Treatment of chronic or relapsing COVID-19 in immunodeficiency.

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.

Innate-like Gene Expression of Lung-Resident Memory CD8+ T Cells during Experimental Human Influenza: A Clinical Study.

Rationale: Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection. Objectives: To investigate the kinetics, phenotypes, and function of influenza virus-specific CD8+ resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection in vivo. Methods: Healthy volunteers, aged 18-55, were inoculated intranasally with influenza A/California/4/09(H1N1). Blood, upper airway, and (in a subgroup) lower airway samples were obtained throughout infection. Symptoms were assessed by using self-reported diaries, and the nasal viral load was assessed by using quantitative PCR. T-cell responses were analyzed by using a three-color FluoroSpot assay, flow cytometry with MHC I-peptide tetramers, and RNA sequencing, with candidate markers being confirmed by using the immunohistochemistry results for endobronchial biopsy specimens. Measurements and Main Results: After challenge, 57% of participants became infected. Preexisting influenza-specific CD8+ T cells in blood correlated strongly with a reduced viral load, which peaked at Day 3. Influenza-specific CD8+ T cells in BAL fluid were highly enriched and predominantly expressed the Trm markers CD69 and CD103. Comparison between preinfection CD8+ T cells in BAL fluid and blood by using RNA sequencing revealed 3,928 differentially expressed genes, including all major Trm-cell markers. However, gene set enrichment analysis of BAL-fluid CD8+ T cells showed primarily innate cell-related pathways and, during infection, included upregulation of innate chemokines (Cxcl1, Cxcl10, and Cxcl16) that were also expressed by CD8+ cells in bronchial tissues. Conclusions: CD8+ Trm cells in the human lung display innate-like gene and protein expression that demonstrates blurred divisions between innate and adaptive immunity. Clinical study registered with www.clinicaltrials.gov (NCT02755948).

'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19.

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.

COVID-19: a retrospective cohort study with focus on the over-80s and hospital-onset disease.

BACKGROUND: Data from the UK COVID-19 outbreak are emerging, and there are ongoing concerns about a disproportionate effect on ethnic minorities. There is very limited information on COVID-19 in the over-80s, and the rates of hospital-onset infections are unknown. METHODS: This was a retrospective cohort study from electronic case records of the first 450 patients admitted to our hospital with PCR-confirmed COVID-19, 77% of the total inpatient caseload to date. Demographic, clinical and biochemical data were extracted. The primary endpoint was death during the index hospital admission. The characteristics of all patients, those over 80 years of age and those with hospital-onset COVID-19 were examined. RESULTS: The median (IQR) age was 72 (56, 83), with 150 (33%) over 80 years old and 60% male. Presenting clinical and biochemical features were consistent with those reported elsewhere. The ethnic breakdown of patients admitted was similar to that of our underlying local population. Inpatient mortality was high at 38%. Patients over 80 presented earlier in their disease course and were significantly less likely to present with the typical features of cough, breathlessness and fever. Cardiac co-morbidity and markers of cardiac dysfunction were more common, but not those of bacterial infection. Mortality was significantly higher in this group (60% vs 28%, p < 0.001). Thirty-one (7%) patients acquired COVID-19 having continuously been in hospital for a median of 20 (14, 36) days. The peak of hospital-onset infections occurred at the same time as the overall peak of admitted infections. Despite being older and more frail than those with community-onset infection, their outcomes were no worse. CONCLUSIONS: Inpatient mortality was high, especially among the over-80s, who are more likely to present atypically. The ethnic composition of our caseload was similar to the underlying population. While a significant number of patients acquired COVID-19 while already in hospital, their outcomes were no worse.

Physical fitness training for stroke patients.

