A Novel HR-pQCT Image Registration Approach Reveals Sex-Specific Changes in Cortical Bone Retraction With Aging

During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort

ObjectiveUveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors.MethodsDESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: P less than 0.05.ResultsAfter 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4–22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84–1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI.ConclusionFive-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.     

Endoscopic internal drainage for the management of leak,fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.     

Effect of age and care organization on sources of variation in kidney transplant waiting list registration

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Study of the Complex Between the Contrast Agent lobitridol (Xenetix®) and Elastase (PPE): A Model for Hydrophobic Site Protection in Drug-Protein Interactions

Purpose. The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix^®), as a model. Methods. The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98. Results. In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. Conclusions. The validation of the 'hydrophobic shielding' concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.     

Surgical pitfalls in a patient with type IV Ehlers-Danlos syndrome and spontaneous colonic rupture

PURPOSE: This paper intends to stress the importance of early diagnosis and discuss surgical treatment of Type IV Ehlers-Danlos syndrome (EDS-4), an autosomal dominant connective tissue disease characterized by typical features of the face and extremities, inappropriate and easy bruising, and extreme tissue fragility, which may lead to dramatic and often fatal complications, mostly spontaneous arterial or intestinal rupture. METHODS: We report the case of a 41-year-old female who presented with spontaneous perforation of the sigmoid colon. RESULTS: The patient was seen over a nine-year period, during which time she required six operations and presented with a great number of surgical complications including stenosis of an end-colostomy, repeated subocclusive episodes caused by intraperitoneal adhesions, and enterocutaneous fistulas, finally ending with an ileostomy and short bowel syndrome. It is only after a difficult laparotomy for ovarian cyst excision, marked by numerous adhesions and friable bowel, that the diagnosis of EDS-4 was considered and established. CONCLUSIONS: In case of “idiopathic” spontaneous perforation of the colon in a young adult, features of EDS-4 should be thoroughly looked into and, if found, skin fibroblast culture with collagen Type III analysis performed. The surgical treatment of choice consists of subtotal colectomy and permanent endileostomy. In case of patient refusal, a second-stage ileorectal anastomosis can be performed but carries the high risk of anastomotic leakage.