Muscle Hemorrhage Research Articles

Quadriceps Crush Contusion in Athletes: The Effectiveness of Orthobiologic Treatment with Platet-Rich Plasma (PRP)

Introduction: Quadriceps contusion is a common injury in contact sports like football, rugby, and basketball, resulting from a direct blow to the anterior thigh. This causes muscle damage, bleeding, and inflammation. While often considered minor, poor management can lead to complications, delayed recovery, and impaired athletic performance. Purpose: The purpose of this review is to evaluate the effectiveness and the role of orthobiologic treatments such as PRP in enhancing healing and functional recovery for a swift return to sport. Summary: Quadriceps contusion, resulting from direct trauma to the quadriceps muscle group, leads to hematoma formation and varying degrees of injury severity. Diagnosis is primarily clinical, often supported by ultrasound and MRI to assess the extent of muscle damage. Treatment is typically non-operative, involving rest, ice, compression, physical therapy, and a gradual return to activity. One significant complication is myositis ossificans, characterized by abnormal bone formation within the muscle, which can cause chronic pain and restricted movement. Recent advances, such as ultrasound-guided PRP injections, offer promising results by enhancing healing, relieving pain, and accelerating functional recovery. PRP therapy, particularly popular among athletes, promotes tissue repair by stimulating cell regeneration and reducing inflammation, helping speed up recovery and potentially lowering the risk of complications like myositis ossificans. Although preliminary evidence supports the effectiveness of PRP in helping athletes return to play sooner, more research is needed to validate its full impact on musculoskeletal injuries. Continued exploration of nonoperative treatment and rehabilitation protocols is also necessary to ensure optimal outcomes. Preventive strategies, including the use of protective gear and conditioning exercises to strengthen muscles, are critical in reducing the risk of injury and enhancing athletic performance.

CHIEF: A retrospective self-control study of children with severe hemophilia A without inhibitors comparing emicizumab to FVIII prophylaxis.

Hemophilia A (HA) is an X-linked bleeding disorder diagnosed by a deficiency in factor VIII (FVIII). For severe HA (SHA), prophylaxis clotting factor concentrates (CFC) has become the standard of care; however, it imparts a high treatment burden and typically results in an annualized bleeding rate (ABR) of 2-6. Emicizumab, a subcutaneously administered FVIII substitute, has become the de facto standard-of-care prophylaxis for children with SHA in many countries. Previous clinical trials of emicizumab have assessed ABR in patients greater than 12years without inhibitors, and in children less than 12years with inhibitors; however, there is little information published regarding the ABR of emicizumab compared to CFC in non-inhibitor SHA children. Using a retrospective electronic medical record chart review, we conducted a self-control analysis of 15 patients less than 12years of age during equivalent periods of CFC versus emicizumab prophylaxis. The mean ABR on CFC and emicizumab was 1.79 and 1.13 (p=.092), respectively, with a substantially decreased rate of joint bleeds (CFC 0.94; emicizumab 0.33; p=.001) and spontaneous bleeds (CFC 0.79; emicizumab 0.23; p=.008). No safety events were recorded for patients while administering emicizumab. The mean annual cost of CFC prophylaxis was $515,340 (SD $199,540), compared to $328,410 (SD $137,230) for emicizumab prophylaxis (p<.001). Emicizumab resulted in an improved ABR compared to CFC, especially for joint and spontaneous bleeds, had fewer administration complications, and was substantially less expensive compared to CFC prophylaxis; however, more research is necessary for a complete understanding of the effect of emicizumab on joint health and muscle bleeds.

Anterior Displacement of the Eyeball in a Patient with Uncontrolled Schizophrenia

