Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B-cell lymphoma.

BACKGROUND: Autoimmune conditions in B-cell lymphomas are frequent. Steroids are standard of care, but many patients require other immunosuppressive agents. Ibrutinib is a Bruton Tyrosine Kinase inhibitor that is approved for B-cell indolent lymphoma treatment. We evaluated the use of ibrutinib in previously treated hematologic immune manifestations associated with B-cell lymphomas. RESULTS: We conducted a retrospective multicentric observational study. Patients presenting with active, relapsed/refractory B-cell lymphoma associated hematological immune manifestation (autoimmune cytopenia, acquired immune-mediated bleeding disorders) were included. Twenty-five patients were identified. Median age at ibrutinib introduction was 69 years (range 44-84) and median number of previous treatment lines before ibrutinib was 2 (1-7). Twenty-two patients (88%) were on concomitant stable treatment at inclusion. Within a median exposure of 8 months (2-35), overall response rate to ibrutinib on immune manifestations was 76% (95% CI, 54.9-90.6); complete response rate 44%. Fourteen patients (63%) were able to be weaned from concomitant treatments. Fourteen patients (56%) presented treatment-related adverse events, mostly Grade 1 or 2. CONCLUSIONS: Ibrutinib in this setting provides good efficacy and safety profile. Clinical trials are needed to define subgroups of patients who will benefit from this strategy and establish its place in the therapeutic arsenal.

Changes in bone mineral density after allogenic stem cell transplantation.

OBJECTIVE: Osteoporosis is a complication after allogenic stem cell transplantation (alloSCT). The purpose of this study was to assess changes in bone mineral density (BMD) 6 months and 3 years after alloSCT, as well as predictors of bone loss. METHODS: A longitudinal, prospective, single-center study was conducted at Lille University Hospital between 2005 and 2016. Clinical, biological, radiologic (thoracic and lumbar spine) and densitometric (DXA) assessments were carried out at baseline (pre-transplant), 6 months and 3 years. Patients with myeloma were not included. RESULTS: Two hundred and fifty-eight patients were included (144 men). Among them, 60.1% had leukemia and 65.8% of them, acute myeloid leukemia. At baseline, 6 months and 3 years, DXA-confirmed that osteoporosis was observed in 17%, 22.8% and 17.5% of the patients, respectively, mainly at the femoral neck. At baseline, 6 months and 3 years, 9 (8.5%), 53 (21.5%) and 38 (16.7%) patients, respectively, were receiving anti-osteoporotic treatment. From baseline to 6-month follow-up, BMD decreased significantly (p<0.001) at the lumbar spine (-36 [95%CI; -51 to -20] mg/cm2 of hydroxyapatite), femoral neck (-43 [95%CI; -57 to -29] mg/cm2 of hydroxyapatite) and total hip (-53 [95%CI; -68 to -39] mg/cm2 of hydroxyapatite). From 6-month to 3-year follow-up, a significant increase in BMD was observed at the lumbar spine only (+31 [95%CI; 20 to 42] mg/cm2 of hydroxyapatite, p<0.001). At all 3 sites, changes in BMD did not differ between patients treated or untreated by anti-osteoporotic treatment from 6-month to 3 year follow-up. Incident fractures were found in 4.1% and 5.7% of the patients at 6 months and 3 years, respectively. Between baseline and 6 months, bone loss at all 3 sites was associated with corticosteroid intake. At the total hip, 23.3% of the decrease in BMD from baseline to 6 months was due to an active hematological disease (p<0.05), a bone marrow stem cells (p<0.01) and a corticosteroid intake (p<0.01). CONCLUSION: Our study found evidence of bone fragility in alloSCT patients. Low BMD persisted at the hip 3 years after transplantation due to slower improvement at this site.

Predictors of anastomotic strictures following œsophageal atresia repair.

