Mutations at the conserved N-Terminal of the human Rhinovirus capsid gene VP4, and their impact on the immune response.

Rhinoviruses (RV) are the major cause of chronic obstructive pulmonary disease and are associated with exacerbation development as well as community-acquired pneumonia in children, leading to substantial morbidity, mortality, and hospital admission. Here we have examined how changes at the amino terminal of the conserved VP4 epitope of different RV serotypes may affect pulmonary cytokine and chemokine responses and disease severity. Samples positive for rhinovirus were used for genetic characterization, followed by profiling gene expression of pulmonary Th1 and Th2 cytokines/chemokines by RT-PCR arrays. Genetic sequencing and homology 3D modeling revealed changes at the amino terminal of the conserved viral protein 4 (VP4) epitope in the RV-A101 serotype, especially serine at several positions that are important for interactive binding with the host immune cells. We found dysregulation of pulmonary gene expression of Th1- and Th2-related cytokines and chemokines in RV-A 101 and RV-C 8 pneumonia patients. These findings might contribute to a better understanding of RV immunity and the potential mechanisms underlying the pathogenesis of severe RV infections, but further functional studies are needed to confirm the causal relationship.

Types of home respiratory support in children with bronchopulmonary dysplasia and factors determining its duration: A scoping review.

Bronchopulmonary dysplasia also known as chronic lung disease of prematurity has changed as a disease entity over the last five decades and children with "new bronchopulmonary dysplasia (BPD)" have better survival rates. This necessitates strategies to prevent severe BPD and provide organized home support. Home respiratory support in these children varies from home oxygen to noninvasive ventilation and tracheostomy ventilation. This review was conducted utilizing Joanna Briggs Institute publications on evidence synthesis and presentation of results for a scoping review. The Preferred Reporting Items for Systematic Review and Meta-Analyses were used to report the results. The risk of bias assessment was done using "The Cochrane Handbook for Systematic Reviews tool for interventional studies." After screening for the duplication of results and applying inclusion and exclusion criteria, twenty-seven studies were assessed by reading the full texts. Out of these, eleven were finally included in this systematic review. The total sample size from all studies was 4794, including 2705 males. The 4/11 studies home oxygen, one study reported continuous positive airway pressure/bilevel positive airway pressure and seven studies used tracheostomy or tracheostomy ventilation. The median duration of post-natal invasive ventilation was higher in those discharged on home oxygen compared to those who did not need oxygen at discharge. There is a significant proportion of children who are tracheostomy ventilated (8.65%) at home. In the absence of established guidelines, these children are vulnerable when it comes to care at home and the timing of decannulation. For home oxygen alone, guidelines by ERS, ATS and BTS have streamlined weaning protocols and the need for having a multi-disciplinary team to care for these children.

Use of abdominal compression device in colonoscopy: a systematic review and meta-analysis.

BACKGROUND/AIMS: Colonoscopy for screening is associated with unpleasant experiences for patients, and abdominal compression devices have been developed to minimize these problems. However, there is a paucity of data supporting the therapeutic benefits of this strategy. This study examined the effects of using an abdominal compression device during colonoscopy on the cecal intubation time (CIT), abdominal compression, patient comfort, and postural changes. METHODS: We searched PubMed and Scopus (from inception to November 2021) for randomized controlled trials that assessed the effects of an abdominal compression device during colonoscopy on CIT, abdominal compression, patient comfort, and postural change. A random-effects meta-analysis was performed. Weighted mean differences (WMDs) and Mantel-Haenszel odds ratios (ORs) were calculated. RESULTS: Our pooled analysis of seven randomized controlled trials revealed that abdominal compression devices significantly reduced CIT (WMD, -0.76 [-1.49 to -0.03] minutes; p=0.04), abdominal compression (OR, 0.52; 95% confidence interval [CI], 0.28-0.94; p=0.03), and postural changes (OR, 0.46; 95% CI, 0.27-0.78; p=0.004) during colonoscopy. However, our results did not show a significant change in patient comfort (WMD, -0.48; 95% CI, -1.05 to 0.08; p=0.09) when using an abdominal compression device. CONCLUSION: Our findings demonstrate that employing an abdominal compression device may reduce CIT, abdominal compression, and postural change but have no impact on patient comfort.

The association of antibiotic exposure with new-onset inflammatory bowel disease: A systematic review and meta-analysis.

INTRODUCTION: The role of antibiotics in the development of inflammatory bowel disease (IBD) remains controversial, primarily due to conflicting data from individual studies. We conduct a systematic review and meta-analysis to study the effect of antibiotic exposure on IBD development. METHODOLOGY: The MEDLINE and Cochrane CENTRAL databases were queried from their inception to April 2021 for published articles studying the association between antibiotic exposure and new-onset IBD. Our analysis was stratified by timing of antibiotic exposure - exposure in childhood and any lifetime exposure. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) from each study were pooled using a random-effects model. RESULTS: 10 case-control studies and 2 cohort studies (N = 29,880 IBD patients and N = 715,548 controls) were included. Patients with Crohn's Disease (CD), compared with controls, were associated significantly with antibiotic exposure in childhood and any lifetime exposure to antibiotics (OR 1.52 [1.23-1.87]; p<0.00001). Patients with Ulcerative Colitis (UC), compared with controls, reported non-significant association with antibiotic exposure in childhood and any lifetime exposure. (OR 1.11 [0.93-1.33]; p = 0.25) CONCLUSION: This meta-analysis suggests that exposure to antibiotics significantly increases the odds of developing CD and IBD. These findings re-emphasize the importance of cautious and judicious use of antibiotics.