Purpose: To report a case in which vision improvement was achieved following surgery for anterior displacement of the eyeball resulting from self-mutilation in a patient with schizophrenia.Case summary: A 37-year-old female patient with schizophrenia was admitted following an attempt at self-mutilation, which led to anterior displacement of her right eyeball. Initial evaluation revealed that reduction was not feasible and visual acuity was finger count at 20 cm in the right eye. Orbital computed tomography indicated 26-mm anterior displacement of the eyeball from the center of the cornea to the interzygomatic line along with a small retrobulbar hemorrhage and edema in the superior rectus muscle. Surgical intervention, consisting of lateral canthotomy, cantholysis, and tarsorrhaphy, was performed for correction. The surgical site was reconstructed 6 days after surgery. A fundus examination conducted 1 month later revealed no abnormalities and best-corrected visual acuity improved to 20/20.Conclusions: Globe subluxation due to self-mutilation is a very rare and urgent condition in both ophthalmic and psychiatric contexts that requires immediate surgical intervention. This case demonstrates that immediate anatomical reduction when there is no direct suspicion of optic nerve damage can be beneficial for the recovery of visual acuity and may lead to a favorable prognosis.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

A clinical practice guideline for primary care physiotherapy in patients with haemophilia.

As a result of centralisation of haemophilia care to a limited number of intramural settings, many persons with haemophilia have to travel long distances to attend their haemophilia specialised treatment centre. However, regular physiotherapy treatment can be provided by primary care physiotherapists in the person's own region. Due to the rarity of the disease most primary care physiotherapists have limited experience with this population. This study aims to provide a clinical practice guideline for primary care physiotherapists working with persons with bleeding disorders. A list of the most urgent key-questions was derived from a previous study. Literature was summarised using the grading of recommendations assessment, development, and evaluation (GRADE) evidence-to-decision framework. Recommendations were drafted based on four 90min consensus meetings with expert physiotherapists. Recommendations were finalised after feedback and >80% consensus of all stakeholders (including PWH, physiotherapists, haematologists and the corresponding societies). A list of 82 recommendations was formulated to support primary care physiotherapists when treating a person with a bleeding disorder. These recommendations could be divided into 13 categories: two including recommendations on organisation of care, six on therapy for adult patients with bleeding disorders and five on therapy adaptations for paediatric care. Therapy recommendations included treatment after a joint- or muscle bleed, haemophilic arthropathy, chronic synovitis, non-haemophilia related conditions and orthopaedic surgery. An evidence-based practice guideline, based on current evidence from literature and clinical expertise, has been developed for primary care physiotherapists treating a person with haemophilia. To improve care, the recommendations should be implemented in daily practice.

Exploring the Challenges of Electrofishing: Impact on the Quality of Binni, a Cyprinid Fish, in Harvesting from Rearing Systems

ABSTRACT This study compared electrofishing (ES) with conventional suffocation (AS) for harvesting fish, analyzing meat quality, biochemical, and microbiological indices. ES-caught fish show delayed rigor mortis, a milder pH decrease, and unaffected biochemical indicators. Although ES fish exhibited higher drip and cooking losses within the initial 24 hours, no significant differences emerged later. Free fatty acids and total volatile base nitrogen were higher in ES fish but remained within acceptable limits. Bacterial load was lower, indicating that electrofishing induces rapid unconsciousness with minimal impact on product quality. Further optimization of electrofishing devices is needed to address potential concerns like muscle bleeding.

Trismus caused by migration of orthodontic archwire into the infratemporal fossa: a case report.

Soft tissue injuries are known complications of orthodontic treatment. Most of the injuries are mild, but severe complications can arise from deeper penetration or dislodgement of brackets and other foreign bodies into the surrounding tissues of the oropharynx and infratemporal fossa. The patient, accompanied by his parents, presented to the Children's Emergency Department with the concern of gradual limitation of mouth opening and eventual trismus, which occurred over a span of 2 weeks. The patient presented with trismus and slight discomfort at the left cheek region. He reported a history of gradual limitation to his mouth opening 2 weeks prior. He was wearing upper and lower fixed orthodontic appliances and the left distal end of the maxillary archwire was found to have migrated into the left infratemporal fossa. Left medial pterygoid muscle inflammation, or bleeding and haematoma formation, or infection within the infratemporal region. The maxillary archwire was removed in the Children's Emergency Department and a computed tomography (CT) scan performed subsequently confirmed the diagnosis of left medial pterygoid muscle inflammation. The patient was started on an intravenous (IV) antibiotic and a 2-day course of IV dexamethasone to reduce the muscle inflammation. By the second day, the patient was able to achieve a mouth opening of 6 mm, and by the second week, the mouth opening had returned to normal. The potential risk of soft tissue injury and complications from orthodontic treatment is generally mild and limited. Soft tissue injuries can be avoided with careful management by the operator with the proper precautions taken. Clinicians should be familiar with the surrounding soft tissue anatomy and be aware of the potential for more severe complications and provide management or referral to the appropriate specialty accordingly.

