Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Dental Students' and Dental School Graduates' Practical Skills: An International Survey of Perceptions of National Dental Associations in Europe.

PURPOSE: Dental students learn knowledge and practical skills to provide oral health care to the population. Practical skills must be maintained or continuously developed throughout a professional career. This cross-sectional survey aimed to evaluate the perception of practical skills of dental students and dental-school graduates by national dental associations (NDAs) in international comparison in the European Regional Organization of the FDI World Dental Federation (ERO-FDI) zone. MATERIALS AND METHODS: A questionnaire of 14 items collected information on pre-/postgraduate areas. RESULTS: A total of 25 countries participated (response rate: 69.4%), with 80.0% having minimum requirements for practical skills acquisition and 64.0% starting practical training in the 3rd year of study. In countries where clinical practical work on patients begins in the 2nd year of study, practical skills of graduates are perceived as average, starting in the 3rd year of study as mainly good, starting in the 4th as varying widely from poor to very good. In total, 76.0% of respondents feel that improvements are needed before entering dental practice. Improvements could be reached by treating more patients in dental school (32.0%), increasing the quantity of clinical training (20.0%), or having more clinical instructors (12.0%). In 56.0% of the countries, it is possible to open one's own dental practice immediately after graduation, and in 16.0%, prior vocational training is mandatory. CONCLUSIONS: All participating countries in the ERO-FDI zone reported practical training in dental school, most starting in the 3rd year of study. The perception of practical skills of dental students and dental-school graduates among NDAs is very heterogeneous. Reasons for the perceived deficiencies should be further explored.

Metabolic and Bariatric Surgery in Patients with Obesity Class V (BMI > 60 kg/m2): a Modified Delphi Study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the preferred method to achieve significant weight loss in patients with Obesity Class V (BMI > 60 kg/m2). However, there is no consensus regarding the best procedure(s) for this population. Additionally, these patients will likely have a higher risk of complications and mortality. The aim of this study was to achieve a consensus among a global panel of expert bariatric surgeons using a modified Delphi methodology. METHODS: A total of 36 recognized opinion-makers and highly experienced metabolic and bariatric surgeons participated in the present Delphi consensus. 81 statements on preoperative management, selection of the procedure, perioperative management, weight loss parameters, follow-up, and metabolic outcomes were voted on in two rounds. A consensus was considered reached when an agreement of ≥ 70% of experts' votes was achieved. RESULTS: A total of 54 out of 81 statements reached consensus. Remarkably, more than 90% of the experts agreed that patients should be notified of the greater risk of complications, the possibility of modifications to the surgical procedure, and the early start of chemical thromboprophylaxis. Regarding the choice of the procedure, SADI-S, RYGB, and OAGB were the top 3 preferred operations. However, no consensus was reached on the limb length in these operations. CONCLUSION: This study represents the first attempt to reach consensus on the choice of procedures as well as perioperative management in patients with obesity class V. Although overall consensus was reached in different areas, more research is needed to better serve this high-risk population.

Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY.

PURPOSE: The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib arm of the phase III OlympiAD trial (7.03 months). This prespecified analysis provides final overall survival (OS) and safety data. METHODS: The open-label, single-arm LUCY trial of olaparib (300 mg, twice daily) enrolled adults with gBRCAm or somatic BRCA-mutated (sBRCAm), HER2-negative mBC. Patients had previously received a taxane or anthracycline for neoadjuvant/adjuvant or metastatic disease and up to two lines of chemotherapy for mBC. RESULTS: Of 563 patients screened, 256 (gBRCAm, n = 253; sBRCAm, n = 3) were enrolled. In the gBRCAm cohort, median investigator-assessed PFS (primary endpoint) was 8.18 months and median OS was 24.94 months. Olaparib was clinically effective in all prespecified subgroups: hormone receptor status, previous chemotherapy for mBC, previous platinum-based chemotherapy (including by line of therapy), and previous cyclin-dependent kinase 4/6 inhibitor use. The most frequent treatment-emergent adverse events (TEAEs) were nausea (55.3%) and anemia (39.2%). Few patients (6.3%) discontinued olaparib owing to a TEAE. No deaths associated with AEs occurred during the study treatment or 30-day follow-up. CONCLUSION: The LUCY patient population reflects a real-world population in line with the licensed indication of olaparib in mBC. These findings support the clinical effectiveness and safety of olaparib in patients with gBRCAm, HER2-negative mBC. CLINICAL TRIAL REGISTRATION: Clinical trials registration number: NCT03286842.

