Antibiotic Prescription and In-Hospital Mortality in COVID-19: A Prospective Multicentre Cohort Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, empiric antibiotics (ATBs) have been prescribed on a large scale in both in- and outpatients. We aimed to assess the impact of antibiotic treatment on the outcomes of hospitalised patients with moderate and severe coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective multicentre cohort study in six clinical hospitals, between January 2021 and May 2021. RESULTS: We included 553 hospitalised COVID-19 patients, of whom 58% (311/553) were prescribed antibiotics, while bacteriological tests were performed in 57% (178/311) of them. Death was the outcome in 48 patients-39 from the ATBs group and 9 from the non-ATBs group. The patients who received antibiotics during hospitalisation had a higher mortality (RR = 3.37, CI 95%: 1.7-6.8), and this association was stronger in the subgroup of patients without reasons for antimicrobial treatment (RR = 6.1, CI 95%: 1.9-19.1), while in the subgroup with reasons for antimicrobial therapy the association was not statistically significant (OR = 2.33, CI 95%: 0.76-7.17). After adjusting for the confounders, receiving antibiotics remained associated with a higher mortality only in the subgroup of patients without criteria for antibiotic prescription (OR = 10.3, CI 95%: 2-52). CONCLUSIONS: In our study, antibiotic treatment did not decrease the risk of death in the patients with mild and severe COVID-19, but was associated with a higher risk of death in the subgroup of patients without reasons for it.

Anticoagulant protein S in COVID-19: low activity, and associated with outcome.

Introduction. COVID-19 disease was associated with both thrombo-embolic events and in-situ thrombi formation in small vessels. Antiphospholipidic antibodies were found in some studies.Aim. Assessment of protein S activity in patients with COVID-19 as a cause of this prothrombotic state, and of the association of protein S activity with worse outcome.Methods. All patients admitted for COVID-19 disease in a university hospital between 15th of May and 15th of July 2020 were prospectively enrolled into this cohort study. Patients treated with antivitamin K anticoagulants and with liver disease were excluded. All patients had protein S activity determined at admission. The main outcome was survival, while secondary outcomes were clinical severity and lung damage.Results. 91 patients were included, of which 21 (23.3%) died. Protein S activity was decreased in 65% of the patients. Death was associated with lower activity of protein S (median 42% vs. 58%, p < 0.001), and the association remained after adjustment for age, inflammation markers and ALAT. There was a dose-response relationship between protein S activity and clinical severity (Kendall_tau coefficient = -0.320, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001) or pulmonary damage on CT scan (Kendall_tau coefficient = -0.290, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001). High neutrophil count was also independently associated with death (p = 0.002).Conclusion. Protein S activity was lower in COVID-19 patients, and its level was associated with survival and disease severity, suggesting that it may have a role in the thrombotic manifestations of the disease.

Macrophage activation syndrome at the onset of glucocorticoid-resistant systemic lupus erythematosus: a case report.

INTRODUCTION: Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory state mediated by uncontrolled cytokine storm and haemophagocytosis. Although rarely reported, MAS might occur in systemic lupus erythematosus (SLE), notably as an inaugural manifestation. Glucocorticoids (GCs) are the cornerstone of SLE therapy. However, in some cases high doses of GCs are required to achieve remission (i.e. glucocorticoid-resistance), leading to significant side effects. CASE REPORT: A 28-year-old Romani male was admitted to our hospital for polyarthralgia, polyserositis and fatigability. The patient had high-grade fever, jaundice and generalized lymphadenopathy. Laboratory tests revealed severe mixed hemolytic autoimmune anemia, leukopenia, hepatocytolysis, coagulation abnormalities, hypertriglyceridemia, biological inflammatory syndrome, hyperferritinemia and persistent proteinuria of nephritic pattern. Imaging studies showed pleuropericardial effusion, hepatosplenomegaly and polysynovitis. Additional blood tests revealed hypocomplementemia and positive ANA, anti-dsDNA and anti-Sm antibodies. Haemophagocytosis was not identified either on bone marrow or axillary lymph node biopsy specimens. However, SLE-associated MAS seemed to fit this set-up. High-dose corticotherapy (6.5 g methylprednisolone followed by prednisone, 1.5 mg/kg/day after discharge) and intravenous cyclophosphamide were necessary to induce and sustain remission. CONCLUSION: MAS is a potentially severe manifestation that should be considered at SLE onset whenever high fever and elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin and procalcitonin are noted. Early diagnosis and prompt treatment lead to remission in two thirds of cases. Glucocorticoid-resistance leads to the use of high-dose corticotherapy or immunosuppressive agents that could elicit serious side effects. New insights into the molecular mechanisms of glucocorticoid-resistance are needed in order to conceive more adequate GC-therapies.

