Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS. METHODS: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age- and sex-matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two-dimensional axial rAMIRA imaging at the inter-vertebral disc levels C2/3-C5/C6 and the lumbar enlargement level Tmax. ALS Functional Rating Scale-revised (ALSFRS-R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed. RESULTS: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at Tmax. Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at Tmax. SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS-R (p < 0.001) and SNIP (p = 0.0016). CONCLUSION: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at Tmax may be an early disease sign. Longitudinal studies are warranted.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS). METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available. RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management. CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

Genetic variability in sporadic amyotrophic lateral sclerosis.

With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), there is a surge in gene testing for this disease. Although there is ample experience with gene testing for C9orf72, SOD1, FUS and TARDBP in familial ALS, large studies exploring genetic variation in all ALS-associated genes in sporadic ALS (sALS) are still scarce. Gene testing in a diagnostic setting is challenging, given the complex genetic architecture of sALS, for which there are genetic variants with large and small effect sizes. Guidelines for the interpretation of genetic variants in gene panels and for counselling of patients are lacking. We aimed to provide a thorough characterization of genetic variability in ALS genes by applying the American College of Medical Genetics and Genomics (ACMG) criteria on whole genome sequencing data from a large cohort of 6013 sporadic ALS patients and 2411 matched controls from Project MinE. We studied genetic variation in 90 ALS-associated genes and applied customized ACMG-criteria to identify pathogenic and likely pathogenic variants. Variants of unknown significance were collected as well. In addition, we determined the length of repeat expansions in C9orf72, ATXN1, ATXN2 and NIPA1 using the ExpansionHunter tool. We found C9orf72 repeat expansions in 5.21% of sALS patients. In 50 ALS-associated genes, we did not identify any pathogenic or likely pathogenic variants. In 5.89%, a pathogenic or likely pathogenic variant was found, most commonly in SOD1, TARDBP, FUS, NEK1, OPTN or TBK1. Significantly more cases carried at least one pathogenic or likely pathogenic variant compared to controls (odds ratio 1.75; P-value 1.64 × 10-5). Isolated risk factors in ATXN1, ATXN2, NIPA1 and/or UNC13A were detected in 17.33% of cases. In 71.83%, we did not find any genetic clues. A combination of variants was found in 2.88%. This study provides an inventory of pathogenic and likely pathogenic genetic variation in a large cohort of sALS patients. Overall, we identified pathogenic and likely pathogenic variants in 11.13% of ALS patients in 38 known ALS genes. In line with the oligogenic hypothesis, we found significantly more combinations of variants in cases compared to controls. Many variants of unknown significance may contribute to ALS risk, but diagnostic algorithms to reliably identify and weigh them are lacking. This work can serve as a resource for counselling and for the assembly of gene panels for ALS. Further characterization of the genetic architecture of sALS is necessary given the growing interest in gene testing in ALS.

Influence of avascular necrosis of the femoral head on hip prosthesis integration: a radiological analysis.

BACKGROUND: Avascular osteonecrosis of the femoral head (AVN) often results in total hip arthroplasty (THA). The cause for increased THA revision rates among patients with AVN is not yet fully understood. PURPOSE: To perform a comparative radiological analysis of implant integration between patients with AVN and osteoarthritis (OA). MATERIAL AND METHODS: After a matched pair analysis of 58 patients, 30 received THA due to OA, 28 due to AVN. X-ray images were evaluated after one week ("baseline") and on average 37.58 months postoperatively ("endline"). The prosthesis was grouped into 10 regions of interest (ROI): seven femoral and three acetabular. Incidence, width, and extent of "radiolucent lines" were measured within each zone. RESULTS: Between baseline and endline, width and extent progressed more noticeably in all femoral and acetabular zones among patients with AVN. In femoral ROI 1, the width increased in 40% of AVN cases compared to 6.7% of OA cases. For acetabular ROI 3, the width increased in 26.7% of AVN cases compared to no perceived changes in the OA group. No signs of prosthetic loosening were found in the AVN group. CONCLUSION: The increase of width and extent of radiolucent lines over time in patients with AVN could be a sign of lack of osteointegration. However, prosthetic loosening in absence of clinical symptoms cannot be deduced from radiological findings after medium-term postoperative follow-up. Further long-term studies are required to monitor how radiolucent lines develop in respect to long-term implant loosening. Dependent on bone quality, individually adapted reaming and broaching of the implant site are recommended.

