Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications.We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I–II cases.p = 0.019), while the positive expression of Syn and CD56 showed borderline significance , but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS.The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes. Melanoma is a type of malignant tumor, which has a relatively good prognosis in the early stage; however, it becomes life-threatening at an advanced stage . TherefoAberrant immunohistochemical expression of melanoma has been previously reported . HMB-45,Although abnormal expression of neuroendocrine markers in melanomas has been reported occasionally, most were case reports and small case series , 11. ThiBecause of the small case series reported in the literature and the lack of correlation with prognosis, we retrospectively examined the expression of the three neuroendocrine markers, CgA, Syn, and CD56, in a large case series of 308 melanoma cases and its correlation with clinicopathological parameters and possible prognostic significance.In a retrospective review of archived pathology files at Peking University Cancer Hospital and Institute in China, 308 melanoma specimens were diagnosed between 2000 and 2020. Previous definitive diagnoses of all cases were based on clinical history, histopathological evaluation, and immunohistochemistry staining, while some cases were diagnosed with the aid of molecular testing. The clinical information and molecular pathology test results of all enrolled patients were obtained by reviewing the electronic medical records. Follow-up information was obtained from medical records or by phone communication. Overall survival (OS) was calculated from the time of melanoma diagnosis to the time of death or the last follow-up. The duration of progression-free survival (PFS) was calculated from the date of surgery to the date of recurrence or progression. The present study was approved by the Ethics Committee of Peking University Cancer Hospital and Institute, and written consent was obtained from all patients.The morphological subtype was determined by reviewing the stored electronic images independently by two pathologists (Wu Y and Lai Y). The clinical staging for melanoma was defined as I–II for tumors confined to the primary location, III for regional lymph node metastasis, and IV for distant metastases .Initially, 4-μm sections were cut from each formalin-fixed and paraffin-embedded melanoma block. Sequential procedures of dewaxed and rehydrated tissue sections were performed, followed by heat-mediated epitope retrieval with 10 mmol/L citrate buffer (pH 6.0). Endogenous peroxidase was inactivated using 3% hydrogen peroxide solution. The sections were incubated with a primary antibody working solution of CgA/Melan-A /CK/EMA/Cam5.2/Vimentin , Syn/S-100/SOX10 , CD117 , and CD56/HMB45  at room temperature for 1 h. Not all markers could be detected as most of the enrolled cases came for consultation, and the immunohistochemical items detected were limited by the number of sections. The intensity score was defined using the following criteria: 0, no staining; 1, weak or partial staining; and 2, strong and diffuse staining.P < 0.05 indicates a statistically significant difference. All statistical analyses were performed using SPSS, version 22.0 .Measurement data are described as median and ranges. The correlation between categorical variables was calculated using Pearson’s chi-square or Fisher’s test. Kaplan-Meier survival curve was used to perform survival analysis, and the log-rank test was applied to evaluate statistical significance. Univariate and multivariate Cox proportional-hazards regression models were used to investigate the association between OS/DFS and clinical and pathological features. The clinical and pathological characteristics of all patients with melanoma are summarized in Table The OS ranged from 0 to 233 months, with a median duration of 16 months. Of the 266 melanoma patients, 126 were alive at the last follow-up, and the 1-, 3-, and 5-year survival rates were 73.3, 41.6, and 30.7%, respectively. In 150 melanoma patients, disease progression occurred in 132 cases, and PFS ranged from 1 to 225 months with a median duration of 10 months. At the last follow-up, 6 patients were lost to follow-up. Of the remaining 144 patients, 18 (12.5%) remained alive without evidence of progression, 68 (47.2%) were alive with disease progression, and 58 (40.3%) died of the disease.In our series, CgA was only positive in 6/304 2.0%) cases, all of which were weakly or focally positive. Syn was positive in 26/304 (8.6%) cases, of which 8 stained diffuse and strongly positive, and 18 stained weakly or focally positive. By comparison, CD56 had a higher positive expression rate in 56/189 (29.6%) cases, of which 35 were diffuse and strongly positive, and 21 were weakly positive. Of the 188 cases in which CgA, Syn and CD56 were detected simultaneously, focal or weak expression of at least one of the studied markers was observed in 70/188 (37.2%) cases (Table .0% casesp = 0.019), while the positive expression of Syn and CD56 showed borderline significance with age , whereas no correlation was observed between neuroendocrine marker expression and age (p = 0.463). CgA, Syn, or CD56 expression did not correlate with staging, but neuroendocrine marker positive expression showed a borderline correlation with staging (p = 0.066). Patients with stage I–II and stage III had similar positive rates, i.e., 34/85 (40.0%) and 12/27 (44.4%), respectively, but it declined to 18/68 (26.5%) in stage IV patients. Sex, specimen type, origin, location, and histological subtype were not related to neuroendocrine marker expression.Associations between neuroendocrine marker expression and clinicopathological features are summarized in Table p = 0.072; HR = 0.548, p = 0.039, respectively), while stage IV patients had a significantly lower OS . In univariate analysis, patients whose primary site was located in the mucosa or others  had shorter OS than those whose primary site was located in the skin , and patients with BRAF mutation had longer OS than those with the wild type . Nevertheless, in multivariate analysis, primary location and BRAF mutation status had no influence on OS. Mucosal melanoma was associated with an increased risk of tumor progression after surgery in univariate and multivariate analyses . Sex  showed borderline significance with PFS . Age (≤55 years) and primary location in the mucosa of stage I–II melanoma patients were significantly correlated with OS in univariate analysis  but not in multivariate analysis. Female sex was an independent factor that predicted longer OS in stage I–II melanoma patients in the multivariate analysis . In the PFS analysis of stage I–II melanoma patients, univariate and multivariate analyses revealed that mucosal location was associated with shorter PFS duration .Kaplan-Meier survival analysis indicated that the OS and DFS between melanoma patients with positive and negative neuroendocrine expression did not show statistically significant differences Fig. . AssociaMelanoma has diverse histopathological morphologies, including loss of melanin, partial or complete loss of melanoma markers and aberrant expression of non-melanocytic markers, representing potentially diagnostic pitfalls . AccuratCgA, Syn, and CD56 are the most frequently used markers of neuroendocrine differentiation, but the expression of one or more of these markers may also be found in a subset of non-neuroendocrine tumors that may obscure the correct diagnosis . AberranNeuroendocrine differentiation in melanoma has been observed, but its prognostic significance is uncertain . The resIt is widely acknowledged that CD56 is a sensitive but non-specific marker of neuroendocrine tumors in comparison to Syn and CgA . AberranOne limitation of our study is that 290 cases enrolled in this series came for consultation, and the results of molecular detection and immunohistochemistry assays were derived from our routine practice. This selection bias, may have affected the results of this study.The expression of neuroendocrine markers seems to be common in melanoma; therefore, we should keep in mind that the cases with aberrant expression of these markers also have the possibility to be melanoma, which should be listed in the differential diagnosis. However, unlike other cancers, neuroendocrine marker expression in melanomas does not indicate a worse prognosis.