Deceleration and Acceleration Capacities in Risk Stratification for Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for both supraventricular and ventricular arrhythmias. Autonomic dysregulation may be responsible for the development of arrhythmias in these patients, and its analysis could be useful for identifying those at high risk for arrhythmias. STUDY QUESTION: Our purpose is to analyze the role of acceleration capacity (AC) and deceleration capacity (DC), novel markers of the autonomic balance, as potential arrhythmic risk predictors in patients with COPD. STUDY DESIGN: We prospectively included 47 patients diagnosed with COPD, and a control group of 64 age-matched subjects without COPD. AC and DC values were obtained using 24-hour Holter monitoring. The arrhythmias were isolated premature atrial complexes, supraventricular tachycardias, isolated premature ventricular beats (PVC), and combined ventricular arrhythmias consisting in ventricular tachycardias or more than 10 PVC per hour. RESULTS: Supraventricular arrhythmias and isolated PVC were more frequent in the COPD group. The DC was significantly lower (3.10 vs. 5.60, P < 0.0001) and AC higher (-4.60 vs. -6.60, P = 0.002) in patients with COPD. DC was identified as a predictor of arrhythmic events with an area under the curve (AUC) for premature atrial complexes >70/d of 0.72 (0.56-0.87, P = 0.013), for supraventricular tachycardias 0.76 (0.62-0.90, P = 0.002), and for combined ventricular arrhythmias 0.69 (0.54-0.82, P = 0.025). AC was predictor only for combined ventricular arrhythmias with an AUC of 0.74 (0.58-0.85, P = 0.002). CONCLUSIONS: Patients with COPD associate a significant autonomic imbalance and a higher incidence of arrhythmias. DC could be a strong predictor for supraventricular and ventricular arrhythmias in patients with COPD with no clinically apparent cardiac disease. AC could be useful alongside with DC regarding the risk for ventricular arrhythmias, but seems to have lesser value as a predictor for supraventricular arrhythmias.

TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms - a multicentric study on 529 patients.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.

Acute Bilateral Phrenic Neuropathy: from Diabetes Mellitus to Focal Guillain-Barré Syndrome.

Bilateral phrenic neuropathy is a rare cause of acute ventilatory failure posing both diagnostic and therapeutic difficulties. We report the case of a 55-years-old diabetic male presenting with acute onset orthopnea. Clinical and radioscopic evaluations suggested bilateral diaphragmatic paralysis, electroneuromyographic studies revealed bilateral acute phrenic neuropathy, and cerebrospinal fluid examination found albuminocytologic dissociation. The administration of high-dose intravenous immunoglobulin was followed by prompt improvement. During the next months the symptoms continued to regress. There were no recurrences. We consider the patient had a spatially limited form of acute inflammatory demyelinating polyradiculoneuropathy. The case underlies the importance of considering an immune mediated etiology in patients with acute bilateral phrenic neuropathy. To the best of our knowledge no similar case has been reported.

Prevalence and Characteristics of Pulmonary Hypertension Associated with COPD - A Pilot Study in Patients Referred to a Pulmonary Rehabilitation Program Clinic.

OBJECTIVES: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmo-nary disease (COPD); its prevalence is currently unknown. The objectives of the study were: (a) to provide data on the prevalence of PH among the COPD patients referred to a pulmonary rehabilitation program; (b) to evaluate possible correlations of PH with the severity of COPD, the presence of hypoxemia and polycythemia. MATERIAL AND METHODS: We retrospectively studied 31 consecutive patients with the diagnosis of COPD hospitalised in our clinic in which echocardiography was performed. Spirometry, peripheral oxygen saturation, haematocrit, echocardiography data, history of exacerbations and cardiac comorbidities were obtained from patients records. PH was defined as systolic pulmonary arterial pressure (sPAP) greater than 35 mmHg or by the presence of right ventricle (RV) abnormalities. OUTCOMES: The prevalence of PH was 38.7%. Resting hypoxemia was significantly more frequent in the PH group than in the non PH patients (p=0.019). Other differences were not statistically significant (severity of bronchial obstruction and polycythemia, cardiac comorbidities). The impact of PH on RV was found in only 5 patients with RV enlargement; no patient had RV hypertrophy or RV systolic dysfunction. Suspected "out of proportion" PH (sPAP greater than 50 mmHg) was encountered in 2 out of 12 patients with PH. CONCLUSIONS: The prevalence of PH in patients with COPD was 38.7%. Resting hypoxemia was significantly more frequent in PH patients. As PH has an important role in the prognosis of COPD patients, it should be evaluated in as many COPD patients as possible.