Vitamin B Complex in Patients with Acute Kidney Injury the Vibaki Trial

Introduction: Acute kidney injury (AKI) is associated with a very high mortality and an increased risk for progression to chronic kidney disease (CKD). Preclinical studies have identified that NAD+ augmentation as a potential strategy for the prevention and treatment of AKI. NAD+ is the final metabolized form of vitamin B3. A recent clinical study found that COVID-19 related AKI was associated with NAD+ biosynthetic impairment arising in the context of ischemic, inflammatory, or toxic kidney injury. Since there is no availability of vitamin B3 in the country, we tested if I.V. vitamin B complex (vitamin B1, B6 and B12) could improve renal recovery in patients with AKI. By oxidation, vitamin B6 through the pathway of pentose phosphate leads to the formation of NADPH (nicotamide adenine phosphate dinucleotide) an analog of NAD+. Method(s): We conducted randomized, blind, placebo-controlled study in hospitalized patients with AKI (NCT04893733). During the study I.V. vitamin B complex or placebo was given twice a day for 5 consecutive days. In each patient, a protocol-based treatment approach for AKI was used (STOP AKI protocol from the ISN 0by25 trial https://doi.org/10.1371/journal.pmed.1003408). Serum creatinine (sCr) was measured using a point of care device (NOVA Biomedical Xpress CREA) at enrollment and every 24 hours for 7 days, and then at day 30, and day 90. We evaluated if vitamin B complex could improve renal recovery in patients with AKI, reduce the risk of De Novo CKD or CKD progression, and improve survival. Result(s): From September 2020 to September 2021, 260 patients were enrolled. Baseline characteristics are shown on table 1. The drop in sCr values by day 7 was higher in the vitamin B complex group (1.04 vs. 0.33 mg/dl;p < 0.001). Complete recovery was higher in patients randomized to vitamin B complex (59.2% vs. 34.6%;p=0.001), no difference was found in terms of partial recovery (26.2% vs. 27.7%;p=0.888). Non-recovery was lower in patients who received vitamin B complex as compared to placebo (16.6% vs. 37.7%;p < 0.001). At 3 months, the incidence of de novo CKD was lower in patients who received vitamin B complex (19.2% vs. 26.9%;p=0.043) in patients with CKD the progression of the disease was lower in patients who received vitamin B complex (13.1% vs. 20.8%;p=0.023). No differences were found in terms of 90-day mortality (Vitamin B complex 74.3% vs. Placebo 80.1%;0.554). The relative risk of Vitamin B complex for renal recovery was 0.37 (95% CI 0.242 - 0.593;p<0,0001) with a NNT of 3.1 patients with a relative risk for CKD progression or De Novo CKD of 0.47 (95% CI 0.28 - 0.79;p = 0.005) with a NNT of 4.8 patients. Conclusion(s): Vitamin B complex could accelerate renal recovery in patients with AKI;reduce the incidence of De Novo CKD and CKD progression. Our results support ongoing studies investigating the therapeutic potential of NAD+ augmentation as a means to mitigate kidney injury. Conflict of interest Potential conflict of interest: Nova Biomedical MedtronicCopyright © 2023

Association of Lactate Dehydrogenase and C-reactive Protein Levels as Predictors of Respiratory Failure in Covid-19

Background and Aim: Inflammatory markers reproduce amount of disease development or revival. They are used to assess improvement or worsening of the illness. Hence the aim of the study was to determine the correlation of laboratory markers (LDH and CRP) and oxygen requirement with clinical severity in Covid 19 subjects. Material(s) and Method(s): There were 216 subjects admitted to the emergency department of the hospital. The incorporated subjects were divided into two groups: group I subjects had covid19 pneumonia and in group 2 subjects did not have covid 19 pneumonia. Blood count and serum values of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were quantified in all subjects enrolled in the research. An automated hematology analyzer was utilized to perform blood count according to the manufacturer's protocol. Serum samples were analyzed on a fully automated clinical chemistry Instrument. Result(s): LDH was amplified in 82% of subjects, CRP resulted elevated in 98% of subjects, only 21% of subjects presented pathological values of white blood cell (WBC), but 18% had a neutrophils count above the upper normal range value, while 89% of subjects had lymphocytes count below the lower normal range value, as formerly reported. Conclusion(s): LDH and CRP could be helpful for the premature identification of subjects who are at elevated risk for acute respiratory failure. They should be considered a helpful test for the early recognition of subjects who need closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis. These subjects could be benefited from a quick hospitalization, a closer observation and correct treatments. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Volumetric modulated arc radiotherapy with concomitant chemotherapy for the anal squamous carcinoma: A Welsh experience

