Glanzmann thrombasthenia (GT) is a rare, autosomal recessive platelet aggregation disorder caused by mutations in the ITGA2B and ITGB3 genes. These mutations result in quantitative or qualitative deficiencies in the alpha IIb beta 3 integrin complex, impairing platelet aggregation and leading to recurrent mucocutaneous bleeding. The key findings include absent or severely reduced platelet aggregation with adenosine diphosphate (ADP), epinephrine, and collagen, while aggregation with ristocetin remains normal. While hundreds of pathogenic variants have been identified, the genetic landscape of GT continues to expand with the discovery of novel mutations. GT treatment focuses on controlling bleeding. Hemopoietic stem cell transplantation (HSCT) offers a curative option for severe cases, while gene therapy is a promising future approach. Here, we report the case of a four-year-old female presenting with recurrent bilateral epistaxis and a significant family history of bleeding diathesis. Whole-exome sequencing (WES) revealed a novel homozygous missense variant in ITGA2B (c.655G>T; p.Gly219Cys). This variant, which is absent from public genomic databases, was predicted to be deleterious by multiple in-silico computational tools, supporting a diagnosis of GT. This case identifies a previously unreported pathogenic variant and underscores the critical role of genetic testing in diagnosing unexplained mucocutaneous bleeding, particularly in cases involving consanguinity.

Von Willebrand factor (VWF) is a key coagulation protein, tethering platelets to the sites of injury through binding sites for platelet glycoprotein Ibα and exposed subendothelial collagen. VWF synthesis occurs in endothelial cells and megakaryocytes, a complex process involving the VWF propeptide, dimerization and multimerization, and glycosylation. Von Willebrand disease results from defects or dysfunction in VWF and includes both quantitative and qualitative issues with the VWF protein. VWF is cleaved by ADAMTS13 and ultimately cleared from circulation. Although it is clear that VWF plays an important role in clot formation, it may also be important in a number of other areas including angiogenesis. Our knowledge of VWF has come a long way in the 100 years since the first publication by Erik von Willebrand in 1926 thanks to a large number of researchers in the VWF biology field.

Musculoskeletal pain (MSP) is a general term for pain varying by source, characterized into nociceptive (tissue pain), neuropathic (nerve pain), and nociplastic (centralized pain). It affects muscles, bones, joints, tendons, and ligaments due to multiple etiologies, including trauma, degenerative changes, or autoimmune and inflammatory disorders, presenting as either acute or chronic pain with symptoms such as sharp, dull, tingling, or burning sensations. It is a leading cause of disability globally, particularly in low and middle-income countries. We want to highlight a real-world implementation that aims to illustrate translational feasibility, and not a comparative efficacy trial on degenerative (wear and tear) conditions such as osteoarthritis and tendinous injuries. Ultrasound-guided musculoskeletal (MSK) injections offer a minimally invasive and accurate treatment option for these two conditions, especially in settings where patients can face barriers to surgical care. Traditionally, management of such cases includes analgesia, physiotherapy, and surgery. This article highlights the implementation of ultrasound-guided musculoskeletal injection procedures in a general medical and surgical clinical setting in southern Trinidad, including hyaluronic acid (HA), platelet-rich plasma (PRP), and diluted corticosteroid injections. Over the course of two years (2023-2025), a total of 115 adult patients with chronic MSP who had an unsatisfactory response to treatment with oral analgesics were treated under ultrasound guidance. The patients largely reported qualitative improvement in pain and increased functionality post-intervention. No major complications due to the procedures were observed. Through this perspective/observational experience, we do not aim to quantify the treatment effect sizes, but rather to bring to attention the practical procedural techniques, associated safety, potential workflow advantages, and practical considerations of ultrasound-guided musculoskeletal injections, thereby highlighting their use as a radiation-free, feasible, and efficient intermediate treatment option in resource-limited settings that have limited access to advanced imaging or surgical services.

Glanzmann thrombasthenia (GT) is an inherited hemorrhagic disorder characterised by impaired platelet functions, manifested clinically as spontaneous bleeding. It is usually inherited in an autosomal recessive manner. Platelet dysfunction in patients with GT is caused by quantitative and/or qualitative deficiencies in αIIbβ3, which result from mutations in the genes encoding αIIbβ3. These genetic alterations lead to platelet dysfunction characterised by impaired fibrinogen binding capacity upon agonist stimulation, defective aggregation and spreading. While classical GT typically exhibits normal platelet counts and morphology, very rare mutations in ITGA2B (encoding αIIb) and/or ITGB3 (encoding β3) cause macrothrombocytopenia or increased platelet anisotropy (heterogeneity of platelet size and morphology). This type of mutation mainly localises in the membrane-proximal region of αIIbβ3 and is inherited in an autosomal dominant manner. This particular type of disorder is called ITGA2B/ITGB3-related macrothrombocytopenia and has been considered a subset of congenital macrothrombocytopenia. Current research suggests that gain-of-function mutations in ITGA2B or ITGB3 underlie the pathogenesis of most ITGA2B/ITGB3-related macrothrombocytopenia and mechanistically distinguish it from classical GT. However, recent reports have documented non-activating ITGB3 mutations that also cause macrothrombocytopenia, presenting a profound challenge to the mechanistic understanding of ITGA2B/ITGB3-related macrothrombocytopenia. This review summarises the reported cases of gain-of-function mutations in ITGA2B and ITGB3 associated with ITGA2B/ITGB3-related macrothrombocytopenia hitherto and discusses the potential molecular pathways contributing to the unique phenotypes in ITGA2B/ITGB3-related macrothrombocytopenia.