OBJECTIVES: To identify the risk factors for anastomotic, refractory and recurrent strictures and to establish whether anastomotic stricture is associated with antireflux surgery. DESIGN: This prospective national multicentre study included all infants born with oesophageal atresia (OA) over an 8-year period. Data on OA and complications were collected at birth and at 1 year old. Univariate and multivariate analyses were conducted. RESULTS: 1082 patients from 37 centres were included in the study. The prevalence of anastomotic stricture at 1 year old was 23.2%. Anastomosis under tension (defined by the surgeon at the time of repair) and delayed anastomosis (defined as anastomosis performed more than 15 days after birth, excluding delays due to prematurity or severe cardiac diseases) were found to be independent risk factors for anastomotic stricture (2.3 (1.42-3.74) and 4.02 (2.12-7.63), respectively). Patients with anastomotic stricture had a 2.3-fold higher rate of fundoplication compared with others (p=0.001). Anastomosis under tension and delayed anastomosis were found to be independent risk factors for recurrent stricture (1.92 (1.10-3.34) and 5.73 (2.71-12.14), respectively), while delayed anastomosis was the only risk factor for refractory stricture (8.30 (3.34-20.64)). There was a 2.39-fold (1.42-4.04) higher rate of fundoplication in the anastomotic stricture group than in the group without anastomotic stricture (p=0.001). CONCLUSIONS: Patient-related anatomical factors leading to anastomosis under tension and delayed anastomosis increase the risk of anastomotic stricture.

Is V-NOTES Hysterectomy as Safe and Feasible as Outpatient Surgery Compared with Vaginal Hysterectomy?

STUDY OBJECTIVE: The vaginal approach is the reference surgical route to perform hysterectomy for benign pathologies. Hysterectomy via transvaginal natural orifice transluminal endoscopic surgery (V-NOTES) is a new technique that would overcome the limitations of vaginal surgery by allowing a complete exploration of the peritoneal cavity and a constant visual control of the adjacent structures. The aim of this study is to assess the V-NOTES technique compared with vaginal hysterectomy (VH). DESIGN: A retrospective cohort study. SETTING: French teaching hospital. PATIENTS: The first 50 V-NOTES hysterectomies were included successively and compared with the last 50 VH performed from March 2019 to November 2020. The study concerned all patients requiring hysterectomy unless it was for endometriosis or cancer (except for grade 1 endometrioid adenocarcinoma). INTERVENTIONS: The baseline characteristics and the surgical outcomes were compared. The main outcome assessed was the performing of outpatient surgery. Secondary end points were uterine weight and intraoperative and postoperative complications. MEASUREMENTS AND MAIN RESULTS: The rate of outpatient surgery did not differ between the 2 surgical techniques (p = .23). The success rate of outpatient management was 77% in the V-NOTES group versus 75% in the VH group (p = .85). There was no difference in surgical outcomes between the 2 groups, except for the rate of salpingectomies or adnexectomies, which was significantly higher in the V-NOTES group, with 100% of patients undergoing one of these procedures, compared with 60% of patients in the vaginal route group (p < .001). There were 2 cases of re-admission in the month following the intervention in the vaginal group and 0 cases in the V-NOTES group. CONCLUSION: Hysterectomy by V-NOTES can be performed as a safe and adequate alternative to VH. This surgical route is a good candidate for outpatient management. However, more studies need to be conducted to confirm these findings.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Predictive factors of urinary incontinence after holmium laser enucleation of the prostate: a multicentric evaluation.

