Histological Evidence Research Articles

The Anticonvulsant Effect of Nonsteroidal Anti-Inflammatory Drug, Fenoprofen, in Pentylenetetrazole-Induced Epileptic Rats: Behavioral, Histological, and Biochemical Evidence.

This study aimed to evaluate the anticonvulsant properties of fenoprofen on the experimental model of pentylenetetrazole (PTZ)-induced epilepsy. Male Wistar rats were randomly grouped into five, and the kindling model was induced by intraperitoneal injection of PTZ 35 (mg/kg) every other day for 1 month. Aside from the control and PTZ groups, three groups received intraperitoneal injections of fenoprofen at doses of 10, 20, and 40 (mg/kg) before each PTZ injection. Rats were challenged with PTZ 70 (mg/kg) 1 week after kindling development. Then rats were subjected to deep anesthesia, and serum and brain samples were prepared. Oxidative stress (OS) markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) were measured in serum samples. Hippocampal tissue was used to investigate the relative expression of OS-related genes (nuclear factor [erythroid-derived 2]-like 2 (Nrf2)/heme oxygenase 1 (Hmox1)) and histological studies. Seizure behavior was assessed based on Lüttjohann's score. In treated groups, the number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration decreased significantly, while myoclonic jerks and GTCS latency increased compared with the PTZ group. The biochemical evaluation revealed the antioxidative effects of fenoprofen. The decreased expression of Nrf2/HO-1 genes in the PTZ group was reversed after fenoprofen administration. The results of the histological study obtained from Nissl staining in the hippocampal tissue also confirmed the protective effect of fenoprofen. The anticonvulsant effects of fenoprofen seem to be through inhibition of OS-related markers, induction of protective effect in hippocampal tissue, and activation of the Nrf2/HO-1 signaling pathway.

Characterization of esophageal biopsies from stem cell transplant patients with and without esophageal graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HSCT). Histologic diagnostic criteria and several grading systems have been described for colonic GVHD; however, for esophageal GVHD (eGVHD) limited reports exist to date. In this study, a total of 130 HSCT patients with esophageal biopsies were included, with a median age of 44 years (2-77) and a male predominance (54.6%). Of these, 82 (63%) had a clinical diagnosis of eGVHD. Cases were divided into two groups: those without apoptotic bodies, dyskeratotic cells or ulceration (group 1, no histologic evidence of eGVHD) (42%) and those with at least one of those features (group 2) (58%). Group 2 cases were associated with extra gastrointestinal tract GVHD (p=0.024), a clinical diagnosis of eGVHD (p=0.001), older age (p<0.001), stem cells derived from peripheral blood (p<0.001), higher number of intraepithelial lymphocytes (p=0.002), presence of acute inflammation (p<0.001) and basal cell hyperplasia (p=0.016). Apoptotic bodies were seen in 65 (89%), dyskeratotic cells in 27 (37%) and an ulcer in 28 (37%) of the group 2 cases. The sensitivity (Sn), specificity (Sp) and accuracy (acc) of the group 2 cases for a clinical diagnosis of eGVHD was 68.3%, 60.4% and 65.4%, respectively. Apoptotic bodies (p=0.012) and dyskeratotic cells (p<0.001) but not ulceration (p=0.881), were associated with a clinical diagnosis of eGVHD. The Sn, Sp and acc for apoptotic bodies, dyskeratotic cells and ulcer were 59.3%, 63.8% and 60.9%, 30.9%, 95.7% and 54.7%, 21.9%, 79.2% and 43.1%, respectively. Cases with only apoptotic bodies or ulceration were considered as possible GVHD, and those with dyskeratotic cells as likely GVHD, which were associated with GVHD specific survival (p=0.030). This study provides a comprehensive characterization of the esophageal histologic findings in HSCT patients. Further studies are needed to corroborate these findings in other patient populations.

