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Objective: To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases., Background: Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management., Methods: We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers., Results: From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates ( P =0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P =0.031) and incomplete resection (≥R1; hazard ratio=0.41; P =0.015)., Conclusions: The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale and Objectives: This study evaluated the diagnostic performance of 18 F-fluorocholine (FCH) PET/CT as the first-line functional imaging method for preoperative localization of hyperfunctioning parathyroid glands (HPGs) in patients with primary hyperparathyroidism (PHPT)., Materials and Methods: This retrospective single-center study included 80 consecutive patients with PHPT, referred for FCH PET/CT between January 2018 and July 2022, and who subsequently underwent surgery. The diagnostic performance of FCH PET/CT was compared to histological results for per-lesion analysis, and to postoperative resolution of biochemical PHPT for per-patient analysis., Results: 18 F-FCH-PET/CT revealed 95 positive foci in 77/80 patients and was negative in 3/80 patients. Postoperative resolution of HPT was obtained in 67/80 patients (84%). Per-lesion analysis showed 80 true positives, five true negatives, 11 false negatives, and eight false positives. Seven PET-positive foci could not be compared to histology. In a first per-lesion analysis, excluding these seven anomalies, sensitivity and positive predictive value (PPV) of FCH PET/CT were 88% (95% CI: 79-94) and 91% (95% CI: 87-94), respectively. In a second per-lesion analysis considering the seven anomalies as false positives (maximum bias analysis), PPV was 84% (95% CI: 80%-87%). By per-patient analysis, FCH PET/CT correctly identified and located all pathological glands in 56/80 (70%, 95% CI: 59-80) patients., Conclusion: 18 F-Fluorocholine PET/CT appears to be an effective pre-surgical imaging method for localization of hyperfunctioning parathyroid tissue in patients with PHPT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate the diagnostic accuracy of drain fluid lipase as an early predictor of postoperative pancreatic fistula and establish the most appropriate day for their measure., Background: Clinically relevant postoperative pancreatic fistula remains a potentially life-threatening complication after pancreatic surgery. Early detection strategies remain key to reduce both the incidence and the burden of pancreatic fistula., Methods: The LIPAse DRAIN (LIPADRAIN) study is a multicenter, prospective diagnostic study conducted in 7 tertiary university hospitals. Drain fluid values to detect clinically relevant postoperative pancreatic fistula from postoperative day 1 to postoperative day 6 were evaluated using receiver operating characteristic curve analysis. A biomarker was considered to be relevant for clinical use if its area under the curve (AUC) was greater than 0.75., Results: Of the 625 patients included in the analysis, clinically relevant postoperative pancreatic fistula occurred in 203 (32%) patients. On postoperative days 3 and 4, drain fluid lipase was a reliable biomarker to detect clinically relevant postoperative pancreatic fistula (AUC: 0.761; 95% confidence interval [CI]: 0.761-0.799 and AUC: 0.784; 95% CI: 0.743-0.821, respectively). On postoperative day 3, with a threshold of 299 units/L, drain fluid lipase yielded a negative predictive value of 51%, sensitivity of 78%, and specificity of 63% for the detection of clinically relevant postoperative pancreatic fistula., Conclusions: In this multicenter prospective study, drain fluid lipase is a reliable biomarker at postoperative days 3 and 4 for the diagnosis of clinically relevant postoperative pancreatic fistula after pancreatic surgery and should be systematically measured on postoperative day 3., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Lower esophageal sphincter achalasia is associated with a higher risk of aspiration during anesthesia. Endoluminal Functional Lumen Imaging Probe (EndoFLIP) is used as an adjunctive tool in both the diagnosis and treatment of achalasia, for which all children require anesthesia. Anesthesia may affect the parameters of the EndoFLIP due to its effect on gut motility. There are no standard anesthesia protocols to help decrease the risk of aspiration and the undesirable effect of anesthesia on EndoFLIP parameters. This study aims to standardize an anesthesia protocol to target both goals., Methods: A protocol was developed to address perioperative management in patients undergoing EndoFLIP for any indication to minimize both anesthetic effect on the esophageal motility as well as perioperative complications. A retrospective data analysis was conducted on patients who underwent EndoFLIP at Cincinnati Children's Hospital Medical Center; pre- and post-protocol implementation data including adverse events was compared., Results: Pre-protocol implementation: 