Evolution of body mass index and complications rate in severely or morbidly obese patients undergoing total knee arthroplasty.

INTRODUCTION: Associations between obesity and knee osteoarthritis or complications after total knee arthroplasty (TKA) are well established. The procedure can significantly improve knee function, favoring weight loss, despite the risk of surgical complications. The main objective of the present study was to assess change in body mass index (BMI) after TKA in patients with severe or morbid obesity (BMI≥35kg/m2). The secondary endpoint was the rate of surgical revision. The hypotheses were that there is no significant change in BMI after TKA and that there is a significant rate of revision. METHODS: This retrospective descriptive study was conducted for the period June 2009 to December 2019. Thirty-three patients (48 knees) were included: 27 women, 6 men; mean age, 66.5 years (range, 55-80). Preoperatively, 11 patients had BMI 35-39.9kg/m2 and 22 BMI≥40 (including 11 with BMI≥45kg/m2). The preoperative axis was in varus for 35 patients (73%, including 54%≥10°) and in valgus for 13 (27% including 33%≥10°). Radiological and clinical evaluation was carried out at 3 months and 1 year postoperatively. At≥2 years, change in BMI and EQ5D functional score were established by telephone survey; >5% change in BMI was considered significant. RESULTS: Mean follow-up was 6.9±2.3 years (range, 2.9-10.5). Twenty-five patients (38 knees) were included for analysis. Mean postoperative BMI was 41±5kg/m2, with a mean decrease of 1.2±3.6kg/m2. At the last follow-up, BMI had increased in 8 patients (32%), including 3 by >5% (12%), and decreased in 16 (64%), including 7 by >5% (28%). The higher the baseline BMI, the greater the decrease: for BMI [35-39.9], -0.81 (range, -6.8; +4.3); for BMI [40-44.5],-1 (range, -9; +5.22); and for BMI>45, -1.54 (range, -3.97; +1.3). EQ5D averaged 0.75 at last follow-up. The higher the preoperative BMI, the more satisfactory the postoperative EQ5D: EQ5D for BMI [35-39.9]=0.71 (range, 0.36; 1); for BMI [40-44.5]=0.75 (range, 0.45; 1); and for BMI>45=0.80 (range, 0.48; 1). Four early surgical site infections (10.5%) and 2 isolated changes of the tibial component for early loosening (5.2%) required surgical revision. CONCLUSION: Patients with severe or morbid obesity had a low tendency to lose weight after TKA, but this does not appear to us to be clinically relevant: the functional results were good. Nevertheless, this series showed a significant rate of revision (15%). TKA was feasible in patients with BMI≥35kg/m2, but requires appropriate patient information. LEVEL OF EVIDENCE: IV.

Surgical technique of anterior cruciate ligament ligamentoplasty with pedicular hamstrings via an inside-out approach: BIOFAST hamstring tendons graft.

This surgical technique of anterior cruciate ligament (ACL) reconstruction uses a 4-stranded hamstring tendons graft (HG), via an inside-out approach with a femoral cortical button and a tibial screw. It offers preservation of the tibial attachment of the hamstrings and enables double tibial fixation: biological and mechanical. This technique, "BIOFAST HG", does not require any calculation of the length of the tunnels, nor the use of different sized, or adjustable, buttons. If the sliding in the femoral tunnel fails, it is possible to easily convert to a so-called "classic technique". The first 60 cases were reviewed with a conversion rate of 3%. This technique allows the benefits of a pedicled graft over the classic HG technique in a simple way, with minimal conversions to the classic technique.

Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract.

