Epigenetic activation of SOX11 is associated with recurrence and progression of ductal carcinoma in situ to invasive breast cancer.

BACKGROUND: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS. METHODS: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts. RESULTS: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. AKT activation correlated with chromatin accessibility and EZH2 enrichment upregulating SOX11 expression. AKT and HER2 inhibitors decreased SOX11 expression along with diminished mammosphere formation. SOX11 was upregulated in HER2+ and basal-like subtypes (P < 0.001). Longitudinal DCIS cohort (n = 194) revealed shorter recurrence-free survival in SOX11+ than SOX11- patients (P = 0.0056 in all DCIS; P < 0.0001 in HER2+ subtype) associated with increased risk of ipsilateral breast event/IBE (HR = 1.9, 95%CI = 1.2-2.9; P = 0.003). DISCUSSION: Epigenetic activation of SOX11 drives recurrence of DCIS and progression to invasive cancer, suggesting SOX11 as a predictive biomarker of IBE.

Pseudomelanosis of the duodenum and stomach.

Pseudomelanosis duodeni is characterized by endoscopic findings of black or black-brown speckled pigmentation in the duodenal mucosa, usually diagnosed via biopsy. This report presents a case of a 75-year-old male presented with left lower abdominal pain, change in bowel habits, and decreased appetite. Gastroduodenoscopy and biopsies of the duodenum and antrum lead to the diagnosis of pseudomelanosis duodeni.

False-Negative 68 Ga-FAPI PET/CT in Pediatric Thyroid Medullary Carcinoma Seen With 68 Ga-DOTATOC PET/CT and 18 F-FDG PET/CT.

ABSTRACT: In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid lesions. This is the case of a 13-year-old boy newly diagnosed with medullary thyroid cancer with high calcitonin level. 68 Ga PET/CT revealed the presence of only a primary thyroid lesion. Proven to be superior in detecting metastasis, 68 Ga-FAPI PET/CT was performed. The results came out negative for primary and potential metastatic lesions. This case sheds shed light on false-negatives reported in 68 Ga-FAPI PET/CT scans in pediatric patients, emphasizing the need for alternate radiotracers when a negative study is met.

Association of Uroguanylin, Body Mass Index, and Waist Circumference: Sex Differences and Obesity Implications among a Sample of Iraqi Adults in Baghdad City.

This research investigates the gender-specific associations of uroguanylin levels with various health-related parameters in Iraqi adults. The results revealed significant differences between genders in food style preferences and waist circumference (WC) risk. Notably, uroguanylin exhibited distinct correlations with low density lipoprotein (LDL) cholesterol, glycated hemoglobin (HbA1c), body mass index (BMI), and WC in females and males, indicating potential gender-specific effects on lipid metabolism, glucose regulation, and adiposity. A total of 140 Iraqi adults (73 females and 67 males) were recruited into the study. Physical activity levels, food style preferences, WC risk, and BMI subgroups, were compared between genders. Additionally, participants' characteristics, including age, height, weight, BMI, blood pressure, cholesterol levels, and uroguanylin concentrations, were analyzed. Significant gender differences were observed in food style preferences, with a higher proportion of males preferring fast food, with a greater percentage of females classified as having a high risk, females exhibited lower height and weight compared to males. HbA1c levels were significantly lower in females, whereas high density lipoprotein (HDL) cholesterol levels were significantly higher in females than in males. Uroguanylin concentrations were also significantly lower in females compared to males. Uroguanylin shows a moderately negative correlation with LDL cholesterol in females but not in males. Furthermore, a strong negative association between uroguanylin and HbA1c in females indicated improved glycemic control with higher uroguanylin levels, whereas an opposite trend was observed in males. No significant association was observed between uroguanylin and BMI in females, a significant positive correlation was found in males. For WC, a weak negative correlation was noted in females, whereas a moderately negative correlation was observed in males. These contrasting correlations imply potential gender-specific effects of uroguanylin on adiposity and body fat distribution.

Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity.

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutes-enriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an objective response rate of 25% in the SER-401 arm and 67% in the placebo arm (though the study was under-powered related to poor accrual during the COVID-19 pandemic). Translational analyses demonstrated that vancomycin preconditioning was associated with the disruption of the gut microbiota and impaired immunity, with incomplete recovery at ICB administration (particularly in patients with high baseline Ruminococcaceae). These results have important implications for future microbiome modulation trials. SIGNIFICANCE: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti-PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials.

Association Between Tranexamic Acid and Decreased Periprosthetic Joint Infection Risk in Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Over 2 Million Patients.

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures. METHODS: A systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up. RESULTS: Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = -0.0038, 95% CI [-0.005 to -0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = -0.0095 [95% CI -0.013 to -0.005], P < .001) in patients followed for more than 90 days. CONCLUSIONS: This meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA.

Cryoballoon pulmonary vein isolation versus radiofrequency ablation of the pulmonary veins and left atrial posterior wall: Patient-reported outcomes.

BACKGROUND: Data are lacking on patient-reported outcomes (PRO) following cryoballoon ablation (CBA) versus radiofrequency ablation (RFA). We sought to evaluate QoL and clinical outcomes of cryoballoon pulmonary vein isolation only (CRYO-PVI-ONLY) versus RFA with PVI and posterior wall isolation (RF-PVI+PWI) in a large prospective PRO registry. METHODS: Patients who underwent AF ablation (2013-2016) at our institution were enrolled in an automated, prospectively maintained PRO registry. CRYO-PVI-ONLY patients were matched (1:1) with RF-PVI+PWI patients based on age, gender, and type of AF (paroxysmal vs. persistent). QoL and clinical outcomes were assessed using PRO surveys at baseline and at 1-year. The atrial fibrillation symptom severity scale (AFSSS) was the measure for QoL. Additionally, we assessed patient-reported clinical improvement, arrhythmia recurrence, and AF burden (as indicated by AF frequency and duration scores). RESULTS: A total of 296 patients were included (148 in each group, 72% paroxysmal). By PRO, a significant improvement in QoL was observed in the overall study population and was comparable between CRYO-PVI-ONLY and RF-PVI+PWI (baseline median AFSSS of 11.5 and 11; reduced to 2 and 4 at 1 year, respectively; p = 0.44). Similarly, the proportion of patients who reported improvement in their overall QoL and AF related symptoms was high and similar between the study groups [92% (CRYO-PVI-ONLY) vs. 92.8% (RF-PVI+PWI); p = 0.88]. Arrhythmia recurrence was significantly more common in the CRYO-PVI-ONLY group (39.7%) compared to RF-PVI+PWI (27.7 %); p = 0.03. Comparable results were observed in paroxysmal and persistent AF. CONCLUSION: CRYO-PVI-ONLY and RF-PVI+PWI resulted in comparable improvements in patient reported outcomes including QoL and AF burden; with RF-PVI+PWI being more effective at reducing recurrences.

The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on revisional bariatrics.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program designated bariatric surgery as a clinical pathway. Among the tiers of the Masters Program, revisional bariatric surgery is the highest tier of "mastery" within the pathway. This article presents the top 10 seminal studies representing the current landscape of revisional bariatrics. METHODS: The literature was systematically searched and seminal articles designated by consensus agreement of the SAGES Metabolic and Bariatric Surgery committee using multiple criteria, including impact on the field, citation frequency, and expert opinion. Articles were reviewed by committee members and presented in summarized fashion. RESULTS: The top 10 papers are presented in grouped thematic categories covering the early evolution of revisional bariatrics, changing criteria for reoperative bariatric surgery, divergence of revision versus conversion bariatric surgery, and recent technologic innovations in revisional bariatric surgery. Each summary is presented with expert appraisal and commentary. CONCLUSION: These seminal papers represent a snapshot of the dynamic field of revisional bariatric surgery and emphasize the need to not only remain current with contemporary trends but also keep a patient-oriented perspective on patient and intervention selection for optimal success.

