients with cryptococcal meningitis: a retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Malignancy in non-HIV infected patients with cryptococcal meningitis: a retrospective study Xiaofeng Xu, Liping Cao, Yijie Wang, Jia Liu, Qing Dong, Chunling Liang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-92814/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Cryptococcal meningitis (CM) was found to be coexist with malignancy in non-human immunodeficiency virus (HIV) infected patients. The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of CM in non-HIV infected patients with malignancy. Methods : A total of 320 CM patients were enrolled for analysis from January 2013-May 2019. One hundred and four patients underwent positron emission computed tomography (PET-CT) examination. The demographics, clinical characteristics, microbiological, radiological, therapeutic outcomes were analyzed in CM patients with and without malignancy. Results : Twelve patients with malignancy were found, of which 7 malignancy before CM (MBC), 5 malignancy after CM (MAC). CM patients with malignancy were older than non-malignancy ones. The prognosis of MBC patients was comparable to that of non-malignancy patients, but was extremely poor in MAC patients. Four out of 5 CM patients, who was suggested diagnosis as malignancy by PET-CT, were finally confirmed. Conclusions : This study found an increase rate of solid malignancies in CM patients. Screening malignancy in older CM patients was very important because it is closely related to prognosis and might affect treatment strategy. PET-CT might be a useful tool for early malignancy screening in CM. Infectious Diseases cryptococcal meningitis malignancy positron emission computed tomography Figures Figure 1 Figure 2 Background Cryptococcal meningitis (CM) is the one of the most common opportunistic infection and often occurs in the patients with human immunodeficiency virus (HIV) infection [ 1 , 2 ]. In non-HIV endemic areas, CM appears in a growing number of other forms of natural or iatrogenic immunosuppressive patients [ 3 ]. In China, about one-third of non-HIV CM patients have predisposing factors, and the prognosis of these people does not seem to be significantly different from that of the immunocompetent population [ 4 ]. Malignancy is also considered to be immune-related diseases. HIV patients and genetic model animals with immunodeficiency has shown an increase in the incidence of malignancy formation [ 5 , 6 ]. Previous retrospective studies have shown that the incidence of cryptococcal infections is higher in the patients with malignancy, especially in hematological malignancy [ 7 – 9 ]. Though the CM and malignancy may associate with immunodeficiency at the same time, the coexistence of malignancy and CM in non-HIV patients is unclear now. In addition, the types of malignancies and their effect on CM prognosis need to be further studied. To the best of our knowledge, no studies have been conducted to evaluate the clinical characteristics and therapeutic outcomes of CM in non-HIV infected patients with malignancy. The objective of this study is to analyze the epidemiological and clinical data of malignancy in non-HIV patients with CM, and assess the application of positron emission computed tomography (PET-CT) in the diagnosis of malignancy in the CM population. Methods Study populations This is a retrospective study approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. All study participants have provided written consent for research and publication. Records of all patients diagnosed with definite CM from January 2013-May 2019 were examined. Figure 1 illustrates the flowchart for the 357 recruited non-HIV infected CM patients. The enrolled CM patients were divided into three groups according to the discovery of malignancy: 1) no malignancy, 2) malignancy before CM (MBC), 3) malignancy after CM (MAC). Definite CM were identified by a positive result of India ink smear, microbiology culture in cerebrospinal fluid (CSF) and histopathological finding in meninges or brain parenchyma (5 to 10 µm encapsulated yeasts). The diagnosis of malignancy before admission depended on the medical history. Patients newly diagnosed with malignancy after admission were confirmed by typical imaging findings and tissue pathology (surgery or biopsy). Patients were excluded if they had a history of immunodeficiency, such as HIV infection, rheumatic diseases, use of immunosuppressants and corticosteroids. PET-CT examination Among these 320 CM patients, 104 of them underwent PET-CT examination. These patients were fasted for at least 4 hours with glucose levels less than 150 mg/dL before starting the scan. PET images of the whole body were obtained by using a PET-CT scanner (Discovery Elite, GE healthcare, Chicago, IL, USA) after intravenous injection of 5.2 MBq per kilogram body weight 18-fluorodeoxyglucose ( 18 F-FDG) up to maximum of 370 MBq (10 mCi). The 3D PET data and CT images were reconstructed for diagnosis. Treatment and outcomes Antifungal treatment was based on amphotericin B, usually in combination with fluconazole/voriconazole and 5-flucytosine. Combination therapy will sterilize CSF within 2 weeks of treatment in most immunocompetent patients [ 10 ], so the patient's first therapeutic evaluation was performed 2 weeks after using the standard antifungal treatment described above. With reference to previous study [ 4 ], “response” was defined as survival within 2 weeks with relief of symptoms and clinical signs, improvement in CSF chemistry and cell count, reduce of cryptococcus counts in CSF. Our standard treatment composed by three stages according to the guidelines, including induction, consolidation and maintenance stages [ 11 ]. If the patient has completed the standard treatment stages, with the clinical symptoms disappear, and negative CSF cryptococcus result, CM was considered to be cured, and patients were marked as “success”. The patients were follow-up with regular rehospitalization, outpatient visits and telephone after discharge until got “success”. The cause and time of death were recorded during follow-up. The cause of death within 6 months in these patients was analyzed. If the patient's death was due to an exacerbation of the central nerve system infection (assessed by radiography and CSF examination) and its associated complications, the cause of death was considered to be “CM-related”. If the patient's death was due to malignancy, which caused organ dysfunction or associated complications, the death was considered to be “malignancy-related”. The cause of death which cannot be attributed to the above two situations was considered as “other”. Statistical analysis All statistical analyses were performed using SPSS (version 16.0, Chicago, IL, USA). Continuous data were analyzed using Student’s t -test after confirming a normal distribution using the Shapiro-Wilk test. Mann-Whitney test was used if the data was not a normal distribution. Chi-square analysis was used to analyze categorical variables. Fisher's exact test was an alternative, if the data does not meet the chi-square requirements. Survival was defined as the time from the diagnosis of CM to the death due to any cause or last follow-up. Survival curves were generated by the Kaplan-Meier product limit method. The difference in survival distribution was evaluated by the log rank test. Results Demographic and clinical features A total of 357 patients were included in this study. Thirty-seven patients were excluded according exclusion criteria mentioned above (Fig. 1 ). Among the enrolled patients, 232 (72.5%) were male and 88 (27.5%) were female, with an average age of 45.92 years. There were no significant differences in gender between malignancy and non-malignancy CM patients. CM patients with malignancy