Rejected

The term "axial spondyloarthritis" (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium.

Alagille syndrome (ALGS) is a rare, debilitating inheritable disease that is associated with refractory pruritus due to chronic cholestasis. The following systemic review and meta-analysis presents the latest evidence for ileal bile acid transport (IBAT) blockers in AGLS patients in order to improve their efficacy. This study adhered to PRISMA 2020 Statement guidelines. A systematic search of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane library was conducted from inception until 23 October 2022. A combination of the following keywords was used: Alagille syndrome, therapeutics, treatment, therapy. Meta-analytical outcomes included effect directions of end-line changes in serum bile acids (sBAs), Itch Scale scores (ItchRO), Multidimensional Fatigue Scale scores, pediatric quality of life (QL), alanine aminotransferase (ALT), and total bilirubin. A total of 94 patients across four trials were enrolled and received maralixibat, odevixibat, or a placebo. There was a significant reduction in ItchRO scores by 1.8 points, as well as in sBAs by 75.8 μmol/L. Both the Multidimensional Fatigue Scale and Pediatric QL scale were also improved by 11.4 and 8.3 points, respectively. However, ALT levels were raised by 40 U/L. The efficacy of IBAT inhibitors across current trials was noted. Future trials may focus on the optimization of dosing regimens, considering gastrointestinal side effects and drug-induced ALT elevation in AGLS patients.

The facilitated activity of -methyl-D-aspartate receptors (NMDARs) in the central and peripheral nervous systems promotes neuropathic pain. Amitriptyline (ATL) and desipramine (DES) are tricyclic antidepressants (TCAs) whose anti-NMDAR properties contribute to their analgetic effects. At therapeutic concentrations <1 µM, these medicines inhibit NMDARs by enhancing their calcium-dependent desensitization (CDD). Li, which suppresses the sodium-calcium exchanger (NCX) and enhances NMDAR CDD, also exhibits analgesia. Here, the effects of different [Li]s on TCA inhibition of currents through native NMDARs in rat cortical neurons recorded by the patch-clamp technique were investigated. We demonstrated that the therapeutic [Li]s of 0.5-1 mM cause an increase in ATL and DES ICs of ~10 folds and ~4 folds, respectively, for the Ca-dependent NMDAR inhibition. The Ca-resistant component of NMDAR inhibition by TCAs, the open-channel block, was not affected by Li. In agreement, clomipramine providing exclusively the NMDAR open-channel block is not sensitive to Li. This Ca-dependent interplay between Li, ATL, and DES could be determined by their competition for the same molecular target. Thus, submillimolar [Li]s may weaken ATL and DES effects during combined therapy. The data suggest that Li, ATL, and DES can enhance NMDAR CDD through NCX inhibition. This ability implies a drug-drug or ion-drug interaction when these medicines are used together therapeutically.

Chronic urticaria is a debilitating skin condition that is defined as itchy hives at least twice a week and lasting for six or more weeks, with or without angioedema. Chronic spontaneous urticaria (CSU) is a form of disease that is witnessed in two-thirds of those with chronic urticaria. This meta-analysis explores the efficacy of differential dosages of omalizumab for outcomes of weekly itching scores, weekly wheal scores, urticarial assessment score 7 (UAS7), and responder rates. Adhering to PRISMA Statement 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Embase, and Web of Science was conducted until 15 September 2022. A combination of the following keywords was used: omalizumab and chronic urticaria. Data comprising clinical trial ID, name, author/year, country, dosage and time of intervention, inclusion criteria, mean age, female gender, and racial grouping information were obtained. The meta-analytical outcomes were analyzed in RevMan 5.4. The risk-of-bias assessment was conducted using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of 10 trials comprising 1705 patients with CSU were included. Notably, 1162 belonged to the intervention group, while 543 were controls. A total of 70.4% of the participants were female in the intervention group, while 65.6% of them were female in the control group. The overall mean age was 38.64 ± 10.66 years. Weekly itch score outcomes were most notable with 150 mg dosage (Cohen's d = -2.6, 95% CI = -4.75, -0.46, = 0.02). The weekly wheal score outcomes had the largest effect size with 300 mg dosage (Cohen's d = -1.45, 95% CI = -2.2, -0.69, = 0.0002). For UAS7 outcomes, the largest effect size was yielded with 150 mg dosage (Cohen's d = -6.92, 95% CI: -10.38, -3.47, < 0.0001). The response rate to omalizumab had a likelihood of being higher with 300 mg of intervention compared to placebo (OR = 8.65, 95% CI = 4.42, 16.93, < 0.0001). Well-rounded urticarial symptom resolution was observed with 150 mg and 300 mg dosages of omalizumab. Improvement of UAS7 was more comparable with 150 mg dosage, whereas the chance of response to treatment was higher with 300 mg dosage. Our findings support omalizumab as an effective intervention for adult and pediatric populations that are resistant to many therapies, including high-dose H1-antihistamines.

