Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND AND AIM: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors, to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted subhazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99, 1.86) (P=0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted subhazard ratio 1.18, 95% CI 1.04 to 1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p=0.018) and those with isolated sarcopenia (p=0.046) than in patients without muscle changes. Lastly, we found a strong correlation between function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with liver cirrhosis. The novelty of this study is the multicentre, prospective nature and the distinguishing impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may have a dominant role in the prognosis of patients with liver cirrhosis.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Long-Term Prognosis among COVID-19 Patients: The Predictive Role Played by Hyperinflammation and Arrhythmic Disorders in Fatal Outcome.

Limited data are available on outcomes among COVID-19 patients beyond the acute phase of the disease. All-cause mortality among our COVID-19 patients one year after hospital discharge and factors/conditions associated with death were evaluated. All patients discharged from our COVID center were periodically evaluated by clinical assessment and by digital healthcare registry consultation. All findings acquired on discharge day represented the baseline data and were utilized for statistics. Of the 208 patients admitted, 187 patients were discharged. Among these, 17 patients died within 12 months (non-survivors). Compared to survivors, non-survivor patients were significantly (p < 0.05) older, exhibited significantly greater comorbidities and prevalence of active malignancy, heart failure, and arrhythmias, and showed significantly higher circulating levels of B-type natriuretic peptide, troponin, C-reactive protein, and d-dimer, as well as a longer heart-rate-corrected QT interval and significantly lower values for the glomerular filtration rate. Following multivariate analysis, cancer, arrhythmias, and high C-reactive protein levels were found to be factors independently associated with death. At the one-year follow-up, about 9% of patients discharged from our COVID center had a fatal outcome. Ageing, myocardial injury, impaired renal function, and, in particular, cancer, hyperinflammation, and arrhythmias represented strong predictors of the worst long-term outcome among COVID-19 patients.

Liver Involvement during SARS-CoV-2 Infection Is Associated with a Worse Respiratory Outcome in COVID-19 Patients.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients.

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma.

Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.

Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios.

Sodium-Glucose Co-Transporters Family: Current Evidence, Clinical Applications and Perspectives.

Sodium-glucose co-transporters (SGLTs) family members are involved in several vital biological functions. Except for SGLT3, they are involved in the mechanisms of active transport of sodium and glucose and several micromolecules. The discovery of functions and mechanisms of SGLT1 inhibition and, in particular, of SGLT2 has radically changed the natural history of some pathologies. SGLT2 inhibitors have revolutionized the therapeutic approach not only of type 2 diabetes mellitus but also of heart failure and chronic kidney failure. Considering the role played by the other SGLTs and the functions still unknown to date, clinical implications of the inhibition of SGLT2 could represent the prelude for a wider modulation of these cotransporters. A better understanding of the role and function of SGLTs could represent a revolution in the therapeutic approach in the hepatological, metabolic, neurological and oncological fields. The purpose of this review is to illustrate the knowledge currently available on SGLTs, its clinical implications and future perspectives.

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus-host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

Predictors of early and late hepatocellular carcinoma recurrence.

Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

Mortality and risk factors of vaccinated and unvaccinated frail patients with COVID-19 treated with anti-SARS-CoV-2 monoclonal antibodies: A real-world study.

OBJECTIVES: There is a scarcity of data on the outcomes and predictors of therapeutic failure of monoclonal antibodies (mAbs) in frail patients with COVID-19. METHODS: Prospective study including consecutive COVID-19 outpatients referred by primary care physicians for mAb treatment. The outcomes evaluated were 60-day mortality, time to SARS-CoV-2 clearance, need for hospitalization, and O2 therapy. RESULTS: Among 1026 COVID-19 patients enrolled, 60.2% received casirivamab/imdevimab and 39.8% sotrivimab. Median age was 63 years, 52.4% were males and median time from positive nasopharyngeal swab to mAbs administration was 3 days (interquartile range, 2-5). 78.1% were vaccinated. Overall, the 60-day mortality was 2.14%. No differences in outcomes were observed between the two mAbs used. No difference was observed in mortality between vaccinated and unvaccinated patients (P = 0.925); although, lower rate of hospitalization (P <0.005), less need for O2 therapy (P <0.0001) and reduced nasopharyngeal swab negativity time (P <0.0001) were observed in vaccinated patients. Early administration of mAbs was associated with lower mortality (P <0.007), whereas corticosteroid use worsened prognosis (P <0.004). The independent predictors associated with higher mortality were older age (P <0.0001), presence of active hematologic malignancies (P <0.0001), renal failure (P <0.041), and need for O2 therapy (P <0.001). CONCLUSION: This study shows similar effectiveness among mAbs used, regardless of vaccination status and identifies patients with COVID-19 in whom mAbs have poor activity.

Non-alcoholic Fatty Liver Disease (NAFLD), Type 2 Diabetes, and Non-viral Hepatocarcinoma: Pathophysiological Mechanisms and New Therapeutic Strategies.

