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Substance use is common among those with heart failure (HF) and is associated with worse clinical outcomes. Alcohol, tobacco, cannabis, and cocaine are commonly abused substances that can contribute to the development and worsening of HF. Heavy alcohol consumption can lead to dilated cardiomyopathy, whereas moderate intake may decrease incident HF. Tobacco increases the risk of HF through coronary artery disease and coronary artery disease–independent mechanisms. Continued smoking worsens outcomes for those with HF and cessation is associated with an improved risk of major adverse cardiac events. Cannabis has complex interactions on the cardiovascular system depending on the method of consumption, amount consumed, and content of cannabinoids. Delta-9-tetrahydrocannabinol can increase sympathetic tone, cause vascular dysfunction, and may increase the risk of myocardial infarction. Cannabidiol is cardioprotective in preclinical studies and is a potential therapeutic target. Cocaine increases sympathetic tone and is a potent proarrhythmogenic agent. It increases the risk of myocardial infarction and can also lead to a dilated cardiomyopathy. The use of beta-blockers in those with HF and cocaine use is likely safe and effective. Future studies are needed to further elucidate the impact of these substances both on the development of HF and their effects on those who have HF.

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Summary Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. Methods In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. Findings Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27–1·43), past tuberculosis (1·26, 1·15–1·38), current tuberculosis (1·42, 1·22–1·64), and both past and current tuberculosis (1·48, 1·32–1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22–1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. Interpretation Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. Funding South African National Government.

ZusammenfassungDesorientierung kann ein frühes Merkmal eines Delirs sein. Für die Überwachung eines Delirs testet die im deutschsprachigen Raum weit verbreitete „Confusion Assessment Method for Intensive Care Unit“ (CAM-ICU) die Orientierung nicht, da intubierte Intensivpatienten sich nicht verbal äußern können. Die Mehrheit der Patienten auf deutschen Intensivstationen ist aber nicht beatmet, sie könnten hinsichtlich ihrer Orientiertheit befragt werden. Die vorliegende Studie untersuchte, ob sich durch das Kriterium „Desorientierung“ bei extubierten Patienten im Vergleich zur CAM-ICU divergierende Befunde ergeben und ob sich die Sensitivität der CAM-ICU durch Kombination mit dem Merkmal „Desorientierung“ („CAM-IMC“) erhöhen lassen. Insgesamt 86 gepaarte Untersuchungen fanden bei 50 extubierten Patienten statt. Ein Delir fand sich bei 19,8 % (n = 17) aller Untersuchungen. Die CAM-ICU hatte eine Sensitivität von 71 % (95%-KI: 44–90 %) und eine Spezifität von 100 % (95–100 %). Für „Desorientierung“ als alleiniges Delir-Merkmal fand sich eine Sensitivität von 77 % (50–93 %) und eine Spezifität von 93 % (89–100 %). Die CAM-IMC erreichte eine Sensitivität von 88 % (64–99 %) bei einer Spezifität von 100 % (95–100 %). Die „Receiver-Operating-Characteristics(ROC)-Analyse“ fand mit einer „area under the curve“ (AUC) von 0,941 (95%-KI: 0,851–1,000) für die CAM-IMC den höchsten Wert im Vergleich zu den anderen Delir-Tests (CAM-ICU, AUC 0,853 [0,720–0,986]; Desorientierung, AUC 0,868 [0,745–0,991]). Diese Arbeit unterstreicht die Wertigkeit des Merkmals „Desorientierung“ für Delir-Tests bei verbal kommunikationsfähigen Patienten und erklärt einige diskrepante Beurteilungen schwierig einzuschätzender Patienten in der täglichen Praxis. Die CAM-IMC scheint als Delir-Test für extubierte Patienten günstigere Eigenschaften als die CAM-ICU zu haben und sollte eingehender überprüft werden.

Purpose of Review In this scoping review, we aimed to (1) provide an overview of chronic sleep reduction by systematically reviewing the existing literature (limited to systematic reviews and meta-analyses), (2) investigate the evidence of the effects of short sleep duration on daytime functioning, and (3) identify research gaps in this field. Recent Findings The results showed that (1) clear definitions of chronicity of sleep reduction are lacking—none of the included reviews/meta-analyses provided a full definition—and (2) short sleep duration appeared to be related to obesity and diabetes, whereas relations with cardiovascular disease (CVD), cognitive functioning, emotional problems, general health, and mortality, showed either small effects and appeared to be complex (e.g., for CVD and cognitive functioning), or studies were scarce or completely lacking (e.g., mortality in children/adolescents and emotional problems in adults). Summary Although short or insufficient sleep is highly prevalent and is associated with impaired mental and physical wellbeing, as well as pervasive negative consequences for daytime functioning, the concepts of “chronicity” and “chronic sleep reduction” have not been clearly defined and its effects on health are therefore still largely unknown. Moreover, there are large research gaps concerning studies on the relations between short sleep and health consequences. Further studies are recommended to define and operationalize chronicity of sleep reduction and develop measurements that adequately represent the complexity of the concept.

BMC public health 21(1), 1295 (2021). doi:10.1186/s12889-021-11206-9, Published by BioMed Central, London

Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in heart failure (HF) populations have become increasingly difficult to conduct and are frequently associated with slow patient enrollment, highly selected populations, extensive data collection, and high costs. The traditional model for HF trials has become particularly difficult to execute in the United States, where challenges to site-based research have frequently led to modest U.S. representation in global trials. In this context, the TRANSFORM-HF (Torsemide Comparison with Furosemide for Management of Heart Failure) trial aims to overcome traditional trial challenges and compare the effects of torsemide versus furosemide among patients with HF in the United States. Loop diuretic agents are regularly used by most patients with HF and practice guidelines recommend optimal use of diuretic agents as key to a successful treatment strategy. Long-time clinical experience has contributed to dominant use of furosemide for loop diuretic therapy, although preclinical and small clinical studies suggest potential advantages of torsemide. However, due to the lack of appropriately powered clinical outcome studies, there is insufficient evidence to conclude that torsemide should be routinely recommended over furosemide. Given this gap in knowledge and the fundamental role of loop diuretic agents in HF care, the TRANSFORM-HF trial was designed as a prospective, randomized, event-driven, pragmatic, comparative-effectiveness study to definitively compare the effect of a treatment strategy of torsemide versus furosemide on long-term mortality, hospitalization, and patient-reported outcomes among patients with HF. (TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure [TRANSFORM-HF]; NCT03296813 )

