Web-based survey investigating cardiovascular complications in hypermobile Ehlers-Danlos syndrome after COVID-19 infection and vaccination.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome is a heritable connective tissue disorder associated with generalized joint hypermobility but also other multisystem comorbidities, many of which may be exacerbated during a viral illness or after a vaccination. We sought to determine whether individuals with hypermobile Ehlers Danlos syndrome report an increase in adverse events, including cardiovascular events, after COVID-19 illness or vaccination. METHODS: A cross-sectional web-based survey was made available from November 22, 2021, through March 15, 2022. 368 respondents primarily from the United States self-reported data including diagnosis. We used a Cox proportional hazards model with time varying indicators for COVID-19 illness or vaccination in the previous 30 days. RESULTS: We found a significantly increased rate of new abnormal heart rhythms reported in the 30 days following COVID-19 illness. No additional cardiovascular events were reported after COVID-19 illness. 2.5% of respondents with COVID-19 illness were hospitalized. We did not find a statistically significant increased rate of cardiovascular events in the 30 days following any COVID-19 vaccination dose. Post COVID-19 vaccination, 87.2% of hypermobile Ehlers-Danlos syndrome respondents endorsed an expected adverse event (EAE), and 3.1% reported an emergency department visit/hospitalization, of those who received at least one vaccine dose. Events possibly reflecting exacerbation of orthostasis/dysautonomia were common. CONCLUSION: Respondents did not report an increased rate of any cardiovascular events in the 30 days following COVID-19 vaccination; however, those with hypermobile Ehlers-Danlos syndrome experienced a high rate of expected adverse events after vaccination consistent with a high baseline prevalence of similar symptoms. No cardiovascular events other than new abnormal heart rhythms were reported at any point after a COVID-19 illness.

Preoperative lumbar epidural steroid injections administered within 6 weeks of microdiscectomy are associated with increased rates of reoperation.

PURPOSE: Lumbar epidural steroid injections (LESIs) are widely utilized for back pain. However, as studies report adverse effects from these injections, defining a safe interval for their use preoperatively is necessary. We investigated the effects of preoperative LESI timing on the rates of recurrent microdiscectomy. METHODS: This study utilized the PearlDiver national insurance claims database. Microdiscectomy patients were stratified by the timing of their most recent LESI prior to surgery into bimonthly cohorts (0-2 months, 2-4 months, 4-6 months). This first cohort was further stratified into biweekly cohorts (0-2 weeks, 2-4 weeks, 4-6 weeks, 6-8 weeks). The 6-month reoperation rate was assessed and compared between each injection cohort and a control group of patients with no injections within 6 months before surgery. Univariate analyses of reoperation were conducted followed by multivariate analyses controlling for risk factors where appropriate. RESULTS: A total of 12,786 microdiscectomy patients were identified; 1090 (8.52%) received injections within 6 months before surgery. We observed a significant increase in the 6-month reoperation rates in patients who received injections within 6 weeks prior to surgery (odds ratio [OR] 1.900, 1.218-2.963; p = 0.005) compared to control. No other significant differences were observed. DISCUSSION: In this study, microdiscectomy performed within 6 weeks following LESIs was associated with a higher risk of reoperation, while microdiscectomy performed more than 6 weeks from the most recent LESI demonstrated no such association with increased risk. Further research into the interaction between LESIs and recurrent disk herniation is necessary.

Diffuse neonatal hemangiomatosis in a very low-birthweight infant treated with erythropoietin.

Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the concomitant development of multiple cutaneous infantile hemangiomas (IH) and visceral hemangiomas. Recently, an association between erythropoietin treatment and an increased incidence of infantile hemangioma was noted. A Japanese male infant was born via cesarean section at 27 weeks of gestation. Following the commencement of erythropoietin treatment for anemia of prematurity, he developed multiple cutaneous hemangiomas, high cardiac output heart failure and hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile hepatic hemannigomas, resulting in the final diagnosis of DNH. The discontinuation of erythropoietin treatment and long-term therapy with propranolol improved the hepatic lesions and cutaneous hemangiomas. The possibility of multiple organ involvement and the exacerbating effects of erythropoietin treatment should be considered in cases in which multiple cutaneous hemangiomas develop in preterm infants receiving erythropoietin treatment.