were older than non-malignancy patients (56.25 vs. 45.52, P ˂ 0.05) (Table 1 ). Table 1 The clinical characteristics and laboratory data of the CM patients without or with malignancy. CM without malignancy Mean ± SD (%) CM with malignancy Mean ± SD (%) P Features Sex (male/female) 225/83 7/5 0.32 Age (years) 45.52 ± 14.88 56.25 ± 14.57 0.02 Symptoms Head ache 293/308 (95.13%) 12/12 (100%) 1.00 Fever 153/308 (49.68%) 5/12 (41.67%) 0.77 Time to admission ≤ 1 month 218/308 (70.78%) 4 /12 (33.33%) 0.01 > 1 month, ˂3 month 69/308 (22.40%) 6/12 (50%) 0.04 ≥ 3 month 21/308 (6.82%) 2/12 (16.67%) 0.26 0.02 Cerebrospinal fluid Total WBC (10 6 /L) 119.06 ± 241.00 171.67 ± 294.67 0.39 Protein (g/L) 1.20 ± 0.99 1.02 ± 0.78 0.64 Glucose (mmol/L) 1.41 ± 1.12 1.79 ± 1.75 0.85 Chloride (mmol/L) 115.17 ± 5.50 113.61 ± 6.54 0.40 Cryptococcus count (/L) 5962.45 (0-125000) 12592.92 (16-64800) 0.29 Lumbar puncture pressure > 330 mmH 2 O 81/308 (26.30%) 2/12 (16.67%) 0.74 > 200, ≤ 330 mmH 2 O 108/308 (35.06%) 4/12 (33.33%) 1.00 ≤ 200 mmH 2 O 119/308 (38.64%) 6/12 (50.00%) 0.55 0.80 Outcomes Response at week 2 295/302 (97.68%) 8/12 (66.67) 0.00 6-month mortality 29/293 (9.90%) 5/12 (41.67%) 0.01 Success 199/234 (85.04%) 6/11 (54.55%) 0.02 CM: cryptococcal meningitis; SD: standard deviation; WBC: white blood cell. Symptoms and time to admission Headache and fever were the two most common initial symptoms, with incidence rates of 95.31% and 49.38%, respectively. The incidence rates of headache and fever were not significantly different between non-malignancy and malignancy patients (Table 1 ). Time to admission (time from initial symptoms to hospitalization and diagnosis of CM) were significantly different between non-malignancy and malignancy patients (Table 1 ). CSF findings At the first lumbar puncture, the CSF open pressure of patients with non-malignancy seemed higher than that of patients with malignancy but did not reach statistical difference (Table 1 ). Non-malignancy CM patients had lower cryptococcus counts than malignancy CM patients, but the difference was not statistically significant (Table 1 ). There were no significant differences in CSF white blood cell (WBC) count, protein, glucose, and chloride concentration between malignancy and non-malignancy CM patients (Table 1 ). Outcomes Most patients (302/308 and 12/12) completed the initial 2 weeks of antifungal treatment. Six patients died or were discharged from treatment within 2 weeks (4 death, 2 discharge). In the non-malignancy CM patients, after the initial 2 weeks of antifungal treatment, the clinical symptoms and signs of 97.68% patients improved, accompanied with decreasing CSF cryptococcus count, which represent the “response” to the treatment. However, the response rate of malignancy CM patients was significantly lower than that of non-malignancy patients (66.67% vs. 97.68%). Seven patients lost follow-up within 6 months, and 28 patients lost follow-up after 6 months. Mortality was finally evaluated in 305 patients at follow up for 6 months. Patients with malignancy had much higher 6-month mortality than non-malignancy patients (Table 1 ). At the end of this study, among the patients without malignancy, 35 patients died, 37 patients had not completed the therapy course yet, and 199 patients antifungal treatment acquired “success”. Among the patients with malignancy, 5/12 (41.67%) died within 6 months, 6 patients antifungal treatment was “success” (one died of tumor recurrence 14 months after successful CM treatment), and one patient still took oral antifungal drugs for about 1 year and was in stable condition. Survival curves for non-malignancy CM and malignancy CM were shown in Fig. 2 . Patients with malignancy had significant lower survival rate than non-malignancy ones ( P < 0.001). Characteristics of MBC and MAC patients The clinical characteristics of MBC were shown in Table 2 . The number of MBC cases was 7, age ranged from 31 to 68 years, with a median of 48.43 years and three of them were male. Six cases were epithelial-derived malignancy. Another case was diffuse large B lymphoma. The diagnosis time from malignancy to CM ranged from 2 to 60 months, with an average of 26.86 months. Most malignancies were treated by surgery and in stable condition. The treatment on CM in these patients was successful. The case with diffuse large B lymphoma has been undergoing antifungal treatment for approximately one year and has not yet cleared cryptococcus at the end of present study. Table 2 The clinical characteristics and prognosis of MBC patients. No. Sex Age Malignancy origin Time from malignancy to CM (month) Malignancy treatment Count (/L) CM Outcomes Note 1 Male 46 Liver 2 Surgery, chemotherapy 2560 Success Malignancy recurrence 2 years later, death 2 Female 61 Vaginal 8 Surgery, radiotherapy, chemotherapy 64800 Success Up to 68 weeks of treatment time 3 Male 40 Pharynx 36 Surgery, radiotherapy 58 Success Completed three stages treatment smoothly 4 Female 31 Thyroid 24 Surgery 26 Success Completed three stages treatment smoothly 5 Female 46 Thyroid 60 Surgery 187 Success Completed three stages treatment smoothly 6 Male 68 Lung 48 Surgery, chemotherapy 22838 Death Malignancy-related, death 7 Female 47 Lymphoma 10 Chemotherapy 20608 Response Still taking oral antifungal drugs CM: cryptococcal meningitis; MBC: malignancy before cryptococcal meningitis; No.: number. The clinical characteristics of MAC were shown in Table 3 . The number of MAC cases was 5, age ranged from 52 to 77, with a median of 67.20 years and four of them were male. MAC patients were significantly older than the MBC patients and more likely to be male. The five patients were confirmed to have epithelial-derived malignancies of the digestive or respiratory system. Four of the MAC patients had not clinical symptoms of the primary malignancy, and the clue of malignancy was mostly provided by PET-CT examination. One MAC patient with gallbladder tumor had mild clinical symptoms, and the tumor was removed by minimally invasive surgery. The treatment of CM in this case was successful. Other patients experienced a series of complications during antifungal therapy. The treatment of malignancies in these patients, such as surgery, radiotherapy or chemotherapy, has no chance to implement. They died within 6 months. Table 3 The clinical characteristics and prognosis of MAC patients. No. Sex Age Malignancy origin Count (/L) CM Outcomes Note 1 Male 64 Lung 650 Death Found clue by routine CT scan, malignancy-related 2 Male 70 Stomach 12222 Death Found clue by PET-CT, malignancy-related 3 Female 73 Gallbladder 550 Success Found clue by PET-CT, removal of malignancy by surgery 4 Male 77 Stomach 16 Death Found clue by PET-CT, other (severe pneumonia during treatment) 5 Male 52 Lung 26600 Death Found clue by PET-CT, CM-related CM: cryptococcal meningitis; MAC: malignancy after cryptococcal meningitis; No.: number. Discussion Although CM is much more common in non-HIV patients with predisposing factors, including malignancy [ 2 , 12 ], there has been little information about the clinical features and prognosis of these patients. To our knowledge, the present study was the largest and most detailed series of CM cases in non-HIV patients with malignancy. In this study, we found that a longer time to diagnosis and worse prognosis in CM patients with malignancies and PET-CT might be a useful tool for screening malignancy in such patients. Early researches have shown that malignancies, especially lymphomas [ 7 – 9 ], appear to be closely associated with cryptococcosis. Since then, there have been many case reports of cryptococcal infections as malignancy complications [ 13 – 15 ]. These pioneering studies warned a close relationship between malignancy and CM, and this may be due to the malignancy-related immune alteration or