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

Die Mortalitat von Patienten mit isoliert auftretenden angeborenen Zwerchfellhernien liegt in spezialisierten Zentren bei 20–40%. Wesentliche, das Outcome beeinflussende Faktoren, sind die bestehende Lungenhypoplasie, eine daraus resultierende pulmonale Hypertonie, sowie das Vorliegen weiterer Fehlbildungen. Begleitfehlbildungen wie angeborene Herzfehler treten bei ca. 18% aller Neonaten mit Zwerchfellhernie auf. Schwere angeborene Herzfehler wie das hypoplastische Linksherz Syndrom zeigen sich in ca. 8% der Falle. In einer retrospektiven Analyse des Patientenkollektivs unserer Klinik zwischen 01/2012 und 12/2018 wurde das pra- und postnatale Management, sowie das Outcome von Neugeborenen mit der Kombination aus angeborenen Herzfehlern und Zwerchfellhernien untersucht. Im Studienzeitraum wurden in unserer Klinik 156 Neugeborene mit Zwerchfellhernie behandelt. Bei 10 Patienten (6,4%) lag zusatzlich ein schwerer, bei 11 Patienten (7,1%) ein moderater Herzfehler vor. 6/21 Patienten verstarben im Verlauf des Krankenhausaufenthaltes, davon 3 am ersten Lebenstag. Es zeigte sich eine deutlich geringere Mortalitat bei Patienten mit Zwerchfellhernie und moderatem Herzfehler im Vergleich zu schwerem Herzfehler (9 vs. 50%). Besonders hoch lag die Mortalitat bei Kindern mit einem univentrikularen Herzen. Trotz einer deutlich reduzierten Prognose bei der Kombination aus angeborenem Herzfehler und Zwerchfellhernie muss nicht generell mit einer infausten Prognose gerechnet werden. In spezialisierten Zentren kann ein kurativer Ansatz erfolgen. The mortality of patients with isolated congenital diaphragmatic hernia (CDH) in specialized centers is 20–40%. The main factors influencing the outcome are the underlying pulmonary hypoplasia, the resulting pulmonary hypertension and the presence of other malformations. Concomitant malformations such as congenital heart defects occur in around 18% of all neonates with a diaphragmatic hernia. Serious congenital heart defects such as hypoplastic left heart syndrome occur in approximately 8% of cases. In a retrospective analysis of the patient collective of our hospital between 01/2012 and 12/2018, the prenatal and postnatal management as well as the outcome of newborns with a combination of congenital heart defects and diaphragmatic hernias were examined. During the study period, 156 newborns with diaphragmatic hernias were treated at our institution. In 10 patients (6.4%) there was also a severe, and in 11 patients (7.1%) a moderate heart defect. 6/21 patients died during their hospital stay, 3 of them on the first day of life. There was a significantly lower mortality in patients with diaphragmatic hernia and moderate heart defects compared to severe heart defects (9 vs. 50%). The mortality in children with a univentricular heart was particularly high. Despite a significantly reduced prognosis for the combination of congenital heart defects and diaphragmatic hernia, generally a poor prognosis does not have to be expected. A curative approach can be achieved in specialized centers.

Purpose To evaluate the feasibility and effect of an approach to adrenal venous sampling (AVS) analysis by combining established selective cortisol and aldosterone indices with the acquisition of a collimated C-arm CT(CACTColl). Methods Overall, 107 consecutive patients (45f,62 m; 54 ± 10 years) undergoing 111 AVS procedures without hormonal stimulation from 7/13 to 2/20 in a single institution were retrospectively analysed. Hormone levels were measured in sequential samples of the suspected adrenal veins and right iliac vein, and selectivity indices (SI) computed. Stand-alone SICortisol and/or SIAldosterone ≥ 2.0 as well as SICortisol and/or SIAldosterone ≥ 1.1 combined with positive right-sided CACTColl of the adrenals (n = 80; opacified right adrenal vein) were defined as a successful AVS procedure. Radiation exposure of CACT was measured via dose area product (DAP) and weighed against an age-/weight-matched cohort (n = 66). Results Preliminary success rates (SICortisol and/or SIAldosterone ≥ 2.0) were 99.1% (left) and 72.1% (right). These could be significantly increased to a 90.1% success rate on the right, by combining an adjusted SI of 1.1 with a positive CACTColl proving the correct sampling position. Sensitivity for stand-alone collimated CACT (CACTColl) was 0.93, with 74/80 acquired CACTColl confirming selective cannulation by adrenal vein enhancement. Mean DAPColl_CACT measured 2414 ± 958 μGyxm2, while mean DAPFull-FOV_CACT in the matched cohort measured 8766 ± 1956 μGyxm2 (p Conclusion Collimated CACT in AVS procedures is feasible and leads to a significant increase in success rates of (right-sided) selective cannulation and may in combination with adapted hormone indices, offer a successful alternative to previously published AVS analysis algorithms with lower radiation exposure compared to a full-FOV CACT.

Multiple medications are proven to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), but data regarding personalized approaches to optimize medication dosing remain limited. Current treatment guidelines recommend up-titration to target or maximally tolerated doses of these medications, yet use and dosing remain suboptimal in clinical practice. Body surface area (BSA) is a readily available clinical metric, used for dosing many medications, closely associated with blood pressure, renal function, and vascular congestion, and may influence efficacy, safety, and tolerability of HFrEF medications. In this review, we examine the rationale, strengths/weaknesses, and potential utility of BSA as a means of optimizing HFrEF medication use and dosing.

There has been a worldwide effort to accelerate the development of safe and effective vaccines for severe acute respiratory syndrome coronavirus-2. When vaccines become licensed and available broadly to the public, the final hurdle is equitable distribution and access for all who are recommended for vaccination. Frameworks and existing systems for allocation, distribution, vaccination, and monitoring for safety and effectiveness are assets of the current immunization delivery system that should be leveraged to ensure the equitable distribution and broad uptake of licensed vaccines. The system should be strengthened to address gaps in access to immunization services and to modernize the public health infrastructure. We offer five recommendations as guideposts to ensure that policies and practices at the federal, state, local, and tribal levels support equity, transparency, accountability, availability, and access to coronavirus disease 2019 vaccines.

PurposePatients with peripheral arterial disease (PAD) or critical limb ischemia (CLI) require revascularization. Traditionally, endovascular therapy (EVT) is performed with iodinated contrast agent (ICM), which can provoke potential deterioration in renal function. CO2 is a safe negative contrast agent to guide vascular procedures, but interpretation of CO2 angiography is challenging. Changes in blood flow following iodine-aided EVT are assessable with 2D-perfusion angiography (2D-PA). The aim of this study was to evaluate 2D-PA as a tool to monitor blood flow changes during CO2-aided EVT.Material and Methods2D-PA was performed before and after ten EVTs (nine stents; one endoprosthesis; 10/2012–02/2020) in nine patients (six men; 65 ± 10y) with Fontaine stage IIb (n = 8) and IV (n = 1). A reference ROI (ROIINFLOW) was placed in the artery before the targeted obstruction and a target ROI (ROIOUTFLOW) distally. Corresponding ROIs were used pre- and post-EVT. Time to peak (TTP), peak density (PD) and area under the curve (AUC) were computed. The reference/target ROI ratios (TTPOUTFLOW/TTPINFLOW; PDOUTFLOW/PDINFLOW; AUCOUTFLOW/AUCINFLOW) were calculated.Results2D-PA was technically feasible in all cases. A significant increase of 82% in PDOUTFLOW/PDINFLOW(0.44 ± 0.4 to 0.8 ± 0.63;p = 0.002) and of 132% in AUCOUTFLOW/AUCINFLOW(0.34 ± 0.22 to 0.79 ± 0.59;p = 0.002) was seen. A trend for a decrease in TTPOUTFLOW/TTPINFLOWwas observed (− 24%; 5.57 ± 3.66 s–4.25 ± 1.64 s;p = 0.6).ConclusionThe presented 2D-PA technique facilitates the assessment of arterial flow in CO2-aided EVTs and has the potential to simplify the assessment of immediate treatment response.

Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and β-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function.NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to β-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

Aim. We investigated different bioactive compounds including epigallocatechin gallate (EGCG), anthocyanidin, resveratrol, phloretin, spermidine, butyrate, and β-hydroxybutyrate with regard to their effect on SIRT3 via NRF2 and modulation of the proinflammatory senescence-associated secretory phenotype (SASP) in senescence induced 3T3-L1 preadipocytes. Methods. For induction of senescence, 3T3-L1 preadipocytes were incubated with bromodeoxyuridine (BrdU) for 8 days. Cell cycle inhibition was observed, and β-galactosidase activity was measured. After BrdU treatment, cells were treated with different bioactive compounds in various concentrations for 96 h. ELISA was used for determining proinflammatory cytokine IL6 in SASP cells. Results. CDKN1a increased significantly after BrdU incubation compared to untreated control ( p < 0.01 ). All secondary plant ingredients used for treatment, but not anthocyanidin 50 μM, decrease CDKN1a expression ( p < 0.05 ), whereas most endogenous substances did not attenuate CDKN1a. IL6 secretion positively correlated with CDKN1a ( p < 0.01 ), whereas EGCG could diminish both, IL6 and CDKN1a with the strongest effect ( p < 0.01 ). Although NRF2 positively correlated with SIRT3 activation ( p < 0.05 ), only resveratrol ( p < 0.01 ) and anthocyanidin ( p < 0.05 ) could activate NRF2 significantly. Solely anthocyanidin 50 μM ( p < 0.05 ) and 100 μM ( p < 0.01 ) and EGCG 50 μM ( p < 0.01 ) could increase SIRT3 expression. Activation of SIRT3 with EGCG correlated with lowered IL6 secretion significantly ( p < 0.05 ) but not with anthocyanidin. Conclusion. Accumulation of senescent cells in adipose tissue plays an important role in obesity and age-related diseases. SIRT3, located in the mitochondria, can regulate ROS via different pathways. Thus, targeting SIRT3 activating compounds such as EGCG may delay senescence of cells and senescence induced inflammatory processes.

Key points Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Abstract Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.

Effective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.

Study design Expert Consensus Study. Objectives This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction. Summary of background data Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes. Methods A multidisciplinary panel with 20 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus. Results Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared to antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months. Conclusions Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

Survivors of central nervous system injury commonly present with spastic hypertonia. The affected muscles are hyperexcitable and can display involuntary static muscle tone and an exaggerated stretch reflex. These symptoms affect posture and disrupt activities of daily living. Symptoms are typically measured using subjective manual tests such as the Modified Ashworth Scale; however, more quantitative measures are necessary to evaluate potential treatments. The hands are one of the most common targets for intervention, but few investigators attempt to quantify symptoms of spastic hypertonia affecting the fingers. We present the isometric force pillow (IFP) to quantify involuntary grip force. This lightweight, computerized tool provides a holistic measure of finger flexion force and can be used in various orientations for clinical testing and to measure the impact of assistive devices.

Background: The global spread of SARS-CoV-2 is a serious public health issue. Large-scale surveillance screenings are crucial but can exceed diagnostic test capacities. We optimized test conditions and implemented high throughput pool testing of respiratory swabs into SARS-CoV-2 diagnostics. Methods: In preparation for pool testing, we determined the optimal pooling strategy and pool size, and evaluated aspects of pre-analytics including method and timepoint of sample collection during course of infection. In addition, we measured the impact of vortexing prior to sample processing, compared pipette- and swab-pooling method as well as the sensitivity of three different PCR assays. Findings: Using optimized strategies for pooling, we systematically pooled 16,164 samples in a period of 18 weeks resulting in a reduction of 14,170 PCR reactions. In a low prevalence setting, we defined a preferable pool size of ten in a two-stage hierarchical pool testing strategy. Vortexing of the swab increased cellular yield by a factor of 2·34, and sampling at or shortly after symptom onset by oropharyngeal or combined nasal/oropharyngeal swabs was associated with higher viral loads. By comparing different pooling strategies, pipette-pooling was more efficient compared to swab-pooling. Interpretation: For implementing pooling strategies into high throughput diagnostics, we recommend to apply a pipette-pooling method, using pool sizes of ten samples, performing sensitivity validation of the PCR assays used, and vortexing swabs prior to analyses. Our data shows, that pool testing for SARS-CoV-2 detection is feasible and highly effective in a low prevalence setting. Funding: No external funding was received. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All samples and clinical data were collected on the wards or outpatient departments of the University Hospital of Cologne. No identifying data were used for the patient’s characterization. According to §15 subparagraph 3 (Professional Code for Physicians in Germany) ethical principles of WMA Declaration of Helsinki were respected, and no ethics committee approval and informed consent were necessary for this study.

Background: Neural impairments that follow hemiparetic stroke may negatively affect passive muscle properties, further limiting recovery. However, factors such as hypertonia, spasticity, and botulinum neurotoxin (BoNT), a common clinical intervention, confound our understanding of muscle properties in chronic stroke.Objective: To determine if muscle passive biomechanical properties are different following prolonged, stroke-induced, altered muscle activation and disuse.Methods: Torques about the metacarpophalangeal and wrist joints were measured in different joint postures in both limbs of participants with hemiparetic stroke. First, we evaluated 27 participants with no history of BoNT; hand impairments ranged from mild to severe. Subsequently, seven participants with a history of BoNT injections were evaluated. To mitigate muscle hypertonia, torques were quantified after an extensive stretching protocol and under conditions that encouraged participants to sleep. EMGs were monitored throughout data collection.Results: Among participants who never received BoNT, no significant differences in passive torques between limbs were observed. Among participants who previously received BoNT injections, passive flexion torques about their paretic wrist and finger joints were larger than their non-paretic limb (average interlimb differences = +42.0 ± 7.6SEM Ncm, +26.9 ± 3.9SEM Ncm, respectively), and the range of motion for passive finger extension was significantly smaller (average interlimb difference = −36.3° ± 4.5°SEM; degrees).Conclusion: Our results suggest that neural impairments that follow chronic, hemiparetic stroke do not lead to passive mechanical changes within the wrist and finger muscles. Rather, consistent with animal studies, the data points to potential adverse effects of BoNT on passive muscle properties post-stroke, which warrant further consideration.

Median arcuate ligament syndrome (MALS) is the chronic symptomatic compression of the celiac artery by the median arcuate ligament. A known potential sequela of MALS is celiac artery aneurysm, which could predispose the diseased artery to dissection. However, the presence of celiac artery dissection and MALS is yet to be reported. Here, we present a case of MALS with a coincident celiac artery aneurysm and dissection.

