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As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease. The fragmented data collected during the initial emergency limited the possibility of investigating the effect of highly correlated covariates and of modeling the interplay between risk factors and medication. The present study is based on comprehensive monitoring of 576 COVID-19 patients. Different statistical approaches were applied to gain a comprehensive insight in terms of both the identification of risk factors and the analysis of dependency structure among clinical and demographic characteristics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2), but whether or not renin-angiotensin-aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial. The survival tree approach was applied to define a multilayer risk stratification and better profile patient survival with respect to drug regimens, showing a significant protective effect of RAASi with a reduced risk of in-hospital death. Bayesian networks were estimated, to uncover complex interrelationships and confounding effects. The results confirmed the role of RAASi in reducing the risk of death in COVID-19 patients. De novo treatment with RAASi in patients hospitalized with COVID-19 should be prospectively investigated in a randomized controlled trial to ascertain the extent of risk reduction for in-hospital death in COVID-19.
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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , SARS-CoV-2 , Anciano , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina , COVID-19/mortalidad , COVID-19/fisiopatología , COVID-19/virología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Sustancias Protectoras , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
PURPOSE: Primary purpose was to assess changes of bone mineral density (BMD) in diffuse large B cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP (like) chemotherapy regimen. Secondary purposes were to assess other body composition features changes and to assess the association of pre-therapy values and their changes over time with survival. MATERIAL AND METHODS: Patients selected underwent R-CHOP(like) regimen for DLBCL, and underwent PET-CT before and after treatment. Main clinical data collected included body mass index, date of last follow-up, date of progression, and date of death. From the low-dose CT images, BMD was assessed at the L1 level; the other body composition values, including muscle and fat distribution, were assessed at the L3 level by using a dedicated software. Descriptive statistics were reported as median and interquartile range, or frequencies and percentages. Statistical comparisons of body composition variables between pre- and post-treatment assessments were performed using the Wilcoxon matched pairs signed rank test. Non-normal distribution of variables was tested with the Shapiro-Wilk test. For qualitative variables, the Fisher exact test was used. Log rank test was used to compare survival between different subgroups of the study population defined by specific body composition cutoffs. The significance level was set at p < 0.05. RESULTS: Eighty-two patients were included. The mean follow-up was 37.5 ± 21.4 months. A significant difference was found in mean BMD before and after R-CHOP(like) treatment (p < 0.0001). The same trend was observed for mean skeletal muscle area (SMA) (p = 0.004) and mean skeletal muscle index (SMI) (p = 0.006). No significant association was demonstrated between body composition variables, PFS and OS. CONCLUSION: R-CHOP(like) treatment in DLBCL patients was associated with significant reduction of BMD, SMA and SMI.
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Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Supervivencia sin Enfermedad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Rituximab/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Vincristina/uso terapéutico , Vincristina/efectos adversos , Doxorrubicina/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of the reported study was to investigate the value of cone-beam computed tomography (CBCT)-based radiomics for risk stratification and prediction of biochemical relapse in prostate cancer. METHODS: The study population consisted of 31 prostate cancer patients. Radiomics features were extracted from weekly CBCT scans performed for verifying treatment position. From the data, logistic-regression models were learned for establishing tumor stage, Gleason score, level of prostate-specific antigen, and risk stratification, and for predicting biochemical recurrence. Performance of the learned models was assessed using the area under the receiver operating characteristic curve (AUC-ROC) or the area under the precision-recall curve (AUC-PRC). RESULTS: Results suggest that the histogram-based Energy and Kurtosis features and the shape-based feature representing the standard deviation of the maximum diameter of the prostate gland during treatment are predictive of biochemical relapse and indicative of patients at high risk. CONCLUSION: Our results suggest the usefulness of CBCT-based radiomics for treatment definition in prostate cancer.