Bone Mineral Density is Associated With Adverse Events but not Patient-Reported Outcomes in Total Hip and Knee Arthroplasty.

BACKGROUND: Although osteoporosis is common in patients undergoing elective total hip arthroplasty (THA) and total knee arthroplasty (TKA), its impact on postoperative outcomes has been inadequately studied. The purpose of this study was to evaluate the impact of bone mineral density (BMD) on adverse events and patient-reported outcomes in THA and TKA. METHODS: A series of 1,306 THA and 1,046 TKA patients who had received osteodensitometry were analyzed retrospectively. Rates of readmission, complication, transfusion, and patient-reported outcome were correlated with BMD. Multivariable logistic regression models were used to assess the relationship between osteoporosis and adverse events. RESULTS: Osteoporosis patients showed higher rates of 90-day readmission (THA: 8.5% versus 4.0%, P = .02; TKA: 8.9% versus 4.4%, P = .04) and transfusion (THA: 6.8% versus 1.2%, P < .001; TKA: 5.4% versus 1.5%, P = .005). After THA, rates of complications requiring intensive care management (5.1% versus 0.7%, P < .001) and rates of medical complications (3.5% versus 0.6%, P = .001) were increased. After TKA, rates of surgical complications (2.8% versus 0.8%, P = .04) were increased. Postoperatively, osteoporosis patients improved to comparable patient-reported outcomes as patients who had normal BMD. Multivariable logistic regression analyses revealed osteoporosis as an independent risk factor for readmissions, complications, and transfusions. CONCLUSION: Osteoporosis is a risk factor for adverse events after THA and TKA. Affected patients show similar improvement of patient-reported outcome compared to patients who have normal BMD. As osteoporosis is modifiable, a systematic screening of patients scheduled for THA or TKA should be discussed.

Surgery Within 24 Hours Reduces Mortality and General Complication Rates in Patients Who Have Periprosthetic Femoral Fractures at the Hip.

BACKGROUND: In patients who have hip fractures, treatment within 24 hours reduces mortality and complication rates. A similar relationship can be assumed for patients who have hip periprosthetic femoral fractures (PPFs) owing to the similar baseline characteristics of the patient populations. This monocentric retrospective study aimed to compare the complication and mortality rates in patients who had hip PPF treated within and after 24 hours. METHODS: In total, 350 consecutive patients who had hip PPF in a maximum-care arthroplasty and trauma center between 2006 and 2020 were retrospectively evaluated. The cases were divided into 2 groups using a time to surgery (TTS) of 24 hours as the cutoff value. The primary outcome variables were operative and general complications as well as mortalities within 1 year. RESULTS: Overall, the mean TTS was 1.4 days, and the 1-year mortality was 14.6%. The TTS ≤ 24 hours (n = 166) and TTS > 24 hours (n = 184) groups were comparable in terms of baseline characteristics and comorbidities. Surgical complications were equally frequent in the 2 groups (16.3 versus 15.2%, P = .883). General complications occurred significantly more often in the late patient care group (11.4 versus 28.3%, P < .001). In addition, the 30-day mortality (0.6 versus 5.5%, P = .012), and 1-year mortality (8.3 versus 20.5%, P = .003) rates significantly increased in patients who had TTS > 24 hours. Cox regression analysis yielded a hazard ratio of 4.385 (P < .001) for the TTS > 24 hours group. CONCLUSIONS: Prompt treatment is required for patients who have hip PPF to reduce mortality and overall complications.