Abstract TP358: Stroke Exacerbates Respiratory Function and Cognition in Mice with Dementia

Introduction: Stroke is a well-established independent risk factor for the development of dementia. Most dementia patients exhibit mixed brain pathologies, with histological evidence of ischemia and Aβ plaque accumulation, observed at autopsy. It is known that apnea/breathing disorders are independent risk factors for cognitive dysfunction and the progression of dementia. Our previous work suggested stroke impairs breathing control in wildtype mice. Here we hypothesize that, in mice with pre-existing dementia, stroke will exacerbate their respiratory dysfunction and further impair cognitive function. Methods: We used Tg-SwDI mice as a model for cerebral amyloid angiopathy (CAA), a major type of dementia. Female (11 to 13 months old) Tg-SwDI mice underwent pd-MCAO (permanent distal middle cerebral artery occlusion surgery) with age and sex matched wildtype and sham controls. Barnes Maze and Novel Object Recognize Test (NORT) were used for cognitive assessment, while whole-body plethysmography captured respiratory metrics, including apnea rate at 6 weeks post-surgery. All data are presented as Mean±SEM. Results: Tg-SwDI mice without stroke showed significant increases in apnea rates (per min) compared to the wide-type mice without stroke (5.8±0.26 vs. 1.04±0.11, p =0.0003, n=7 and 5) and displayed worsen performance in Barnes Maze (escape latency 59.5±11.6 vs. 23.7±6.1, p =0.044, n=7 and 5) and NORT (percentage time spent with novel object 42.0±5.8% vs. 61.9±6.2%, p =0.019, n=7 and 5). pd-MCAO increased apnea events in Tg-SwDI group (9.5±0.91 vs. 5.8±0.26, p =0.0009, n=9 and 7) vs. Tg-SwDI mice without stroke. Tg-SwDI mice with pd-MCAO exhibited worsen performance in Barnes Maze escape latencies (93.7±10.4 vs. 59.5±11.6, p =0.027, n=9 and 7) compared with Tg-SwDI mice without stroke. There was also a non-significant reduced novel object interaction time in NORT (36.8%±3.54 vs. 42.0%±5.8, p =0.43, n=9 and 7). Conclusions: Stroke worsens both respiratory dysfunction and cognitive memory impairment in CAA mice. The increased breathing disorder may be a contributing factor for worsened cognition in CAA mice.

What is new in the management of coeliac disease?

Coeliac disease is the most common immune-mediated enteropathy, affecting approximately 1 % of the population worldwide. Currently, the vast majority of individuals remain undiagnosed. Coeliac disease is triggered by gluten ingestion in genetically predisposed individuals carrying the human leukocyte antigen (HLA) genes; HLA-DQ2 and HLA-DQ8. Patients with coeliac disease present with a wide spectrum of gastrointestinal and extraintestinal manifestations and, in some cases, without any symptoms. The diagnosis of coeliac disease in adults is based on a combination of clinical suspicion, positive serological markers and histological evidence of small intestinal atrophy on duodenal biopsies. The only effective treatment is a strict, lifelong gluten-free diet. However, up to 20 % of patients report persistent or recurrent symptoms. In this review, we provide a comprehensive update on coeliac disease, focusing on its relevance to the different medical specialities and highlighting the need for a multidisciplinary approach to its diagnosis and management. Clinicians practicing internal medicine have a unique opportunity to diagnose this multisystem autoimmune disease. By doing so, they would avoid delays in diagnosis for these patients. A low threshold for serological testing is recommended.

Proteome Analysis Reveals Paraspinal Muscle Fiber Type Changes in Patients with Degenerative Lumbar Scoliosis.

Degenerative lumbar scoliosis (DLS) is a common aging-related spinal deformity. Paraspinal muscle degeneration is highly correlated with the rapid progression of DLS. However, understanding of the role of the degeneration is limited because of a lack of histologic and molecular evidence. Our study profiled the proteomic alteration of paraspinal muscles and investigated the muscle fiber type transition that occurs in DLS, along with its correlation with clinical parameters. Cross-sectional basic science study using clinical data and biological samples. Paraspinal muscle samples were collected intraoperatively from the concave and convex sides of the apex vertrebrae in patients with DLS (n = 10) and either side of L3 level from age- and sex-matched participants without DLS (n = 10). Analysis was perfomed using isobaric tagging for relative and absolute quantitation (iTRAQ) and liquid chromatography with tandem mass spectrometry on muscle tissue from the convex side of spines in patients with DLS and in participants without DLS to identify differentially expressed proteins (DEPs). Western blotting was used to validate the DEPs. The measurement of acidity/basicity of ATPase (pH = 9.4), succinic acid dehydrogenase staining, and real-time quantitative polymerase chain reaction were performed to assess the muscle fiber type change in DLS. The Pearson correlation coefficient was used to analyze the correlation between the myofiber transition and the Cobb angle of the main curve. This study was supported by the National Natural Science Foundation of China (NSFC) (No. 82272545), $ 8,000-10,000 and the Jiangsu Provincial Key Medical Center, and the China Postdoctoral Science Foundation (2021M701677, $ 5,000-7,000). We identified 62 DEPs, of which 16 were downregulated and 46 were upregulated. Gene ontology indicated significant changes in biological processes including muscle contraction. Protein-protein interaction network analysis showed that structural muscle proteins such as MYH1 (myosin heavy chain 1) and TNNT3 (troponin T) were the key nodes. Western blotting further validated the downregulation of MYH1. Histologically, ATPase staining showed a significant reduction of type II muscle fibers in DLS, consistent with the functional changes of the DEPs. Furthermore, we found that the reduction of type II muscle fibers percentage was correlated with the severity of DLS. This study is the first to elucidate the underlying molecular basis and pathways that implicate the paraspinal muscle fiber type transition in DLS. Type II myofiber percentage was diminished both on the concave side and the convex side of the paraspinal muscles in DLS, especially on the convex side, which may play an important role in the onset and/or progression of the disease. This study shows a potential molecular basis for histopathologic change in the paraspinal muscles of DLS and provides a potential tool for assessing paraspinal muscle quality and predicting the poor prognosis of DLS.