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Adenocarcinoma/diagnóstico por imagen , Biología Computacional , Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje Automático , Neoplasias de la Próstata/diagnóstico por imagen , Radioterapia de Intensidad Modulada , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Curva ROC , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Thyroid Imaging Reporting and Data Systems (TIRADSs) have been largely diffused for their high accuracy in risk stratification of thyroid nodules (TNs) and their selection for fine-needle aspiration cytology (FNAC). The most popular TIRADSs are ACR-, EU-, and K-TIRADS, with some discrepancies each other. One major difference is that ACR-TIRADS includes a recommendation in favor of follow-up in TNs having a major diameter insufficient to indicate FNAC. The present study aimed to explore prevalence and significance of this recommendation. EU- and K-TIRADS were used as comparator. A retrospective series of thyroidectomies was searched according to a pre-defined protocol. The study period was 2019-2023. Preoperative ultrasound images were reviewed by radiologists blinded of clinical data. Matching of TIRADS and histology was performed later. Histology was the gold standard. The study series included 39 TNs classified as category 3, 4, or 5 and assessed for follow-up according to ACR-TIRADS. The overall cancer frequency was 25.6%, being 13% in category 3, 20% in category 4, and 83.3% in category 5. The category assessment according to ACR-, EU-, and K-TIRADS was not significantly different. EU-TIRADS indicated FNAC in 10 TNs of which two cancers and eight benign lesions. K-TIRADS recommended FNAC in 32 TNs of which seven cancers and 25 benign lesions. TNs assessed for follow-up according to ACR-TIRADS are cancer in one-fourth of cases. EU- and, especially, K-TIRADS allow us to select for FNAC cancers, with the burden of non-negligible frequency of unnecessary FNACs.
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AIMS: A few studies have evaluated the performance of the American College of Radiology Thyroid Imaging Reporting And Data System (ACR-TIRADS) in pediatric and elderly patients and found differences between the latter two age groups and middle adulthood. Thus, the present study was undertaken to explore the possible variation of ACR-TIRADS performance across different ages of patients. METHODS: A retrospective population undergoing thyroidectomy was selected to use histology as the reference standard. Ultrasound images were reviewed, and alignment of ACR-TIRADS with the corresponding histological diagnosis was made afterwards. Results of the age groups were compared. The ACR-TIRADS diagnostic performance was calculated considering the assessment of nodules across risk categories (i.e., from TR1 to TR5), rate of unnecessary FNAC (UN-FNAC), and rate of necessary but non-performed FNAC (NNP-FNAC). RESULTS: Overall, 114 patients with a total of 220 nodules (46 carcinomas) were included. The rate of UN-FNAC was 66.3%, being 93.1% in TR3, 82.1% in TR4, and 31.4% in TR5. There were 15 NNP-FNACs. No significant difference was observed between age groups in terms of sample size, nodule, cancer, and FNAC. The nodule assessment according to ACR-TIRADS categories did not vary across ages. Sensitivity and specificity recorded in three age tertiles were not significantly different. CONCLUSIONS: The present study shows that the performance of ACR-TIRADS is not significantly influenced by patient age.
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Background: Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Methods: Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Results: Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 µg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) µg/kg/day, 75% with a dose of 1.38 µg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Conclusions: Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted.
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Hipotiroidismo , Tiroxina , Femenino , Masculino , Humanos , Persona de Mediana Edad , Tiroxina/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Peso Corporal , TirotropinaRESUMEN
BACKGROUND: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was firstly described in 2016. Since NIFTP is thought a non-malignant tumor, the Bethesda system for thyroid cytology proposes two estimations of risk of malignancy of the diagnostic categories, one considering NIFTP as cancer and another one considering it as a benign neoplasm. The present study aimed to review NIFTPs in a single center, re-assess them across categories of three Thyroid Imaging Reporting and Data Systems (TIRADSs), and define the indication for biopsy according to the category-specific size cut-offs. METHODS: The study period was from 2017 to 2023. The institutional database was searched for histologically proven NIFTPs with preoperative ultrasound images. NIFTPs were re-assessed according to the American College of Radiology (ACR), European (EU), and Korean (K) TIRADSs. The indication for biopsy was defined according to TIRADS category-specific size threshold. RESULTS: Twenty NIFTPs from 19 patients were included. The median size of the NIFTPs was 23 mm. According to ultrasound, 80-85% of NIFTPs were at low-intermediate risk and 5-15% at high risk without significant difference among the tree TIRADSs (p = 0.91). The indication for FNA, according to three TIRADSs, was found in 52-58% of cases with no significant difference among systems (p = 0.96). CONCLUSION: NIFTPs have heterogeneous presentation according to TIRADSs with very low indication rate for FNA.
