Evaluation of microalbuminuria in patients with systemic sclerosis as an indicator of early renal damage and increased morbidity

AbstractIntroductionRenal involvement and systemic vascular damage have been shown to be significantly affecting prognosis in systemic sclerosis.Aim of workMicroalbuminuria detection in SSc patients as an indicator of early renal involvement and its correlation with various SSc clinical, laboratory parameters and severity of organ systems’ damage assessed by Scleroderma Assessment Questionnaire.Patients and methodsForty SSc patients (33 females and 7 males) with mean age of 27.48±12.56years and mean disease duration of 6.2±4.14years were included. Twenty-four (60%) had lSSc; 13 (32.5%) had dSSc and 3 (7.5%) patients had SSc sine scleroderma.ResultsEight (20%) had microalbuminuria and 9 (22.5%) patients had decreased creatinine clearance. Albumin/creatinine ratio was significantly higher among dSSc patients compared to those with lSSc and SSc sine scleroderma (X2=9.077; p=0.01). Albumin/creatinine ratio showed significant positive correlations with telangiectasia (r=0.322; p=0.04) and mRodnan’s skin score (r=0.352; p=0.026) and negative correlations with inter-incisor distance (r=−0.525; p=0.001) and pleurisy (r=−0.446; p=0.004). Albumin/creatinine ratio correlated significantly and positively with IMSS and IDS indices of SAQ (r=0.378, 0.32; p=0.016, 0.044, respectively). SSc patients with microalbuminuria showed significantly higher mean IDS than those without (1.058 vs. 0.631, p=0.04). No statistically significant correlations were found between creatinine clearance and the different demographic, clinical features and the indices of SAQ.ConclusionMicroalbuminuria compared to creatinine clearance may be a more sensitive indicator of early renal affection and predictor of increased morbidity

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Comparative study of epidural morphine and epidural dexmedetomidine used as adjuvant to levobupivacaine in major abdominal surgery

Background: A lot of researches have been done to find an adjuvant in regional anesthesia that inhibits pain without any side effects. Aim: This study was conducted to evaluate the onset, extent and duration of sensory and motor block, and side effects of morphine and dexmedetomidine when used as adjuvants to levobupivacaine in epidural anesthesia in major abdominal surgery. Materials and methods: A prospective randomized study was conducted on 60 patients classified as American Society of Anesthesiologists status I and status II who underwent abdominal surgery. Patients were randomly allocated into two groups; group I levobupivacaine morphine group (LM), group II: levobupivacaine dexmedetomidine group (LD), comprising of 30 patients each. Group I patients received 20 ml of 0.5% levobupivacaine (150 mg) and 0.005 % morphine. Group II patients received 20 ml of 0.5% levobupivacaine and 1.5 μg/kg dexmedetomidine. The onset, extent and duration of sensory and motor blocks, abdominal muscle relaxation, and side effects were recorded. Results: There were no statistically significant differences between the two groups as regards onset of sensory block or sensory level achieved. Time to reach motor block was shorter in the LM group than the LD group. There were no significant differences between the time of total regression of sensory or motor black and abdominal muscle relaxation. As regards side effects, more patients in the LM group suffered from pruritis and more patients suffered from dry mouth in the LD group. Conclusion: Dexmedetomidine is a good alternative to morphine as an adjuvant to levobupivacaine in epidural anesthesia in major abdominal surgeries

Assessment of tumor necrosis factor superfamily member 10 (TNFSF10) gene variants in systemic lupus erythematosus patients

Aim of the work: To investigate the association between tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) 1525 G > A (TNF supefamily member 10; TNFSF10, rs1131568) and 1595 C > T (TNFSF10 rs1131580) genetic variants and systemic lupus erythematosus (SLE) susceptibility in Egyptian patients and their relationship with clinical and laboratory outcomes of the disease. Patients and methods: A total of 123 SLE patients and 110 age- and sex-matched healthy control subjects were tested for TRAIL 1525 G > A and 1595 C > T genotyping by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), followed by confirmation of random samples from each genotype by direct sequencing technique. Disease activity was determined using the SLE Disease Activity Index (SLEDAI). Results: The patients were 107 females and 16 males with mean age 32.87 ± 9.6 years. The median value of SLEDAI of the patients was 18 (12–27). The two genetic variants of TRAIL, 1525 G > A and 1595 C > T, were in complete linkage disequilibrium. There was a significant increase in the frequencies of combined genotypes (GA + AA)/(CT + TT) and A/T alleles of TRAIL 1525/1595 variants among SLE cases when compared with the control group (OR = 1.7, 95 % CI = 1.0 – 2.98, p = 0.048; OR = 1.7, 95 % CI = 1.1 – 2.8, p = 0.02, respectively). Additionally, the A/T variants of TRAIL 1525/1595 were associated with higher risks of developing lupus nephritis (OR = 2.6, 95 % CI = 1.2 – 5.7, p = 0.015) and higher disease activity (OR = 3.8, 95 % CI = 1.3 – 10.9, p = 0.010). Conclusion: TRAIL 1525 G > A and 1595 C > T gene variants confer susceptibility to SLE, which is significantly related to the clinical phenotypes of SLE and associated with higher disease activity

Effect of sodium hypochlorite on Fasciola gigantica eggs and the intermediate host, Lymnaea natalensis: A scanning electron microscopy study

AbstractThe liver fluke Fasciola is one of the commonest causative agents of liver disease in the world. Infection with this organism is of veterinary and medical importance, particularly in areas of high-density cattle and sheep production. Sodium hypochlorite (NaOCl) has been suggested for use in the control of Fasciola transmission. The current study was designed to evaluate the effect of NaOCl on the eggs and their intermediate hosts (Lymnaea natalensis snails) by scanning electron microscopy. Exposure of eggs to NaOCl had markedly deleterious effects on the whole body surface, from smooth to oedematous and disrupted, and on their integrity. These effects were concentration-dependent. Treatment of the intermediate host with various concentrations of NaOCl increased the mortality rate, and the effect was also dependent on concentration and length of exposure. Scanning electron microscopy of the snail foot region showed extensive alterations of the surface, with damage in some areas, after treatment with 10ppm NaOCl for 15min. Sodium hypochlorite may therefore be a useful control measure for eliminating both Fasciola eggs and the intermediate snail host