Telemedicine-Based Risk Program to Prevent Falls Among Older Adults: Protocol for a Randomized Quality Improvement Trial.

BACKGROUND: The Center for Disease Control and Prevention's Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative offers health care providers tools and resources to assist with fall risk screening and multifactorial fall risk assessment and interventions. Its effectiveness has never been evaluated in a randomized trial. OBJECTIVE: This study aims to describe the protocol for the STEADI Options Randomized Quality Improvement Trial (RQIT), which was designed to evaluate the impact on falls and all-cause health expenditures of a telemedicine-based form of STEADI implemented among older adults aged 65 years and older, within a primary care setting. METHODS: STEADI Options was a pragmatic RQIT implemented within a health system comparing a telemedicine version of the STEADI fall risk assessment to the standard of care (SOC). Before screening, we randomized all eligible patients in participating clinics into the STEADI arm or SOC arm based on their scheduled provider. All received the Stay Independent screener (SIS) to determine fall risk. Patients were considered at risk for falls if they scored 4 or more on the SIS or answered affirmatively to any 1 of the 3 key questions within the SIS. Patients screened at risk for falls and randomized to the STEADI arm were offered a registered nurse (RN)-led STEADI assessment through telemedicine; the RN provided assessment results and recommendations to the providers, who were advised to discuss fall-prevention strategies with their patients. Patients screened at risk for falls and randomized to the SOC arm were asked to participate in study data collection only. Data on recruitment, STEADI assessments, use of recommended prevention services, medications, and fall occurrences were collected using electronic health records and patient surveys. Using staff time diaries and administrative records, the study prospectively collected data on STEADI implementation costs and all-cause outpatient and inpatient charges incurred over the year following enrollment. RESULTS: The study enrolled 720 patients (n=307, 42.6% STEADI arm; n=353, 49% SOC arm; and n=60, 8.3% discontinued arm) from September 2020 to December 2021. Follow-up data collection was completed in January 2023. As of February 2024, data analysis is complete, and results are expected to be published by the end of 2025. CONCLUSIONS: The STEADI RQIT evaluates the impact of a telemedicine-based, STEADI-based fall risk assessment on falls and all-cause health expenditures and can provide information on the intervention's effectiveness and cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05390736, http://clinicaltrials.gov/ct2/show/NCT05390736. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/54395.

Novel PUF60 variant suggesting an interaction between Verheij and Cornelia de Lange syndrome: phenotype description and review of the literature.

Verheij syndrome [VRJS; OMIM 615583] is a rare autosomal dominant neurodevelopmental disorder characterized by distinct clinical features, including growth retardation, intellectual disability, cardiac, and renal anomalies. VRJS is caused by deletions of chromosome 8q24.3 or pathogenic variants in the PUF60 gene. Recently, pathogenic PUF60 variants have been reported in some individuals with VRJS, contributing to the variability in the clinical presentation and severity of the condition. PUF60 encodes a protein involved in regulating gene expression and cellular growth. In this report, we describe a new case of VRJS with developmental delay, cardiac-, and renal abnormalities, caused by a heterozygous pathogenic PUF60 variant. Surprisingly, DNA methylation analysis revealed a pattern resembling the Cornelia de Lange syndrome (CdLS) episignature, suggesting a potential connection between PUF60 and CdLS-related genes. This case report further delineates the clinical and molecular spectrum of VRJS and supports further research to validate the interaction between VRJS and CdLS.

Retraction: Cecal Lipoma: A Rare Etiology of Acute Appendicitis in Adults.

[This retracts the article DOI: 10.7759/cureus.19423.].

Retraction: Mesenteric Panniculitis: A Rare Condition in a Patient With Rheumatoid Arthritis.

[This retracts the article DOI: 10.7759/cureus.20136.].

Implant-assisted removable partial dentures: Part I. a scoping review of clinical applications.