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Adenocarcinoma Folicular , Glándula Tiroides , Neoplasias de la Tiroides , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma Folicular/diagnóstico por imagen , Adenocarcinoma Folicular/epidemiología , Adenocarcinoma Folicular/patología , Biopsia con Aguja Fina , Estudios Retrospectivos , Medición de Riesgo , Glándula Tiroides/patología , Glándula Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/epidemiología , UltrasonografíaRESUMEN
Objective: Calcitonin (Ctn) measurement is crucial for the early diagnosis of medullary thyroid carcinoma (MTC). However, Ctn levels can be skewed/elevated due to other reasons, and the Ctn upper reference value remains controversial. In this field, studies have heterogeneous settings, published data are controversial, and no evidence has been achieved. The study's aim was to evaluate all previously investigated Ctn determinants in a population with histological exclusion of MTC. Methods: The institutional records from 2010 to 2022 were reviewed to select patients with thyroid nodules who had undergone total thyroidectomy with histological exclusion of MTC and who had tested for Ctn just before surgery. Thyroid features, demographic and anthropometric data, comorbidities, medications, and lifestyle information were collected. Univariate and multivariate analyses were performed. Results: A total of 127 cases were included. The median age for thyroidectomy was 51 years. Median Ctn was 1.04 pg/mL (interquartile range (IQR) 1.04-2.77), with two cases having values above 10 pg/mL. In univariate analysis, Ctn was correlated with gender (p < 0.001), body weight (p = 0.016), height (p = 0.031), body surface area (p = 0.016), thyroid size (p = 0.03), thyroglobulin (p < 0.001), and chronic kidney disease (p < 0.001). After multivariate analysis, the model with the highest accuracy included gender, chronic kidney disease, and thyroid-stimulating hormone (TSH) with an adjusted R-squared of 0.4. Conclusions: This study demonstrates, in a population histologically proven as MTC-free, that the Ctn value is mainly influenced by gender, anthropometric/thyroid features, and chronic kidney disease, with the further impact of TSH.
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The application of single-cell technologies in clinical nephrology remains elusive. We generated an atlas of transcriptionally defined cell types and cell states of human kidney disease by integrating single-cell signatures reported in the literature with newly generated signatures obtained from 5 patients with acute kidney injury. We used this information to develop kidney-specific cell-level information ExtractoR (K-CLIER), a transfer learning approach specifically tailored to evaluate the role of cell types/states on bulk RNAseq data. We validated the K-CLIER as a reliable computational framework to obtain a dimensionality reduction and to link clinical data with single-cell signatures. By applying K-CLIER on cohorts of patients with different kidney diseases, we identified the most relevant cell types associated with fibrosis and disease progression. This analysis highlighted the central role of altered proximal tubule cells in chronic kidney disease. Our study introduces a new strategy to exploit the power of single-cell technologies toward clinical applications.
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OBJECTIVE: The aim was to evaluate if bariatric surgery can affect the LT4 performance. The endpoints were the following: 1) difference between LT4 daily dose before and 1 year after surgery, 2) difference between LT4 dose per weight before and 1 year after surgery, 3) difference among LT4 preparations. METHODS: The study period was between January 2018 and May 2022. Inclusion criteria were a) adults undergone bariatric surgery, b) with proven autoimmune hypothyroidism, c) on LT4 therapy before bariatric surgery, d) using any commercialized LT4 preparation. Excluded were patients a) proven to have or suspected for pre-surgical intestinal malabsorption, b) with other potential interfering factors on LT4 absorption; c) with heart, renal, and/or hepatic failure, d) with recent/current infection/inflammation, e) in pregnancy, f) with incomplete data about LT4 therapy. RESULTS: According to the selection criteria, 40 patients were included. Both TSH and LT4 daily doses were not significantly different with respect to baseline values. On the contrary, the LT4 dose per weight was significantly increased, especially in RYGB patients. An increased LT4 dose per weight was observed with the reduction of weight. CONCLUSION: One year after bariatric surgery 1) the daily dose of LT4 remains unchanged, and 2) despite the significant weight reduction, LT4 dose per weight increases. Most data are referred to LT4 tablet and the performance of LT4 caps should be further investigated.
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Cirugía Bariátrica , Hipotiroidismo , Adulto , Femenino , Embarazo , Humanos , Tiroxina/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Cirugía Bariátrica/métodos , Pérdida de Peso , Comprimidos/uso terapéutico , TirotropinaRESUMEN
PURPOSE: While calcitonin (CT) measurement is recognized as the most accurate tool to diagnose medullary thyroid carcinoma (MTC), its routine use in patients with thyroid nodule (TN) is not universally accepted. The present study raised the question whether a TN patient with an initial normal CT can have suspicious CT levels (i.e., at least >20 pg/ml) later during his follow-up. METHODS: The historical database of our institution was searched to select TN patients undergone multiple CT tests, having an initial normal CT, and clinically followed up for years. The event of a CT above 20 pg/ml (mild-to-moderate suspicion) and 100 pg/ml (high suspicion) was searched in the follow-up of the included patients. RESULTS: According to the study design, the study sample encompassed 170 patients (131 female, 39 male) with initial CT value ≤10 pg/ml. On the first CT test, patients were 54.8 years and median CT was 2.1 pg/ml in both females and males. Over a period of 14.5 years and a median clinical follow-up of patients of 53.0 (23.9-102.5) months, MTC could be excluded by histology or cytology in 109 (64%) and clinically in the remaining ones. On the follow-up over time, no patients had CT >20 pg/ml and only two cases had CT just above 10 pg/ml. CONCLUSION: According to the present results, one single CT testing with normal value could be reasonably used as a rule-out strategy in patients with TN to avoid further CT measurements.