Globally, prostate cancer (PCa) is the commonest non-cutaneous male malignancy. It is more aggressive among black men with little known reasons as to the cause and continued trend among black men. This disproportionate pattern of PCa especially among black men of African ancestry resident in Africa calls for a closer look. Nigeria and South Africa, combined, have the highest cumulative risk incidence of PCa in Africa. The present study investigated the clinicopathologic behaviour of PCa among Nigerian and South African black men and the relationship between the disease and socio-demographic characteristics alongside medical co-morbidities.A retrospective cross-sectional study was undertaken in which de-identified records of 234 black men with pathologically confirmed PCa between 2007 and 2017 from two tertiary hospitals, in Nigeria  and South Africa , were reviewed.p < 0.001). Risk stratification using PSA, Gleason scores and T-staging showed that 84.2% (n = 197) of all the men presented with high-risk PCa disease. There was a statistically significant difference between Nigerian and South African black men (p = 0.003) in terms of disease risk at presentation. Logistic regression analysis showed that age (Adjusted OR 1.053 (95% CI 1.003–1.106), p = 0.003) and country of residence (Adjusted OR 4.281 (95% CI 1.690–10.844), p = 0.002) had a statistically significant relationship with high risk of PCa while disease co-morbidities (like diabetes and hypertension) and rural/urban location in both countries did not.Median age at presentation from both countries was 66 years  while the median PSA at presentation was 46 ng/ml (IQR 16–336.5 ng/ml). Half of the men (117/234) presented with locally advanced disease while metastatic disease was observed in 65.9% (27/41) of Nigerian men and 34.1% (14/41) of South African men. Thirty-three per cent of the men presented with organ-confined disease. Overall, Nigerian men presented with less organ-confined disease and significantly higher stage of disease (Disparities exist between PCa presentation and clinicopathologic behaviour among Nigerian and South African black men. Nigerian men showed higher disease risk at presentation. Environmental-genetic interactions need further exploration in the aetio-pathogenesis of PCa in black men of African ancestry. Prostate cancer (PCa) represents a foremost cancer among men and the commonest non-cutaneous malignancy globally in men . It is aMedical co-morbidities such as cardiovascular diseases like hypertension, type 2 diabetes and benign prostate hyperplasia (BPH) could impact on the presentation of prostate cancer and eventually determine its outcome during or after treatment . Men witWe therefore set out to look at the clinical and pathological characteristics of PCa (presenting prostate specific antigen (PSA) level, histopathological type, tumour grade and stage of disease) among black men of Nigeria and South Africa; with a view to compare the characteristics of the disease and its association with socio-demographic characteristics and medical co-morbidities among black men from both countries.This was a retrospective cross-sectional study in which we abstracted anonymized data from de-identified hospital records of eligible black patients with PCa managed at National Hospital, Abuja, Nigeria and Tygerberg Hospital, Cape Town, South Africa between 2007 and 2017 using data extraction sheets. The data from Nigeria was abstracted from patient notes in clinical folders while those from South Africa were data collected prospectively into a secured database. Ethical approval to undertake the study was granted by the National Hospital, Abuja, Nigeria and Stellenbosch University, South Africa .We used consecutive sampling technique on all the eligible patients records till the projected sample size of 234 (117 from each country) was reached. As a result of the generally late or poor health-seeking behaviour among Africans, the number of patients presenting in the hospitals for diagnosis and treatment of PCa is small across Africa and due to this , 8, we nOur selection criteria were male patients with complete data, seen and managed in either hospitals, racially classified or self-identified as black, with confirmed histopathological PCa diagnosis, according to the International Society of Urologic Pathology (ISUP) guidelines of 2005 and 2014 , 20. To We collected data such as age at diagnosis, demography , medical co-morbidities and presenting pathologies . We used the Union for International Cancer Control (UICC) 2009 Tumour -Node-Classification (TNM) 7 for our T-definitions  UICC/TN.Using PSA value at presentation, the patients were classified into low, intermediate and high-risk PSA categories. We also looked at the Gleason scores (GS) pathology grading to identify well (GS = 2–6), moderately (GS = 7) and poorly differentiated diseases GS = 8–10) , 20. We 0 , 20. WUsing a standard multi-variate logistic regression analysis, we further identified if there was any association between high risk PCa and socio-demographic factors like age, self-reported cigarette smoking and alcohol history, rural/urban residence, medical co-morbidities  as well as country of residence (with South Africa as reference category). The dependent variable was high risk prostate cancer while the independent variables included the socio-demographic characteristics, medical co-morbidities and country of residence. All P-values were two-sided, and significance was set at 95%.Our data were analysed using STATA IC 15 software statistical package.Data from 234 black male patients from both countries were analysed. Median age of disease presentation was 66 years . The social demographics and pathologic characteristics of the men are summarized in Table Adenocarcinoma of the prostate gland was the commonest histological variant with 99.1% (232/234) of the men presenting with such in both countries (117 Nigerians and 115 South Africans). Only 0.9% (2/234) of the men (who were South Africans) presented with Squamous Cell Carcinoma histological variant in the available records reviewed in this study period. .χ2 = 5.43, p = 0.066) in PSA categories between the men in the entire cohort.Median PSA at presentation for the entire cohort was 46 ng/ml (IQR 16–336.5 ng/ml). Maximum PSA recorded was 9890 ng/ml, while the minimum recorded was 1.3 ng/ml. Men were classified into high risk PSA > 20 ng/ml), moderate risk (PSA = 10-20 ng/ml) and low risk (PSA < 10 ng/ml) categories based on PSA at presentation  between staging presentations in both countries with the Nigerian men presenting with higher stage of clinical disease  presented with locally advanced stage of clinical disease; 61.5% (72/117) of these were Nigerians and 38.5% were South Africans. Forty-one men (41/234) presented with metastatic disease from both countries; of which 65.9% (27/41) were Nigerians and 34.1% (14/41) were South Africans. Seventy-six men (76/234) had organ-confined disease, out of which 23.7% (18/76) were Nigerians and 76.3% (58/76) were South Africans. There is a statistically significant difference  with 52.4% (55/105) being Nigerians and 47.6% (50/105) South Africans. Eighty-eight men presented with moderately differentiated disease (GS = 7) with 58% (51/88) being Nigerians and 42% (37/88) South Africans while 36 men presented with well differentiated disease (GS = 2–6). Of the well-differentiated diseases, 30.6% (11/36) were Nigerians and 69.4% (25/36) were South Africans. Five South Africans had no record of GS grading.p = 0.003) in terms of disease risk at presentation, with Nigerian men having higher disease risk category  and this included 54.8% (108/197) Nigerians and 45.2% (89/197) South Africans. Twenty-two men had intermediate risk disease (PSA = 10–20 or GS = 7 or T2b) with 27.3% (6/22) being Nigerians and 72.7% (16/22) South Africans. Fifteen men had low-risk disease  with 20% (3/15) being Nigerians and 80% (12/15) being South Africans. There exists a statistically significant difference between Nigerians and South African black men  as well as country of residence on PCa risk category.p = 0.003) and country of residence (Adjusted OR 4.281 (95% CI 1.690–10.844), p = 0.002) were shown to be statistically significant in the association with high risk of prostate cancer disease.After adjusting for the other co-variates Table , only agProstate cancer is predominantly a disease of the ageing man. Among the strong risk factors associated with PCa, older age, family history and African ancestry have been identified , 24. TheThe predominant histopathology variant in this study was Adenocarcinoma from both countries. Only 0.9% of the South African black men presented with squamous-cell carcinoma. This is not unexpected with the anatomy of the prostate gland. Similar predominant patterns of Adenocarcinoma variant were shown in studies from Trinidad and Tobago , Burkinap = 0.06) between black men from South Africa and Nigeria. This observation is in tandem with the earlier findings that black men of African ancestry usually present with higher PSAs consistent with more aggressive disease. It could also be implied that irrespective of country of residence, black men usually present in similar patterns of higher risk of disease category when analysing within the context of PSA alone.Our study showed that most of the men from both countries presented with PSA > 20 ng/ml, indicating a higher risk category of disease at presentation. Head-to-head categorical analysis of both countries also showed that there was no statistically significant difference in the median PSA at presentation  and of this South Africans were more. Most of the samples (44.9%) were poorly differentiated (GS = 8–10) and Nigerians had more poorly differentiated diseases. Sanchez-Ortiz et al. in their analysis of non-palpable PCa disease had similar findings of 43% of poorly differentiated disease versus 37% when African-American men were matched with White men in the US . Magoha p < 0.001) in staging presentation in both countries, with the Nigerian men presenting with a higher stage of disease. It could be that there is poor awareness of PCa in Nigeria when compared to South Africa, leading to late presentation of disease [The staging presentation in our study was a combination of imaging and clinical records found in patients notes. It was noted that the South African records were more complete with respect to T-stage category of disease when compared to Nigeria. This might be due to more widespread use of imaging modalities  such as  disease . Moreove disease –44 that p = 0.003) between Nigerian and South African black men in terms of disease risk presentation, buttressing the earlier finding that PCa seems to be more aggressive among the Nigerian group. This was further corroborated with our regression analysis when we tried to establish the relationship between high risk PCa disease at presentation and socio-demographic factors like age, urban/rural location, smoking history, hypertension, type 2 diabetes mellitus, BPH and country of origin. Only age (Adjusted OR 1.053 (95% CI 1.003–1.106), p = 0.003) and country of residence (Adjusted OR 4.281 (95% CI 1.690–10.844), p = 0.002) were found to be statistically significant, after adjusting for other co-variates. Our findings indicated that being in Nigeria had four times the risk of presenting with the high risk PCa disease as against South Africa. It should be noted that the choice of these disease co-morbidities in our analysis was not because of any special relationship with PCa. However, these were the most co-morbidities reported in the patient records available to us in this study and could also impact on the timing of presentation of these patients in seeking the diagnosis and treatment of PCa [When the men in our studies were further risk stratified into low, intermediate and high risk PCa disease category using an adaptation of D’Amico’s criteria  by combit of PCa , 46.It is unknown why the Nigerian group were more at risk of presenting with high-risk disease, but we speculate that there might be genetic and/or environmental factors that influence tumour pathology. Fernandez and Zeigler-Johnson et al.  have shoOur study has several limitations which must be acknowledged as these might have impacted in the results we obtained. There were incomplete data for most patients from both countries. For example, only two South Africans in the entire cohort had lymph nodal status report, others were either not available or could not be assessed from the records. There is also the possibility of under or over-representing any of the population samples due to the consecutive sampling technique which we employed. This may have introduced selection bias into the study. It is also possible that our number of high-risk patients might have been inflated due to the addition of the metastatic patients to the high-risk category when we adapted the D’Amico’s criteria to our disease risk categorization.The aggressive nature of PCa among black men, irrespective of place of residence, is incontestable globally , 12, 40.


