Rejected

Hemorrhage and trauma-induced coagulopathy cause significant morbidity and mortality in trauma patients. Although blood products are the cornerstone of resuscitation, these resources are scarce, necessitating alternatives. This review examines the use of alternative blood products in trauma as well as the literature supporting their use.

Effective rabbit analgesia is challenging, and there are few studies available on the newer COX-2 selective NSAIDs, such as robenacoxib. This study aimed to establish the pharmacokinetics of oral and subcutaneous robenacoxib, describe its inhibitory actions on COX enzymes, and develop dosing, using six healthy New Zealand white rabbits. Pharmacokinetics were determined from plasma concentrations after oral administration of robenacoxib (0.83-0.96 mg/kg) and also after subcutaneous administration (2 mg/kg). The inhibitory actions of robenacoxib were evaluated by measuring plasma concentrations of thromboxane B (TBX ) and prostaglandin E (PGE ) as surrogate markers of cyclooxygenase enzyme isoform inhibition. The mean maximum concentration for oral and subcutaneous administration was 0.23 μg/ml and 5.82 μg/ml, respectively. Oral robenacoxib administration did not demonstrate a significant difference between any time point for PGE or TBX , though subcutaneous administration did for both. There was no significant difference in PGE or TBX concentrations at any time point when comparing subcutaneous versus oral routes. Although the results support that plasma robenacoxib exceeds the therapeutic levels compared to dogs and cats, there was little significance in the difference in the changes associated with COX-1 and COX-2 inhibition. Further studies are warranted to determine appropriate dosing, safety, and efficacy in rabbits.

Ischemia with nonobstructive coronary arteries (INOCA) is a prevailing finding in patients with angina. However, the main factors underlying the risk of being rehospitalized for chest pain in patients with INOCA remain mostly unknown.

To study the oral 11 beta-hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitor BI 187004 (NCT02150824), as monotherapy and in combination with metformin, versus placebo in patients with type 2 diabetes mellitus (T2DM) affected by overweight or obesity.

Cannabis contains over 500 distinct compounds, which include cannabinoids, terpenoids, and flavonoids. However, very few of these compounds have been studied for their beneficial effects. There is an emerging concept that the constituents of the cannabis plant may work in concert to achieve better therapeutic benefits. This study is aimed at determining if the combination of a minor cannabinoid (cannabidiol, CBD) and a terpene (beta-caryophyllene, BCP) works in concert and if this has any therapeutic value. We used an inflammatory pain model (formalin) in mice to test for any functionality of CBD and BCP in combination. First, we determined the analgesic effect of CBD and BCP individually by establishing dose-response studies. Second, we tested the analgesic effect of fixed-ratio combinations and monitored any adverse effects. Finally, we determined the effect of this combination on inflammation. The combination of CBD and BCP produces a synergistic analgesic effect. This effect was without the cannabinoid receptor-1 side effects. The analgesic effect of CBD and BCP in combination involves an inflammatory mechanism. The combination of these two constituents of the cannabis plant, CBD and BCP, works in concert to produce a therapeutic effect with safety profiles through an inflammatory mechanism.

Pruritus is a hallmark feature in pemphigoid diseases, where it can be severe and greatly impact the quality of life of affected patients. Despite being a key symptom, the exact pathophysiological mechanisms involved in pruritus in pemphigoid are yet to be fully elucidated and effective therapies addressing them are limited. This review summarizes the present understanding of pruritus specific to pemphigoid diseases, especially the pruritogens that induce it, and the therapeutic options that have been explored so far. The majority of the available evidence is on bullous pemphigoid and epidermolysis bullosa acquisita. Histamine derived from basophils correlates with pruritus severity, with omalizumab demonstrating promising efficacy in pruritus for bullous pemphigoid. IL-4/-13 contribute to itch in bullous pemphigoid with dupilumab being evaluated in clinical trials. Other pruritogens of interest include substance P, tryptase, and thymic stromal lymphopoetin, with therapies targeting them requiring further investigation. Scratching behaviors contribute directly to blister formation through various mechanisms, such as pathological autoantibody recruitment, T helper cell type 1 polarization, and exposure of intracellular autoantigens. Treatments addressing these pathways may contribute to decreasing disease severity. Additional studies are needed to fully characterize how pruritus is regulated in pemphigoid diseases, to help pave the way to develop novel and effective therapeutics that will not only address pruritic symptoms but also decrease disease severity.

