Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center,randomized, double-blind,phase III clinical trial

Clinical Rheumatology - To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing...     

Association of serum levels and receptor genes BsmI,TaqI and FokI polymorphisms of vitamin D with the severity of multiple sclerosis

PurposeMultiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Vitamin D has a major role in preventing inflammatory disorders. Therefore, any alteration in vitamin D receptor (VDR) might be a genetic risk factor for MS development. This study aimed to evaluate the effect of serum levels and VDR FokI, BsmI, and TaqI gene polymorphisms on the severity of MS.MethodsThis case-control study recruited 160 MS patients (71.9% females, mean age of 34.3 ± 8.3 years) and 162 (66.7% females, mean age 35.4 ± 7.9 year) age, sex, and ethnicity matched healthy controls. FokI (rs2228570), BsmI (rs1544410), and TaqI (rs731236) polymorphisms were carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Demographic, clinical parameters, and the levels of vitamin D were compared between groups.ResultsWe found that the frequency of FokI and TaqI polymorphisms significantly differed between the patients and the controls (p = 0.0127 and p = 0.0236, respectively). The MS patients had low levels of vitamin D compared to the controls (p = 0.011). In addition, TaqI T/C polymorphism significantly decreased the levels of vitamin D in the MS patients (p = 0.002). However, there was no significant association between FokI or BsmI SNPs and the levels of vitamin D in MS patients (p > 0.5).ConclusionOur results suggest that FokI and TaqI polymorphisms of VDR are associated with MS risk and TaqI polymorphism is associated with Vitamin D levels in MS patients. Meanwhile, no difference was observed between VDR gene polymorphisms and any types of MS.     

The use of immunohistochemistry for IgG4 in the diagnosis of autoimmune pancreatitis: A systematic review and meta-analysis

BackgroundThe diagnosis of autoimmune pancreatitis (AIP) remains challenging, especially when serum IgG4 is normal or imaging features are indeterminate. We performed a systematic review and meta-analysis to evaluate the performance of IgG4 immunostaining of pancreatic, biliary, and ampullary tissues as a diagnostic aid for AIP.MethodsA comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted until February 2020. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy.ResultsThe meta-analysis included 20 studies comprising 346 patients with AIP and 590 patients with other pancreatobiliary diseases, including 371 pancreatobiliary malignancies. The summary estimates for tissue IgG4 in discriminating AIP and controls were as follows: diagnostic odds ratio 38.86 (95% confidence interval (CI), 18.70–80.75); sensitivity 0.64 (95% CI, 0.59–0.69); specificity 0.93 (95% CI, 0.91–0.95). The area under the curve was 0.939 for tissue IgG4 in discriminating AIP and controls. Subgroup analysis revealed no significant difference in diagnostic accuracy according to control groups (pancreatobiliary cancer versus other chronic pancreatitis) and sampling site (pancreas versus bile duct/ampulla).ConclusionsCurrent data demonstrate that IgG4 immunostaining of pancreatic, biliary, and ampullary tissue has a high specificity but moderate sensitivity for diagnosing AIP. IgG4 immunostaining may be useful in supporting a diagnosis of AIP when AIP is clinically suspected, but a combination of imaging and serology does not provide a conclusive diagnosis.     

Trends in Prevalence of Serious Psychological Distress and Depression Among Adults with Stroke in the United States

ObjectivesTo examine national trends in prevalence of serious psychological distress and depression among adults with stroke in the United States (US) from 2004 to 2017, and variations across sociodemographic subgroups.MethodsData were obtained from the household components of the 2004-2017 Medical Expenditure Panel Survey, a nationally representative survey in the US. History of stroke or transient ischemic attack was based on self-report. Psychological distress was measured by the Kessler-6 scale, and depressive symptoms were measured by the 2-item Patient Health Questionnaire. Logistic regression models were used to examine the trends in prevalence of serious psychological distress and depression overall and by age, sex, and race/ethnicity.ResultsAmong 10889 participants with stroke or transient ischemic attack, 60.0% were aged ≥ 65, 54.4% were female, and 72.2% were non-Hispanic white. The prevalence of serious psychological distress decreased from 14.9% in 2004-2005 to 11.3% in 2016-2017, corresponding to 7% lower odds every 2 years (adjusted odds ratio [aOR0.93, 95% confidence interval [CI]=0.89-0.97); and the prevalence of depression decreased from 23.1% in 2004-2005 to 18.3% in 2016-2017, corresponding to 5% lower odds every 2 years (aOR=0.95, 95% CI=0.92-0.98), after adjustment for sociodemographic characteristics, functional limitations, and antidepressant use. The trends varied significantly by age, but not sex and race/ethnicity. The overall decline was mainly driven by older adults above age 64.ConclusionsPrevalence of serious psychological distress and depression among US adults with stroke decreased from 2004 to 2017, but the burden of mental health problems remained high.     