Delirium is one of the most common complications in older surgical patients. Although previous studies reported that preoperative malnutrition was related with postoperative delirium (POD), there was lack of evidence to illustrate the relationship between malnutrition and emergency delirium (ED). The objective of this study was to investigate the relationship between preoperative malnutrition and ED in older patients undergoing noncardiac surgery.The study was carried out in accordance with STROBE guidelines. This was a secondary analysis of a prospective cohort study. Older patients (65–90 years) who underwent noncardiac surgery under general anesthesia were enrolled in Peking University First Hospital.915 patients were enrolled. The incidence of malnutrition was 53.6 % (490/915). The incidence of emergency delirium was 41.8 % (205/490) in malnutrition group and 31.5 % (134/425) in control group, P < 0.001. After adjusting confounding factors , duration of surgery, pain score, low body temperature and allogeneic blood transfusion), malnutrition was not associated with increased risk of emergency delirium .Malnutrition was common in older patients undergoing non-cardiac surgery, but it’s not related with emergence delirium after adjusted for confounders.http://www.chictr.org.cn) .Chinese Clinical Trial Registry (The online version contains supplementary material available at 10.1186/s12877-021-02270-2. Malnutrition has been considered as a great challenge to patient’s safety in perioperative settings , 2. It iDelirium is one of the most common complications in older surgical patients. It is manifested as acute disturbance of attention and cognitive function, abnormal sleep cycle and disorganized thinking . AccordiAlthough previous studies reported that preoperative malnutrition was related with POD, there was lack of evidence to illustrate the relationship between malnutrition and ED. Two cohort studies reported that preoperative malnutrition was associated with increased risk of postoperative delirium in patients undergoing on pump coronary artery bypass grafting , 14. TheThis study was designed to investigate the relationship between preoperative malnutrition and emergence delirium in older patients after non-cardiac surgery.Present study was secondary analysis of a prospective observational study which was approved by the Clinical Research Ethics Committee of Peking University First Hospital on August 4, 2017  and registered with Chinese Clinical Trial Registry on September 19, 2017  [, BeijingOlder patients (aged 65–90 years) were included if they were scheduled to undergo noncardiac surgery with an expected duration ≥ 2 h under general anesthesia. Patients who met any of the following criteria were excluded: (1) refused to participate in the study; (2) previous history of schizophrenia, epilepsy, Parkinson’s Disease, or myasthenia gravis; (3) unable to communicate due to severe dementia, comatose or language barrier; (4) traumatic brain injury or neurosurgery; (5) an American Society of Anesthesiologists (ASA) classification of IV or above; or (6) Emergency surgery.Preoperative malnutrition was defined as nutritional risk screening 2002 (NRS2002) ≥ 3. NRS 2002 contains two components: nutritional status and disease severity, giving a total score of 0–6 (Supplementary Table SEmergence delirium was defined as any episode of delirium during PACU stay and was assessed by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) at 10 and 30 min after PACU admission, and before PACU discharge , 18.Before assessing delirium assessment, the level of sedation/agitation was evaluated with the Richmond Agitation Sedation Scale (RASS) . If the All investigators who were in charge of delirium assessment were trained to use the CAM-ICU by a psychiatrist . ConfusiAll patients received standard monitoring on arrival in the operating room including electrocardiogram, non-invasive blood pressure, pulse oxygen saturation, and urine output. During general anesthesia, end-tidal carbon dioxide and bispectral index (BIS) were monitored. Invasive arterial pressure and central venous pressure were used if considered as necessary.Anesthesia induction was completed by propofol and/or etomidate, opioids (sufentanil and/or remifentanil) and muscle relaxants (rocuronium or cisatracurium). Anesthesia maintenance was conducted by infusion of propofol and/or sevoflurane inhalation. Nitrous oxide could be used as supplementary in necessary. Opioids and muscle relaxants were administered when considered necessary. The target was to maintain bispectral index between 40 and 60.Muscle relaxants were stopped for at least 30 min before the end of surgery; propofol infusion and/or sevoflurane inhalation were decreased or stopped according to BIS monitoring; sufentanil was administered in necessary. At the end of surgery, Neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg) were used to reverse residual effect of neuromuscular blockade. Patients were extubated when they met the following criteria: (1) easy to wake up; (2) sufficient reflexes that protect the airway; (3) adequate gas exchange ; and (4) acceptable hemodynamic status (systolic blood pressure ≥ 90 mmHg and heart rate ≤ 100 beats per minute).As a routine practice, patients were transferred to the PACU after extubation. Patients were monitored in PACU for at least 30 min and then transferred to the general ward when the Aldrete score was higher than 9. Pain severity was assessed with the numeric rating scale . Moderate to severe pain (NRS pain score > 3) was managed with intravenous opioids and/or non-steroid anti-inflammatory drugs (NSAIDs). Tympanic temperature was measured with an infrared ear thermometer. Patients with hypothermia (< 36 °C) were managed with warm air blanket.Primary outcome was to investigate the relationship between malnutrition and occurrence of emergence delirium.Baseline data included demographics, education, diagnosis, comorbidities, smoking, alcoholism, Charlson Comorbidity Index , and ASAPostoperative data during PACU stay included NRS pain score, tympanic temperature, and length of PACU stay. In the general wards, patients were followed up twice daily until the 5th day after surgery for the occurrence of delirium and non-delirium complications. From the 6th day after surgery, patients were followed up weekly until discharge. For those who were discharged from the hospital, follow-ups were performed by telephone interview.As a secondary analysis, we calculated the statistical power based on available data. The incidence of ED was 41.8 % (205/490) in malnutrition group and 31.5 % (134/425) in control group. Assuming significance at 0.05, this would yield a power of 0.90.Normality of continuous data was tested by Kolmogorov-Smirnov method in prior. Data with normal distribution were presented as mean ± standard deviations (SD) and differences between groups were compared by independent t sample. Data without normal distribution were presented as median (IQR) and differences between groups were compared by Mann-Whitney U test. Categorical data was presented by number (percentage) and differences between groups were compared by Chi-square test.The relationship between malnutrition and ED was firstly analyzed by univariate analysis, followed by multivariable logistic regression analysis adjusted for confounding factors including the baseline characteristics and perioperative variables that showed an imbalance between patients with and without ED .Two-sided P < 0.05 was considered as statistical significance. Statistical analysis was performed using SPSS 24 Inc. Chicago, IL, USA.From September 21, 2017 to April 10, 2019, 984 patients met with inclusion criteria. Finally, 915 patients were included with mean age of 71.6 ± 5.2 years, Fig. The mean age of patients with malnutrition was higher than that of patients in control group , Table According to NRS 2002, the incidence of malnutrition was about 53.6 % (490/915) in elderly patients undergoing non-cardiac surgery. Median score of NRS 2002 in malnutrition group was 3  whereas 2  in control group (P < 0.001).The incidence of ED in malnutrition group was 41.8 % 205/490) which was higher than 31.5 % (134/425) in control group (P = 0.001), Fig. 05/490 whIn univariate analysis, malnutrition was related with increased risk of ED , Table Present study found that malnutrition was common in elderly patients undergoing non-cardiac surgery but it’s not associated with occurrence of emergence delirium after adjusted for confounders.Perioperative malnutrition has raised up more concern because it’s highly related with poor patient’s outcome , 2, 23. CAM-ICU was employed to diagnose ED in present study. One strength of this study was that we assessed the phenotype of ED . It seemAlthough previous studies had reported the association between malnutrition and postoperative delirium, this study did not find the relationship between malnutrition and ED , 30, 31.Beyond our result, the association between malnutrition and ED and POD should be investigated by further studies. First, metabolic abnormalities (such as ω-fatty acids insufficiency and glutamate–glutamine cycle dysfunction) possibly increase the vulnerability of the brain . The vulMultivariable analysis showed that age, cognitive impairment, allogeneic blood transfusion, temperature < 36 °C at PACU admission and average NRS pain score in PCAU were related with increased risk of ED. This finding was in accordance with previous studies , 34, 35.The strengths of present study included a relatively large sample size and strictly assessed delirium. This study had two limitations. First, our result was generated from a single center study which might limit its generality. Second, this was a cohort study which could not answer the causal relationship between malnutrition and delirium. Third, we did not collect the information of long-term medications. Previous studies showed that medications  might be associated with delirium . As manyOur result showed that malnutrition was common in older patients undergoing non-cardiac surgery. The incidence of emergence delirium was higher in patients with malnutrition than control group. However, malnutrition was not related with emergence delirium after adjusted for confounders. Further studies are needed to elucidate the relationship between malnutrition and emergence delirium.Additional file 1:Table S1. Nutritional risk screening 2002 scale (NRS-2002).