60 cases (median age of 13.8 years, 30 [50%] females) with 2 cases of adverse events (3.3%). Post-protocol implementation: 71 cases (median age of 14.6 years, 37 [52.1%] females) with no adverse events (0/71 = 0%). In comparison between pre- and post-protocol cases, no significant difference was noted in gender, age, and adverse events. Post-protocol procedures were found to be significantly shorter (median time of 89 vs. 79 min, p = 0.004)., Conclusions: Our anesthesia protocol provides a standardized way of administering anesthesia minimizing impact on EndoFLIP parameters and aspiration for patients with achalasia., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers., Methods: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later., Results: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports., Conclusions: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Pharyngeal contractile integral (PhCI) is the product of mean pharyngeal contractile amplitude, length, and duration, and provides a single metric for the vigor of entire pharyngeal contraction. A major limitation in children is lack of characterization of PhCI on high-resolution pharyngeal manometry. We aimed to determine and compare the values of PhCI in children with the abnormal and normal videofluoroscopic study of swallow (VFSS)., Methods: Children who underwent high-resolution pharyngeal and esophageal manometry (HRPM/HREM), as well as VFSS, were divided into two groups; "normal VFSS" and "abnormal VFSS" groups. PhCI was calculated from the pharyngo-esophageal manometry analysis software (MMS, v9.5, Laborie Medical Technologies), and compared in these two groups., Results: Of 67 children, 9 had abnormal VFSS (mean age 64 ± 50 months; 66.7% males), while 58 had normal VFSS (mean age 123 ± 55 months; 47% males). The mean PhCI in abnormal and normal VFSS groups was 82.00 ± 51.90 and 147.28 ± 53.89 mmHg.s.cm, respectively (p = 0.001). Subjects with abnormal VFSS were significantly younger than those with normal VFSS (p = 0.003). However, after adjusting for the VFSS result, age was no longer related to PhCI (p = 0.364). In subgroup analysis of children presenting with dysphagia, the mean PhCI in abnormal (9 subjects) and normal (36 subjects) VFSS groups was 82.00 ± 51.90 and 141.86 ± 50.39 mmHg.s.cm, respectively (p = 0.003)., Conclusions: PhCI was significantly lower in children with abnormal VFSS than in those with normal VFSS. We did not find a significant impact of age on PhCI in our pediatric populations., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery., Background: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence., Methods: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded., Results: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016)., Conclusions: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prophylactic central neck dissection (pCND) remains controversial during the initial surgery for preoperative and intraoperative node-negative (cN0) papillary thyroid carcinoma (PTC)., Methods: Patients undergoing thyroidectomy with or without pCND (Nx) for PTC in nine French surgical departments, registered in the EUROCRINE® national data in France between January 2015 and June 2021, were included in a cohort study. Demographic and clinicopathological characteristics, complications, and recurrence rates were compared using multivariate regression analysis., Results: A total of 1905 patients with cN0 PTC were enrolled, including 1534 who had undergone pCND and 371 who hadn't (Nx). Of these, 1546 (81.2%) were female, and the median age was 49 years (range: 15-89 years). Patients who had undergone pCND were more likely to have multifocal tumors (n = 524 [34.2%] vs. n = 68 [18.3%], p < .001) and larger tumors (15.3 vs. 10.2 mm, p = .01) than patients with Nx. Of the patients with pCND, 553 (36%) had positive central LN (N1a), with a median of 1 N1 (IQR 0-5). pCND was associated with a higher temporary hypocalcemia rate (n = 25 [8%] vs. n = 15 [4%], p < .001). The rates of permanent hypocalcemia and temporary and permanent recurrent laryngeal nerve (RLN) palsy were not significantly different between the two groups (p > .2). After adjusting for covariates (age, sex, multifocality, and pathological T stage) in a multivariable Cox PH model, the performance of lymph node dissection (pCND vs. no-pCND) was not associated with PTC recurrence (p = .2)., Conclusion: pCND in PTC does not reduce recurrence and is associated with a two-fold increase in the incidence of transient hypoparathyroidism. These data should be considered while issuing further guidelines regarding the treatment of patients with cN0 PTC., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background & Aims: Disorders of gut-brain interaction (DGBI) are complex conditions that result in decreased quality of life and a significant cost burden. Linaclotide, a guanylin cyclase C (GCC) receptor agonist, is approved as a DGBI treatment. However, its efficacy has been limited and variable across DGBI patients. Microbiota and metabolomic alterations are noted in DGBI patients, provoking the