Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review Ad Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). STUDY QUESTION: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? DATA SOURCES: MEDLINE, Embase, Scopus, and Cochrane databases. STUDY DESIGN: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. RESULTS: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. CONCLUSION: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients with Unresectable HCC.

BACKGROUND & AIMS: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC. METHODS: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients. RESULTS: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients. CONCLUSIONS: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays.

A Case of Coil-Assisted Retrograde Transvenous Obliteration to Treat Colonic Varices.

Colonic variceal bleeding is a rare cause of lower gastrointestinal (GI) bleeding, which carries a high mortality rate. Due to limited data, the optimal management of colonic variceal bleeding is not known. Coil-assisted retrograde transvenous obliteration (CARTO) has been shown to be very effective in managing non-esophageal variceal bleeding, but only a few cases demonstrate its effectiveness in treating colonic variceal bleeding. Here we present a case of colonic variceal bleeding treated with CARTO in order to expand on the limited body of evidence showing its efficacy in effectively treating this rare cause of life-threatening GI bleeding.

The Egyptian journey from having the highest prevalence of hepatitis C virus to being the first to achieve "gold tier" in conquering the disease.

Hepatitis C virus (HCV) is a major global health concern, particularly in Egypt, due to historic schistosomiasis control efforts that inadvertently led to widespread HCV transmission. This study aimed to evaluate the efficacy of Egypt's national strategies in controlling and reducing the prevalence of HCV, including introducing sofosbuvir and implementing the "100 Million Healthy Lives" campaign. The approach includes a review of epidemiological data, an analysis of the national HCV control strategies implemented, and an assessment of their outcomes, focusing on the period from 2006 to 2022. Significant milestones were achieved, including a drastic reduction in new HCV infections from 300 per 100,000 in 2014 to 9 per 100,000 in 2022 and successful treatment of over 4 million people. Egypt has become the first country in the world to achieve the "gold tier" status based on World Health Organization criteria on the path to eradication of HCV. Egypt's comprehensive approach can serve as a model for similar endemic regions. Other nations with high HCV prevalence might benefit from adopting similar multidimensional strategies, emphasizing prevention and treatment.

Stereotactic Ablative Radiotherapy for Oligoprogressive Cancers: Results of the Randomized Phase II STOP Trial.

PURPOSE: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. METHODS: We enrolled patients with 1-5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), randomized 1:2 between continued SOC treatment vs. SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all non-hematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events (AEs), and duration of systemic therapy post-randomization. RESULTS: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. Median age was 67 years and 39 (43%) were female. The most common primary sites were lung (44%), genitourinary (23%) and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm but curves cross and 2-year PFS was 9% vs. 24% respectively, p=0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p=0.22). Lesional control was superior with SABR (70% vs. 38% respectively, p=0.0015). There were 2 (3.4%) grade 3 and no grade 4/5 AEs attributable to SABR. CONCLUSION: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Racial and ethnic disparities in gallbladder cancer: A two-decade analysis of incidence and mortality rates in the US.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy that is usually diagnosed at a late stage. Prior data showed increasing incidence of GBC in the US. However, little is known about race/ethnic-specific incidence and mortality trends of GBC per stage at diagnosis. Therefore, we aimed to conduct a time-trend analysis of GBC incidence and mortality rates categorized by race/ethnicity and stage-at-diagnosis. METHODS: Age-adjusted GBC incidence and mortality rates were calculated using SEER*Stat software from the United States Cancer Statistics database (covers ~98% of US population between 2001 and 2020) and NCHS (covers ~100% of the US population between 2000 and 2020) databases, respectively. Race/Ethnic groups were Non-Hispanic-White (NHW), Non-Hispanic-Black (NHB), Hispanic, Non-Hispanic-Asian/Pacific-Islander (NHAPI), and Non-Hispanic-American-Indian/Alaska-Native (NHAIAN). Stage-at-diagnoses were all stages, early, regional, and distant stages. Joinpoint regression was used to generate time-trends [annual percentage change (APC) and average APC (AAPC)] with parametric estimations and a two-sided t-test (p-value cut-off 0.05). RESULTS: 76,873 patients were diagnosed with GBC with decreasing incidence rates in all races/ethnicities except NHB who experienced an increasing trend between 2001 and 2014 (APC = 2.08, p < 0.01) and plateauing afterward (APC = -1.21, p = 0.31); (AAPC = 1.03, p = 0.03). Among early-stage tumors (9927 patients), incidence rates were decreasing only in Hispanic (AAPC = -4.24, p = 0.006) while stable in other races/ethnicities (NHW: AAPC = -2.61, p = 0.39; NHB: AAPC = -1.73, p = 0.36). For regional-stage tumors (29,690 patients), GBC incidence rates were decreasing only in NHW (AAPC = -1.61, p < 0.001) while stable in other races/ethnicities (NHB: AAPC = 0.73, p = 0.34; Hispanic: AAPC = -1.58, p = 0.24; NHAPI: AAPC = -1.22, p = 0.07). For distant-stage tumors (31,735 patients), incidence rates were increasing in NHB (AAPC = 2.72, p < 0.001), decreasing in Hispanic (AAPC = -0.64, p = 0.04), and stable in NHW (AAPC = 0.07, p = 0.84) and NHAPI (AAPC = 0.79, p = 0.13). There were 43,411 deaths attributed to GBC with decreasing mortality rates in all races/ethnicities except NHB who experienced a stable trend (AAPC = 0.25, p = 0.25). CONCLUSION: Nationwide data over the last two decades show that NHB patients experienced increasing GBC incidence between 2001 and 2014 followed by stabilization of the rates. This increase was driven by late-stage tumors and occurred in the first decade. NHB also experienced non-improving GBC mortality, compared to other race and ethnic groups who had decreasing mortality. This can be due to lack of timely-access to healthcare leading to delayed diagnosis and worse outcomes. Future studies are warranted to investigate contributions to the revealed racial and ethnic disparities, especially in NHB, to improve early detection.