Although effective therapies exist, treatment rates of anxiety disorders (AD) are low, raising the question why affected individuals do not receive treatment. We provide data from the nationally representative German Health Interview and Examination Survey-2011 (DEGS1) on the help-seeking behavior and perceived treatment barriers of 650 subjects with Diagnostic and Statistical Manual of Mental Disorders’ (DSM-IV AD). Only 26% of all cases with AD in the community reported having had contact with mental health services because of their anxiety problems in their lifetime. 16% were currently receiving professional help, most frequently by psychotherapists (8%), psychiatrists (5%) and general practitioners (5%). 40% of all cases never even considered seeking help and 31% reported barriers to treatment, such as self-reliance (18%) or beliefs that treatments were ineffective (9%), unavailable (8%) or too stigmatizing (7%). Measures to increase treatment rates should thus target individual as well as public attitudes and health literacy to increase awareness of and access to evidence-based interventions.The online version of this article (10.1007/s10597-020-00767-5) contains supplementary material, which is available to authorized users. Anxiety disorders (AD) are the most prevalent group of mental disorders and are responsible for high levels of individual and societal disease burden . disorder-specific help-seeking and its barriers.To date, extensive data on general service use in AD is available , fear of stigma and reliance on self-management strategies  disorder-specific help-seeking rates for different health sectors and providers, (2) information on the extent and type of treatment with the most frequently utilized specialized services, (3) predictors of help-seeking, and (4) information on treatment barriers and dropout reasons in AD.Data for this study stem from the German Health Interview and Examination Survey for Adults—Mental Health module , a nationally representative survey designed to examine prevalence, impairment, and help-seeking for mental disorders in the German adult population , agoraphobia (AG), social anxiety disorder (SAD), GAD and SPEC. Diagnoses were assessed using the DIA-X software, a computerized German version of the Composite International Diagnostic Interview . The CIDI included a section on service use behaviors and disability, placed at the end of the interview. Participants were first asked whether they had ever thought about or had been recommended professional help due to mental health or psychosomatic problems. They were then presented a list with 27 services to indicate which of them they had ever contacted because of mental health problems. The list of services included primary care , inpatient  and outpatient institutions , as well as complementary institutions . For each institution, in-depth questions were asked to explore occasion, duration and type of intervention. This information was used to calculate 12-month vs. lifetime help-seeking rates.“Have you ever talked to a professional, e.g. medical doctor, psychologist, social worker, counsellor, clergy, about these problems?”). For SPEC, the question: “For what reason did you visit or contact these institutions?”, asked in the CIDI’s service use section, was used to indicate disorder-specific help-seeking.Participants were considered as help-seekers if they had (1) used at least one health service from the list of health care services and (2) had at least once talked to a professional about their anxiety symptoms. The latter information was included in the CIDI’s diagnostic section for each AD  due to mental or psychological problems” at any day within the past four weeks.“Has it ever happened that you thought about or have been recommended professional help, but then did not do it? Why was that?” Participants who never thought about seeking help were not asked for barriers and are here reported as individuals with “unperceived barriers”. Participants who reported to have discontinued at least one treatment were asked for dropout reasons using a list of 16 possible dropout reasons (yes/no). Item lists for services, barriers and dropout reasons are available in the supplement.The CIDI’s service use section also included gated questions regarding treatment barriers and potential reasons for dropout. Those who agreed to have ever thought about seeking professional help (see above) were then asked for treatment barriers using a list of 13 possible barriers (yes/no): α = 0.05.Statistical analyses were conducted using Stata 14.2 (StataCorp SD = 1.7) different services in their lifetime. The number of services contacted was highest in SAD  and lowest in GAD .Among all cases with a 12-month AD, 26.0% reported lifetime use of mental health services due to their disorder. Rates ranged from 9.5% in SPEC to 67.3% in PD .In the past year, 15.9% of all cases with 12-month AD contacted mental health services to manage their disorder, ranging from 3.9% in SPEC to 41.8% in PD  and higher education emerged as a predictor . The OR for more three or more comorbid AD was 13.22 (CI = 6.71–26.06). In a multivariate regression including all variables, only age ≥65 years  and the need factors “anxiety comorbidity”  and “presence of disability”  remained as predictors.In univariate regressions using the complete sample (N = 650), predisposing and enabling factors , as well as all need factors were associated with help-seeking  answered more detailed questions on treatment characteristics . Psychiatrists predominantly delivered psychopharmacological interventions (76.9%) or some type of individual psychotherapy (56.2%). Cognitive behavioral therapy (CBT) was rarely mentioned (2.6%), despite being a first line treatment. The average time-lapse from first treatment contact to the last was 11.3 years , with an average of 5.6 sessions per year , and a total number of about 30 sessions. On average, treatment by psychiatrists may thus be described as long-lasting treatment with rare contact.Treatment sessions with psychotherapists was delivered as a short-term treatment in about 40% of cases  and as a long-term treatment in 60% of cases . Duration of psychotherapy sessions was usually 50 min, as prescribed by reimbursement rules in Germany. 29.7% of participants with psychotherapy reported specifically having received some form of CBT, 70.1% any other type of psychotherapy. On average, patients reported having been in psychotherapy for 4.2 years  and received 23.2 sessions per year .Treatment by OR = 1.70, CI = 1.20–2.41).In both groups (psychiatrists and psychotherapists), about 50% of patients reported being fully or largely satisfied with their psychotherapeutic or psychiatric therapies. Dissatisfaction with treatment was associated with higher probability of dropout (χ2(1) = 9.86, p = 0.022). The frequency of specific barriers did not differ in help-seekers vs. non-seekers, and the number of perceived barriers  was not associated with help-seeking . Of the specific barriers, only self-reliance was associated with help-seeking .31.3% (N = 187) of all cases reported barriers to treatment Table . AnotherRegarding specific AD, cases with PD most frequently had considered seeking help (81.8%), compared to 58.4% and 34.6% of SPEC without comorbid AD. Treatment barriers were most frequently reported in GAD (46.6%) and least frequently in SPEC (28.2%). Overall, the ranking of different barriers was comparable between diagnoses. By visual inspection, cases with PD more frequently reported perceived ineffectiveness of treatment, while cases with SAD were more frequently deterred by social consequences of seeking treatment , and cases with GAD less frequently reported self-reliance.Of the 187 cases with lifetime help-seeking, 27.2% (N = 43) reported discontinuation of at least one mental health treatment. Among those, the most frequent dropout reasons were negative experiences with the provider , negative experiences with treatment , and perceived ineffectiveness of treatment (26.9%). Stigma (2.1%) and social pressure from others (1.8%) were rarely a reason for discontinuation  did not experience barriers to treatment, but simply had never thought about seeking help. The main explicit barriers were self-reliance  and assumed ineffectiveness of treatments (9%). A potential explanation of these major barriers might be limited health literacy. Mental health literacy refers to the amount of knowledge and beliefs about mental disorders, including the ability to recognize specific disorders and knowing where to seek help , driven primarily by long waiting periods. The average waiting time for outpatient psychological treatment in Germany is 20 weeks  have already been successfully targeted in the German population, whereas others are still prominent. These are a lack of awareness and, supposedly, mental health literacy for anxiety symptoms and treatments, delayed availability of treatments, and stigma-related barriers.Among those who crossed the Rubicon to seek formal help for their AD, psychiatrists and psychotherapists were the most frequently used providers. This is encouraging, as psychiatrists and psychotherapists are supposed to be the qualified specialists for diagnostics and treatment of AD. Several points however raise further questions: First, 40% of psychiatric and 20% of psychotherapeutic patients reported only a maximum of five contacts. These patients likely did not get a minimally adequate treatment . Third, 12-month use of inpatient services may have been underestimated because hospitalized individuals were not recruited for the survey. Fourth, we relied on participants’ self-report, which is subject to memory bias. For example, some help-seekers may not be aware whether they saw a psychiatrist, psychotherapist, or other medical practitioner. Fifth, 27% of the sample had multiple AD, which may have blurred the distinctions between disorders. Sixth, we did not differentiate primary AD and AD secondary to other problems, which may explain partly why individuals did not seek help due to symptoms of anxiety. Seventh, the item to examine disorder-specific help-seeking for SPEC differed from the other AD  which may have diminished help-seeking percentages in phobias. However, estimates of general service use, that were not biased by the type of question, were also substantially lower in SPEC (Supplement B). Finally, to detect help-seekers we asked participants whether they had ever talked to a professional about their AD. It is therefore possible that participants had used mental health services due to their AD before (mean duration of AD was 8.5 years), but only for other reasons in the last 12 months. This may have resulted in overestimated 12-month help-seeking percentages.Limitations included, first, that we used cross-sectional data, preventing straightforward causal inferences. Second, we examined 12-month AD, whereas individuals with former, now remitted episodes of AD were not included. This resulted in a high mean age of onset Below is the link to the electronic supplementary material.