Social exclusion (ostracism) is a major psychosocial factor contributing to the development and persistence of psychiatric disorders and is also related to their social stigma. However, its specific role in different disorders is not evident, and comprehensive social psychology research on ostracism has rather focused on healthy individuals and less on psychiatric patients. Here, we systematically review experimental studies investigating psychological and physiological reactions to ostracism in different responses of psychiatric disorders. Moreover, we propose a theoretical model of the interplay between psychiatric symptoms and ostracism. A systematic MEDLINE and PsycINFO search was conducted including 52 relevant studies in various disorders (some of which evaluated more than one disorder): borderline personality disorder (21 studies); major depressive disorder (11 studies); anxiety (7 studies); autism spectrum disorder (6 studies); schizophrenia (6 studies); substance use disorders (4 studies); and eating disorders (2 studies). Psychological and physiological effects of ostracism were assessed with various experimental paradigms: e.g., virtual real-time interactions (Cyberball), social feedback and imagined scenarios. We critically review the main results of these studies and propose the overall concept of a vicious cycle where psychiatric symptoms increase the chance of being ostracized, and ostracism consolidates or even aggravates psychopathology. However, the specificity and stability of reactions to ostracism, their neurobiological underpinnings, determinants, and moderators (e.g., attachment style, childhood trauma, and rejection sensitivity) remain elusive.

Background Adaptation to aortic valve stenosis leads to myocardial hypertrophy, which has been associated with inflammation, fibrosis and activation of the endocannabinoid system. Since the endocannabinoid system and the CB2 receptor provide cardioprotection and modulate immune response in experimental ischemia, we investigated the role of CB2 in a mouse model of cardiac pressure overload. Methods Transverse aortic constriction was performed in CB2 receptor-deficient (Cnr2−/−) mice and their wild-type littermates (Cnr2+/+). After echocardiography and Millar left heart catheter hemodynamic evaluation hearts were processed for histological, cellular and molecular analyses. Results The endocannabinoid system showed significantly higher anandamide production and CB2 receptor expression in Cnr2+/+ mice. Histology showed non-confluent, interstitial fibrosis with rare small areas of cardiomyocyte loss in Cnr2+/+ mice. In contrast, extensive cardiomyocyte loss and confluent scar formation were found in Cnr2−/− mice accompanied by significantly increased apoptosis and left ventricular dysfunction when compared with Cnr2+/+ mice. The underlying cardiac maladaptation in Cnr2−/− mice was associated with significantly reduced expression of myosin heavy chain isoform beta and less production of heme oxygenase-1. Cnr2−/− hearts presented after 7 days with stronger proinflammatory response including significantly higher TNF-alpha expression and macrophage density, but lower density of CD4+ and B220+ cells. At the same time, we found increased apoptosis of macrophages and adaptive immune cells. Higher myofibroblast accumulation and imbalance in MMP/TIMP-regulation indicated adverse remodeling in Cnr2−/− mice. Conclusions Our study provides mechanistic evidence for the role of the endocannabinoid system in myocardial adaptation to pressure overload in mice. The underlying mechanisms include production of anandamide, adaptation of contractile elements and antioxidative enzymes, and selective modulation of immune cells action and apoptosis in order to prevent the loss of cardiomyocytes.

Several studies have shown high prevalence rates of sleep problems among medical students, including insufficient sleep duration, poor sleep quality, and excessive daytime sleepiness. This review aims to systematically summarize the existing literature on sleep problems among medical students and consequently estimate the prevalence of these disturbances. The MEDLINE, EMBASE, ScienceDirect, and ProQuest Medical databases, the Google Scholar engine, and reference lists of retrieved articles were systematically searched and evaluated for quality. Forty–three studies involving a total of 18,619 students from 13 countries were included in the analyses. Results showed that the mean pooled sleep duration (K = 16, N = 10,512) was 6.3 h per night for medical students, [95% confidence interval (CI) 6.0–6.6]. The results also indicated that 55% [95% CI 48.0%–62.0%] of students reported poor sleep quality (K = 33, N = 15,462) according to the Pittsburgh Sleep Quality Index (PSQI); the mean pooled score of 6.3. Excessive daytime sleepiness (K = 18, N = 5688) was reported by 31.0% [95% CI 24.4%–37.7%] of students according to the Epworth Sleepiness Scale (ESS). Age and gender were not significant moderators for sleep quality or excessive daytime sleepiness. Some differences were obtained between countries, suggesting that cultural values, local conditions, and environment all have an impact on sleep practices and attitudes. Sleep problems are highly prevalent among medical students and are therefore a severe problem. Prevention and intervention programs targeting these are therefore highly recommended for future studies.

Objective The flexion and extension synergies were quantified at the paretic elbow, forearm, wrist, and finger joints within the same group of participants for the first time. Differences in synergy expression at each of the four joints were examined, as were the ways these differences varied across the joints. Methods Twelve post-stroke individuals with chronic moderate-to-severe hemiparesis and six age-matched controls participated. Participants generated isometric shoulder abduction (SABD) and shoulder adduction (SADD) at four submaximal levels to progressively elicit the flexion and extension synergies, respectively. Isometric joint torques and EMG were recorded from shoulder, elbow, forearm (radio-ulnar), wrist, and finger joints and muscles. Results SABD elicited strong wrist and finger flexion torque that increased with shoulder torque level. SADD produced primarily wrist and finger flexion torque, but magnitudes at the wrist were less than during SABD. Findings contrasted with those at the elbow and forearm, where torques and EMG generated due to SABD and SADD were opposite in direction. Conclusions Flexion and extension synergy expression are more similar at the hand than at the shoulder and elbow. Specific bulbospinal pathways that may underlie flexion and extension synergy expression are discussed. Significance Whole-limb behavior must be considered when examining paretic hand function in moderately-to-severely impaired individuals.

Tasks of daily life require the independent use of the arms and hands. Individuals with hemiparetic cerebral palsy (HCP) often experience difficulty with fine motor tasks demonstrating mirrored movements between the arms. In this study, bilateral muscle activations were quantified during single arm isometric maximum efforts and submaximal reaching tasks. The magnitude and direction of mirrored activation was examined in 14 individuals with HCP and 9 age-matched controls. Participants generated maximum voluntary torques (MVTs) in five different directions and completed ballistic reaches while producing up to 80% of shoulder abduction MVT. Electromyography (EMG) signals were recorded from six upper extremity muscles bilaterally. Participants with HCP demonstrated more mirrored activation when volitionally contracting the non-paretic (NP) arm than the paretic arm (F = 83.543, p < 0.001) in isometric efforts. Increased EMG activation during reach acceleration resulted in a larger increase in rest arm co-activation when reaching with the NP arm compared to the paretic arm in the HCP group (t = 8.425, p < 0.001). Mirrored activation is more pronounced when driving the NP arm and scales with effort level. This directionality of mirroring is indicative of the use of ipsilaterally terminating projections of the corticospinal tract (CST) originating in the non-lesioned hemisphere. Peripheral measures of muscle activation provide insight into the descending pathways available for control of the upper extremity after early unilateral brain injury.

