One-year outcomes following rehabilitation for chronic hip-related groin pain: ancillary analysis of a pilot randomized clinical trial

Purpose: Rehabilitation to address modifiable factors associated with chronic hip-related groin pain (CHRGP) may lead to reduced pain and improved function, yet little is known about its effectiveness. We assessed the preliminary effects of two interventions that target two distinct mechanisms, sensory disturbances and abnormal movement patterns. Sensory disturbances such as peripheral and central sensitization may contribute to pain persistence long after initial injury. Joint mobilization (JtMob) may impart a neurophysiological response within the nervous system that results in pain reduction and improved mobility. Abnormal movement patterns may create altered mechanical stresses on hip joint structures, resulting in pain and activity limitations. Movement pattern training (MoveTrain) may improve movement patterns and thus patient function. Method(s): Patients with CHRGP, 18-40, were enrolled. Assessments included self-report questionnaires, clinical exam, and quantitative sensory testing. Outcomes included the Hip disability and Osteoarthritis Outcome Score (HOOS), a patient-reported outcome;frontal plane kinematics of hip, pelvis, and trunk during single leg squat;and pain pressure threshold (PPT) assessed at the anterior groin of the most bothersome hip and dominant thenar eminence (local and generalized pressure hypersensitivity, respectively). Patients were randomized to JtMob or MoveTrain in a 1:1 ratio stratified by sex and HOOS Symptoms. Treatment for both groups included 10 individualized visits over 12 weeks with a trained physical therapist (PT);assessment of patient goals and education which focused on patient-specific tasks reported by the patient to be symptom-producing;instruction in a home exercise program (HEP);and handouts that provided education, description and benefits of assigned treatment and instructions for HEP. The key element of JtMob was PT-provided manual techniques using specific criteria to determine the joint mobilization techniques and parameters used for each patient. The patient's symptom report to each technique was monitored and if indicated, the technique modified according to our outlined procedures. The HEP included flexibility exercises. The key element of MoveTrain was task-specific instruction to correct abnormal movement patterns displayed during daily and patient-specific tasks. For example, hip adduction was minimized during a step descent. The HEP included repeated practice of modified tasks. Task difficulty was progressed based on each patient's performance. Immediately after treatment completion, patients returned for follow up assessment. To assess treatment sustainability after the active treatment phase, we collected HOOS at 6 and 12 months (extended follow-up), and kinematics and PPT at 12 months. Data from patients who provided any data after baseline were analyzed with a repeated measures analysis of variance (RM-ANOVA) with baseline value as a covariate, patient as a random effect, and an autoregressive covariance structure. After adjusting for baseline, the between-group difference in change from post-treatment to each extended follow-up results from pre-planned statistical contrasts in a RM-ANOVA that includes main effects for treatment group, visit and the group by visit interaction. The within-group treatment effect at each extended follow-up was calculated by subtracting the earlier time point from the later follow-up within each treatment group. Dependent samples t-tests were used to assess the degree of within-group change. Result(s): Demographics and outcome data are provided in Tables 1 and 2, respectively. Thirty-three patients with CHRGP were randomized and 29 (88%) provided post-treatment data. Four patients did not complete treatment or post-treatment testing (3 due to COVID pandemic, 1 lost to follow up);6 patients did not complete 12 month laboratory testing (due to pandemic), but did complete 12 month questionnaires. Previously, we reported that both groups reported clinically important improvements in HOOS subscales and MoveTrain group improved hip and pelvis kinematics immediately after treatment compared to baseline. After adjusting for baseline, there were no between-group differences in change in outcomes between post-treatment and extended follow-up when comparing JtMob and MoveTrain, indicating that treatment effects immediately post-treatment were maintained at 12 months after treatment completion. Conclusion(s): Our preliminary findings suggest that 12 weeks of JtMob or MoveTrain, may result in improvements in patient-reported pain and function and these effects may persist 12 months after treatment completion. A future, larger trial to definitively assess the efficacy of JtMob and MoveTrain and identify factors associated with long-term outcomes will improve our ability to develop treatment strategies for people with CHRGP. [Formula presented] [Formula presented]Copyright © 2023