The efficacy of Hemospray in managing bleeding related to gastrointestinal tumors: systematic review and meta-analysis.

INTRODUCTION: Gastrointestinal (GI) bleeding stemming from malignant tumors is increasingly recognized, due to advancements in oncology and detection methods. Traditional endoscopic hemostatic techniques have shown variable success rates in managing hemorrhagic GI neoplasms. Hemospray, an emerging endoscopic hemostatic powder, offers promise in treating upper GI bleeding, potentially extending its utility to neoplastic bleeding sites. This meta-analysis aims to evaluate Hemospray's efficacy in managing bleeding related to GI tumors. METHODS: We searched Embase, Scopus, Web of Science, Medline/PubMed, and Cochrane. Inclusion criteria encompassed studies focusing on malignancy-related GI bleeding and interventions utilizing Hemospray. Comparative studies contrasted Hemospray with standard endoscopic treatments (SET), while noncomparative studies assessed Hemospray's efficacy independently. The risk of bias was assessed using appropriate tools, and statistical analyses were performed using Review Manager and open Meta analyst software. RESULTS: We included 19 studies in our meta-analysis. Hemospray demonstrated higher rates of immediate hemostasis compared to SET (odds ratio: 17.14, 95% confidence interval: 4.27-68.86), with consistent outcomes across studies. Rebleeding rates at 14 and 30 days were comparable between Hemospray and SET groups, suggesting similar efficacy in long-term hemostasis. Hemospray showed a significantly lower need for nonendoscopic hemostasis compared to SET (odds ratio: 0.51, 95% confidence interval: 0.30-0.87), indicating a potential reduction in supplementary interventions. Safety assessments revealed no confirmed adverse events directly linked to Hemospray. CONCLUSION: This meta-analysis highlights Hemospray's efficacy in achieving immediate hemostasis in GI tumor-related bleeding, with potential benefits in reducing supplementary interventions and improving patient outcomes. Despite comparable rebleeding rates, Hemospray emerges as a valuable adjunctive therapy in managing malignant GI bleeding.

Growth hormone augmentation in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and metabolic dysregulation. Growth hormone (GH) augmentation has emerged as a potential therapeutic intervention for treating MASLD. This systematic review and meta-analysis aimed to evaluate the impact of GH augmentation on different parameters of MASLD. A systematic literature search identified randomized controlled trials investigating GH augmentation in MASLD patients. Search results were screened via Covidence and the Risk of Bias 2 tool was used to assess bias in randomized controlled trials. Statistical analysis utilized RevMan v5.3. We combined dichotomous outcomes employing odds ratios and continuous outcomes utilizing mean difference (MD), each with a 95% confidence interval (CI). Statistical significance was indicated by a P-value less than 0.05. Heterogeneity was evaluated using I2 tests. Our results showed that GH augmentation resulted in a significant reduction in both relative (MD: -46.26; 95% CI: -71.52, -21.00; P = 0.0003) and absolute (MD: -5.15; 95% CI: -7.93, -2.37; P = 0.0003) hepatic fat fraction. GH augmentation significantly reduced alanine aminotransferase (MD: -5.97; 95% CI: -10.31, -1.62; P = 0.007) and gamma-glutamyl transferase (MD: -16.18; 95% CI: -30.76, -1.59; P = 0.03) levels. No significant changes were observed in hemoglobin A1c, C-reactive protein, fasting serum glucose, BMI, triglycerides, and low-density lipoprotein cholesterol levels. Our meta-analysis highlights GH augmentation as a promising therapy for reducing liver steatosis and improving liver enzyme levels in MASLD patients. Further large-scale trials are warranted to examine the long-term effects, safety profiles, and potential impact on various measures.