lymphocyte-depleting chemotherapeutic regimens [ 9 ]. Unlike previous studies that found CM in malignancy patients, our present study focused on CM patients, retrospectively analyzed and looked for potential malignant tumors. We found that most patients in our study had solid malignancies (except one lymphoma), and they were all epithelial origin. In immunocompromised genetically modified mice and immunodeficiency populations, the incidence of malignancy has increased significantly [ 16 – 18 ]. These phenomena were thought to be related to the decline in the ability of immunosurveillance. According to this perspective, CM and malignancy may share the same immune abnormality mechanism. In current study, the incidence of CM with malignancy was 3.75%, which was much higher than that of the general population [ 19 ]. Two recent retrospective studies have reported even higher rates of malignancy in CM patients [ 20 , 21 ]. We found that malignancy was usually found in older CM patients, older than 50 years should be more vigilant about the possibility of malignancy. Up to 50% of CM patients with malignancy were hospitalized between 1 and 3 months after clinical symptoms appear, while 70.78% of non-malignancy CM patients were within one month of onset. This discrepancy suggested a significant difference in the severity of clinical symptoms between the two groups, which might be more prominent in patients without malignancy. Comparing the intracranial pressure between the two groups did not reach a statistical difference, we considered the possible reason was that CM patients with malignancy were older. It is generally believed that the elderly are less sensitive to pain. Therefore, the clinical symptoms in CM patients with malignancy were atypical, which caused a delay in CM diagnosis. Literature review analysis found that only less than 15% of patients with cryptococcus infection associated with malignancy were solid [ 9 ]. However, recent studies have found that the incidence of CM patients with solid malignancies was roughly equivalent with haematologic [ 20 , 21 ]. The present study described 12 malignancies in 320 CM patients, of which only one was haematologic. In the 7 MBC patients, the types of malignancy and the affected organs were varied, and they had good antifungal response and low mortality. In contrast, 5 MAC patients mainly involved the digestive and respiratory systems, with a mortality rate of 80%. We suggest that three main reasons might respond for the poor prognosis of MAC: 1) they were older, and senior has been confirmed to indicate a poor prognosis of CM [ 21 , 22 ], 2) when the malignancy was found, most of the patients lost the chance to treat the malignancy due to CM, 3) the patients and his family abandoned active therapy. Early screening of malignancies is difficult [ 23 ]. The sensitivity of different tests in screening of different types of malignancies is inconsistent. Of the 5 MAC patients in this study, only one patient found a lung cancer in routine chest CT. PET-CT is a non-invasive imaging test that has a unique advantage in the detection of early malignancies [ 24 , 25 ]. In a variety of solid tumor and organ infiltrating leukemias, lesions of less than 5 mm can be found by PET-CT with 18 F-FDG radioactive probes [ 26 , 27 ]. In the 104 patients who underwent PET-CT examinations, five patients were prompted to have suspected malignancies, and 4 were eventually confirmed. Therefore, we recommend routine PET-CT examinations for CM patients older than 50 years in order to detect possible early malignancy in time. Our study had limitation. In view of the economic cost, not all patients undergo detailed malignancy screening. The possibility of missed malignancy diagnosis may exist. The clues of this possibility can be observed in the lower malignancy rate in without PET-CT patients than in PET-CT ones. Conclusion The results of present study suggested an increase in the incidence of solid malignancies in CM patients and those patients had a poor prognosis if the malignancies were newly diagnosed. These malignancies were relatively insidious, PET-CT might provide useful clue for finding the malignancies in CM patients older than 50 years. Abbreviations 18F-FDG: 18-fluorodeoxyglucose; CSF: Cerebrospinal fluid; CM: Cryptococcal meningitis; HIV: human immunodeficiency virus; MAC: malignancy after cryptococcal meningitis; MBC: malignancy before cryptococcal meningitis; PET-CT: positron emission computed tomography; WBC: white blood cell Declarations Acknowledgements The authors wish to thank the CM patients and their families for agreeing to participate in this study. The authors also wish to thank the staff of the Department of Neurology of the Third Affiliated Hospital of Sun Yat-sen University. Declarations The authors declare no conflict of interest Authors’ contributions XX and LC collaborated in the conception, organization, execution of the research project, statistical analysis design, and drafted the manuscript. YW and JL collaborated in interpretation data, statistical analysis. QD collaborated in review and critique of the manuscript. CL collaborated in collection of medical records. YJ and FP collaborated in the conception, organization, and the review and critique of the manuscript. Funding This work was funded by National Natural Science Foundation of China (81671182). Availability of data and materials The datasets analyzed during the current study are not yet publicly available but are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and the protocol was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. Informed consent and its written form were obtained from all participants. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details 1 Department of Neurology, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China. 2 Department of Neurology, The First Affiliated Hospital of Guizhou University of traditional Chinese Medicine, P. R. China. 3 Department of Medical Records, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China. References Rajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873-81. Williamson PR, Jarvis JN, Panackal AA, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nat Rev Neurol. 2017;13(1):13-24. George IA, Spec A, Powderly WG, Santos CAQ. Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non-HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A Population-Based Study. 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The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease. Blood. 2014;124(23):3356-64. Kunawudhi A, Wong AK, Alkasab TK, Mahmood U. Accuracy of FDG-PET/CT for Detection of Incidental Pre-Malignant and Malignant Colonic Lesions - Correlation with Colonoscopic and Histopathologic Findings. Asian Pac J Cancer Prev. 2016;17(8):4143-47. Sim YT, Poon FW. Imaging of solitary pulmonary nodule-a clinical review. Quant Imaging Med Surg. 2013;3(6):316-26. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-92814","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":3611273,"identity":"4361e37b-3f2d-40d3-8e42-9c669aff823b","order_by":0,"name":"Xiaofeng Xu","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaofeng","middleName":"","lastName":"Xu","suffix":""},{"id":3611274,"identity":"a6945db1-dc03-4eaa-95a7-a53a1eda5605","order_by":1,"name":"Liping Cao","email":"","orcid":"","institution":"The First Affiliated Hospital of Guizhou university of traditional chinses medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liping","middleName":"","lastName":"Cao","suffix":""},{"id":3611275,"identity":"4d47d3f5-573c-43ee-be1c-e5f24827a26c","order_by":2,"name":"Yijie Wang","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yijie","middleName":"","lastName":"Wang","suffix":""},{"id":3611276,"identity":"bee698ec-ceb3-453a-b96e-4e68daa6a47b","order_by":3,"name":"Jia Liu","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Liu","suffix":""},{"id":3611277,"identity":"f23d4a10-13ff-4f6b-98fe-6c23b467accf","order_by":4,"name":"Qing Dong","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Dong","suffix":""},{"id":3611278,"identity":"66ad0c56-cd2c-4c4a-8159-c83cf1d9f056","order_by":5,"name":"Chunling Liang","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chunling","middleName":"","lastName":"Liang","suffix":""},{"id":3611279,"identity":"95790108-a4e9-400b-9234-3e743debd9a7","order_by":6,"name":"Ying Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACxmYwJcHAIP/44IMPBjZ2JGhhSEs2nFGQlkyKhTlm0jwfDjE2EFLH3M787OHXNos8eYcDBtI2BgeYGdgPH92A32Fs5saybRLFhgcbEoxzDO7wMfCkpd3Ar4XBTFqyTSJxYzPDgeQcg2fMDBI8ZgS0sH+DaGljbDhsYXCYsYGwFh4zyY9ALfN5mIE2EqmlTJrhnETiBgk2ZsYeg7RkNkJ+Mew/vk3yR1ld4vwZ/N9//PhjY8fPfvgYfi0NwIDmZWNgMDgAFWHDpxwE5EGO+/EHyGggpHQUjIJRMApGLAAAVzxJONXMiUgAAAAASUVORK5CYII=","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Jiang","suffix":""},{"id":3611280,"identity":"7af1b499-bd2c-4afc-90c0-ded91d703959","order_by":7,"name":"Fuhua Peng","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fuhua","middleName":"","lastName":"Peng","suffix":""}],"badges":[],"createdAt":"2020-10-14 20:16:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-92814/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-92814/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":3090646,"identity":"bca45598-dda6-4abc-8b3b-024949628cb3","added_by":"auto","created_at":"2020-10-20 19:30:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":252991,"visible":true,"origin":"","legend":"Flow chart displaying the enrollment of study participants.","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-92814/v1/88cd129b72430971fbbcc211.jpg"},{"id":3090647,"identity":"12387de7-cdaa-41fb-83c3-a26bb0f0388e","added_by":"auto","created_at":"2020-10-20 19:30:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":149179,"visible":true,"origin":"","legend":"Survival curves for the CM without or with malignancy. ","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-92814/v1/c3e4189fd34ef3c77092fb5d.jpg"},{"id":13604466,"identity":"73e0411b-578a-418f-8255-49201334c101","added_by":"auto","created_at":"2021-09-17 05:59:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":501279,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-92814/v1/8e35c437-931f-4d73-bf24-4fc155048169.pdf"}],"financialInterests":"","formattedTitle":"Malignancy in non-HIV infected patients with cryptococcal meningitis: a retrospective study","fulltext":[{"header":"Background","content":"\u003cp\u003eCryptococcal meningitis (CM) is the one of the most common opportunistic infection and often occurs in the patients with human immunodeficiency virus (HIV) infection [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. In non-HIV endemic areas, CM appears in a growing number of other forms of natural or iatrogenic immunosuppressive patients [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. In China, about one-third of non-HIV CM patients have predisposing factors, and the prognosis of these people does not seem to be significantly different from that of the immunocompetent population [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eMalignancy is also considered to be immune-related diseases. HIV patients and genetic model animals with immunodeficiency has shown an increase in the incidence of malignancy formation [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. Previous retrospective studies have shown that the incidence of cryptococcal infections is higher in the patients with malignancy, especially in hematological malignancy [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Though the CM and malignancy may associate with immunodeficiency at the same time, the coexistence of malignancy and CM in non-HIV patients is unclear now. In addition, the types of malignancies and their effect on CM prognosis need to be further studied.\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, no studies have been conducted to evaluate the clinical characteristics and therapeutic outcomes of CM in non-HIV infected patients with malignancy. The objective of this study is to analyze the epidemiological and clinical data of malignancy in non-HIV patients with CM, and assess the application of positron emission computed tomography (PET-CT) in the diagnosis of malignancy in the CM population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eStudy populations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a retrospective study approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. All study participants have provided written consent for research and publication.\u003c/p\u003e\n\u003cp\u003eRecords of all patients diagnosed with definite CM from January 2013-May 2019 were examined. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the flowchart for the 357 recruited non-HIV infected CM patients. The enrolled CM patients were divided into three groups according to the discovery of malignancy: 1) no malignancy, 2) malignancy before CM (MBC), 3) malignancy after CM (MAC). Definite CM were identified by a positive result of India ink smear, microbiology culture in cerebrospinal fluid (CSF) and histopathological finding in meninges or brain parenchyma (5 to 10\u0026nbsp;\u0026micro;m encapsulated yeasts). The diagnosis of malignancy before admission depended on the medical history. Patients newly diagnosed with malignancy after admission were confirmed by typical imaging findings and tissue pathology (surgery or biopsy). Patients were excluded if they had a history of immunodeficiency, such as HIV infection, rheumatic diseases, use of immunosuppressants and corticosteroids.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePET-CT examination\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003cp\u003eAmong these 320 CM patients, 104 of them underwent PET-CT examination. These patients were fasted for at least 4 hours with glucose levels less than 150\u0026nbsp;mg/dL before starting the scan. PET images of the whole body were obtained by using a PET-CT scanner (Discovery Elite, GE healthcare, Chicago, IL, USA) after intravenous injection of 5.2\u0026nbsp;MBq per kilogram body weight 18-fluorodeoxyglucose (\u003csup\u003e18\u003c/sup\u003eF-FDG) up to maximum of 370\u0026nbsp;MBq (10\u0026nbsp;mCi). The 3D PET data and CT images were reconstructed for diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment and outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003cp\u003eAntifungal treatment was based on amphotericin B, usually in combination with fluconazole/voriconazole and 5-flucytosine. Combination therapy will sterilize CSF within 2 weeks of treatment in most immunocompetent patients [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e], so the patient's first therapeutic evaluation was performed 2 weeks after using the standard antifungal treatment described above. With reference to previous study [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e], \u0026ldquo;response\u0026rdquo; was defined as survival within 2 weeks with relief of symptoms and clinical signs, improvement in CSF chemistry and cell count, reduce of cryptococcus counts in CSF. Our standard treatment composed by three stages according to the guidelines, including induction, consolidation and maintenance stages [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. If the patient has completed the standard treatment stages, with the clinical symptoms disappear, and negative CSF cryptococcus result, CM was considered to be cured, and patients were marked as \u0026ldquo;success\u0026rdquo;. The patients were follow-up with regular rehospitalization, outpatient visits and telephone after