Hasil untuk "Diseases of the musculoskeletal system"

Kristin M D'Silva, Naomi Serling-Boyd, Rachel Wallwork et al.

Tanja C. Maisenbacher, Mika F. Rollmann, Maximilian M. Menger et al.

Aims: Fracture nonunion represents a major complication in orthopaedic surgery, occurring in 5% to 10% of fracture patients. Fracture nonunions are associated with pain and loss of function, and lead to a substantial socioeconomic burden. The present retrospective cohort study analyzed direct and indirect costs and length of hospital stay, number of surgical procedures, and hospital (re-)admissions of nonunion patients. Methods: Data from 18- to 65-year-old patients surgically treated for lower limb fractures and nonunions in a German level I trauma centre between 2012 and 2018 were analyzed. A total of 193 patients with nonunion were included, and 2,511 patients with fractures served as the control group. Direct costs were calculated using reimbursement according to the diagnosis-related group (DRG). Indirect costs were calculated including daily sickness allowance and productivity loss. Results: The median healing time of nonunion patients was 45 weeks. Treatment expenses showed a 2.6-fold increase in direct costs, a 3.3-fold increase in indirect costs, and a 3.3-fold increase in total costs for nonunion patients compared to the control group. As every patient with a nonunion suffered from a fracture prior to nonunion treatment, costs were calculated by adding the median direct costs of €10,487 (IQR 9,173 to 15,262), median daily sickness allowance of €23,046 (IQR 14,892 to 36,264), median productivity loss of €85,714 (IQR 60,949 to 126,650), and median total socioeconomic burden of €123,334 (IQR 88,630 to 176,329). Conclusion: Nonunions not only pose a significant burden on the injured individual and on healthcare systems, but also have a substantial socioeconomic impact. High direct and indirect costs illustrate that healing complications need to be detected and addressed as early as possible. Cite this article: Bone Joint Res 2025;14(4):1–10.

Tomo Nozawa, Naomi Iwata, Toru Igarashi et al.

Abstract Background In 2018, intravenous abatacept was approved for the treatment of refractory polyarticular-course juvenile idiopathic arthritis (JIA) in Japan. However, reports describing the effectiveness and safety of abatacept in clinical practice in Japanese patients with refractory polyarticular-course JIA are limited. Therefore, this postmarketing surveillance study aimed to evaluate the real-world safety and effectiveness of abatacept in Japanese pediatric patients with refractory polyarticular-course JIA. Methods This study evaluated patients included in an all-case postmarketing surveillance study between February 2018 and August 2020 who were treated with intravenous abatacept. Data on the safety and effectiveness of the registered patients were collected during the 52-week follow-up period. Disease activities were evaluated using Juvenile Arthritis Disease Activity Score 27 (JADAS-27). The effect of abatacept on a child’s growth was assessed using the height and weight standard deviation scores (SDS). Results A total of 82 patients were registered in this study, of whom 14.6% and 85.4% were males and females, respectively. The proportion of patients with oligoarticular, rheumatoid factor (RF)-negative polyarticular, and RF-positive polyarticular JIA was 12.2, 28.0, and 54.9%, respectively. The incidence of adverse drug reactions (ADRs) and serious ADRs was 22.0% and 2.4%, respectively. During the study period, 64.7% of the patients achieved JADAS-27 low disease activity or less. A significant difference in JADAS-27 scores in patients with RF-positive polyarticular JIA was observed between baseline and 24 or 52 weeks after abatacept administration. The height and weight SDS tended to improve during abatacept treatment. Conclusions Abatacept is effective in polyarticular-course JIA, particularly in RF-positive patients, and in restoring a child’s growth. Additionally, the incidence of ADRs is similar to that observed in the clinical trial. The results of the study suggest that abatacept is a useful therapeutic option for treating refractory polyarticular-course JIA in real-world settings in Japan.

Alexandra Rydz, Fangfang Fu, Zhe Lu et al.