BACKGROUND: Levels of physical activity and physical fitness are low after stroke. Interventions to increase physical fitness could reduce mortality and reduce disability through increased function. OBJECTIVES: The primary objectives of this updated review were to determine whether fitness training after stroke reduces death, death or dependence, and disability. The secondary objectives were to determine the effects of training on adverse events, risk factors, physical fitness, mobility, physical function, health status and quality of life, mood, and cognitive function. SEARCH METHODS: In July 2018 we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and four additional databases. We also searched ongoing trials registers and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses and assessed the quality of the evidence using the GRADE approach. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 75 studies, involving 3017 mostly ambulatory participants, which comprised cardiorespiratory (32 studies, 1631 participants), resistance (20 studies, 779 participants), and mixed training interventions (23 studies, 1207 participants). Death was not influenced by any intervention; risk differences were all 0.00 (low-certainty evidence). There were few deaths overall (19/3017 at end of intervention and 19/1469 at end of follow-up). None of the studies assessed death or dependence as a composite outcome. Disability scores were improved at end of intervention by cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% CI 0.19 to 0.84; 8 studies, 462 participants; P = 0.002; moderate-certainty evidence) and mixed training (SMD 0.23, 95% CI 0.03 to 0.42; 9 studies, 604 participants; P = 0.02; low-certainty evidence). There were too few data to assess the effects of resistance training on disability. Secondary outcomes showed multiple benefits for physical fitness (VO2 peak and strength), mobility (walking speed) and physical function (balance). These physical effects tended to be intervention-specific with the evidence mostly low or moderate certainty. Risk factor data were limited or showed no effects apart from cardiorespiratory fitness (VO2 peak), which increased after cardiorespiratory training (mean difference (MD) 3.40 mL/kg/min, 95% CI 2.98 to 3.83; 9 studies, 438 participants; moderate-certainty evidence). There was no evidence of any serious adverse events. Lack of data prevents conclusions about effects of training on mood, quality of life, and cognition. Lack of data also meant benefits at follow-up (i.e. after training had stopped) were unclear but some mobility benefits did persist. Risk of bias varied across studies but imbalanced amounts of exposure in control and intervention groups was a common issue affecting many comparisons. AUTHORS' CONCLUSIONS: Few deaths overall suggest exercise is a safe intervention but means we cannot determine whether exercise reduces mortality or the chance of death or dependency. Cardiorespiratory training and, to a lesser extent mixed training, reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve fitness, balance and the speed and capacity of walking. The magnitude of VO2 peak increase after cardiorespiratory training has been suggested to reduce risk of stroke hospitalisation by ˜7%. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription, the range of benefits and any long-term benefits.

Return to Employment After Stroke in Young Adults: How Important Is the Speed and Energy Cost of Walking?

Background and Purpose- A quarter of individuals who experience a stroke are under the age of 65 years (defined as young adults), and up to 44% will be unable to return to work poststroke, predominantly because of walking difficulties. No research study has comprehensively analyzed walking performance in young adult's poststroke. The primary aim of this study is to investigate how a stroke in young adults affects walking performance (eg, walking speed and metabolic cost) compared with healthy age-matched controls. The secondary aim is to determine the predictive ability of walking performance parameters for return to employment poststroke. Methods- Forty-six individuals (18-40 years: n=6, 41-54 years: n=21, 55-65 years: n=19) who have had a stroke and 15 healthy age-matched able-bodied controls were recruited from 6 hospital sites in Wales, United Kingdom. Type, location, cause of stroke, and demographic factors (eg, employment status) were recorded. Temporal and spatial walking parameters were measured using 3-dimensional gait analysis. Metabolic energy expenditure and metabolic cost of walking were captured during 3 minutes of walking at self-selected speed from measurements of oxygen consumption. Results- Stroke participants walked slower (P<0.004) and less efficiently (P<0.002) than the controls. Only 23% of stroke participants returned to employment poststroke. Walking speed was the strongest predictor (sensitivity, 0.90; specificity, 0.82) for return to work (P=0.004) with a threshold of 0.93 m/s identified: individuals able to walk faster than 0.93 m/s were significantly more likely to return to work poststroke than those who walked slower than this threshold. Conclusions- This study is the first to capture walking performance parameters of young adults who have had a stroke and identifies slower and less efficient walking. Walking speed emerged as the strongest predictor for return to employment. It is recommended that walking speed be used as a simple but sensitive clinical indicator of functional performance to guide rehabilitation and inform readiness for return to work poststroke.

Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways.

Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1ß and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myeloid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb.

Nasosorption as a Minimally Invasive Sampling Procedure: Mucosal Viral Load and Inflammation in Primary RSV Bronchiolitis.

Background: Existing respiratory mucosal sampling methods are flawed, particularly in a pediatric bronchiolitis setting. Methods: Twenty-four infants with bronchiolitis were recruited: 12 were respiratory syncytial virus (RSV)-positive, 12 were RSV-negative. Infants were sampled by nasosorption and nasopharyngeal aspiration (NPA). Results: Nasosorption was well tolerated and identified all RSV+ samples. RSV load measured by nasosorption (but not NPA) correlated with length of hospital stay (P = .04) and requirement for mechanical ventilation (P = .03). Nasosorption (but not NPA) levels of interferon γ, interleukin 1ß, CCL5/RANTES, and interleukin 10 (IL-10) were elevated in RSV+ bronchiolitis (all P < .05), furthermore CCL5 and IL-10 correlated with RSV load (P < .05). Conclusions: Nasosorption allowed measurement of RSV load and the mucosal inflammatory response in infants.