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Conservadores de la Densidad Ósea , Carcinoma Medular , Neoplasias de la Tiroides , Nódulo Tiroideo , Biomarcadores de Tumor , Calcitonina , Hormonas y Agentes Reguladores de Calcio , Carcinoma Medular/diagnóstico , Carcinoma Neuroendocrino , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico por imagenRESUMEN
Background: Red blood cell (RBC) transfusions in surgical patients are associated with increased morbidity a hospital stay. However, little is known about how clinical and economic outcomes differ between appropriately and inappropriately transfused patients. We hypothesized that inappropriate RBC transfusions in elective surgical patients would significantly increase hospital cost. The aim of this study was to quantify the economic burden associated with inappropriate RBC transfusions. Methods: We retrospectively included all adult patients admitted for elective non-cardiac surgery between January 2014 and March 2020. Patients were divided into three groups (not transfused, appropriately transfused and inappropriately transfused). The primary outcome was the excess in hospital cost in patients inappropriately transfused compared to non-transfused patients. Costs were calculated using a bottom-up approach and involving cost calculation on a granular level. According to international guidelines, transfusions were considered appropriate if administered with an ASA score of 1-2 and the last hemoglobin level measured before transfusion < 70 g/L, or with an ASA score ≥ 3 and the last hemoglobin level < 80 g/L. Cases where RBC transfusions were deemed necessary regardless of the Hb levels were reviewed by the patient blood management (PBM) board and classified accordingly. Secondary outcomes included total transfusion rate, transfusion index, and length of hospital stay. Statistical analysis was carried out by multivariable regression models. Results: During the study period there were 54,922 consecutive surgical admissions, of these 1,997 received an RBC transfusion, with 1,125 considered inappropriate. The adjusted cost of each inappropriate RBC transfusions was estimated in United States dollars (USD) 9,779 (95% CI, 9,358 - 10,199; p < 0.001) and totaled USD 11,001,410 in our series. Inappropriately transfused patients stayed 1.6 times (95% CI, 1.5-1.6; p < 0.001) longer in hospital (10.6 days vs. 6.7 days) than non-transfused patients and a mean 2.35 RBC units per patient were administered. Conclusion: Inappropriate RBC transfusions in elective surgical patients seem to be common and may represent a significant economic burden. In our experience, inappropriate transfusions significantly increased hospital costs by an average of USD 9,779 compared to non-transfused patients. Through specific PBM policy, hospitals may improve cost-effectiveness of their elective surgical activity by lowering inappropriate transfusions.
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BACKGROUND: Myocardial injury (MINJ) is a well-recognized prognostic marker in different acute cardio-respiratory illnesses, nonetheless, its relevance in Influenza remains poorly defined. Our aim was to assess incidence, correlates, short and mid-term prognostic role of MINJ in Influenza. METHODS: Hospitalized patients (pts) with laboratory confirmed Influenza A or B underwent highly sensitive cardiac T Troponin (hs-cTnT) measurement at admission in four regional Swiss hospitals during the 2018-2019 epidemic. MINJ was defined as hs-cTnT >14 ng/L. Clinical, laboratory and outcome data were prospectively collected. The primary endpoint was mortality at 28 days while the composite of mortality, admission to intensive care unit (ICU) or need for mechanical ventilation at 28-days and mortality at 30-months were set as secondary endpoints. RESULTS: The presence of MINJ was assessed within 48 h from admission in 145 consecutive hospitalized pts, being evident in 94 (65.5%) pts and associated with older age, higher C-reactive protein levels, renal impairment or chronic obstructive pulmonary disease. At a 28-days follow-up, 7 deaths (4.8%) occurred, all in patients with MINJ at admission (log-rank p = 0.048). MINJ was strongly associated with occurrence of death, ICU admission or mechanical ventilation (OR 5.74, 95% CI 1.28-53.29; p = 0.015). After a median follow-up of 32.7 months (IQR 32.2-33.4), 15 (10.3%) deaths occurred, all among pts with MINJ at index hospitalization leading to a higher mortality at follow-up among patients with MINJ (log-rank p = 0.003). CONCLUSIONS: MINJ is common in patients hospitalized for Influenza and is able to stratify the risk of short-term adverse events and mid-term mortality.