Abstract Background Delays in access to care in rheumatology are well documented. Many factors contribute to these delays and studies in adult populations indicate that incomplete referral letters may play a role. This study aims to describe the content of referral letters to pediatric rheumatology and to investigate the impact of incomplete letters on time to triage and accessing care. Findings Methods We evaluated referrals to a tertiary care pediatric rheumatology centre for eight components of comprehensive referral letters. In addition, we compared time-to-triage and percentage of patients receiving rheumatic diagnoses between letters with sufficient content for immediate triage versus incomplete letters requiring further information. Logistic regression models identified factors associated with delayed triage. Results Further information was requested for 67/447 (15%) referrals, resulting in median delay in time-to-triage of seven days. Delayed triage was associated with four factors: lack of musculoskeletal physical examination, referral from family physicians versus other specialty, missing information regarding management, and lack of rheumatic diagnosis of concern. Rheumatic diagnoses resulted from 42% of all referrals overall, specifically from 170/384 (44%) of immediately triaged referrals and 19/63 (30%) of referrals requiring further information. Rheumatic diagnoses resulted less commonly from family physician referrals. Conclusions Missing important details in referrals to pediatric rheumatology contribute to delayed assessment. These findings can inform initiatives to educate physicians around relevant content of referral letters to facilitate timely access to care.

Michael Kimmeyer, MD, Tilman Hees, MD, Laurens Allaart, MD et al.

Background: Tendon transfers of the latissimus dorsi transfer (LDT) or the lower trapezius transfer (LTT) are treatment options for irreparable posterosuperior irreparable rotator cuff tears (PSIRCT). There is still no consensus on which type of tendon transfer is superior in the treatment of PSIRCT. Due to the differences in the anatomy and biomechanics, we hypothesize that there are different clinical situations in which either LDT or LTT should be preferred. The aim of this study was to evaluate the clinical and radiological outcomes of LDT and LTT in patients with PSIRCT to establish a clinical algorithm for the treatment decision. Materials and methods: This is a retrospective, single-center observational study. Included were patients who underwent arthroscopically assisted LDT (aaLDT) or arthroscopically assisted LTT (aaLTT) for PSIRCT. In all patients, range of motion (ROM), external rotation strength, visual analog scale of pain and subjective shoulder value were determined pre- and postoperatively. Constant–Murley score was evaluated at the final follow-up. The complication rate, failure of the tendon transfer, and revision rate were analyzed. Results: In total, 29 aaLDT (age 64 years, median follow-up time 45 months) and 8 aaLTT (age 54 years, median follow-up time 34 months) were included. Active ROM, visual analog scale and subjective shoulder value was significantly improved in both cohorts. At follow-up, the median Constant–Murley score was 73 (aaLDT) and 77 (aaLTT), respectively. The failure rate, including revision surgery, was 14% (aaLDT) and 13% (aaLTT), respectively. Low functional findings preoperatively were correlated to a lower functional outcome at follow-up in both groups. Painful loss of anterior elevation and loss of external rotation had no significant impact on functional outcomes in aaLDT. Conclusion: Following the treatment algorithm based on the clinical examination, clinical outcome parameters, active ROM and pain could be significantly improved. A good preoperative function was associated with a good clinical outcome in both transfers. A low failure and revision rate supports the good decision-making of the algorithm presented.

Lok Yee Joyce Li, Ping Hui Chen

Abstract Introduction Referral mechanism among clinical physicians and occupational physicians is important for diagnosis of occupational diseases(ODs). Previous study identified criteria additional to ICD codes to enhance positive predictive value by comparing demographic factors between probable cases and possible/non-related cases. We further aim to apply these predictors of work-relatedness in clinical trials to develop a validated screening tool and strengthen the referral system. Methods In Taiwan, Network of Occupational Diseases and Injuries Service(NODIS) is an important surveillance system of ODs. In NODIS, musculoskeletal diseases (MSDs) are the most reported cases. Among adult patients who visited OPD of Orthopedic and Rehabilitation, we screen those with diagnoses of MSD ICD codes. Selected patients are invited to OPD of Occupational Medicine, where informed consent is obtained and a physician-guided questionnaire is conducted. Patients eligible for ODs are reported in NODIS and we analyze demographic factors between probable cases and possible/non-related cases. Results There are 4651 confirmed cases of occupational MSDs, and 62.37% (2901/4651) cases are classified as probable cases. In binomial regression model, longer tenure, ever taking leaves due to MSDs, construction and manufacturing industries and main MSDs in OD list are all significant predictors of work-relatedness. Discussion and Conclusion Each MSD has its unique predictor of work-relatedness, and we identify high-risk characteristics, like age, gender, tenure, industry, sick leave status. Using each predictor’s coefficient, we generate a set of referral criteria to refer cases with odds ratio of 2 or above, which enables better referral mechanism. Through trial validation, we identify significant factors which can be incorporated in occupational MSDs screening and referral mechanism.

Youliang Ren, Jason Weeks, Thomas Xue et al.