Muscle Oxygenation of the Paretic and Nonparetic Legs During and After Arterial Occlusion in Chronic Stroke

Oxygen delivery and demand are reduced in the paretic leg post-stroke, reflecting decreased vascular function and reduced muscle quantity and quality. However, it is unknown how muscle oxygenation, the balance between muscle oxygen delivery and utilization, is altered in chronic stroke during and after occlusion-induced ischemia.ObjectivesThe objective was to determine muscle oxygen consumption rate, microvascular responsiveness and reactive hyperemia in the paretic and nonparetic legs during and after arterial occlusion post-stroke.Materials and MethodsMuscle oxygen saturation was measured with near-infrared spectroscopy on the vastus lateralis of each leg during 3-minute arterial occlusion and recovery (3 min). Muscle oxygen consumption was derived from the desaturation slope during ischemia, microvascular responsiveness was derived from the resaturation slope after ischemia and reactive hyperemia was derived from the area under the curve above baseline after ischemia. Results: Eleven subjects (91% male; 32.2±6.1 months post-stroke; age 62.9±13.6 years) with a hemiparetic gait pattern participated. There was no significant between-leg muscle oxygenation difference at rest (paretic: 64.9±16.6%; nonparetic: 70.6±15.6%, p = 0.13). Muscle oxygen consumption in the paretic leg (-0.53±0.24%/s) was significantly reduced compared to the nonparetic leg (-0.70±0.36%/s; p = 0.03). Microvascular responsiveness was significantly reduced in the paretic leg compared to the nonparetic leg (paretic: 4.6±1.8%/s; nonparetic: 5.7±1.6%/s, p = 0.04). Reactive hyperemia was not significantly different between legs (paretic:4384±2341%·s; nonparetic: 3040±2216%·s, p = 0.07).ConclusionMuscle oxygen consumption and microvascular responsiveness are impaired in the paretic compared to the nonparetic leg, suggesting both reduced skeletal muscle aerobic function and reduced ability to maximally perfuse muscle tissue.     

Does the asymmetry and extension function of the preoperative cervical paraspinal extensor predict postoperative cervical sagittal deformity in patients who undergo modified laminoplasty?

BACKGROUND CONTEXTA previous study found that the cross-sectional area (CSA) of the preoperative cervical paraspinal extensors (CPEs) was associated with loss of cervical lordosis after laminoplasty, while a recent study found that CPE asymmetry was associated with symptoms of degenerative cervical myelopathy. Whether preoperative CPE asymmetry can predict cervical sagittal deformity (CSD) after laminoplasty is unknown.PURPOSETo assess whether asymmetry, degree of degeneration, and extension function of the CPE can be used as predictors of postoperative CSD in patients who undergo laminoplasty.STUDY DESIGNA retrospective study.PATIENT SAMPLEFrom January 2017 to December 2019, 55 patients with multilevel cord compression and myelopathic symptoms were enrolled.OUTCOME MEASURESThe visual analog scale (VAS), neck disability index (NDI), and modified Japanese Orthopedic Association (mJOA) were used to assess cervical spinal function and quality of life.METHODSFrom January 2017 to December 2019, 55 patients undergoing modified laminoplasty were included. The following parameters were measured preoperatively and 24 months postoperatively on X-ray: (1) C0–C2 Cobb angle; (2) C2–C7 Cobb angle (CL); (3) T1 slope (T1S); (5) C2–C7 sagittal vertical axis (SVA); (6) T1S minus CL; (7) Preoperative extension function: Extension CL minus Neutral CL (EF). Preoperative global alignment parameters: (8) spino cranial angle, (9) C7-S1 sagittal vertical axis (C7 SVA), (10) pelvic incidence, (11) lumbar lordosis, (12) thoracic kyphosis. (13) Preoperative CPE parameters: Summation of bilateral total cross-sectional area (STCSA), summation of bilateral total cross-sectional area ratio (STCSAR), total cross-sectional area asymmetry, summation of bilateral functional cross-sectional area of muscle (SFCSA), summation of bilateral functional cross-sectional area of muscle ratio (FCSAR), and functional cross-sectional area of muscle asymmetry (FCSAA). The VAS, mJOA, and NDI were used to evaluate cervical spine function and quality of life. Patients were divided into the CSD group and the non-deformed group (N-CSD) group postoperatively, and the parameters between the two groups were compared. The Pearson correlation coefficient was used to evaluate the relationship between the parameters, and multiple regression analysis and ROC curve analysis were used to determine the predictors and key values.RESULTSCompared with functional scores, mJOA in the CSD group was significantly lower than that in the N-CSD group, while NDI and VAS were significantly higher. Postoperative CL was significantly correlated with EF, SFCSA/STCSA (C3–C6), SFCSAR (C4 and C6), STCSAR (C6), and FSCAA (C6). T1S minus CL was significantly correlated with EF, SFCSA/STCSA (C3–4 and C6), SFCSAR (C4 and C6), STCSAR (C6) and FSCAA (C6). C2–7 SVA was significantly correlated with EF, SFCSAR (C4 and C6), STCSAR (C6), and FSCAA (C6). Multiple regression analysis showed that FCSAA (C6), SFCSAR (C6), SFCSAR (C4), and EF were significant predictors of postoperative CSD. ROC curve analysis showed that the optimal cutoff points were 18.405, 2.95, 4.47, and 11.96.CONCLUSIONSThe present study found that preoperative extension dysfunction of CPEs, asymmetry at the C6 level cervical extensors, and cervical extensor CSAs without fatty infiltration at the C4 and C6 levels were associated with cervical sagittal imbalance after modified laminoplasty. These factors can be considered when future spine surgeons formulate surgical plans.     