PURPOSE: This scoping review aimed to systematically map research regarding implant-assisted removable partial dentures (IARPDs), and identify existing gaps in knowledge. STUDY SELECTION: Two reviewers independently conducted a search of the MEDLINE-PubMed and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for Scoping Review and included articles published in English up to August 31, 2022, including human studies, reviews, and in vitro studies. Expert opinions, animal studies, and clinical studies involving complete overdentures were excluded, and ten aspects for establishing the treatment strategy for IARPDs were examined. RESULTS: One hundred and twelve articles were chosen. There were two treatment modalities: IARPDs retained by implant- and tooth-supported surveyed single crowns (SCs) or fixed partial dentures (FPDs). In IARPDs retained by tooth-supported surveyed SCs or FPDs, the survival rate of dental implants for IARPDs was relatively higher with a wide range of marginal bone loss and many complications, but with improved functional performance, oral health-related quality of life, and patient satisfaction. There were limited data on survival or success rates and designs of IARPDs, attachment selections, length and diameter, inclination, placement sites, and loading protocols of implants, regardless of prosthetic types. There was limited information on maxillary IARPDs except for survival rates of implants. CONCLUSIONS: Although IARPDs could become a useful treatment strategy, there is limited scientific consensus with gaps in knowledge about their use. Additional well-designed clinical and in vitro studies are necessary to scientifically establish IARPDs as definitive prostheses in implant dentistry.

Implant-assisted removable partial dentures: Part II. a systematic review of the effects of implant position on the biomechanical behavior.

PURPOSE: This systematic review aimed to evaluate the effects of implant placement sites on the biomechanical behavior of implant-assisted removable partial dentures (IARPDs) using finite element analysis (FEA). STUDY SELECTION: Two reviewers independently conducted manual searches of the PubMed, Scopus, and ProQuest databases for articles investigating implant location in IARPDs using FEA, according to the 2020 Systematic Reviews and Meta-analyses statement. Studies published in English up to August 1, 2022, were included in the analysis based on the critical question. RESULTS: Seven articles meeting the inclusion criteria were systematically reviewed. Six studies investigated mandibular Kennedy Class I and one study investigated mandibular Kennedy Class II. Implant placement reduced the displacement and stress distribution of the IARPD components, including dental implants and abutment teeth, regardless of the Kennedy Class type and dental implant placement site. Most of the included studies showed that, based on the biomechanical behavior, the molar region, rather than the premolar region, is the preferred implant placement site. None of the selected studies investigated the maxillary Kennedy Class I and II. CONCLUSIONS: Based on the FEA regarding mandibular IARPDs, we concluded that implant placement in both the premolar and molar regions improves the biomechanical behaviors of IARPD components, regardless of the Kennedy Class. Implant placement in the molar region results in more suitable biomechanical behaviors compared with implant placement in the premolar region in Kennedy Class I. No conclusion was reached for Kennedy Class II due to the lack of relevant studies.

The impact of COVID-19 on antibiotic resistance and clinical outcomes among critically ill patients.

BACKGROUND: There is conflicting evidence regarding the impact of the Coronavirus 2019 (COVID-19) pandemic on antimicrobial resistance, with few studies conducted in low- and middle-income countries. We investigated the impact of the COVID-19 pandemic on multidrug resistant organisms (MDROs) among critically ill patients and their clinical outcomes. METHODS: This was a retrospective observational study of patients admitted to the medical Intensive Care Unit at Jordan University Hospital and had blood, urine, or bronchoalveolar bacterial cultures taken during 2 time periods: prepandemic (ie, 1/2016 to 1/2019) and pandemic (ie, 1/2020 to 1/2023). We compared the clinical outcomes (ie, in-hospital deaths, the need for O2 devices, intubation, the length of hospital stay, and the occurrence of complications) and prevalence of MDROs between the 2 periods and conducted multivariate analyses. RESULTS: There were 1,254 patients (479 prepandemic and 775 postpandemic. The percentage of patients who had MDROs was significantly higher among patients with a culture taken during the pandemic (82.4%) compared to before it (17.6%) (P-value=.000). Multivariate analysis demonstrated that patients cultured during the pandemic were more than 3 times as likely to have an MDRO (odds ratio = 3.210; 95% confidence interval: 2.236-4.609). CONCLUSIONS: The increase in MDROs during the COVID-19 pandemic is an alarming threat to public health; thus, investigating the antibiotic resistance situation as the pandemic subsides is crucial.

