Gut microbiota shifts from onset to remission in immune checkpoint inhibitor-induced enterocolitis: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. CASE PRESENTATION: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. CONCLUSIONS: Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.

Multicenter study comparing EUS-guided hepaticogastrostomy and ERCP for malignant biliary obstruction in patients with accessible papillae.

BACKGROUND: One advantage of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is that it is difficult for reflux cholangitis, caused by duodenal pressure increasing due to duodenal obstruction, to occur. In addition, since stent deployment is performed away from the malignant stricture site, longer stent patency than with endoscopic retrograde cholangiopancreatography (ERCP) may be obtained. However, no study has previously compared EUS-HGS and ERCP for patients without duodenal obstruction or surgically altered anatomy. The aim of the present study was to compare clinical outcomes between EUS-HGS and ERCP in normal anatomy patients without duodenal obstruction. METHOD: In the ERCP group, patients who initially underwent biliary drainage were included. In the EUS-HGS group, patients who underwent EUS-HGS due to failed biliary cannulation were included. Patients with an inaccessible papilla, such as with surgically altered anatomy or duodenal obstruction, were excluded. RESULTS: A total of 314 patients who underwent ERCP and EUS-HGS were enrolled in this study. Of the 314 patients, 289 underwent biliary stenting under ERCP guidance, and 25 patients underwent biliary stenting under EUS-HGS. After propensity score-matching analysis, the adverse event rate tended to be lower in the EUS-HGS group than in the ERCP group. Although overall survival was not significantly different between the EUS-HGS and ERCP groups (p = .228), stent patency was significantly longer in the EUS-HGS group (median 366.0 days) than in the ERCP group (median 76.5 days). CONCLUSIONS: EUS-HGS had a lower adverse event rate, shorter procedure time, and longer stent patency than ERCP in cases of normal anatomy without duodenal obstruction.

Computer-Vision-Oriented Adaptive Sampling in Compressive Sensing.

Compressive sensing (CS) is recognized for its adeptness at compressing signals, making it a pivotal technology in the context of sensor data acquisition. With the proliferation of image data in Internet of Things (IoT) systems, CS is expected to reduce the transmission cost of signals captured by various sensor devices. However, the quality of CS-reconstructed signals inevitably degrades as the sampling rate decreases, which poses a challenge in terms of the inference accuracy in downstream computer vision (CV) tasks. This limitation imposes an obstacle to the real-world application of existing CS techniques, especially for reducing transmission costs in sensor-rich environments. In response to this challenge, this paper contributes a CV-oriented adaptive CS framework based on saliency detection to the field of sensing technology that enables sensor systems to intelligently prioritize and transmit the most relevant data. Unlike existing CS techniques, the proposal prioritizes the accuracy of reconstructed images for CV purposes, not only for visual quality. The primary objective of this proposal is to enhance the preservation of information critical for CV tasks while optimizing the utilization of sensor data. This work conducts experiments on various realistic scenario datasets collected by real sensor devices. Experimental results demonstrate superior performance compared to existing CS sampling techniques across the STL10, Intel, and Imagenette datasets for classification and KITTI for object detection. Compared with the baseline uniform sampling technique, the average classification accuracy shows a maximum improvement of 26.23%, 11.69%, and 18.25%, respectively, at specific sampling rates. In addition, even at very low sampling rates, the proposal is demonstrated to be robust in terms of classification and detection as compared to state-of-the-art CS techniques. This ensures essential information for CV tasks is retained, improving the efficacy of sensor-based data acquisition systems.

Correction: Tatsumi et al. Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis. J. Clin. Med. 2023, 12, 7165.

Text Correction [...].

Pathogenic role and diagnostic utility of interferon-α in histiocytic necrotizing lymphadenitis.

PURPOSE: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. METHODS: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. RESULTS: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. CONCLUSION: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.

Changes in alanine aminotransferase and body composition and metabolic factors among individuals receiving medical health checkups.

AIM: To examine the relationship between changes in alanine aminotransferase (ALT) and those in body composition and metabolic factors in participants receiving medical health checkups (4350 men [mean age 52.5 years] and 5398 women [mean age 50.5 years]) METHODS: We divided the participants into four types based on their ALT value at baseline and 1 year: A, ALT ≤30 (baseline) and ≤30 (1 year); B, ALT ≥31 (baseline) and ≤30 (1 year); C, ALT ≤30 (baseline) and ≥31 (1 year); and D, ALT ≥31 (baseline) and ≥31 (1 year). The change in each body composition-related parameter (waist circumference, fat mass, fat-free mass, fat mass to fat-free mass ratio, etc.) after 1-year was defined as Δ. RESULTS: The mean changes in waist circumference (cm) in the four types (A, B, C, and D) were -0.33, -1.54, 0.66, and -0.29 (overall p < 0.0001) in men, and -0.19, -0.90, 0.30, and 0.090 (overall p < 0.0001) in women. The mean changes in fat mass (kg) in the four types were -0.027, -0.86, 0.62, and 0.092 (overall p < 0.0001) in men, and 0.0067, -0.48, 0.39, and 0.063 (overall p < 0.0001) in women. The mean changes in fat-free mass (kg) in the four types were -0.028, -0.55, 0.42, and -0.034 (overall p < 0.0001) in men, and -0.0091, -0.34, 0.12, and -0.045 (overall p = 0.0012) in women. The mean changes in fat mass to fat-free mass ratio in the four types were -0.00042, -0.0120, 0.00837, and 0.00171 (overall p < 0.0001) in men, and -0.00013, -0.00817, 0.00730, and 0.00628 (overall p < 0.0001) in women. CONCLUSION: A decrease in ALT to ≤30 IU/L may be associated with improved body composition balance, but caution should be exercised for the decrease in muscle mass.

