Antibiotics and Liver Cirrhosis: What the Physicians Need to Know

The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.

Transmission of B.1.617.2 Delta Variant between vaccinated healthcare workers in Delhi, India

Breakthrough infections with SARS-CoV-2 Delta variant have been reported in vaccine recipients and in individuals infected with previous variants, however the potential for doubly vaccinated individuals to transmit the virus is unclear. We here analyse data from health care workers in two hospitals in India, constructing probable transmission networks from epidemiological and virus genome sequence data. Among known cases we identify a high probability that doubly vaccinated individuals transmitted SARS-CoV-2, and potential cases of virus transmission between individuals who had received two doses of vaccine. Our findings highlight the need for ongoing infection control measures even in highly vaccinated populations.

Cohort study of the characteristics and outcomes in patients with COVID-19 and in-hospital cardiac arrest

ObjectiveWe studied characteristics, survival, causes of cardiac arrest, conditions preceding cardiac arrest, predictors of survival and trends in the prevalence of COVID-19 among in-hospital cardiac arrest (IHCA) cases.Design and settingRegistry-based observational study.ParticipantsWe studied all cases (≥18 years of age) of IHCA receiving cardiopulmonary resuscitation in the Swedish Registry for Cardiopulmonary Resuscitation during 15 March 2020 to 31 December 2020. A total of 1613 patients were included and divided into the following groups: ongoing infection (COVID-19+; n=182), no infection (COVID-19–; n=1062) and unknown/not assessed (n=369).Main outcomes and measuresWe studied monthly trends in proportions of COVID-19 associated IHCAs, causes of IHCA in relation to COVID-19 status, clinical conditions preceding the cardiac arrest and predictors of survival.ResultsThe rate of COVID-19+ patients suffering an IHCA increased to 23% during the first pandemic wave (April), then abated to 3% in July, and then increased to 19% during the second wave (December). Among COVID-19+ cases, 43% had respiratory insufficiency or infection as the underlying cause of the cardiac arrest, compared with 18% among COVID-19– cases. The most common clinical sign preceding cardiac arrest was hypoxia (57%) among COVID-19+ cases. OR for 30-day survival for COVID-19+ cases was 0.50 (95% CI 0.33 to 0.76), compared with COVID-19– cases.ConclusionDuring pandemic peaks, up to one-fourth of all IHCAs are complicated by COVID-19, and these patients have halved chance of survival, with women displaying the worst outcomes.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil

Background: Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, although not yet recognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum in Bahia, Brazil and investigated the virological and immunological factors associated with co-infection. Methodology and Principal Findings: We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n=5,346 and CSC-II, n=317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected at the time of HIV-1 diagnosis between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house immunoassay (ELISA) with SLA (Soluble Leishmania Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46% and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10/IP-10 (p=0.0076) and a tendency of increased CXCL9/MIG (p =0.061) in individuals with DP serology for L. infantum, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. Conclusions/Significance: This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

Type I Interferon Induction and Exhaustion during Viral Infection: Plasmacytoid Dendritic Cells and Emerging COVID-19 Findings

Type I Interferons (IFN-I) are a family of potent antiviral cytokines that act through the direct restriction of viral replication and by enhancing antiviral immunity. However, these powerful cytokines are a caged lion, as excessive and sustained IFN-I production can drive immunopathology during infection, and aberrant IFN-I production is a feature of several types of autoimmunity. As specialized producers of IFN-I plasmacytoid (p), dendritic cells (DCs) can secrete superb quantities and a wide breadth of IFN-I isoforms immediately after infection or stimulation, and are the focus of this review. Notably, a few days after viral infection pDCs tune down their capacity for IFN-I production, producing less cytokines in response to both the ongoing infection and unrelated secondary stimulations. This process, hereby referred to as “pDC exhaustion”, favors viral persistence and associates with reduced innate responses and increased susceptibility to secondary opportunistic infections. On the other hand, pDC exhaustion may be a compromise to avoid IFN-I driven immunopathology. In this review we reflect on the mechanisms that initially induce IFN-I and subsequently silence their production by pDCs during a viral infection. While these processes have been long studied across numerous viral infection models, the 2019 coronavirus disease (COVID-19) pandemic has brought their discussion back to the fore, and so we also discuss emerging results related to pDC-IFN-I production in the context of COVID-19.

A review on current strategies and emerging treatments in management of silicosis: An ayurveda perspective

Silicosis is a possibly deadly, irreversible, fibrotic pneumonic sickness that may create resulting to the inward breath of a lot of silica dust over the long haul. As a rule, silicosis just creates resulting to significant word related presentations. The sickness has a long idleness period and may clinically present as an intense, quickened, or ongoing infection.In this audit the medicines that can lessen the aggravation and scarring in which are as nodular injuries in the upper projections of the lungs. The principle point of audit is to the likely home grown treatment for silicosis. This survey zeroed in on different medicines which incorporate natural plants, neutraceuticals, polyherbals, and herbominerals and furthermore cell based treatment for silicosis.From that review we presume that the natural treatment which is utilized in treatment of silicosis is potential treatments which incorporate huge quantities of home grown plants, polyherbals, neutraceuticals and herbominerals likewise incorporate the new treatment for silicosis is the cell based treatment.

Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics

Ongoing infection with, and associated viral reproduction of, SARS-CoV-2 provides opportunities for the virus to acquire advantageous mutations, which may alter viral transmissibility and disease severity, and allow escape from natural or vaccine-derived immunity. The number of countries reporting Variants of Concern (VOCs) with such mutations continues to rise. Here, we investigate two scenarios for third waves of the COVID pandemic: one driven by increased transmissibility, and another driven by immune escape. We do this using three mathematical models: a parsimonious susceptible-latent-infectious-recovered (SEIR) deterministic model with homogeneous mixing, an age-structured SARS-CoV-2 transmission model and a stochastic importation model. We calibrated our models to the situation in England in May 2021, although the insights will generalise to other contexts. We therefore accurately captured infection dynamics and vaccination rates, and also used these to explore the potential impact of a putative new VOC-targeted vaccine. Epidemiological trajectories for putative VOCs are wide-ranging and heavily dependent on their transmissibility, immune escape capability, and the time at which a postulated VOC-targeted vaccine may be introduced. We demonstrate that a VOC with either a substantial transmission advantage over resident variants, or the ability to evade vaccine-derived and prior immunity, is expected to generate a wave of infections and hospitalisations comparable to those seen in the winter 2020-21 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

Despite extensive and ongoing studies of SARS-CoV-2 and evidence that pregnant women are at increased risk of severe COVID-19, the effect of maternal infection on the developing infant remains unclear. To determine the potential impact of exposure to SARS-CoV-2 in utero on the neonate, we have assessed the immunological status of infants born to mothers with confirmed SARS-CoV-2 infection during gestation. No evidence of vertical transmission of SARS-CoV-2 was observed, but transfer of maternal SARS-CoV-2 specific IgG to infants was apparent, although to a lesser extent in cases of active or recent maternal infection. Infants born to mothers with recent/ongoing infection had elevated circulating pro-inflammatory cytokines and enhanced percentages of innate immune cells compared to that seen in infants born to uninfected mothers. In tandem, higher frequencies of FOXP3+ regulatory T cells and circulating IL-10 demonstrated a further nuance to the neonatal effector response. Interestingly, cytokine functionality was enhanced in infants born to mothers exposed to SARS-CoV-2 at any time during pregnancy. This indicates that maternal SARS-CoV-2 infection influences in utero priming of the fetal immune system.

Hepatitis E Virus Immunoglobulin M (IgM) and associated risk factors in southwest, Nigeria

Hepatitis E is one of the most frequent causes of acute hepatitis worldwide, with an estimated 20 million infections and 70,000 deaths attributed to hepatitis E virus (HEV) genotypes 1 and 2 every year. This study was designed to determine the prevalence of HEV immunoglobulin M (IgM) in southwest (SW) Nigeria. Venous blood samples totalling 359 were collected from pregnant women on routine check, apparently healthy prospective blood donors and sick individuals presenting with fever and abdominal disturbance from health facilities in Ekiti, Lagos, Osun and Oyo states, of Nigeria. A structured questionnaire form was administered to gather socio-demographic data, health and travel history from each consenting participant. The screening for HEV IgM was done using HEV IgM ELISA kit. Statistical analyses, including descriptive analysis, correlations and binary logistic regression were carried out using SPSS version 21. In all, 131 samples (36.5%) tested positive for HEV IgM. Osun state had the highest occurrence of HEV IgM (n = 49; 13.6%,) while Ekiti had the least (n= 22; 6.1%). Apparently healthy participants with detectable HEV IgM were 52 (14.5%) while pregnant womenwere 51 (14.2%). Risk factors implicated in this study were flooding and injection drug use. The overall HEV prevalence reported in this study was higher than previous reports in Nigeria . Higher HEV prevalence in this study could be due to a larger coverage area in the country as well as detection of ongoing infection. The detection of HEV IgM in pregnant women and apparently healthy prospective blood donors indicated ongoing infection with risk of spread to susceptibles since HEV is neither routinely screened for among pregnant women nor among prospective blood donors. Keywords: Hepatitis E, IgM, Pregnancy, Apparently healthy, ELISA Depth, Geothermal Energy

Spontaneously Regressing Neonatal Oral Aphthous Ulceration of the Palate

Background. Neonatal oral aphthous ulceration of the palate also known as Bednar’s aphthae is not an uncommon presentation. They clinically present as spontaneously regressing, shallow, and symmetrical ulcers on the posterior palate of newborns from 2 days up to 6 weeks of age. Case Presentation. We, herein, report a case of a one-month-old baby girl who presented with an ulcer in the posterior palate and intermittent mild fever. The patient was admitted and monitored in the ward. Haematologic investigations disclosed features of ongoing infection. Nasogastric feeding was commenced to avoid any irritation of the ulcer, and glycerine was applied on the ulcer. Antibiotic therapy was continued because of the intermittent mild fever. The lesion healed spontaneously within one week, and fever subsided afterwards. Currently, the patient is faring healthily without any complications. Conclusion. Although Bednar’s aphthae is not a rare presentation, clinicians are often met with a diagnostic dilemma due to the alarming clinical presentation of this condition. Therefore, it leads to overinvestigation and overtreatment. With this case report, we would like to highlight the importance of being aware of this condition to provide the patients with the appropriate treatment.