Changes in serum collagen markers, IGF-I, and knee joint laxity across the menstrual cycle.

Variations in serum markers of collagen production (CICP) and degradation (ICTP), insulin-like growth factor I (IGF-I) and anterior knee laxity (AKL) were measured in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral contraceptives] over 5 consecutive days at menses (M1-M5, 1st pill week), the initial estrogen rise near ovulation (O1-O5, 2nd pill week), the initial progesterone rise of the early luteal phase (EL1-EL5, 3rd pill week) and post-progesterone peak of the late luteal phase (LL1-LL5, 4th pill week). ICTP was higher in oral contraceptive women (5.3 ± 1.7 vs. 3.7 ± 1.3 µg/L; p = 0.030), primarily during days near ovulation and the early luteal phase when concentrations decreased in eumenorrheic women (p = 0.04). IGF-I concentrations increased during menses then decreased and remained lower during the early and late luteal phase in oral contraceptive women, resulting in lower concentrations compared to eumenorrheic women at EL2 and LL1 (p = 0.03). CICP decreased in early and late luteal days (p <0.01), and there was a trend toward lower concentrations in eumenorrheic versus oral contraceptive women (85.7 ± 35.7 ng/ml vs. 123.2 ± 49.8 ng/ml; p = 0.07). Lower CICP and greater IGF-I concentrations predicted greater AKL across the 20 cycle days in both groups (R(2) = 0.310 and 0.400). Sex hormone concentration changes across the menstrual cycle are of sufficient magnitude to influence collagen metabolism, and may indirectly influence knee structure and function.

Endogenous regeneration after collagenase-induced knee joint damage in the adult newt Notophthalmus viridescens.

OBJECTIVES: To determine whether adult newts (Notophthalmus viridescens) are able to repair experimentally-induced joint damage in order to generate a model system for the study of endogenous joint regeneration. METHODS: Joint instability and articular cartilage lesions of the knee joint of adult newts (N viridescens) were induced by intra-articular injection of collagenase. The changes over time were analysed clinically, by MRI, histologically and by reverse transcription PCR to detect selected relevant markers. RESULTS: After rapid onset of disease with joint luxation, loss of proteoglycans and cartilage volume, the signs ameliorated continuously by regeneration of the affected joint compartments. The majority of joints were morphologically intact and functionally operative after 10 weeks. Upregulation of chondrogenic key genes, homogenous expression levels of factors implicated in cartilage homeostasis and limb regeneration as well as the distribution of the blastemal marker 22/18 in both treated and untreated knees suggest that joint regeneration in adult newts only partially invokes pathways of embryological organogenesis. CONCLUSIONS: Newts are able to regenerate articular cartilage injuries and to restore tissue integrity and function after induction of damage using a procedure known to induce experimental osteoarthritis in murine models. Further analysis of the underlying molecular mechanisms may contribute to the development of novel treatment approaches in joint failure.

Trachlight management of succinylcholine-induced subluxation of the Temporo-mandibular joint: a case report and review of the literature.

PURPOSE: We present a case of spontaneous subluxation of the Temporo-mandibular joint (TMJ) induced by succinylcholine, to compare our experience with previous cases reported in the literature, and to review the pathophysiology, preoperative screening, and intraoperative management of TMJ instability. CLINICAL FEATURES: A 39-yr-old female with primary hyperparathyroidism and a normal airway examination presented for elective parathyroidectomy. Following induction of anesthesia and the administration of succinylcholine prior to jaw manipulation, her mouth could not be opened, and we suspected spontaneous subluxation of the TMJ. We secured the airway with the use of a Trachlight and, subsequently, reduced the joint. Postoperatively, a history of mild TMJ-related symptoms was elicited. CONCLUSION: Instability of the TMJ is not uncommon, and has several implications for airway management, highlighting the importance of preoperative screening. Limited mouth opening, due to spontaneous subluxation of the TMJ following succinylcholine-induced muscle relaxation in the absence of airway manipulation, has only twice been reported in the literature. This report highlights how tracheal intubation may be accomplished using the Trachlight, in order to secure the airway prior to reduction of the subluxed joint.