The COVID-19 pandemic brought attention to post-viral smell distortion, or parosmia, which is defined as a qualitative dysfunction resulting from distorted odor perception in the presence of an odorous medium (1). Very often, qualitative and quantitative alterations occur simultaneously. Patients severely affected by qualitative odor disorders find that their quality of life has deteriorated (2). For quantitative loss from viruses, the role of olfactory training has been emphasized (3), along with high volume steroid nasal irrigations (4), and even injections with platelet-rich plasma (5). However, there has been no high-level evidence demonstrating an effective treatment for qualitative olfactory disorders.

von Willebrand disease (VWD) is a hereditary bleeding disorder first described by Erik von Willebrand in 1926. The disease is characterized by frequent bruising, bleeding from minor wounds, nosebleeds, heavy menstrual bleeding, bleeding after tooth extraction, gastrointestinal bleeding, and joint bleeds. The underlying cause of VWD was identified 45 years later as a deficiency of von Willebrand factor (VWF), a high-molecular-weight protein that circulates with factor VIII in plasma. The clinical diagnosis of VWD involves the presence of bleeding symptoms, detection of at least one abnormality of VWF function in laboratory tests, and demonstration of familial inheritance. VWD presents a broad spectrum of clinical and laboratory abnormalities, making the diagnostic process complex. Integrating clinical and laboratory data into the diagnostic pathway using a Bayesian approach can help build evidence for a diagnosis. Over the years, several diagnostic assays have been developed to measure the quantitative and qualitative properties of VWF. Automated laboratory assays for measuring VWF have been implemented in recent decades, and assessment tools for clinical evaluation of bleeding severity have been developed. Laboratory diagnosis involves screening and first-level diagnostic tests to measure VWF antigen, VWF-platelet binding activity, and factor VIII coagulant activity. Second-level subtyping tests are required to characterize the phenotypic defects of the type 2 variants and classify the patients. Proper diagnosis and classification of VWD are essential in order to recognize patients who may benefit from treatment, determine the optimal treatment modality, and prevent overdiagnosis.

Von Willebrand disease (VWD) is a highly heterogeneous inherited bleeding disorder caused by reduced levels or activity of von Willebrand factor (VWF). VWD is associated with a wide spectrum of clinical and laboratory phenotypes, but diagnosis is based on three main criteria: a positive bleeding history, low levels of circulating VWF and autosomal inheritance patterns. VWD is classified into quantitative VWF deficiencies (type 1, partial and type 3, almost total) and peculiar qualitative defects (type 2 A, B, M, and N). The prevalence of VWD has been estimated by epidemiological investigations to be ~1%, but a clearcut diagnosis in clinical practice is often not possible because of several confounding factors influencing plasma VWF levels, especially in mild cases. The prevalence of clinically relevant VWD could range from 1/1,000-10,000 inhabitants based on patients referred to tertiary care centers. Recent genetic prevalence data however suggest that pathogenic VWF variants or putative disease alleles may be significantly more common than 1%.

Left panel: Scheme of the XPAG-ITP trial. The dexamethasone monotherapy (DEX) arm consisted of DEX 40 mg/day for days 1-4 for one to three cycles every 28 days to a maximum of 12 weeks, cycles 2 + 3 were optional. Patients randomised to eltrombopag combined with dexamethasone (ETB + DEX) received eltrombopag (ETB) in combination with a short course of high-dose DEX beginning on day 1 (40 mg/day during days 1-4). The starting dose of ETB was 50 mg/day for 2 weeks; thereafter, the ETB dose was increased by 25 mg for all patients who did not achieve the target platelet count of ≥50 × 10[9]/L. The ETB tapering was performed by decreasing the dose by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Right upper panel: Clinical outcomes in patients treated with first-line ETB + DEX. Patients displayed a qualitatively longer response duration and qualitatively reduced usage of rescue medication. Right lower panel: The immunological T-cell response was different in treatment responders and non-responders. Patients with sustained response (responders) displayed a high T-cell clonality at baseline. Clones are depicted as bubbles (right side).

Shoulder disorders, including rotator cuff-related pain, adhesive capsulitis, impingement, glenohumeral osteoarthritis (GHOA), acromioclavicular (AC) pathology, instability, and biceps/superior labrum anterior to posterior (SLAP) lesions, are prevalent causes of pain, disability, and healthcare utilization. Contemporary care emphasizes non-operative strategies as first-line management, with surgery reserved for refractory symptoms or specific structural indications. The researcher conducted a systematized narrative review of adult non-operative management for common shoulder pathologies. Targeted searches of Medical Literature Analysis and Retrieval System Online (MEDLINE) (via PubMed), the Cochrane Library, and guideline repositories (American Academy of Orthopaedic Surgeons (AAOS)/American Shoulder and Elbow Surgeons (ASES)/American Physical Therapy Association (APTA)/American College of Rheumatology (ACR)) were performed from 2010 to October 2025. The researcher prioritized clinical practice guidelines, Cochrane and systematic reviews (including network meta-analyses), and randomized trials. Studies focused on non-operative interventions with patient-centered outcomes were qualitatively synthesized by pathology; no quantitative pooling was performed. Exercise-based rehabilitation is the cornerstone across conditions, producing clinically meaningful pain and functional gains and, in subacromial pain, outcomes comparable to surgery. For adhesive capsulitis, intra-articular corticosteroid, hydrodilatation, and suprascapular nerve block yield short-term benefits that are greatest when paired with mobilization and stretching. In GHOA, individualized range of motion (ROM) maintenance and strengthening, activity adaptation, and time-limited injections (corticosteroid; hyaluronic acid with variable evidence) dominate care; platelet-rich plasma remains investigational. For instability, early ROM followed by rotator cuff/scapular strengthening and proprioceptive training is standard, with bracing for select athletes. Acute low-grade AC injuries respond to brief sling use.