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT) Purpose: To describe the five-year treatment outcomes of patients with anal squamous carcinoma treated with concurrent chemoradiotherapy (CRT) specified with volumetric modulated arc radiotherapy (VMAT) at a Welsh tertiary referral centre. Methods and materials: A total of 80 anal cancer patients received radical CRT between 2016 and 2021. CRT consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumour volumes (GTV), and the elective nodes were prescribed 40 Gy/28 fractions (1.42 Gy/daily) for patients having a cT1/2N0M0. Patients with cT3-T4/N0-N1a-cM0 were prescribed 53.2 Gy/28 fractions (1.9 Gy daily) to the GTV;gross nodal volumes were prescribed 50.4 Gy/28 fractions (1.8 Gy daily) if sized <=3 cm or 53.2 Gy/28 fractions (1.9 Gy daily) if >3 cm;elective nodal areas were given 40 Gy/28 fractions (1.42 Gy daily). Mitomycin and capecitabine were administered concurrently. The primary outcome was colostomy-free survival (CFS). Secondary outcomes were cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS) and adverse effects. Result(s): Median follow-up was 31.3 months (3-61). The five-year CFS was 94.3% (95% CI: 50.0%-96.5%). The five-year CSS, DFS and OS were 92% (95% CI: 60.5-95%), 86.7% (95% CI: 58-89%) and 67.9% (95% CI: 56.6-75.1%) respectively. A total of four (5%) local recurrences and one (1.3%) regional recurrence was observed. A total of seven patients (8.7%) had distant metastasis (liver was a frequent site;57.1%);three patients (3.7%) died of COVID pneumonia. Late toxicities were as: vaginal stenosis (6.3%), sexual dysfunction (1.25%) and urine incontinence (1.25%). Second malignancies were as: lung (2.5%), gastric (1.3%), pancreatic cancer (1.3%) and cholangiocarcinoma (1.3%). Conclusion(s): Our experience supports the use of VMAT on a routine basis for the CRT of anal squamous cell carcinoma. Copyright © 2022

Does expanded access to primary prophylaxis with G-CSF decrease the burden of febrile neutropenia?

Category: Management/measurement of side-effects of treatment (acute or late), including patient-reported outcome measures (PROMs) Purpose: Guidelines recommend primary prophylaxis (PP) with haematopoietic colony stimulating factors (CSFs) in chemotherapy with a >=20% risk of febrile neutropenia (FN). During the COVID-19 pandemic, guidelines temporarily supported routine use of G-CSF as PP for intermediate risk regimens. Our retrospective real-world data compares hospital admissions for FN during a period of expanded access (June to December 2020) against baseline use (June to December 2019) in a district general UK hospital. Methods and materials: The process measure was the proportion of patients prescribed PP with G-CSF when initiating a new intermediate/low-risk regimen/month. The outcome measure was the monthly rate of hospital admissions for FN in intermediate/low-risk regimens. Statistical process control (SPC) charts and chi-square tests were used for analysis. Result(s): Use of G-CSF as PP showed statistically significant special cause variation on SPC p-charts consistent with policy change. Median PP prescription rate in June to December 2019 was 0.9% (interquartile range (IQR) 0-2.6%) and June to December 2020 was 34.8% (IQR 29%-43%). Monthly G-CSF prescriptions for all indications was a median of 3% (2019) versus 70% (2020). However, the trends in admissions for FN were stable on SPC p-charts with a median monthly event rate of 0.63% in 2019 and 0.66% in 2020. Summary statistics showed 12 events/698 unique patients in 2019 (1.72%) and ten events/618 patients in 2020 (1.62%), (p=0.8). Conclusion(s): Despite significantly increased use of PP with G-CSF for intermediate/low-risk chemotherapy, the burden of hospitalisations for FN remained unchanged and was lower than expected. Copyright © 2022