Clinico-haematobiochemical and cardiac alterations in Trypanosoma evansi infected buffaloes of Andhra Pradesh, India.

The present research aimed to document the incidence, clinical signs, haematological, and serum biochemical alterations, as well as electrocardiography and echocardiography findings in 62 buffaloes (selected from a total of 240) infected with Trypanosoma evansi. The study spanned one year, from January 2022 to December 2022. Morphological identification of Trypanosoma evansi was done by the presence of a centrally positioned nucleus with a small sub-terminal kinetoplast at the posterior position through microscopic examination of Giemsa stained peripheral blood smears. The incidence of trypanosomosis were determined to be 26% (62/240) using stained blood smear examination and 41% (98/240) through polymerase chain reaction assay. Clinical signs exhibited by buffaloes with trypanosomosis included the lack of rumination (94%; 58/62), anorexia (90%; 56/62), emaciation (87%; 54/62), loss of milk yield (84%; 52/62), ocular discharges (82%; 51/62), depressed demeanour (81%; 50/62), sunken eye balls (61%; 38/62), fever (60%; 37/62), scleral congestion (56%; 35/62) and intermittent fever (42%; 26/62). Cardiovascular clinical findings in affected buffaloes included tachycardia (44%; 27/62), cardiac arrhythmia (24%; 15/62), cardiac murmurs (19%; 12/62) and muffled heart sounds (18%; 11/62). In the present study, buffaloes with trypanosomosis exhibited significant reduction in haemoglobin (p = 0.008), packed cell volume (p = 0.004), total erythrocyte count (p = 0.003), mean corpuscular volume (p = 0.042), total leucocyte count (p = 0.048) and absolute neutrophil count (p = 0.012); a significant increase in absolute eosinophil count (p = 0.011) and absolute monocyte count (p = 0.008) compared to the apparently healthy buffaloes. Additionally significant decrease in albumin (p = 0.001), A/G ratio (p = 0.007), calcium (p = 0.008), glucose (p = 0.007), phosphorous (p = 0.048), sodium (p = 0.008), potassium (p = 0.041) and chloride (p = 0.046) were observed in buffaloes with trypanosomosis compared to healthy ones. Buffaloes with trypanosomosis also showed significant increase in globulin (p = 0.004), aspartate aminotransferase (p = 0.008), bilirubin (p = 0.034), blood urea nitrogen (p = 0.071), creatinine (p = 0.029), cholesterol (p = 0.046), lactate dehydrogenase (p = 0.009), gamma-glutamyl transferase (p = 0.004) and creatine kinase-myoglobin binding levels (p = 0.005). Electrocardiography explorations in buffaloes with trypanosomosis revealed sinus tachycardia, low voltage QRS complex, ST segment elevation, wide QRS complex, sinus arrhythmia, sinus bradycardia, wandering pace maker, first degree atrio ventricular block, biphasic T wave and tall T wave. Echocardiography examination unveiled cardiac chamber dilatation, ventricular wall thickening and indications of pericarditis/cardiac tamponade. Necropsy was carried on the dead buffaloes during the study period disclosed severely congested blood vessels on epicardial surface, endocardial haemorrhages, and presence of pericardial fluid. Histopathological examination of the heart revealed hyaline degeneration, haemorrhages in the cardiac muscles and varying degrees of degenerative changes. Additionally, the pericardium displayed increased thickness due to presence of more elastic fibres, fibroblast cells in the myocardium, discontinuity of muscle layers, vascular congestion, perivascular mono nuclear cell infiltration and augmented thickness of the endocardium with fibroblast cell proliferation. The study's conclusion highlights cardiac alterations as secondary complications in buffaloes infected with Trypanosoma evansi. Further investigations are recommended to elucidate therapeutic modifications and refine the treatment paradigm.

A Modified 4-in-1 Stanisavljevic Procedure for Treating Obligatory or Congenital Patellar Dislocations in Children: A Surgical Technique.