Abstract Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve “target-and-release” drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Baohui Yang, Teng Lu, Xijing He et al.

Abstract Background There are many classification systems for atlantoaxial dislocation (AAD). Among these systems, the definitions of irreducible AAD remain vague, and its treatments are not unified. Objective To explore the surgical strategies and efficacy for the treatment of os odontoideum (OO) with AAD. Methods The clinical data of 56 OO patients with AAD who underwent surgery from January 2017 to June 2021 were retrospectively analyzed. AAD was classified into four types, Type I and type II were treated with posterior fixation and fusion. Type III received posterior fixation and fusion after irreducible dislocations were converted to reducible dislocations by translateral mass release or transoral release. Type IV required transoral release for conversion into reducible dislocations before posterior fixation and fusion. The operation time, blood loss, and complications were recorded. The preoperative and postoperative neurological function changes were assessed using the Japanese Orthopedic Association (JOA) score. Postoperative fusion status was assessed by X-ray. Results There were 40 cases of type I-II, 14 cases of type III, and two cases of type IV AAD. The operation times of single posterior fixation and fusion, combined translateral mass release and combined transoral release were 130.52 ± 37.12 min, 151.11 ± 16.91 min and 188.57 ± 44.13 min, the blood loss were 162.63 ± 58.27 mL, 235.56 ± 59.94 mL, 414.29 ± 33.91 mL, respectively. One patient with type III died, one with type III underwent revision surgery due to infection, and three patients with type I had further neurological deterioration after operation. fifty-five patients were followed up for 12–24 months. The follow-up results showed that enough decompression was achieved and that fixation and fusion were effective. The JOA score increased from 9.58 ± 1.84 points preoperative to 13.09 ± 2.68 points at 3 months after operation, 14.07 ± 2.83 points at 6 months and 14.25 ± 2.34 at 12 months after operation, all significant differences compared with preoperative results (P < 0.05). Conclusion OO patients with irreducible AAD can be treated by translateral mass release or transoral release combined with posterior fixation and fusion, while some of those with bony fusion can be treated by transoral release combined with posterior fixation and fusion.

Eleftherios Pelechas, Evripidis Kaltsonoudis, Paraskevi V. Voulgari et al.

H. Mark Kenney, Chia-Lung Wu, Alayna E. Loiselle et al.

Abstract Background Lymphatic dysfunction exists in tumor necrosis factor transgenic (TNF-Tg) mice and rheumatoid arthritis (RA) patients. While joint-draining TNF-Tg popliteal lymphatic vessels (PLVs) have deficits in contractility during end-stage arthritis, the nature of lymphatic muscle cells (LMCs) and their TNF-altered transcriptome remain unknown. Thus, we performed single-cell RNA-sequencing (scRNAseq) on TNF-Tg LMCs in PLVs efferent to inflamed joints versus wild-type (WT) controls. Methods Single-cell suspensions of PLVs were sorted for smooth muscle cells (SMCs), which was validated by Cspg4-Cre;tdTomato reporter gene expression. Single-cell RNA-seq was performed on a 10x Genomics platform and analyzed using the Seurat R package. Uniform Manifold Approximation and Projections (UMAPs) and Ingenuity Pathway Analysis software were used to assess cell clusters and functional genomics in WT vs. TNF-Tg populations. Results Fluorescent imaging of Cspg4-Cre;tdTomato vessels demonstrated dim PLVs and strong reporter gene expression in the adjacent superficial saphenous vein, which was corroborated by flow cytometry of LMCs and vascular smooth muscle cells (VSMCs) from these vessels. Due to their unique morphology, these populations could also be readily detected by scatter analysis of cells from non-fluorescent mice. Bioinformatics analysis of flow sorted WT and TNF-Tg cells identified 20 unique cell clusters that together were 22.4% LMCs, 15.0% VSMCs, and 62.6% non-muscle cells of 8879 total cells. LMCs and M2-macrophages were decreased, while inflammatory monocytes were increased in TNF-Tg lower limb vasculature. SMC populations were defined by Cald1, Tpm1, and Pdgfrb expression and were enriched in myofibroblast-like gene expression. TNF-Tg LMCs exhibited enhanced functional genomics associated with cell death, phagocyte recruitment, and joint inflammation. Among the most prominent TNF-induced genes in SMCs were Mmp3, Cxcl12, and Ccl19, and the most downregulated genes were Zbtb16, Galnt15, and Apod. Conclusions Single-cell RNA-seq can be used to investigate functional genomics of lower limb vasculature in mice. Our findings confirm the inflammatory transcriptome of TNF-Tg vessels and altered gene expression in SMC populations. This study further supports a potential role of mesenchymal stromal cells in inflammatory-erosive arthritis pathogenesis, and warrants future studies to define the effects of this TNF-altered transcriptome on PLV function and joint homeostasis.

