Lung Ultrasonography Accuracy for Diagnosis of Adult Pneumonia: Systematic Review and Meta-Analysis.

BACKGROUND: Pneumonia is a ubiquitous health condition with severe outcomes. The advancement of ultrasonography techniques allows its application in evaluating pulmonary diseases, providing safer and accessible bedside therapeutic decisions compared to chest X-ray and chest computed tomography (CT) scan. Because of its aforementioned benefits, we aimed to confirm the diagnostic accuracy of lung ultrasound (LUS) for pneumonia in adults. METHODS: A systematic literature search was performed of Medline, Cochrane and Crossref, independently by two authors. The selection of studies proceeded based on specific inclusion and exclusion criteria without restrictions to particular study designs, language or publication dates and was followed by data extraction. The gold standard reference in the included studies was chest X-ray/CT scan or both. RESULTS: Twenty-nine (29) studies containing 6702 participants were included in our meta-analysis. Pooled sensitivity, specificity and PPV were 92% (95% CI: 91-93%), 94% (95% CI: 94 to 95%) and 93% (95% CI: 89 to 96%), respectively. Pooled positive and negative likelihood ratios were 16 (95% CI: 14 to 19) and 0.08 (95% CI: 0.07 to 0.09). The area under the ROC curve of LUS was 0. 9712. CONCLUSIONS: LUS has high diagnostic accuracy in adult pneumonia. Its contribution could form an optimistic clue in future updates considering this condition.

Continuous Wave Transscleral Cyclophotocoagulation and Endoscopic Cyclophotocoagulation in Childhood Glaucoma: A Meta-Analysis.

PRCIS: Transscleral cyclophotocoagulation (TS-CPC) and endoscopic cyclophotocoagulation (ECP) were effective in reducing intraocular pressure (IOP) and glaucoma medications in childhood glaucoma. OBJECTIVE: To report the outcomes of continuous wave TS-CPC and ECP in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic search of relevant databases. We collected data on age, follow-up duration, type of glaucoma, previous surgical interventions, preoperative and postoperative IOP, preoperative and postoperative number of glaucoma medications, adverse events, number of sessions, and success rates at different time points. The main outcome measures are the amount of IOP and glaucoma medication reduction. RESULTS: We included 17 studies studying 526 patients (658 eyes); 11 evaluated the effectiveness of TS-CPC (268 patients, 337 eyes), 5 evaluated ECP (159 patients, 197 eyes), and one study compared both techniques (56 patients, 72 eyes for TS-CPC vs 43 patients, 52 eyes for ECP). The median duration of follow-up was 28 months in the TS-CPC group and 34.4 months in the ECP group. The mean number of treatment sessions was 1.7 in the TS-CPC and 1.3 in the ECP. In the TS-CPC group, the mean IOP was significantly reduced from 31.2 ± 8 to 20.8 ± 8 mm Hg at the last follow-up ( P < 0.001). The mean number of glaucoma medications was reduced from 2.3 ± 1.3 to 2.2 ± 1.3 ( P = 0.37). In the ECP group, there was also a significant reduction in the mean IOP from 32.9 ± 8 mm Hg with a mean of 1.7 ± 0.7 glaucoma medications to 22.6 ± 9.8 mm Hg ( P < 0.0001) on 1.2 ± 1.1 medications ( P = 0.009) at the last follow-up. CONCLUSION: Both TS-CPC and ECP were effective in reducing the IOP and glaucoma medications in childhood glaucoma. Multiple treatment sessions were required.

Isolated eyelid neonatal Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a condition characterized by clonal proliferation of the phagocytic cells derived from the bone marrow. In this article, we present an exceedingly rare case of congenital/neonatal LCH in a 3-week-old girl who initially presented with an isolated swelling of the eyelid, initially misdiagnosed as a chalazion. Subsequently, a biopsy was performed, and histopathological evaluation confirmed the diagnosis of LCH. A staging work-up revealed no evidence of multisystem involvement, and thus, local steroid injection was performed as the initial treatment for the residual lesion. Cases of localized LCH that manifest as eyelid masses are rare, and most reported cases involve children over the age of one year. To the best of our knowledge, this case represents the first reported instance of neonatal LCH presenting as an eyelid mass. Although neonatal LCH is rare, ophthalmologists must be aware of this presentation and include it in the differential diagnosis for eyelid lesions in infants during the first month of life.

Ahmed and Baerveldt Glaucoma Drainage Devices in Childhood Glaucoma: A Meta-Analysis.