OBJECTIVE: To evaluate predictive factors of urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP). METHODS: Patients (n = 2346) were included in a retrospective multicentric study from April 2012 to November 2017. Patients' characteristics (age, BMI, percentage with diabetes), preoperative data (IPSS score, whole gland volume, urinary drainage), operative data (enucleation time, enucleation efficiency, tissue enucleated weight, total delivered energy) and postoperative data were recorded. Absence of UI was defined as no pads at 3 and 6 months. Surgeon experience was stratified in three categories: beginners (< 21 cases), intermediate (21-40 cases) and experienced (> 40 cases). Multivariate logistic regression analysis was performed. RESULTS: UI was observed in 14.5% of patients (340/2346) at 3 months (95%CI 13-16%) and in 4.2% (98/2346) at 6 months (95%CI 3-5%). On multivariate analysis at 3 months, increasing age (OR per SD = 1.3 [1.14-1.48]), elevated BMI (OR per SD = 1.23 [1.09-1.38]), preoperative urinary drainage (OR = 0.62 [0.45-0.85]), increasing enucleated tissue weight (OR per SD = 1.29 [1.16-1.45]) and experienced surgeon with at least 40 cases (OR = 0.56 [0.42-0.75]) were significantly associated with UI. At 6 months, increasing age (OR per SD = 1.25 [1.01-1.53]), elevated BMI (OR per SD = 1.25 [1.03-1.5]), increasing whole gland volume (OR per one SD log = 1.24 [1.01-1.53]) and diabetes disorder (OR = 1.7 [1.03-2.78]) were significantly associated with UI. CONCLUSION: UI after HoLEP was observed in 14.5% of patients at 3 months and 4.2% at 6 months, with stress UI in half of the cases. Surgeon experience with at least 40 cases was the main predictive factor of 3 months UI after HoLEP and diabetes disorder of persistent UI at 6 months.

Impact on Prognosis of the Surgical Route, Laparoscopy or Laparotomy, for the Surgical Staging of Early Stage Ovarian Cancer-A Study from the FRANCOGYN Group.

BACKGROUND AND OBJECTIVE: according to the latest ESMO-ESGO recommendations, laparotomy is the standard surgical approach to treat and stage patients with presumed early stage epithelial ovarian cancer (EOC). A few studies have investigated the efficacy and the safety of laparoscopy for the staging of early stage EOC, and this question is still in the center of debates. Recurrence-free survival (RFS) and overall survival (OS) benefits of the minimally invasive surgery (MIS) have still to be specified. The aim of this multicenter and retrospective study is to assess the survival outcomes of laparoscopic staging in comparison with laparotomic staging for patients presenting with an early stage EOC. METHODS: data of patients with early stage EOC (FIGO I-IIA) who underwent primary surgery between 2000 and 2018 were extracted from the FRANCOGYN database. OS and RFS of these two groups, constituted according to the surgical route, were compared using Log rank test. RESULTS: of the 144 patients included, 107 patients underwent laparotomy and 37 underwent laparoscopy for a staging purpose. The median follow-up was 36.0 months (18.0 to 58.0). For the laparoscopy and the laparotomy group, the median follow-up period was 24 (11.0 to 50.0) and 42.0 (24.0 to 66.0) months, respectively, (p < 0.001). Tumor recurrence occurred in 33 (23%) patients: 2 (5.4%) in the laparoscopy group and 31 (29%) in the laparotomy group (p = 0.08). The OS rate at 5 years was 97.3% after laparoscopy and 79.8% after laparotomy (p = 0.19). CONCLUSIONS: there is no difference associated with the laparoscopic approach for the staging of early stage EOC on RFS and OS in comparison with laparotomy. MIS may be proposed as a safe and adequate alternative to laparotomy when performed by well-trained surgeons.

Bone and joint complications in patients with hereditary hemochromatosis: a cross-sectional study of 93 patients.

