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A collar is a protective factor against early periprosthetic fracture for cementless stems in total hip arthroplasty
No full textInternational audienceAims Periprosthetic fractures (PPFs) are a significant complication in total hip arthroplasty (THA), with their incidence varying from 0.1% to 5.2% in registries. The use of a collared femoral stem may reduce the risk of PPF by enhancing the distribution of load and the stability of the implant. The aim of this study was to compare the effect of collared versus collarless stems on the incidence of PPFs in a large cohort of patients. Methods This retrospective study involved all primary THAs performed in a single centre between 1 January 2010 and 31 December 2020. Of the 2,182 THAs performed in 1,767 patients, 559 in 447 patients were excluded for the following reasons: having cemented stems, patients with a femoral neck fracture, dysplasia of the hip, or an oncological indication for surgery. A total of 1,623 THAs in 1,320 patients were included. The data which were collected included the patients’ demographics, the surgical approach, the implant characteristics, and the incidence of PPF. Univariate and multivariate analyses were conducted using the Bursac’s logistic regression model considering factors such as sex, age, BMI, surgical approach, and the presence of a collar. Results There were nine PPFs within 90 days of surgery: five in the collared stem group (0.4%) and four in the collarless stem group (1.6%). Multivariate analysis revealed that the presence of a collar was the only significant independent predictive factor of a reduced rate of PPFs (p = 0.048). Other factors such as sex, age, BMI, and surgical approach did not show significant correlations. Conclusion The collared stem was a protective factor against early femoral PPF when cementless stems were used in primary THA. These results support the preference for collared versus collarless cementless stems, particularly in patients who are at a high risk of PPF, to enhance the initial stabilty of the stem and reduce complications. Cite this article: Bone Joint J 2025;107-B(5 Supple A):70–75
Maladies rares, un sujet pour les médecins généralistes ?
No full textInternational audienceOver the past 20 years, ambitious public policies have been implemented in France to address the issue of “rare diseases”. The law on public health policy promulgated on August 9, 2004 makes the fight against these diseases one of five public health priorities. As a result, France was the first country in Europe to set up a National Public Health Plan for Rare Diseases (PNMR). Today, on an international scale, France is undoubtedly one of the best-endowed countries in terms of expert centers and reference centers, which cover the entire country. Indeed, the stakes are high: more than 3 million people are affected by a rare disease, and despite the progress made by the three National Plans for Rare Diseases (PNMR) deployed since 2005, misdiagnosis remains a complex challenge. General practitioners are in the front line when it comes to referring patients presenting an atypical clinical picture potentially suggestive of a rare disease. But what exactly is their relationship with the complex subject of rare diseases?Depuis 20 ans, des politiques publiques ambitieuses sont déployées en France sur la question des « maladies rares ». La loi relative à la politique de santé publique promulguée le 9 août 2004 fait de la lutte contre ces pathologies l’une des cinq priorités de santé publique. De ce fait, la France est le premier pays d’Europe à avoir mis en place un Plan National de Santé Publique Maladies Rares (PNMR). Elle est aujourd’hui, à l’échelle internationale, sans doute l’un des pays les mieux dotés en centres experts et centres de références, qui maillent l’ensemble du territoire national. L’enjeu est, en effet, significatif : plus de 3 millions de personnes sont affectées par une maladie rare et, malgré les avancées permises par les trois Plans nationaux Maladies Rares (PNMR) déployés depuis 2005, l’errance diagnostique reste un défi complexe à relever. Les médecins généralistes sont en 1ère ligne dans l’orientation de patients présentant un tableau clinique atypique potentiellement suspect de maladie rare. Mais quel est, au juste, leur rapport à ce sujet complexe des maladies rares
Immune Checkpoint Inhibitor Myocarditis and Left Ventricular Systolic Dysfunction