M. Tantari, S. Bogliolo, M. Morotti et al.

Simple Summary The prognosis of cervical cancer is significantly influenced by lymph node involvement. The lymphatic system is the primary way of metastasis for cervical carcinoma, and lymph-vascular space invasion (LVSI) is considered the most important risk factor for pelvic lymph node metastasis (PLNM). Previous studies have not clarified the correlation between lymphangiogenesis and an increased risk of metastasis and tumor recurrence. The evaluation and identification of several markers of lymphangiogenesis may identify patients with high risk of PLNM. Our findings suggest that the lymphatic spread does not required the proliferation of new lymphatic endothelial cells. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. Abstract Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

D. Dona’, C. Montagnani, C. di Chiara et al.

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. Methods: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. Results: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale’s severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. Conclusions: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

I. Criado, Wendy G Nieto, Guillermo Oliva-Ariza et al.

Simple Summary Assessment of the status of the immune system in both health and disease requires robust and reliable reference ranges for the different blood leukocyte (sub)populations that take into consideration factors that might influence their distribution, such as age, sex, ethnicity and the presence vs. absence of low-count monoclonal B-cell lymphocytosis with a chronic-lymphocytic-leukemia-like phenotype (MBLlo). It should be noted that despite MBLlo being highly prevalent in the general population and being associated with immune impairment, MBLlo individuals have not been previously excluded in the definition of normal leukocyte ranges. Here, we provide reference cell-count ranges for the major leukocyte populations identified in blood using an optimized and fully validated 8-color flow-cytometry antibody combination based on the largest (n = 706) cohort reported to date of Caucasian adult donors from the general population, grouped by age and sex, and highlight the altered immune profiles associated with MBLlo (622 non-MBL and 84 MBLlo subjects). Abstract Reference ranges of blood-circulating leukocyte populations by, e.g., age and sex, are required for monitoring immune-cell kinetics. Most previous reports in which flow cytometry has been used to define the reference ranges for leukocyte counts included a limited number of donors and/or cell populations and/or did not consider age and sex simultaneously. Moreover, other factors not previously considered in the definition of normal ranges, such as the presence of chronic-lymphocytic-leukemia (CLL)-like low-count monoclonal B-cell lymphocytosis (MBLlo), might also be associated with an altered distribution of leukocytes in blood in association with an immunodeficiency and increased risk of infection and cancer. Here, we established reference cell-count ranges for the major populations of leukocytes in blood of non-MBL and MBLlo adult Caucasians matched by age and sex using the EuroFlow Lymphocyte Screening Tube (LST). A total of 706 Caucasian adult donors—622 non-MBL and 84 MBLlo—were recruited from the general population. Among non-MBL donors, the total leukocyte, neutrophil, basophil dendritic cell and monocyte counts remained stable through adulthood, while the absolute numbers of T- and B-cell populations and plasma cells decreased with age. The number of eosinophils and NK-cell increased over time, with clear differences according to sex for certain age ranges. In MBLlo subjects, few differences in the absolute cell counts by age (vs. non-MBL) were observed, and MBLlo men and women showed similar trends to non-MBL subjects except for the B-cell count drop observed in >70 y-men, which was more pronounced in MBLlo vs. non-MBL controls. Building robust age- and sex-matched reference ranges for the most relevant immune-cell populations in the blood of non-MBL donors is essential to appropriately identify an altered immune status in different clinical settings and highlight the altered immune-cell profiles of MBLlo subjects.

S. Siddi, I. Giné-Vázquez, R. Bailón et al.

Background: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDD) and Multiple Sclerosis (MS). Methods: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse Central Nervous System) programme. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. Results. Participants with MDD (N=255) and MS (N=214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. Lower mean HR and HR variation were observed between pre and during lockdown during the day for MDD and during the night for MS. HR variation during rest periods also decreased between pre-and post-lockdown in both clinical conditions. We observed a reduction of physical activity for MDD and MS upon the introduction of lockdowns. The group with MDD exhibited a net increase in social interaction via social network apps over the three periods. Conclusions: Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.

Magnhild H. Dagestad, Nils Vetti, Per M. Kristoffersen et al.

