Gut microbiome dynamics and predictive value in hospitalized COVID-19 patients: a comparative analysis of shallow and deep shotgun sequencing.

The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative results of the reverse transcription polymerase chain reaction in the respiratory tract. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings. Our study demonstrated the diverse effects of various combinations of clinical parameters, microbiome profiles, and patient metadata on the precision of outcome prognostication in patients. It indicates that microbiological data possesses greater reliability in forecasting patient outcomes when contrasted with clinical data or metadata. Furthermore, we established that shallow shotgun sequencing presents a viable and cost-effective diagnostic alternative to deep sequencing within clinical environments.

Malnutrition and Erythropoietin Resistance among Patients with End-Stage Kidney Disease: Where Is the Perpetrator of Disaster?

BACKGROUND: Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance. METHODS: Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn. RESULTS: Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI. CONCLUSION: Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth.

How Is Body Composition and Nutrition Status Associated with Erythropoietin Response in Hemodialyzed Patients? A Single-Center Prospective Cohort Study.

Background: Anemia is the most common finding in patients with end-stage kidney disease undergoing renal replacement therapy. A certain percentage of patients does not respond adequately to erythropoietin (EPO) treatment, not being able to reach desirable hemoglobin levels even when treated with large-dose EPO and intravenous/oral iron. In our study, we wanted to further investigate how nutritional status is associated with erythropoietin responsiveness. To quantify EPO response, we used the Erythropoietin Resistance Index (ERI), which is defined as the weekly weight-adjusted dose of EPO divided by the hemoglobin level. Patients and methods: Seventy-eight patients undergoing hemodialysis were included. All of them were measured by a SECA mBCA body composition analyzer and evaluated by Kalantar-Zadeh's MIS score. Routine biochemical tests were also taken into account. The Shapiro-Wilk test was used to study the distributions of quantitative variables, which were significantly different from normal (p < 0.05). We used nonparametric Mann-Whitney U-test to compare groups. Correlations were studied by means of Spearman's rank correlation coefficient. Bonferroni correction for multiple testing was performed. To find independent determinants of ERI, we additionally performed multivariate analysis using the General Linear Model (GLM). Results: In terms of body composition, factors that are associated with high ERI are low BMI, low fat mass, low visceral fat volume, high total body water percentage, low phase angle and low fat-free mass. In addition to body composition parameters, total MIS score and IL-6 serum levels correlated positively with ERI value. IL-6 was an independent determinant of ERI value, based on multivariate analysis. After correction for multiple analysis, BMI and eGFR both remained significant factors associated with EPO response. Conclusions: It seems crucial to prevent inflammatory malnutrition as a part of a holistic approach to anemia treatment in dialysis patients.

Pentoxifylline as a Potential Adjuvant Therapy for COVID-19: Impeding the Burden of the Cytokine Storm.

The outburst of inflammatory response and hypercoagulability are among the factors contributing to increased mortality in severe COVID-19 cases. Pentoxifylline (PTX), a xanthine-derived drug registered for the treatment of vascular claudication, has been reported to display broad-spectrum anti-inflammatory and immunomodulatory properties via adenosine A2A receptor (A2AR)-related mechanisms, in parallel to its rheological actions. Prior studies have indicated the efficacy of PTX in the treatment of various pulmonary diseases, including the management of acute respiratory distress syndrome of infectious causes. Therefore, PTX has been proposed to have potential benefits in the treatment of SARS-CoV-2 symptoms, as well as its complications. The aim of this review is to discuss available knowledge regarding the role of PTX as a complementary therapeutic in SARS-CoV-2.

Delirium Severely Worsens Outcome in Patients with COVID-19-A Retrospective Cohort Study from Temporary Critical Care Hospitals.