Enhanced TLR7 immunity drives innate protection against SARS-CoV-2 with chilblains as collateral damage

Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. These cases occurred mostly in patients who were asymptomatic and showed negative results from PCR and serology tests for SARS-CoV-2. We hypothesized that chilblain patients are predisposed to mount a robust innate immunity against the virus, which clinically manifests as chilblains and promotes early viral clearance, thereby preventing pulmonary disease and precluding adaptive responses. By profiling skin lesions in the early stage following chilblain onset, we uncover a transient IRF7-dependent type I interferon (IFN) signature that is driven by the acral infiltration of systemically activated plasmacytoid dendritic cells (pDCs). Patients' peripheral blood mononuclear cells (PBMCs) demonstrate increased production of IFNalpha when exposed to SARS-CoV-2 and influenza A, but not herpes simplex virus 1 (HSV-1), indicating a heightened ability to detect RNA -but not DNA- viruses. Further investigations revealed enhanced responsiveness of pDCs in chilblain patients to the RNA sensor TLR7, but not the DNA sensor TLR9. Collectively, our study establishes a two-step model for the immunopathology of SARS-CoV-2-related chilblains: enhanced TLR7 immunity in pDCs, likely triggered by SARS-CoV-2 exposure at the mucosal site, leads to prompt viral clearance, which explains the lack of infection markers in most cases. Subsequently, systemic spread of activated pDCs and infiltration of the toes in response to mechanical stress or acral coldness, may result in IFN-mediated tissue damage with development of chilblains.Copyright © 2023

A pattern of respiratory dysfunction in mild cases of postCOVID-19 athletes: an emerging hypothesis

The purpose of this study was to investigate fitness indicators through cardiac stress test in post-COVID-19 athletes, who were not hospitalized, vs healthy ones. Forty male professional Greek soccer players, were divided into two groups: previously infected with COVID-19 and non-hospitalized (n=20, Age: 25.2+/-4.1 yrs, BSA: 1.9+/-0.2 m2, body fat: 11.8+/-3.4 %) vs. control (n=20, Age: 25.1+/-4.4 yrs, BSA: 2.0+/-0.3 m2, body fat: 10.8+/-4.5 %). Inclusion criteria were: age >=20-to-<=30 yrs, training age >=6 yrs, without recent injury (>12 months) and asymptomatic infected with COVID-19 (<7 days). For each athlete, prior to assessment cardiopulmonary function (CPF) were recorded body composition, spirometry and lactate blood level. Differences between groups were assessed with the independent samples t-test (<0.05). Several differences were detected between the two groups (COVID-19 vs. non-COVID-19 athletes, Table 1) during CPF. Results didn't showed differences between groups in VO2max (55.7+/-4.4 vs. 55.4+/-4.6 ml/min/kg Table 1. Results between groups (*p<0.05, #p<0.001) Post-COVID-19 athletes characterized by increased respiratory work at both rest and maximum effort as well as hyperventilation during exercise, which may explain increased metabolic needs and mechanical stress.

A CASE OF ANKLE SURGERY CAUSING SEVERE IDIOPATHIC PULMONARY FIBROSIS (IPF) EXACERBATION: SHOULD I ALLOW MY PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS UNDERGO SURGERY?