Hyperventilation is common in pulmonary arterial hypertension and may be related to autonomic imbalance. Patients underwent exercise testing and hyperoxic breathing before and after bisoprolol treatment. We found that neither beta blocker treatment nor hyperoxic breathing in patients reduced hyperventilation at rest and during exercise, although it reduced heart rate. PAH is incurable, and treatment options are limited. The main symptoms of PAH are  dyspnoea, impaired exercise performance and reduced quality of life.Pulmonary arterial hypertension (PAH) is a rare but severe disease, characterized by obstructive remodelling of pulmonary arteries and leading to right ventricular failure.2) during exercise.35 Hyperventilation in PAH is related to disease severity6 and is associated with hypocapnia, a strong and independent prognostic value for survival. In addition, it may further exaggerate the feelings of dyspnoea. The mechanisms underlying hyperventilation in PAH are poorly understood, but include increased dead space ventilation and, possibly, autonomic imbalance and hypoxemia, leading to alveolar hyperventilation.810PAH patients often present with an increased minute volume (VE) at rest (i.e. hyperventilation) and a steeper slope of ventilation relative to carbon dioxide production  both at rest and during exercise compared to patients not on beta blockers. However, we are not aware of studies on the effect of long-term beta blocker use on ventilation in PAH patients. Yet, acute hyperoxic breathing showed to increase ventilatory efficiency in PAH patients during, but not at the start of exercise.It has been shown previously that four months of carvedilol treatment improves ventilatory efficiency in chronic heart failure patients.14 to investigate whether long-term beta blocker treatment or acute hyperoxic breathing, known to reduce sympathetic activity, lowers ventilation in PAH patients.Thus, we hypothesized that lowering sympathetic activity and/or acute hyperoxic breathing will reduce hyperventilation. We took advantage of the bisoprolol trial in PAH In short, all idiopathic PAH patients above 18 years of age and in New York Heart Association (NYHA) class II and III were screened for eligibility. Patients received six months of bisoprolol and placebo treatment in a cross-over manner, in random order. At baseline, before cross-over and at the end of the study, patients underwent CPET, arterial blood gas (ABG) analysis and ventilatory measurements. ABG was taken from the radial artery after at least 10 min of supine rest. Ventilatory measurements were performed in absolute resting condition, in a supine position in a quiet room. After breathing room-air for at least 10 min, VE, tidal volume (VT), respiratory rate (RR) and end-tidal CO2 (PETCO2) were measured breath-by-breath using a metabolic cart  and analysed as 20 s averages. Oxygen saturation (SaO2) was measured by pulse-oximetry  and heart rate by electrocardiography . After 10 min, the inspired oxygen fraction (FiO2) was changed. Measurements were performed with an FiO2 of 21% and 40%, in random order, both for 10 min. Blinding codes were broken on the last day of the third admission or at early termination of the study. However, all data were analysed in a blinded fashion. Statistics were performed using GraphPad Prism 7. Two-way repeated measures ANOVA was used to test for the effects of bisoprolol at baseline and after treatment, and to test the effects of hyperoxic breathing both after placebo and bisoprolol treatment. p < 0.05 was considered statistically significant. Continuous variables are presented as mean  ±  standard deviation (SD).Informed consent was obtained from all patients and a Data Safety Monitoring Board (DSMB) was appointed. The trial was registered at clinicaltrials.gov before recruitment was initiated . The study design and in- and exclusion criteria, and the cardiopulmonary exercise testing (CPET) protocol have been described in detail elsewhere. As such, a complete paired set of data is available from 15 patients.Eighteen patients were enrolled into the study from February 2011 until January 2014, of whom 17 underwent CPET and ventilatory measurements at baseline. Fifteen out of 17 patients received placebo for the full six months during the placebo arm of the study. In the bisoprolol arm of this study, 16 patients received bisoprolol for six months.ETCO2 and PaCO2. There were no signs of metabolic alkalosis.As a reflection of our general PAH population, NYHA class II and III were equally represented, mean age was 46 ± 14 years and there was a strong female predominance . Average mean arterial pressure (mPAP) was 48 ± 11 mmHg and 6-minute walking distance 468 ± 84 m. Results of CPET, ABG and ventilatory measurements at baseline and after placebo and bisoprolol treatment are shown in p = 0.004) at rest in normoxia, suggesting decreased sympathetic nerve activity. However, minute ventilation, tidal volume or respiratory rate were unchanged. No changes in PETCO2 or PaCO2 were observed, indicating an unchanged ventilation and perfusion. At baseline, VE/VCO2 slope was elevated (43.3 ± 10.8), indicating reduced ventilatory efficiency during exercise. Bisoprolol did not reduce heart rate at the start of CPET or at maximum exercise. Neither ventilatory efficiency, VEpeak, RRpeak, VTpeak or PETCO2 were changed after bisoprolol treatment.The reached dosage of bisoprolol (4.5  ±  3.3 mg on average) was associated with a reduction in heart rate of 12 bpm (2 = 40% significantly increased SaO2 with 3.9% (p = 0.0012) and decreased heart rate with 3.6 bpm (p = 0.0044). However, no effect was found on ventilation as reflected by VE, RR, VT and PETCO2. In addition, no interaction-effect between bisoprolol treatment and hyperoxic breathing at rest was found for any of the outcome variables, indicating no cumulative or opposing effects of bisoprolol and hyperoxic breathing.Ten minutes of hyperoxic breathing with FiOCollectively, our results show that ventilation at rest is not affected by bisoprolol or hyperoxic breathing, either alone or in combination. Furthermore, bisoprolol did not improve ventilatory inefficiency during exercise. The reductions in heart rate following bisoprolol treatment and hyperoxic breathing strongly suggest decreased SNS activity. or the level and short duration of hyperoxia. However, oxygen has also central effects on respiratory centres in the brain stem, possibly via ROS signalling, which causes long-lasting increases in ventilation. Whilst the use of this effect is unknown, it may have masked the initial reduction in ventilation due to peripheral chemoreceptor silencing. Alternatively, other factors may drive ventilation in PAH, including mechanical forces in the pulmonary circulation, low work rate lactic acidosis, hyperkalaemia and altered central regulation of breathing.18 Given the strong prognostic value of VE/VCO2 and hypocapnia, unravelling the aetiology of hyperventilation in PAH may help to improve treatment and thereby enhance survival and quality of life.Limitations of the present study are the small sample size and the wide range of bisoprolol doses in our patients. We did not directly measure sympathetic nerve activity or chemoreceptor activity, and therefore cannot prove nor exclude the role of the sympathetic nervous system in hyperventilation in PAH. The lack of effect in the current study may thus be related to the relatively low dose of bisoprolol, the type of beta blocker,Click here for additional data file.Supplemental material, sj-pdf-1-pul-10.1177_20458940211057890 for Bisoprolol and/or hyperoxic breathing do not reduce hyperventilation in pulmonary arterial hypertension patients by Eva L. Peters, Jasmijn S.J.A van Campen, Herman Groepenhoff, Frances S. de Man, Anton Vonk Noordegraaf and Harm J. Bogaard in Pulmonary CirculationClick here for additional data file.Supplemental material, sj-pdf-2-pul-10.1177_20458940211057890 for Bisoprolol and/or hyperoxic breathing do not reduce hyperventilation in pulmonary arterial hypertension patients by Eva L. Peters, Jasmijn S.J.A van Campen, Herman Groepenhoff, Frances S. de Man, Anton Vonk Noordegraaf and Harm J. Bogaard in Pulmonary Circulation


Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, and the risk relates to pre-existing risk factors and ADT modalities. Despite ethnic differences in the prevalence of CV risk factors and variations of CV mortality, data on ADT-related cardiotoxicities in the Asian population remain inconclusive. Our registry-based study investigated ADT-related major adverse cardiovascular events (MACE) after primary or salvage RT.Our study combined two prospectively established registry databases from National Cancer Center Singapore and National Heart Center Singapore. The primary endpoint is time to first MACE after treatment. MACE is defined as myocardial infarction, stroke, unstable angina, or cardiovascular death. Two types of propensity score adjustments, including ADT propensity score as a covariate in the multivariable regression model and propensity score weighting, were applied to balance baseline features and CV risk factors between RT alone and RT + ADT groups.n = 494) or RT + ADT (n = 1446) were included. After a median follow-up of 10 years (RT) and 7.2 years (RT+ ADT), the cumulative incidence of MACE at 1, 3 and 9 years was 1.2, 5 and 16.2% in RT group, and 1.1, 5.2 and 17.6% in RT + ADT group, respectively. There were no differences in the incidence of MACE between 2 groups . Pre-treatment CV risk factors were common (80%), and CV disease (15.9%) was the second leading cause of death after prostate cancer (21.1%). On univariate analysis, older age, Indians and Malays, pre-existing CV risk factors, and history of MACE were associated with higher MACE risk. After propensity score adjustments, there remained no significant differences in MACE risk between RT + ADT and RT group on multivariable analysis.From 2000 to 2019, 1940 patients received either RT alone (In our registry-based study, ADT is not associated with increased risk of major cardiovascular events among Southeast Asian men with prostate cancer after curative radiotherapy.The online version contains supplementary material available at 10.1186/s40959-022-00131-4. Since the effect of castration on serum phosphatases in prostate cancer patients was first reported in 1941, androgen-deprivation therapy (ADT) has become the mainstay treatment for advanced and metastatic prostate cancer. Combined with radiotherapy (RT), ADT has been shown in several randomized trials to improves survival in intermediate-and high-risk localized disease, as well as locally advanced and node-positive disease . HoweverPatients received curative radiotherapy are often diagnosed at an advanced age, and preexisting CV risk factors are common. ADT is most commonly given in the form of gonadotrophin-releasing hormone (GnRH) agonist with radiotherapy. In several retrospective studies, GnRH agonist is associated with higher CV risk compared with orchiectomy and GnRH antagonists –9. RecenCardiovascular disease has become the leading cause of death in men with prostate cancer in the United States . CardiovOutcomes Research in DRO Cancer Care (“Outcomes Study”) (CIRB ref.: 2016/2020/B) is a prospectively established registry database at National Cancer Centre