Short-Term Evolution of MASLD Following Roux-en-Y Gastric Bypass: A Focus on Fibrotic MASH.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes simple steatosis and metabolic dysfuncion-associated steatohepatitis (MASH), with fibrosis in MASH serving as a critical prognostic marker. This study investigates the effects of Roux-en-Y gastric bypass (RYGB) on fibrotic MASH, assessed using the fibrotic NASH index (FNI) and the non-invasive NASH detection score (NI-NASH-DS), as well as provides further data on the diagnostic accuracy of both scores. A retrospective cohort study was conducted involving 104 individuals (91.3% female, mean age 39.4 ± 8.6years) who underwent RYGB. Histopathological evaluations during surgery identified fibrotic MASH, and FNI and NI-NASH-DS values were calculated at baseline and 1year post-surgery. At the time of surgery, participants had a mean BMI of 35.3 ± 2.8kg/m2, which decreased to 27.1 ± 4.0kg/m2 1year after surgery. The mean % total weight loss (%TWL) was 23.8 ± 10.1%, and the mean % excess weight loss (%EWL) was 82.4 ± 37.3%. Fibrotic MASH was present in 17.3% of participants pre-operatively. The mean FNI score significantly decreased after surgery (p < 0.0001). Female gender (p < 0.001) and histological evidence of lobular inflammation (p < 0.001) were independently associated with the improvement of FNI. The FNI demonstrated high diagnostic accuracy (sensitivity: 61.1%, specificity: 96.4%, overall accuracy: 90.2%). NI-NASH-DS had a 60% accuracy in detecting MASH, alongside an 85.9% specificity. RYGB seemingly promotes improvement of fibrotic MASH as evaluated by FNI, highlighting its potential as a therapeutic intervention to mitigate MASLD progression. Both FNI and NI-NASH-DS are helpful and inexpensive tools for assessing MASH.

A case report of gastric antral vascular ectasia treated by endoscopic band ligation combined with lauromacrogol injection.

Gastric antral vascular ectasia (GAVE) is a rare acquired lesion characterized by vascular dilation in the gastric antrum, frequently results in occult or overt gastrointestinal bleeding. Endoscopic intervention remains the cornerstone of therapy. Argon plasma coagulation was previously considered a first treatment option. But recently, endoscopic band ligation (EBL) has emerged as an alternative, increasingly favored for its safety and efficacy. Nonetheless, a consensus on the most effective treatment approach has yet to be established. A 74-year-old female was hospitalized for persistent chest tightness and dyspnea for 1 year. Physical examination showed an anemic appearance with normal blood pressure. Upon admission to the hospital, the blood routine examination revealed severe anemia and the fecal occult blood test was persistently positive. The endoscopic observations and histological evidence led to a diagnosis of GAVE for the patient. Considering the poor response to prior pharmacotherapy, endoscopic intervention was selected for this hospitalization. The initial EBL alone did not yield particularly satisfactory results. Combining EBL with lauromacrogol injection as a subsequent treatment resulted in encouraging outcomes. At the 6-week follow-up, the patient exhibited a negative fecal occult blood test, normalization of hemoglobin level, and endoscopic images demonstrated near complete resolution of vascular ectasias. The combination of EBL with lauromacrogol injection has shown a satisfactory short-term outcome, providing a new option for the endoscopic management of GAVE. However, its long-term efficacy still requires further observation.

