The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions.

In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse testis. We have demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilization of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O2. Through the generation of a germline-specific Epas1 knockout mouse line, and through modulation of EPAS1 levels in primary cultures of spermatogonia with the small drug molecule Daprodustat, we have demonstrated that EPAS1 is required for robust SSC function in regenerative conditions (post-transplantation and post-chemotherapy), via the regulation of key cellular processes such as metabolism. These findings shed light on the relationship between hypoxia and male fertility and will potentially facilitate optimization of in vitro culture conditions for infertility treatment pipelines using SSCs, such as those directed at pediatric cancer survivors.

Dietary Interventions for the Treatment of Inflammatory Bowel Diseases: An Updated Systematic Review and Meta-analysis.

BACKGROUND & AIMS: This study aimed (1) to systematically review controlled trials of solid food diets for the treatment of inflammatory bowel disease (IBD); and (2) to grade the overall quality of evidence. METHODS: Systematic review of prospective controlled trials of solid food diets for the induction or maintenance of remission in IBD. Two authors independently performed study selection, data extraction, and assessment of certainty of evidence. Meta-analyses were performed on studies with quantitative data on response, remission, and relapse. RESULTS: There were 27 studies for meta-analysis. For induction of remission in Crohn's disease (CD), low refined carbohydrate diet and symptoms-guided diet outperformed controls, but studies had serious imprecision and very low certainty of evidence. The Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence). PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence). For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence). CONCLUSIONS: Among the most robust dietary trials in IBD currently available, certainty of evidence remains very low or low. Nonetheless, emerging data suggest potential benefit with PEN for induction and maintenance of remission in CD. Reduction of red meat and refined carbohydrates might not reduce risk of CD relapse. As more dietary studies become available, the certainty of evidence could improve, thus allowing for more meaningful recommendations for patients.

Digital rehabilitation for hand and wrist pain: a single-arm prospective longitudinal cohort study.

Introduction: Wrist and hand represent the third most common body part in work-related injuries, being associated with long-term absenteeism. Telerehabilitation can promote access to treatment, patient adherence, and engagement, while reducing health care-related costs. Objective: Report the results of a fully remote digital care program (DCP) for wrist and hand pain (WP). Methods: A single-arm interventional study was conducted on individuals with WP applying for a DCP. Primary outcome was the mean change in the Numerical Pain Rating Scale after 8 weeks (considering a minimum clinically important change of 30%). Secondary outcomes were: disability (Quick Disabilities of the Arm, Shoulder, and Hand questionnaire), analgesic intake, surgery intention, mental health (patient health questionnaire [PHQ-9] and generalized anxiety disorder [GAD-7]), fear-avoidance beliefs (FABQ-PA), work productivity and activity impairment, and engagement. Results: From 189 individuals starting the DCP, 149 (78.8%) completed the intervention. A significant pain improvement was observed (51.3% reduction (2.26, 95% CI 1.73; 2.78)) and 70.4% of participants surpassing minimum clinically important change. This change correlated with improvements in disability (52.1%), FABQ-PA (32.2%), and activities impairment recovery (65.4%). Improvements were also observed in other domains: surgery intent (76.1%), mental health (67.0% in anxiety and 72.7% in depression), and overall productivity losses (68.2%). Analgesic intake decreased from 22.5% to 7.1%. Mean patient satisfaction score was 8.5/10.0 (SD 1.8). Conclusions: These findings support the feasibility and utility of a fully remote DCP for patients with WP. Clinically significant improvements were observed in all health-related and productivity-related outcomes, alongside very high patient adherence rates and satisfaction. This study strengthens that management of WP is possible through a remote DCP, decreasing access barriers and potentially easing health care expenditure.

Clinical features associated with the invasive component in lentigo maligna of the head and neck: A retrospective study of 175 cases.

BACKGROUND: Lentigo maligna (LM) can develop into lentigo maligna melanoma (LMM) with risk of metastatic dissemination. LMM may be underestimated on the basis of the initial biopsy. The invasion may affect both the therapeutic options and the prognosis. OBJECTIVES: To identify the clinical features associated with invasive forms of LM and factors associated with its recurrence. METHODS: A retrospective, single-centre study of consecutive LM and LMM histologically confirmed and treated by surgery between 2009 and 2014. RESULTS: In total, 175 patients with LM/LMM were surgically treated in our establishment. In men, lesions were more likely to be in the "peripheral zone" (41.8%), while in women they were seen more often in the "central zone" (P=0.001). In multivariate analysis, only the peripheral zone was found to be associated with a risk of invasion (P=0.008). The rate of recurrence was 9% and lesions were more likely to be primary LMM (P=0.0006) excised with clear margins. CONCLUSION: The treatment of choice in LM with non-clear margins must be re-excision, especially for lesions situated in the peripheral zone. Close follow-up is recommended due to risk of recurrence, even in the case of clear margins.

Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

Adult-Attained Height and Colorectal Cancer Risk: A Cohort Study, Systematic Review, and Meta-Analysis.

BACKGROUND: The influence of anthropometric characteristics on colorectal neoplasia biology is unclear. We conducted a systematic review and meta-analysis to determine if adult-attained height is independently associated with the risk of colorectal cancer or adenoma. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and Web of Science from inception to August 2020 for studies on the association between adult-attained height and colorectal cancer or adenoma. The original data from the Johns Hopkins (Baltimore, MD) Colon Biofilm study was also included. The overall HR/OR of colorectal cancer/adenoma with increased height was estimated using random-effects meta-analysis. RESULTS: We included 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. Thirty-three studies reported data for colorectal cancer incidence per 10-cm increase in height; 19 yielded an HR of 1.14 [95% confidence interval (CI), 1.11-1.17; P < 0.001), and 14 engendered an OR of 1.09 (95% CI, 1.05-1.13; P < 0.001). Twenty-six studies compared colorectal cancer incidence between individuals within the highest versus the lowest height percentile; 19 indicated an HR of 1.24 (95% CI, 1.19-1.30; P < 0.001), and seven resulting in an OR of 1.07 (95% CI, 0.92-1.25; P = 0.39). Four studies reported data for assessing colorectal adenoma incidence per 10-cm increase in height, showing an overall OR of 1.06 (95% CI, 1.00-1.12; P = 0.03). CONCLUSIONS: Greater adult attained height is associated with an increased risk of colorectal cancer and adenoma. IMPACT: Height should be considered as a risk factor for colorectal cancer screening.

Asynchronous and Tailored Digital Rehabilitation of Chronic Shoulder Pain: A Prospective Longitudinal Cohort Study.

BACKGROUND: Chronic shoulder pain (SP) is responsible for significant morbidity, decreased quality of life and impaired work ability, resulting in high socioeconomic burden. Successful SP management is dependent on adherence and compliance with effective evidence-based interventions. Digital solutions may improve accessibility to such treatments, increasing convenience, while reducing healthcare-related costs. PURPOSE: Present the results of a fully remote digital care program (DCP) for chronic SP. PATIENTS AND METHODS: Interventional, single-arm, cohort study of individuals with chronic SP applying for a digital care program. Primary outcome was the mean change between baseline and 12 weeks on the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire. Secondary outcomes were change in pain (NPRS), analgesic consumption, intention to undergo surgery, anxiety (GAD-7), depression (PHQ-9), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI) and engagement. RESULTS: From 296 patients at program start, 234 (79.1%) completed the intervention. Changes in QuickDASH between baseline and end-of-program were both statistically (p < 0.001) and clinically significant, with a mean reduction of 51.6% (mean -13.45 points, 95% CI: 11.99; 14.92). Marked reductions were also observed in all secondary outcomes: 54.8% in NPRS, 44.1% ceased analgesics consumption, 55.5% in surgery intent, 37.7% in FABQ-PA, 50.3% in anxiety, 63.6% in depression and 66.5% in WPAI overall. Higher engagement was associated with higher improvements in disability. Mean patient satisfaction score was 8.7/10.0 (SD 1.6). CONCLUSION: This is the first real-world cohort study reporting the results of a multimodal remote digital approach for chronic SP rehabilitation. High completion and engagement rates were observed, which were associated with clinically significant improvement in all health-related outcomes, as well as marked productivity recovery. These promising results support the potential of digital modalities to address the global burden of chronic musculoskeletal pain.

Telerehabilitation of acute musculoskeletal multi-disorders: prospective, single-arm, interventional study.