In May 2021, the Alpha variant (B.1.1.7) of SARS-CoV-2 was found in 91% of the SARS-CoV-2 cases in Germany. Not much is known about the symptoms, courses of disease, and infectiousness in pediatric patients with the Alpha variant. Objective: The aim of this retrospective analysis was to gain information on the infection with the Alpha variant in children and adolescents. Methods: Between 12 January 2021 and 3 June 2021, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 were included. Data were collected on standardized questionnaires. The analysis of data was anonymized and retrospective. Results: We investigated 3544 NAATs, 95 children were tested positive (2.7%) for SARS-CoV-2. For the sub-analysis, 65 children were analyzed. In 59 children, the Alpha variant was found (90.8%), and 54.2% (n = 32/59) were symptomatic. The most common symptoms were fever, cough, and rhinitis. The median Ct value was 24.0 (min 17.0, max 32.7). Conclusions: We can underline early findings that children are still less effected by SARS-CoV-2 infection with the spread of the Alpha variant. We found no evidence that children infected with the Alpha variant showed more severe symptoms or suffered from a more severe clinical course than those infected with the wild type.

Study Design: Retrospective cohort study. Objectives: The current evidence regarding how level of lumbar pedicle subtraction osteotomy (PSO) influences correction of sagittal alignment is limited. This study sought to investigate the relationship of lumbar level and segmental angular change (SAC) of PSO with the magnitude of global sagittal alignment correction. Methods: This study retrospectively evaluated 53 consecutive patients with adult spinal deformity who underwent lumbar PSO at a single institution. Radiographs were evaluated to quantify the effect of PSO on lumbar lordosis (LL), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), T1-spinopelvic inclination (T1SPI), T1-pelvic alignment (TPA), and sagittal vertical axis (SVA). Results: Significant correlations were found between PSO SAC and the postoperative increase in LL ( r = 0.316, P = .021) and PT ( r = 0.352, P = .010), and a decrease in TPA ( r = −0.324, P = .018). PSO level significantly correlated with change in T1SPI ( r = −0.305, P = .026) and SVA ( r = −0.406, P = .002), with more caudal PSO corresponding to a greater correction in sagittal balance. On multivariate analysis, more caudal PSO level independently predicted a greater reduction in T1SPI (β = −3.138, P = .009) and SVA (β = −29.030, P = .001), while larger PSO SAC (β = −0.375, P = .045) and a greater number of fusion levels (β = −1.427, P = .036) predicted a greater reduction in TPA. Conclusion: This study identified a gain of approximately 3 degrees and 3 cm of correction for each level of PSO more caudal to L1. Additionally, a larger PSO SAC predicted greater improvement in TPA. While further investigation of these relationships is warranted, these findings may help guide preoperative PSO level selection.

Background While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients. Methods 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. Findings We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms. Interpretation The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19. Funding COVIM:„NaFoUniMedCovid19"(FKZ: 01KX2021)

A muscle’s structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. We combined in vivo imaging methods (second-harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-suppression MRI) to quantify functionally meaningful architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number (SSN) and physiological cross-sectional area (PCSA) were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. The interlimb differences in SSN and PCSA were significantly larger for stroke participants than for participants without stroke (P = 0.0126 and P = 0.0042, respectively), suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. The paretic biceps brachii had ∼8,200 fewer serial sarcomeres and ∼2 cm(2) smaller PCSA on average than the contralateral limb (both P < 0.0001). This was manifested by substantially smaller muscle volumes (112 versus 163 cm(3)), significantly shorter fascicles (11.0 versus 14.0 cm; P < 0.0001), and comparable sarcomere lengths (3.55 versus 3.59 μm; P = 0.6151) between limbs. Most notably, this study provides direct evidence of the loss of serial sarcomeres in human muscle observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments.

OBJECTIVES Cardiac biomarkers are indicators of irreversible cell damage. Current myocardial infarction (MI) definitions require concomitant clinical characteristics. For perioperative MI, a correlation of biomarker elevations and mortality has been suggested. Definitions emerged relying on cardiac biomarker release only. This approach is questionable as several clinical and experimental scenarios exist where relevant biomarker release can occur apart from MI. METHODS We reviewed the clinical and basic science literature and revealed important aspects regarding the use and interpretation of cardiac biomarker release with special focus on their interpretation in the perioperative setting. RESULTS Ischaemic biomarkers may be released without cell death in multiple conditions, such as after endurance runs in athletes, temporary inotropic stimulation in animal models and flow variations in in vitro cell models. In addition, access through atrial tissue during cannulation or concomitant valve procedures adds sources of enzyme release that may not be related to ventricular ischaemia (i.e. MI). Such non-cell death-related mechanisms may explain the lack of poor correlations of enzyme release and long-term outcomes in recent trials. In addition, the 3 main biomarkers, troponin T, I and creatine kinase myocardial band, differ in their release kinetics, which may differentially trigger MI events in trial patients. CONCLUSIONS The identification of irreversible myocardial injury in cardiac surgery based only on biomarker release is unreliable. Cell death- and non-cell death-related mechanisms create a mix in the perioperative setting that requires additional markers for proper identification of MI. In addition, the 3 most common ischaemic biomarkers display different release kinetics adding to the confusion. We review the topic.

Aging is a natural process that causes alterations in the neuromuscular system, which contribute to weakness and reduced quality of life. Reduced firing rates of individual motor units (MUs) likely contribute to weakness, but the mechanisms underlying reduced firing rates are not clear. Persistent inward currents (PICs) are crucial for the initiation, gain control, and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since the concentration of monoamines (i.e. serotonin and norepinephrine) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (P = 0.0292), and ΔF was reduced by ~1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted ΔF in older adults (P = 0.0261), resulting in a reduction of ~1pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in older adults, and, further, age is a significant predictor of estimates of PICs in older adults. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and weakness in older individuals.KEY POINTSPersistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem.During aging, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons.Here we show that estimates of persistent inward currents (ΔF) of both elbow flexor and extensor motor units are reduced in older adults.Estimates of persistent inward currents have a negative relationship with age in the older adults, but not young.This novel mechanism may play a role in alteration motor firing rates that occurs with aging, which may have consequences for motor control.

