Lauren A. Henderson, Scott W. Canna, Grant S. Schulert
et al.
Poor outcomes in COVID‐19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID‐19.
Significance Cartilage is essential in vertebrate development and adulthood. Cartilage growth plates ensure skeletal growth until closing at puberty, and articular cartilage ensures lifelong structural and functional integrity of joints. Chondrocytes build cartilage in development, governed by the transcription factor SOX9. Using mouse models and transcriptome profiling approaches, we show here that SOX9 also has key roles to maintain growth plates open postnatally and to protect adult articular cartilage from osteoarthritic degradation. In particular, SOX9 safeguards the lineage fate of chondrocytes by preventing their dedifferentiation into skeletogenic mesenchymal progenitors followed by redifferentiation into osteoblasts. These findings provide insights into cellular plasticity and its molecular control in developmental, physiological, and pathological processes within and beyond the skeletal system.
Thomas Hügle, Heino Prillwitz, Godehard Scholz
et al.
Abstract Background Sleep impairment is common in rheumatoid arthritis (RA) but has not been extensively studied with wearables and self-observation following treatment. This study investigates the impact of upadacitinib (UPA) on subjective (self-reported) and objective (actigraphy-based) sleep quality in RA patients. Methods SLEERA is a sub-study of UPHOLD, an international observational cohort study (NCT04497597) that assessed sleep quality in RA patients after UPA treatment. Subjective sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) at baseline and post-treatment months 3, 6, 12 and 24. Objective sleep quality was assessed by actigraphy at baseline and post-treatment month 3. Results Among 39 patients, 76% had impaired subjective sleep quality at baseline (total PSQI: 7.84). Actigraphy sleep efficiency was 85.1%, 85.6% and 82.1% in patients with good (PSQI ≤ 5), moderate (PSQI > 5 and ≤ 8) and poor (PSQI > 8) sleep quality. After 3 months of UPA treatment, the total PSQI significantly improved (-2.42, p < 0.001), while actigraphy outcomes remained unchanged across the whole cohort. Of 19 patients with impaired sleep quality at baseline, 8 achieved good sleep quality, accompanied by improvements in actigraphy-based sleep efficiency (+ 1.5%), total wake time (-7.3 min) and movement index (-0.7%). Shifts from objectively impaired to good sleep efficiency were only observed in patients achieving remission or normative values of pain and fatigue. Conclusions Sleep impairment in RA patients can improve with treatment. Actigraphy showed improvements, particularly in patients with high subjective sleep impairment who achieve remission. Trial registration NCT04497597.
S Venkatesh Kumar, Ashwath Ahila Baskar, K G Sathyendra
et al.
Introduction:
Talus fractures are uncommon and complex injuries associated with significant trauma and complications. The incidence of associated malleolar injury with talus fracture is rare.
Case Report:
We share this unusual case of a Hawkins type-3 talus neck fracture along with a serious Grade 3B medial malleolus fracture and ankle subluxation, which was treated with cleaning the wound, realigning the ankle, and surgery to fix the bones. Post-operatively, the wound was healthy and free of infection. Despite being told to avoid weight-bearing for three months, the patient lost follow-up after a month and started occasional partial weight bearing. During the 10th post-operative week, we found a mild degree of talar neck collapse and Hawkins sign radiologically. The range of motion for the ankle was dorsiflexion of 0–15° and plantar flexion of 0–30°, with minimal swelling and pain on weight bearing.
Conclusion:
This case highlights the rarity and complexity of a talar neck fracture with ipsilateral medial malleolar fracture and ankle dislocation. Positive early outcomes were achieved through timely surgery within 10 h, careful soft tissue management, and appropriate fixation. The presence of a partial Hawkins sign post-operatively indicated preserved talar vascularity and reduced risk of avascular necrosis.
Orthopedic surgery, Diseases of the musculoskeletal system
Mahnuma Mahfuz Estee, Yuanyuan Wang, Stephane Heritier
et al.