Singapore. Outcomes Study collects comprehensive real-world data (RWD) through Electronic Medical Record (EMR) and patient-reported outcomes (PRO) during cancer patients’ entire treatment and follow-up period. Singapore Cardiac Data Bank (SCDB) was established in 2000 as a national data bank of cardiovascular diseases and procedures (NIH: NCT03760705). SCDB modules include various intervention procedures and cardiac surgery . IndividThe current study included Singapore male residents with non-metastatic prostate cancer who started treatment from January 2000 to September 2019. Initial data collection of medical history was made by the treating radiation oncologist at the first consultation. Physicians systemically assessed cardiovascular risk factors including Body Mass Index (BMI), smoking history, diabetes mellitus, hypercholesterolemia, hypertension, stroke, coronary artery disease, type of intervention or surgery for cardiac conditions, medications, and other significant cardiac histories through EMR and history taking. New cardiovascular events after treatment and cause of death were verified by board certified cardiologists.The decision on ADT was made by oncologists according to D’Amico risk classification in localized disease or pathological findings and PSA after radical prostatectomy , 4, 18. The primary endpoint was time to first Major Adverse Cardiovascular Events (MACE) after the start of treatment for prostate cancer. MACE was defined as myocardial infarction, stroke, unstable angina requiring intervention, or cardiovascular death. The start date of treatment was defined as the start of ADT for patients who had received RT and ADT (RT + ADT) and the start of RT for RT only patients. Time to MACE was censored at the initiation of palliative systemic therapy  when patients developed recurrence or metastases. Alive or lost to follow-up patients without recurrence, metastases or MACE were censored at their date of the last follow-up.Baseline characteristics of the two treatment groups were compared using the Chi-square or Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. A competing risk approach was used to estimate the cumulative incidence of MACE as the cause of failure, with deaths due to non-cardiovascular causes as competing events. Comparison of cumulative incidence curves was made using the Gray’s test.p < 0.05 were included in the multivariable model. Proportional hazard (PH) assumption was verified for each variable included in the multivariable model by including a time-by-variable interaction term for each variable.Univariate and multivariable Fine and Gray’s regression model was used to examine the association of ADT and other covariates with time to first MACE. Variables with univariate p < 0.05.Sensitivity analysis was performed to assess the impact of unbalanced baseline characteristics on the association of ADT with the risk of MACE via 2 types of propensity score adjustments. The first adjustment was made by including the probability of receiving ADT (p) as a covariate in the multivariate Fine and Gray’s regression model for time to first MACE. The second adjustment was made via propensity score weighting where each RT + ADT patient was assigned a weight of (1/p) and each RT only patient was assigned a weight of (1/1-p). The probability of receiving ADT was derived based on a logistic regression analysis with all baseline characteristics included as covariates in the model. Goodness of fit and discrimination ability of the fitted logistic model were assessed based on the Hosmer-Lemeshow test and area under the receiver operating characteristics curve (AUC), respectively. All statistical analyses were performed using Stata 15.0. Statistical significance was defined as 2-sided n = 1702, 87.7%) received primary radiotherapy; 12.3% (n = 238) were treated as salvage or adjuvant radiation. Among the RT + ADT patients, 96.9% (n = 1401) received GnRH agonists  and 61.5% (n = 889) received more than 6 months’ hormonal treatment.The study cohort consisted of 1940 patients was analyzed, of which 494 received RT only and 1446 received RT + ADT. The baseline characteristics were summarized in Table p = 0.010), on account of the higher percentage of patients in this group with hypertension, dyslipidemia and diabetes (Supplementary Table p = 0.002) (Supplementary Table Preexisting cardiovascular risk factors were common in our study population. Over 80% of the patients had at least one risk factor across the three main domains: lifestyle (such as smoking and obesity defined as BMI > 27.5), cardiovascular , and history of MACE. CV risk factors were more common in RT + ADT patients , as well as other deaths not related to prostate cancer and CV diseases  than RT alone group.The median follow-up duration was 10 years  for RT alone group and 7.2 years  for RT + ADT group. This could be attributed to the higher incidence of deaths over time within the RT + ADT patients. The risk of all causes mortality amongst RT + ADT group was 1.23 times (95% CI 0.99–1.52) that of RT alone group (Supplement Table p = 0.969)   . In particular, the incidence of new MACE at 1,2 and 3 years was 3.2, 5.4, and 7.9% in the RT group, and 3.0, 6.5, and 11.7% in the RT + ADT group, respectively. In terms of mortality, cardiovascular disease was the second most common cause of death (17.8%) after prostate cancer (21.1%)  Fig. . Subgroup < 0.001). Adjusting for all statistically significant factors in univariate analysis, there remained no significant differences in the risk of MACE between RT + ADT and RT groups on multivariable analysis.On univariate analysis, older age (above 70), Malays and Indians (relative to Chinese), baseline CV risk factor and GnRH antagonist were associated with greater CV risk Table . Patientp = 0.409) and a high discrimination ability (AUC = 0.812). The conclusion that ADT was not associated with the risk of MACE from the main analysis remained unchanged in both propensity score adjustments  between degarelix or leuprolide groups [Cardiovascular disease is the leading cause of non-cancer deaths in men with prostate cancer. The incidence of secondary CV events after ADT varies greatly depending on underlying CV risk factors. A longitudinal study (RADICAL PC) reported that two-thirds of a cohort of 2492 men with prostate cancer had high CV risk with 22% having established CV disease . In our e groups . In the e groups . GnRH ane groups . In our e groups , 19, ADTThe different findings on ADT-related cardiotoxicities between our cohort and previous studies in Caucasian population could be multi-factorial. First, identifying men at risk for secondary CV events after ADT remains challenging. The current approach mainly relies on routine CV risk factors assessment. Novel cardiac blood biomarkers including N-terminal pro-B-type natriuretic peptide (NTproBNP) C-reactive protein (CRP), and high-sensitivity troponin (hsTn) are being evaluated to predict ADT-related CV toxicities . Novel pOur observational study does have several limitations and needs interpretation within context. First, there is an inherent limitation for all retrospective studies, and the selection for ADT was not randomly assigned. It remains possible preexisting CV risk factors affect the decision on choice and duration of ADT. To minimize the selection bias, we performed a sensitivity analysis with propensity score adjustment for unbalanced baseline characteristics, and the conclusion remains the same. Second, despite initial cardiovascular risk assessment by oncologists, further management of various risk factors was done by the primary care physicians or cardiologists. However, prescription information within the EMR of the public healthcare system accurately determines the duration of ADT and other medications for primary or secondary prevention of cardiovascular disease. Third, Singapore Cardiac Databank includes information from the public healthcare system and may under-represented some of CV events from private providers. However, the database includes 80% of hospital care delivered in public institutions and reflects the nationwide pattern of practice. The strengths of the current study are the large size and complete long-term follow-up in the Southeast Asian men with prostate cancer from two prospectively established registry databases. Compared with previous studies of the Chinese or Japanese population, our study included a more diversified multi-ethnic group from Southeast Asia.Cardiotoxicities associated with anticancer therapies are increasingly recognized and the prevention remains challenging in cancer survivorship . ExcessiIn our registry-based observational study, ADT was not found to be associated with increased risk of major cardiovascular event among Southeast Asian men received curative radiotherapy in two types of propensity score adjustments.Additional file 1: Table SA1. Baseline cardiovascular disease risk factor by treatment group. Table SA2. Baseline drug use and surgery/intervention for IHD by treatment group. Table SA3. Multivariable logistic regression of receiving RT + ADT treatment. Table SA4. Univariate and multivariable analysis of MACE after start of treatment with treatment propensity score included as a covariate. Table SA5. Univariate and multivariable analysis of MACE after start of treatment with treatment propensity score weighting. Table SA6. Cumulative Incidence Rate of Mortality by Causes. Table SA7. MACE by Type of Event.


In our multivariable model, coccidioidomycosis-associated hospitalisation was associated with age group 40–49 years  = 1.50  1.43–1.59)), African American race ), residing in a large rural town ), uncomplicated diabetes (aOR = 1.47 (95% CI 1.41–1.52)) chronic obstructive pulmonary disease (aOR = 1.59 (95% CI 1.54–1.65)) and higher number of comorbidities (aOR = 1.02 (95% CI 1.02–1.03) for each point in the Elixhauser score). Identifying persons at highest risk for hospitalisation with coccidioidomycosis may be helpful for future prevention efforts.Coccidioidomycosis is endemic in the Southwestern United States. Disseminated infection can be life-threatening and is responsible for hospitalisation and significant healthcare resource utilisation. There are limited data evaluating factors associated with hospitalisation for coccidioidomycosis. We conducted a cross-sectional study to assess incidence and factors associated with coccidioidomycosis-associated hospitalisation in California and Arizona. We analysed hospital discharge data obtained from the State Inpatient Dataset for California and Arizona between 2005 and 2011 and performed multivariable logistic regression examining factors associated with coccidioidomycosis-associated hospitalisation. During our time frame, we found 23 758 coccidioidomycosis-associated hospitalisations. Coccidioidomycosis incidence was over sixfold higher in Arizona compared to California (198.9  Coccidioides species spores. This infection is most frequently found in areas where the soil is dry and alkaline, including the southwestern United States, parts of Mexico and Central and South America [Coccidoides spp. spores for populations in endemic areas, specifically military personnel, prisoners and solar panel workers [Coccidioidomycosis is a fungal infection caused by the inhalation of  America , 2. The  America . However America . Additio