Delirium is a sign of deterioration of homeostasis and worse prognosis. The aim of this study was to investigate the frequency, risk factors and prognosis of delirium in patients with COVID-19 in a temporary acute setting hospital. A retrospective cohort analysis of data collected between October 2020 and February 2021 from two temporary acute care hospitals was performed. All consecutive hospitalized patients ≥18 years old with COVID-19 were included. An assessment of consciousness was carried out at least two times a day, including neurological examination. Delirium was identified through retrospective chart review according to DSM-5 criteria if present at least once during hospitalization. Analysis included 201 patients, 39 diagnosed with delirium (19.4%). Delirious patients were older (p < 0.001), frailer (p < 0.001) and the majority were male (p = 0.002). Respiratory parameters were worse in this group with higher oxygen flow (p = 0.013), lower PaO2 (p = 0.043) and higher FiO2 (p = 0.006). The mortality rate was significantly higher in patients with delirium (46.15% vs 3.70%, p < 0.001) with OR 17.212 (p < 0.001) corrected for age and gender. Delirious patients experienced significantly more complications: cardiovascular (OR 7.72, p < 0.001), pulmonary (OR 8.79, p < 0.001) or septic (OR 3.99, p = 0.029). The odds of mortality in patients with COVID-19 presenting with delirium at any point of hospitalization were seventeen times higher.

Spontaneous Pneumothorax in COVID-19 Patients Treated with High-Flow Nasal Cannula outside the ICU: A Case Series.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic and a burden to global health at the turn of 2019 and 2020. No targeted treatment for COVID-19 infection has been identified so far, thus supportive treatment, invasive and non-invasive oxygen support, and corticosteroids remain a common therapy. High-flow nasal cannula (HFNC), a non-invasive oxygen support method, has become a prominent treatment option for respiratory failure during the SARS-CoV-2 pandemic. HFNC reduces the anatomic dead space and increases positive end-expiratory pressure (PEEP), allowing higher concentrations and higher flow of oxygen. Some studies suggest positive effects of HFNC on mortality and avoidance of intubation. Spontaneous pneumothorax has been observed in patients suffering from SARS-CoV-2 pneumonia. Although the viral infection itself contributes to its development, higher PEEP generated by both HFNC and mechanical ventilation is another risk factor for increased alveoli damage and air-leak. Herein, we present three cases of patients with no previous history of lung diseases who were diagnosed with COVID-19 viral pneumonia. All of them were supported with HFNC, and all of them presented spontaneous pneumothorax.

Paraplegia Caused by Spontaneous Spinal Hemorrhage in a Patient Undergoing Rivaroxaban Therapy.

BACKGROUND Spinal hematomas can be post-traumatic, iatrogenic, or spontaneous. A spontaneous spinal hematoma is a rare finding, but one with very serious clinical implications. There are some risk factors linked to its occurrence, e.g. arteriovenous malformations, lumbar puncture, coagulopathy, neoplasms, or therapeutic anticoagulation. At present, only a few cases of spontaneous spinal hematoma (SSH) associated with new oral anticoagulants (NOACs) have been described, three of which were linked with rivaroxaban. CASE REPORT We report the case of an 82-year-old Caucasian woman with persistent atrial fibrillation treated with rivaroxaban, who presented to the Urology Department with acute-onset back pain which was thought to be due to urolithiasis. No kidney stones were found, but her creatinine serum level was elevated, so she was transferred to our clinic for further treatment. During hospitalization she quickly developed paraplegia with urine and stool retention. MRI was performed, and demonstrated an acute epidural hemorrhage in her thoracic and lumbar spine. The neurosurgeons disqualified this patient from surgical intervention due to the extent of the hematoma and its location. The patient was referred to the Neurology Department for treatment and rehabilitation, but, to the best of our knowledge, she did not recover her motor function. CONCLUSIONS Although rivaroxaban has been shown to be more effective than warfarin in stroke prevention in patients with atrial fibrillation, physicians must remember that its use also carries the risk of major bleeding. SSH occurrence should be taken into account in a patient taking NOACs who develops paraplegia, even if there is no history of trauma prior to admission.