Restrictive Versus Permissive Use of Broad-spectrum Antibiotics in Patients Receiving Allogeneic Stem Cell Transplantation and With Early Fever Due to Cytokine Release Syndrome: Evidence for Beneficial Microbiota Protection Without Increase in Infectious Complications.

BACKGROUND: Intestinal microbiome contributes to the pathophysiology of acute gastrointestinal (GI) graft-versus-host disease (GvHD) and loss of microbiome diversity influences the outcome of patients after allogeneic stem cell transplantation (SCT). Systemic broad-spectrum antibiotics have been identified as a major cause of early intestinal dysbiosis. METHODS: In 2017, our transplant unit at the university hospital in Regensburg changed the antibiotic strategy from a permissive way with initiation of antibiotics in all patients with neutropenic fever independent of the underlying cause and risk to a restrictive use in cases with high likelihood of cytokine release syndrome (eg, after anti-thymocyte globulin [ATG] therapy). We analyzed clinical data and microbiome parameters obtained 7 days after allogeneic SCT from 188 patients with ATG therapy transplanted in 2015/2016 (permissive cohort, n = 101) and 2918/2019 (restrictive cohort, n = 87). RESULTS: Restrictive antibiotic treatment postponed the beginning of antibiotic administration from 1.4 ± 7.6 days prior to 1.7 ± 5.5 days after SCT (P = .01) and significantly reduced the duration of antibiotic administration by 5.8 days (P < .001) without increase in infectious complications. Furthermore, we observed beneficial effects of the restrictive strategy compared with the permissive way on microbiome diversity (urinary 3-indoxylsulfate, P = .01; Shannon and Simpson indices, P < .001) and species abundance 7 days post-transplant as well as a positive trend toward a reduced incidence of severe GI GvHD (P = .1). CONCLUSIONS: Our data indicate that microbiota protection can be achieved by a more careful selection of neutropenic patients qualifying for antibiotic treatment during allogeneic SCT without increased risk of infectious complications.

Intestinal IgA-positive plasma cells are highly sensitive indicators of alloreaction early after allogeneic transplantation and associate with both graft-versus-host disease and relapse-related mortality.

Intestinal immunoglobulin A (IgA) is strongly involved in microbiota homeostasis. Since microbiota disruption is a major risk factor of acute graft-versus-host disease (GvHD), we addressed the kinetics of intestinal IgA-positive (IgA+) plasma cells by immunohistology in a series of 430 intestinal biopsies obtained at a median of 1,5 months after allogeneic stem cell transplantation (allo-SCT) from 115 patients (pts) at our center. IgA+ plasma cells were located in the subepithelial lamina propria and suppressed in the presence of histological aGvHD (GvHD Lerner stage 0: 131+/-8 IgA+ plasma cells/mm2; stage 1-2: 108+/-8 IgA+ plasma cells/mm2; stage 3-4: 89+/-16 IgA+ plasma cells/mm2; P=0.004). Overall, pts with IgA+ plasma cells below median had an increased treatment related mortality (P=0.04). Time courses suggested a gradual recovery of IgA+ plasma cells after day 100 in the absence but not in the presence of GvHD. Vice versa IgA+ plasma cells above median early after allo-SCT were predictive of relapse and relapse-related mortality (RRM): pts with low IgA+ cells had a 15% RRM at 2 and at 5 years, while pts with high IgA+ cells had a 31% RRM at 2 years and more than 46% at 5 years; multivariate analysis indicated high IgA+ plasma cells in biopsies (hazard ratio =2.7; 95% confidence interval: 1.04-7.00) as independent predictors of RRM, whereas Lerner stage and disease stage themselves did not affect RRM. In contrast, IgA serum levels at the time of biopsy were not predictive for RRM. In summary, our data indicate that IgA+ cells are highly sensitive indicators of alloreaction early after allo-SCT showing association with TRM but also allowing prediction of relapse independently from the presence of overt GvHD.