America . Recentl workers –7.Coccidioidomycosis cases are poorly understood. However, climate change, and increased migration of susceptible person to endemic areas have been suggested as possible explanations for this increase [In the U.S., coccidioidomycosis is a nationally notifiable disease. Data from the Centers for Disease Control and Prevention's National Notifiable Disease Surveillance System (NNDSS) have demonstrated secular shifts in coccidioidomycosis incidence. For example, coccidioidomycosis incidence has increased from 5.3/100 000 population in 1998 to 42.6/100 000 population in 2011 [Coccidioidomycosis represents a substantial healthcare burden within California and Arizona, two highly endemic states where greater than 95% of all cases are reported –13. MediWhile there are data examining risk factors for coccidioidomycosis, there are limited studies evaluating factors associated with coccidioidomycosis hospitalisation. Moreover, several of these studies utilised national administrative data sources that do not hone down on the U.S. states that are most affected by coccidioidomycosis –21. Thervs. hospitalisation associated with other causes in California and Arizona. Hospital discharge data were obtained from the State Inpatient Dataset (SID) for both California and Arizona for years 2005–2011. The SID represents all-payer inpatient discharge information collected from nonfederal  hospitals. Combining both California and Arizona SID for years 2005–2011 resulted in a cohort of over 33.0 million inpatient stays.We conducted a cross-sectional study to assess the sociodemographic and comorbidity factors associated with coccidioidomycosis-associated hospitalisation The study population included all inpatient discharges for The Healthcare Cost and Utilization Project (HCUP)-defined hospitals from California and Arizona for the years 2005–2011. A coccidioidomycosis case was defined as a primary or secondary diagnosis identified by the International Statistical Classification of Diseases and Related Health Problems version 9 (ICD-9) codes assigned for coccidioidomycosis . PopulatOur primary outcome was coccidioidomycosis-associated hospitalisation. To assess factors that may be associated with these hospitalisations, we examined a pre-selected group of sociodemographic and patient-level comorbidity factors. These factors were chosen based on possible associations suggested by the medical literature to be associated with a higher rate of coccidioidomycosis infection or severe coccidioidomycosis infection , 19 and We hypothesised rural persons were at a higher risk given the relative lack of pavement, more contact with soil and potentially more exposure to the outdoor environment. Urbanisation was stratified into four rural–urban patient locations, urban (metropolitan), large rural town (micropolitan), small rural town and isolated small rural area. The stratification used by HCUP to generate the condensed urbanisation variable within the SID database is based on rural–urban commuting areas (RUCA) and assignment into ZIP codes using population and commuting information from the 2000-year Census . PatientEnvironmental factors such as seasonal rainfall, earthquakes and soil disruptions have been shown to be associated with higher incidences of reported coccidioidomycosis cases , 28. We P value of <0.20 in these analyses were included in a logistic multivariable regression analysis. To assess multicollinearity among variables in our multivariable model, variance decomposition proportion (VDP) analysis was performed using the SAS macro COLLIN [® version 9.2  [Our study population consisted of persons hospitalised due to coccidioidomycosis, cases and non-cases. Non-cases represent hospitalised patients admitted for non-coccidioidomycosis diagnoses. Bivariate analyses were performed and all factors with a o COLLIN . All anaarolina) .vs. 29.6/100 000 population . A significant negative correlation was found between seasonal rainfall and coccidioidomycosis-associated hospitalisations for California for the 1-, 2- and 3-month lag times but not for the zero month lag time .In bivariate analysis, we found numerous predictors associated with coccidioidomycosis-associated hospitalisations that were included in our multivariable analysis . In multCompared to those living in urban areas, coccidioidomycosis-associated hospitalisation was associated with residence in a large rural area (aOR 2.28 (95% CI 2.19–2.39)) and inversely associated with isolated rural areas (aOR 0.95 (95% CI 0.84–0.91))). Compared to those residing in higher (fourth quartile) income areas, coccidioidomycosis-associated hospitalisation was lower in those residing in first quartile (aOR 0.87 (95% CI 0.84–0.91)), second quartile (aOR 0.78 (95% CI 0.74–0.81)) and third quartile areas (aOR 0.87 (95% CI 0.83–0.81)). Coccidioidomycosis-associated hospitalisation was associated with Arizona residence  (aOR 6.42 (95% CI 6.25–6.60)).Higher Elixhauser score was associated with coccidioidomycosis-associated hospitalisation (aOR = 1.02 (95% CI 1.02–1.03)) for each point in the Elixhauser score). Persons with AIDS and obesity had reduced odds of coccidioidomycosis-associated hospitalisation (aOR 0.75 (95% CI 0.58–0.99) and aOR 0.78 (95% CI 0.74–0.83), respectively). Uncomplicated diabetes (aOR 1.47 (95% CI 1.41–1.52)) and chronic pulmonary disease (aOR 1.59 (95% CI 1.54–1.65)) showed an increase in the odds of coccidioidomycosis-associated hospitalisation. Coccidioidomycosis-associated hospitalisation was associated with an increased mortality compared to the referent group who were alive at hospital discharge.  (aOR 1.12 (95% CI 1.03–1.22)).Using very large HCUP administrative datasets we had several novel observations related to coccidioidomycosis-associated hospitalisation, including relative incidence, association with important clinical, demographic and climatic factors, specifically rainfall. To the best of our knowledge, this is the first study to evaluate sociodemographic and comorbidity predictors of hospitalisations associated with coccidioidomycosis using a large inpatient population-based dataset.et al. similarly found an increased relative risk for hospitalisation among African Americans consistent with our findings [We found many sociodemographic predictors such as gender, age, race/ethnicity and place of residence that had relationships with coccidioidomycosis-associated hospitalisation. Not surprisingly, African Americans had the highest odds of coccidioidomycosis-associated hospitalisation of any racial/ethnic group. African-American race is associated with a higher risk of disseminated infection and greater disseminated disease's severity ; thus thfindings . We founfindings . ElderlyInterestingly, we found that lower income patient household (first through third quartile) had a lower odds for coccidioidomycosis-associated hospitalisation. This finding surprised us and the reasons for this association are unclear. It is possible that higher-income populations have better insurance and thus might have their coccidioidomycosis infection managed as an outpatient with a primary care provider, or perhaps are diagnosed earlier, preventing the need for coccidioidomycosis-associated hospitalisation.Hospitalised patients in Arizona were at a much higher risk for coccidioidomycosis-associated hospitalisation than patients residing in California. Our findings are consistent with overall coccidioidomycosis incidence ; a 2016 study found that Arizona accounted for 66% of cases while California accounted for 31%  which suWe also found that several comorbidities that were associated with coccidioidomycosis-associated hospitalisation, including uncomplicated diabetes and chronic obstructive pulmonary disease. Supporting our findings, a prior study showed diabetes to be a contributing cause of death in coccidioidomycosis patients,  suggestiInterestingly, in our multivariable model, obese patients were at reduced risk of coccidioidomycosis-associated hospitalisation, which was an unexpected and novel finding. Possible reasons for this relationship are not readily apparent. Perhaps obese patients who were hospitalised were more likely to be hospitalised due to complications of obesity, such as cardiovascular disease. Higher comorbidity score was associated with coccidioidomycosis-associated hospitalisation (aOR = 1.02 (95% CI 1.02–1.03)) for each point in the Elixhauser score), suggesting that more severe forms of coccidioidomycosis requiring hospitalisation are more common in those with underlying co-morbidities. Studies examining coccidioidomycosis-associated death, which is obviously another severe complication of coccidioidomycosis, found several comorbidities associated with death . Our stuCoccidioides arthrospores are present at a higher concentration in the soil after heavy rains and as the soil dries up wind or soil disruption spreads the arthrospores [The association between climate and coccidioidomycosis incidence is based on the ‘grow’ and ‘blow’ hypotheses . This hyrospores , 42. Introspores . AlternaOur study had limitations. First, our case definition included patients with a primary or secondary diagnosis code for coccidioidomycosis. Inclusion of a secondary diagnosis could result in an overestimation for the incidence of disease due to diagnostic coding error since the hospitalisation may have been due to a non-coccidioidomycosis primary diagnosis and the patient may have had chronic coccidioidomycosis that did not trigger the hospitalisation. However, among cases included based on a secondary diagnosis of coccidioidomycosis the two most prevalent primary diagnoses were HIV and pneumonia. Since HIV infection without complications is not a reason for hospitalisation and pneumonia could be related to coccidioidomycosis pulmonary infection, these patients' hospitalisations may be due to coccidioidomycosis. Additionally, our investigation followed previously reported methods for epidemiological study inclusion criteria . Second,Our investigation has strengths. First, ours is the first study to examine the association between coccidioidomycosis-associated hospitalisation and comorbidity measures including the relatively new Elixhauser index. Secondly, to our knowledge, our study is novel in that it utilised a large population-based cohort consisting of hospitalised patients from two highly endemic areas, Arizona and California where prior studies used both inpatient or outpatient cohorts from individual endemic states. Finally, we examined a large period of time from multiple SID databases, thus avoiding relationships that may be present only in low or high incidence years and the peculiarities specific to more epidemic years.In conclusion, we found multiple sociodemographic predictors and comorbidities associated with coccidioidomycosis-associated hospitalisation in an inpatient dataset consisting of individual-level data obtained from the State Inpatient Datasets for Arizona and California. Disseminated coccidioidomycosis confers a high mortality rate and significant cost . TherefNone.The data that support the findings of this study are available from HCUP. Restrictions apply to the availability of these data, which were used under agreement for this study. Data are available from Deborah Kupferwasser with the permission of the HCUP.