Body Composition in Patients With Metabolic Dysfunction-associated Steatotic Liver Disease: Impact of Body Surface Area.

BACKGROUND/AIM: To examine the relationship between the body surface area (BSA) and body composition in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, 2,141 men and 986 women). MATERIALS AND METHODS: BSA and body composition parameters were examined. RESULTS: The median body mass index (BMI) was 25.0 kg/m2 for both men and women (p=0.7754). The median body surface area (BSA) was 1.854 m2 for men and 1.618 m2 for women (p<0.0001). In men, the median fat mass was 17.7 kg, whereas in women, it was 22.1 kg (p<0.0001). Additionally, the median fat-free mass was 55.4 kg in men and 39.3 kg in women (p<0.0001).). In male cases, BSA significantly correlated with fat mass (r=0.82, p<0.0001) and fat-free mass (r=0.95, p<0.0001). In female cases, BSA significantly correlated with fat mass (r=0.87, p<0.0001) and fat-free mass (r=0.94, p<0.0001). CONCLUSION: BSA could be a useful marker for the estimation of body composition in patients with MASLD.

Effect of sarcopenia on short-term outcomes of gastric endoscopic submucosal dissection.

BACKGROUND: Sarcopenia has been reported to be associated with short-term outcomes after gastric endoscopic submucosal dissection (ESD). The "strength, assistance with walking, rising from a chair, climbing stairs, and falls" (SARC-F) questionnaire has been widely used as a screening tool for sarcopenia; however, SARC-F combined with body mass index and age (SARC-F+EBM) has recently been reported to be more useful than SARC-F alone. This study aimed to investigate the association between sarcopenia, measured using SARC-F+EBM, and short-term outcomes after gastric ESD. METHODS: Patients who underwent gastric ESD at our institution between May 2020 and June 2023 were included, and their medical records were reviewed retrospectively. A SARC-F+EBM score ≥ 12 indicated sarcopenia. We evaluated the incidence of adverse events and the length of hospital stay in the sarcopenia and non-sarcopenia groups. RESULTS: Overall, 263 patients (64 and 199 in the sarcopenia and non-sarcopenia groups, respectively) were investigated. The incidence of adverse events with a Common Terminology Criteria for Adverse Events grade ≥ 3 was not significantly different between the sarcopenia and non-sarcopenia groups (6.2% vs. 8.5%, p = 0.791). The proportion of patients with an extended hospital stay (≥ 10 days) was significantly higher in the sarcopenia group than that in the non-sarcopenia group (12.5% [8/64] vs. 3.5% [7/199], p = 0.012). Multivariate analysis showed that sarcopenia and lesions that present technical difficulty in ESD were independent risk factors for extended hospital stays (≥ 10 days). Of the eight cases having extended hospital stays in the sarcopenia group, four were due to the management after gastric ESD, three were due to family circumstances, and one was due to decreased activities of daily living. CONCLUSIONS: Sarcopenia is not a predictor of adverse events associated with gastric ESD. However, patients with sarcopenia may be hospitalized for longer owing to non-ESD-related factors.

Comparing the Effects of Anti-TNF Agent and Ustekinumab on Small Bowel Inflammation in Crohn's Disease: Inverse Probability Weighting With Stabilized Weights of Propensity Scores.

Background: Endoscopic mucosal healing serves as a critical predictor for achieving long-term remission in Crohn's disease treatment. Recent data indicate that the effectiveness of healing varies based on the location of gastrointestinal inflammation. Additionally, reports suggest that antitumor necrosis factor-α (anti-TNF-α) agents exhibit reduced efficacy in treating small intestinal inflammation compared to colorectal inflammation. Conversely, limited research exists regarding the impact of the anti-IL12/23 agent ustekinumab (UST) on small intestinal inflammation. This study aimed to compare the effects of anti-TNF-α agents and UST on small intestinal inflammation using propensity score analysis. Methods: This retrospective observational study involved 70 patients with Crohn's disease who had inflammation in the small intestine and had initiated treatment with either anti-TNF agents or UST between March 2015 and August 2021. Endoscopic findings were evaluated before treatment commencement and at 1-2 years post-treatment initiation. The propensity score was employed to compare the efficacy of TNF agents and UST on small bowel inflammation. Results: Ustekinumab exhibited greater improvement in the small intestinal endoscopy score than anti-TNF-α antibodies according to the propensity score analysis (inverse probability weighting; P = .0448). However, no significant disparity was observed in the overall improvement of endoscopic scores between UST and anti-TNF-α antibodies (P = .5938). Conclusions: This study suggests that UST might be more effective than anti-TNF-α agents in treating small intestinal inflammation in Crohn's disease.