ABSTRACT Background Back pain poses a significant global burden, within which individuals with more severe symptoms consume higher healthcare expenses than those with lesser back pain. Whether measures of body composition predict high‐intensity back pain and/or high‐disability in population‐based cohorts is unknown. This study aimed to examine the association between body composition at baseline and their change in the prior 5 years (between 2001–2005 and 2006–2010) and incident high‐intensity back pain and/or high‐disability in long‐term follow‐up, 10 years later (2016–2021) in a population‐based cohort of men. Method This study examined men with no or low‐intensity back pain and disability (Graded Chronic Pain Scale) at back pain study baseline (2006–2010) within the Geelong Osteoporosis Study. Those developing high‐intensity pain and/or high disability at follow‐up (2016–2021) were identified. Weight, body mass index (BMI), abdominal circumferences, fat mass and lean mass (dual energy X‐ray absorptiometry) were assessed prebaseline (2001–2005) and at baseline. The association of body composition at baseline and change in body composition from prebaseline to baseline with incident high‐intensity pain and/or high disability at follow‐up were examined using multivariable logistic regression. Result Of 695 participants with no or low‐intensity pain and disability at baseline, 441 (62.3%) completed follow‐up with a mean age of 54.3 ± 14.1 years: 37 (8.3%) developed high‐intensity pain and/or high‐disability, 33 (7.5%) developed high‐intensity pain and 14 (3.2%) high disability. No measures of body composition at baseline were associated with incident high‐intensity pain and/or high disability at follow‐up in the whole population. In subgroup analysis, among men aged over 60 years, but not younger, higher lean mass was associated with decreased likelihood of high‐intensity pain and/or high‐disability (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76, 0.97, interaction p < 0.001). In the whole population, examination of the relationship between change in measures of body composition between prebaseline and baseline, only a one unit increase in BMI, equivalent to 3.1‐kg weight gain, was associated with increased incident high disability (OR 1.63, 95% CI 1.06, 2.51). Conclusion In a population‐based sample, without severe back pain and disability, in older men aged ≥60 years, higher lean mass was protective of incident high‐intensity pain and/or high disability. An increase in BMI, over 5 years, equivalent to 3.1‐kg weight gain, was associated with incident back pain related high disability 10 years later. These results demonstrate another detrimental consequence of weight gain and highlight the importance of maintaining muscle mass in older men.
Diseases of the musculoskeletal system, Human anatomy
Abstract Distal radius fractures (DRFs) are among the most commonly encountered types of fractures in clinical practice. Conventional treatment methods include surgical intervention and traditional small splint fixation following manual reduction based on Traditional Chinese Medicine (TCM). However, these conventional small splints do not adequately meet the current demands for personalized and precision medicine. To address this issue, this study proposes a novel personalized distal radius fixation splint utilizing 3D printing technology. Firstly, a customized splint model that conforms to the patient’s fracture surface is established through three-dimensional scanning of the fracture site. Subsequently, the Tyson polygon structure and Grasshopper software are employed to parameterize the hollowing-out process of the splint, resulting in a personalized splint with a three-dimensional hollow-out structure. During the static analysis of the 3D hollow splint model, forces of 100 N and 150 N were applied. Under a force of 100 N, the maximum deformation of the splint was measured at 0.52 mm with a maximum strain value of 0.02 mm/mm and a maximum equivalent stress level of 19.415 MPa. However, when subjected to a force of 150 N, the maximum deformation increased to 0.78 mm with a corresponding increase in maximum strain value to 0.03 mm/mm and an elevated maximum equivalent stress level measuring 29.122 MPa. Additionally, this study also examined the flexural strength and weight of the 3D-printed splint in comparison to the conventional small splint. The test results demonstrate that, under pressure of 150 N, the radial offset of the 3D printed splint is reduced by 1.7 mm compared to that of the traditional small splint, with a corresponding decrease in stress by 0.01 MPa as well. In terms of weight, a set of 3D printed splints weighs 89 g while a set of conventional splints weighs 102 g, resulting in a significant reduction of 13 g for the 3D printed splints compared to their traditional counterparts. These findings indicate clear advantages associated with utilizing 3D-printed splints in terms of minimizing offset and reducing overall weight.