discharge until got \u0026ldquo;success\u0026rdquo;. The cause and time of death were recorded during follow-up. The cause of death within 6 months in these patients was analyzed. If the patient's death was due to an exacerbation of the central nerve system infection (assessed by radiography and CSF examination) and its associated complications, the cause of death was considered to be \u0026ldquo;CM-related\u0026rdquo;. If the patient's death was due to malignancy, which caused organ dysfunction or associated complications, the death was considered to be \u0026ldquo;malignancy-related\u0026rdquo;. The cause of death which cannot be attributed to the above two situations was considered as \u0026ldquo;other\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003cp\u003eAll statistical analyses were performed using SPSS (version 16.0, Chicago, IL, USA). Continuous data were analyzed using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test after confirming a normal distribution using the Shapiro-Wilk test. Mann-Whitney test was used if the data was not a normal distribution. Chi-square analysis was used to analyze categorical variables. Fisher's exact test was an alternative, if the data does not meet the chi-square requirements. Survival was defined as the time from the diagnosis of CM to the death due to any cause or last follow-up. Survival curves were generated by the Kaplan-Meier product limit method. The difference in survival distribution was evaluated by the log rank test.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eDemographic and clinical features\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 357 patients were included in this study. Thirty-seven patients were excluded according exclusion criteria mentioned above (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Among the enrolled patients, 232 (72.5%) were male and 88 (27.5%) were female, with an average age of 45.92\u0026nbsp;years. There were no significant differences in gender between malignancy and non-malignancy CM patients. CM patients with malignancy were older than non-malignancy patients (56.25 \u003cem\u003evs.\u003c/em\u003e 45.52, \u003cem\u003eP\u003c/em\u003e ˂ 0.05) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe clinical characteristics and laboratory data of the CM patients without or with malignancy.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCM without malignancy\u003c/p\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCM with malignancy\u003c/p\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eFeatures\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex (male/female)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e225/83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7/5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.32\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.52\u0026thinsp;\u0026plusmn;\u0026thinsp;14.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56.25\u0026thinsp;\u0026plusmn;\u0026thinsp;14.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSymptoms\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHead ache\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e293/308 (95.13%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12/12 (100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.00\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFever\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e153/308 (49.68%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5/12 (41.67%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.77\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTime to admission\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;1 month\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e218/308 (70.78%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 /12 (33.33%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;1 month, ˂3 month\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e69/308 (22.40%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/12 (50%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;3 month\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21/308 (6.82%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2/12 (16.67%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.26\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCerebrospinal fluid\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal WBC (10\u003csup\u003e6\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e119.06\u0026thinsp;\u0026plusmn;\u0026thinsp;241.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e171.67\u0026thinsp;\u0026plusmn;\u0026thinsp;294.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.39\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProtein (g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.64\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlucose (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.85\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChloride (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e115.17\u0026thinsp;\u0026plusmn;\u0026thinsp;5.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e113.61\u0026thinsp;\u0026plusmn;\u0026thinsp;6.54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.40\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCryptococcus count (/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5962.45 (0-125000)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12592.92 (16-64800)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.29\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLumbar puncture pressure\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;330 mmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e81/308 (26.30%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2/12 (16.67%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.74\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;200, \u0026le;\u0026thinsp;330 mmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e108/308 (35.06%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4/12 (33.33%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.00\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026le;\u0026thinsp;200 mmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e119/308 (38.64%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/12 (50.00%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.55\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.80\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eResponse at week 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e295/302 (97.68%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8/12 (66.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6-month mortality\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29/293 (9.90%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5/12 (41.67%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e199/234 (85.04%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6/11 (54.55%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eCM: cryptococcal meningitis; SD: standard deviation; WBC: white blood cell.