Two cases of complicated jejunal diverticulosis in a low-resource peripheral teaching hospital.

Jejunal diverticula, like other intestinal diverticula, can become complicated and present as acute abdomen. Diagnosis is difficult and management in complicated cases can be surgical as well as conservative. We present two cases of complicated jejunal diverticulosis that presented with acute abdomen and were managed surgically. Post-operative recovery was satisfactory. Jejunal diverticula is a diagnostic challenge in a low-resource peripheral hospital.

In children with primary ciliary dyskinesia, which type of lung function test is the earliest determinant of decline in lung health: A systematic review.

BACKGROUND: Primary ciliary dyskinesia is a rare genetic disorder characterized by recurrent sinopulmonary infections and worsening obstructive lung disease. Kidney and brain involvement is less common and is associated with overlapping ciliopathies/syndromes. The lungs are impacted early in the course of the disease, so it is vital to monitor lung function and recognize any decline by doing appropriate lung function tests. This systematic review compares different lung function tests and analyzes which one becomes abnormal earlier in the disease. METHODS: A systematic review was conducted following the methodology in the "Cochrane Handbook on Systematic Reviews for diagnostic tests." The Preferred Reporting Items for Systematic Review and Meta-Analyses were used to report the results. The risk of bias assessment was done using "The Cochrane Handbook for Systematic Reviews tool for interventional studies." A meta-analysis was not performed due to the small sample size. All studies were analyzed by using Joanna Briggs Institute's critical appraisal tool. RESULTS: After screening for the duplication of results and applying inclusion and exclusion criteria, 14 studies were assessed by reading the full texts. Out of these, eight were finally included in this systematic review. The total sample size from all studies was 165, including 80 males. All the studies used spirometry as a lung function test, whereas multiple breath washout was used in five studies. Other tests used for comparison were computed tomography (CT), magnetic resonance imaging (MRI), cardiopulmonary exercise testing, 6-min walk test, DLCO, maximal inspiratory pressure, maximal expiratory pressure, and PaO2 . Lung clearance index (LCI) by multiple breath washout had a stronger association with the structural changes on CT/MRI than spirometry indices like forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25% to 75% of lung volume (FEF 25-75). CONCLUSIONS: Based on the evidence from this systematic review, LCI becomes abnormal earlier than FEV1 or FEF 25-75 and positively correlates with the findings on high-resolution CT. It has limitations like the lack of reference values and a complex technique to perform the test.

Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings. METHODS: This was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup. RESULTS: In our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m2, with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings. CONCLUSION: We describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

Influenza co-infection associated with severity and mortality in COVID-19 patients.

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

Campylobacter coli bacteraemia: how common is it?

Campylobacter species are known to cause enteritis. However, over the past 40-50 years, there have been reports of varying presentations, such as cellulitis, spondylodiscitis and bacteraemia. Of the Campylobacter species, Campylobacter jejuni is the most common culprit for causing bacteraemia, however, Campylobacter coli bacteraemia is becoming more prevalent. Here, we discuss an unusual case of C. coli bacteraemia in a patient with decompensated liver cirrhosis.

Complicated Colonic Diverticulitis Presenting as Vaginal Bleeding: An Unusual Presentation.

Colonic diverticula are small outpouchings from the colonic lumen secondary to mucosal herniation through the colonic wall. Clinical presentation usually involves an acute or subacute onset of abdominal pain typically localized in the left lower abdominal quadrant as well as nausea, low-grade fever, bowel habit changes, and elevated inflammatory markers. We present a case of complicated colonic diverticulitis with vaginal fistula with eventual formation of abdominal abscess, presenting as vaginal bleeding and pelvic pain.

COVID-19 in a Three-Year-Old Girl With Total Anomalous Pulmonary Venous Return: A Case Report.

Total anomalous pulmonary venous return (TAPVR) is a rare congenital heart disease (CHD) with an incidence of less than 1%. It is known that coronavirus disease 2019 (COVID-19) has a worse prognosis in those with underlying disorders. Children with congenital heart defects can contract COVID-19 irrespective of their surgical correction status. We report a case of a three-year-old girl with unoperated TAPVR, who presented with respiratory distress, lethargy, and reduced feeding. Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate came back positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There was no growth of any other viral or bacterial pathogens. Throughout her admission, she had an overall mild course of the disease and did not need mechanical ventilation. Oxygen was given via nasal cannula to maintain SpO2 in the target range. Chest X-ray (CXR) showed bilateral patchy consolidation while a chest CT with contrast showed significant venous congestion. Her length of hospital stay was 25 days. Infection with SARS-CoV-2 did not cause a critical disease and was not different clinically to any other bacterial or viral infection. The potential risk of further cardiac deterioration in COVID-19 in any CHD should be handled with caution as these children can decompensate rapidly.

Prolonged expiratory apnoea with cyanosis in Arnold Chiari II malformation.

Apnoea associated with Arnold Chiari malformation is a known entity and can be obstructive or central. Differentiating between two types is vital to deciding management pathway and prognosticating disease process.