Inguinal hernia treatment in Switzerland: inpatient vs. outpatient setting - HerStAmb Study (prospective observational two-centre comparative study).

PURPOSE: Since 01/2018, AVOS (ambulant vor stationär = outpatient to inpatient) regulation has been progressively implemented in hernia surgery in Switzerland. The aim of this prospective, observational, two-centre comparative study was to compare the outcome of outpatient and inpatient post-operative care in terms of AVOS by examining the re-admission rate, complication rate and quality of life in patients with primary unilateral inguinal hernia repair. METHODS: The study ran between 01/2019 and 04/2020 and included 237 patients with a primary unilateral inguinal hernia. Treatment setting was decided according to AVOS guidelines. Primary endpoint was re-admission rate within 6 weeks postoperatively. Secondary endpoints were the complication rate and patient outcome (quality of life) at 6 weeks follow-up postoperatively, as measured by the Short Form 36 Health Survey Questionnaire (SF-36). RESULTS: Complications occurred in 11 (14%) inpatient patients, but none required re-admitting for revision until follow-up at 6 weeks after discharge. In the outpatient group, there were 27 (17%) complications reported, while 6 (4%) of these patients crossed over to the inpatient group immediately after surgery. None of the other complications required re-admission until follow-up at 6 weeks. No significant relationship between treatment setting and number of complications/re-admission rate (p=0.458, p=0.061) was observed. The mean outcome (SF-36) between the treatment groups was not significantly different (p=0.16-0.856). CONCLUSION: In terms of AVOS selection criteria in Switzerland, primary unilateral inguinal hernia can be safely treated in both treatment settings. Re-admission rates, complications and quality of life do not significantly differ. Day surgery in terms of AVOS might be as effective and efficient, both from the patient's perspective and that of the institution. TRIAL REGISTRATION NUMBER: NCT05234242.

Avascular necrosis of the femoral head: three-dimensional measurement of drilling precision reveals high accuracy and no difference between fluoroscopically controlled core decompression and cancellous bone grafting.

INTRODUCTION: Avascular osteonecrosis of the femoral head (AVN) is a widespread disease affecting mostly young and active people, often exacerbating in progressive stages, ending in joint replacement. The most common joint preserving operative therapy for early stages is core decompression (CD), optional with cancellous bone grafting (CBG). For success it is vital that the necrotic area is hit and the sclerotic rim is broken by drilling into the defect zone to relieve intraosseous pressure. The aim of this study was to investigate if both techniques are precise enough to hit the center of the necrosis and if there is a difference in precision between drilling with small pins (CD) and the trephine (CBG). PATIENTS AND METHODS: 10 patients underwent CD, 12 patients CBG with conventional C-arm imaging. Postoperatively 3D MRI reconstructions of the necrotic area and the drilling channels were compared. The deviation of the drilling channel from the center of the necrotic area was measured. PROMs (HHS, HOOS, EQ-5D, SF-36) were evaluated to compare the clinical success of these procedures. RESULTS: Neither with CD nor with CBG the defect zone was missed. The drilling precision of both procedures did not differ significantly: distance to center 3.58 mm for CD (range 0.0-14.06, SD 4.2) versus 3.91 mm for CBG (range 0.0-15.27, SD 4.7). PROMs showed no significant difference. CONCLUSION: Concerning the most important difference between the two procedures-the surgical higher demanding technique of CBG-we suggest applying the less invasive technique of CD alone.

Delay of total joint replacement is associated with a higher 90-day revision rate and increased postoperative complications.