This systematic review and meta-analysis aimed to synthesize the evidence on the adverse events (AEs) of coronavirus disease 2019 (COVID-19) vaccinations in Saudi Arabia. A computerized search in MEDLINE via PubMed and OVID, Scopus, CENTRAL, and Web of Science was conducted using relevant keywords. The NIH tools were used for the quality assessment. A total of 14 studies (16 reports) were included. The pooled analysis showed that the incidence of AEs post-COVID-19 vaccination was 40.4% (95% CI:6.4% to 87%). Compared to the AstraZeneca vaccine, the Pfizer-BioNTech vaccine was associated with a lower risk ratio (RR) of wheezing (RR = 0.04), fever (RR = 0.32), chills (RR = 0.41), headache (RR = 0.47), dizziness (RR = 0.49), and joint pain (RR = 0.51). The Pfizer-BioNTech vaccine was associated with significantly higher RR of general allergic reactions (RR = 1.62), dyspnea (RR = 1.68), upper respiratory tract symptoms (RR = 1.71), and lymphadenopathy (RR = 8.32). The current evidence suggests that the incidence of AEs following COVID-19 vaccines is 40%; however, most of these AEs were mild and for a short time. The overall number of participants with AEs was higher in the Pfizer group compared to the AstraZeneca group; however, the AstraZeneca vaccine was associated with a higher RR of several AEs.

Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.

Infection is an infrequent complication of lower extremity prosthetic joint surgery. Approximately one third develop within 3 months (early), another third within 1 year (delayed), and the remainder more than 1 year (late) after surgery. The diagnosis of periprosthetic joint infection is not always straightforward. Pain, the most common symptom, is present in 90%-100% of patients. The presence of fever is more variable, ranging from less than 5% to more than 40% of patients with infection. Erythema and joint swelling are often present in acute infections, but are less common in chronic infections. Erythrocyte sedimentation rate, C-reactive protein and interleukin-6 levels are useful "rule out" tests, while peripheral blood leukocyte count and serum tumor necrosis factor α are not helpful. The diagnosis of periprosthetic joint infection often requires a combination of blood, synovial fluid, and tissue sample tests, as well as imaging. Plain radiographs lack sensitivity and specificity. Molecular imaging is useful for evaluating painful joint replacements. Bone scintigraphy is most useful as a screening test. If it is negative then infection and aseptic loosening are unlikely. Combined labeled leukocyte/bone marrow imaging is a very specific test for diagnosing lower extremity joint arthroplasty infection; sensitivity is more variable. Despite more than two decades of investigation, there still is no consensus on the value of F-FDG for diagnosing periprosthetic joint infection. Differing test probabilities, an inability to discriminate between infection and inflammation secondary to physiologic reactions, and lack of standardized interpretative criteria are obstacles to incorporating F-FDG into the routine diagnostic imaging workup of periprosthetic joint infection. Preliminary results for gallium-68 citrate, fluorine-18, and technetium-99m labeled antimicrobial fragments are encouraging but no large scale trials with these agents have been conducted. Limited data suggest that labeled leukocyte/bone marrow SPECT/CT and F-FDG-PET/CT are specific but not sensitive for diagnosing periprosthetic infection of shoulder arthroplasties. There are minimal data on molecular imaging for monitoring treatment response in periprosthetic infections.

This study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990-2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. Leading DALYs risk factors included smoking, high body mass index, and high fasting plasma glucose. Spain scored 74/100 among all health-related Sustainable Development Goals (SDGs) indicators, ranking 20 of 195 countries and territories. We forecasted that by 2030, Spain would outpace Japan, the United States, and the European Union. Behavioural risk factors, such as smoking and poor diet, and environmental factors added a significant burden to the Spanish population's health in 2019. Monitoring these trends, particularly in light of COVID-19, is essential to prioritise interventions that will reduce the future burden of disease to meet population health and SDG commitments.