Myotonic Dystrophy type 1 (DM1) is multi-systemic muscular dystrophy, affecting 1 in 3000 people, characterized by muscle wasting, myotonia, cardiac and gastrointestinal abnormalities and cognitive impairment, among other symptoms. DM1 is caused by a (CTG)n repeat expansion in the 3’ UTR of the ubiquitously expressed gene DMPK. The (CUG)n containing RNAs resulting from the transcription of this diseased DMPK gene aggregate in the nucleus, forming foci which sequester muscleblind-like (MBNL) family proteins, a group of splicing factors that play significant roles in the juvenile-to-adult development of many tissues. Recent studies show that DM1 patients have increased susceptibility toward glucose intolerance, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome. Furthermore, DM1 patients are abnormally sensitive to a wide range of analgesics and anesthetics, with complications ranging from prolonged anesthesia recovery to heightened pulmonary dysfunction. These findings suggest a predisposition for liver damage and dysfunction in DM1 patients; however, this possibility has gone uninvestigated. To understand the effects of DM1 in the liver, we generated a hepatocyte-specific DM1 mouse model in which we can induce the expression of CUG containing RNA, specifically in the liver. Through these mice, we demonstrate that the expression of the toxic RNA in hepatocytes sequesters MBNL proteins, causing a reduction in mature hepatocellular activity, however, we find that, in contrast to other tissues, loss of MBNL1 activity only reproduces a small portion of the transcriptome changes in DM1 afflicted hepatocytes. We characterized the transcriptomic changes driven by DM1 in the liver and show that these lead to changes in hepatocellular morphology, inflammation, and necrosis, as well as excessive lipid accumulation and fatty liver disease. We further demonstrate that DM1 mice livers are defective in drug metabolism and clearance, and when challenged, exhibit marked impairment against zoxazolamine-induced paralysis and acetaminophen-induced hepatotoxicity. Together, these results reveal that the expression of CUG repeat containing RNA disrupts the normal hepatic functions and predisposes the liver to injury, fatty liver disease, and drug clearance pathologies that may jeopardize the health of DM1 patients and complicate the treatment of DM1.

BackgroundWhile the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalization. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence we focus on mild COVID-19 in non-hospitalized patients.MethodsWe included 958 patients with confirmed SARS-CoV-2 infection in this study. Patients were observed for seven months from April 6thto December 2nd2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarized presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model.FindingsWe observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8.6% (38/442) of patients presented with shortness of breath, 12.4% (55/442) with anosmia, 11.1% (49/442) with ageusia and 9.7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27.8% (123/442) and 34.8% (123/353) at month 4 and 7 post-infection, respectively. This corresponds to 12.8% patients with long-lasting symptoms relative to the initial total cohort (123/958). A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk to develop long-term symptoms.InterpretationThe on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalized patients was observed at four and seven months post-infection and summarized as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19.FundingCOVIM:„NaFoUniMedCovid19”(FKZ: 01KX2021)Research in contextEvidence before this studyData about long-term health consequences after SARS-CoV-2 infection and COVID-19 is scarce and most available data describe health consequences in hospitalized patients during acute COVID-19. However, these studies do not take into account the vast majority of patients with a milder course of infection (WHO score1-3).Added value of this studyOur cohort consists of mostly mild COVID-19 cases that have been prospectively followed for a median time of 6.8 months. At least one trained physician critically reviewed the patients’ reported symptoms at each visit. We assessed SARS-CoV-2 IgG at each visit to correlate reported symptoms with serological data. At 4 months after SARS-CoV-2 infection, shortness of breath occurred in 8.6% (38/442), anosmia in 12.4% (55/442), ageusia in 11.1% (49/442), and fatigue in 9.7% (43/442) of patients. At least one characteristic symptom was present in 27.8% (123/442) and 34.8% (123/353) at months 4 and 7 post-infection, respectively. Symptoms were summarized as post-COVID syndrome (PCS). Relative to our initial total cohort (123/958), this corresponds to 12.8% patients with long-lasting symptoms. Lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk of developing long-term symptoms.Implications of all available evidenceWe believe that our findings have important implications for the fields of infectious diseases and public health, because we show long-term health consequences may occur even after very mild COVID-19 in the outpatient setting. As up to 81% of all SARS-CoV-2 infected patients present with mild disease, it can be expected that PCS will affect a larger number of individuals than initially assumed, posing major medical, social and economic challenges.

Chemosaturation percutaneous hepatic perfusion (CS-PHP) allows selective intrahepatic delivery of high dose cytotoxic melphalan in patients with curatively untreatable liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. Aim of this study was to investigate the response to therapy, survival and safety of the CS-PHP procedure in patients with liver-dominant metastatic uveal melanoma (UM). Overall response rate (ORR) and disease control rate (DCR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic progression-free survival (mhPFS) were analyzed using Kaplan-Meier estimation. Adverse events were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5. Overall, 30 patients were treated with 70 CS-PHP in a salvage setting from October 2014 to January 2019. In total, ORR and DCR were 42.3 % and 80.8 %, respectively. Overall, mOS was 12 (95 % confidence interval (CI) 7-15) months, and both, mPFS and mhPFS were 6 months, respectively (95 % CI 4-10; 95 % CI 4-13). Adverse events (AE) most frequently included significant but transient hematologic toxicities (87 % of grade 3/4 thrombocytopenia), less frequent AEs were hepatic injury extending to liver failure (3 %), cardiovascular events including one case of ischemic stroke (3 %). Salvage treatment with CS-PHP is effective in selected patients with UM. The interventional procedure is safe. Serious hepatic and cardiovascular events, although rare, require careful patient selection and should be closely monitored. · CS-PHP is safe for selected patients with liver-dominant metastatic uveal melanoma.. · CS-PHP resulted in hepatic disease control in 80 % of patients.. · Hematologic events following CS-PHP are common but manageable..· Dewald CL, Hinrichs JB, Becker LS et al. Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma. Fortschr Röntgenstr 2021; 193: 928 - 936.ZIEL: Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit. · CS-PHP ist eine sichere Behandlungsform für selektierte Patienten mit hepatisch metastasiertem Aderhautmelanom.. · CS-PHP führte bei 80 % der Patienten zu einer intrahepatischen Krankheitsstabilisierung.. · Hämatologische Nebenwirkungen nach CS-PHP sind häufig, aber therapierbar..· Dewald CL, Hinrichs JB, Becker LS et al. Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma. Fortschr Röntgenstr 2021; 193: 928 – 936.

Objectives The aims of this study were to evaluate the isolated prevalence of real-time reverse transcriptase-polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 on the ocular surface without systemic infection in hospitalized asymptomatic patients and to determine the risk for ophthalmologists and medical staff to be infected by prescreened asymptomatic patients in a tertiary eye care center. Methods In this prospective, observational study, bilateral swaps of the conjunctiva in the lower fornices as well as nasopharyngeal swaps were collected in 1145 hospitalized asymptomatic patients of a tertiary eye care center. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for each swap to evaluate the prevalence of SARS-CoV-2. Demographic data and potential risk factors for an isolated infection of the ocular surface were noted. Results Two thousand two hundred eighty-eight (99.9%) of all 2290 tested eyes had negative results in the RT-PCR analysis of the conjunctival swabs. One patient had bilateral false-positive results in the conjunctival swabs. None of the 1145 patients had any positive RT-PCR-confirmed result in the nasopharyngeal swabs. Conclusions The risk for an isolated conjunctival viral activity in patients with a negative nasopharyngeal swab-based RT-PCR seems to be absent or extremely low, suggesting no need to perform additional conjunctival swabs in patients with negative nasopharyngeal swabs. Furthermore, the risk of a work-related SARS-CoV-2 infection due to direct contact with preselected asymptomatic patients in an eye care center is very low, especially when additional hygiene standards and safe distances are respected carefully. This might reassure medical staff and reduce the fear of SARS-CoV-2 infection.