IMPORTANCE: Identification of geographic population-based differences in genotype and phenotype heterogeneity are important for targeted and patient-specific diagnosis and treatment, counseling, and screening strategies. OBJECTIVE: To report disease-causing variants and their detailed phenotype in patients with bilateral congenital cataract from a single center in Switzerland and thereby draw a genetic map and perform a genotype-phenotype comparison of this cohort. DESIGN, SETTING, AND PARTICIPANTS: This clinical and molecular-genetic cohort study took place through the collaboration of the Department of Ophthalmology at the University Hospital Zurich and the Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland. Thirty-seven patients from 25 families with different types of bilateral congenital cataract were included. All participating family members received a comprehensive eye examination. Whole exome sequencing was performed in the index patients, followed by a filtering process to detect possible disease-associated variants in genes previously described in association with congenital cataract. Probable disease-causing variants were confirmed by Sanger sequencing in available family members. All data were collected from January 2018 to June 2020, and the molecular-genetic analyses were performed from January 2019 to July 2020. MAIN OUTCOMES AND MEASURES: Identification of the underlying genetic causes of bilateral congenital cataract, including novel disease-causing variants and phenotype correlation. RESULTS: Among the 37 patients (18 [49%] male and 19 [51%] female; mean [SD] age, 17.3 [15.9] years) from 25 families, pathogenic variants were detected in 20 families (80% detection rate), which included 13 novel variants in the following genes: BCOR, COL4A1, CRYBA2, CRYBB2, CRYGC, CRYGS, GJA3, MAF, NHS, and WFS1. Putative disease-causing variants were identified in 14 of 20 families (70%) as isolated cases and in 6 of 20 families (30%) with syndromic cases. A recessive variant in the CRYBB2 gene in a consanguineous family with 2 affected siblings showing a nuclear and sutural cataract was reported in contrast to previously published reports. In addition, the effect on splicing in a minigene assay of a novel splice site variant in the NHS gene (c.[719-2A>G]) supported the pathogenicity of this variant. CONCLUSIONS AND RELEVANCE: This study emphasizes the importance of genetic testing of congenital cataracts. Known dominant genes need to be considered for recessive inheritance patterns. Syndromic types of cataract may be underdiagnosed in patients with mild systemic features.

Whole Exome Sequencing in Coloboma/Microphthalmia: Identification of Novel and Recurrent Variants in Seven Genes.

Coloboma and microphthalmia (C/M) are related congenital eye malformations, which can cause significant visual impairment. Molecular diagnosis is challenging as the genes associated to date with C/M account for only a small percentage of cases. Overall, the genetic cause remains unknown in up to 80% of patients. High throughput DNA sequencing technologies, including whole-exome sequencing (WES), are therefore a useful and efficient tool for genetic screening and identification of new mutations and novel genes in C/M. In this study, we analyzed the DNA of 19 patients with C/M from 15 unrelated families using singleton WES and data analysis for 307 genes of interest. We identified seven novel and one recurrent potentially disease-causing variants in CRIM1, CHD7, FAT1, PTCH1, PUF60, BRPF1, and TGFB2 in 47% of our families, three of which occurred de novo. The detection rate in patients with ocular and extraocular manifestations (67%) was higher than in patients with an isolated ocular phenotype (46%). Our study highlights the significant genetic heterogeneity in C/M cohorts and emphasizes the diagnostic power of WES for the screening of patients and families with C/M.

Genotype-phenotype spectrum in isolated and syndromic nanophthalmos.

PURPOSE: To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients with MFRP variants, based on a detailed literature review of genotype-phenotype correlations. METHODS: Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole-exome sequencing and variant calling in core genes including MFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRF and FAM111A. A minigene assay was performed for functional characterization of a splice site variant. RESULTS: Seven patients, aged between three and 65 years, from five unrelated families were included. Novel pathogenic variants in MFRP (c.497C>T, c.899-3C>A, c.1180G>A), and PRSS56 (c.1202C>A), and a recurrent de novo variant in FAM111A (c.1706G>A) in a patient with Kenny-Caffey syndrome type 2, were identified. In addition, we report co-inheritance of MFRP-related nanophthalmos and ADAR-related Aicardi-Goutières syndrome. CONCLUSION: Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenic MFRP variants. Furthermore, heterozygous carriers of MFRP and PRSS56 should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients.

Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes.