Associations Between Inactivity and Cognitive Function in Older Intensive Care Unit Survivors.

BACKGROUND/INTRODUCTION: Critically ill older adults are profoundly inactive while in the intensive care unit (ICU), and this inactivity persists after discharge from the ICU. Older ICU survivors who were mechanically ventilated are at high risk for post-ICU cognitive impairment. OBJECTIVES/AIMS: The present study examined the relationship between the ratio of daytime to nighttime activity and executive function in older ICU survivors. METHODS: This was a secondary analysis of pooled data from 2 primary studies of older adults who were functionally independent prior to hospitalization, mechanically ventilated while in ICU, and within 24 to 48 hours post-ICU discharge. Actigraphy recorded daytime activity (mean activity counts per minute, 6 am to 9:59 pm) and nighttime activity (mean activity counts per minute, 10 pm to 5:59 am). A daytime-to-nighttime activity ratio was calculated by dividing daytime activity by nighttime activity. The NIH Toolbox Dimensional Change Card Sort Test assessed cognitive flexibility (DCCST: fully corrected T score). Multivariate regression examined the association between the daytime-to-nighttime activity ratio and DCCST scores, adjusting for 2 covariates (age in years and NIH Toolbox Grip Strength fully corrected T score). RESULTS: The mean daytime-to-nighttime activity ratio was 2.10 ± 1.17 (interquartile range, 1.42). Ratios for 6 participants (13.6%) were less than 1, revealing higher activity during nighttime hours rather than daytime hours. Higher daytime-to-nighttime ratios were associated with better DCCST scores (ß = .364, P = .005). CONCLUSIONS: The proportion of daytime activity versus nighttime activity was considerably low, indicating severe alterations in the rest/activity cycle. Higher daytime-to-nighttime activity ratios were associated with better executive function scores, suggesting that assessment of daytime activity could identify at-risk older ICU survivors during the early post-ICU transition period. Promotion of daytime activity and nighttime sleep may accelerate recovery and improve cognitive function.

Effect of intraoral administration of parathyroid hormone on osseous and soft tissue healing around implants in ovariectomized rat maxillae.

OBJECTIVES: Intermittent administration of parathyroid hormone (PTH) increases systemic bone mass. However, the effect of PTH on osseous and soft tissue healing around implants in osteoporosis patients remains unclear. This study aimed to investigate the effects of PTH on tissue healing around implants in ovariectomized rats and to compare systemic and intraoral administration routes. MATERIAL AND METHODS: Implants were placed at the healed sites of ovariectomized rats 3 weeks after maxillary first molar extraction. Rats were randomly divided into two groups that received either daily systemic subcutaneous or local intraoral PTH administration. Maxillae were dissected to examine bone architectures with micro-computed tomography images. Histomorphometric and immunohistochemical analyses were performed to evaluate osseous and soft tissue healing around the implants. RESULTS: Regardless of the administration route, PTH significantly increased bone area and the numbers of osteoblasts, osteoclasts, and osteocytes in the first and second inside and outside areas of implant threads, in addition to decreasing the number of sclerostin+ osteocytes. However, the intraoral PTH administration route was superior to the systemic route by significantly improving bone quality and promoting collagen production in the connective tissue around implants. CONCLUSIONS: Parathyroid hormone administration promoted both osseous and soft tissue healing around implants, irrespective of administration route. Interestingly, intraoral administration improved the evaluated parameters more than systemic administration. Thus, the intraoral route could become a useful treatment strategy for implant treatment in osteoporosis patients.