PURPOSE: Delay of elective surgeries, such as total joint replacement (TJR), is a common procedure in the current pandemic. In trauma surgery, postponement is associated with increased complication rates. This study aimed to evaluate the impact of postponement on surgical revision rates and postoperative complications after elective TJR. METHODS: In a retrospective analysis of 10,140 consecutive patients undergoing primary total hip replacement (THR) or total knee replacement (TKR) between 2011 and 2020, the effect of surgical delay on 90-day surgical revision rate, as well as internal and surgical complication rates, was investigated in a university high-volume arthroplasty center using the institute's joint registry and data of the hospital administration. Moreover, multivariate logistic regression models were used to adjust for confounding variables. RESULTS: Two thousand four hundred and eighty TJRs patients were identified with a mean delay of 13.5 ± 29.6 days. Postponed TJR revealed a higher 90-day revision rate (7.1-4.5%, p < 0.001), surgical complications (3.2-1.9%, p < 0.001), internal complications (1.8-1.2% p < 0.041) and transfusion rate (2.6-1.8%, p < 0.023) than on-time TJR. Logistic regression analysis confirmed delay of TJRs as independent risk factor for 90-day revision rate [OR 1.42; 95% CI (1.18-1.72); p < 0.001] and surgical complication rates [OR 1.51; 95% CI (1.14-2.00); p = 0.04]. CONCLUSION: Alike trauma surgery, delay in elective primary TJR correlates with higher revision and complication rates. Therefore, scheduling should be performed under consideration of the current COVID-19 pandemic. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

[Outcome of joint replacement in patients with underlying rheumatoid disease]. / Outcome nach Gelenkersatz bei Patienten mit rheumatoider Grunderkrankung.

BACKGROUND: Artificial joint replacement is a meaningful treatment option for patients with advanced rheumatic degenerative joint diseases. The aim of this study was to investigate the influence of the underlying rheumatic diseases on postoperative complications and patient-reported outcome (PRO) after elective total joint replacement (TJR). MATERIAL AND METHODS: In a retrospective analysis of 9149 patients with elective total knee or total hip arthroplasty (TKR and THR), complication rates and PRO of patients with and without rheumatic diseases (RD) were compared. Multivariate logistic regression models were used to determine whether the underlying rheumatic disease was an independent risk factor for various complications. RESULTS: In the univariate analyses the RD patients had an increased risk of medical complications (7.1% vs. 5.2%; p = 0.028) and Clavien-Dindo grade IV complications (2.8% vs. 1.8%; p = 0.048) after TJR. This was confirmed in multivariate statistical analyses (p < 0.034). The rates for operative revisions and surgical complications were comparable (2.5% vs. 2.4%; p = 0.485). Analysis of the PRO showed a higher responder rate in patients with RD after TKR (91.9% vs. 84.5%, p = 0.039). In contrast, the responder rate in patients with RD after THR was comparable (93.4% vs. 93.2%, p = 0.584). CONCLUSION: Despite increased postoperative complication rates, patients with underlying rheumatic diseases showed a comparable outcome 1 year after TJR. After TKR the RD patients showed even higher responder rates. Although RD patients are a vulnerable patient group, they can still benefit from joint replacement.

The Effect of SMN Gene Dosage on ALS Risk and Disease Severity.

OBJECTIVE: The role of the survival of motor neuron (SMN) gene in amyotrophic lateral sclerosis (ALS) is unclear, with several conflicting reports. A decisive result on this topic is needed, given that treatment options are available now for SMN deficiency. METHODS: In this largest multicenter case control study to evaluate the effect of SMN1 and SMN2 copy numbers in ALS, we used whole genome sequencing data from Project MinE data freeze 2. SMN copy numbers of 6,375 patients with ALS and 2,412 controls were called from whole genome sequencing data, and the reliability of the calls was tested with multiplex ligation-dependent probe amplification data. RESULTS: The copy number distribution of SMN1 and SMN2 between cases and controls did not show any statistical differences (binomial multivariate logistic regression SMN1 p = 0.54 and SMN2 p = 0.49). In addition, the copy number of SMN did not associate with patient survival (Royston-Parmar; SMN1 p = 0.78 and SMN2 p = 0.23) or age at onset (Royston-Parmar; SMN1 p = 0.75 and SMN2 p = 0.63). INTERPRETATION: In our well-powered study, there was no association of SMN1 or SMN2 copy numbers with the risk of ALS or ALS disease severity. This suggests that changing SMN protein levels in the physiological range may not modify ALS disease course. This is an important finding in the light of emerging therapies targeted at SMN deficiencies. ANN NEUROL 2021;89:686-697.