Temporal Spatial and Metabolic Measures of Walking in Highly Functional Individuals With Lower Limb Amputations.

OBJECTIVE: To record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses, and after completion of comprehensive rehabilitation compared with able-bodied persons. DESIGN: Cross-sectional. SETTING: Multidisciplinary comprehensive rehabilitation center. PARTICIPANTS: Severely injured UK military personnel with amputation and subsequent completion of their rehabilitation program (n=30; unilateral transtibial: n=10, unilateral transfemoral: n=10, and bilateral transfemoral: n=10) were compared with able-bodied persons (n=10) with similar age, height, and mass (P>.537). Total number of participants (N = 40). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at a self-selected speed. RESULTS: The individuals with amputation were all men, with a mean age of 29±4 years and a mean New Injury Severity Score of 31±16. Walking speed, stride length, step length, and cadence of individuals with a unilateral transtibial or transfemoral amputation were comparable with able-bodied persons, and only individuals with a bilateral transfemoral amputation had a significantly slower walking speed (1.12m/s, P=.025) and reduced cadence (96 steps per minute, P=.026). Oxygen cost for individuals with a unilateral transtibial amputation (0.15mL/kg/m) was the same as for able-bodied persons (0.15mL/kg/m) and significantly increased by 20% (0.18mL/kg/m, P=.023) for unilateral transfemoral amputation and by 60% (0.24mL/kg/m, P<.001) for bilateral transfemoral individuals with amputation. CONCLUSIONS: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable with a small number of studies reporting similar outcomes for individuals with a unilateral transtibial amputation, but the results from this study are better than those on individuals with transfemoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation program. This suggests that such a program may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve.

Assessment of urine drug screen utility at autopsy to predict laboratory postmortem blood toxicology.

When faced with increasing drug-related deaths and decline in practicing forensic pathologists, the need to quickly identify toxicology-related deaths is evident in order to appropriately triage cases and expedite turnaround times. Lateral flow immunoassays conducted pre-autopsy offer quick urine drug screen (UDS) results in minutes and are used to inform the need for autopsy. Over 1000 medicolegal cases were reviewed to compare UDS results to laboratory enzyme-linked immunosorbent assay (ELISA) blood results to evaluate how well autopsy UDS predicted laboratory findings. Mass spectral analysis was performed on ELISA-positive specimens and these data were used to investigate UDS false-negative (FN) results when possible. Five different UDS devices (STAT One Step Drug of Abuse dip card and cassette, Premiere Biotech multi-drug and fentanyl dip cards and ATTEST 6-acetylmorphine (6-AM) dip card) were tested encompassing 11 drug classes: 6-AM, amphetamine/methamphetamine, benzodiazepines, benzoylecgonine, fentanyl, methadone, opioids, phencyclidine, and delta-9-tetrahydrocannabinol. Sensitivity, specificity, efficiency, and positive and negative predictive values >80% indicated that UDS was useful for predicting cases involving benzoylecgonine, methadone, methamphetamine, and phencyclidine. UDS was unreliable in predicting amphetamine, benzodiazepines, fentanyl, and opiates-related cases due to a high percentage of FN (up to 11.2%, 8.0%, 12.4%, and 5.5%, respectively) when compared to ELISA blood results. For the later analytes, sensitivities were as low as 57.5%, 60.0%, 72.2%, and 66.7%, respectively. Overall results support that UDS cannot replace laboratory testing. Because UDS is subject to false-positive and FN results users must understand the limitations of using UDS for triage or decision-making purposes.

Factors Influencing Patient Confidence in Screening Mammography.

