Does Air Pollution Impact on Semen Parameters? Findings from a Real-Life, Cross-Sectional Study in Italian Infertile Men.

PURPOSE: In industrialized countries, air pollutants levels have been monitored closely for environmental and research issues. Using Italian data, we aimed to investigate the association between air pollutants levels and semen parameters in a cohort of non-Finnish white-European men presenting for couple's infertility. MATERIALS AND METHODS: Complete demographic and laboratory data from 1,152 infertile men consecutively assessed between January 2015 and January 2018 were analyzed. Semen analyses were based on the 2010 World Health Organization reference criteria. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). We analyzed the annual average level of the three main markers of air pollution (Pm10, Pm2.5, and NO2) between 2014 and 2018. Descriptive statistics, linear and logistic regression analyses tested the association between air pollutants levels and semen parameters. RESULTS: Of 1,152 men, 87 (7.55%) had normal sperm parameters at first semen analysis. Of 1,065 patients with abnormal semen analyses, 237 (22.25%), 324 (30.42%), and 287 (26.95%) patients presented 1, 2 or 3 abnormalities, respectively, and 217 (20.38%) were azoospermic. At linear regression analysis, Pm10, Pm2.5, and NO2 were negatively associated with sperm morphology (Pm10: ß=-0.5288 µg/m3, p=0.001; Pm2.5: ß=-0.5240 µg/m3, p=0.019; NO2: ß=-0.4396 µg/m3, p<0.0001). Furthermore, the adjusted odds of normal sperm morphology <4% were 1.06 (95% confidence interval [CI], 1.03-1.09; p=0.007) for Pm10, 1.07 (95% CI, 1.03-1.11; p=0.007) for Pm 2.5, and 1.03 (95% CI, 1.02-1.05; p=0.001) for NO2, respectively. CONCLUSIONS: In a large homogenous cohort of infertile men, Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology. Conversely, no clear association was observed with other macroscopic sperm parameters.

Morbidity and mortality in men: Role of androgens.

In this narrative review we provide an overview of the current literature on male hypogonadism and related comorbidities, also depicting the role of testosterone therapy (TTh) in the various settings. Male hypogonadism has been associated with major comorbidities such as type 2 diabetes mellitus, obesity and cardiovascular diseases, promoting a vicious cycle that may lead to further hypogonadism. The biological underpinnings of this association are currently under investigations, but clearly emerges the relevance of the hypothalamic-pituitary-gonadal axis. Hypogonadism has also been associated with increased risk of mortality. As such, TTh has the potential to oppose these patterns and improve cardiovascular and metabolic health in hypogonadal men. Clinical and observational data suggest that in males with hypogonadism, TTh, together with lifestyle changes and diabetes medications, may improve glycemia, reduce risk of progression to diabetes and provides positive effects on cardiovascular risk. Conversely, available data does not fully support any increased risk of prostate cancer in men under TTh. Of clinical relevance, a possible harmful role of hypogonadal status in men with COVID-19 eventually emerged.

Testosterone in males with COVID-19: a 12-month cohort study.

BACKGROUND: Male patients with COVID-19 have been found with reduced serum total testosterone (tT) levels and with more severe clinical outcomes. OBJECTIVES: To assess total testosterone (tT) levels and the probability of recovering eugonadal tT levels during a minimum 12-month timespan in a cohort of men who have been followed over time after the recovery from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical and hormonal values were collected for the overall cohort. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics was used to compare hormonal levels at baseline versus 7-month (FU1) versus 12-month (FU2) follow-up, respectively. Multivariate cox proportional hazards regression model was used to identify the potential predictors of eugonadism recovery over time among patients with hypogonadism at the time of infection. RESULTS: Of the original cohort of 286 patients, follow-up data were available for 121 (42.3%) at FU1 and 63 (22%) patients at FU2, respectively. Higher median interquartile range (IQR) tT levels were detected at FU2 (13.8 (12.3-15.3) nmol/L) versus FU1 (10.2 [9.3-10.9] nmol/L) and versus baseline (3.6 [3.02-4.02] nmol/L) (all p < 0.0001), whilst both LH and E2 levels significantly decreased over the same time frame (all p ≤ 0.01). Circulating IL-6 levels further decreased at FU2 compared to FU1 levels (19.3 vs. 72.8 pg/ml) (p = 0.02). At multivariable cox regression analyses, baseline tT level (HR 1.19; p = 0.03 [1.02-1.4]) was independently associated with the probability of tT level normalization over time, after adjusting for potential confounders. CONCLUSIONS: Circulating tT levels keep increasing over time in men after COVID-19. Still, almost 30% of men who recovered from COVID-19 had low circulating T levels suggestive for a condition of hypogonadism at a minimum 12-month follow-up.