PRCIS: The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group. PURPOSE: To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model. RESULTS: Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg ( P < 0.00001) for AGV and 14.62 ( P < 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 ( P < 0.00001) fewer medications in the AGV group and 0.95 ( P < 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63% vs 83%, respectively ( P < 0.0001) and 3 years (43% vs 79%, respectively ( P < 0.0001)]; however, the success was higher for AGV at 5 years (63% vs 56% in the BGI group, P < 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28% and 27%, respectively. CONCLUSIONS: The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.

British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

BACKGROUND: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. METHODS: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. RESULTS: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. CONCLUSIONS: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

Structure of the C1r-C1s interaction of the C1 complex of complement activation.

The multiprotein complex C1 initiates the classical pathway of complement activation on binding to antibody-antigen complexes, pathogen surfaces, apoptotic cells, and polyanionic structures. It is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2 as a Ca2+-dependent complex. Here we have determined the structure of a complex between the CUB1-EGF-CUB2 fragments of C1r and C1s to reveal the C1r-C1s interaction that forms the core of C1. Both fragments are L-shaped and interlock to form a compact antiparallel heterodimer with a Ca2+ from each subcomponent at the interface. Contacts, involving all three domains of each protease, are more extensive than those of C1r or C1s homodimers, explaining why heterocomplexes form preferentially. The available structural and biophysical data support a model of C1r2C1s2 in which two C1r-C1s dimers are linked via the catalytic domains of C1r. They are incompatible with a recent model in which the N-terminal domains of C1r and C1s form a fixed tetramer. On binding to C1q, the proteases become more compact, with the C1r-C1s dimers at the center and the six collagenous stems of C1q arranged around the perimeter. Activation is likely driven by separation of the C1r-C1s dimer pairs when C1q binds to a surface. Considerable flexibility in C1s likely facilitates C1 complex formation, activation of C1s by C1r, and binding and activation of downstream substrates C4 and C4b-bound C2 to initiate the reaction cascade.

Eosinophilic oesophagitis.

Eosinophilic oesophagitis is a chronic immune-mediated inflammatory disorder of the oesophagus, characterized by symptoms of dysphagia or food bolus obstruction. Diagnosis is supported by typical histological findings. This article covers pertinent aspects of the disease, pathogenic explanations and treatment options.

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease.

OBJECTIVE: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). DESIGN: 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). RESULTS: 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD+HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. CONCLUSION: In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.

The effects of sleeve gastectomy on gastro-esophageal reflux and gastro-esophageal motility.

Sleeve gastrectomy is an increasingly performed bariatric procedure associated with low morbidity and good short to medium term effects on weight loss and comorbid conditions. Studies assessing the prevalence of post-operative gastro-esophageal reflux disease (GERD), show sleeve gastrectomy may provoke de novo GERD symptoms or worsening of pre-existing GERD. Pathophysiological mechanisms of GERD after sleeve gastrectomy include a hypotensive lower esophageal sphincter, increased gastro-esophageal pressure gradient and intra-thoracic migration of the remnant stomach. A reduction in the compliance of the gastric remnant may provoke an increase in transient lower esophageal sphincter relaxations. Time-resolved MRI suggests relative gastric stasis in the proximal remnant and increased emptying from the antrum. A lack of standardisation of technique, along with heterogeneity of studies assessing GERD may explain the wide variability in reported results. Simultaneous and careful repair of an associated hiatus hernia may result in a reduction in the prevalence of post-operative GERD.

Objective detection of esophagopharyngeal reflux in patients with hoarseness and endoscopic signs of laryngeal inflammation.

