The effect of COVID-19 epidemic on vital signs in hospitalized patients: a pre-post heat-map study from a large teaching hospital.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p = < 0.002). Gender was not associated with mortality. Overall mortality in COVID-19 hospitalized patients was 18%, ranging from 1.4% in patients below 65 years to about 30% in patients over 65 years. Heat maps analysis demonstrated that COVID-19 patients had an increased frequency in episodes of compromised respiratory rate, acute desaturation, and fever. COVID-19 epidemic profoundly affected the incidence of severe derangements in vital signs in a large academic hospital. We validated heat maps as a method to analyze the clinical stability of hospitalized patients. This method may help to improve resource allocation according to patient characteristics.

Blood Thiol Redox State in Chronic Kidney Disease.

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.

Environmental triggers for connective tissue disease: the case of COVID-19 associated with dermatomyositis-specific autoantibodies.

PURPOSE OF REVIEW: The aim of the present review is to analyze the link between autoimmune diseases and environmental factors, in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) as it shares numerous features with the interstitial lung disease associated with connective tissue diseases positive for rare autoantibodies directed at highly specific autoantigens (i.e., MDA5 and RIG1) among the intracellular sensors of SARS-CoV-2 in the innate response against viruses. RECENT FINDINGS: As shown in recent publications and in our original data, specific autoantibodies may be functionally relevant to COVID-19 infection. We evaluated sera from 35 hospitalized patients with COVID-19 to identify antinuclear antibodies and autoantibodies directed against specific antigenic targets, and we identified anti-nuclear antibodies (ANA) in 20/35 of patients with COVID-19 (57%), in patients with need for supplemental oxygen (90% vs. 20% in ANA-negative cases; P < 0.0001). In 7/35 COVID-19 sera, we detected anti-MJ/NXP2 (n = 3), anti-RIG1 (n = 2), anti-Scl-70/TOPO1 (n = 1), and anti-MDA5 (n = 1), overall associated with a significantly worse pulmonary involvement at lung computerized tomography scans. Eleven (31%) patients were positive for antibodies against the E2/E3 subunits of mitochondrial pyruvate dehydrogenase complex. SUMMARY: Viral infections such as COVID-19 are associated with ANA and autoantibodies directed toward antiviral signaling antigens in particular in patients with worse pulmonary involvement.

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.

High mortality in COVID-19 patients with mild respiratory disease.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS-CoV-2, presenting with mild symptoms, and requiring hospitalization in a non-intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non-invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 103 /mm3 ) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality of patients with COVID-19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID-19.

Geriatric Nutritional Risk Index Is Predictive of Subjective Global Assessment and Dialysis Malnutrition Scores in Elderly Patients on Hemodialysis.

OBJECTIVE: Malnutrition is a frequent complication in patients on hemodialysis (HD), even if its adequate appraisal remains one of the most complicated challenges in the HD scenario because of the limits of current malnutrition biomarkers. The aim of our study was to assess the relation of subjective nutritional tools Subjective Global Assessment (SGA) and Dialysis Malnutrition Score (DMS) with the objective malnutrition tool Geriatric Nutritional Risk Index (GNRI) in elderly patients on HD. METHODS: This is a cross-sectional study involving 71 patients on maintenance HD. Mann-Whitney U and chi-square tests were used to compare data of male and female patients on HD. Linear and logistic regression models were used to assess the variables tested in all patients. RESULTS: GNRI was not different between male and female patients on HD, and it was negatively related to SGA and DMS: B, -0.05 (95% confidence interval, -0.08 to -0.02) P = 0.00 and B, -0.30 (95% confidence interval, -0.47 to -0.14) P = .00, respectively. Both continuous and categorical GNRI data were predictive of SGA = 3: Odds Ratio (OR), 0.74 (0.63 to 0.87) P = 0.00 and OR, 6.74 (1.54 to 29.45) P = 0.01, respectively. Similarly, GNRI data were related to DMS > 13: OR, 0.85 (0.76 to 0.85) P = 0.00 and 3.29 (1.08 to 10.05) P = 0.03, respectively. Continuous GNRI data remained significant in both male and female patients separately, whereas categorical GNRI data, only in male patients. CONCLUSIONS: GNRI is a reliable nutritional tool predictive of subjective malnutrition scores SGA and DMS, pointing out a relation between objective and subjective malnutrition indexes in both genders.

A central role for intermolecular dityrosine cross-linking of fibrinogen in high molecular weight advanced oxidation protein product (AOPP) formation.