BACKGROUND: The aim of this study was to determine the frequency and characteristics of bone and joint complications, specifically bone fragility, joint replacement surgery, and arthropathy, in hereditary hemochromatosis (HH) and related factors. METHODS: This study was a cross-sectional observational study of 93 patients with HH. Radiographs of the hands, wrists, knees, and ankles were scored for joint space narrowing, erosions and cysts, osteophytes, and chondrocalcinosis. Prevalent (vertebral and non-vertebral) fragility fractures were recorded and bone mineral density (BMD) was systematically evaluated by dual energy X-ray absorptiometry. Bone fragility was defined as (i) a T-score ⩽ -2.5 at any site with or without a prevalent fragility fracture, or (ii) a T-score between -1.0 and -2.5 at any site and a prevalent fragility fracture. RESULTS: The mean age of the patients was 60.0 (11.2) years, and 58.0% of them were men. The frequency of radiographic MCP2-3 arthropathy was 37.6% (95% CI 0.28-0.48). Radiographic MCP2-3 arthropathy was independently associated with older age [OR 1.17 (1.09-1.26) per year, p < 0.0001], male sex [OR 3.89 (1.17-12.97), p = 0.027] and C282Y+/+ genotype [OR 4.78 (1.46-15.68), p = 0.010]. The frequency of joint replacement surgery was 12.9% (95% CI 0.07-0.21). The frequency of bone fragility was 20.4% (95% CI 0.13-0.30). Bone fragility was independently associated with hepatic cirrhosis [OR 8.20 (1.74-38.68), p = 0.008]. DISCUSSION: Radiographic MCP2-3 arthropathy was found to occur in 37.6% of patients with HH. The association observed between this form of arthropathy and C282Y homozygosity, male sex, and older age suggests that demographic characteristics and genetic background are likely to be major determinants of this joint disorder and play a more important role than severity of iron overload. Bone fragility was observed in a fifth of the patients with HH, independently of genetic background and severity of iron overload, and was strongly associated with hepatic cirrhosis. CONCLUSION: Future investigations should focus on pathogenesis and early identification of patients at risk of developing bone and joint complications secondary to HH.

Identification of prognostic markers in diffuse midline gliomas H3K27M-mutant.

Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M-mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M-mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M-mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c-MET and p53), next-generation sequencing and comparative genomic hybridization array. Forty-nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M-mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M-mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity.

Ten-year outcomes of cementless anatomical femoral implants after 3D computed tomography planning. Follow-up note.

BACKGROUND: Pre-operative 3D planning based on computed tomography (CT) imaging is used to optimise the restitution of normal hip anatomy during primary total hip arthroplasty (THA). Although CT planning has been proven effective and reproducible, its influence on long-term THA outcomes is unknown. In this 10-year follow-up study of patients managed with the same technique of CT-planned primary anatomical THA, the objectives were to assess femoral implant survival, long-term functional outcomes, 10-year outcomes of titanium modular femoral necks, and associations with the dislocation rate. Hypothesis Pre-operative CT planning of primary THA ensures achievement of the NICE criterion of a lower than 5% femoral revision rate within 10 years. MATERIAL AND METHODS: The study included 61 patients (61 hips) managed between 2004 and 2007 by CT-planned primary THA via the posterior approach, with an uncemented anatomical femoral component (SPS®, Symbios); when deemed necessary by the surgeon to restore normal anatomy, a titanium modular femoral neck was used (35/61 patients). After 10 years, 17 patients had died and 3 were lost to follow-up, leaving 41 patients with a mean age of 76 years (range, 60-91 years) for re-evaluation. Clinical outcomes were assessed by determining the Harris Hip Score (HHS) and the Postel-Merle d'Aubigné (PMA) score, which were compared to baseline values. Radiographs were evaluated using the AGORA Roentgenographic Assessment system (ARA). RESULTS: The 10-year femoral component survival rate was 96% (95%CI, 88;99%). Revision was required in 4 patients, to treat delayed peri-prosthetic fractures (n=2) or to correct initial cup malposition (n=2). No changes occurred from 2010 to last follow-up in the mean HHS (90 [95%CI, 84;95] and 91 [95%CI, 77;96], respectively) or mean PMA score (16 [95%CI, 14;17] and 15.5 [95%CI, 14;16.5], respectively). The mean ARA score was 5.2 (range, 3-6) at last follow-up. No complications related to the use of modular femoral necks were recorded. Dislocation occurred in 2 patients, but in neither was the pre-operative plan followed during surgery. DISCUSSION: The SPS® stem produced good 10-year clinical and radiographic outcomes. No patients experienced complications related to use of a titanium modular femoral neck. The restoration of anatomical hip geometry made possible by pre-operative CT planning provided sustained clinical improvements with a low complication rate. LEVEL OF EVIDENCE: IV, retrospective observational cohort study.