Craniocervical instability in patients with Ehlers-Danlos syndrome: controversies in diagnosis and management

Ehlers-Danlos syndrome (EDS) is a rare hereditary condition that can result in ligamentous laxity and hypermobility of the cervical spine. A subset of patients can develop clinical instability of the craniocervical junction associated with pain and neurological dysfunction, potentially warranting treatment with occipitocervical fixation (OCF). Surgical decision-making in patients with EDS can be complicated by difficulty distinguishing from hypermobility inherent in the disease and true pathological instability necessitating intervention. Here we comprehensively review the available medical literature to critically appraise the evidence behind various proposed definitions of instability in the EDS population, and summarize the available outcomes data after OCF. Several radiographic parameters have been used, including the clivo-axial angle, basion-axial interval, and pB-C2 measurement. Despite increasing recognition of EDS by spine surgeons, there remains a paucity of data supporting proposed radiographic parameters for spinal instability among EDS patients. Furthermore, there is a lack of high-quality evidence concerning the efficacy of surgical treatments for chronic debilitating pain prevalent in this population. More standardized clinical measures and rigorous study methodologies are needed to elucidate the role of surgical intervention in this complex patient population.     

Dexmedetomidine promotes liver regeneration in mice after 70% partial hepatectomy by suppressing NLRP3 inflammasome not TLR4/NFκB

Inflammasome activation is mediated by NOD-like receptors (NLRs) that play important role in cellular proliferation. NLRP3 senses the widest array of stimuli. But its role in the liver regeneration after partial hepatectomy (PHx) is still unknown. Dexmedetomidine (Dex) has been documented to protect the liver against ischemia-reperfusion injury via the suppression of the TLR4/NF-κB pathway, which is important for NLRP3 inflammasome activation and liver regeneration. We tested whether Dex contributes to liver regeneration, and investigated its consequent effect on inflammasome activation. In vitro, L02 human liver cells were treated with Dex at different concentrations. The 70% PHx was performed in C57 BL/6 mice as PHx group, and sham-operated animals as Sham group, Dex-treated animals were assigned into two groups: Dex + PHx, which received single intraperitoneal injections of Dex (25 μg/kg) before PHx 30 mins; Dex + PHx + Dex, which received additional Dex (25 μg/kg) after PHx for 3 days. Dex significantly inhibited the proliferation of Lo2 cells in vitro and decreased the expression of TLR4/NFκB. In vivo, Dex + PHx exhibited promoted effect on liver regeneration and liver function recovery via inhibiting NLRP3 inflammasome activation. Dex + PH + Dex inhibited the liver regeneration, which may be associated with suppressed expression levels of TLR4/NFκB pathway. Though Dex pretreatment contributed to liver regeneration and function recovery via inflammation suppression, excessive inflammation suppression accompanied with TLR4 suppression could be related to the diminished liver regeneration, suggesting that TLR4/NFκB played important role in liver regeneration and Dex + PHx might be a useful therapeutic strategy to promote liver regeneration in clinical.