Remimazolam for sedation in gastrointestinal endoscopy: A comprehensive review.

Worldwide, a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient comfort. Propofol, benzodiazepines and opioids continue to be widely used. However, in recent years, Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal (GI) endoscopy. It is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural sedation. Remimazolam has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase, volume of distribution, total body clearance, and negligible drug-drug interactions. It also has satisfactory efficacy and has achieved high rates of successful sedation in GI endoscopy. Furthermore, studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol, which is currently a gold standard for procedural sedation in most parts of the world. However, the use of Propofol is associated with hemodynamic instability and respiratory depression. In contrast, Remimazolam has lower incidence of these adverse effects intra-procedurally and hence, may provide a safer alternative to Propofol in procedural sedation. In this comprehensive narrative review, highlight the pharmacologic characteristics, efficacy, and safety of Remimazolam for procedural sedation. We also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.

Efficacy of orlistat in obese patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials.

Objective: Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease worldwide. Orlistat blocks intestinal fat absorption, leading to decreased liver fat content. Therefore, it is a viable option for NAFLD management. Methods: We performed a systematic review and metaanalysis using randomized controlled trials (RCTs). We used mean difference (MD) to pool continuous outcomes presented with the corresponding confidence interval (CI). Results: We included four RCTs with a total of 379 patients. Orlistat was effective in reducing liver fat content (MD: -5.02, 95% CI [-7.23, -2.82], P = 0.00001), alanine transferase (MD: -10.03, 95% CI [-17.80, -2.26], P = 0.01), aspartate transferase (MD: -4.29, 95% CI [-7.59, -0.99], P = 0.01), waist circumference (MD: -3.18, 95% CI [-4.25, -2.10], P = 0.00001), body mass index (MD: -1.03, 95% CI [-1.34, -0.73], P = 0.00001), total cholesterol (MD: -3.75, 95% CI [-4.02, -3.49], P = 0.00001), and low-density lipoprotein (MD: -3.83, 95% CI [-4.05, -3.61], P = 0.00001). However, orlistat was associated with increased serum triglycerides (MD: 7.46, 95% CI [6.48, 8.44], P = 0. 00001). Conclusion: Orlistat is a viable option for NAFLD management; however, it increases triglyceride levels. Larger RCTs are required.

A Comprehensive Analysis of Reported Adverse Events and Device Failures Associated with Esophageal Self-Expandable Metal Stents: An FDA MAUDE Database Study.

INTRODUCTION: Esophageal Stents are used to maintain esophageal lumen patency in esophageal strictures caused by intrinsic and/or extrinsic malignancies and the occlusion of concomitant esophageal fistulas. While data on the efficacy and safety of esophageal stents exist, comprehensive evaluation of adverse events is limited. The aim of this study is to investigate the reported adverse events and device failures associated with esophageal self-expandable metal stents (SEMS) using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: Post-marketing surveillance data for the esophageal SEMSs were analyzed using the FDA's MAUDE database from January 2014 to December 10, 2023. The outcomes of interest were patient-related adverse events and device failures. Statistical analysis was performed using Microsoft Excel 2010 and SPSS. Pooled numbers and percentages were calculated for each adverse event. Continuous variables underwent analysis using a two-tailed student t test, and significance was set to p ≤ 0.05. RESULTS: During the study period, 548 MAUDE reports revealed 873 device failures and 186 patient-related adverse events. The most common device issues were stent activation, positioning, or separation problems (4 n = 403; 46.2%), followed by device detachment or migration (n = 109, 12.5%), and material problems (n = 93, 10.7%). Patient complications included dysphagia/odynophagia (10%), perforation, pain, and bleeding (each 7.6%). The most common device failures in over-the-wire (OTW) stents and through-the-scope (TTS) stents were activation, positioning, or separation problems (TTS: n = 183, 52.6% vs OTW: n = 220, 41.9%). Compared to OTW stents, TTS stents had higher migration and breakage (13.5% vs. 11.8%, p = 0.24), and (9.2% vs. 6.7%, p = 0.08) respectively, while OTW stents had more challenges with stent advancement or removal (5.1% vs. 0.3%, p < 0.001 and 4.6% vs 3.4%, p = 0.19, respectively) and material problems (14.7% vs. 4.6%, p < 0.001). Activation, positioning, and separation problems were the most frequent device failures in fully covered (FC) and partially covered (PC) stents (FC: n = 62, 32.8%, PC: n = 168, 43.5%). FC stents had higher migration rates (20.6% vs 9.8%, p < 0.001), while PC stents exhibited more material problems (17.4% vs. 5.8%, p < 0.001) and difficulties with advancing the stents (6.7% vs. 0%, p < 0.001). CONCLUSION: Our examination showed a prevalence of reported device complications associated with stent activation, positioning, and separation problems. Dysphagia or odynophagia emerged as the most frequently reported patient complication. Furthermore, our analysis, provides insights into TTS vs. OTW and FC vs. PC esophageal SEMSs, enabling endoscopists and manufacturers to better understand adverse events and potentially optimize device design for future iterations.