Cryptococcal meningitis (CM) remains a leading cause of death in HIV-infected patients, despite advances in CM diagnostic and therapeutic strategies. This study was performed with the aim to develop and validate a novel scoring model to predict mortality risk in HIV-infected patients with CM (HIV/CM).Data on HIV/CM inpatients were obtained from a Multicenter Cohort study in China. Independent risk factors associated with mortality were identified based on data from 2013 to 2017, and a novel scoring model for mortality risk prediction was established. The bootstrapping statistical method was used for internal validation. External validation was performed using data from 2018 to 2020.+ T-cell count, and urea levels, were associated with poor prognosis in HIV/CM patients. The novel scoring model could effectively identify HIV/CM patients at high risk of death on admission . When the cut-off value of 5.5 points or more was applied, the sensitivity and specificity was 74.1 and 83.8%, respectively. Our scoring model showed a good discriminatory ability, with an area under the curve of 0.879 for internal validation via bootstrapping, and an area under the curve of 0.886 for external validation.We found that six predictors, including age, stiff neck, impaired consciousness, intracranial pressure, CD4Our developed scoring model of six variables is simple, convenient, and accurate for screening high-risk patients with HIV/CM, which may be a useful tool for physicians to assess prognosis in HIV/CM inpatients. Cryptococcus neoformans, is a leading opportunistic infection in humans, and a common cause of meningitis in adults living with Human Immunodeficiency Virus (HIV) [Cryptococcal meningitis (CM), caused by infection with the fungal pathogen us (HIV) –4. Despius (HIV) . It has us (HIV) , 7.+ T-cell counts have been evaluated for their potential to predict mortality in HIV infected patients with CM (HIV/CM patients) [Previous studies have focused on identifying key predictors of early mortality in patients who died within 2 to 10 weeks of initiating treatment. Many potential risk factors, like age, impaired consciousness, and CD4atients) –10. Alsoatients) , 5, 8. Aatients) .We therefore comprehensively considered clinical symptoms and signs of CM, characteristics of cerebrospinal fluid changes in CM, and prognosis in CM, and have developed a scoring model to accurately clinically classify and stage CM for attending clinicians working in primary hospital settings. Using the proposed scoring model, clinicians may accurately predict clinical outcomes in HIV/CM patients at admission from assessment of basic clinical parameters, thus facilitating expeditious and appropriate therapeutic interventions .This retrospective multi-center cohort study included HIV-infected patients diagnosed with CM from 2013 to 2020 at the following 10 Chinese medical centers: Chongqing Public Health Medical Center, The First Hospital of Changsha, Liuzhou General Hospital, Guiyang Public Health Clinical Center, Public Health Clinical Center of Chengdu, Yunnan Provincial Infectious Disease Hospital, The Fourth Affiliated Hospital of Harbin Medical University, Guangxi Longtan Hospital, The First Affiliated Hospital of Zhejiang University, and The Sixth People’s Hospital of Zhengzhou. Data from all 10 centers from 2013 to 2017 were used to develop the derivation cohort. The validation cohort was based on data obtained from 6 of the 10 mentioned medical centers above between 2018 and 2020.+ T-cell count, HIV RNA viral load, ICP, CSF glucose, clinical outcome, and other clinical data were analyzed. The observation starting point was HIV-associated CM diagnosis after admission to hospital. The observation endpoint was patient death, or survival at 28 days after HIV/CM diagnosis. The survival rate during the 28 days post-diagnosis was calculated as the endpoint event.The patients’ clinical data, including age, headache, maximum body temperature, stiff neck, impaired consciousness, weight loss, neutrophil count, total bilirubin (TBIL), hemoglobin (HGB), platelet (PLT), urea, creatinine, CD4Cryptococcus neoformans in CSF via India ink staining, CSF culture or CSF cryptococcal antigen assay [Confirmation of HIV infection was established by positivity of the HIV antibody test via Western Blot, and a positive HIV RNA polymerase chain reaction . The diaen assay , 15.Categorical variables were compared using the Chi-squared test or Fisher’s Exact test, and continuous variables were compared using Student’s t-test or the Mann-Whitney U-test. The Kolmogorov–Smirnov test was used to assess the normality of the sample data distribution. Data are presented as mean ± standard deviation, or median (interquartile range) for continuous variables, and as frequency and percentage for categorical variables.p values less than 0.1 in the above steps were further included in the multivariate logistic regression analysis. Multivariate analyses were performed to identify predicted risk factors for death. From the logistic regression model, coefficient scores were extracted and assigned for each factor with their respective β coefficients. To make the scores approach an integer or relative integer, and in order to be intuitive for the user, we arbitrarily assigned the regression coefficient of ICP (0.788) as equivalent to one risk point (risk score = 1), and all other β coefficients were then divided by 0.788 to determine the score of coefficient for each risk factor (rounded to the nearest number in units of 0.5). For example, the coefficient of 1.505 associated with CD4+ T-cell counts ≤50 cells/μL was divided by 0.788, and the answer thus obtained  was rounded-off to 2.0. A specific risk score is derived by a calculation of each coefficient score multiplied by each point score. The risk score for an individual was obtained by summation of the scores for each of the risk factors.In the derivative cohort, the relationship between baseline demographic characteristics, clinical characteristics, and laboratory data and all-cause mortality (as measured at day 28) were examined by univariate analyses. Variables with To verify the validity of the scoring model, a receiver operating characteristic curve (ROC) was plotted and an area under the curve (AUC) was calculated . The perp-value < 0.05 was considered to be statistically significant.Statistical analyses were performed using the SPSS software package for Windows  and R statistical software . For all tests, a A total of 903 HIV/CM patients from 10 participating hospitals were screened in this study. Of these, 348 patients were excluded due to data loss , and three patients were excluded for being under 18 years of age. As a result, 386 patients were assigned to the derivation cohort, of which 328 survived and 58 died. The all-cause mortality rate was 15.0%. Of the 169 patients in the validation cohort, 23 patients succumbed to CM, with an all-cause mortality rate of 13.6%. A flow chart of our study population selection and study process is shown in Fig. p < 0.0001). In addition, HIV RNA viral load, CSF glucose, and urea levels were associated significantly with patient mortality (p < 0.05). However, the analysis of other clinical and laboratory data, comorbidity and complications, including presence of headache, weight loss, neutrophil count, creatinine, CD4+ T-cell count, sex, ART at hospital admission, high body temperature, seizures, time from symptom onset to hospital admission, whether in association with bacterial pneumonia, pneumocystis pneumonia, tuberculosis, cytomegalovirus infection, diabetes, liver cirrhosis, and cerebral infarction did not differ statistically between the survival and non-survival populations  + 1 × (ICP) + 2.5 × (impaired consciousness) + 2 × (stiff neck) + 1 × (urea) + 1.5 × (age).The 12 variables with a re Table  assignedre Table  multiplip < 0.001) , and had an AUC of 0.876  Fig. . Using tp < 0.001)  according to their respective scores. The results indicated that patients with higher scores showed poorer prognosis in our cohort. In the derivation cohort, the cumulative mortality rate in the high-risk group was 44.8% (43/96), which was significantly higher than the mortality rate in the low-risk group  (p = 0.712), indicating that the model had a favorable goodness of fit.The AUC of the score for predicting mortality risk was 0.879 . Sensitivity of the risk scoring model was calculated to be 73.9% , specificity was 85.6% , PPV was 44.7% , NPV was 95.4% , and the Youden index was 62.8%. This indicates that the predictive model is effective in predicting mortality in HIV/CM inpatients. Table p < 0.001) .The performance of the new scoring model is externally verified by the validation cohort. The comparison results from the validation cohort showed that the model had good performance in predicting mortality  . In a re2O, and more than a quarter having an opening ICP of above 350 mmH2O [2O) is associated with altered mental status, visual and hearing loss, other symptoms of cranial nerve dysfunction, and even impaired consciousness or death. In a large trial of CM treatment, almost all the early deaths (13/14) and 40% of the deaths during weeks 3 through week 10 were associated with elevated ICP (>250 mmH2O) [2O pressure group and > 350 mmH2O pressure group, than those with pretreatment opening pressures <250 mmH2O  [2O) had a higher mortality rate  than those who had a normal ICP at baseline  [2O or less, or 50% of the initial opening pressure measured [2O), additional LP (including daily LP) may be performed as necessary until the pressure is adequately controlled [Elevated ICP is common during the diagnostic workup for CM, with more than half of HIV/CM patients reportedly having an opening ICP of over 250 mmH50 mmH2O . Raised 0 mmH2O) . Graybilnalysis) . Another, 26.1%) . Consistmeasured . At the measured . Of notentrolled . In a st+ T-cell count is associated with a poor prognosis of CM. Pastick’s study found that a CD4+ T-cell count of < 50 cells/μL was an important predictor of epilepsy in patients with HIV/CM [+ T-cell count of < 50 cells/μL was associated with higher 18-week mortality, compared to a CD4+ T-cell count of 50–100 cells/μL and 100–200 cells/μL [+ T-cell levels in HIV/CM helps identify patients with increased risk of poor prognosis. Impaired consciousness and stiff neck are common clinical manifestations and symptoms in patients with CM, and their incidence was significantly higher in patients with unfavorable outcomes [Low CD4h HIV/CM . A studycells/μL . This fioutcomes . Wu et aoutcomes . High urIn summary, our novel scoring model is likely to be useful for predicting outcomes in patients with HIV/CM. Utilizing our scoring model, clinicians may stratify affected patients so that they may decide upon appropriate patient-specific treatment regimens, or, if indicated, make early referrals to specialist care, particularly in primary care settings. Higher scores obtained via our novel system may serve as an early warning for this particular group of patients. Low scores may indicate that affected patients may be placed in a milder risk category, which may help reduce inappropriate utilization and wastage of expensive medical resources . AdditioThe present study has limitations. First, as our study was retrospective in nature, it therefore may be susceptible to the various limitations inherent to retrospective studies in general. Second, the participants in our study were all Chinese nationals, and whether our proposed scoring model can successfully be used for other population or racial groups is unknown, and warrants further research. Additionally, there are a few potential risk factors for which we did not have adequate information in our data set, and were not included in our data analysis, and inclusion of these risk factors into our model may further improve the prognostic accuracy of our mortality risk score. These potential risk factors include cryptococcal antigen titers (CrAg titers) in both serum and CSF, body mass index (BMI), CSF protein levels, CSF chloride levels, dose and course length for Amphotericin B, and other central nervous system symptoms . There is evidence that the higher CrAg titers in both serum and CSF are associated with an increased risk of mortality in HIV/CM , and thuIn conclusion, our study outlines a simple and useful scoring model developed to predict mortality in HIV/CM. The sensitivity, specificity, and accuracy of the scoring system after verification are meaningful and applicable to clinical medical practice in areas where HIV/CM prevalence and mortality remains notably high. We envision that our scoring model may be widely used in these settings in order to effect demonstrable reductions in HIV/CM mortality.