Side-to-side magnetic duodeno-ileostomy in adults with severe obesity with or without type 2 diabetes: early outcomes with prior or concurrent sleeve gastrectomy.

BACKGROUND: Conventional metabolic/bariatric surgical anastomoses with sutures/staples may cause severe adverse events (AEs). OBJECTIVES: The study aim was to evaluate the feasibility, safety, and effectiveness of primary and revisional side-to-side duodeno-ileostomy (DI) bipartition using a novel magnetic compression anastomosis device (Magnet Anastomosis System [MS]). SETTING: Multicenter: private practices and university hospitals. METHODS: In patients with body mass index ([BMI, kg/m2] ≥35.0 to ≤50.0 with/without type 2 diabetes [T2D] glycosylated hemoglobin [HbA1C > 6.5 %]), two linear MS magnets were delivered endoscopically to the duodenum and ileum with laparoscopic assistance and aligned, initiating magnet fusion and gradual DI (MagDI). The MagDI-after-SG group had undergone prior sleeve gastrectomy (SG); the MagDI + SG group underwent concurrent SG. AEs were graded by Clavien-Dindo Classification (CDC). RESULTS: Between November 22, 2021 and May 30, 2023, 43 patients (88.0% female, mean age 43.7 ± 1.3 years) underwent the study procedures. The MS met feasibility criteria of magnet device placement, creation of patent anastomoses confirmed radiologically, and magnet passage in 100.0% of patients. There were 64 AEs, most were CDC grade I and II, significantly fewer in the MagDI-after-SG group (P < .001). No device-related AEs including anastomotic leakage, bleeding, obstruction, infection, or death. The MagDI-after-SG group experienced 6-month mean weight loss of 8.0 ± 2.5 kg (P < .01), 17.4 ± 5.0% excess weight loss (EWL). The MagDI + SG group had significantly greater weight loss (34.2 ± 1.6 kg, P < .001), 66.2 ± 3.4% EWL. All patients with T2D improved. CONCLUSIONS: In early results of a multicenter study, the incisionless, sutureless Magnet System formed patent, complication-free anastomoses in side-to-side DI with prior or concurrent SG.

Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial.

Importance: Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor. Objective: To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors. Design, Setting, And Participants: The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Participants had advanced or recurrent dMMR and microsatellite instability-high (MSI-H) or polymerase epsilon (POLE)-altered solid tumors. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months. Interventions: Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. Main Outcomes and Measures: The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. Results: The efficacy population included 327 patients (median [range] age, 63 [24-85] years; 235 [71.9%] female; 7 [2.1%] Asian, 6 [1.8%] Black, and 206 [63.0%] White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. All patients had at least 1 previous line of therapy. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months); 72.2% of responders (104 of 144) had a response lasting 12 or more months. Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months); probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median overall survival was not reached (95% CI, 31.6 months to not reached). The most frequent immune-related adverse events were hypothyroidism (25 [6.9%]), alanine aminotransferase increase (21 [5.8%]), and arthralgia (17 [4.7%]). No new safety concerns were identified. Conclusions And Relevance: In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need. Trial Registration: ClinicalTrials.gov Identifier: NCT02715284.

The Efficacy and Safety of Laparoscopic Single-Anastomosis Duodeno-ileostomy with Sleeve Gastrectomy (SADI-S) in Mid- and Long-Term Follow-Up: a Systematic Review.