Abstract Background Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. Methods We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). Results The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p < 0.001 to 0.02): MC-ADC (10− 6 mm2/s) 1201/796/576, MC-ADC% 36/21/14, and MC-ADC-ratio 5.9/4.2/3.1. MC-ADC and MC-ADC% had moderate to high ability to discriminate between the MC type groups (AUC 0.73–0.91). MC-ADC-ratio had low to moderate ability (AUC 0.67–0.85). At L4-S1, widest/narrowest LoA were for MC-ADC 20 ± 407/12 ± 254, MC-ADC% 1.6 ± 18.8/1.4 ± 10.4, and MC-ADC-ratio 0.3 ± 4.3/0.2 ± 3.9. Difference between observers > 50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17–20%). Conclusions The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.

Fareeha Amjad, Mohammad A. Mohseni-Bandpei, Syed Amir Gilani et al.

Abstract Background Lumbar radiculopathy is an extensively common complaint reported by patients of low back pain (LBP), resulting in several impairments. A comparatively novel technique, non-surgical spinal decompression (NSD), is introduced, which uses a sensitive computerized feedback mechanism and decompresses the spinal nerve roots through segmental distraction. The objective of this study was to determine the effects of NSD therapy in addition to routine physical therapy on pain, lumbar range of motion (ROM), functional disability, back muscle endurance (BME), and quality of life (QOL) in patients with lumbar radiculopathy. Methods A total of sixty patients with lumbar radiculopathy were randomly allocated into two groups, an experimental (n = 30) and a control (n = 30) group, through a computer-generated random number table. Baseline values were recorded before providing any treatment by using a visual analogue scale (VAS), Urdu version of Oswestry disability index (ODI-U), modified-modified Schober’s test (MMST), prone isometric chest raise test, and Short Form 36-Item Survey (SF-36) for measuring the pain at rest, functional disability, lumbar ROM, BME, and QOL, respectively. All patients received twelve treatment sessions over 4 weeks, and then all outcome measures were again recorded. Results By using the ANCOVA test, a statistically significant (p < 0.05) between-group improvement was observed in VAS, ODI-U, BME, lumbar ROM, role physical (RP), and bodily pain (BP) domains of SF-36, which was in favour of NSD therapy group. The between-group difference was 1.07 ± 0.32 cm (p < .001) for VAS, 5.65 ± 1.48 points (p < .001) for ODI-U, 13.93 ± 5.85 s (p = 0.002) for BME, 2.62 ± 0.27 cm (p < .001) for lumbar flexion, 0.96 ± 0.28 (p < .001) for lumbar extension, 5.77 ± 2.39 (p = 0.019) for RP and 6.33 ± 2.52 (p = 0.016) for BP domain of SF-36. For these outcomes, a medium to large effect size (d = 0.61–2.47, 95% CI: 0.09–3.14) was observed. Conclusion It was concluded that a combination of non-surgical spinal decompression therapy with routine physical therapy is more effective, statistically and clinically, than routine physical therapy alone in terms of improving pain, lumbar range of motion, back muscle endurance, functional disability, and physical role domain of quality of life, in patients with lumbar radiculopathy, following 4 weeks of treatment. Trial registration WHO Iranian registry of clinical trials ( IRCT20190717044238N1 ) Dated: 23.12.2019.

Hoda M. Abdel-Naby, Sarah S. El-Tawab, Mohamed M. Rizk et al.

Abstract Background Interleukin-17 (IL-17) is a cytokine that promotes activation of multiple catabolic pathways resulting in cartilage and tissue damage. It has features making it increasingly attractive as a biological marker, especially in rheumatoid arthritis (RA) and osteoarthritis (OA). However, its expression is heterogeneous; not all patients’ exhibit high IL-17 levels, and its level along the disease course is still challenging to predict. Aim of the work The objectives of this study were to compare serum IL-17 levels in patients with early knee OA and in RA patients, to determine its correlation with disease activity in RA and to determine if it is correlated with functional scores in both RA and OA. Subjects and methods Twenty early knee OA patients (32.7 ± 3.7) years were included. Diagnosis of early OA was based on Luyten et al. 2012 early knee OA classification (early OA 2012). This study also included 25 RA patients aged 32.8 ± 5.1 years, and the diagnosis was according to 2010 ACR-EULAR classification criteria for RA. The current work also included a control group of 20 healthy volunteers aged 31.9 ± 3.2 years. The serum IL-17 level was assessed by using the ELISA technique. Results Serum IL-17 level was significantly high in early knee OA patients (5.2 pg/ml) and was significantly higher in RA patients (5.9 pg/ml) compared to the control group (4.9 pg/ml) (P < 0.001). Conclusions The increased serum IL-17 level in patients with early knee OA suggests its pathogenic role in the disease. Serum IL-17 positive correlation with the severity of knee OA-related pain proposes that it may be a potential marker to target for early treatment of knee OA-related pain.