Ptosis Correction Through Anterior Displacement of Levator Aponeurosis Within the Corneal Region.

Upper eyelid ptosis is a common aesthetic concern among Asian patients, resulting in a tired and drowsy appearance that affects their attractiveness. The levator advancement technique is widely used for ptosis correction; however, achieving precise results remains challenging. This study introduces a modified approach to improve the accuracy of levator aponeurosis advancement by focusing on precise measurements and anterior displacement within a defined corneal range. The study included patients with mild to moderate ptosis. We measured the mean margin reflex distance 1 (MRD-1) preoperatively and 12months postoperatively. Histological evidence was obtained through staining of levator aponeurosis complexes using Hematoxylin and Eosin and Masson's trichrome. In this prospective study, 29 patients showed a significant increase in mean MRD-1 from 2.56 ± 0.84mm (range 1.02-3.98mm) preoperatively to 4.38 ± 0.55mm (range 3.09-5.35mm) at the 12-month follow-up (paired t-test; P < 0.001). Masson's staining revealed that the levator aponeurosis tissue primarily consists of collagen fibers, which minimize potential errors due to their toughness and lack of elasticity during the surgical procedure. The modified technique enhances the accuracy of levator aponeurosis advancement in ptosis correction, resulting in minimal surgical trauma and high patient satisfaction. Our technique appears to have a low incidence of severe adverse effects, based on the available data from the current case series. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

P0410 Clinical outcomes of endoscopically confirmed immune checkpoint inhibitor-induced colitis: A multicentre retrospective study

Abstract Background Immune checkpoint inhibitors (CPIs) have transformed cancer outcomes, but frequently trigger CPI-induced colitis (CPI-c) leading to significant morbidity and prolonged immunosuppression. This study characterises CPI-c patients (pts) using robust definitions. Additionally, the impact of macroscopic inflammation (endoscopic and histological evidence) compared to microscopic inflammation (histological only) on clinical outcomes remains unclear. Methods Retrospective outcome data were obtained from consecutive CPI-c pts from 2 U.K centres. Pts with diarrhoea and histological ± endoscopic colonic inflammation were included. Factors associated with macroscopic inflammation were analysed using Chi squared tests and multivariable logistic regression. Results Of 161 pts (55% male, median age 64), cancers included melanoma (50%), renal (18%), lung (16%) and others (16%). CPI therapies included anti-PD-1/L1 monotherapy (41%), dual anti-CTLA-4/PD-1 (47%) and chemoimmunotherapy (6%). Toxicity onset was earlier with dual anti-PD-(L)1/CTLA-4 therapy vs. anti PD-(L)1 monotherapy (47 vs.150 days, p &amp;lt; 0.001). The average bowel frequency was 8x/day (range 2-20); 115 (71%) had nocturnal symptoms; 28 (17%) had bloody stool and 63% required hospitalisation. 89 pts (54%) were corticosteroid (cs) refractory, requiring biologics (infliximab (IFX), 73; vedolizumab, 13). 41/73 (56%) responded to IFX, and 5/13 (38%) to vedolizumab. Three underwent colectomy for refractory colitis. Macroscopic inflammation occurred in 78%, while 22% had microscopic inflammation. Time to endoscopy did not differ between groups. Among macroscopic cases, 91 (70%) had mild (Mayo 1), while 30% had moderate or severe inflammation (Mayo 2-3). CTCAE grade did not correlate with endoscopic severity. In the regression analysis, male sex (OR 3.25 p&amp;lt;0.01) and dual anti-CTLA-4/PD-1 (OR 2.63 p&amp;lt;0.01) predicted macroscopic inflammation. Age, cancer, CTCAE grade, duration of diarrhoea, concurrent CMV colitis, number of cs tapers, duration of cs therapy, hospitalisation and recurrence of colitis were not predictive. Macroscopic inflammation correlated with higher faecal calprotectin (FC) levels (889 vs 414, p=0.02) and biologic escalation (52.7% vs 30.6%, p&amp;lt;0.05). 30% received CPI re-challenge, with colitis relapse in 13/45 (29%). No relapses exceeded initial CTCAE or endoscopic severity. Conclusion This study represents one of the largest real-world cohorts of robustly defined CPI-c pts. Pts with macroscopic inflammation have a more aggressive clinical course, marked by higher FC levels and greater need for biologic escalation, emphasising the need for heightened monitoring in this group. Reassuringly, CPI re-challenge did not lead to more severe colitis relapses than the initial episode.