Basic Principles and Role of Endoscopic Ultrasound in Diagnosis and Differentiation of Pancreatic Cancer from Other Pancreatic Lesions: A Comprehensive Review of Endoscopic Ultrasound for Pancreatic Cancer.

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Pancreatic lesions consist of both neoplastic and non-neoplastic lesions and often pose a diagnostic and therapeutic challenge due to similar clinical and radiological features. In recent years, pancreatic lesions have been discovered more frequently as incidental findings due to the increased utilization and widespread availability of abdominal cross-sectional imaging. Therefore, it becomes imperative to establish an early and appropriate diagnosis with meticulous differentiation in an attempt to balance unnecessary treatment of benign pancreatic lesions and missing the opportunity for early intervention in malignant lesions. Endoscopic ultrasound (EUS) has become an important diagnostic modality for the identification and risk stratification of pancreatic lesions due to its ability to provide detailed imaging and acquisition of tissue samples for analysis with the help of fine-needle aspiration/biopsy. The recent development of EUS-based technology, including contrast-enhanced endoscopic ultrasound, real-time elastography-endoscopic ultrasound, miniature probe ultrasound, confocal laser endomicroscopy, and the application of artificial intelligence has significantly augmented the diagnostic accuracy of EUS as it enables better evaluation of the number, location, dimension, wall thickness, and contents of these lesions. This article provides a comprehensive overview of the role of the different types of EUS available for the diagnosis and differentiation of pancreatic cancer from other pancreatic lesions while discussing their key strengths and important limitations.

Etrolizumab as an induction and maintenance therapy for ulcerative colitis: A systematic review and meta-analysis of randomized controlled trials.

Background and Aim: Etrolizumab is a gut-targeted anti-ß7 integrin monoclonal antibody. However, the evidence of etrolizumab efficacy and safety in ulcerative colitis remains inconclusive. Therefore, we aim to evaluate the safety and efficacy of etrolizumab as an induction and maintenance therapy for active moderate to severe ulcerative colitis. Methods: We synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, Web of Science, and Cochrane Library until April 2023. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42023437040. Results: Five RCTs with 1849 participants were included. The etrolizumab group had a significant clinical response (RR: 1.28 with 95% CI [1.08, 1.51], P = 0.005), clinical remission rates during the induction phase (RR: 2.47 with 95% CI [1.48, 4.11], P = 0.0005), compared with the placebo group in ulcerative colitis; however, there was no statistically significant difference between the two groups, regarding the corticosteroids-free remission rate (RR: 1.92 with 95% CI [0.94, 3.92], P = 0.07). Moreover, endoscopic improvement, endoscopic remission, and histologic remission rates were observed more in the etrolizumab group during both the induction and maintenance phases. For safety outcomes, etrolizumab was significantly safer, but any adverse event was higher in the etrolizumab group than in the placebo. Conclusion: Etrolizumab shows its effectiveness as both an induction and maintenance therapy for moderate or severe UC. The findings demonstrate its positive impact on clinical, endoscopic, and histologic remission rates. Regarding safety, other than any side effects, etrolizumab showed a good safety than a placebo.

Assessment of burnout, resilience, and thriving among academic health professionals: findings from an international study.