BACKGROUND: Acute musculoskeletal (MSK) pain is very common and associated with impaired productivity and high economic burden. Access to timely and personalized, evidence-based care is key to improve outcomes while reducing healthcare expenditure. Digital interventions can facilitate access and ensure care scalability. OBJECTIVE: Present the feasibility and results of a fully remote digital care program (DCP) for acute MSK conditions affecting several body areas. METHODS: Interventional single-arm study of individuals applying for digital care programs for acute MSK pain. Primary outcome was the mean change between baseline and end-of-program in self-reported Numerical Pain Rating Scale (NPRS) score and secondary outcomes were change in analgesic consumption, intention to undergo surgery, anxiety (GAD-7), depression (PHQ-9), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI-GH) and engagement. RESULTS: Three hundred forty-three patients started the program, of which 300 (87.5%) completed the program. Latent growth curve analysis (LGCA) revealed that changes in NPRS between baseline and end-of-program were both statistically (p < 0.001) and clinically significant: 64.3% reduction (mean - 2.9 points). Marked improvements were also noted in all secondary outcomes: 82% reduction in medication intake, 63% reduction in surgery intent, 40% in fear-avoidance beliefs, 54% in anxiety, 58% in depression and 79% recovery in overall productivity. All outcomes had steeper improvements in the first 4 weeks, which paralleled higher engagement in this period (3.6 vs 3.2 overall weekly sessions, p < 0.001). Mean patient satisfaction score was 8.7/10 (SD 1.26). STRENGTHS AND LIMITATIONS: This is the first longitudinal study demonstrating the feasibility of a DCP for patients with acute MSK conditions involving several body areas. Major strengths of this study are the large sample size, the wide range of MSK conditions studied, the breadth of outcomes measured, and the very high retention rate and adherence level. The major limitation regards to the absence of a control group. CONCLUSIONS: We observed very high completion and engagement rates, as well as clinically relevant changes in all health-related outcomes and productivity recovery. We believe this DCP holds great potential in the delivery of effective and scalable MSK care. TRIAL REGISTRATION: NCT, NCT04092946 . Registered 17/09/2019.

Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.

Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial.

BACKGROUND: Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner. METHODS: In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16. RESULTS: Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline. CONCLUSION: These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Fish Oil for Inflammatory Bowel Disease: Panacea or Placebo?

Dietary supplements have increasingly gained popularity over the years not only to replete micronutrient deficiencies but for their use in treatment of disease. The popularity of dietary supplements for inflammatory bowel diseases (IBD) arises from their perceived ease of use, potential disease-modifying benefits, and perceived safety. Overall, randomized controlled trials have not consistently shown a benefit of fish oil for the maintenance of remission with Crohn's disease. The inconsistency of these findings highlights the need for more studies that are powered to clarify the context in which omega-3 fatty acids might have a role in the treatment algorithm of IBD.

[Impact on quality of life and autonomy of patients aged over 75 years treated with anti-PD-1 for metastatic melanoma: A single-centre prospective study]. / Impact sur la qualité de vie et l'autonomie des patients de plus de 75 ans traités par anti-PD-1 pour un mélanome métastatique : étude prospective monocentrique.

INTRODUCTION: We previously studied anti-PD-1 safety in elderly (≥80 years) patients and reported a retrospective two-centre cohort with a similar safety profile in elderly and in younger patients. Quality-of-life evaluation data is still lacking in this specific population. MATERIALS AND METHODS: A prospective, single-centre study in patients aged over 75 years presenting metastatic melanoma treated with anti-PD-1. The endpoint was monitoring of quality of life (by a specific survey) and onco-geriatric assessment at the beginning of therapy, then at 3 and 6 months (nutritional status, comorbidities, autonomy, thymic and cognitive disorders). RESULTS: Fourteen patients were included of median age 86.5 years [range: 78-94] from March to September 2018. General status was good, with a median Charlson score of 0 [extremes 0-4]. Nine patients were evaluated at 3 months and six patients at 6 months. There was no significant difference in quality-of-life scores obtained at baseline, 3 months and 6 months. DISCUSSION: This study shows that neither quality of life nor autonomy appears to be affected by anti-PD-1 treatment in patients aged over 75 years. However, these results should be interpreted with caution due to the small number of patients included, the short follow-up period and the single-centre data. Nevertheless, the prospective analysis and the complete onco-geriatric evaluation and monitoring yielded unique and original data.

Correction to: Anatomical Configuration of the Stomach Post-Endoscopic Sleeve Gastroplasty (ESG)-What Are the Sutures Doing?

The name of author Vivek Kumbhari was misspelled in the original article.

GSTO1-1 is an upstream suppressor of M2 macrophage skewing and HIF-1α-induced eosinophilic airway inflammation.