Orthopedic surgery, Diseases of the musculoskeletal system
AbstractInflammation plays a crucial role in the development of various disease conditions or is closely associated with them. Inflammatory cytokines like TNF often engage in interactions with other cytokines and growth factors, including TGFβ, to orchestrate inflammatory process. Basal/endogenous TGFβ signaling is a universal presence, yet the precise way TNF communicates with TGFβ signaling to regulate inflammation and influence inflammatory levels in macrophages has remained elusive. To address this question, this study utilized genetic approaches and a combination of molecular and cellular methods, including conditional TGFβ receptor knockout mice, human cells, RNAseq, ATACseq and Cut & Run‐seq. The results reveal that the TGFβ signaling functions as a vital homeostatic pathway, curtailing uncontrolled inflammation in macrophages in response to TNF. Conversely, TNF employs two previously unrecognized mechanisms to suppress the TGFβ signaling. These mechanisms encompass epigenetic inhibition and RBP‐J‐mediated inhibition of the TGFβ signaling pathway by TNF. These mechanisms empower TNF to diminish the antagonistic influence exerted by the TGFβ signaling pathway, ultimately enhancing TNF's capacity to induce heightened levels of inflammation. This reciprocal suppression dynamic between TNF and the TGFβ signaling pathway holds unique physiopathological significance, as it serves as a crucial “braking” mechanism. The balance between TNF levels and the activity of the endogenous TGFβ signaling pathway plays a pivotal role in determining the overall extent of inflammation. The potential for therapeutically augmenting the TGFβ signaling pathway presents an intriguing avenue for countering the impact of TNF and, consequently, developing innovative strategies for inflammation control.
Hip ultrasound, according to Graf, is a standardized sonographic method for the detection of developmental dysplasia of the hip (DDH) during the neonatal period. Graf established his method during the 1980s in his home country Austria. It was implemented in the Austrian Mother-Child Health Passport in 1992. Since then it served as a general screening method. The aim of this paper is to present the effects of general hip ultrasound screening in Austria by reviewing and analysing the literature of Austrian authors. This article described how the method was further developed and which prerequisites are currently required for a correct diagnosis. Moreover, it reports about the education in ultrasound screening according to Graf in Austria.
Juan Manuel Franco-García, Ángel Denche-Zamorano, Jorge Carlos-Vivas
et al.
Subjective cognitive impairment in older persons has a substantial influence on their quality of life and can progress to serious illnesses such as dementia. Physical activity level can help prevent cognitive decline and improve cognitive performance. The aim of this study was to investigate the association between frequency of physical activity and subjective cognitive impairment in Spanish adults aged 65 and over, and to identify different risk factors. Using data from the EHSS20 survey, the study focused on 7082 participants who provided information on cognitive impairment and physical activity. Key predictor variables included age, gender, BMI, marital status, and education level. A significant relationship was found between BMI category and gender, with 66.5% of the population being overweight or obese. Men were more likely to be overweight than women. Socio-demographic factors such as educational level, marital status, and physical activity frequency showed dependent associations with sex. Women had a higher prevalence of subjective cognitive impairment than men. A strong association was found between frequency of physical activity and subjective cognitive impairment, with inactive older people having the highest prevalence of subjective cognitive impairment. Older women who engage in little physical exercise and have less education are at risk for subjective cognitive impairment. Furthermore, for both men and women, being overweight was associated with a more reduced risk than obesity. Significant relationships were also discovered between subjective cognitive impairment, frequency of physical exercise, gender, BMI, and degree of education. In conclusion, older, sedentary women with high BMI and less education are more likely to experience subjective cognitive impairment.