This systematic review of 10 studies aimed to investigate the mid- and long-term results of duodeno-ileostomy with sleeve gastrectomy (SADI-S) according to the PRISMA guideline. Related articles, which reported outcomes of laparoscopic SADI-S with follow-up ≥ 3 years, were selected and analyzed. The percentage of excess weight loss (EWL) was 70.9-88.7%, and 80.4% at 6, and 10 years, respectively. The more common late complications were malabsorption (6.3%) and gastroesophageal reflux disease (GERD) (3.6%). The remission rates of hypertension, diabetes, GERD, obstructive sleep apnea, and dyslipidemia were 62.9%, 81.3%, 53.2%, 60.9%, and 69.7%, respectively. In conclusion, SADI-S is a safe and effective surgical technique with durable weight loss and a high rate of comorbidity resolution in mid and long term.

Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index.

Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC.

Unravelling the skills and motivations of Magdalenian artists in the depths of Atxurra Cave (Northern Spain).

Atxurra cave has a decorated assemblage composed of more than a hundred engraved animal depictions. All of them are located in deep parts of the cave and most of them are hidden in raised areas, away from the main path. The main sector is the "Ledge of the Horses", located at 330 m from the entrance of the cave. It is a space of 12 m long and 1.5 m wide, elevated 4 m above the cave floor. This area includes almost fifty engraved and painted animals accompanied by a dozen flint tools, three fireplaces, and around one hundred charcoal fragments from torches. This extraordinary archaeological record allows us to value the complexity of the artistic production inside the caves during the Upper Palaeolithic. Our study has confirmed that there is planning prior to artistic production, both in terms of the iconographic aspects (themes, techniques, formats), its location (visibility, capacity), and the lighting systems. Furthermore, the data indicates the panel was decorated to be seen by third parties from different positions and was expressly illuminated for this purpose. This evidence supports the role of rock art as a visual communication system in Upper Palaeolithic societies.

Comparative analysis of 5-year efficacy and outcomes of single anastomosis procedures as revisional surgery for weight regain following sleeve gastrectomy.

BACKGROUND: It is imperative to assess the results of revisional procedures following Sleeve Gastrectomy (SG), given the substantially growing population of patients who experience weight regain within a few years after undergoing this procedure. OBJECTIVE: Examine the comparative effectiveness of the Single Anastomosis Duodeno-Ileal Bypass (SADI-S) and the One Anastomosis Gastric Bypass (OAGB-MGB) as revisional procedures, with respect to their impact on weight loss, resolution of comorbidities, incidence of complications, and rates of reoperation in patients who had weight regain after SG with up to or more than 5 years of follow-up. SETTING: Hamad General Hospital, Academic tertiary referral center, Qatar. METHODS: This study retrospectively analyzed a database of patients who underwent the Single Anastomosis Duodeno-Ileal Switch (SADI-S) or the One Anastomosis Gastric Bypass - Mini Gastric Bypass- (OAGB-MGB) as revisional procedures for weight recidivism after a primary Laparoscopic Sleeve Gastrectomy (LSG). The follow-up period was at least 5 years, during which the impact of both procedures on weight loss, comorbidities, nutritional deficiencies, complications, and outcomes were compared. RESULTS: The study comprised 91 patients, with 42 and 49 in the SADI-S and OAGB-MGB groups, respectively. Significant weight loss (measured by total weight loss percentage, TWL%) was observed at the 5-year follow-up for the SADI-S group compared to the OAGB-MGB group (30.0 ± 18.4 vs. 19.4 ± 16.3, p = 0.008). Remission of comorbidities, specifically diabetes mellitus and hypertension, was more prevalent in the SADI-S group. Notably, the OAGB-MGB group had a higher incidence of complications (28.6% vs. 21.42%) and reoperations (5 patients vs. 1 in the SADI-S group). No mortality events were reported in either group. CONCLUSION: While both the OAGB-MGB and SADI-S have demonstrated efficacy as revisional procedures for weight regain following SG, the SADI-S exhibits superior outcomes compared to the OAGB-MGB with regard to weight loss, resolution of comorbidities, complication rates, and reoperation rates.