P0425 Factors Associated with Biopsy-Proven Cuffitis in Ulcerative Colitis Patients Following Colectomy with Ileal Anal-Pouch Anastomosis

Abstract Background Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment in patients with refractory/complicated ulcerative colitis (UC). Inflammation of the small rectal remnant below IPAA lines (“cuff”) is designated cuffitis. Despite its clinical significance and characteristic endoscopic and histologic features, risk factors are vague. This study aimed to decipher demographic, disease, and surgery-related risk factors for histologically proven cuffitis. Methods In a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center), consenting patients were followed prospectively, with routine clinical, laboratory, and endoscopic evaluations. Patients after IPAA due to UC having≥1 cuff biopsy during follow-up were included. Histological cuff samples were scored based on the validated NANCY index. Cuffitis, the primary outcome, was defined as evidence of moderate-to-severe histologic inflammation (NANCY score 3-4). Univariate Cox models were used to assess hazard ratios (HRs) of various factors with the occurrence of cuffitis. Results Of 400 patients followed at the pouch clinic, 182 consented to prospective follow-up, and 116 underwent cuff biopsy, each having a median of 2 biopsies. Most patients had histological evidence of moderate-to-severe cuffitis (n=76, 65.5%). Significant associations with cuffitis included disease duration ≤10 years before surgery (HR 15.4, 95%CI; 4.0-59.1, p&amp;lt;0.001); body mass index ≤ 18.5 (HR 3.83, 95%CI; 1.75-8.4, p&amp;lt;0.001); Arab descent (HR 3.2, 95%CI; 1.1-9, p=0.03); immediate postoperative complications (HR 2.0, 95%CI; 1.24-3.2, p=0.004); strong association with pre-operative biologic treatment was observed, with a single biologic (anti-TNF 90%) used before colectomy having a HR of 5 (95%CI;2.6-9.7, p&amp;lt;0.001) and multiple biologics having a HR of 14 (95%CI; 6.1-34, p&amp;lt;0.001). Interestingly, refractory UC as the indication for IPAA (vs dysplasia) was not independently associated with an increased risk of cuffitis. Conclusion Several demographic, disease, and surgery-related factors associated with post-IPAA cuffitis were identified. These may be incorporated into decision-making processes. Furthermore, closer postoperative follow-up may be warranted in specific patient subgroups. ese patients may benefit from closer post-operative follow-up.

A Single Early Life Acetaminophen Exposure Causes Persistent Abnormalities in the Murine Lung.

Whether early life acetaminophen (APAP) exposures injure the developing lung is controversial. We sought to correlate murine pulmonary developmental expression profiles of Cyp2e1 to susceptibility to APAP exposure. P14 C57BL/6 mice were exposed to APAP (140 mg/kg x 1, IP) and assessed for evidence of a histologic, metabolic, functional, and/or transcriptional pulmonary response. Similar experiments were performed in P14 IL6-/- mice given the controversial role of IL6 in APAP-induced tissue injury. No evidence of hepatic injury was noted in APAP exposed P14 mice. In contrast, within 6 hours of exposure pulmonary tissue demonstrated histologic and functional evidence of injury and increased mitochondrial load by fluorescent lifetime imaging microscopy (FLIM). The pulmonary transcriptional response was marked by increased expression of Cyp2e1, Nrf2 targets, and pro-inflammatory genes. Specifically, APAP exposure increased pulmonary IL6 mRNA, protein and associated STAT3 signaling. In contrast, IL6-/- demonstrated attenuated STAT3 signaling and injury at 6 hours of exposure. At P28, functional and stereologic assessment of both WT and IL6-/- mice exposed to a single dose of APAP at P14 revealed persistent abnormalities consistent with lung enlargement and alveolar simplification. Developmentally regulated surges in pulmonary Cyp2e1 expression correlate with sensitivity to APAP exposures that do not cause recognizable hepatic injury. A single exposure during this developmental window is enough to cause persistent functional and stereological abnormalities. These results highlight the need to further study the relationship between developmentally-regulated pulmonary Cyp2e1 expression, APAP exposures and long-term pulmonary dysfunction.

The membrane attack complex drives thrombotic microangiopathy in complement mediated atypical hemolytic uremic syndrome.