Background: Congenital abnormalities are defects present at birth and are increasingly becoming an important cause of neonatal mortality. They can also result in disability in majority of the survivors.
Objective: To describe the pattern and outcome of major congenital abnormalities (MCA) in a tertiary hospital in Lagos, Nigeria.
Methods: The labour ward and labour ward theatre delivery records and admission records of the in-born ward of the neonatal unit of a tertiary hospital were reviewed retrospectively from January 2007 to December 2014. The MCA were classified according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, (ICD-10). Multiple abnormalities were counted once by the system with the most major anomaly. Abnormalities were grouped according to organ systems, sex and yearly distribution. Statistical analysis was based on systemic type, and neonatal outcome.
Results: Out of 14581 deliveries during the study period, 167 had MCA, giving an incidence of 11.5 per 1000 total births; 71 (42.5%) were females, 91 (54.5%) were male and 5(3.0%) had indeterminate sex. There was an increase in the yearly incidence from 2007-2014 The most frequent abnormalities were in the central nervous system (31.7%), musculoskeletal system (18.6%), complex congenital abnormalities group (15.5%) and urogenital system (11.4%). Fifty six (31.8%) infants died in the first week of life contributing 12.6% to the overall early neonatal mortality during the study period. Overall case fatality rate was 42.0%; case fatality was highest in the other abnormalities group, followed by chromosomal, cardiovascular and genitourinary system abnormalities respectively.
Conclusion: The incidence of MCA in this study is high especially in the central nervous system. There was a steady increase
in the yearly incidence during the study period. The overall case fatality rate was also very high with a high contribution to early neonatal deaths
Ananya Nandy, Ron C. M. Helderman, Santosh Thapa
et al.
AbstractBone formation is a highly energy-demanding process that can be impacted by metabolic disorders. Glucose has been considered the principal substrate for osteoblasts, although fatty acids are also important for osteoblast function. Here, we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation. As such, we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast maturation. Inhibiting cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast function. The fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted conditions. In vivo, conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid metabolism. Collectively, our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets, which are released via lipolysis to support cellular bioenergetic status when nutrients are limited. Perturbations in this process result in impairment of bone formation, specifically reducing ATP production and overall osteoblast function.
Abstract Background Sarilumab, an IL-6 receptor antagonist, is a first-line biologic disease-modifying anti-rheumatic drug for rheumatoid arthritis. The identification of genetic biomarkers as predictors of response to sarilumab could allow for a personalized treatment strategy to improve clinical outcomes. Methods We conducted a retrospective cohort study of 62 patients treated with sarilumab to determine whether single-nucleotide polymorphisms (SNP) in the IL6R gene could predict efficacy and toxicity responses. Six SNPs previously described in the IL6R gene (rs12083537, rs11265618, rs4329505, rs2228145, rs4537545, and rs4845625) were genotyped in DNA samples obtained from these patients. Using parametric tests, we evaluated the association between these polymorphisms and clinicopathological features. Treatment response was assessed six months after treatment initiation. Satisfactory response was based on EULAR criteria. Low disease activity was determined according to DAS28 and CDAI and quantitative improvements in DAS28 and CDAI scores. Results Three SNPs (rs4845625, rs4329505 and rs11265618) were significantly associated with response outcomes. All of the SNPs, except for rs12083537, had at least one significant association with dyslipidemia or hepatotoxicity. Conclusions These findings support the potential clinical value of SNPs, particularly rs4845625, as potentially useful biomarkers to predict response to sarilumab in patients with RA.
Bhavya Pahwa, Anish Tayal, Dhiman Chowdhury
et al.
Objective: We conducted a cross-sectional study to assess the preference of spine surgeons between MD for microdiscectomy and endoscopic discectomy (ED) surgery for the management of lumbar pathologies in a lower-middle-income country (LMIC).