Expression Analysis of hsa-miR-181a-5p, hsa-miR-143-3p, hsa-miR-132-3p and hsa-miR-23a-3p as Biomarkers in Colorectal Cancer-Relationship to the Body Mass Index.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-5p could be considered as a biomarker in CRC patients with BMI ≥ 25 Kg/m2 and emerges as a tumor location marker. We conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, and hsa-miR-143-3p and hsa-miR-181a-5p expression analysis could be useful in the clinical management of CRC.

Combined Effect of Genetic Variants on Long-Term Weight Response after Bariatric Surgery.

The pathophysiology of body weight control involves complex interactions between hormonal, environmental, behavioral and genetic factors. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of 13 genes encoding gastrointestinal peptides, their receptors or the proteins involved in their expression, with long-term weight response in a cohort of 375 patients undergoing bariatric surgery (BS). To evaluate weight response, we combined several variables to define specific response phenotypes six years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed via allelic discrimination using Taqman® probes (Applied Biosystems, Foster City, CA, USA). The genotype association study was performed using the SNPstat program, with comparisons adjusted for sex, age, initial body mass index, type 2 diabetes, hypertension diagnosis and the type of surgery. We identified eight genetic variants associated with the weight response to BS, independently of the presurgery patient profile and the type of surgical technique, from which we calculated the unweighted risk score (RS) for each phenotype. The highest scoring category in each RS was significantly associated with lower weight loss (p = 0.0001) and greater weight regain (p = 0.0012) at the end of the follow-up.

Screening for Obstructive Sleep Apnea in truck drivers / Rastreio de Síndrome de Apneia Obstrutiva do Sono em motoristas

Abstract Professional drivers show a higher prevalence of obstructive sleep apnea (OSA) compared with the general population. OSA has been widely associated with an increased risk of traffic accidents. This article aims to investigate the presence of risk factors for OSA, its prevalence and the value of screening tools in a truck drivers' cohort. Descriptive and analytical prospective study. Demographic, anthropometric, Epworth Sleepiness Scale, STOP-Bang and Berlin Questionnaire were used to select subjects with suspicion of OSA. Polysomnography (PSG) was performed in individuals with positive screening. Mean age was 44.6±7 years, mean body mass index was 28.7±4 kg/m². Of the 281 truck drivers screened, 88 were positive for potential OSA. Of these, 63 completed PSG study and the diagnosis was confirmed in 85.7% (prevalence of 19.2%). The following variables showed a positive correlation with the apnea-hypopnea index: neck circumference and STOP-Bang. The combination of a predominantly male population, obesity, age distribution and lifestyle could account for the high prevalence of OSA in this specific population. Questionnaires proved to be a valuable screening tool. Screening, treatment, and management of OSA should be a priority as a public safety policy.

Resumo A prevalência de Síndrome de Apneia Obstrutiva do Sono (SAOS) em motoristas profissionais é superior à da população geral e esta tem sido amplamente associada ao risco aumentado de acidentes rodoviários. Este artigo tem por objetivos investigar fatores de risco de SAOS, estimar a sua prevalência e o valor de instrumentos de rastreio numa amostra de motoristas de pesados. Estudo prospetivo descritivo e analítico. Rastreio realizado com recurso a dados demográficos, antropométricos, Escala de Sonolência de Epworth, STOP-Bang e Questionário de Berlim. Nos indivíduos com rastreio positivo foi realizada polissonografia (PSG). A idade média era de 44,6±7 anos, índice de massa corporal 28,7±4 kg/m². Dos 281 motoristas incluídos, 88 apresentavam risco elevado de SAOS. Destes, 63 realizaram PSG, com confirmação diagnóstica em 85,7% (prevalência de 19,2%). O perímetro cervical e STOP-Bang apresentaram correlação positiva com o índice de apneia-hipopneia. A combinação de género predominantemente masculino, obesidade, distribuição de idade e estilo de vida pode justificar a elevada prevalência de SAOS nesta população. O uso de questionários é uma medida eficaz de rastreio. Nos motoristas, o rastreio e tratamento de SAOS deveria ser uma medida de saúde pública prioritária.

