Frailty is a clinical state in which there is an increase in an individual’s vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. Physical frailty is an important medical syndrome. The group defined physical frailty as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy.Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons.For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (≥5%) due to chronic disease should be screened for frailty.
Identification of single-gene causes of steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding of the pathogenesis of this disease. Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q 10 (CoQ 10 ) biosynthesis. Mutations in ADCK4 resulted in reduced CoQ 10 levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic syndrome-associated phenotypes. Furthermore, ADCK4 was expressed in glomerular podocytes and partially localized to podocyte mitochondria and foot processes in rat kidneys and cultured human podocytes. In human podocytes, ADCK4 interacted with members of the CoQ 10 biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7. Knockdown of ADCK4 in podocytes resulted in decreased migration, which was reversed by CoQ 10 addition. Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ 10 treatment. These data indicate that individuals with SRNS with mutations in ADCK4 or other genes that participate in CoQ 10 biosynthesis may be treatable with CoQ 10 .
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Summary Background Total hip replacement is a common and highly effective operation. All hip replacements would eventually fail if in situ long enough and it is important that patients understand when this might happen. We aimed to answer the question: how long does a hip replacement last? Methods We did a systematic review and meta-analysis with a search of MEDLINE and Embase from the start of records to Sept 12, 2017. We included articles reporting 15-year survival of primary, conventional total hip replacement constructs in patients with osteoarthritis. We extracted survival and implant data and used all-cause construct survival as the primary outcome. We also reviewed reports of national joint replacement registries, and extracted data for a separate analysis. In the meta-analyses, we weighted each series and calculated a pooled survival estimate for each source of data. This study was registered with PROSPERO (CRD42018085642). Findings We identified 140 eligible articles reporting 150 series, and included 44 of these series (13 212 total hip placements). National joint replacement registries from Australia and Finland provided data for 92 series (215 676 total hip replacements). The 25-year pooled survival of hip replacements from case series was 77·6% (95% CI 76·0–79·2) and from joint replacement registries was 57·9% (95% CI 57·1–58·7). Interpretation Assuming that estimates from national registries are less likely to be biased, patients and surgeons can expect a hip replacement to last 25 years in around 58% of patients. Funding National Institute for Health Research, National Joint Registry for England, Wales, Northern Ireland and Isle of Man, and The Royal College of Surgeons of England.
Summary Background Knee replacements are the mainstay of treatment for end-stage osteoarthritis and are effective. Given time, all knee replacements will fail and knowing when this failure might happen is important. We aimed to establish how long a knee replacement lasts. Methods In this systematic review and meta-analysis, we searched MEDLINE and Embase for case series and cohort studies published from database inception until July 21, 2018. Articles reporting 15 year or greater survival of primary total knee replacement (TKR), unicondylar knee replacement (UKR), and patellofemoral replacements in patients with osteoarthritis were included. Articles that reviewed specifically complex primary surgeries or revisions were excluded. Survival and implant data were extracted, with all-cause survival of the knee replacement construct being the primary outcome. We also reviewed national joint replacement registry reports and extracted the data to be analysed separately. In the meta-analysis, we weighted each series and calculated a pooled survival estimate for each data source at 15 years, 20 years, and 25 years, using a fixed-effects model. This study is registered with PROSPERO, number CRD42018105188. Findings From 4363 references found by our initial search, we identified 33 case series in 30 eligible articles, which reported all-cause survival for 6490 TKRs (26 case series) and 742 UKRs (seven case series). No case series reporting on patellofemoral replacements met our inclusion criteria, and no case series reported 25 year survival for TKR. The estimated 25 year survival for UKR (based on one case series) was 72·0% (95% CI 58·0–95·0). Registries contributed 299 291 TKRs (47 series) and 7714 UKRs (five series). The pooled registry 25 year survival of TKRs (14 registries) was 82·3% (95% CI 81·3–83·2) and of UKRs (four registries) was 69·8% (67·6–72·1). Interpretation Our pooled registry data, which we believe to be more accurate than the case series data, shows that approximately 82% of TKRs last 25 years and 70% of UKRs last 25 years. These findings will be of use to patients and health-care providers; further information is required to predict exactly how long specific knee replacements will last. Funding The National Joint Registry for England, Wales, Northern Ireland, and Isle of Man and the Royal College of Surgeons of England.
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