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Gripe Humana , Biomarcadores , Proteína C-Reactiva , Humanos , Gripe Humana/diagnóstico , Pronóstico , Estudios Prospectivos , Troponina TRESUMEN
Artificial intelligence (AI) uses mathematical algorithms to perform tasks that require human cognitive abilities. AI-based methodologies, e.g., machine learning and deep learning, as well as the recently developed research field of radiomics have noticeable potential to transform medical diagnostics. AI-based techniques applied to medical imaging allow to detect biological abnormalities, to diagnostic neoplasms or to predict the response to treatment. Nonetheless, the diagnostic accuracy of these methods is still a matter of debate. In this article, we first illustrate the key concepts and workflow characteristics of machine learning, deep learning and radiomics. We outline considerations regarding data input requirements, differences among these methodologies and their limitations. Subsequently, a concise overview is presented regarding the application of AI methods to the evaluation of thyroid images. We developed a critical discussion concerning limits and open challenges that should be addressed before the translation of AI techniques to the broad clinical use. Clarification of the pitfalls of AI-based techniques results crucial in order to ensure the optimal application for each patient.
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Aims: Myocardial injury (MINJ) in Coronavirus disease 2019 (COVID-19) identifies individuals at high mortality risk but its clinical relevance is less well established for Influenza and no comparative analyses evaluating frequency and clinical implications of MINJ among hospitalized patients with Influenza or COVID-19 are available. Methods and results: Hospitalized adults with laboratory confirmed Influenza A or B or COVID-19 underwent highly sensitive cardiac T Troponin (hs-cTnT) measurement at admission in four regional hospitals in Canton Ticino, Switzerland. MINJ was defined as hs-cTnT >14 ng/L. Clinical, laboratory and outcome data were retrospectively collected. The primary outcome was mortality up to 28 days. Cox regression models were used to assess correlations between admission diagnosis, MINJ, and mortality. Clinical correlates of MINJ in both viral diseases were also identified. MINJ occurred in 94 (65.5%) out of 145 patients hospitalized for Influenza and 216 (47.8%) out of 452 patients hospitalized for COVID-19. Advanced age and renal impairment were factors associated with MINJ in both diseases. At 28 days, 7 (4.8%) deaths occurred among Influenza and 76 deaths (16.8%) among COVID-19 patients with a hazard ratio (HR) of 3.69 [95% confidence interval (CI) 1.70-8.00]. Adjusted Cox regression models showed admission diagnosis of COVID-19 [HR 6.41 (95% CI 4.05-10.14)] and MINJ [HR 8.01 (95% CI 4.64-13.82)] to be associated with mortality. Conclusions: Myocardial injury is frequent among both viral diseases and increases the risk of death in both COVID-19 and Influenza. The absolute risk of death is considerably higher in patients admitted for COVID-19 when compared with Influenza.
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Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.
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Although rare, immune checkpoint inhibitor (ICI)-related myocarditis can be life-threatening, even fatal. In view of increased ICI prescription, identification of clinical risk factors for ICI-related myocarditis is of primary importance. This study aimed to assess whether pre-existing cardiovascular (CV) patient conditions are associated with the reporting of ICI-related myocarditis in VigiBase, the WHO global database of suspected adverse drug reactions (ADRs). In a (retrospective) matched case-control study, 108 cases of ICI-related myocarditis and 108 controls of ICI-related ADRs other than myocarditis were selected from VigiBase. Drugs labeled as treatment for CV conditions (used as a proxy for concomitant CV risk factors and/or CV diseases) were found to be associated more strongly with the reporting of ICI-related myocarditis than with other ICI-related ADRs (McNemar's chi-square test of marginal homogeneity: p = 0.026, Cramer's coefficient of effect size: Φ = 0.214). No significant association was found between pre-existing diabetes and ICI-related myocarditis reporting (McNemar's test of marginal homogeneity: p = 0.752). These findings offer an invitation for future prospective pharmacoepidemiological studies to assess the causal relationship between pre-existing CV conditions and myocarditis onset in a cohort of cancer patients followed during ICI treatment.