Patellar instability and dislocation pose complex clinical and surgical challenges, especially in children. Congenital (fixed) and obligatory (habitual) dislocations present significant anatomical and etiological complexity, frequently leading to deformities and functional impairments, which can range from walking difficulties to sports limitations. Conservative treatment is often inadequate. We describe a surgical technique for treating congenital or obligatory patellar dislocations in patients with various underlying diagnoses-including Down syndrome, nail-patella syndrome, and skeletal dysplasia-that involves extensive subperiosteal quadriceps realignment, distal realignment (Roux-Goldthwait or tibial tuberosity transfer), and optional medial plication. This modified 4-in-1 technique follows the principles described in 1976 by Stanisavljevic, which involves subperiosteal quadriceps mobilization, thus minimizing muscle damage, bleeding, and postoperative muscular adherences. In 24 patients treated at our institution between 2002 and 2021 (35 knees; age range = 5.5-16.8 years; 13 girls, 11 boys), with a mean follow-up of 8.2 years (2.4-20 years), we achieved satisfactory improvements in patellar stability, range of motion, and quality of life with a modified 4-in-1 Stanisavljevic technique. A total of 9 patients (7 with obligatory dislocations and 2 with congenital dislocations) could engage in recreational or competitive sports. The average postoperative pediatric International Knee Documentation Committee (pedi-IKDC) score was 78.45 ± 22.3 (range = 0-100); a patient with DiGeorge syndrome and 1 with multiple epiphyseal dysplasia had scores of 35 and 48, respectively. We found at our institution that a modified 4-in-1 Stanisavljevic technique produced favorable outcomes in patellar stability, range of motion, and quality of life in pediatric patients with congenital or obligatory patellar dislocation. More study is warranted to determine the procedure's overall benefits for children with obligatory or congenital dislocations of complex etiology.

Ultrasound in addition to clinical assessment of acute musculoskeletal complaints in bleeding disorders: impact on patient management

BackgroundUltrasound is increasingly used for musculoskeletal assessment in hemophilia care. ObjectivesTo evaluate the impact of point-of-care ultrasound added to clinical assessment for diagnosis and treatment of acute musculoskeletal episodes in a heterogeneous cohort of children and adults with hemophilia and von Willebrand disease (VWD). MethodsThis prospective cross-sectional study consecutively included children and adults with hemophilia or VWD who visited the outpatient clinic with acute musculoskeletal complaints between March 2020 and May 2023. For all episodes, initial diagnosis and treatment determined by clinical assessment were recorded on a case report form. Subsequently, a physiotherapist (M.A.T. and J.B.) with knowledge of the clinical diagnosis performed point-of-care ultrasound. After ultrasound, updated diagnosis and treatment were recorded. Diagnosis and treatment before and after ultrasound were compared, and proportions of change with 95% CIs were determined. ResultsWe evaluated 77 episodes in 67 patients (median age, 24 years; IQR, 13-42 years). Before ultrasound, 37 joint bleeds, 13 muscle bleeds, and 27 other diagnoses were diagnosed. After ultrasound, 33 joint bleeds, 11 muscle bleeds, and 33 other diagnoses were confirmed. The diagnosis changed in 28 of 77 episodes (36%; 95% CI, 26%-48%). Nine joint bleeds and 2 muscle bleeds were missed by clinical assessment. Ultrasound findings changed treatment strategy in 30 of 77 episodes (39%; 95% CI, 28%-51%). ConclusionUltrasound in addition to clinical assessment of acute musculoskeletal complaints in people with hemophilia and VWD has an impact on diagnosis (36%) and treatment (39%), which supports the use of ultrasound in acute musculoskeletal complaints in hemophilia and VWD.