Methodology: An online survey assessing the preference of spine surgeons for various lumbar pathologies was developed and disseminated in “Neurosurgery Cocktail” a social media platform. Statistical analyses were performed using SPSS software with a level of significance <0.05.
Results: We received responses from 160 spine surgeons having a median experience of 6.75 years (range 0–42 years) after residency. Most of the spine surgeons preferred MD over ED, preference being homogeneous across all lumbar pathologies. In ED, the interlaminar approach was preferred more frequently than the transforaminal approach. The most commonly chosen contraindication for the interlaminar approach and transforaminal approach was ≥ 3 levels lumbar disc herniation (LDH) (n = 117, 73.1%) and calcified LDH (n = 102, 63.8%), respectively. There was no significant association between the type of approach preferred (MD vs. ED; and interlaminar vs. translaminar endoscopic approach) with the type of workplace and the level of experience.
Conclusion: Spine surgeons were inclined toward MD over ED, due to various reasons, such as a steep learning curve, lack of training opportunities, and upfront expenses. There is a pressing need for the upliftment of ED in LMICs which requires global action.
Lisa Abernathy-Close, Stephanie Lazar, Jasmine Stannard
et al.
Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.
Abstract Background Oestrogen deficiency reduces skeletal muscle mass and force generation in postmenopausal women. Muscle mass is maintained by satellite cells, which are regulated by oestrogen. Although oestrogen therapy enhances muscle hypertrophy induced by resistance training in postmenopausal women, the molecular mechanism is unclear. Methods Adult female rats (10 weeks old) were divided into six groups: sham sedentary (Sham‐Sed), sham climbing training (Sham‐CT), ovariectomy sedentary (OVX‐Sed), ovariectomy climbing training (OVX‐CT), ovariectomy plus oestrogen treatment sedentary (OVX+E‐Sed), and ovariectomy plus oestrogen treatment climbing training (OVX+E‐CT). At 8 weeks after ovariectomy, rats in the training group were trained (one session every 3 days for 8 weeks) to climb a ladder while bearing a load. Oestrogen treatment involved subcutaneous insertion of a 17β‐oestradiol pellet. After 8 weeks, the flexor hallucis longus muscle was collected and analysed. Results Following climbing training, the flexor hallucis longus muscle mass and muscle‐to‐body weight ratios were dramatically increased by training (main effect of training, P < 0.01); the OVX+E‐CT group showed the highest values (main effect of group, P < 0.01). The cross‐sectional area of all muscle fibre types was increased by training (main effect of training, P < 0.01). Particularly, the cross‐sectional area of MHC IIa in the OVX+E‐CT group was significantly larger than that in the Sham‐CT and OVX‐CT groups. Satellite cell numbers were increased in all training groups (main effect of training, P < 0.05), and the myonuclear number was increased by training (main effect of training, P < 0.01), but there was no main group effect. The myonuclear domain size of all muscle fibre types and MHC IIa was increased in all training groups (main effect of training, P < 0.01) and showed a main group effect (P < 0.01). The myonuclear domain sizes of all muscle fibre types and MHC IIa in the OVX+E‐CT group were significantly larger than those in the Sham‐CT and OVX‐CT groups. The total RNA contents revealed main effects of training and the group (P < 0.01); the OVX+E‐CT group showed the highest contents (main effect of group, P < 0.01). The mRNA and protein levels of rpS6 were increased in the OVX+E‐Sed and CT groups (main effects of group, P < 0.05). Particularly, the 28S ribosomal RNA content in OVX+E‐Sed group was significantly higher than that in the OVX‐Sed group. Conclusions Oestrogen enhanced the resistance training‐induced increase in myonuclear domain size but did not affect satellite cells and ribosome biogenesis.
Diseases of the musculoskeletal system, Human anatomy