BACKGROUND: Advanced oxidation protein products (AOPPs) are dityrosine cross-linked and carbonyl-containing protein products formed by the reaction of plasma proteins with chlorinated oxidants, such as hypochlorous acid (HOCl). Most studies consider human serum albumin (HSA) as the main protein responsible for AOPP formation, although the molecular composition of AOPPs has not yet been elucidated. Here, we investigated the relative contribution of HSA and fibrinogen to generation of AOPPs. METHODS: AOPP formation was explored by SDS-PAGE, under both reducing and non-reducing conditions, as well as by analytical gel filtration HPLC coupled to fluorescence detection to determine dityrosine and pentosidine formation. RESULTS: Following exposure to different concentrations of HOCl, HSA resulted to be carbonylated but did not form dityrosine cross-linked high molecular weight aggregates. Differently, incubation of fibrinogen or HSA/fibrinogen mixtures with HOCl at concentrations higher than 150 µM induced the formation of pentosidine and high molecular weight (HMW)-AOPPs (>200 k Da), resulting from intermolecular dityrosine cross-linking. Dityrosine fluorescence increased in parallel with increasing HMW-AOPP formation and increasing fibrinogen concentration in HSA/fibrinogen mixtures exposed to HOCl. This conclusion is corroborated by experiments where dityrosine fluorescence was measured in HOCl-treated human plasma samples containing physiological or supra-physiological fibrinogen concentrations or selectively depleted of fibrinogen, which highlighted that fibrinogen is responsible for the highest fluorescence from dityrosine. CONCLUSIONS: A central role for intermolecular dityrosine cross-linking of fibrinogen in HMW-AOPP formation is shown. GENERAL SIGNIFICANCE: These results highlight that oxidized fibrinogen, instead of HSA, is the key protein for intermolecular dityrosine formation in human plasma.

The Renal Connexome and Possible Roles of Connexins in Kidney Diseases.

Connexins are membrane-spanning proteins that allow for the formation of cell-to-cell channels and cell-to-extracellular space hemichannels. Many connexin subtypes are expressed in kidney cells. Some mutations in connexin genes have been linked to various human pathologies, including cardiovascular, neurodegenerative, lung, and skin diseases, but the exact role of connexins in kidney disease remains unclear. Some hypotheses about a connection between genetic mutations, endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) in kidney pathology have been explored. The potential relationship of kidney disease to abnormal production of connexin proteins, mutations in their genes together with ER stress, or the UPR is still a matter of debate. In this scenario, it is tantalizing to speculate about a possible role of connexins in the setting of kidney pathologies that are thought to be caused by a deregulated podocyte protein expression, the so-called podocytopathies. In this article, we give examples of the roles of connexins in kidney (patho)physiology and propose avenues for further research concerning connexins, ER stress, and UPR in podocytopathies that may ultimately help refine drug treatment.

Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN).

OBJECTIVES: The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-α (IL-6Rα), in patients with ankylosing spondylitis (AS). METHODS: Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety. RESULTS: Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints. The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred. CONCLUSIONS: The ALIGN study shows that IL-6Rα blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.

Renal dysfunction in acute congestive heart failure: a common problem for cardiologists and nephrologists.

The term acute heart failure (AHF) refers to a clinical syndrome with typical symptoms and signs, in which a structural or functional heart abnormality leads to defective oxygen delivery. The term cardiorenal syndrome has been proposed to outline the strict interplay between cardiac and renal function. In the setting of acute cardiac decompensation, acute kidney injury (AKI) is generally referred to as cardiorenal syndrome type 1. In this review, we summarize the fundamental pathophysiological aspects of both AHF and AHF-related AKI. We also review the latest therapeutic options, including both pharmacological ones, such as loop diuretics, potassium-sparing diuretics and vaptans, and non-pharmacological ones, such as ultrafiltration, and their impact on patients' outcome. We discuss the pathophysiology of diuretic resistance, a common occurrence in these patients, reviewing the available strategies to treat it and highlighting how a close collaboration between cardiologists and nephrologists is frequently crucial for the management of this complication. Finally, we discuss three new promising non-pharmacological tools for the prevention of AHF recurrence, including two methods that exploit sympathetic denervation and one technique that acts by increasing vagal tone.

McKittrick-Wheelock syndrome: a rare cause of acute renal failure and hypokalemia not to be overlooked.

McKittrick-Wheelock syndrome is a rare disorder in which a colorectal tumor (usually a villous adenoma) determines secretory mucous diarrhea, which in turn leads to prerenal acute renal failure, hyponatremia, hypokalemia and metabolic acidosis. Even though the outcome is usually favorable with complete recovery after surgery, the diagnosis is often delayed, making the patient susceptible to life-threatening complications, mainly severe acidosis and hypokalemia. We present two paradigmatic cases with extreme electrolytes imbalance and complete recovery following the appropriate treatment. The pathogenesis of this degenerative condition is discussed in detail.

Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity.