Voclosporin for Lupus Nephritis: Assessment of Long-Term Safety and Efficacy Including Renal Outcome Over 3 Years of Treatment in the Phase 3 AURORA 1 and AURORA 2 Studies

Background: In AURORA 1, adding voclosporin to mycophenolate mofetil (MMF) and low-dose steroids led to significant reductions in proteinuria at 1 year in patients with lupus nephritis (LN). We report on the recently completed AURORA 2 study evaluating voclosporin compared to placebo in patients treated for an additional 2 years after AURORA 1. Method(s): Patients with LN completing AURORA 1 were eligible to continue on the same double-blinded treatment of voclosporin or placebo in AURORA 2;all patients recieved MMF and low-dose steroids. Outcomes assessed over the 3 year treatment period of both studies included adverse events (AEs), eGFR, urine protein-creatinine ratio (UPCR), good renal outcome and renal flare. Good renal outcome was defined based on achievement of an adequate response (i.e. sustained reduction in UPCR to <=0.7 mg/mg) and without renal flare (i.e. an increase to UPCR >1 mg/mg from a post-response UPCR of <0.2 mg/mg or an increase to UPCR >2 mg/mg from a post-response UPCR of 0.2 to 1.0 mg/mg), as adjudicated by a blinded Clinical Endpoints Committee. Result(s): Overall rates of serious AEs in the voclosporin (26.7% of 116 patients) and control arm (28.0% of 100 patients) were similar. There were no deaths in the voclosporin arm during AURORA 2;four deaths occured in the control arm (pulmonary embolism, n=1;coronavirus infection, n=3). Mean corrected eGFR was within the normal range and stable over the study period. The reductions in UPCR achieved in AURORA 1 were maintained in AURORA 2 and significantly more patients in the voclosporin arm achieved a good renal outcome (66.4% in voclosporin vs 54.0% in control;p-value=0.045). Renal flare occurred in 24 of 101 patients with adequate response in the voclosporin arm and 19 of 73 patients in the control arm (23.8% in voclosporin vs 26.0% in control;p-value=0.662);69.8% of all patients with renal flares completed study treatment. Conclusion(s): Voclosporin was well-tolerated over three years of treatment. The significant reductions in proteinuria initially achieved in AURORA 1 were maintained throughout AURORA 2 and more patients in the voclosporin arm achieved a good renal outcome. These data provide evidence of a long-term treatment benefit of voclosporin in patients with lupus nephritis.

VIRAL FALLOUT: SEMEN PROTEOME REVEALS THAT COVID-19 DYSREGULATES SEVERAL BIOLOGICAL PROCESSES LINKED TO MALE REPRODUCTIVE FUNCTION

OBJECTIVE: The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), poses several catastrophic threat s globally including those on economy, lifestyle and health. Although the respiratory tract is the primary proliferation site of the virus, its effects on other organs and organ systems is devastating. One of the potential tar-gets for SARS-CoV-2 invasion is the male reproductive system owing to the presence of viral receptors i.e., ACE2 and TMPRSS2 in the testis. Currently there are differing views in literature on whether SARS-CoV-2 infection has any short term and long term effects on male fertility. This pilot study was aimed to assess the impact of viral infection on crucial reproductive processes at the molecular level even after recovery. MATERIALS AND METHODS: We performed a label free quantitative proteomic analysis of semen procured from 17 COVID-19 recovered and 10 healthy fertile individuals using high resolution mass spectrometry. RESULTS: Our proteomic analysis resulted in the identification of 48 differentially expressed proteins of which 27 were upregulated and 21 were downregulated in recovered individuals. Further bio-informatic analysis revealed the dysregulation of several biological processes linked to male reproductive functions. Pathways like regulation of cell motility, regulation of adhesion, sperm-egg recognition, response to testosterone, extracellular matrix adhesion and endopeptidase activity were found to be downregulated in the recovered group. Moreover, the down regulation of two candidate proteins;Semenogelin 1 and Prosaposin which are related to male fertility were also validated using targeted proteomic approach CONCLUSIONS: This extensive proteomic study sheds light on the possible effects of SARS-CoV2 infection on reproductive functions and subsequently on male fertility even after apparent recovery from viral infection. IMPACT STATEMENT: The semen proteomic analysis of the COVID-19 recovered patients portrays a clear scenario of alteration of reproductive function in response to viral infection after clinical recovery, thus corroborating a possibility of virus-mediated impact on male infertility. A similar kind of study on large cohort will also direct the way to combat the viral effect on male reproductive function. This study would guide clinicians in counselling couples affected by COVID-19 as to the possible short term and long term effects on male reproductive potential.