Purpose: The aim of this study was to investigate the molecular basis of childhood glaucoma in Switzerland to recommend future targeted genetic analysis in the Swiss population. Methods: Whole-exome sequencing and copy number variation (CNV) analysis was performed in a Swiss cohort of 18 patients from 14 unrelated families. Identified variants were validated by Sanger sequencing and multiplex ligation-dependent probe amplification. Breakpoints of structural variants were determined by a microarray. A minigene assay was conducted for functional analysis of a splice site variant. Results: A diagnosis of primary congenital glaucoma was made in 14 patients, of which six (43%) harbored pathogenic variants in CYP1B1, one (7%) a frameshift variant in FOXC1, and seven (50%) remained without a genetic diagnosis. Three patients were diagnosed with glaucoma associated with nonacquired ocular anomalies, of which two patients with mild ocular features of Axenfeld-Rieger syndrome harbored a FOXC1 duplication plus an additional FOXC1 missense variant, and one patient with a Barkan membrane remained without genetic diagnosis. A diagnosis of juvenile open-angle glaucoma was made in one patient, and genetic analysis revealed a FOXC1 duplication. Conclusions: Sequencing of CYP1B1 and FOXC1, as well as analysis of CNVs in FOXC1, should be performed before extended gene panel sequencing. Translational Relevance: The identification of the molecular cause of childhood glaucoma is a prerequisite for genetic counseling and personalized care for patients and families.

Were protective procedures against SARS-CoV-2 effective in an orthopaedic and trauma centre during the lockdown period? A retrospective study.

PURPOSE: The SARS-CoV-2 epidemic started in December 2019 in Wuhan. The lockdown was declared on March 16, 2020 in France. Our centre had to adapt daily practices to continue to take care of bone and soft tissue tumours and emergencies. Through this study, we wanted to assess the various procedures implemented during the lockdown period between March 17 and May 10. METHODS: A monocentric retrospective cohort study was conducted in Cochin Hospital (Paris, France). Patients included were those who had surgery during the lockdown period. To take care of COVID-19 positive and negative patients, various procedures have been set up: reverse transcriptase polymerase chain reaction (RT-PCR) tests for all hospitalized patients, a specific unit for COVID-positive patients, a specific surgical room, and use of protective personal equipment. To allow the effectiveness of the procedures implemented, we evaluated the number of complications attributed to SARS-CoV-2 and the number of patients who became COVID positive during hospitalization. RESULTS: During the lockdown period, there were 199 procedures of three types of procedures in our centre: 79 traumatology procedures (39.7%), 76 of bone and soft tissues tumours (38.2%), and 44 procedures related to infection (22.1%). We observed 13 complications (6.5%) during hospitalization, and only one patient became COVID-19 positive during the hospitalization. CONCLUSION: The COVID-19 epidemic has been a challenge for organization and adaptation to manage all COVID-19 positive and COVID negative. Through this study, we wanted to assess our procedures taken. They had been effective due to the low number of contamination and complications.

Influence of regular aspirin intake on PSA values, prostate cancer incidence and overall survival in a prospective screening trial (ERSPC Aarau).

OBJECTIVES: To analyze the influence of aspirin (ASA) intake on PSA values and prostate cancer (PCa) development in a prospective screening study cohort. METHODS: 4314 men from the Swiss section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were included. A transrectal prostate biopsy was performed in men with a PSA level ≥ 3 ng/ml. Mortality data were obtained through registry linkages. PCa incidence and grade, total PSA, free-to-total PSA and overall survival were compared between ASA users and non-users. RESULTS: Median follow-up time was 9.6 years. In 789 men (18.3%) using aspirin [ASA +], the overall PCa incidence was significantly lower (6.8% vs. 9.6%, p = 0.015), but the multivariate Cox regression analysis showed no significant decrease in risk of PCa diagnosis (HR 0.84, p = 0.297). Total PSA values were significantly lower in ASA users for both baseline (1.6 vs. 1.8 ng/ml, p = 0.007) and follow-up visits (1.75 vs. 2.1 ng/ml, p < 0.001). Multivariate Cox regression analysis predicted significantly higher overall mortality risk among ASA users (HR 1.46, p = 0.009). CONCLUSIONS: In our study population, PCa incidence was significantly reduced among patients on aspirin. While we did not observe a statistically significant PCa risk reduction during the follow-up period, we found lower PSA values among ASA users compared to non-users, with a more distinct difference after 4 years of ASA intake, suggesting a cumulative effect and a potential protective association between regular ASA intake and PCa development. As for clinical practice, lowering PSA cutoff values by 0.4 ng/ml could be considered in long-term ASA users to avoid a potential bias towards delayed PCa detection.