Introduction: Burnout, resilience, and thriving significantly impact academics, particularly in health professions, where responsibilities are extensive. This study aimed to explore these constructs among academic health professionals, examining sociodemographic and work-related factors influencing these outcomes. Methods: A cross-sectional study was conducted among academic health professionals via web-based professional networks from August 2022 to February 2023. Validated tools were used, and descriptive and inferential statistics were applied. Results: 505 participants were included, predominantly female (63%), with a mean age of 38.15 ± 9.6 years. High burnout was reported by 10.9%, 13.7% experienced exhaustion, and 6.3% were disengaged. Resilience and thriving were moderate at 59.2 and 51.9%, respectively. Age correlated negatively with burnout (r = -0.131, p = 0.003) but positively with resilience (r = 0.178, p < 0.001). Females reported higher exhaustion (p = 0.014), while males showed greater resilience (p = 0.016). Instructors exhibited lower resilience compared to assistant professors (p < 0.001) and associate professors (p < 0.001). Those at public universities reported higher exhaustion than those at private universities (p < 0.001). Conclusion: Variable levels of burnout, resilience, and thriving were observed among academic health professionals, influenced by sociodemographic and work-related factors. Interventions targeting resilience and thriving may mitigate burnout risk and enhance engagement among academics in health professions.

Treatment of excessive gingival display using conventional esthetic crown lengthening versus computer guided esthetic crown lengthening: (a randomized clinical trial).

BACKGROUND: Surgical guides have been proposed in an attempt to reach more predictable outcomes for esthetic crown lengthening. The objective of the present study was to evaluate the effectiveness of esthetic crown lengthening using 3D-printed surgical guides in the management of excessive gingival display due to altered passive eruption type 1B. MATERIALS AND METHODS: Sixteen patients diagnosed with altered passive eruption type 1B, were divided into two groups. In the control group, the procedure was carried out conventionally, and in the study group, a dual surgical guide was used. The parameters of wound healing (swelling, color, probing depth, bleeding index, and plaque index), pain scores, gingival margin stability, and operating time were assessed at 1 week, 2 weeks, 3 months, and 6 months postoperatively. RESULTS: There was no statistically significant difference in terms of wound healing, pain scores, and gingival margin stability between both groups at different time intervals (P = 1), however, there was a statistical difference between both groups in terms of operating time with the study group being significantly lower (P < 0.001). CONCLUSION: Digitally assisted esthetic crown lengthening helps shorten the operating time and reduces the possibility of human errors during the measurements. This will be useful in helping practitioners achieve better results. PRACTICAL IMPLICATIONS: The conventional method remains to be the gold standard. However, shorter operating time and lower margins for errors will help reduce costs as the chair side time is reduced as well as the possibility for a second surgery is lower. This will improve patient satisfaction as well.

Chronic Hepatitis E Virus Manifesting as Elevated Transaminases in a Heart Transplant Patient.

Hepatitis E virus (HEV) is a common cause of viral hepatitis worldwide. Genotypes 1 and 2 cause acute hepatitis in endemic regions (Asia and Africa), whereas genotypes 3 and 4 (America and Europe) result in sporadic acute or chronic hepatitis, specifically in certain groups. HEV infections are rising because of increased transplantation rates and immunosuppression. We report a 75-year-old heart transplant patient with nonspecific symptoms, diagnosed with HEV chronic hepatitis. Despite ribavirin-induced hemolytic anemia, the patient achieved sustained virological response and normalization of liver enzymes.

Intermittent fasting regimens for metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed , EMBASE , WOS , SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, -0.32; 95% CI, -0.55 to -0.09; P  < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, -39.83; 95% CI, -64.78 to -14.87; P  < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction ( P  < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial.

OBJECTIVES: To evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3-5 days of microbiologically active IV therapy. METHODS: A multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3-5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). RESULTS: In the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference -3.7%, 95% CI -16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DISCUSSION: In patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Frailty in end-stage liver disease: Understanding pathophysiology, tools for assessment, and strategies for management.

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical decisions regarding patients' eligibility for critical care and transplantation. This, in turn, can guide the development of an individualized treatment plan for each patient with cirrhosis, with a focus on prioritizing exercise, proper nutrition, and appropriate treatment of hepatic complications as the primary lines of treatment. In this review, we aim to explore the topic of frailty in liver diseases, with a particular emphasis on pathophysiology, clinical assessment, and discuss strategies for preventing frailty through effective treatment of hepatic complications. Furthermore, we explore novel assessment and management strategies that have emerged in recent years, including the use of wearable technology and telemedicine.