Combined plasma levels of IL-10 and testosterone, but not soluble HLA-G5, predict the risk of death in COVID-19 patients.

BACKGROUND: The identification of biomarkers correlated with coronavirus disease 2019 (COVID-19) outcomes is a relevant need for clinical management. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by elevated interleukin (IL)-6, IL-10, HLA-G, and impaired testosterone production. OBJECTIVES: We aimed at defining the combined impact of sex hormones, interleukin-10, and HLA-G on COVID-19 pathophysiology and their relationship in male patients. MATERIALS AND METHODS: We measured by chemiluminescence immunoassay, electrochemiluminescent assays, and enzyme-linked immunosorbent assay circulating total testosterone, 17ß-estradiol (E2 ), IL-10, and -HLAG5 as well as SARS-CoV-2 S1/S2 Immunoglobulin G from 292 healthy controls and 111 COVID-19 patients with different disease severity at hospital admission, and in 53 COVID-19 patients at 7-month follow-up. RESULTS AND DISCUSSION: We found significantly higher levels of IL-10, HLA-G, and E2 in COVID-19 patients compared to healthy controls and an inverse correlation between IL-10 and testosterone, with IL-10, progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at the 7-month follow-up. The risk of death in COVID-19 patients with low testosterone increased in the presence of high IL-10. A negative correlation between SARS-CoV-2 Immunoglobulin G and HLA-G or IL-10 at hospitalization was observed. At the 7-month follow-up, IL-10 and testosterone normalized, and  HLA-G decreased. CONCLUSION: Our findings indicate that combined evaluation of IL-10 and testosterone predicts the risk of death in men with COVID-19 and support the hypothesis that IL-10 fails to suppress excessive inflammation by promoting viral spreading.

The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

Acute Kidney Injury at Hospital Admission for SARS-CoV-2 Infection as a Marker of Poor Prognosis: Clinical Implications for Triage Risk Stratification.

BACKGROUND/AIMS: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. METHODS: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). RESULTS: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). CONCLUSIONS: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.

Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has taken a catastrophic toll on society, health-care systems and the economy. Notably, COVID-19 has been shown to be associated with a higher mortality rate in men than in women. This disparity is likely to be a consequence of a failure to invest in men's health, as it has also been established that men have a lower life expectancy and poorer outcomes from non-communicable diseases than women. A variety of biological, social and economic factors have contributed to the sex disparities in mortality from COVID-19. A streamlined men's health programme - with the urologist as the gatekeeper of men's health - is needed to help prevent future tragedies of this nature.

A virus-free cellular model recapitulates several features of severe COVID-19.

As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.

Testosterone in males with COVID-19: A 7-month cohort study.

BACKGROUND: Circulating testosterone levels have been found to be reduced in men with severe acute respiratory syndrome coronavirus 2 infection, COVID-19, with lower levels being associated with more severe clinical outcomes. OBJECTIVES: We aimed to assess total testosterone levels and the prevalence of total testosterone still suggesting for hypogonadism at 7-month follow-up in a cohort of 121 men who recovered from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as total testosterone ≤9.2 nmol/L. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and total testosterone levels at follow-up assessment. RESULTS: Circulating total testosterone levels increased at 7-month follow-up compared to hospital admittance (p < 0.0001), while luteinizing hormone and 17ß-estradiol levels significantly decreased (all p ≤ 0.02). Overall, total testosterone levels increased in 106 (87.6%) patients, but further decreased in 12 (9.9%) patients at follow-up, where a total testosterone level suggestive for hypogonadism was still observed in 66 (55%) patients. Baseline Charlson Comorbidity Index score (OR 0.36; p = 0.03 [0.14, 0.89]) was independently associated with total testosterone levels at 7-month follow-up, after adjusting for age, BMI, and IL-6 at hospital admittance. CONCLUSIONS: Although total testosterone levels increased over time after COVID-19, more than 50% of men who recovered from the disease still had circulating testosterone levels suggestive for a condition of hypogonadism at 7-month follow-up. In as many as 10% of cases, testosterone levels even further decreased. Of clinical relevance, the higher the burden of comorbid conditions at presentation, the lower the probability of testosterone levels recovery over time.

Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study.

BACKGROUND: Patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus. Interleukin (IL)-1 or IL-6 inhibitors have been used to treat this patient population, but the comparative effectiveness of these different strategies remains undetermined. We aimed to compare IL-1 and IL-6 inhibition in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. METHODS: This cohort study included patients admitted to San Raffaele Hospital (Milan, Italy) with COVID-19, respiratory insufficiency, defined as a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of 300 mm Hg or less, and hyperinflammation, defined as serum C-reactive protein concentration of 100 mg/L or more or ferritin concentration of 900 ng/mL or more. The primary endpoint was survival, and the secondary endpoint was a composite of death or mechanical ventilation (adverse clinical outcome). Multivariable Cox regression analysis was used to compare clinical outcomes of patients receiving IL-1 inhibition (anakinra) or IL-6 inhibition (tocilizumab or sarilumab) with those of patients who did not receive interleukin inhibitors, after accounting for baseline differences. All patients received standard care. Interaction tests were used to assess the probability of survival according to C-reactive protein or lactate dehydrogenase concentrations. FINDINGS: Of 392 patients included between Feb 25 and May 20, 2020, 275 did not receive interleukin inhibitors, 62 received the IL-1 inhibitor anakinra, and 55 received an IL-6 inhibitor (29 received tocilizumab and 26 received sarilumab). In the multivariable analysis, compared with patients who did not receive interleukin inhibitors, patients treated with IL-1 inhibition had a significantly reduced mortality risk (hazard ratio [HR] 0·450, 95% CI 0·204-0·990, p=0·047), but those treated with IL-6 inhibition did not (0·900, 0·412-1·966; p=0·79). In the multivariable analysis, there was no difference in adverse clinical outcome risk in patients treated with IL-1 inhibition (HR 0·866, 95% CI 0·482-1·553; p=0·63) or IL-6 inhibition (0·882, 0·452-1·722; p=0·71) relative to patients who did not receive interleukin inhibitors. For increasing C-reactive protein concentrations, patients treated with IL-6 inhibition had a significantly reduced risk of mortality (HR 0·990, 95% CI 0·981-0·999; p=0·031) and adverse clinical outcome (0·987, 0·979-0·995; p=0·0021) compared with patients who did not receive interleukin inhibitors. For decreasing concentrations of serum lactate dehydrogenase, patients treated with an IL-1 inhibitor and patients treated with IL-6 inhibitors had a reduced risk of mortality; increasing concentrations of lactate dehydrogenase in patients receiving either interleukin inhibitor were associated with an increased risk of mortality (HR 1·009, 95% CI 1·003-1·014, p=0·0011 for IL-1 inhibitors and 1·006, 1·001-1·011, p=0·028 for IL-6 inhibitors) and adverse clinical outcome (1·006, 1·002-1·010, p=0·0031 for IL-1 inhibitors and 1·005, 1·001-1·010, p=0·016 for IL-6 inhibitors) compared with patients who did not receive interleukin inhibitors. INTERPRETATION: IL-1 inhibition, but not IL-6 inhibition, was associated with a significant reduction of mortality in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. IL-6 inhibition was effective in a subgroup of patients with markedly high C-reactive protein concentrations, whereas both IL-1 and IL-6 inhibition were effective in patients with low lactate dehydrogenase concentrations. FUNDING: None.

Severely low testosterone in males with COVID-19: A case-control study.

BACKGROUND: Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19). OBJECTIVES: We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory-confirmed COVID-19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID-19, and clinical outcomes. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health-significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes. RESULTS: Overall, a significantly lower levels of LH and tT were found in patients with COVID-19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E2 (p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS-CoV-2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL-6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters. CONCLUSIONS: We unveil an independent association between SARS-CoV-2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis.

The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9 ± 8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p < 0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.

Novel Coronavirus Disease (COVID-19) in Italian Patients: Gender Differences in Presentation and Severity.