Diagnostic Value of Sternocleidomastoid Muscle Hemorrhage on Clavicular Periosteum in Hanging Deaths

Diagnostic Value of Sternocleidomastoid Muscle Hemorrhage on Clavicular Periosteum in Hanging Deaths

IBC-Oxford University2023_BJSPoster_1Laparoscopic Sleeve Gastrectomy in a Patient with Severe Haemophilia A

Abstract Introduction Haemophilia A is an X linked inherited bleeding disorder caused by deficiency in coagulation factor VIII (FV III). To prevent spontaneous bleeding in muscles and joints, patients with severe Haemophilia A should receive prophylactic replacement therapy with dosing adjusted according to body weight. Case presentation A 19-year-old male patient who is well known to have Haemophilia A, that has been diagnosed shortly after birth during routine circumcision. The patient had presented to our clinic with BMI of 53.9 kg/m2. He was counselled for laparoscopic sleeve gastrectomy after failure of many trials to lose weight. He and his father were counselled for procedure pros and cons. Routine preoperative work up had been performed (Full labs, Abdomen Ultrasound, Dietician consultation, Anaesthesia consultation, Cardiology consultation). Haematological consultation had been done and consultant opinion was to give prophylactic factor VIII 7500 IU: 2 hours prior to surgery, 24 hours after surgery, 72 hours after surgery Extra precaution had been taken in the perioperative period in the form of careful cannulation, IM injections had been avoided completely, no anticoagulants, 1:1 Nursing care, careful patient handling and positioning, continuous monitoring (planned ICU admission for first 24 hours then HDU admission for 48 hours), senior Anaesthetist and senior Anaesthesia technician, on-table gastroscopy, smooth bougie tube placement (size 36F), careful haemostasis by way of slow Harmonic sealing, clipping of short gastrics, 1 minute stapler compression (All green reloads), full stapler line plication and omental patching, maintenance of stable blood pressure during surgery. Patient had an uneventful postoperative recovery, apart from mild bilateral subconjunctival haemorrhages that had subsided spontaneously. Conclusion Laparoscopic sleeve gastrectomy can be performed smoothly in patients with Haemophilia A with proper perioperative multidisciplinary care management.

Zinc-Mediated Endoplasmic Reticulum Stress and Metallothionein Alleviate Arsenic-Induced Cardiotoxicity in Cyprinus Carpio.

Arsenic (As) is a natural component of the Earth's crust, and its inorganic form is highly toxic. The problem of As pollution in water is extremely urgent, and its impact on aquatic organisms should be widely considered. Here, 120 common carp were selected as the test subjects and were exposed to environmentally relevant concentrations of As (2.83 mg L- 1) for 30 days. Histomorphological observations showed the adverse effects of As on the heart: irregular arrangement of myocardial fibers, rupture of muscle fiber bundles, inflammatory infiltration, and hemorrhages. Mechanistically, abnormal expression of factors related to As-induced inflammation (TLR4/MYD88/NF-κB pathway), endoplasmic reticulum stress (CHOP, GRP78, ATF6, PERK, IRE1) and oxidative stress (SOD, CAT, Nrf2, HO-1) was observed. Then, we tried to find a protective agent against As-induced myocardial injury. As one of the important metal elements for maintaining cell growth and immunity, zinc (Zn, 1 mg L- 1) significantly alleviated the pathological abnormalities induced by As, and the changes in physiological and biochemical indices in response to As exposure were significantly alleviated by Zn administration, which was accompanied by the restoration of metallothionein (ZIP8, Znt1, Znt5, Znt7) and heat shock protein (HSP60, HSP70, HSP90) expression. These results suggest for the possibilty of developing Zn as a candidate therapeutic agent for As induced aquatic toxicology.

Increased Circulating Levels of YKL-40 Protein in Children and Adolescents with Hemophilia: Correlation with the Degree of Hemophilic Arthropathy