No full textInternational audienceBackground: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.Objectives: The aim of this study was to identify factors associated with LVEF <50% vs ≥50% at the time of hospitalization for ICI-M. A secondary objective was to evaluate the relationship between LVEF and 30-day all-cause mortality.Methods: The International ICI-Myocarditis Registry, a retrospective, international, multicenter database, included 757 patients hospitalized with ICI-M. Patients were stratified by LVEF as reduced LVEF (<50%) or preserved LVEF (≥50%) on admission. Cox proportional hazards models were used to assess the associations between LVEF and clinical events, and multivariable logistic regression was conducted to examine factors linked to LVEF.ResultsOf 757 patients, 707 had documented LVEFs on admission: 244 (35%) with LVEF <50% and 463 (65%) with LVEF ≥50%. Compared with patients with LVEF ≥50%, those with LVEF <50% were younger (<70 years), had a body mass index of <25 kg/m2, and were more likely to have received chest radiation (24.2% vs 13.5%; P < 0.001). Multivariable analysis identified predictors of LVEF <50%, including exposure to v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated protein kinase inhibitors, pre-existing heart failure, dyspnea at presentation, and at least 40 days from ICI initiation to ICI-M onset. Conversely, myositis symptoms were associated with LVEF ≥50%. LVEF <50% was marginally associated with 30-day all-cause mortality (unadjusted log-rank P = 0.062; adjusted for age, cancer types, and ICI therapy, HR: 1.50; 95% CI: 1.02-2.20).Conclusions: Dyspnea, time from ICI initiation, a history of heart failure, and prior cardiotoxic therapy may be predictors of an initial LVEF <50% in patients with ICI-
No difference in 5‐year survivorship between cemented versus cementless total knee arthroplasty in a cohort of 5266 patients using a deep‐dish mobile bearing implant
No full textInternational audienceAbstract Purpose The best fixation method for total knee arthroplasty (TKA) remains controversial. The aim of this study is to compare the effect of cemented and cementless fixation on prosthesis survivorship. Our primary hypothesis is that there is no difference in survivorship between cemented and cementless TKA. Our secondary hypothesis is that there is no difference in aseptic revisions and functional outcomes between cemented and cementless TKA at mid‐term follow‐up. Methods A multicentre retrospective study was done using data collected prospectively in a large cohort. The same deep‐dish mobile bearing design was used for both cemented and cementless TKA. Patients were divided into two groups according to the fixation method. The survival rate between cemented and cementless TKA was compared. Functional outcomes were collected preoperatively and at the 5‐year follow‐up. Results Of the 5266 primary TKA included, 4549 were cementless, and 717 were cemented. At 5 years, there was no significant difference between the survivorship of the cementless (98.7% [95% confidence interval, CI: 98.2–99.1]) and cemented TKA (97.6%, [95% CI: 94.1–99.1]) ( p = 0.468). There was no significant difference in the surgery‐free survival at 5 years between cementless (95.8% [95% CI: 94.9–96.5]) and cemented TKA (95.5% [95% CI: 92.1–97.5]) ( p = 0.508) as well as in aseptic revision: cementless (96.9% [95% CI: 96.2–97.5]) and cemented TKA (97.5 [95% CI: 95.5–98.6]) ( p = 0.355). There was no significant difference in the functional outcomes at 5 years. Conclusion There was no observed difference in survivorship between cemented and cementless TKA at 5 years in this cohort of 5266 patients. Additionally, rates of reoperation and aseptic revision were similar across both fixation methods, and clinical outcomes did not differ significantly. Therefore, it may be suggested that cementless fixation is a safe option for primary TKA. Level of Evidence Level III
PRRT plus holmium‐166‐ SIRT ( HEPAR PLuS ) versus PRRT ‐only in patients with metastatic neuroendocrine tumors: A propensity‐score matched analysis
No full textInternational audienceAbstract Patients with bulky neuroendocrine liver metastases (NELM) undergoing PRRT with [ 177 Lu]Lu‐DOTATATE have a worse survival than patients with limited liver metastases. Previously, the safety and efficacy of additional selective internal radiotherapy (SIRT), using holmium‐166 ( 166 Ho)‐microspheres, directly following PRRT in patients with NELM were confirmed in the prospective HEPAR PLuS study. The aim of the current study was to provide insight into the efficacy and survival benefit of PRRT + 166 Ho‐SIRT over PRRT‐only by means of a propensity score matched historical cohort. A multicenter retrospective data collection was performed to match patients treated with PRRT‐only to the prospectively collected HEPAR PLuS study patients. Demographic, clinical, laboratory, and imaging data were collected. The primary endpoint was the proportion of patients with progression‐free survival (PFS) at 2 years after the start of PRRT. Secondary endpoints included the proportion of patients with 2‐year hepatic PFS (hPFS), general PFS and hPFS, objective response rates (ORR), and overall survival (OS). Twenty‐four patients were 1:1 matched and included in the analysis. All key matching criteria were balanced between cohorts if feasible. The proportion of patients with PFS and hPFS at 2 years was 68% and 82% after PRRT + 166 Ho‐SIRT versus 55% and 50% after PRRT only. Time to median PFS was comparable (31 vs. 30 months). An initial delay in hepatic progression or death of any cause was observed in PRRT + 166 Ho‐SIRT mNET patients (75% probability of PFS at 27 vs. 22 months), most notably in intestinal tumors (75% probability of PFS at 26 vs. 15 months). Best ORR was 71% after PRRT + 166 Ho‐SIRT versus 25% after PRRT only. This study showed that 166 Ho‐SIRT after PRRT (vs. PRRT‐only) had a positive effect on the liver disease progression in patients with NELM, increasing the 2‐year hPFS rate and tumor response and delaying hepatic progression or death. However, this effect did not translate into improving general PFS and OS