Introduction of complement (C) inhibition into clinical practice has revolutionized the treatment of patients with complement-mediated atypical hemolytic syndrome (aHUS). Our C3D1115N mouse model, engineered around a gain of function point mutation in C3, is associated with complement mediated aHUS in man, allowing us to study the clinical disease in a preclinical model. Backcrossing our model onto C7 deficient and C5aR1 deficient mice enabled further determination of the roles of the C5a-C5aR1 axis and C5b-9 (the membrane attack complex) on kidney disease. C7 deficiency completely abolished both clinical and histological evidence of disease. Removing C5aR1 (CD88) attenuated the risk of developing clinical disease, but mice still developed thrombotic microangiopathy. Therapeutic inhibition strengthened our genetic findings showing both anti-C7 therapy and an oral C5aR1 antagonist, when used before evidence of significant kidney injury, prevented mice from succumbing to disease. However, there was ongoing histological disease within mice treated with the C5aR1 antagonist. Our data suggest that both C5aR1 and C7 play a role in the development of the conditions required for thrombotic microangiopathy of the kidney. While disrupting the C5a-C5aR1 axis is beneficial, our genetic and therapeutic studies showed that thrombotic microangiopathy of the kidney can still develop and ultimately our data confirms that the membrane attack complex is required to develop thrombotic microangiopathy of the kidney. Overall, our study shows that in addition to requiring alternative pathway dysregulation, local generation of membrane attack complex within the kidney is also critical to drive disease pathology in complement-mediated aHUS.

Long-term effect of Roux-en-Y gastric bypass versus sleeve gastrectomy on reflux and Barrett's oesophagus: a randomized controlled trial.

Laparoscopic sleeve gastrectomy (LSG) is a potentially refluxogenic operation while Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is regarded as an anti-reflux procedure. The aim of this study is to compare long-term incidence of Barrett's Oesophagus (BO) and gastroesophageal reflux disease (GORD) following LSG and LRYGB. Participants of a double-blinded randomized controlled trial comparing banded LRYGB and LSG for remission of type 2 diabetes were contacted to take part. A gastroscopy was performed. Primary outcome was endoscopic and histologic evidence of BO. Secondary outcomes included reflux and regurgitation scores, presence of oesophagitis, proton-pump inhibitor (PPI) usage, Body Mass Index (BMI), and percentage excess weight loss (%EWL). Forty-eight of 109 patients were enrolled into the study (LSG 26 vs. LRYGB 22). Mean follow-up was 7.5 years for the LSG group, and 7.4 years for the RYGB group (P = 0.22). 8 LSG patients had BO while 3 LRYGB patients had BO (30.8%vs13.6%, P = 0.19). There was no significant difference in the mean reflux (8.1 ± 9.4(0-36) vs. 9.3 ± 8.8(0-34), P = 0.47) and regurgitation scores (7.7 ± 6.9(0-22) vs. 11.5 ± 10.5(0-44), P = 0.23) for LSG versus LRYGB patients or between those with and without BO. PPI usage before and after surgery was 6/26 (23.1%) versus 13/26 (50.0%) and 8/22 (36.4%) versus 12/22 (54.5%) for LSG and LRYGB patients respectively. PPI usage in patients with and without BO was 7/11 versus 18/37. EWL was significantly greater (P = 0.0013) in the LRYGB group (74.8 ± 28.1%) compared to LSG group (49.7 ± 18.7%). Long-term incidence of BO trended towards but was not significantly higher for LSG compared to LRYGB group. We support routine endoscopic surveillance for bariatric patients.

Histological pattern of non-infectious thoracic aortitis impacts mortality.

Non-infectious aortitis encompasses various histological patterns, but their specific cardiovascular outcomes remain unclear. To evaluate the mortality associated with non-infectious surgical thoracic aortitis. This retrospective multicenter study included patients who underwent thoracic aortic surgery and had histological evidence of aortitis. The study analyzed the characteristics of patients with non-infectious aortitis presenting either a granulomatous/giant cell histological pattern or a lymphoplasmacytic pattern. Factors associated with mortality were identified using multivariate analysis. Among 5666 patients who underwent thoracic aortic surgery, 197 were found to have non-infectious aortitis with either a granulomatous/giant cell histological pattern (n=138) or a lymphoplasmacytic pattern (n=59). The overall standardized mortality rate (SMR) for patients with non-infectious surgical thoracic aortitis was 1.61 (95% CI: 1.05; 2.39), with 31.5% of patients dying within 10 years of the initial procedure. After a median follow-up of 3.5 years [IQR: 0.5-6.8] post-surgery, 31% of deaths were due to aortic dissection or rupture. The 10-year cumulative incidence of death was 40.1% (95% CI, 17.7-61.8) for patients with a granulomatous/giant cell pattern and 14.4% (95% CI, 2.6-35.6) for those with a lymphoplasmacytic pattern. Granulomatous/giant cell histological pattern (HR 4.71 [vs lymphoplasmacytic pattern]; 95% CI, 1.37-16.2; p=0.023) and aortic dissection at diagnosis (HR 6.07 [vs aneurysm]; 95% CI, 2.89-12.7; p<0.0001) were independently associated with increased mortality. This multicenter study found that 31.5% of patients with non-infectious surgical thoracic aortitis are expected to die within 10 years of their initial surgery. The granulomatous/giant cell histological pattern is associated with higher mortality.