hypothesis that the microbiota may impact the GCC response to current therapeutics., Methods: Human-derived intestinal organoids were grown from pediatric DGBI, non-IBD colon biopsies (colonoids). Colonoids were treated with 250 nM linaclotide and assayed for cGMP to develop a model of GCC activity. Butyrate was administered to human colonoids overnight at a concentration of 1 mM. Colonoid lysates were analyzed for cGMP levels by ELISA. For the swelling assay, colonoids were photographed pre- and post-treatment and volume was measured using ImageJ. Principal coordinate analyses (PCoA) were performed on the Bray-Curtis dissimilarity and Jaccard distance to assess differences in the community composition of short-chain fatty acid (SCFA) producing microbial species in the intestinal microbiota from pediatric patients with IBS and healthy control samples., Key Results: Linaclotide treatment induced a significant increase in [cGMP] and swelling of patient-derived colonoids, demonstrating a human in vitro model of linaclotide-induced GCC activation. Shotgun sequencing analysis of pediatric IBS patients and healthy controls showed differences in the composition of commensal SCFA-producing bacteria. Butyrate exposure significantly dampened linaclotide-induced cGMP levels and swelling in patient-derived colonoids., Conclusions & Inferences: Patient-derived colonoids demonstrate that microbiota-derived butyrate can dampen human colonic responses to linaclotide. This study supports incorporation of microbiota and metabolomic assessment to improve precision medicine for DGBI patients., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020., Background: Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers., Methods: Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database., Results: Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs., Conclusions: These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Opportunities for care improvement exist within virtual care, which continues to emerge as an increasingly viable heath care option., Problem: Competing care priorities presented a challenge to nurse leaders, resulting in a modern solution to optimize resources using virtual care., Methods: A new model of care delivery, the virtual discharge (VDC) protocol, was established as a partnership between bedside nurses and a virtual nurse team., Interventions: Using existing telehealth technology, virtual nurses delivered remote discharge education to patients on a 30-bed orthopedic unit., Results: During the pilot, 269 VDC sessions totaled more than 101 hours of discharge education. Patient satisfaction communication scores improved significantly, and patients maintained a low 7-day readmission rate., Conclusion: This care model using emerging technology to deliver effective discharge education was highly satisfactory for patients and bedside nurses. Nurse leaders should seek opportunities to maximize the benefits of virtual technology in health care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: An important component of plastic surgery residency training is independent cosmetic patient management. A resident cosmetic clinic was created at Oregon Health & Science University in 2007 to expand this experience. The cosmetic clinic has traditionally been most successful in offering nonsurgical facial rejuvenation with neuromodulators and soft tissue fillers. This study focuses on the demographics of the patient population and the treatments provided over a 5-year period and compares this experience to those of the same program's attending cosmetic clinics., Methods: A retrospective chart review of all patients seen at Oregon Health & Science University's Plastic and Reconstructive Surgery Resident Cosmetic Clinic between January 1, 2017, and December 31, 2021 was performed. Patient demographics, type of injectable received (neuromodulator versus soft tissue filler), location of injection, and additional cosmetic procedures were evaluated., Results: Two hundred patients met the study criteria, which included 114 seen in the resident clinic (RC), 31 seen in attending clinic (AC), and 55 patients seen in both. A primary analysis compared the two groups seen in the resident and attending only clinics. The average age of patients seen in the RC was younger, 45 versus 51.5 (P ≤ 0.05). There was a trend toward more patients in the RC being involved in healthcare as compared to those patients seen in the AC, but this difference was not found to be statistically significant. The median number of neuromodulator visits in the RC was 2 (1, 4) versus 1 (1, 2) in the AC (P ≤ 0.05) The most common location for neuromodulator injections in both clinics was the corrugators., Conclusions: Patients in the resident cosmetic clinic were younger females, most receiving neuromodulator injections. No statistically significant differences were identified in patient population, injections received, and location of injections between the two clinics, indicating a similar trainee skill set and patient care plan between the two clinics., (Copyright © 2022. Published by Elsevier Inc.)