OBJECTIVE: Satavaptan, a vasopressin V2 receptor antagonist, has been shown to improve the control of ascites in cirrhosis in short-term phase II studies. The aim of this study was to evaluate the efficacy and safety of satavaptan in three different populations of patients with cirrhosis and ascites. METHODS: 1200 patients were included in three randomised double-blind studies comparing satavaptan with placebo in uncomplicated ascites (study 1: n=463 patients) and difficult-to-treat ascites, with and without concomitant diuretic treatment (studies 2 and 3: n=497 and n=240 patients, respectively). RESULTS: Satavaptan was not more effective than placebo in the control of ascites in any of the populations studied as estimated by the primary efficacy endpoints: worsening of ascites (study 1) and the cumulative number of large-volume paracenteses during 12 weeks (studies 2 and 3). Nevertheless, some of the secondary efficacy endpoints related to the treatment of ascites were met in the three studies, suggesting a slight advantage of satavaptan over placebo in delaying ascites formation. Moreover, satavaptan was more effective than placebo in improving the serum sodium concentration in patients with hyponatraemia. The incidence of major complications of cirrhosis during follow-up did not differ significantly between the satavaptan and placebo groups in the three studies. Overall, the rate of any treatment-related adverse events, serious treatment-related events and treatment-related events leading to permanent discontinuation of treatment did not differ significantly between the treatment groups. However, in study 2 mortality was higher in patients treated with satavaptan compared with placebo (HR 1.47; 95% CI 1.01 to 2.15); no significant differences in mortality between the two groups were observed in the other two studies. No specific cause for the increased mortality was identified. Most deaths were associated with known complications of liver cirrhosis. CONCLUSION: Satavaptan, alone or in combination with diuretics, is not clinically beneficial in the long-term management of ascites in cirrhosis.

Integrated protocol for the prevention and treatment of skin ulcers in patients with end-stage renal disease.

Chronic Kidney Disease (CKD) is an escalating global health concern, affecting more than 10 % of the general population worldwide, amounting to over 800 million individuals. One of its major complications for patients is the high prevalence of skin ulcers . This study aims to develop a protocol for ulcer management within the context of a hospital-based dialysis center. The success of this strategy is deeply rooted in the collaboration of a multidisciplinary team, continually enriched by specialist training. The clinical nurse specialist (CNS) in wound care plays a pivotal role in this approach. By employing a systematic methodology, the protocol is tailored to emphasize holistic care for patients diagnosed with end-stage renal disease undergoing hemodialysis. It accentuates the significance of proactive prevention, in-depth patient education, and the immediate identification of early wound signs. The research underscores the necessity to further weave in specialized training for ulcer care, ensuring each hospital visit is maximized for efficiency and effectiveness. Central to this protocol is the understanding that CKD is a growing concern, that the optimal management of ulcers relies heavily on multidisciplinary collaboration, and that an emphasis on prevention, patient education, and timely wound recognition is crucial to enhance patient care and experience.

Multimodal deep learning for COVID-19 prognosis prediction in the emergency department: a bi-centric study.

Predicting clinical deterioration in COVID-19 patients remains a challenging task in the Emergency Department (ED). To address this aim, we developed an artificial neural network using textual (e.g. patient history) and tabular (e.g. laboratory values) data from ED electronic medical reports. The predicted outcomes were 30-day mortality and ICU admission. We included consecutive patients from Humanitas Research Hospital and San Raffaele Hospital in the Milan area between February 20 and May 5, 2020. We included 1296 COVID-19 patients. Textual predictors consisted of patient history, physical exam, and radiological reports. Tabular predictors included age, creatinine, C-reactive protein, hemoglobin, and platelet count. TensorFlow tabular-textual model performance indices were compared to those of models implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular fastai and XGBoost models, with AUC 0.87 ± 0.02, F1 score 0.62 ± 0.10 and an MCC 0.52 ± 0.04 (p < 0.32). As for ICU admission, the combined model MCC was superior (p < 0.024) to the tabular models. Our results suggest that a combined textual and tabular model can effectively predict COVID-19 prognosis which may assist ED physicians in their decision-making process.

Short-Term Adverse Events and Antibody Response to the BNT162b2 SARS-CoV-2 Vaccine in 4156 Health Care Professionals.

Short-term adverse events are common following the BNT162b2 vaccine for SARS-Cov-2 and have been possibly associated with IgG response. We aimed to determine the incidence of adverse reactions to the vaccine and the impact on IgG response. Our study included 4156 health-care professionals who received two doses of the BNT162b2 vaccine 21 days apart and obtained 6113 online questionnaires inquiring about adverse events. The serum response was tested in 2765 subjects 10 days after the second dose. Adverse events, most frequently a local reaction at the site of injection, were reported by 39% of subjects. Multivariate analysis showed that female sex (odds ratio­OR­1.95; 95% confidence interval­CI­1.74−2.19; p < 0.001), younger age (OR 0.98 per year, p < 0.001), second dose of vaccine (OR 1.36, p < 0.001), and previous COVID-19 infection (OR 1.41, p < 0.001) were independently associated with adverse events. IgG response was significantly higher in subjects with adverse events (1110 AU/mL­IQR 345-1630 vs. 386 AU/mL, IQR 261-1350, p < 0.0001), and the association was more pronounced in subjects experiencing myalgia, fever, and lymphadenopathy. We demonstrate that a more pronounced IgG response is associated with specific adverse events, and these are commonly reported by health care professionals after the BNT162b2 vaccine for SARS-Cov-2.