EClinicalMedicine 39, 101082 (2021). doi:10.1016/j.eclinm.2021.101082, Published by Elsevier, Amsterdam

A hallmark impairment in a hemiparetic stroke is a loss of independent joint control resulting in abnormal co-activation of shoulder abductor and elbow flexor muscles in their paretic arm, clinically known as the flexion synergy. The flexion synergy appears while generating shoulder abduction (SABD) torques as lifting the paretic arm. This likely be caused by an increased reliance on contralesional indirect motor pathways following damage to direct corticospinal projections. The assessment of functional connectivity between brain and muscle signals, i.e., brain-muscle connectivity (BMC), may provide insight into such changes to the usage of motor pathways. Our previous model simulation shows that multi-synaptic connections along the indirect motor pathway can generate nonlinear connectivity. We hypothesize that increased usage of indirect motor pathways (as increasing SABD load) will lead to an increase of nonlinear BMC. To test this hypothesis, we measured brain activity, muscle activity from shoulder abductors when stroke participants generate 20% and 40% of maximum SABD torque with their paretic arm. We computed both linear and nonlinear BMC between EEG and EMG. We found dominant nonlinear BMC at contralesional/ipsilateral hemisphere for stroke, whose magnitude increased with the SABD load. These results supported our hypothesis and indicated that nonlinear BMC could provide a quantitative indicator for determining the usage of indirect motor pathways following a hemiparetic stroke.

Hemiparetic stroke in adulthood often results in the grouped movement pattern of the upper extremity flexion synergy thought to arise from an increased reliance on cortico-reticulospinal pathways due to a loss of lateral corticospinal projections. It is well established that the flexion synergy induces reaching constraints in individuals with adult-onset hemiplegia. The expression of the flexion synergy in individuals with brain injuries onset earlier in the lifespan is currently unknown. An early unilateral brain injury occurring prior to six months post full-term may preserve corticospinal projections which can be used for independent joint control and thus minimizing the expression of the flexion synergy. This study uses kinematics of a ballistic reaching task to evaluate the expression of the flexion synergy in individuals with pediatric hemiplegia (PH) ages six to seventeen years. Fifteen individuals with brain injuries before birth (n = 8) and around full-term (n = 7) and nine age-matched controls with no known neurological impairment completed a set of reaches in an admittance controlled robotic device. Descending drive, and the possible expression of the upper extremity flexion synergy, was modulated by increasing shoulder abduction loading. Individuals with early-onset PH achieved lower peak velocities when reaching with the paretic arm compared to controls; however, no differences in reaching distance were found between groups. Relative maintenance in reaching seen in individuals with early brain injuries highlights minimal expression of the flexion synergy. We interpret this conservation of independent control of the paretic shoulder and elbow as the use of more direct corticospinal projections instead of indirect cortico-reticulospinal pathways used in individuals with adult-onset hemiplegia.

After a hemiparetic stroke, the contralesional upper limb is left with significant motor impairments including: weakness, spasticity, and abnormal joint torque patterns resulting in the flexion synergy (i.e. abnormal coupling between shoulder abduction and elbow/wrist and finger flexion). These impairments, and in particular the flexion synergy, limit ability to reach to the full extent of their limb workspace. Motor control of the trunk is also altered post stroke, with compromised ability to stabilize the trunk and excessive trunk movement during reaching, abnormal isometric torque coupling patterns in the transverse and sagittal planes and weakness. These motor impairments in both trunk and arm limit their ability to perform activities of daily living. While the effect of stroke on reaching has been studied extensively, less is known about the impact of deficits in trunk motor control on reaching ability and the impact of the flexion synergy on trunk postural control. Methods for investigating altered trunk control, specifically during a reach when concurrent loads that elicit the flexion synergy are imposed on the limb and trunk, are limited. Specifically, trunk deficits have yet to be studied in the context of the flexion synergy whereby loads imposed on the arm to elicit shoulder abduction have a negative impact on reaching and potentially on trunk posture. In order to address this gap, we developed a system that integrates a robotic device to simulate varied reaching environments, surface electromyography to measure primary trunk and arm muscle activity, and a two-camera motion capture system that uses reflective markers to measure trunk and arm movement. Feasibility and usability of the system was established during evaluation of reaching ability with varying levels of shoulder abduction loads while the trunk is either restrained or unrestrained in two participants with stroke and a healthy control.Clinical Relevance— The system presented here is capable of monitoring changes in trunk postural control after a hemiparetic stroke during a reaching task as a first step in furthering our understanding of changes in trunk motor control during reaching with the goal of developing more targeted and effective interventions for stroke rehabilitation.

Cardiac surgery and subsequent treatment in the intensive care unit (ICU) has been shown to be associated with functional decline, especially in elderly patients. Due to the different assessment tools and assessment periods, it remains yet unclear what parameters determine unfavorable outcomes. This study sought to identify risk factors during the entire perioperative period and focused on the decline in activity of daily living (ADL) half a year after cardiac surgery. Follow-ups of 125 patients were available. It was found that in the majority of patients (60%), the mean ADL declined by 4.9 points (95% CI, &minus, 6.4 to &minus, 3.5, p &lt, 0.000). In the &ldquo, No decline&rdquo, group, the ADL rose by 3.3 points (2.0 to 4.6, 0.001). A multiple regression analysis revealed that preoperative cognitive impairment (MMSE &le, 26, Exp(B) 2.862 (95%CI, 1.192&ndash, 6.872), p = 0.019) and duration of postoperative delirium &ge, 2 days (Exp(B) 3.534 (1.094&ndash, 11.411), p = 0.035) was independently associated with ADL decline half a year after the operation and ICU. Of note, preoperative ADL per se was neither associated with baseline cognitive function nor a risk factor for functional decline. We conclude that the preoperative assessment of cognitive function, rather than functional assessments, should be part of risk stratification when planning complex cardiosurgical procedures.

Study Design: Retrospective case series. Objective: The purpose of this study is to evaluate the clinical and radiographic outcomes following revision surgery following Harrington rod instrumentation. Methods: Patients who underwent revision surgery with a minimum of 1-year follow-up for flatback syndrome following Harrington rod instrumentation for adolescent idiopathic scoliosis were identified from a multicenter dataset. Baseline demographics and intraoperative information were obtained. Preoperative, initial postoperative, and most recent spinopelvic parameters were compared. Postoperative complications and reoperations were subsequently evaluated. Results: A total of 41 patients met the inclusion criteria with an average follow-up of 27.7 months. Overall, 14 patients (34.1%) underwent a combined anterior-posterior fusion, and 27 (65.9%) underwent an osteotomy for correction. Preoperatively, the most common lower instrumented vertebra (LIV) was at L3 and L4 (61%), whereas 85% had a LIV to the pelvis after revision. The mean preoperative pelvic incidence–lumbar lordosis mismatch and C7 sagittal vertical axis were 23.7° and 89.6 mm. This was corrected to 8.1° and 28.9 mm and maintained to 9.04° and 34.4 mm at latest follow-up. Complications included deep wound infection (12.2%), durotomy (14.6%), implant related failures (14.6%), and temporary neurologic deficits (22.0%). Eight patients underwent further revision surgery at an average of 7.4 months after initial revision. Conclusions: There are multiple surgical techniques to address symptomatic flatback syndrome in patients with previous Harrington rod instrumentation for adolescent idiopathic scoliosis. At an average of 27.7 months follow-up, pelvic incidence–lumbar lordosis mismatch and C7 sagittal vertical axis can be successfully corrected and maintained. However, complication and reoperation rates remain high.