Analytical Study Based Modeling for Covid-19 Using Advance Technology

Computer based intelligence innovations and apparatuses assume a key job in each part of the COVID-19 emergency reaction. Understanding the infection and quickening clinical exploration on medications and medicines is one of the factor. Recognizing and diagnosing the infection, and anticipating its advancement helping with forestalling or easing back the infection's spread through reconnaissance and contact following reacting to the wellbeing emergency through customized data and learning checking the recuperation and improving early admonition instruments. To help encourage the utilization of AI all through the emergency, strategy creators ought to energize the sharing of clinical, sub-atomic, and logical datasets and models on synergistic stages to help AI specialists assemble successful instruments for the clinical network, and ought to guarantee that scientists approach the essential processing limit. To understand the full guarantee of AI to battle COVID-19, arrangement producers must guarantee that AI frameworks are reliable and lined up with the OECD AI Principles: they should regard human rights and protection;be straightforward, logical, vigorous, secure and safe;and on-screen characters engaged with their turn of events and utilize ought to stay responsible. Before the world was even mindful of the danger presented by the coronavirus (COVID-19), manmade reasoning (AI) frameworks had distinguished the episode of an obscure kind of pneumonia in the People's Republic of China (in the future "China"). By analyzing different aspects, the intelligent system plays the vital role to generate COVID-19 awareness and which ultimately reduce the infection to others. Proposed paper focus on awareness. © 2021 IEEE.

Observational evidence of NAD+ biosynthetic impairment and urinary metabolomic alterations in covid-related AKI

Background: Acute kidney injury (AKI) is a frequent extrapulmonary manifestation of COVID-19 and is associated with increased morbidity and mortality. We investigated alterations in the urine metabolome associated with AKI among patients with COVID-19, with the hypothesis that changes in nicotinamide adenine dinucleotide (NAD+) metabolism described in ischemic, toxic, and inflammatory AKI will be also associated with AKI in patients with COVID-19. Methods: This is a case-control study among two adult populations with COVID-19: critically ill patients hospitalized in Boston, Massachusetts, and a general hospitalized patient population in Birmingham, Alabama. Cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Controls had no AKI by KDIGO criteria. Metabolites were measured by liquid chromatography -mass spectrometry. Results: 14 cases and 14 controls were included from Boston, and 8 cases and 10 controls included from Birmingham. Urinary quinolinate to tryptophan ratio, an indicator which increases with impaired NAD+ biosynthesis, was higher among cases than controls at each location and pooled across locations (median [IQR]: 1.34 [0.59-2.96] in cases, 0.31 [0.13-1.63] in controls, unadjusted p = 0.0013;p=0.03 in analyses adjusted for age and sex). We identified alterations in tryptophan, nicotinamide, and other components of energy metabolism as well as decreases in purine metabolites which contributed to a distinct urinary metabolomic signature that could reliably differentiate patients with and without AKI (supervised random forest class error: 1/14 for AKI and 1/14 for no AKI groups in Boston, 0/8 for AKI and 0/10 for no AKI groups in Birmingham). Conclusions: Conserved urinary metabolic alterations spanning multiple biochemical pathways distinguish AKI vs. non-AKI in the context of COVID-related hospitalization at two large academic medical centers. AKI is further associated with derangements in NAD+ biosynthesis that suggest impaired energy metabolism in the kidney. Augmenting renal NAD+ by administering biosynthetic precursors may present a novel therapeutic opportunity to mitigate COVID-19 associated AKI.

Safety of emergency, elective and day case operating during the winter period at East Suffolk and North Essex NHS Foundation Trust: lessons from the outcomes of 4,254 surgical patients from the first COVID-19 wave.