Characterising ALS disease progression according to El Escorial and Gold Coast criteria.

BACKGROUND: The Gold Coast criteria (GCC) have been proposed as a means of selecting patients for amyotrophic lateral sclerosis (ALS) clinical trials. We aimed to characterise disease progression according to the GCC. METHODS: Data from population-based ALS registries from the Netherlands and Belgium were analysed. The GCC additionally define ALS as lower motor neuron (LMN) dysfunction in ≥2 body regions without upper motor neuron dysfunction. Therefore, the revised El Escorial criteria (rEEC) were supplemented with a 'Gold Coast ALS' category for patients with only LMN dysfunction in ≥2 body regions. We assessed survival time, ALS Functional Rating Scale (ALSFRS-R) progression rates and between-patient variability per diagnostic category. RESULTS: We included 5957 ALS patients, of whom 600 (10.1%) fulfilled the GCC but not the rEEC, and 95 (1.6%) fulfilled only the rEEC. ALSFRS-R progression rates were similar for the rEEC (0.84 points/month) and GCC (0.81 points/month) with similar variability (standard deviation of 0.59 vs. 0.60) and median survival time (17.8 vs.18.7 months). Survival time and average progression rates varied (p<0.001) between categories. Per category, however, there was considerable between-patient variability with progression rates ranging from: -2.10 to -0.14 (definite), -1.94 to -0.06 (probable), -2.10 to -0.02 (probable laboratory supported), -1.79 to -0.02 (possible) and -1.31 to 0.08 (Gold Coast). CONCLUSIONS: The GCC broaden the definition of ALS, allowing more patients to participate in trials, while minimally impacting population heterogeneity. Given the large variability per diagnostic category, selecting only specific categories for trials may not result in a more homogeneous study population.

Reinnervation as measured by the motor unit size index is associated with preservation of muscle strength in amyotrophic lateral sclerosis, but not all muscles reinnervate.

INTRODUCTION/AIMS: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known whether MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response to reinnervation after motor unit loss. METHODS: Fifty-seven patients with ALS were assessed at 3-month intervals for 12 months in four centers. Muscles examined were abductor pollicis brevis, abductor digiti minimi, biceps brachii, and tibialis anterior. Results were split into two groups: muscles with increases in MUSIX and those without increases. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential amplitude, and Medical Research Council strength score were investigated. RESULTS: One hundred thirty-three muscles were examined. Fifty-nine percent of the muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (58% decline in MUNIX at 12 months, P < .001) than muscles that did not increase MUSIX (34.6% decline in MUNIX at 12 months, P < .001). However, longitudinal changes in muscle strength were similar. When motor unit loss was similar, the absence of a MUSIX increase was associated with a significantly greater loss of muscle strength (P = .002). DISCUSSION: MUSIX increases are associated with greater motor unit loss but relative preservation of muscle strength. Thus, MUSIX appears to be measuring a clinically relevant response that can provide a quantitative outcome measure of reinnervation in clinical trials. Furthermore, MUSIX suggests that reinnervation may play a major role in determining the progression of weakness.

Long-term outcomes of transplant kidneys donated after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. METHODS: We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. RESULTS: The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182-372}] in DBD recipients and 24.5 years [289 months (95% CI 245-333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (-0.6 versus -0.3 mL/min/year) between the two groups for graft survival >20 years. CONCLUSIONS: This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts.