Prophylactic lymph node dissection is considered only for papillary cancers. It is not indicated for vesicular cancers or oncocytic cancers, nor should it entail a secondary surgical intervention in the event of an incidental discovery of papillary cancer on a thyroidectomy specimen. Prophylactic lymph node dissection means a cervical lymph node dissection in the absence of any pre- or intraoperative evidence (biological, cytological, histological, clinical or ultrasound) of lymph node metastases. There is currently no evidence in the literature that prophylactic central dissection improves overall survival, which is similar for N0 and NX patients. Yet although prophylactic lymph node dissection is not justified by overall survival, it does seem to reduce the risk of locoregional recurrence in the case of micro-N1, and it allows occult metastases to be detected and a tumour to be reclassified. This enables patients at risk of recurrence to be more surely identified and therapeutic strategy and follow-up adapted accordingly. Prophylactic homolateral central lymph node dissection is warranted for papillary cancers with largest ultrasound diameter 4cm and above and/or with intraoperative macroscopic evidence of perithyroid tissue invasion. The benefits and risks of lymph node dissection must be assessed and discussed on a case-by-case basis. Only a central lymph node dissection homolateral to the tumour is recommended, except for bilateral or isthmic cancers, for which a prophylactic bilateral central lymph node dissection may be considered. This bilateral lymph node dissection incurs an increased risk of complications (parathyroids, recurrent laryngeal nerve). Prophylactic lateral lymph node dissection is not recommended., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective(s): Patients with intracranial tumors have a higher risk of thromboembolic events. This risk increases at the time of surgical intervention. We have noted an anecdotal increase in perioperative flap thrombosis in patients undergoing free tissue transfer for intracranial tumor resection. This study aims to formally evaluate this risk., Methods: A multi-institutional retrospective chart review was performed of patients who underwent free tissue transfer for scalp/cranial reconstruction. Perioperative thrombosis and free flap outcomes were evaluated., Results: The 209 patients who underwent 246 free tissue transfers were included in the study. The 28 free flap scalp reconstructions were associated with intracranial tumors, 19 were performed following composite cranial resections with associated dural resection/reconstruction, and 199 were performed in the absence of intracranial tumors (control group). There was a significantly higher incidence of perioperative flap thrombosis in the intracranial tumor group (11/28, 39%) when compared to controls (38/199, 19%) (p = 0.0287). This was not seen when scalp tumors extended to the dura alone (4/19, 21%, p = 0.83). Therapeutic anticoagulation used for perioperative thrombosis (defined as intraoperative or in the immediate postoperative phase up to 5 days) was associated with a lower risk of flap failure, although this was not statistically significant (p = 0.148). Flap survival rates were equivalent between flaps performed for intracranial pathology (93.3%) and controls (95%)., Conclusion: There is an increase in perioperative flap thrombosis in patients with intracranial tumors undergoing free tissue scalp reconstruction. Anticoagulation appears to mitigate this risk., Level of Evidence: This recommendation is based on level 3 evidence (retrospective case-control studies, systematic review of retrospective studies, and case reports) Laryngoscope, 133:1103-1109, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Tuberculosis (TB) is a major health problem characterized by an immuno-endocrine imbalance: elevated plasma levels of cortisol and pro- and anti-inflammatory mediators, as well as reduced levels of dehydroepiandrosterone. The etiological agent, Mycobacterium tuberculosis (Mtb), is captured by pulmonary macrophages (Mf), whose activation is necessary to cope with the control of Mtb, however, excessive activation of the inflammatory response also leads to tissue damage. Glucocorticoids (GC) are critical elements to counteract the immunoinflammatory reaction, and peroxisome proliferator-activated receptors (PPARs) are also involved in this