GOALS: We aimed to quantify pharyngeal exposure to gastric contents in patients diagnosed with reflux-related hoarseness and healthy controls using new diagnostic techniques. BACKGROUND: Hoarseness with typical signs on laryngoscopy is commonly thought to be caused by esophagopharyngeal reflux. New methods are proposed to assess pharyngeal exposure to gastric contents. They are suggested to measure: (1) liquid or mixed gas-liquid acid and nonacid reflux with impedance pH, (2) aerosolized acid reflux (Dx-pH measuring system), and (3) pepsin in the saliva. STUDY: Twenty-one patients with hoarseness and positive laryngoscopy and 10 controls underwent simultaneous impedance pH, Dx-pH monitoring, and saliva pepsin sampling (5 samples in 24 h). RESULTS: Of the 21 patients, 10 had impedance pH-detected reflux plus at least 1 other test positive. These patients were more likely to have symptomatic relief after proton pump inhibitor therapy. Three of the 21 patients had all 3 tests positive and 4 had all tests negative. None of the controls had impedance pH-detected reflux. Two controls had a positive Dx-pH "RYAN score" and 1 control had >1 saliva sample positive for pepsin. Only 11% of Dx-pH drops to pH<4, 15% pH drops to pH<5, and 10% of pH drops to pH<5.5 coincided with impedance pH-detected reflux in the esophageal body. Positive pepsin saliva samples were preceded by more reflux events [3 (range, 0 to 10)] in the previous 60 minutes than negative samples [0 (range, 0 to 7)] (P<0.0001). CONCLUSION: A subgroup of patients with hoarseness (10/21) had objective detection of the esophagopharyngeal reflux. We propose that these patients are more likely to benefit from further intense antireflux therapy. Detection of pepsin in the saliva may be a useful screening tool in these patients.

Paediatric endoscopy performed by adult-service gastroenterologists.

BACKGROUND: Children often travel from district hospitals to teaching centres for endoscopic procedures by paediatric gastroenterologists. A 10-year district hospital experience of 'adult-service' gastroenterologists endoscoping children is reported with the aim of quantifying the workload, indications, sedation/anaesthesia practices, findings and safety of paediatric endoscopy performed by adult-service gastroenterologists. METHODS: Data on endoscopic procedures in patients younger than 16 years of age between 1997 and 2006 were obtained from hospital case-notes and computerized endoscopy/histology databases and were analysed. RESULTS: A total of 174 procedures (118 gastroscopies, 41 colonoscopies and 15 flexible sigmoidoscopies) were performed in 162 children. The median (interquartile range) age was 11.5 (5-14) years. Sixty-nine percent of patients were referred by paediatricians and 31% by general practitioners /other adult specialties. Children referred as outpatients waited a total of 50 (23.5-95) days from referral to procedure. Inpatient children waited 3 (1-4) days for their procedure. General anaesthesia was used in 89% (63 of 71) endoscopic procedures in children aged below 11 years and 100% of 47 procedures in children aged below 6 years. In contrast, 96% (99 of 103) procedures in children aged 11 years or older were done in the endoscopy unit with intravenous or no sedation. Organic disease was identified from 90 (52%) procedures. The most common diagnoses were coeliac disease (41), inflammatory bowel disease (26), gastro-oesophageal reflux (six) and foreign body removal (seven). No endoscopic complications occurred. CONCLUSION: General gastroenterologists supported by paediatricians can provide endoscopic services for children safely and promptly in their local hospital. This is appropriate for the management of common gastrointestinal problems affecting children.

Calcium channel TRPV6 expression in human duodenum: different relationships to the vitamin D system and aging in men and women.

UNLABELLED: Intestinal absorption of calcium affects bone mineralization and varies greatly. In human duodenum, expression of the calcium channel TRPV6 was directly related to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median vitamin D receptor levels were more significant in women. INTRODUCTION: The TRPV6 calcium channel/transporter is implicated in animal studies of intestinal calcium absorption, but in humans, its role and relationship to differences in mineral metabolism is unclear. We aimed to characterize TRPV6 expression in human intestine including defining relationships to the vitamin D endocrine system. MATERIALS AND METHODS: TRPV6 transcript expression was determined in endoscopic mucosal biopsies obtained from normal duodenum. Expression was compared with that in ileum and with in situ hybridization in archival tissues and related to sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to other transcripts involved in calcium absorption including the vitamin D receptor (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. RESULTS: TRPV6 transcripts were readily detected in duodenum but not in ileum. Expression was highest in villous epithelial cells. Sequence variants in the coding and upstream regions of the gene did not affect TRPV6 expression. The relationship between duodenal TRPV6 expression and 1,25(OH)(2)D differed in men and women. In men, linear regression showed a strong association with 1,25(OH)(2)D (r = 0.87, p < 0.01), which was unaffected by age. In women, there was no significant overall relationship with 1,25(OH)(2)D, but there was a significant decrease with age (r = -0.69, p < 0.001). Individual expression of TRPV6 and VDR was significantly correlated. The group of older women (>50) had lower median levels of both TRPV6 and VDR transcripts than younger women (p < 0.001 and 0.02, respectively). CONCLUSIONS: Duodenal TRPV6 expression is vitamin D dependent in men, but not in older women, where expression of TRPV6 and VDR are both reduced. These findings can explain, at least in part, the lower fractional calcium absorption seen in older postmenopausal women.