BACKGROUND: There is limited evidence on perioperative outcomes of surgical patients during the COVID-19 pandemic to inform continued operating into the winter period. METHODS: We retrospectively analysed the rate of 30-day COVID-19 transmission and mortality of all surgical patients in the three hospitals in our trust in the East of England during the first lockdown in March 2020. All patients who underwent a swab were swabbed on or 24 hours prior to admission. RESULTS: There were 4,254 patients and an overall 30-day mortality of 0.99%. The excess surgical mortality in our region was 0.29%. There were 39 patients who were COVID-19 positive within 30 days of admission, 12 of whom died. All 12 were emergency admissions with a length of stay longer than 24 hours. There were three deaths among those who underwent day case surgery, one of whom was COVID-19 negative, and the other two were not swabbed but not suspected to have COVID-19. There were two COVID-19 positive elective cases and none in day case elective or emergency surgery. There were no COVID-19 positive deaths in elective or day case surgery. CONCLUSIONS: There was a low rate of COVID-19 transmission and mortality in elective and day case operations. Our data have allowed us to guide patients in the consent process and provided the evidence base to restart elective and day case operating with precautions and regular review. A number of regions will be similarly affected and should perform a review of their data for the winter period and beyond.

Running a cardiology consult service during a pandemic: Experiences from the front lines

ABSTRACT: Millions of deaths worldwide have been attributed to the novel coronavirus (COVID-19). As case counts increased in the United States and resurgence occurred in Europe, health care systems across the country prepared for the influx of acutely ill patients. In response to this, our cardiology consult service was called to aid in the management of COVID-19 patients. We describe our experiences and the changes that were implemented.

Ultrasound-guided central vein cannulation in COVID positive patients in ICU

Introduction: Traditionally, central lines are put blindly using anatomical landmarks, which often result in complications, such as, difficulty in access, misplaced lines, pneumothorax, bleeding from inadvertent arterial punctures, etc. •Ultrasonography provides “real-time” imaging, i.e., the needle can be visualized entering the vein that may result in a less associated complication. Objectives: To perform a study regarded •Ease of cannulation. •Time consumed. Materials and methods: Twenty-five critical care patients at the intensive care units of SVP Hospital, Ahmedabad, who needed central venous cannulation, with informed written consent. Results: Out of 25 patients, all (100%) cannulated successfully. In only 1 patient, carotid artery was punctured and was cannulated in second attempt. •96% of patients are cannulated in the first attempt. •Complication rate is 4%. Discussions: After three or more attempts at insertion, mechanical complications increase by six times compared with a single attempt. In the USG-guided approach, most patients are cannulated in the first attempt compared to a conventional method. In the USG technique, access time required is much less. In most patients where Trendelenburg's position may be difficult where USG comes like a gift. Conclusion:: We came to the conclusion that the USG approach took less time, required less attempts, and had a lower incidence of complications for cannulation of the internal jugular vein as compared to a conventional method.

An online international pharmacy summer course during the COVID-19 pandemic

The University of Southern California School of Pharmacy has offered a residential summer course for international undergraduate pharmacy students for many years, with a focus on clinical therapeutics. In 2020, the COVID-19 pandemic made it impossible to offer the on-campus course. After some discussion, the course was moved online, with the goals of maintaining links with international partners and providing students with a virtual study abroad experience. This article describes the planning and implementation of this course, which was held for two weeks in July 2020 for 19 students from South Korea, Taiwan and Saudi Arabia. The course included an integrated science and clinical approach to diabetes and drug-drug interactions. The facilitation of active learning and problem-solving in transnational student groups through Zoom meetings are described. A post-course survey of students provided positive feedback on the content and online delivery of the course.

Analytical study on COVID-19 to predict future infected cases ratio in India using Machine Leaning

COVID-19 is real a worldwide terrific problem. This paper focuses on the different aspects of data analytics and visualization by using various datasets supported by authorized sources. It also discusses the practical aspects using open source tools and python library support. Here chapter focuses on comparative analysis also. It also visualize analytical aspects by different aspects such as country wise, date wise and so on. In this paper, the COVID infected cases and its reaction on people will be discussed. This case study will predict the COVID-19 infected cases and death ratio with symptoms in future. This paper focus on data visualization, data analytics and comparative study based on practical aspects. Machine Learning plays a vital role to predict the cases by providing learning instances. © 2021 Institute of Physics Publishing. All rights reserved.