BACKGROUND: Glutathione S-transferases omega class 1 (GSTO1-1) is a unique member of the GST family regulating cellular redox metabolism and innate immunity through the promotion of LPS/TLR4/NLRP3 signalling in macrophages. House dust mite (HDM) triggers asthma by promoting type 2 responses and allergic inflammation via the TLR4 pathway. Although linked to asthma, the role of GSTO1-1 in facilitating type 2 responses and/or HDM-driven allergic inflammation is unknown. OBJECTIVE: To determine the role of GSTO1-1 in regulating HDM-induced allergic inflammation in a preclinical model of asthma. METHODS: Wild-type and GSTO1-1-deficient mice were sensitized and aeroallergen challenged with HDM to induce allergic inflammation and subsequently hallmark pathophysiological features characterized. RESULTS: By contrast to HDM-challenged WT mice, exposed GSTO1-1-deficient mice had increased numbers of eosinophils and macrophages and elevated levels of eotaxin-1 and -2 in their lungs. M1 macrophage-associated factors, such as IL-1ß and IL-6, were decreased in GSTO1-1-deficient mice. Conversely, M2 macrophage factors such as Arg-1 and Ym1 were up-regulated. HIF-1α expression was found to be higher in the absence of GSTO1-1 and correlated with the up-regulation of M2 macrophage markers. Furthermore, HIF-1α was shown to bind and activate the eotaxin-2 promotor. Hypoxic conditions induced significant increases in the levels of eotaxin-1 and -2 in GSTO1-deficient BMDMs, providing a potential link between inflammation-induced hypoxia and the regulation of M2 responses in the lung. Collectively, our results suggest that GSTO1-1 deficiency promotes M2-type responses and increased levels of nuclear HIF-1α, which regulates eotaxin (s)-induced eosinophilia and increased disease severity. CONCLUSION & CLINICAL IMPLICATION: We propose that GSTO1-1 is a novel negative regulator of TLR4-regulated M2 responses acting as an anti-inflammatory pathway. The discovery of a novel HIF-1α-induced eotaxin pathway identifies an unknown connection between hypoxia and the regulation of the severity of allergic inflammation in asthma.

Yogurt consumption and colorectal polyps.

Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case-control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case-case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.

[Synergistic effect of anti-PD1 immunotherapy then radiotherapy in advanced basal cell carcinoma]. / Synergie de la séquence immunothérapie par anti-PD1 et radiothérapie au cours d'un carcinome basocellulaire avancé.

INTRODUCTION: Vismodégib is the first-line treatment for non-operable or metastatic locally advanced basal cell carcinomas (LABCC), although complete response is rare and adverse effects are common. Immune checkpoint inhibitors are currently being evaluated in this indication. Herein we report a case of LABCC that responded dramatically to sequenced "immunotherapy then radiotherapy". OBSERVATION: A 47-year-old male presented peri- and intra-orbital infiltrative LABCC that had been present for more than 10 years. After an initial response to vismodégib, further disease progression resulted in the introduction of successive lines of treatment (radiotherapy, platinum salts and itraconazole) without any significant response. Compassionate treatment with pembrolizumab was initiated. After eight courses, major clinical progression occurred with intraoral extension responsible for respiratory discomfort. Following withdrawal of pembrolizumab, high-energy radiotherapy was started with a spectacular response, both clinically and in terms of imaging. DISCUSSION: The efficacy of "radiotherapy-immunotherapy" sequencing in melanoma has been reported, due in particular to the abscopal effect and radiosensitisation. In our case, where the sequence was inverted, immunotherapy may have enhanced the effects of radiotherapy through "immunosensitisation", whereas radiotherapy alone had previously been ineffective. This observation underlines the potential value of these treatments, either combined or in sequence, and their synergistic effects and optimal association require further evaluation.

Anatomical Configuration of the Stomach Post-Endoscopic Sleeve Gastroplasty (ESG)-What Are the Sutures Doing?

INTRODUCTION AND AIM: Endoscopic sleeve gastroplasty (ESG) is a procedure in which endoscopically placed sutures involute the stomach and promote weight loss. There is limited data on the durability of these sutures. PATIENTS AND METHODS: This was a single center series of 5 patients who underwent ESG performed by a single endoscopist. Patients underwent repeat endoscopy for different clinical indications. RESULTS: ESGs were successfully reversed at 3 weeks and 1 month following index ESG without significant fibrosis or scaring. At 8 and 14 months, a few sutures had dehisced though there were extensive areas of fibrosis. By 2 years, most of the sutures had dehisced; however, the gastric volume remained reduced. CONCLUSION: This case series offers an intriguing evaluation of the anatomical changes induced by ESG.