To evaluate feasibility, frequency and severity of peri-procedural complications and post-procedural adverse events (AEs) in patients with advanced cholangiocarcinoma or liver metastasis of uveal melanoma and prior hemihepatectomy undergoing chemosaturation percutaneous hepatic perfusion (CS-PHP) and to analyze therapy response and overall survival compared to a matched group without prior surgery. CS-PHP performed between 10/2014 and 02/2018 were retrospectively assessed. To determine peri-procedural safety and post-procedural adverse events, hospital records and hematological, hepatic and biliary function were categorized using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (1–5; mild-death). Significance was tested using Wilcoxon signed-rank and Mann–Whitney U test. Kaplan–Meier estimation and log-rank test assessed survival. Overall 21 CS-PHP in seven patients (4/7 males; 52 ± 10 years) with hemihepatectomy (grouphemihep) and 22 CS-PHP in seven patients (3/7 males; 63 ± 12 years) without prior surgery (groupnoresection) were included. No complications occurred during the CS-PHP procedures. Transient changes (CTCAE grade 1–2) of liver enzymes and blood cells followed all procedures. In comparison, grouphemihep presented slightly more AEs grade 3–4 (e.g. thrombocytopenia in 57% (12/21) vs. 41% (9/22; p = 0.37)) 5–7 days after CS-PHP. These AEs were self-limiting or responsive to treatment (insignificant difference of pre-interventional to 21–45 days post-interventional values (p > 0.05)). One patient in grouphemihep with high tumor burden died eight days following CS-PHP. No deaths occurred in groupnoresection. In comparison, overall survival after first diagnosis was insignificantly shorter in groupnoresection (44.7(32–56.1) months) than in grouphemihep (48.3(34.6–72.8) months; p = 0.48). The severity of adverse events following CS-PHP in patients after hemihepatectomy was comparable to a matched group without prior liver surgery. Thus, the performance of CS-PHP is not substantially compromised by a prior hemihepatectomy.

Successful execution of daily activities requires accurate perception of the torques one generates about multiple joints. Even so, previous studies are mostly limited to an individual’s perception when torques are generated about a single joint. Consequently, this study investigates how accurately individuals judge torques at their arm during a multi-joint task. The accuracy of fifteen right-hand dominant participants (age: 60 ± 10 years) in matching isometric elbow torques, within the same arm, was quantified during single- and/or multi-joint tasks. Participants generated and matched elbow torques when the shoulder was: (1) not abducted (single-to-single-joint), (2) abducted (multi-to-multi-joint), and (3) abducted and then not abducted (multi-to-single-joint). The constant error for the multi-to-single-joint condition (dominant: 6.9 ± 5.9 Nm, non-dominant: 6.0 ± 5.5 Nm) was greater than that for the single-to-single-joint condition (dominant: 2.7 ± 3.1 Nm, non-dominant: 3.4 ± 2.8 Nm) (p < 0.001) and multi-to-multi-joint condition (dominant: 3.0 ± 2.8 Nm, non-dominant: 3.9 ± 2.7 Nm) (p < 0.001). The constant error for the multi-to-multi-joint condition did not significantly differ from that of the single-to-single-joint condition (p $$=$$ = 0.780). Findings indicate that in older adults the perception of a self-generated torque during a 2-degree-of-freedom (DOF), multi-joint task is largely influenced by the motor commands associated with the 2-DOF task and is not specific to the DOF at each joint.

Background: Information regarding the treatment of high-grade spondylolisthesis (HGS) in adults has been previously described; however, previous descriptions of the evaluation and surgical management of HGS do not represent more recent and now established approaches. The purpose of the current review is to discuss current concepts in the evaluation and management of patients with HGS. Methods: Literature review. Results: HGS is diagnosed in up to 11.3% of adults with spondylolisthesis and typically presents as nonspecific lower back pain. Regarding evaluation, a thorough history and physical examination should be performed, which may help predict the presence of HGS. Diagnostic imaging, and specifically the use of spino-pelvic parameters, are now commonly implicated in guiding treatment course and prognosis. When surgical intervention is indicated, surgical approaches include in situ fusion variations, reduction and partial reduction with fusion, and vertebrectomy. Although the majority of studies suggest improvements with these approaches, the literature is limited by a low level of evidence with regards to the superiority of one technique when compared with others. Conclusions: HGS is a unique cause of low back pain in adults that carries considerable morbidity, but rarely presents with neurologic symptoms. Although the definitions, classifications, and methods of diagnosis of this spinal deformity have been established and accepted, the ideal surgical management of this deformity remains highly debated. Fusion in situ techniques are often technically easier to perform and provide lower risk of neurologic complications, whereas reduction and fusion techniques offer greater restoration of global spino-pelvic balance. Preoperative spino-pelvic parameters may have utility in assisting in procedural selection; however, future, higher-quality and longer-term studies are warranted to determine the optimal surgical intervention among the widely available techniques currently used, and to better define the indications for these interventions.

Muscle tissue is prone to changes in composition and architecture following stroke. Changes in muscle tissue of the extremities are thought to increase passive muscle stiffness and joint impedance. These effects likely compound neuromuscular impairments exacerbating movement function. Unfortunately, conventional rehabilitation is devoid of quantitative measures yielding to subjective assessment of passive joint mobility and end feel. Shear wave ultrasound elastography is a conventional tool used by ultrasonographers that may be readily available for use in the rehabilitation setting as a quantitative measure, albeit at the muscle-tissue level, filling the gap. To support this postulation, we evaluated thecriterionvalidity of shear wave ultrasound elastography of the biceps brachii by investigating the relationship to a laboratory-based criterion measure for quantifying elbow joint impedance in individuals with moderate to severe chronic stroke. Measurements were performed under passive conditions at seven positions spanning the arc of elbow joint extension in both arms of twelve individuals with hemiparetic stroke. Surface electromyography was utilized for threshold-based confirmation of muscle quiescence. A significant moderate relationship was identified near end range of elbow extension and all metrics were greater in the paretic arm. Data supports the progression toward clinical application of shear wave ultrasound elastography in evaluating altered muscle mechanical properties in stroke stipulating the confirmation of muscle quiescence. Considering the lack of bedside robotics in clinical practice, shear wave ultrasound elastography will likely augment the conventional method of manually testing joint mobility. Tissue-level measurement may also assist in identifying new therapeutic targets for patient-specific impairment-based interventions.New & NoteworthyMethods for quantifying passive (non-reflex mediated) joint mobility are absent in stroke rehabilitation. Rehabilitation specialists are left to subjective assessment of the impact on function. Here, we compare the application of shear wave ultrasound elastography for estimating mechanical properties of muscle with a robotic method (criterion measure) of measuring passive elbow extension joint impedance. Data support the clinical application of shear wave ultrasound elastography, especially with the absence of bedside robotics.