regard. The primary forms of these receptors are PPARϒ, PPARα, and PPARβ/δ, the former being the most involved in anti-inflammatory responses. In this work, we seek to gain some insight into the contribution of PPARϒ in immuno-endocrine-metabolic interactions by focusing on clinical studies in pulmonary TB patients and in vitro experiments on a Mf cell line., Methods and Results: We found that TB patients, at the time of diagnosis, showed increased expression of the PPARϒ transcript in their peripheral blood mononuclear cells, positively associated with circulating cortisol and related to disease severity. Given this background, we investigated the expression of PPARϒ (RT-qPCR) in radiation-killed Mtb-stimulated human Mf. The Mtb stimulation of Mf derived from the human line THP1 significantly increased the expression of PPARϒ, while the activation of this receptor by a specific agonist decreased the expression of pro- and anti-inflammatory cytokines (IL-1β and IL-10). As expected, the addition of GC to stimulated cultures reduced IL-1β production, while cortisol treatment together with the PPARϒ agonist lowered the levels of this proinflammatory cytokine in stimulated cultures. The addition of RU486, a glucocorticoid receptor antagonist, only reversed the inhibition produced by the addition of GC., Conclusion: The current results provide a stimulating background for further analysis of the interconnection between PPARs and steroid hormones in the context of Mtb infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor VEG declared being in a different faculty from the affiliation they share with the author(s) ACC, NBG, FNP at the time of review., (Copyright © 2023 Díaz, D’Attilio, Penas, Bongiovanni, Massa, Cevey, Santucci, Bottasso, Goren and Bay.)

Objectives: Chronic constipation occurs frequently in children with autism spectrum disorder (ASD). The primary objective was to determine whether chronic constipation is associated with a higher rate of abnormal colonic motor activity in ASD children than in non-ASD children. A secondary goal was to determine if clinical variables could identify children with ASD at risk for possessing abnormal colonic motility., Methods: A retrospective, propensity-matched, case-control study compared colonic manometry (CM) of an ASD cohort and non-ASD controls with chronic constipation. Clinical variables were evaluated as potential predictors for abnormal colonic motility., Results: Fifty-six patients with ASD and 123 controls without the diagnosis of ASD who underwent CM were included. Propensity score resulted in 35 matched cohorts of ASD and controls. The rate of abnormal CM findings between ASD and matched controls (24% vs 20%, P = 0.78) did not differ significantly. A prediction model of abnormal CM that included ASD diagnosis, duration of constipation, and soiling achieved a sensitivity of 0.94 and specificity of 0.65. The risk for abnormal colonic motility increased 11% for every 1-year increase in duration of constipation. Odds for abnormal motility were 30 times higher in ASD children with soiling than controls with soiling (P < 0.0001)., Conclusions: Chronic constipation does not appear to be associated with a higher rate of abnormal colonic motility in children with ASD. Clinical information of disease duration and presence of soiling due to constipation show promise in identifying patients with ASD at a greater risk for abnormal colonic motility., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: Previous studies in TB patients showed an immuno-endocrine imbalance characterized by a disease-severity associated increase in plasma levels of proinflammatory cytokines and glucocorticoids (GCs). To analyze the potential immunomodulatory effect of circulating GCs over peripheral blood mononuclear cells (PBMC) from TB patients, we investigated the expression of positively (anti-inflammatory-related genes ANXA1; FKBP51; GILZ, NFKBIA, and NFKBIB) and negatively (inflammatory genes: IL-6, IL-1β, and IFN-γ) Glucocorticoids Receptors (GR)-regulated genes. Plasma concentrations of cytokines and hormones, together with specific lymphoproliferation were also assessed., Materials and Methods: Gene expression was quantified by RT-qPCR, specific lymphoproliferation by 3 H-thymidine incorporation, whereas plasma cytokines and hormones levels by ELISA., Key Findings: Transcripts of ANXA1, GILZ, NFKBIB, and NFKBIA appeared significantly