Type IIA secretory phospholipase A2 up-regulates cyclooxygenase-2 and amplifies cytokine-mediated prostaglandin production in human rheumatoid synoviocytes.

Human type IIA secretory phospholipase A2 (sPLA2-IIA) is induced in association with several immune-mediated inflammatory conditions. We have evaluated the effect of sPLA2-IIA on PG production in primary synovial fibroblasts from patients with rheumatoid arthritis (RA). At concentrations found in the synovial fluid of RA patients, exogenously added sPLA2-IIA dose-dependently amplified TNF-alpha-stimulated PGE2 production by cultured synovial fibroblasts. Enhancement of TNF-alpha-stimulated PGE2 production in synovial cells was accompanied by increased expression of cyclooxygenase (COX)-2 and cytosolic phospholipase A2 (cPLA2)-alpha. Blockade of COX-2 enzyme activity with the selective inhibitor NS-398 prevented both TNF-alpha-stimulated and sPLA2-IIA-amplified PGE2 production without affecting COX-2 protein induction. However, both sPLA2-IIA-amplified PGE2 production and enhanced COX-2 expression were blocked by the sPLA2 inhibitor LY311727. Colocalization studies using triple-labeling immunofluorescence microscopy showed that sPLA2-IIA and cPLA2-alpha are coexpressed with COX-2 in discrete populations of CD14-positive synovial macrophages and synovial tissue fibroblasts from RA patients. Based on these findings, we propose a model whereby the enhanced expression of sPLA2-IIA by RA synovial cells up-regulates TNF-alpha-mediated PG production via superinduction of COX-2. Therefore, sPLA2-IIA may be a critical modulator of cytokine-mediated synovial inflammation in RA.

Increased expression of human type IIa secretory phospholipase A2 antigen in arthritic synovium.

OBJECTIVE: To determine the localisation and level of expression of human type IIa secretory phospholipase A2 (sPLA2) in the synovium of rheumatoid arthritis (RA), osteoarthritis (OA), and non-arthritic (NA) patients and to examine the relation between sPLA2 and histological features of inflammation. METHODS: Immunoperoxidase staining using the anti-sPLA2 monoclonal antibody 9C1 was performed on frozen sections of knee synovium of 10 RA, 10 OA, and 10 NA patients. sPLA2 positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double labelling immunofluorescence confocal microscopy with antibodies to CD14 or CD45 and 9C1 was used to determine cell type specificity. Inflammation was assessed by semiquantitative scoring of lining layer thickness and mononuclear cell infiltrates (MC) and a cumulative inflammation score, generated by summing the two parameters. Scores in each group were compared using non-parametric statistical analysis. RESULTS: sPLA2 was localised to endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in all tissue sections. In RA and OA sections, staining was seen in both macrophage-like and fibroblast-like cells in the synovial lining layer (LL) and subsynovial lining layer (SLL). Perineural cells stained positively. Subintimal lymphoid aggregates (LA) were negative in all sections. The RA group showed significantly greater staining in extravascular synovial tissue (median 3.6, range 1.5-6.0) than the OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups (p < 0.05). LL staining was significantly higher in RA than both OA and NA sections (p < 0.05). The OA group showed a trend to higher staining scores than the NA group that did not reach significance. There was a significant correlation between the sPLA2 staining score and inflammation score within the RA patient group (p < 0.05). CONCLUSIONS: The synovium is a site of increased expression of sPLA2 antigen in both RA and OA relative to NA. Its presence in both fibroblast and macrophage-like cells in the LL and SLL of synovial tissue in RA and OA, but not NA, indicates that the enzyme is specifically induced in these regions in both conditions with expression in the LL being particularly characteristic of RA. The widespread expression of sPLA2 in synovium suggests it is likely to play a significant part in synovial pathology.

Vascular dendritic cells and atherosclerosis.

CD1a positive cells of dendritic shape were detected in the intima of human arteries by immunohistochemical investigation. Analysis of contiguous parallel sections showed that the CD1a positive cells also stained with S-100 and expressed HLA-DR. The CD1a+/S-100+/HLA-DR+ vascular dendritic cell is a type of dendritic cell which participates in atherosclerotic lesion formation. This finding has important implications for understanding atherogenesis and offers a link between immune mechanisms and atherosclerotic lesion formation.