Elevation of a collagenase generated type II collagen neoepitope and proteoglycan epitopes in synovial fluid following induction of joint instability in the dog.

CLINICAL RELEVANCE: Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations. OBJECTIVE: The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA. DESIGN: A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 +/- 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(-) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed. RESULTS: Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(-) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture. CONCLUSIONS: Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(-) epitope in synovial fluid were significantly increased by 4 weeks and remained elevated for at least 16 weeks after CCL rupture. This suggests that in dogs the COL2-3/4C long neoepitope and 3B3(-) epitope are sensitive markers for changes in joint cartilage turnover in joints that are developing OA.

A randomized controlled trial of piroxicam in the management of acute ankle sprain in Australian Regular Army recruits. The Kapooka Ankle Sprain Study.

Three hundred sixty-four Australian Regular Army recruits with acute ankle sprains sustained during training were randomized to treatment with either piroxicam or placebo. Compared with the placebo group, subjects treated with piroxicam had less pain, were able to resume training more rapidly, were treated at lower cost, and were found to have increased exercise endurance on resumption of activity. Nausea was the only side effect reported significantly more often in the treatment group than in the placebo group (6.8% versus 0.3%). Interestingly, subjects treated with piroxicam showed some evidence of local abnormalities such as instability and reduced range of movement. We conclude that nonsteroidal antiinflammatory agents should form an integral part of the treatment of acute ankle sprains.

Musculoskeletal changes in children prenatally exposed to polychlorinated biphenyls and related compounds (Yu-Cheng children).

Fifty-five Yu-Cheng (oil-disease) children born between 1978 and 1985 to mothers who ate PCB-contaminated rice oil in 1978-1979 were studied and compared to age- and sex-matched control subjects in 1991. The children's growth profiles, bone mineral density and soft tissue composition, joint laxity, and serum parathyroid hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared. The Yu-Cheng children were 3.1 cm (p < .05) smaller and had less total lean mass and soft tissue mass as compared to the matched control subjects. All other parameters studied were similar in both groups. The shorter height and decreased total lean mass and soft tissue content were only seen in the Yu-Cheng children who were the first born after the ingestion, but not in subsequent children. This was most likely due to decreased body burdens of the PCBs and related contaminants over time in the mothers.

Articular mobility in systemic lupus erythematosus (SLE).

The study was prompted by the suggestion that inflammatory polyarthritis and corticosteroids increase articular mobility. Ninety female patients with systemic lupus erythematosus (SLE) of whom 85 had polyarthritis and at least 75 of whom had received corticosteroid therapy were studied and compared to an equal number of carefully matched controls. The difference between the number of hypermobile patients [6 (7%)] and controls [5 (6%)] was not significant. There was also no significant difference when either the pooled mobility scores or the pooled hand scores of the patients and controls were compared. No significant association between articular mobility and either age at onset of disease, duration of disease or corticosteroid therapy was demonstrated. There was a significant association between deformity and duration of disease (p = 0.04) but not with mobility score. We conclude that SLE patients do not have a hypermobile tendency and therefore that neither SLE nor corticosteroids predispose to increased articular mobility. There is also no association between articular mobility and deformity.

Volar intercalated segment instability as a result of spontaneous rupture of the supporting ligaments of the wrist due to longterm systemic steroid medication.

Linscheid and Dobyns (1972), in a classical article on post-traumatic instability of the wrist described two major types of instability, dorsal and volar. The dorsal intercalated segment instability (D.I.S.I.) was the more common and occurred with scapholunate dissociation and displaced scaphoid fractures. The instability occurred in these conditions as a result of the scaphoid losing its ability to support the carpus. They presented five cases of volar intercalated segment instability (V.I.S.I.) of which four were related to congenital ligament laxity and not to traumatic ligament disruption. In the one case of traumatic origin they felt that the capitolunate ligament was ruptured. However, more recent publications by Taleisnik, Prietto (1982) and Reagan, (1984) have proposed that for V.I.S.I. to occur the lunate triquetral interosseous ligament must be disrupted. We report this case as it demonstrates which ligamentous structures are torn for V.I.S.I. to occur. In addition, these ligament disruptions were pathological and occurred spontaneously as a result of longterm systemic steroid medication.