BACKGROUND: We aimed to assess factors associated with patients' confidence in the ability of screening mammography to detect breast cancer. METHODS: Data were analyzed from a cross-sectional, prospective survey conducted in 2017 of women without a breast cancer history who were undergoing screening mammography at our institution. RESULTS: In total, 390 women completed the survey questions relevant to this study. Most respondents were 46 years or older (89.7%), White (87.6%), and college-educated (66.1%). Approximately 80% of respondents reported having confidence in the ability of screening mammography to detect breast cancer. Factors significantly associated with lower confidence in screening mammography were higher education (P = .01) and dense breast tissue (P < .001). Age (P = .12), race (P = .64), family history of breast cancer (P = .17), prior abnormal mammogram (P = .07), and mammogram frequency (P = .42) were nonsignificant. Women with a college education or higher were less likely to report confidence in routine mammography than women with less education (odds ratio [OR]= 0.43; 95% CI, 0.20-0.84; P = .02). Compared with women who reported their breast tissue as not dense, women who were aware they had increased breast density (OR = 0.16; 95% CI, 0.04-0.49; P = .004) or were unaware whether they had increased breast density (OR = 0.17; 95% CI, 0.04-0.51; P = .005) reported less confidence in screening mammography. DISCUSSION: Most respondents were confident in the ability of screening mammography to detect breast cancer. Confidence was inversely associated with education level and self-reported increased breast density. CONCLUSIONS: These findings highlight the importance of continued patient education about the effectiveness of screening mammography for patients with dense breast tissue.

Quantitative analysis of torsional stiffness in supplemental one-third tubular plate fixation in the management of isolated syndesmosis injuries: a biomechanical study.

BACKGROUND: Disruption of the distal tibia and fibula articulation or syndesmosis can occur without fracture, and isolated syndesmotic disruption is often treated operatively. Following syndesmotic screw removal, a period of protected weight-bearing usually follows to allow the screw holes to heal. Our hypothesis was that supplementing transsyndesmotic fixation with a one-third tubular plate would potentially increase the torsional stiffness about the ankle, thus reducing the risk of fracture after screw removal and potentially allowing a faster return to weight-bearing and sport. METHODS: Ten pairs of fresh frozen cadaveric specimens were divided into 2 groups. In group 1 (7 pairs), each left extremity underwent the placement, and subsequent removal, of a 4.5-mm transsyndesmotic screw in a tricortical fashion. The matching right extremity underwent the same procedure but with the addition of a one-third tubular plate, which remained in situ after screw removal. In group 2 (3 pairs), the left specimens had a screw placed and removed while the right limbs remained intact. All specimens were tested under an axial preload and a torsional load until failure. RESULTS: In group 1, the results demonstrated an increase in torsional stiffness in 5 of 7 specimens with supplemental fixation of a one-third tubular plate. In group 2, the presence of the screw hole alone reduced the torsional stiffness in all specimens tested when compared with intact specimens. However, neither of these differences were statistically significant. CONCLUSION: From this study, we can conclude that the use of supplementary one-third tubular plate fixation demonstrated a trend toward increasing the torsional stiffness following transsyndesmotic screw removal. CLINICAL RELEVANCE: We believe the trend toward improved stiffness justifies the continued use of our technique, although further studies are necessary to confirm it.

Cross-sectional study evaluating the impact of SARS-CoV-2 variants on Long COVID outcomes in UK hospital survivors.

OBJECTIVES: COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination. DESIGN: Prospective observational cross-sectional study. SETTING: Secondary care tertiary hospital in the UK. PARTICIPANTS: This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021). OUTCOME MEASURES: Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively. RESULTS: 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44). CONCLUSIONS: Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Early and Midterm Complications of the Continent Catheterizable Indiana Pouch Urinary Diversion: A 7-year Experience.

OBJECTIVES: To describe the most recent 7 year experience with 137 Indiana pouch patients at a single institution and provide data on complications with this type of urinary diversion during the first postoperative year. METHODS: We queried our bladder cancer database to identify all patients who underwent cystectomy with continent catheterizable urinary reservoir between 2012 and 2018. Pre-, intra-, and postoperative data were collected. Complications were stratified into early (within 90 days) and midterm (90-365 days). The primary outcomes were postoperative complications, and overall and cancer-specific mortality. RESULTS: A total of 137 patients underwent open cystectomy with Indiana pouch creation. Of these, 93% were radical cystectomies. On average, the operation took 422 minutes. There were 53 (39%) patients who experienced any type of complication during the first postoperative year (Clavien II-V). Twenty-five patients (18.2%) readmitted in the early postoperative period vs 18 (13.1%) patients midterm. There were 10 (7.3%) patients that required early reoperation and 11 (8%) in the midterm period. The overall mortality rate was 1.5% early and 3.7% midterm, with the majority of the mortality rate attributed to cancer progression (85.7%). CONCLUSION: Patients undergoing continent catheterizable reservoir urinary diversion appear to have comparable complication rates to other urinary diversions published in the literature. At high-volume urologic institutions, Indiana Pouch creation is a suitable option for select patients desiring a continent diversion.

