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The On&Out study is aimed at assessing the effectiveness, cost-utility and physiological underpinnings of the FIBROWALK multicomponent intervention conducted in two different settings: online (FIBRO-On) or outdoors (FIBRO-Out). Both interventions have proved to be efficacious in the short-term but there is no study assessing their comparative effectiveness nor their long-term effects. For the first time, this study will also evaluate the cost-utility (6-month time-horizon) and the effects on immune-inflammatory biomarkers and Brain-Derived Neurotrophic Factor (BDNF) levels of both interventions. The objectives of this 6-month, randomized, controlled trial (RCT) are 1) to examine the effectiveness and cost-utility of adding FIBRO-On or FIBRO-Out to Treatment-As-Usual (TAU) for individuals with fibromyalgia (FM); 2) to identify pre-post differences in blood biomarker levels in the three study arms and 3) to analyze the role of process variables as mediators of 6-month follow-up clinical outcomes. Participants will be 225 individuals with FM recruited at Vall d'Hebron University Hospital (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs. TAU + FIBRO-On vs. TAU + FIBRO-Out. A comprehensive assessment to collect functional impairment, pain, fatigue, depressive and anxiety symptoms, perceived stress, central sensitization, physical function, sleep quality, perceived cognitive dysfunction, kinesiophobia, pain catastrophizing, psychological inflexibility in pain and pain knowledge will be conducted pre-intervention, at 6 weeks, post-intervention (12 weeks), and at 6-month follow-up. Changes in immune-inflammatory biomarkers [i.e., IL-6, CXCL8, IL-17A, IL-4, IL-10, and high-sensitivity C-reactive protein (hs-CRP)] and Brain-Derived Neurotrophic Factor will be evaluated in 40 participants in each treatment arm (total n = 120) at pre- and post-treatment. Quality of life and direct and indirect costs will be evaluated at baseline and at 6-month follow-up. Linear mixed-effects regression models using restricted maximum likelihood, mediational models and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. This study has been approved by the Ethics Committee of the Vall d'Hebron Institute of Research. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. Trial registration number NCT05377567 (clinicaltrials.gov).

The dominant collagen of the cartilaginous matrix in adults is type II collagen. The amount of type II collagen in the intercellular matrix of cartilage is significantly reduced against the background of musculoskeletal system diseases. The basis of articular cartilage is hyaline cartilage tissue consisting of chondrocytes with tissue-specific antigens that induce the production of antibodies in patients with osteoarthritis (OA). Today, new approaches are being considered in the treatment of OA with the use of udenatured type II collagen (UC-II). Such molecular mechanisms of action of UC-II as the formation of a systemic response through oral tolerance are discussed, since the induction of tolerance is the immune pathway, by default, in the intestine. A number of experimental, preclinical (on volunteers) and clinical studies have shown the effectiveness and safety of the use of UC-II in OA. Standardized extracts of UC-II exhibit anti-inflammatory, immunoregulatory, chondroprotective effects, contributing to the reduction of pain symptoms of OA. Against the background of taking UC-II with induced OA, there is a statistically significant decrease in the level of proinflammatory cytokines, such as interleukin (IL-1β, IL-6), tumor necrosis factor alpha (TNF), C-reactive protein (CRP) in serum and the level of max proteinases (MMP-3), nucleated factor «kappa-bi» (NF-κB) in the knee joint. UC-II significantly inhibits the production of prostaglandin E2 (by 20%) and the expression of genes encoding proinflammatory proteins. In experimental models and in OA patients, a decrease in the severity of pain syndrome, an increase in endurance, mobility and an improvement in the functional state of the joints were noted. Clinically, no changes in the structure of the muscle fiber were detected with increased physical exertion. With OA on the background of UC-II (10-40 mg/s), there was a statistically significant decrease in joint pain according to WOMAC. A promising direction of OA therapy is the combination of UC-II with chondroitin sulfate and glucosamine sulfate.

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.

Knee osteoarthritis (OA) is a leading cause of disability in the elderly population. Chronic disabling pain is associated with maladaptive neuroplastic changes in brain networks, commonly associated with central sensitization. The main clinical features of nociplastic pain conditions include combined peripheral and central sensitization, and it is crucial to recognize this type of pain, as it responds to different therapies than nociceptive and neuropathic pain.

Dhat syndrome is a culture-bound psychiatric syndrome most commonly found in the Indian subcontinent. It has been characterized as the experiential fear of losing semen through ejaculation, nocturnal emission, or other means. While Dhat syndrome is common in the Indian subcontinent, given the lack of representativeness, generalizability, and closer connection to Ayurvedic system, there have been limited studies or recognition of symptoms among healthcare providers around the world. In this review, we describe Dhat syndrome, its epidemiology, risk factors, comorbidities, diagnosis, treatment, and its management. For patients with Dhat syndrome, it becomes important to appreciate how generalized depression and anxiety may persist alongside the disorder and those symptoms can be common and non-specific. Related to its strong cultural connection with South Asia such as the belief on Dhat's role in health and vitality influence, it also becomes important to recognize that the syndrome can be found in other populations and the importance of cultural humility and nonconfrontational approach for patient care. In summary, this review provides an informative understanding of Dhat syndrome for non-Indian clinicians who may not be prepared for a patient encounter with vague somatic symptoms in the context of semen loss. Treatment for Dhat syndrome is the same as treatments for major depressive disorder.

Knee OA-related pain varies in impact across individuals and may relate to central nervous system alterations like accelerated brain aging processes. We previously reported that older adults with chronic musculoskeletal pain had a significantly greater brain-predicted age, compared to pain-free controls, indicating an "older" appearing brain. Yet this association is not well understood. This cross-sectional study examines brain-predicted age differences associated with chronic knee osteoarthritis pain, in a larger, more demographically diverse sample with consideration for pain's impact.

Outcomes after traumatic hip fracture have shown to be significantly improved with timely surgical management. This study determined whether there were differences in efficacy of fascia iliaca compartment block (FICB) on pain outcomes in patients with hip fracture, once stratified by time to surgery.

Multiple rice bodies in the wrist is a rare disorder that requires surgery, and there are still many uncertainties regarding its diagnosis and treatment.

Primary testicular neuroendocrine tumors (TNETs) are sporadic, accounting for only 0.23% of all testicular tumors. Few cases have been reported in the literature, and no uniform treatment protocol exists. We report a case of a primary TNET with liver lymph node metastasis diagnosed at the age of 24 years and discuss its clinicopathological features, diagnosis, differential diagnosis, treatment, and prognosis.

Pancreatitis is a severe inflammatory pancreatic disease commonly due to bile duct stones or excessive alcohol usage, with clinical manifestations of abdominal pain, nausea, fever, and fluid collections. Healthy persons with less symptomatic pancreatitis are quite rare. Herein, we report a case of a patient with an undetermined onset of pancreatitis mimicking left arm cellulitis due to thrombotic vasculitis of the brachiocephalic vein.