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eSymptoms and time to admission\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHeadache and fever were the two most common initial symptoms, with incidence rates of 95.31% and 49.38%, respectively. The incidence rates of headache and fever were not significantly different between non-malignancy and malignancy patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Time to admission (time from initial symptoms to hospitalization and diagnosis of CM) were significantly different between non-malignancy and malignancy patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003cp\u003eCSF findings\u003c/p\u003e\n\u003cp\u003eAt the first lumbar puncture, the CSF open pressure of patients with non-malignancy seemed higher than that of patients with malignancy but did not reach statistical difference (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Non-malignancy CM patients had lower cryptococcus counts than malignancy CM patients, but the difference was not statistically significant (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no significant differences in CSF white blood cell (WBC) count, protein, glucose, and chloride concentration between malignancy and non-malignancy CM patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003cp\u003eOutcomes\u003c/p\u003e\n\u003cp\u003eMost patients (302/308 and 12/12) completed the initial 2 weeks of antifungal treatment. Six patients died or were discharged from treatment within 2 weeks (4 death, 2 discharge). In the non-malignancy CM patients, after the initial 2 weeks of antifungal treatment, the clinical symptoms and signs of 97.68% patients improved, accompanied with decreasing CSF cryptococcus count, which represent the \u0026ldquo;response\u0026rdquo; to the treatment. However, the response rate of malignancy CM patients was significantly lower than that of non-malignancy patients (66.67% \u003cem\u003evs.\u003c/em\u003e 97.68%).\u003c/p\u003e\n\u003cp\u003eSeven patients lost follow-up within 6 months, and 28 patients lost follow-up after 6\u0026nbsp;months. Mortality was finally evaluated in 305 patients at follow up for 6\u0026nbsp;months. Patients with malignancy had much higher 6-month mortality than non-malignancy patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). At the end of this study, among the patients without malignancy, 35 patients died, 37 patients had not completed the therapy course yet, and 199 patients antifungal treatment acquired \u0026ldquo;success\u0026rdquo;. Among the patients with malignancy, 5/12 (41.67%) died within 6 months, 6 patients antifungal treatment was \u0026ldquo;success\u0026rdquo; (one died of tumor recurrence 14\u0026nbsp;months after successful CM treatment), and one patient still took oral antifungal drugs for about 1\u0026nbsp;year and was in stable condition. Survival curves for non-malignancy CM and malignancy CM were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Patients with malignancy had significant lower survival rate than non-malignancy ones (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of MBC and MAC patients\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003cp\u003eThe clinical characteristics of MBC were shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The number of MBC cases was 7, age ranged from 31 to 68 years, with a median of 48.43\u0026nbsp;years and three of them were male. Six cases were epithelial-derived malignancy. Another case was diffuse large B lymphoma. The diagnosis time from malignancy to CM ranged from 2 to 60 months, with an average of 26.86\u0026nbsp;months. Most malignancies were treated by surgery and in stable condition. The treatment on CM in these patients was successful. The case with diffuse large B lymphoma has been undergoing antifungal treatment for approximately one year and has not yet cleared cryptococcus at the end of present study.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe clinical characteristics and prognosis of MBC patients.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo.\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMalignancy origin\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTime from malignancy to CM (month)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMalignancy treatment\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCount (/L)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCM Outcomes\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNote\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLiver\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery, chemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2560\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMalignancy recurrence 2\u0026nbsp;years later, death\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e61\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVaginal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery, radiotherapy, chemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e64800\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUp to 68 weeks of treatment time\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePharynx\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery, radiotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCompleted three stages treatment smoothly\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThyroid\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCompleted three stages treatment smoothly\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThyroid\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCompleted three stages treatment smoothly\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLung\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery, chemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22838\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeath\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMalignancy-related, death\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymphoma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20608\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eResponse\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStill taking oral antifungal drugs\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eCM: cryptococcal meningitis; MBC: malignancy before cryptococcal meningitis; No.: number.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe clinical characteristics of MAC were shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. The number of MAC cases was 5, age ranged from 52 to 77, with a median of 67.20\u0026nbsp;years and four of them were male. MAC patients were significantly older than the MBC patients and more likely to be male. The five patients were confirmed to have epithelial-derived malignancies of the digestive or respiratory system. Four of the MAC patients had not clinical symptoms of the primary malignancy, and the clue of malignancy was mostly provided by PET-CT examination. One MAC patient with gallbladder tumor had mild clinical symptoms, and the tumor was removed by minimally invasive surgery. The treatment of CM in this case was successful. Other patients experienced a series of complications during antifungal therapy. The treatment of malignancies in these patients, such as surgery, radiotherapy or chemotherapy, has no chance to implement. They died within 6\u0026nbsp;months.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe clinical characteristics and prognosis of MAC patients.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo.\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMalignancy origin\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCount (/L)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCM Outcomes\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNote\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLung\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e650\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeath\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFound clue by routine CT scan, malignancy-related\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStomach\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12222\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeath\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFound clue by PET-CT, malignancy-related\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGallbladder\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e550\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSuccess\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFound clue by PET-CT, removal of malignancy by surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStomach\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeath\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFound clue by PET-CT, other (severe pneumonia during treatment)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLung\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeath\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFound clue by PET-CT, CM-related\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eCM: cryptococcal meningitis; MAC: malignancy after cryptococcal meningitis; No.: number.