Ryan J. Malonis, J. T. Earnest, A. S. Kim et al.

Significance Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and Mayaro virus (MAYV), cause febrile illness, rash, and a debilitating chronic polyarthritis in humans. Currently, there are no approved vaccines or antiviral therapies for the prevention or treatment of alphavirus infection. Here, we identified and characterized 33 monoclonal antibodies (mAbs) from a CHIKV-convalescent donor that cross-react with other arthritogenic alphaviruses. We demonstrate that five broadly neutralizing mAbs can inhibit multiple arthritogenic alphaviruses and map their epitopes through binding and viral escape mutant analysis. Finally, we show that two mAbs, DC2.M16 and DC2.M357, protect against alphavirus disease in mice. These studies inform our understanding of how the human immune system combats alphavirus infection and may guide the development of antiviral treatments and vaccines. Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAbs) from a CHIKV-convalescent donor. We characterized 33 human mAbs that cross-reacted with CHIKV and MAYV and engaged multiple epitopes on the E1 and E2 glycoproteins. We identified five mAbs that target distinct regions of the B domain of E2 and potently neutralize multiple alphaviruses with differential breadth of inhibition. These broadly neutralizing mAbs (bNAbs) contain few somatic mutations and inferred germline–revertants retained neutralizing capacity. Two bNAbs, DC2.M16 and DC2.M357, protected against both CHIKV- and MAYV-induced musculoskeletal disease in mice. These findings enhance our understanding of the cross-reactive and cross-protective antibody response to human alphavirus infections.

Jogender Kumar, S. Saini, V. Sundaram et al.

Background & objectives: Congenital anomalies lead to significant morbidity and mortality. Systematically published data on the prevalence and spectrum of congenital anomalies from India are scarce. This study was aimed to ascertain the prevalence, spectrum, trend, and outcome of congenital anomalies at a tertiary care centre in north India over two decades. Methods: Electronic records of all live births from January 1998 to December 2017 were retrieved, and the neonates with congenital anomaly were included in this retrospective analysis. International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) was used for uniformity and international comparison. The further sub-categorization was done as per the WHO birth defects surveillance manual. The prevalence of individual as well as overall congenital anomalies was calculated. Run charts were used to analyze the trends. Results: In the two decades studied (1998-2017), there were 86850 live births, of which 1578 [1.82%, 95% confidence interval (CI): 1.73-1.91%] neonates had a major congenital anomaly. The overall prevalence of anomalies was 182 (95% CI: 173-191) per 10,000 live births. Malformation of the circulatory system was the most common (28.0%) followed by musculoskeletal (18.6%) and urinary system (14.3%). Congenital anomaly-related death rate was 6.78 per 1000 live births. No significant trend was observed in the annual prevalence, individual malformations or contribution of congenital anomalies to overall mortality over the two decades. Interpretation & conclusions: Our results showed a high prevalence of congenital anomalies which could be responsible for significant mortality, warranting the need for a national surveillance programme and birth defect services. It is important to have a national database to know the overall burden and spectrum of congenital anomalies in the country.

Jenna M. Leser, Anicca Harriot, Heather V. Buck et al.

The decline in the mass and function of bone and muscle is an inevitable consequence of healthy aging with early onset and accelerated decline in those with chronic disease. Termed osteo-sarcopenia, this condition predisposes the decreased activity, falls, low-energy fractures, and increased risk of co-morbid disease that leads to musculoskeletal frailty. The biology of osteo-sarcopenia is most understood in the context of systemic neuro-endocrine and immune/inflammatory alterations that drive inflammation, oxidative stress, reduced autophagy, and cellular senescence in the bone and muscle. Here we integrate these concepts to our growing understanding of how bone and muscle senses, responds and adapts to mechanical load. We propose that age-related alterations in cytoskeletal mechanics alter load-sensing and mechano-transduction in bone osteocytes and muscle fibers which underscores osteo-sarcopenia. Lastly, we examine the evidence for exercise as an effective countermeasure to osteo-sarcopenia.