In recent years, the incidence of non-viral hepatocellular carcinoma (HCC) has increased dramatically, which is probably related to the increased prevalence of metabolic syndrome, together with obesity and type 2 diabetes mellitus (T2DM). Several epidemiological studies have established the association between T2DM and the incidence of HCC and have demonstrated the role of diabetes mellitus as an independent risk factor for the development of HCC. The pathophysiological mechanisms underlying the development of Non-alcoholic fatty liver disease (NAFLD) and its progression to Non-alcoholic steatohepatitis (NASH) and cirrhosis are various and involve pro-inflammatory agents, oxidative stress, apoptosis, adipokines, JNK-1 activation, increased IGF-1 activity, immunomodulation, and alteration of the gut microbiota. Moreover, these mechanisms are thought to play a significant role in the development of NAFLD-related hepatocellular carcinoma. Early diagnosis and the timely correction of risk factors are essential to prevent the onset of liver fibrosis and HCC. The purpose of this review is to summarize the current evidence on the association among obesity, NASH/NAFLD, T2DM, and HCC, with an emphasis on clinical impact. In addition, we will examine the main mechanisms underlying this complex relationship, and the promising strategies that have recently emerged for these diseases' treatments.

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination.

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.

GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives.

To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.

Non-invasive respiratory support in SARS-CoV-2 related acute respiratory distress syndrome: when is it most appropriate to start treatment?

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most severe complications of SARS-CoV-2 infection. Non-Invasive Respiratory Support (NRS) as Continuous Positive Airway Pressure (CPAP) and/or Non-Invasive Ventilation (NIV) has been proven as effective in the management of SARS-CoV-2-related ARDS. However, the most appropriate timing for start NRS is unknown. METHODS: We conducted a prospective pilot study including all consecutive patients who developed moderate SARS-CoV-2-related ARDS during hospitalization. Patients were randomly divided into two intervention groups according to ARDS severity (assessed by PaO2/FiO2-P/F) at NRS beginning: group A started CPAP/NIV when P/F was ≤ 200 and group B started CPAP/NIV when P/F was ≤ 150. Eligible patients who did not give their consent to CPAP/NIV until the severe stage of ARDS and started non-invasive treatment when P/F ≤ 100 (group C) was added. The considered outcomes were in-hospital mortality, oro-tracheal intubation (OTI) and days of hospitalization. RESULTS: Among 146 eligible patients, 29 underwent CPAP/NIV when P/F was ≤ 200 (Group A), 68 when P/F was ≤ 150 (Group B) and 31 patients agreed to non-invasive treatment only when P/F was ≤ 100 (Group C). Starting NRS at P/F level between 151 and 200 did not results in significant differences in the outcomes as compared to treatment starting with P/F ranging 101-150. Conversely, patients undergone CPAP/NIV in a moderate stage (P/F 101-200) had a significantly lower in-hospital mortality rate (13.4 vs. 29.0%, p = 0.044) and hospitalization length (14 vs. 15 days, p = 0.038) than those in the severe stage (P/F ≤ 100). Age and need for continuous ventilation were independent predictors of CPAP/NIV failure. CONCLUSIONS: Starting CPAP/NIV in patients with SARS-CoV-2-related ARDS in moderate stage (100 > P/F ≤ 200) is associated to a reduction of both in-hospital mortality and hospitalization length compared to the severe stage (P/F ≤ 100). Starting CPAP/NIV with a P/F > 150 does not appear to be of clinical utility.

The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial.

BACKGROUND: Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. METHODS: Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0-1 risk factor (absent/low); 2-3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. RESULTS: Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04-3.52, P = 0.038 and 1.96, 95%CI 1.02-3.8, P = 0,045, respectively, vs absent/low risk group). CONCLUSIONS: This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.

Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient's morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improvement of extrahepatic diseases. There is a lack of a thorough analysis of the available treatments for extrahepatic HBV manifestations. In 90% to 100% of cases, the NAs stop the HBV replication, and they produce a clinical response in the majority of patients with mild to moderate extrahepatic signs/symptoms. Arthritis can definitely disappear after the HBV elimination and, in some cases, the HBV eradication following NAs therapy appears to improve the renal function in HBV-related nephropathies. Plasma exchange can be used in subjects who are suffering from the most aggressive forms of cryoglobulinemic vasculitis and glomerulonephritis, progressive peripheral neuropathy, and life-threatening cases, and this can be combined with glucocorticosteroids and antiviral agents. In selected refractory patients, the use of rituximab in conjunction with NAs therapy can be considered. The review provides an update on extrahepatic conditions that are linked to HBV and the impact of treating HBV with NAs.

Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study.

Background. Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). Methods. The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. Results. 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9−22 days). Cox's multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan−Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. Conclusion. This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.

COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring.

Background: The heart is commonly involved in COVID-19, and rhythm disorders have been largely reported. Objective: To evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19. Methods: Each patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias). Results: Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07-1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38-68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003-1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20-302.51); p = 0.0004]. Conclusion: Arrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards.

Platypnea-orthodeoxia syndrome in SARS-CoV-2 related ARDS: a case report.

Platypnea-Orthodeoxia Syndrome (POS) is an often misdiagnosed clinical condition characterized by dyspnea and hypoxia in sitting or semi-sitting position, reversible in supine position. Although POS is typically associated with intracardiac shunts, it seems frequent also in SARS-CoV-2 related Acute Respiratory Distress Syndrome (ARDS). In fact, the prevalent involvement of the lung bases due to interstitial pneumonia can determine refractory positional hypoxemia, with marked desaturation in the sitting position and regression or improvement in the supine position, configuring the clinical picture of the POS. We present a clinical case of POS associated with acute respiratory distress from SARS-CoV-2 pneumonia in which refractory hypoxia would have required support by invasive mechanical ventilation if the syndrome had not been identified.