Introduction: Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency of coagulation factors VIII and IX, respectively. Recurrent joint bleeding (hemarthrosis) is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to hemophilic arthropathy, that severely affects the quality of life of patients. Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a 40-kDa heparin-human cartilage glycoprotein without enzymatic activity, that is encoded by the CHI3L1 gene in humans and its name derives from the one letter code for the three terminal amino acids - tyrosine (Y), lysine (K) and leucine (L). YKL-40 is secreted in vitro and in vivo in the arthritic joint by various cell types, such as activated macrophages, chondrocytes, synoviocytes and neutrophils. Actually, it is a major protein that has been identified in the chondrocytes from arthritic knee joints.In fact, synovial as well as serum YKL-40 levels are found increased in joint diseases like rheumatoid arthritis and osteoarthritis, indicating its potential role as a biomarker of inflammation and tissue remodeling or degradation, whereas it is absent in normal joints. In our knowledge, there are not any reports linking YKL-40 expression with hemophilic arthropathy, thus we aimed to investigate if this protein could be implicated in hemophilic arthropathy severity, by measuring its circulating levels and correlate them with hemophilic arthropathy features and laboratory parameters in children and adolescents with hemophilia A and B. Patients and Methods: Eighty children and adolescents (median age:14 years, range 10-18 years) with severe (n= 60), moderate (n= 8) and mild (n= 12) hemophilia A or B (n= 7), on prophylaxis or on demand treatment (n= 12) were included in the study, while 35 apparently healthy male individuals matched for age served as controls. No signs of hemophilic arthropathy (NHAP), i.e. Hemophilia Joint Health Score 2.1 ≤ 2 and Hemophilia Early Detection Arthropathy with Ultrasound Score ≤ 1, were detected in 34/80 patients with median age of 13.5 years. In 37/80 patients with median age of 14.25 years arthropathy (HAP) was confirmed, while 18/80 patients with median age of 15.75 years presented with acute bleeding (AB)-hemarthrosis or muscle bleed- at the time of the laboratory evaluation. In patients and controls YKL-40 concentrations were determined by means of an immunoenzymatic technique. Results: We found that: a) Circulating YKL-40 levels in patients with hemophilia were significantly higher compared to controls, 21.9±2.3 ng/mL (95% Confidence Intervals of the mean (CI): 19.6;24.2 ng/mL) vs 17.0±2.5 ng/mL (CI: 14.5;19.4 ng/mL), respectively, p=0.003. b) Patients with arthropathy (HAP) tend to express higher circulating YKL-40 levels (25.5±2.0 ng/mL) than patients without arthropathy (NHAP)(20.1±1.8 ng/mL) and patients with acute bleeding (AB) (19.7±2.4 ng/mL), respectively, p-trend=0.06. Conclusions: To the best of our knowledge, this is the first study to evaluate the potential clinical significance of circulating YKL-40 levels in patients with hemophilia and demonstrated that it could reflect hemophilic arthropathy activity in clinical or even in subclinical level. As YKL-40 in synovial fluid is derived from cells in the inflamed/damaged synovium, such as chondrocytes, we postulate that it may be involved in the pathophysiology of the hemophilic arthropathy processes and reflect local disease activity. Further studies are essential on the role of YKL-40 in the evolution of hemophilic arthropathy, in order to fully elucidate its clinical significance and prognostic utility.

Emicizumab Efficacy in Severe Hemophilia (A): Experience in Ecuador

Introduction: In Ecuador, there are 1708 cases of hemophilia in a population of 17,643,060 habitants; according to the World Federation of Hemophilia (WFH) Annual Global Survey Report 2020 released in October 2021. Eleven patients use emicizumab in Ecuador (ten patients under ministerial authorization, and one patient through private insurance); being the first administered in June 2021. Objectives: To describe the demographic characteristics of patients receiving emicizumab in Ecuador. To determine efficacy and response with emicizumab: based on annual bleeding rate (ABR), performance status assessment, activity, and participation. Methods: Population: Pediatric Severe Hemophilia A (PwHA) patients (&amp;lt;12 years) and adults/adolescents (&amp;gt;12 years), both from the public and private health sector. Study design: Retrospective, multicentric study, with a case-report research design. The sources of information were the medical records of the patients. Efficacy variables: ABR was calculated by: (number of bleeds/number of days times 365.25). Body structure and function was assessed with the Hemophilia Joint Health Score 2.1 (HJHS). Activity and participation were assessed with the Functional Independence Score in Hemophilia (FISH). Statistic analysis: Shapiro-Wilk test to know the distribution of the sample, t-Test paired tests (parametric), Wilcoxon statistic (non-parametric); Descriptive statistics: relative frequencies, measures of central tendency and dispersion, column graphs. Analysis and results: Ten patients with an average (Q1,Q3) age of 11.5 years (7.15) were registered. The youngest patient was one year old and the oldest, fifty years old. 90% (n:9) had hemophilia A with high-response inhibitors. Prior to starting emicizumab: 20% (n:2) presented Central Nervous System bleeding, 30% (n:3) had muscle bleeding, and 10% (n:1) developed catheter-associated infection. The mean ABR was 10 pre-emicizumab events, and 0.3 post-emicizumab events (p=0.002), with follow-ups at 22 months (n: 2), 17 months (n:2), 3 months (n:2 ), 4 months (n: 3), 5 months (n: 1). The mean HJHS (±SD, n) was 20.9 (± 20,096, 10) pre-emicizumab, and 9.7 (± 16.52, 10) (p=0.003) The mean by FISH (±SD, n) was 16.2 (± 8.59, 10) pre-emicizumab, and from 22.6 (± 11.62, 10) with the use of emicizumab. The use of the t-Test for paired samples determined that there are statistically significant differences between the pre-emicizumab and post-emicizumab groups for the variables ABR, HJHS and FISH (95% confidence level). Conclusion: The use of Emicizumab allowed better control of joint bleeding; and it contributed favorably in the evolutionary course of both the functional state and the activity. It is essential to corroborate these results with a longer follow-up and a larger sample size. Bibliography: 1. Alvarez Roman M: Spanish guidelines for the management of hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25:676-684. 4. Ellsworth P, Ma A: Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 5. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637

Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia

The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0-to-4 grade scale as follows: absent (0†), mild (†), moderate (††), severe (†††), and very severe (††††). Serum levels of myokines: irisin, myostatin, IL-8, and lL-6 were determined with multiplex bead-based immunoassay. 119 patients (mean age: 67.58±9.60years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+≥moderate (††): claudication (n=14): 4; 28.57%; CLTI (n=25): 16; 64.00%; P=0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+≥moderate (††): claudication (n=13): 7; 53.85%; CLTI (n=27): 21; 77.78%; P=0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL)-6 and IL-8. CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL-8 and IL-6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro-inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.

Heterotopic Ossification in Hemophilia: A Multi-Center Case Series

CONCLUSION Heterotopic Ossification (HO), or Myositis Ossificans Traumatica, is the post-traumatic formation of unwanted abnormal benign lamellar ectopic bone within extra skeletal tissue locations. HO can form in varying sizes and sites in the body and can significantly impair muscle performance, range of motion (ROM), and function. Since the recent adoption of diagnostic musculoskeletal ultrasound (MSKUS) in hemophilia care, providers and physical therapists have deepened their understanding of hemarthropathic and hemarthrosis progression. MSKUS has also aided in detecting soft tissue injuries, muscle hematoma, and resultant HO formation. Despite advances in therapies for hemophilia, HO is emerging as an unforeseen complication of contusion and injury-related muscle bleeding in hemophilia. Its detection is important as delayed or inappropriate rehabilitation may prolong recovery and disability time. This multicenter retrospective case series sought to verify and confirm HO detection and investigate whether specific types and severities of hemophilia are at increased risk of HO. Deidentified data and MSKUS images from 29 cases were collected from 9 Hemophilia Treatment Centers from the USA, the Netherlands, and Canada from 2016 to June 2023. The case series was declared exempt from IRB approval. Diagnostic and evaluative data was compiled in Redcap. Images were reviewed and diagnostically confirmed by an RMSK-certified Doctor of Physical Therapy and a Radiologist. A single clinic subset was compared to the national hemophilia incidence taken from the ATHN dataset 2022. We detected HO formation in 29 patients across 9 HTCs. Trauma-induced HO was observed in all bleeding disorder types and severities. (See Table 1). The patients' ages at the time of the inciting injury ranged from 7-56 years, with a mean age of 22.3 and a median of 16.The study's highest incidence of HO cases occurred in patients with type A hemophilia totaling 22/29 subjects or 74.8% of all cases. Except for one severe A, one severe B and a moderate B, the patients were not on prophylactic hemostatic management at the time of injury. The majority of HO (n=24, 82.8%) occurred in the anterior and lateral compartments of the thigh and hip. There were 5 incidents in the upper extremity (4 in the upper anterior arm, 1 in the hand). 24 cases were due to blunt trauma except for 4 in the psoas at the level of the anterior hip and 1 in the elbow flexors of the upper arm. HO formation was mostly associated with deep muscle bleeds next to the bony cortex (n=24). HO was detected on average at 22.97 days after injury (median 21, range 11 to 60), with most detected with MSKUS (n=24) by the physical therapist (n=22) and physician (n=2) in clinic. At the Washington Center for Bleeding Disorders (WACBD), where strict MSKUS follow-up was possible in 7 patients, HO induction was confirmed at day 23, 26, 18, 11, 14, 20, and 22 for a mean of 19.14 days (SD = 5.24). Our study shows that HO occurs regularly in Hemophilia despite its omission in the recently revised 2020 World Federation of Hemophilia guidelines. Notably, the severity or type did not appear to be the sole determinant of HO formation, as the combined total of mild and moderate hemophilia genotypes was 21 (72.4%). Conversely, though limited by the study's small sample size, 74.8% of the HO incidence was reported in type A hemophilia, which appears to be an overrepresentation when compared to the ATHN dataset 2022 report, which indicates an overall 45.59% type A hemophilia incidence. The increased detection of HO in hemophilia may be explained by the growing use of MSKUS by HTC physicians and physical therapists. MSKUS has the advantages of safety and earlier HO detection than radiography. As shown in Fig. 1, HO bears the sonographic signature of hyperechoic contours and deeper acoustic shadowing. The WACBD conducted a review yielding an HO incidence of 23.68% (9 of 38 contusion events) compared to 9-17% in the non-hemophilia population. Though the single-center report is of limited significance, the suggestion of increased HO risk to hemophilia patients merits further study. This case series acknowledges HO as a complication of deep contusions in people with bleeding disorders, especially those not on hemostatic prophylaxis. Further study is needed to determine HO's incidence and risk in Hemophilia. Hemophilia treatment guidelines must be revised to include this complication.