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":" \u003cp\u003eAlthough CM is much more common in non-HIV patients with predisposing factors, including malignancy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], there has been little information about the clinical features and prognosis of these patients. To our knowledge, the present study was the largest and most detailed series of CM cases in non-HIV patients with malignancy. In this study, we found that a longer time to diagnosis and worse prognosis in CM patients with malignancies and PET-CT might be a useful tool for screening malignancy in such patients.\u003c/p\u003e \u003cp\u003eEarly researches have shown that malignancies, especially lymphomas [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], appear to be closely associated with cryptococcosis. Since then, there have been many case reports of cryptococcal infections as malignancy complications [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. These pioneering studies warned a close relationship between malignancy and CM, and this may be due to the malignancy-related immune alteration or lymphocyte-depleting chemotherapeutic regimens [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Unlike previous studies that found CM in malignancy patients, our present study focused on CM patients, retrospectively analyzed and looked for potential malignant tumors. We found that most patients in our study had solid malignancies (except one lymphoma), and they were all epithelial origin. In immunocompromised genetically modified mice and immunodeficiency populations, the incidence of malignancy has increased significantly [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These phenomena were thought to be related to the decline in the ability of immunosurveillance. According to this perspective, CM and malignancy may share the same immune abnormality mechanism.\u003c/p\u003e \u003cp\u003eIn current study, the incidence of CM with malignancy was 3.75%, which was much higher than that of the general population [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Two recent retrospective studies have reported even higher rates of malignancy in CM patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. We found that malignancy was usually found in older CM patients, older than 50\u0026nbsp;years should be more vigilant about the possibility of malignancy. Up to 50% of CM patients with malignancy were hospitalized between 1 and 3\u0026nbsp;months after clinical symptoms appear, while 70.78% of non-malignancy CM patients were within one month of onset. This discrepancy suggested a significant difference in the severity of clinical symptoms between the two groups, which might be more prominent in patients without malignancy. Comparing the intracranial pressure between the two groups did not reach a statistical difference, we considered the possible reason was that CM patients with malignancy were older. It is generally believed that the elderly are less sensitive to pain. Therefore, the clinical symptoms in CM patients with malignancy were atypical, which caused a delay in CM diagnosis.\u003c/p\u003e \u003cp\u003eLiterature review analysis found that only less than 15% of patients with cryptococcus infection associated with malignancy were solid [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, recent studies have found that the incidence of CM patients with solid malignancies was roughly equivalent with haematologic [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The present study described 12 malignancies in 320 CM patients, of which only one was haematologic. In the 7 MBC patients, the types of malignancy and the affected organs were varied, and they had good antifungal response and low mortality. In contrast, 5 MAC patients mainly involved the digestive and respiratory systems, with a mortality rate of 80%. We suggest that three main reasons might respond for the poor prognosis of MAC: 1) they were older, and senior has been confirmed to indicate a poor prognosis of CM [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], 2) when the malignancy was found, most of the patients lost the chance to treat the malignancy due to CM, 3) the patients and his family abandoned active therapy.\u003c/p\u003e \u003cp\u003eEarly screening of malignancies is difficult [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The sensitivity of different tests in screening of different types of malignancies is inconsistent. Of the 5 MAC patients in this study, only one patient found a lung cancer in routine chest CT. PET-CT is a non-invasive imaging test that has a unique advantage in the detection of early malignancies [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In a variety of solid tumor and organ infiltrating leukemias, lesions of less than 5\u0026nbsp;mm can be found by PET-CT with \u003csup\u003e18\u003c/sup\u003eF-FDG radioactive probes [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In the 104 patients who underwent PET-CT examinations, five patients were prompted to have suspected malignancies, and 4 were eventually confirmed. Therefore, we recommend routine PET-CT examinations for CM patients older than 50\u0026nbsp;years in order to detect possible early malignancy in time.\u003c/p\u003e \u003cp\u003eOur study had limitation. In view of the economic cost, not all patients undergo detailed malignancy screening. The possibility of missed malignancy diagnosis may exist. The clues of this possibility can be observed in the lower malignancy rate in without PET-CT patients than in PET-CT ones.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eThe results of present study suggested an increase in the incidence of solid malignancies in CM patients and those patients had a poor prognosis if the malignancies were newly diagnosed. These malignancies were relatively insidious, PET-CT might provide useful clue for finding the malignancies in CM patients older than 50\u0026nbsp;years.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003e18F-FDG: 18-fluorodeoxyglucose; CSF: Cerebrospinal fluid; CM: Cryptococcal meningitis; HIV: human immunodeficiency virus; MAC: malignancy after cryptococcal meningitis; MBC: malignancy before cryptococcal meningitis; PET-CT: positron emission computed tomography; WBC: white blood cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank the CM patients and their families for agreeing to participate in this study. The authors also wish to thank the staff of the Department of Neurology of the Third Affiliated Hospital of Sun Yat-sen University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXX and LC collaborated in the conception, organization, execution of the research project, statistical analysis design, and drafted the manuscript. YW and JL collaborated in interpretation data, statistical analysis. QD collaborated in review and critique of the manuscript. CL collaborated in collection of medical records. YJ and FP collaborated in the conception, organization, and the review and critique of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by National Natural Science Foundation of China (81671182).