Clinical follow-up of 2 families with glomerulopathy caused by COQ8B gene variants and literature review.

Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B (COQ8B) can cause primary CoQ10 deficiency. COQ8B-related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood. The disease often progresses to kidney failure and the renal histopathology is most commonly focal segmental glomerulosclerosis (FSGS). Four SRNS cases (2 females and 2 males) from 2 unrelated families who were followed clinically for nearly 3 years. Clinical exome testing and analyses were performed by MyGenostics Laboratory in China to evaluate unexplained proteinuria given the strong family history of glomerular disease and histologic evidence of SRNS. Pathogenic variants were identified in COQ8B in the exome studies and confirmed by direct sequencing. Clinical exome sequencing revealed biallelic variants of the COQ8B gene in 2 families. In the Family 1, the oldest of three affected siblings died of renal failure at 11 years of age. Based on the results of genetic testing which identified a homozygous variant of COQ8B, the other two affected siblings with mild proteinuria and normal renal function were treated with CoQ10 oral supplementation at an early stage. Coenzyme Q10 treatment was effective in reducing proteinuria levels in both patients from Family 1 over the first 6 months and the two patients still have low-level proteinuria and normal renal function at nearly three years. In Family 2, clinical exome sequencing revealed a compoundheterozygous variants of COQ8B in a patient with biopsy- proven FSGS. His disease was unresponsive to prior treatment with glucocorticoids and cyclosporine. Oral CoQ10 was initiated based on his genetic diagnosis and was it was effective in reducing proteinuria over the first 5 months months of therapy. However after 1 year, his disease progressed tokidney failure. Kidney transplantation was performed at 5 years of age and his condition has been stable without rejection and no recurrence of disease. COQ8B gene variant-related glomerulopathy often presents as SRNS without obvious extrarenal manifestations. The histopathology is mainly FSGS and follows an autosomal recessive mode of inheritance. Some patients may benefit from early coenzyme Q10 supplementation. For patients whose disease progresses to kidney failure, kidney transplantation can be an effective treatment. For children with unexplained proteinuria and abnormal renal function, genetic testing should be performed early in the course of disease to guide therapy where possible and improve prognosis.

Nephroprotective Effects of Curcumin in Murine Models of Focal and Segmental Glomerulosclerosis.

This study aims to explore the reno-protective effect of Curcumin in focal and segmental glomerulosclerosis (FSGS) in Murine models, a common chronic glomerulopathy that leads to end stage renal disease. Adult Wistar rats were used in this experiment. One group was treated with intravenous Adriamycin (ADR) injection to induce FSGS similar to that seen in humans and a second group was co-administered ADR and Curcumin (ADR-CUR). Saline treated rats served as controls. Renal injury was assessed by measuring the levels of serum creatinine, blood urea nitrogen (BUN), triglyceride and urinary protein. The homogenates of renal cortex were used to estimate the renal content of the inflammatory marker, tumor necrosis factor-a (TNF-a); oxidative stress marker, Malonaldehyde (MDA); and two anti-oxidants superoxide dismutase (SOD) and reduced glutathione (GSH). In addition, the rat kidneys were harvested by ends of week-8 and week-12 and examined for histological abnormalities. The ADR-treated rats showed biochemical and histological evidence of FSGS, in the form of proteinuria, elevated serum creatinine, BUN and triglycerides, elevated renal TNF-a and MDA, and segmental glomerulosclerosis. The ADR-CUR treated rats showed significant correction of all these variables. Co-administration with Curcumin resulted in improvement of the proteinuria, serum creatinine, BUN and triglyceride. The renal tissue levels of anti-oxidants SOD and GSH increased and that of TNF-a and MDA decreased and the histology revealed reduction in the extent of segmental glomerulosclerosis. The FSGS associated renal damage was notably antagonized by curcumin treatment. Our findings confirm the reno-protective effects of Curcumin as a potential therapeutic agent in protection against the progression of FSGS and indicate that it is mitigated by inhibition of oxidant injury and inflammation and also by promotion of antioxidants. Curcumin ameliorated the ADR-induced FSGS in murine models. It may be a promising compound in the treatment of FSGS in human subjects. More human studies are needed to further elucidate its effects in FSGS.