Widespread use of proton pump inhibitors or potassium-competitive acid blocker has changed the status of gastrointestinal bleeding in patients with ischemic heart disease: real-world data from high volume centers.

BACKGROUND: Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used. METHODS: This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding). RESULTS: Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment. CONCLUSIONS: Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.

Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.

BACKGROUND: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). AIMS: To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. METHODS: A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group). RESULTS: Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. CONCLUSIONS: Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

ALBI score predicts morphological changes in esophageal varices following direct-acting antiviral-induced sustained virological response in patients with liver cirrhosis.

BACKGROUND: This study aimed to clarify the morphological changes in esophageal varices after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) in patients with cirrhosis. METHODS: A total of 243 patients underwent esophagogastroduodenoscopy before DAA treatment and after achieving SVR. Morphological changes in esophageal varices were investigated using esophagogastroduodenoscopy. RESULTS: This study comprised 125 males and 118 females with a median age of 68 years. Esophageal varices at baseline were classified into no varix in 155 (63.8%), F1 in 59 (24.3%), F2 in 25 (10.3%) and F3 in 4 (1.6%) patients. The improvement, unchanged, and aggravation rates of esophageal varices after SVR were 11.9%, 73.3%, and 14.8%, respectively. High ALBI score at SVR12 was an independent factor associated with post-SVR esophageal varices aggravation (p = 0.045). Time-dependent receiver operating characteristic (ROC) curve analysis revealed a cut-off value of - 2.33 for ALBI score at SVR12 in predicting post-SVR esophageal varices aggravation. Of the 155 patients without esophageal varices at baseline, 17 developed de novo post-SVR esophageal varices. High ALBI score at SVR12 was a significant independent factor associated with de novo post-SVR esophageal varices (p = 0.046). ROC curve analysis revealed a cut-off value of - 2.65 for ALBI score at SVR12 in predicting de novo post-SVR esophageal varices. CONCLUSIONS: Patients with cirrhosis can experience esophageal varices aggravation or de novo esophageal varices, despite achieving SVR. In particular, patients with high ALBI score at SVR12 have a high likelihood of developing post-SVR esophageal varices aggravation or de novo post-SVR esophageal varices.

Complications of antibiotic cement spacers used for elbow infections.

BACKGROUND: Antibiotic cement spacers have been widely used in the treatment of joint infections. There are no commercially available antibiotic spacers for the elbow. Instead, they are typically fashioned by the surgeon at the time of surgery using cement alone or a combination of cement with sutures, Steinmann pins, external fixator components, or elbow arthroplasty components. There is no consensus regarding the ideal elbow antibiotic spacer and no previous studies have examined the complications associated with these handmade implants in relation to their unique structural design. METHODS: We retrospectively reviewed 55 patients who had 78 static antibiotic cement spacers implanted between January 1998 and February 2021 as part of a 2-stage treatment plan for infection of an elbow arthroplasty, other elbow surgery, or primary elbow infection. Several antibiotic spacer structures were used during the study period. For analysis purposes, the spacers were classified into linked and unlinked spacers based on whether there was a linking mechanism between the humerus and the ulna. Complications related to these spacers that occurred either during the implantation, between implantation and removal, or during removal were recorded and analyzed from chart review and follow-up x rays. Reoperations due to spacer-related complications were also recorded. RESULTS: Among the 55 patients (78 spacers), there were 23 complications, including 17 minor and 6 major complications. The most common complication of unlinked spacers (intramedullary [IM] dowels, beads and cap spacer) was spacer displacement. Other complications included IM dowel fracture and difficulty locating beads during spacer removal. The major complications of linked cement spacers included two periprosthetic humerus fractures after internal external fixator cement spacers and re-operation due to breakage and displacement of one bushing cement spacer. The major complications of unlinked cement spacers included two reoperations due to IM dowel displacement and one reoperation due to displacement of beads. Among patients who had removal of all components and those with native joints, there was no statistically significant difference between internal external fixator cement spacers and unlinked cement spacers in minor complication rates (30% vs. 16%, P = .16), major complication rates (7% vs. 8%, P = .85) and reoperation rates (0% vs. 8%, P = .12). CONCLUSIONS: Static handmade antibiotic elbow spacers have unique complications related to their structural designs. The most common complication of linked and nonlinked cement spacers were failure of the linking mechanism and displacement, respectively. Surgeons should keep in mind the possible complications of different structures of cement spacers when choosing 1 antibiotic spacer structure over another.