Screening for Obstructive Sleep Apnea in truck drivers.

Professional drivers show a higher prevalence of obstructive sleep apnea (OSA) compared with the general population. OSA has been widely associated with an increased risk of traffic accidents. This article aims to investigate the presence of risk factors for OSA, its prevalence and the value of screening tools in a truck drivers' cohort. Descriptive and analytical prospective study. Demographic, anthropometric, Epworth Sleepiness Scale, STOP-Bang and Berlin Questionnaire were used to select subjects with suspicion of OSA. Polysomnography (PSG) was performed in individuals with positive screening. Mean age was 44.6±7 years, mean body mass index was 28.7±4 kg/m². Of the 281 truck drivers screened, 88 were positive for potential OSA. Of these, 63 completed PSG study and the diagnosis was confirmed in 85.7% (prevalence of 19.2%). The following variables showed a positive correlation with the apnea-hypopnea index: neck circumference and STOP-Bang. The combination of a predominantly male population, obesity, age distribution and lifestyle could account for the high prevalence of OSA in this specific population. Questionnaires proved to be a valuable screening tool. Screening, treatment, and management of OSA should be a priority as a public safety policy.

Side-to-side magnet anastomosis system duodeno-ileostomy with sleeve gastrectomy: early multi-center results.

INTRODUCTION: Gastrointestinal anastomoses with classical sutures and/or metal staples have resulted in significant bleeding and leak rates. This multi-site study evaluated the feasibility, safety, and preliminary effectiveness of a novel linear magnetic compression anastomosis device, the Magnet System (MS), to form a side-to-side duodeno-ileostomy (DI) diversion for weight loss and type 2 diabetes (T2D) resolution. METHODS: In patients with class II and III obesity (body mass index [BMI, kg/m2] ≥ 35.0- ≤ 50.0 with/without T2D [HbA1C > 6.5%]), two linear MS magnets were delivered endoscopically to the duodenum and ileum with laparoscopic assistance and aligned, initiating DI; sleeve gastrectomy (SG) was added. There were no bowel incisions or retained sutures/staples. Fused magnets were expelled naturally. Adverse events (AEs) were graded by Clavien-Dindo Classification (CDC). RESULTS: Between November 22, 2021 and July 18, 2022, 24 patients (83.3% female, mean ± SEM weight 121.9 ± 3.3 kg, BMI 44.4 ± 0.8) in three centers underwent magnetic DI. Magnets were expelled at a median 48.5 days. Respective mean BMI, total weight loss, and excess weight loss at 6 months (n = 24): 32.0 ± 0.8, 28.1 ± 1.0%, and 66.2 ± 3.4%; at 12 months (n = 5), 29.3 ± 1.5, 34.0 ± 1.4%, and 80.2 ± 6.6%. Group mean respective mean HbA1C and glucose levels dropped to 1.1 ± 0.4% and 24.8 ± 6.6 mg/dL (6 months); 2.0 ± 1.1% and 53.8 ± 6.3 mg/dL (12 months). There were 0 device-related AEs, 3 procedure-related serious AEs. No anastomotic bleeding, leakage, stricture, or mortality. CONCLUSION: In a multi-center study, side-to-side Magnet System duodeno-ileostomy with SG in adults with class III obesity appeared feasible, safe, and effective for weight loss and T2D resolution in the short term.

A bacterial signature-based method for the identification of seven forensically relevant human body fluids.