Infection-Related Stillbirths: A Detailed Examination of a Nine-Year Multidisciplinary Study.

Although several conditions and specific risk factors have been associated with stillbirth (SB), in most of the cases it is difficult to identify the definitive etiopathology and cause of death. Specifically, the role of infections in SB is still debated. Our aim was to study maternal, placental, and fetal tissues in cases of SB in order to define the causative link between infections and fetal death, through a multidisciplinary clinical audit. Between 2014 and 2022, microbiological investigations on maternal, placental and fetal samples of SB cases were performed according to a standardized protocol including serology, cultures, and molecular biology. Autopsies and placental examination were mandatory in all SB cases. A total of 182 cases of SB were investigated. Bacteria were detected in 22.2% of vaginal swabs, 65% of placental biopsies, 29% of fetal blood, and 14.1% of oropharyngeal swabs. Vaginal and oropharyngeal swabs were positive for urogenital mycoplasmas in 25.2% and 8.6%, respectively. Positive results of microbiological investigations, in association with histological features suggestive of infection, were observed in six cases, indicating that fetal death was likely related to a bacterial infection. In one case, a high SARS-CoV-2 load was found in the placenta of a SB due to placental abruption. Infections were likely associated with fetal death in 3.8% of cases. Thus, in developed countries, an infection, defined when positive microbiological findings are associated with histological evidence of organ damage, is a minor contributory factor in SB.

Perifoveal vascular anomalous complex and telangiectatic capillaries: An overview of two entities potentially sharing a common pathophysiology.

Focal capillary ectasia in the macular region can manifest in distinct clinical scenarios, which can be categorized into two main entities: perifoveal vascular anomalous complex (PVAC) and telangiectatic capillaries (TelCaps). PVAC represents a primary, idiopathic condition, whereas TelCaps occur secondary to underlying vascular disorders, including diabetic macular edema and retinal vein occlusion. We provide a comprehensive analysis of these two entities, encompassing their clinical presentations, multimodal imaging findings, histological evidence, and differential diagnosis from other retinal microvascular abnormalities, such as Type 1 macular telangiectasia, adult-onset Coats disease, Type 3 macular neovascularization in age-related macular degeneration, and retinal arterial macroaneurysms. Although PVAC and TelCaps are distinct entities, they may share common pathogenic mechanisms, including progressive endothelial dysfunction, pericyte loss, and intraluminal deposition of blood components. Selective laser photocoagulation has emerged as a promising therapeutic approach for both conditions. The proposed standardization of nomenclature for accurate reporting and meaningful cross-study comparisons is expected to facilitate future advancements in this field, ultimately leading to improved patient outcomes.

Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease

Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease

Fatal systemic bacterial infections in two harbour porpoises (Phocoena phocoena) secondary to bite wounds from grey seals (Halichoerus grypus).

Mycoplasma phocicerebrale, the causative agent of seal ('speck') finger, a zoonotic disease, is a common commensal in the oral cavity of various seal species. Historically associated with seal hunters, it remains a significant risk for those handling or rehabilitating marine mammals. While primarily known for causing severe cellulitis in humans, M.phocicerebrale can also lead to severe infections in seals, including osteomyelitis and sepsis. Recent studies have revealed the predatory behaviour of grey seals (Halichoerus grypus) on harbour porpoises (Phocoena phocoena). Examination of scarring patterns on stranded animals suggest that some initial predation attempts are unsuccessful, and porpoises escape only to succumb to infection originating from bite wounds. Here we describe two cases in which the isolation of M.phocicerebrale and other bacterial species from chronically infected bite wounds, the lungs and other internal organs of harbour porpoises suggest failed predation attempts by grey seals. Therefore, the impact of delayed, indirect mortality from sympatric predation attempts may be a significant additional and underestimated cause of mortality in harbour porpoises. One of the cases examined in this study involved a harbour porpoise with gross and histological evidence of a failed predation attempt and a fatal systemic M.phocicerebrale infection. These findings highlight the severe consequences of such infections and underscore the importance of understanding the ecological implications of grey seal predation on harbour porpoise populations.