Homicidio por combinación de métodos de asfixia

IntroductionHomicide by combination of suffocation methods is observed mainly in elderly people or with some physical impediment capable of counteracting the aggression. Material and methodsA retrospective observational study was carried out on 634 autopsies. Five met the characteristics of homicides by combination of asphyxiation methods. ResultsTwo men and three women, average age 69 years, with negative toxicological studies, victims of a single aggressor, presented peri orificial skin lesions (mouth and nose), muscle hemorrhages in the thorax, rib fractures, blunt injuries to the head interpreted as like submission. DiscussionIn the combination of asphyxia methods the findings that must be seen together: Head injuries to subdue the victim, skin lesions on the neck, face, inner face of the lips, rib fractures, and counter-pressure injuries to the back, buttocks, or elbows. Contextualized together, can explain the dynamics of this homicidal modality.

Cerebral Ischaemia Secondary to Anticoagulant Treatment in a Haemophiliac Patient: A Case Report

We report the case of a 21-year-old patient who had been treated for haemophilia A since the age of 8. He had a family history of haemophilia, as his maternal uncle also suffered from the disease. During his life, he had suffered several episodes of joint and muscle haemorrhages for which he had received replacement therapy with recombinant factor VIII (Kogenate). However, three months after his last treatment, the patient developed headaches and neurological deficits, in particular paresthesias in his lower limbs. Cerebral magnetic resonance imaging (MRI) revealed nodular and focal signal abnormalities in several brain regions, as well as minimal triventricular hydrocephalus with intraventricular haemorrhage. This clinical and radiological presentation led to the diagnosis of cerebral ischaemia secondary to anticoagulant treatment.

Joint Dysfunction as a Cause of Spontaneous Subclinical Bleeding in Infants with Hemophilia.

Hemophilia is an inherited hemorrhagic disorder; its main clinical manifestations being bleeding in muscles and joints. Ankles, knees, and elbows are the most frequently affected joints, followed by shoulders and hips. The clinical signs of joint involvement are reduced mobility, swelling and walking difficulties. Bleeding episodes in patients with hemophilia are usually divided into traumatic and spontaneous, but we believe that the latter are not truly spontaneous but rather the result of joint stresses owing to motion actions that create dysfunctions starting from infancy. Pharmacological prophylaxis with factor replacement therapies or non-replacement drugs markedly reduces musculoskeletal hemorrhages. However, the onset of subclinical joint stress can be reduced only by associating this therapeutic approach with the accurate observation of the child motion patterns and restoring them if dysfunctional, thereby primarily preventing subclinical bleeding and ultimately the onset or progression of hemophilic arthropathy.