BACKGROUND: In the first wave of the novel coronavirus (severe acute respiratory syndrome coronavirus 2) infections, Italy experienced a heavy burden of hospital admissions for acute respiratory distress syndromes associated with the novel coronavirus disease (COVID-19). Early evidence suggested that females are less affected than males. OBJECTIVE: This study aimed to assess the gender-related differences in presentation and severity among COVID-19 patients admitted to IRCCS San Raffaele Hospital, Milan, Italy. MATERIALS AND METHODS: This prospective observational study included all patients admitted to the hospital between February 25 and April 19, 2020, with a positive real-time reverse-transcriptase polymerase chain reaction for COVID-19. The following data were collected: date of admission, gender, age and details of intensive care unit admission and outcomes. RESULTS: A total of 901 patients with COVID-19 were admitted to the hospital and provided consent for the study. Of these, 284 were female (31.5%). The percentage of admitted female patients significantly increased over time (25.9% of all admissions in the first half of the study period vs. 37.1% in the second half; P < 0.001). Females accounted for 14.4% of all COVID-19 intensive care unit admissions. There was no gender-based difference in the overall hospital mortality: 20.1% for females and 19.2% for males (P = 0.8). CONCLUSIONS: In our hospital, which was in the epicenter of the first wave of COVID-19 pandemic in Italy, female patients were few, presented late and were less critical than male patients.

Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. METHODS: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). RESULTS: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). DISCUSSION/CONCLUSION: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.

Low testosterone levels predict clinical adverse outcomes in SARS-CoV-2 pneumonia patients

BACKGROUND: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men has suggested a potential role for testosterone (T) in determining gender-disparity in the SARS-CoV-2 clinical outcomes. OBJECTIVES: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the Respiratory Intensive Care Unit (RICU) MATERIALS AND METHODS: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the Respiratory Intensive Care Unit (RICU) of the "Carlo Poma" Hospital in Mantua were analyzed. Several biochemical risk factors (i.e., blood count and leucocyte formula, C- Reactive Protein (CRP), procalcitonin (PCT), Lactic Dehydrogenase (LDH), Ferritin, D-Dimer, Fibrinogen, Interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), Sex Hormone Binding Globulin (SHBG), and Luteinizing Hormone (LH) were determined. RESULTS: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs. groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (i.e. the neutrophil count, LDH and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase of both ICU transfer or mortality risk was observed in men with TT<5 nmol/L or cFT< 100 pmol/L. DISCUSSION AND CONCLUSION: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS-CoV-2 infected men admitted to RICU.

SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project.

Preliminary published data depict a much greater prevalence of males with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS-CoV-2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS-CoV-2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS-CoV-2 infection. Another option is that SARS-CoV-2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.

European Association of Urology Guidelines Office Rapid Reaction Group: An Organisation-wide Collaborative Effort to Adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 Era.

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.

Assessing the Burden of Nondeferrable Major Uro-oncologic Surgery to Guide Prioritisation Strategies During the COVID-19 Pandemic: Insights from Three Italian High-volume Referral Centres.

The coronavirus 2019 (COVID-19) pandemic has led to an unprecedented emergency scenario for all aspects of health care, including urology. At the time of writing, Italy was the country with the highest rates of both infection and mortality. A panel of experts recently released recommendations for prioritising urologic surgeries in a low-resource setting. Of note, major cancer surgery represents a compelling challenge. However, the burden of these procedures and the impact of such recommendations on urologic practice are currently unknown. To fill this gap, we assessed the yearly proportion of high-priority major uro-oncologic surgeries at three Italian high-volume academic centres. Of 2387 major cancer surgeries, 32.3% were classified as high priority (12.6% of radical nephroureterectomy, 17.3% of nephrectomy, 33.9% of radical prostatectomy, and 36.2% of radical cystectomy cases). Moreover, 26.4% of high-priority major cancer surgeries were performed in patients at higher perioperative risk (American Society of Anesthesiologists score ≥3), with radical cystectomy contributing the most to this cohort (50%). Our real-life data contextualise ongoing recommendations on prioritisation strategies during the current COVID-19 pandemic, highlighting the need for better patient selection for surgery. We found that approximately two-thirds of elective major uro-oncologic surgeries can be safely postponed or changed to another treatment modality when the availability of health care resources is reduced. PATIENT SUMMARY: We used data from three high-volume Italian academic urology centres to evaluate how many surgeries performed for prostate, bladder, kidney, and upper tract urothelial cancer can be postponed in times of emergency. We found that approximately two-thirds of patients with these cancers do not require high-priority surgery. Conversely, of patients requiring high-priority surgery, approximately one in four is considered at high perioperative risk. These patients may pose challenges in allocation of resources in critical scenarios such as the current COVID-19 pandemic.