SESSION TITLE: Critical Diffuse Lung Disease Cases 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 12:45 pm INTRODUCTION: Acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are well recognized in the progression of this uniformly fatal disease. Here we describe a case of AE of undiagnosed IPF after ankle surgery. Our aim is to discuss the role of non-pulmonary surgery as a precipitating factor and its outcome. CASE PRESENTATION: The patient is a 61-year-old male with a medical history of chronic smoking, recent open reduction internal fixation of left ankle 5 days before the presentation, comes to the emergency room with acute onset, gradually worsening shortness of breath along with non-productive cough and pleuritic chest pain. He denied any sick contacts, COVID exposure, travel history, inhalation of toxic fumes, or any chemical/pets/bird exposure. He was saturating around 85% on room air, was switched to a nasal cannula with improvement in saturation. Computed tomography (CT) of the chest showed no evidence of pulmonary embolism but diffuse ground-glass opacities (GGO) were noted bilaterally with no effusion or emphysematous changes, which were new compared to CT chest 10 days prior (that is 5 days before ankle surgery) which showed only mild reticular opacity along anterior convexity of the lungs bilaterally. He was started on intravenous steroids with gradual improvement in clinical status. Bronchoscopy biopsies revealed no malignant cells, bronchoalveolar lavage with no infections, and a negative serum autoimmune panel. He was discharged with outpatient follow-up for a repeat CT chest 6 weeks later which showed improvement in GGO (not back to baseline) and he was still requiring oxygen support. DISCUSSION: The most common triggers for IPF are smoking, environmental toxins, viral (COVID infection) or bacterial infections, medications like antidepressants, beta-blockers, NSAIDs. There is increasing evidence that surgery can cause acute respiratory worsening in IPF, presumably through increased mechanical stress to the lungs. Prolonged mechanical ventilation, high tidal volume, and high concentration of supplemental oxygen during surgery have been proposed as potential causes(1). As per the results from the retrospective study, the incidence of postoperative AE of IPF in patients undergoing non-pulmonary surgery is slightly lower than in patients undergoing pulmonary surgery (2,3). As in our case, non-pulmonary surgery procedures can pose risk for IPF exacerbation, but at this time we have limited research evidence to conclude if this exacerbation can alter the course of the disease. Some studies showed preoperative elevated C-reactive protein as a possible risk factor for AE of IPF after a non-pulmonary surgery but a multicenter study is needed to clarify the preoperative risk factors for AE of IPF after non-pulmonary surgery. CONCLUSIONS: We need further studies to check risk factors and disease course alteration, to have better guidance to classify preoperative risk in our IPF patients. Reference #1: Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Proposal, PMID: 2441663 Reference #2: Exacerbations in idiopathic pulmonary fibrosis triggered by pulmonary and non-pulmonary surgery: a case series and comprehensive review of the literature, PMID: 22543997 Reference #3: Postoperative acute exacerbation of interstitial pneumonia in pulmonary and non-pulmonary surgery: a retrospective study DISCLOSURES: No relevant relationships by Arundhati Chandini Arjun No relevant relationships by Harshil Fichadiya no disclosure submitted for Boning Li;No relevant relationships by Gaurav Mohan No relevant relationships by Rana Prathap Padappayil No relevant relationships by Raghu Tiperneni

COMPARISON OF MOVEMENT PATTERN TRAINING AND JOINT MOBILIZATION FOR CHRONIC PREARTHRITIC HIP DISORDERS: A PILOT RANDOMIZED CLINICAL TRIAL