Enhanced recovery after surgery (ERAS) protocols have been propagated in general surgery since the mid-1990s due to medical and health economic advantages for patients as well as hospitals. A comprehensive implementation in Germany is not yet established, although the demographic change requires more than ever concepts for the safe treatment of multimorbid frail patients. The aim of this review is to present modern ERAS concepts, to discuss an extension to prehabilitation measures for frail patients and to present aspects of structural feasibility.

Back pain is common and costly, with negative impacts on both individuals and the health care system. Rural, remote, and Indigenous populations are at greater risk of experiencing back pain compared to urban and non-Indigenous populations. Potential barriers to health care access among Canadians with chronic back pain (CBP) have been identified; however, no study has used lived experiences of people with CBP to drive the selection, analysis, and interpretation of variables most meaningful to patients.

The authors aimed to compare the effects of a one-time ultrasound (US)-guided subacromial corticosteroid injection and three-time ozone (O-O) injection in patients with chronic supraspinatus tendinopathy.

Fragility fractures of the sacrum (FFS) have been detected more and more frequently in recent times, and the incidence will continue to increase due to increasing life expectancy. The aim of this study was to compare the clinical outcome of conservative, interventional and surgical treatment of FFS.

Quadratus lumborum block (QLB) is a fascial plane block. There is no randomized study on the efficacy of QLB for lumbar surgery. We evaluated the efficacy of QLB for postoperative pain management and patient satisfaction after lumbar disc herniation surgery (LDHS).

Occupations or activities where donning head-supported mass (HSM) is commonplace put operators at an elevated risk of chronic neck pain. Yet, there is no consensus about what features of HSM influence the relative contributions to neck loads. Therefore, we tested four hypotheses that could increase neck loads: (i) HSM increases gravitational moments; (ii) more muscle activation is required to stabilize the head with HSM; (iii) the position of the HSM centre of mass (COM) induces gravitational moments; and (iv) the added moment of inertia (MOI) from HSM increases neck loads during head repositioning tasks. We performed a sensitivity analysis on the C5-C6 compression evaluated from a 24-degree freedom cervical spine model in OpenSim for static and dynamic movement trials. For static trials, we varied the magnitude of HSM, the position of its COM, and developed a novel stability constraint for static optimization. In dynamic trials, we varied HSM and the three principle MOIs. HSM magnitude and compression were linearly related to one another for both static and dynamic trials, with amplification factors varying between 1.9 and 3.9. Similar relationships were found for the COM position, although the relationship between C5-C6 peak compression and MOI in dynamic trials was generally nonlinear. This sensitivity analysis uncovered evidence in favour of hypotheses (i), (ii) and (iii). However, the model's prediction of C5-C6 compression was not overly sensitive to the magnitude of MOI. Therefore, the HSM mass properties may be more influential on neck compression than MOI properties, even during dynamic tasks.