PARKIN Inactivation Links Parkinson's Disease to Melanoma
No full textInternational audienceBackground: Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression.Methods: An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided.Results: Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation.</div
Treatment of Transient Hypothyroxinemia of Prematurity Does Not Improve Neurodevelopment at Two Years of Age
No full textInternational audienceABSTRACT Aim Transient hypothyroxinemia of prematurity (THOP) has been associated with suboptimal neurodevelopment. We aimed to assess neurodevelopment in very preterm infants with treated and untreated THOP. Methods This study was a multicentre, cohort study, based on prospectively collected data in four French level III neonatal intensive care units. Infants born before 32 weeks of gestation between 2009 and 2020 who underwent a thyroid function test were included. THOP was defined as low free thyroxine and unelevated thyroid stimulating hormone. Infants were classified as no THOP, treated THOP, and untreated THOP. The primary outcome was suboptimal neurodevelopment at 2 years of age evaluated by clinical examination. Results Three hundred and seventy‐three infants (54% male) born at a median gestational age of 28 weeks of gestation were included. There was no significant difference in neurodevelopment at 2 years of age when comparing the no THOP to the THOP group (Odds Ratio (OR) 1.4, 95% confident Interval (CI) 0.8–2.3) nor when comparing the treated with the untreated THOP group (OR 0.8, 95% CI 0.3–1.9). Results remained unchanged after adjusting for confounding factors. Conclusion In very preterm infants treated THOP was not associated with improved neurodevelopment compared to untreated THOP. Numerous biases could have limited treatment effect
TREOCAPA: prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen—statistical analysis plan for the randomized phase III group sequential trial
No full textInternational audienceBackgroundPersistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Controversies persist about the management of PDA in extremely preterm infants. PDA is associated with morbidities, but no therapeutic strategy has resulted in an improved neonatal outcome. Acetaminophen appears to be a promising alternative with possibly fewer adverse effects. The primary objective is to determine whether a prophylactic pharmacological intervention with acetaminophen may increase the survival without severe morbidity at postmenstrual age of 36 weeks.Methods and analysisTREOCAPA phase III is a randomized, multicenter, double-blind, stratified, placebo-controlled superiority trial, two arms in a 1:1 ratio performed in 43 NICUs of 14 European countries, evaluating whether the intervention increases the survival without severe morbidity by 10%, from 50% in control arm to 60% in treatment arm, until the age of 36 postmenstrual weeks. To detect this difference, 794 patients were required using a group sequential design. Recruitment has been closed, with 803 patients enrolled. Patients eligible for inclusion are preterm infants with a gestational age between 23 and 28 weeks. In the acetaminophen group, 20 mg/kg loading dose within 12 h after birth, followed by 7.5 mg/kg quarter in die (QID) for 5 days, will be administered to the 27–28 weeks gestational age group, and 25 mg/kg loading dose then 10 mg/kg QID will be administered to the 23–26 weeks gestational age group. The severe morbidities include severe bronchopulmonary dysplasia (BPD grade 3) according to NIH consensus, necrotizing enterocolitis (NEC) of Bell’s stage II or III, intraventricular hemorrhage (IVH) grade III–IV according to Papile classification, or cystic leukomalacia.DiscussionWhatever the results, the conclusions of this study should be informative for the neonatal scientific community. The results will either confirm the benefit of treatment in increasing survival without severe morbidity, or indicate a worsening of outcomes with prophylactic acetaminophen treatment, or show no difference in the primary outcome. In the latter case, ultrasonographic assessments of ductus arteriosus status on day 7 may help explain the absence of a difference. This could indicate that acetaminophen is ineffective in promoting ductal closure or that early closure of the ductus arteriosus is inconsequential if, despite more frequent closures, there is no associated improvement in outcomes