Purpose: A clear need exists to rigorously assess treatment strategies for chronic prearthritic hip disorders (PAHD). We assessed the preliminary effects of two physical therapist-led interventions that target two distinct mechanisms, abnormal movement patterns and sensory disturbances. Abnormal movement patterns, such as excessive hip adduction, may create altered mechanical stresses on hip joint structures, resulting in subsequent injury, pain and activity limitations. Movement pattern training (MoveTrain) may improve movement patterns and patient-reported outcomes, however further investigation is needed to be definitive. Sensory disturbances such as peripheral sensitization and central sensitization (aka nociplastic pain) may also contribute to pain persistence long after an initial injury. Joint mobilization (JtMob) is proposed to impart a neurophysiological response within the peripheral and central nervous system that results in pain reduction and improved mobility, yet the investigation of JtMob for the treatment of PAHD is limited. Methods: Patients, 18-40 years, with chronic PAHD were recruited. Baseline assessment included self-report questionnaire completion, clinical examination and quantitative sensory testing. The primary outcome was the Hip disability and Osteoarthritis Outcome Score (HOOS), a hip-specific, patient-reported outcome measure. Secondary outcomes included movement evoked pain assessed with a repetitive step down task and a repetitive deep squat task, and pain pressure threshold assessed at the anterior groin of the most bothersome hip (local pressure hypersensitivity) and the dominant thenar eminence (generalized pressure hypersensitivity). After baseline assessment, patients were randomized into 1 of 2 treatment groups, MoveTrain or JtMob. Randomization was stratified by sex and HOOS Symptoms quartile, as determined from data collected during previous study. Treatment was provided by 4 experienced physical therapists (2 in each treatment arm) who were trained in standardized procedures. Treatment for both groups included 10 supervised sessions over 12 weeks and incorporated assessment of patient goals, patient education and instruction in a home program. Patient education focused on patient-specific tasks, such as work or fitness activities, identified by each patient to be symptom-producing. The goal of MoveTrain was to reduce stresses on the hip joint by optimizing the biomechanics of daily and patient-specific tasks. The key element of MoveTrain was task-specific instruction to correct abnormal movement patterns demonstrated during daily tasks and patient-specific tasks. For example, hip adduction and femoral internal rotation were minimized during step-down tasks. The home program included repeated practice of the modified tasks. Difficulty of the tasks were progressed based on each patient’s performance. The goal of JtMob was to reduce pain and improve pain-free motion of the hip. The key element of JtMob was manual techniques provided by the physical therapist. Specific criteria were used to determine the joint mobilization techniques and parameters used for each patient. The patient’s symptom report to each technique was monitored and if indicated, the technique modified according to our outlined procedures. The home program included flexibility exercises. Immediately after treatment completion, patients returned for follow up assessment. Data collected at baseline and post-treatment were analyzed with analysis of covariance (ANCOVA) using a generalized linear model where change is the dependent variable and baseline is the covariate. The adjusted immediate treatment effect was calculated by subtracting the least squares mean change between baseline and post for MoveTrain minus JtMob from the ANCOVA, and assesses the between-group difference in change after adjusting for baseline. Results: Thirty-three patients with PAHD were randomized. Demographics are provided in Table 1. Four patients did not complete treatment or post-treatment testing (3 due to COVID pandemic, 1 lost t follow up);7 patients did not complete post-treatment laboratory testing (due to COVID), but did complete post-treatment questionnaires. Both groups demonstrated clinically important within-group improvements in the HOOS subscales and movement evoked pain ratings after treatment (Table 2). No changes were noted in pain pressure threshold for either group. After adjusting for baseline, there were no between-group differences in change in outcomes when comparing MoveTrain and JtMob. Conclusions: Our preliminary findings suggest that 12 weeks of physical therapist-led intervention, including either MoveTrain or JtMob, may result in improvements in patient-reported pain and activities limitations. Further investigation is needed to determine the sustained effects of each treatment and to determine if specific patient factors are associated with treatment prognosis. [Formula presented] [Formula presented]

Biphasic effect of mechanical stress on lymphocyte activation.

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C-Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C-Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA-seq data of hypertensive and normotensive COVID-19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress.

Alveolar cells under mechanical stressed niche: critical contributors to pulmonary fibrosis.

Pulmonary fibrosis arises from the repeated epithelial mild injuries and insufficient repair lead to over activation of fibroblasts and excessive deposition of extracellular matrix, which result in a mechanical stretched niche. However, increasing mechanical stress likely exists before the establishment of fibrosis since early micro injuries increase local vascular permeability and prompt cytoskeletal remodeling which alter cellular mechanical forces. It is noteworthy that COVID-19 patients with severe hypoxemia will receive mechanical ventilation as supportive treatment and subsequent pathology studies indicate lung fibrosis pattern. At advanced stages, mechanical stress originates mainly from the stiff matrix since boundaries between stiff and compliant parts of the tissue could generate mechanical stress. Therefore, mechanical stress has a significant role in the whole development process of pulmonary fibrosis. The alveoli are covered by abundant capillaries and function as the main gas exchange unit. Constantly subject to variety of damages, the alveolar epithelium injuries were recently recognized to play a vital role in the onset and development of idiopathic pulmonary fibrosis. In this review, we summarize the literature regarding the effects of mechanical stress on the fundamental cells constituting the alveoli in the process of pulmonary fibrosis, particularly on epithelial cells, capillary endothelial cells, fibroblasts, mast cells, macrophages and stem cells. Finally, we briefly review this issue from a more comprehensive perspective: the metabolic and epigenetic regulation.