No impact of sex on surgical site infections in abdominal surgery: a multi-center study.

OBJECTIVE: Male sex is controversially discussed as a risk factor for surgical site infections (SSI). The aim of the present study was to evaluate the impact of sex on SSI in abdominal surgery under elimination of relevant confounders. METHODS: Clinicopathological data of 6603 patients undergoing abdominal surgery from a multi-center prospective database of four Swiss hospitals including patients between 2015 and 2018 were assessed. Patients were stratified according to postoperative SSI and risk factors for SSI were identified using univariate and multivariate analysis. RESULTS: In 649 of 6603 patients, SSI was reported (9.8%). SSI was significantly associated with reoperation (22.7% vs. 3.4%, p < 0.001), increased mortality rate (4.6% vs. 0.9%, p < 0.001), and increased rate of length of hospital stay > 75th percentile (57.0% vs. 17.9%, p < 0.001). In univariate analysis, male sex was a significant risk factor for SSI (p = 0.01). In multivariate analysis including multiple confounders' such as comorbidities and perioperative factors, there was no association between male sex and risk of SSI (odds ratio (OR) 1.1 [CI 0.8-1.4]). Independent risk factors for SSI in multivariate analysis were BMI ≥ 30 kg/m2 (OR 1.8 [CI 1.3-2.3]), duration of surgery > 75th percentile (OR 2.3 [1.8-2.9]), high contamination level (OR 1.3 [1.0-1.6]), laparotomy (OR 1.3 [1.0-1.7]), previous laparotomy (OR 1.4 [1.1-1.7]), blood transfusion (OR 1.7 [1.2-2.4]), cancer (OR 1.3 [1.0-1.8] and malnutrition (OR 2.5 [1.8-3.4]). CONCLUSION: Under elimination of relevant confounders, there is no significant correlation between sex and risk of SSI after abdominal surgery.

Pelvic tilt impacts cup orientation on CT: how accurate is the gold standard?

BACKGROUND: Computed tomography (CT) is the gold standard for the accurate measurement of cup inclination and anteversion in total hip arthroplasty (THA). However, functional cup position strongly depends on the tilt of the pelvis and thus pelvic tilt in the supine position on the CT table harbors the risk of misinterpretation. PURPOSE: To evaluate the influence of pelvic tilt on cup measurements in postoperative CT scans. MATERIAL AND METHODS: This is a secondary outcome analysis of a prospective study. In 123 patients undergoing THA, anatomic cup inclination and anteversion as measured on postoperative 3D-CT scans were compared between: (i) the anterior pelvic plane (APP) resembling neutral pelvic tilt; and (ii) the coronal plane representing the standard planes on CT. Furthermore, the effect of the variation on cup positions within Lewinnek's safe zone in relation to the applied reference plane was assessed. RESULTS: Mean pelvic tilt in supine position was -3.5° ± 5.6°. This resulted in a mean difference for anteversion between APP und coronal plane of 2.1° ± 3.7° and of 2.1° ± 1.9° for cup inclination, respectively. The change varied up to 20.2° for cup inclination and up 12.2° for cup anteversion. The overall conversion rate for inclination and/or anteversion regarding Lewinnek's safe zone was high at 23.6% (29/123). CONCLUSION: Pelvic tilt affects cup orientation on CT scans depending on the applied reference plane. Standard CT planes should be corrected regarding pelvic tilt before measurements to avoid errors in measurement.

Hospital frailty risk score predicts adverse events in spine surgery.