Detection and identification of body fluids plays a crucial role in criminal investigation, as it provides information on the source of the DNA as well as corroborative evidence regarding the crime committed, scene, and/or association with persons of interest. Historically, forensic serological methods have been chemical, immunological, catalytic, spectroscopic, and/or microscopic in nature. However, most of these methods are presumptive, with few robust confirmatory exceptions. In recent years several new molecular methods (mRNA, miRNA, DNA methylation, etc.) have been proposed; although promising, these methods require high quality human DNA or RNA. Additional steps are required in RNA based methods. Additionally, RNA based methods cannot be used for old cases where only DNA extracts remain to sample from. In this study, a novel non-human DNA (microbiome) based method was developed for the identification of the majority of forensically relevant human biological samples. Eight hundred and twelve (n = 812) biological samples (semen, vaginal fluid, menstrual blood, saliva, feces, urine, and blood) were collected and preserved using methods commonly used in forensic laboratories for evidence collection. Variable region four (V4) of 16 S ribosomal DNA (16 S rDNA) was amplified using a dual-indexing strategy and then sequenced on the MiSeq FGx sequencing platform using the MiSeq Reagent Kit v2 (500 cycles) and following the manufacturer's protocol. Machine learning prediction models were used to assess the classification accuracy of the newly developed method. As there was no significant difference in bacterial communities between vaginal fluid, menstrual blood, and female urine, these were combined as female intimate samples. Except in urine, the bacterial structures associated with male and female body fluid samples were not significantly different from one another. The newly developed method accurately identified human body fluid samples with an overall accuracy of more than 88%. This newly developed bacterial signature-based method is fast (no additional steps are needed as the same DNA can be used for both body fluid identification and STR typing), efficient (consume less sample as a single test can identify all major body fluids), sensitive (needs only 5 pg of bacterial DNA), accurate, and can be easily added into a forensic high throughput sequencing (HTS) panel.

Impact of the 21-Gene Assay in Patients with High-Clinical Risk ER-Positive and HER2-Negative Early Breast Cancer: Results of the KARMA Dx Study.

BACKGROUND: The 21-gene Oncotype DX Breast Recurrence Score® assay is prognostic and predictive of chemotherapy benefit for patients with estrogen receptor-positive, HER2- early breast cancer (EBC). The KARMA Dx study evaluated the impact of the Recurrence Score® results (RS) on the treatment decision for patients with EBC and high-risk clinicopathological characteristics for whom chemotherapy (CT) was considered. METHODS: Eligible patients with EBC were candidates for the study if CT was considered standard recommendation by local guidelines. Three high-risk EBC cohorts were predefined: (A) pT1-2, pN0/N1mi, and grade 3; (B) pT1-2, pN1, and grades 1-2; and (C) neoadjuvant cT2-3, cN0, and Ki67 ≤ 30%. Treatment recommendations before and after 21-gene testing were registered, as well as treatment received and physicians' confidence levels in their final recommendations. RESULTS: A total of 219 consecutive patients were included from eight Spanish centers: 30 in cohort A, 158 in cohort B, and 31 in cohort C. Ten patients were excluded from the final analysis as CT was not initially recommended. After 21-gene testing, treatment decisions changed from CT + endocrine therapy (ET) to ET alone for 67% of the whole group. In total, 30% (95% confidence interval [CI] 15% to 49%), 73% (95% CI 65% to 80%), and 76% (95% CI 56% to 90%) of patients ultimately received ET alone in cohorts A, B, and C, respectively. Physicians' confidence in their final recommendations increased in 34% of cases. CONCLUSIONS: Use of the 21-gene test resulted in an overall 67% reduction in CT recommendation in patients considered candidates for CT. Our findings indicate the substantial potential of the 21-gene test to guide CT recommendations in patients with EBC considered to be at high risk of recurrence based on clinicopathological parameters, regardless of nodal status or treatment setting.