Orthopedic Management of Patients with Pompe Disease: A Retrospective Case Series of 8 Patients

Introduction. Pompe disease (PD), a lysosomal storage disease as well as a neuromuscular disorder, is a rare disease marked by progressive muscle weakness. Enzyme replacement therapy (ERT) in recent years allowed longer survival but brought new problems to the treatment of PD with increasing affection of the musculoskeletal system, particularly with a significantly higher prevalence of scoliosis. The present paper deals with the orthopedic problems in patients with PD and is the first to describe surgical treatment of scoliosis in PD patients. Patients and Methods. The orthopedic problems and treatment of eight patients with PD from orthopedic consultation for neuromuscular disorders are retrospectively presented. We analyzed the problems of scoliosis, hip dysplasia, feet deformities, and contractures and presented the orthopedic treatment options. Results. Six of our eight PD patients had scoliosis and two young patients were treated by operative spine stabilization with benefits for posture and sitting ability. Hip joint surgery, operative contracture release, and feet deformity correction were performed with benefits for independent activity. Conclusion. Orthopedic management gains importance due to extended survival and musculoskeletal involvement under ERT. Surgical treatment is indicated in distinct cases. Further investigation is required to evidence the effect of surgical spine stabilization in PD

Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

IntroductionPrevious studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysisThe BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and disseminationThe BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration numberNCT04647396

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \uc3\ua2 '0.24 to \uc3\ua2 '0.73; P < 1.49 \uc3\u97 10 \uc3\ua2 '4), and lower thickness in the precentral gyri bilaterally (d = \uc3\ua2 '0.34 to \uc3\ua2 '0.52; P < 4.31 \uc3\u97 10 \uc3\ua2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \uc3\ua2 '1.73 to \uc3\ua2 '1.91, P < 1.4 \uc3\u97 10 \uc3\ua2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \uc3\ua2 '0.36 to \uc3\ua2 '0.52; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \uc3\ua2 '0.29 to \uc3\ua2 '0.54; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \uc3\ua2 '0.27 to \uc3\ua2 '0.51; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \uc3\ua2 '0.0018; P < 1.49 \uc3\u97 10 \uc3\ua2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed

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Effect of Intraoperative Handovers of Anesthesia Care on Mortality, Readmission, or Postoperative Complications Among Adults The HandiCAP Randomized Clinical Trial

IMPORTANCE Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. OBJECTIVE To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality. DESIGN, SETTING, AND PARTICIPANTS This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours. INTERVENTIONS A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol. MAIN OUTCOMES AND MEASURES The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay. RESULTS Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR. 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881(33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5 .9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 128; P = .91). None of the 19 prespecified secondary end points differed significantly. CONCLUSIONS AND RELEVANCE Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days