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are not yet publicly available but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and the protocol was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. Informed consent and its written form were obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Neurology, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Neurology, The First Affiliated Hospital of Guizhou University of traditional Chinese Medicine, P. R. China. \u003csup\u003e3\u003c/sup\u003eDepartment of Medical Records, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRajasingham R, Smith RM, Park BJ, et al. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis. 2017;17(8):873-81.\u003c/li\u003e\n\u003cli\u003eWilliamson PR, Jarvis JN, Panackal AA, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nat Rev Neurol. 2017;13(1):13-24.\u003c/li\u003e\n\u003cli\u003eGeorge IA, Spec A, Powderly WG, Santos CAQ. Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non-HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A Population-Based Study. Clin Infect Dis. 2018;66(4):608-11.\u003c/li\u003e\n\u003cli\u003eZhu LP, Wu JQ, Xu B, Ou XT, Zhang QQ, Weng XH. Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997-2007. Med Mycol. 2010;48(4):570-79.\u003c/li\u003e\n\u003cli\u003eShankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107-11.\u003c/li\u003e\n\u003cli\u003eEngels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123(1):187-94.\u003c/li\u003e\n\u003cli\u003eKaplan MH, Rosen PP, Armstrong D. Cryptococcosis in a cancer hospital: clinical and pathological correlates in forty-six patients. Cancer. 1977;39(5):2265-74.\u003c/li\u003e\n\u003cli\u003eKontoyiannis DP, Peitsch WK, Reddy BT, et al. Cryptococcosis in patients with cancer. Clin Infect Dis. 2001;32(11):E145-50.\u003c/li\u003e\n\u003cli\u003eSchmalzle SA, Buchwald UK, Gilliam BL, Riedel DJ. Cryptococcus neoformans infection in malignancy. Mycoses. 2016;59(9):542-52.\u003c/li\u003e\n\u003cli\u003eSaag MS, Graybill RJ, Larsen RA, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):710-18.\u003c/li\u003e\n\u003cli\u003ePerfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291-322.\u003c/li\u003e\n\u003cli\u003eHenao-Martinez AF, Chastain DB, Franco-Paredes C. Treatment of cryptococcosis in non-HIV immunocompromised patients. Curr Opin Infect Dis. 2018;31(4):278-85.\u003c/li\u003e\n\u003cli\u003eTakase K, Yoshida T, Nakamura T, Seki S, Sato H, Yamamoto T. Cryptococcal Meningitis in a Patient with Breast Cancer Receiving Everolimus: A Case of Successful Treatment with Continuous Cerebrospinal Fluid Drainage. Brain Nerve. 2018;70(11):1301-05.\u003c/li\u003e\n\u003cli\u003eTo CA, Hsieh RW, McClellan JS, et al. Cryptococcal osteomyelitis and meningitis in a patient with non-hodgkin's lymphoma treated with PEP-C. BMJ Case Rep. 2012; bcr0820114578\u003c/li\u003e\n\u003cli\u003eMarchand T, Revest M, Tattevin P, et al. Early cryptococcal meningitis following treatment with rituximab, fludarabine and cyclophosphamide in a patient with chronic lymphocytic leukemia. Leuk Lymphoma. 2013;54(3):643-5.\u003c/li\u003e\n\u003cli\u003eGirardi M, Oppenheim DE, Steele CR, et al. Regulation of cutaneous malignancy by gammadelta T cells. Science. 2001;294(5542):605-9.\u003c/li\u003e\n\u003cli\u003eStreet SE, Hayakawa Y, Zhan Y, et al. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med. 2004;199(6):879-84.\u003c/li\u003e\n\u003cli\u003eSmyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol. 2006;90:1-50.\u003c/li\u003e\n\u003cli\u003eBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.\u003c/li\u003e\n\u003cli\u003eHakyemez IN, Erdem H, Beraud G, et al. Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study. Eur J Clin Microbiol Infect Dis. 2018;37(7):1231-40.\u003c/li\u003e\n\u003cli\u003eTsai WC, Lien CY, Lee JJ, et al. The clinical characteristics and therapeutic outcomes of cryptococcal meningitis in elderly patients: a hospital-based study. Bmc Geriatr. 2019;19(1):91.\u003c/li\u003e\n\u003cli\u003eQu J, Zhou T, Zhong C, Deng R, Lu X. Comparison of clinical features and prognostic factors in HIV-negative adults with cryptococcal meningitis and tuberculous meningitis: a retrospective study. BMC Infect Dis. 2017;17(1):51.\u003c/li\u003e\n\u003cli\u003eRebbeck TR, Burns-White K, Chan AT, et al. Precision Prevention and Early Detection of Cancer: Fundamental Principles. Cancer Discov. 2018;8(7):803-11.\u003c/li\u003e\n\u003cli\u003eSanli Y, Zukotynski K, Mittra E, et al. Update 2018: 18F-FDG PET/CT and PET/MRI in Head and Neck Cancer. Clin Nucl Med. 2018;43(12):e439-52.\u003c/li\u003e\n\u003cli\u003eEvens AM, Kostakoglu L. The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease. Blood. 2014;124(23):3356-64.\u003c/li\u003e\n\u003cli\u003eKunawudhi A, Wong AK, Alkasab TK, Mahmood U. Accuracy of FDG-PET/CT for Detection of Incidental Pre-Malignant and Malignant Colonic Lesions - Correlation with Colonoscopic and Histopathologic Findings. Asian Pac J Cancer Prev. 2016;17(8):4143-47.\u003c/li\u003e\n\u003cli\u003eSim YT, Poon FW. Imaging of solitary pulmonary nodule-a clinical review. Quant Imaging Med Surg. 2013;3(6):316-26.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cryptococcal meningitis, malignancy, positron emission computed tomography","lastPublishedDoi":"10.21203/rs.3.rs-92814/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-92814/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBackground\u003c/em\u003e:\u003c/strong\u003e Cryptococcal meningitis (CM) was found to be coexist with malignancy in non-human immunodeficiency virus (HIV) infected patients. The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of CM in non-HIV infected patients with malignancy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMethods\u003c/em\u003e:\u003c/strong\u003e A total of 320 CM patients were enrolled for analysis from January 2013-May 2019. One hundred and four patients underwent positron emission computed tomography (PET-CT) examination. The demographics, clinical characteristics, microbiological, radiological, therapeutic outcomes were analyzed in CM patients with and without malignancy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e\u003cem\u003eResults\u003c/em\u003e:\u003c/strong\u003e Twelve patients with malignancy were found, of which 7 malignancy before CM (MBC), 5 malignancy after CM (MAC). CM patients with malignancy were older than non-malignancy ones. The prognosis of MBC patients was comparable to that of non-malignancy patients, but was extremely poor in MAC patients. Four out of 5 CM patients, who was suggested diagnosis as malignancy by PET-CT, were finally confirmed.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConclusions\u003c/em\u003e:\u003c/strong\u003e This study found an increase rate of solid malignancies in CM patients. Screening malignancy in older CM patients was very important because it is closely related to prognosis and might affect treatment strategy. PET-CT might be a useful tool for early malignancy screening in CM.\u003c/p\u003e","manuscriptTitle":"Malignancy in non-HIV infected patients with cryptococcal meningitis: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-20 19:30:17","doi":"10.21203/rs.3.rs-92814/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e18a0fb-a024-4319-a764-9f0e7ef05754","owner":[],"postedDate":"October 20th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":836199,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2020-12-30T22:54:27+00:00","versionOfRecord":[],"versionCreatedAt":"2020-10-20 19:30:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-92814","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-92814","identity":"rs-92814","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}