The gait profile score characterises walking performance impairments in young stroke survivors.

BACKGROUND: The Gait Profile Score (GPS) provides a composite measure of the quality of joint movement during walking, but the relationship between this measure and metabolic cost, temporal (e.g. walking speed) and spatial (e.g. stride length) parameters in stroke survivors has not been reported. RESEARCH QUESTION: The aims of this study were to compare the GPS (paretic, non-paretic, and overall score) of young stroke survivors to the healthy able-bodied control and determine the relationship between the GPS and metabolic cost, temporal (walking speed, stance time asymmetry) and spatial (stride length, stride width, step length asymmetry) parameters in young stroke survivors to understand whether the quality of walking affects walking performance in stroke survivors. METHODS: Thirty-nine young stroke survivors aged between 18 and 65years and 15 healthy age-matched able-bodied controls were recruited from six hospital sites in Wales, UK. Joint range of motion at the pelvis, hip, knee and ankle, and temporal and spatial parameters were measured during walking on level ground at self-selected speed with calculation of the Gait Variable Score and then the GPS. RESULTS: GPS for the paretic leg (9.40° (8.60-10.21) p < 0.001), non-paretic leg (11.42° (10.20-12.63) p < 0.001) and overall score (11.18° (10.26-12.09) p < 0.001)) for stroke survivors were significantly higher than the control (4.25° (3.40-5.10), 5.92° (5.11 (6.73)). All parameters with the exception of step length symmetry ratio correlated moderate to highly with the GPS for the paretic, non-paretic, and/or overall score (ρ = <-0.732 (p < 0.001)). SIGNIFICANCE: The quality of joint movement during walking measured via the GPS is directly related to the speed and efficiency of walking, temporal (stance time symmetry) and spatial (stride length, stride width) parameters in young stroke survivors.

Testicular tumors in the pediatric patient.

Testicular cancer is a rare malignancy that demonstrates variability in histopathologic features, treatment protocols, and outcomes based on a patient's age at presentation. In the pediatric population, puberty provides an important timestamp for evaluating and understanding the disease process. Prepubertal males, often designated as < 11 years of age, are more likely to present with benign disease. In contrast, the majority of post-pubertal testicular masses are malignant. Other factors, such as race/ethnicity, family history, and personal medical history can influence a patient's risk for malignancy as well. Serum tumor markers (STM) and histologic evaluation are key for diagnosis and for determining management. While normal STMs in a pre-pubertal patient likely qualify a patient for testis-sparing surgery, radical orchiectomy is the gold standard for post-pubertal patients, regardless of STM levels. Cross-sectional imaging is essential for staging and may be done before or after surgical intervention depending on the clinical scenario. Excellent survival outcomes are often achieved regardless of disease risk, with low-stage disease managed safely with surveillance. Surveillance usually consists of STM and imaging monitoring. If adjuvant therapy is indicated, a multi-disciplinary team approach is paramount. This approach should include following pediatric vs. adult protocols based of the patient's pubertal status in order to achieve optimal oncologic outcomes.

Higher knee contact forces might underlie increased osteoarthritis rates in high functioning amputees: A pilot study.

High functioning military transtibial amputees (TTAs) with well-fitted state of the art prosthetics have gait that is indistinguishable from healthy individuals, yet they are more likely to develop knee osteoarthritis (OA) of their intact limbs. This contrasts with the information at the knees of the amputated limbs that have been shown to be at a significantly reduced risk of pain and OA. The hypothesis of this study is that biomechanics can explain the difference in knee OA risk. Eleven military unilateral TTAs and eleven matched healthy controls underwent gait analysis. Muscle forces and joint contact forces at the knee were quantified using musculoskeletal modeling, validated using electromyography measurements. Peak knee contact forces for the intact limbs on both the medial and lateral compartments were significantly greater than the healthy controls (P ≤ .006). Additionally, the intact limbs had greater peak semimembranosus (P = .001) and gastrocnemius (P ≤ .001) muscle forces compared to the controls. This study has for the first time provided robust evidence of increased force on the non-affected knees of high functioning TTAs that supports the mechanically based hypothesis to explain the documented higher risk of knee OA in this patient group. The results suggest several protentional strategies to mitigate knee OA of the intact limbs, which may include the improvements of the prosthetic foot control, socket design, and strengthening of the amputated muscles.