increased in patients, whereas FKBP51, IL-6, IL-1β, and NF-κB remained unchanged. Upon analyzing according to disease severity, mRNA levels for ANXA1 and NFKBIB were even higher in moderate and severe patients. GILZ was increased in moderate cases, with NFKBIA and IL-1 β being higher in severe ones, who also displayed increased GRβ transcripts. TB patients had reduced plasma DHEA concentrations together with increased pro and anti-inflammatory cytokines (IFN-γ, IL-6, and IL-10) cortisol and cortisol/DHEA ratio, more evident in progressive cases, in whom their PBMC also showed a decreased mycobacterial-driven proliferation. The cortisol/DHEA ratio and GRα expression were positively correlated with GR-regulated genes mainly in moderate patients., Significance: The increased expression of cortisol-regulated anti-inflammatory genes in TB patients-PBMC, predominantly in progressive disease, seems compatible with a relatively insufficient attempt to downregulate the accompanying inflammation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bongiovanni, Díaz, Santucci, D’Attilio, Bottasso, Hernández Pando and Bay.)

Background: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC., Methods: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT imaging. Primary study outcome was overall survival., Results: Skeletal muscle area at C3 was strongly correlated with the L3 level in both men (n = 188; r = 0.77; p < 0.001) and women (n = 65; r = 0.80; p < 0.001), and C3 sarcopenia thresholds of 14.0 cm 2 /m 2 (men) and 11.1 cm 2 /m 2 (women) were best predictive of L3 sarcopenia thresholds. Applying these C3 thresholds to a cohort of patients with neck imaging alone revealed that C3 sarcopenia was independently associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85) but not women (HR = 1.18, 95% CI, 0.76, 1.85)., Conclusions: This study identifies sarcopenia thresholds at the C3 level that best predict L3 sarcopenia in men and women. In HNC, C3-defined sarcopenia is associated with poor survival outcomes in men, but not women, suggesting sarcopenia may differentially affect men and women with HNC., Competing Interests: Author YC is currently employed by Seagen Inc, although this employment resulted after data and analyses were completed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olson, Edwards, Degnin, Santucci, Buncke, Hu, Chen, Fuller, Geltzeiler, Grossberg and Clayburgh.)

Allocation of cells to an endodermal fate in the gastrulating embryo is driven by Nodal signaling and consequent activation of TGFβ pathway. In vitro methodologies striving to recapitulate the process of endoderm differentiation, however, use TGFβ family member Activin in place of Nodal. This is despite Activin not known to have an in vivo role in endoderm differentiation. In this study, five epiblast stem cell lines were subjected to directed differentiation using both Activin A and Nodal to induce endodermal fate. A reporter line harboring endoderm markers FoxA2 and Sox17 was further analyzed for TGFβ pathway activation and WNT response. We demonstrated that Activin A-treated cells remain more primitive streak-like when compared to Nodal-treated cells that have a molecular profile suggestive of more advanced differentiation. Activin A elicited a robust TGFβ/SMAD activity, enhanced WNT signaling activity and promoted the generation of DE precursors. Nodal treatment resulted in lower TGFβ/SMAD activity, and a weaker, sustained WNT response, and ultimately failed to upregulate endoderm markers. This is despite signaling response resembling more closely the activity seen in vivo. These findings emphasize the importance of understanding the downstream activities of Activin A and Nodal signaling in directing in vitro endoderm differentiation of primed-state epiblast stem cells., (© 2022 Wiley Periodicals LLC.)

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is used to identify open chromatin regions in cells. This can be used to identify putative regulatory regions, determine dynamics and mechanisms of transcription factors when coupled with ChIP-seq and predict interactions between proteins and chromatin. Compared to previous methods, MNase-seq and DNase-seq, ATAC-seq requires only 50,000 cells, orders of magnitude fewer cells. In addition, the ATAC-seq protocol takes one day to progress from cells to sequencing ready libraries., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)