PURPOSE: The Hospital Frailty Risk Score (HFRS) is derived from routinely collected data and validated as a geriatric risk stratification tool. This study aimed to evaluate the utility of the HFRS as a predictor for postoperative adverse events in spine surgery. METHODS: In this retrospective analysis of 2042 patients undergoing spine surgery at a university spine center between 2011 and 2019, HFRS was calculated for each patient. Multivariable logistic regression models were used to assess the relationship between the HFRS and postoperative adverse events. Adverse events were compared between patients with high or low frailty risk. RESULTS: Patients with intermediate or high frailty risk showed a higher rate of reoperation (19.7% vs. 12.2%, p < 0.01), surgical site infection (3.4% vs. 0.4%, p < 0.001), internal complications (4.1% vs. 1.1%, p < 0.01), Clavien-Dindo IV complications (8.8% vs. 3.4%, p < 0.001) and transfusion (10.9% vs. 1.5%, p < 0.001). Multivariable logistic regression analyses revealed a high HFRS as independent risk factor for reoperation [odds ratio (OR) = 1.1; 95% confidence interval (CI) 1.0-1.2], transfusion (OR = 1.3; 95% CI 1.2-1.4), internal complications (OR = 1.2; 95% CI 1.1-1.3), surgical site infections (OR = 1.3; 95% CI 1.2-1.5) and other complications (OR = 1.3; 95% CI 1.2-1.4). CONCLUSION: The HFRS can predict adverse events and is an easy instrument, fed from routine hospital data. By identifying risk patients at an early stage, the individual patient risk could be minimized, which leads to less complications and lower costs. LEVEL OF EVIDENCE: Level III - retrospective cohort study TRIAL REGISTRATION: The study was approved by the local ethics committee (20-1821-104) of the University of Regensburg in February 2020.

Special orthopaedic geriatrics (SOG) - a new multiprofessional care model for elderly patients in elective orthopaedic surgery: a study protocol for a prospective randomized controlled trial of a multimodal intervention in frail patients with hip and knee replacement.

BACKGROUND: Due to demographic change, the number of older people in Germany and worldwide will continue to rise in the coming decades. As a result, the number of elderly and frail patients undergoing total hip and knee arthroplasty is projected to increase significantly in the coming years. In order to reduce risk of complications and improve postoperative outcome, it can be beneficial to optimally prepare geriatric patients before orthopaedic surgery and to provide perioperative care by a multiprofessional orthogeriatric team. The aim of this comprehensive interventional study is to assess wether multimorbid patients can benefit from the new care model of special orthopaedic geriatrics (SOG) in elective total hip and knee arthroplasty. METHODS: The SOG study is a registered, monocentric, prospective, randomized controlled trial (RCT) funded by the German Federal Joint Committee (GBA). This parallel group RCT with a total of 310 patients is intended to investigate the specially developed multimodal care model for orthogeriatric patients with total hip and knee arthroplasty (intervention group), which already begins preoperatively, in comparison to the usual orthopaedic care without orthogeriatric co-management (control group). Patients ≥70 years of age with multimorbidity or generally patients ≥80 years of age due to increased vulnerability with indication for elective primary total hip and knee arthroplasty can be included in the study. Exclusion criteria are age < 70 years, previous bony surgery or tumor in the area of the joint to be treated, infection and increased need for care (care level ≥ 4). The primary outcome is mobility measured by the Short Physical Performance Battery (SPPB). Secondary outcomes are morbidity, mortality, postoperative complications, delirium, cognition, mood, frailty, (instrumental) activities of daily living, malnutrition, pain, polypharmacy, and patient reported outcome measures. Tertiary outcomes are length of hospital stay, readmission rate, reoperation rate, transfusion rate, and time to rehabilitation. The study data will be collected preoperative, postoperative day 1 to 7, 4 to 6 weeks and 3 months after surgery. DISCUSSION: Studies have shown that orthogeriatric co-management models in the treatment of hip fractures lead to significantly reduced morbidity and mortality rates. However, there are hardly any data available on the elective orthopaedic care of geriatric patients, especially in total hip and knee arthroplasty. In contrast to the care of trauma patients, optimal preoperative intervention is usually possible. TRIAL REGISTRATION: German Clinical Trials Register DRKS00024102. Registered on 19 January 2021.