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Background In facial reanimation, dual-innervated gracilis free functional muscle transfers (FFMTs) may have amalgamated increases in tone, excursion, synchroneity, and potentially spontaneity when compared with single innervation. The ideal staging of dual-innervated gracilis FFMTs has not been investigated. We aim to compare objective long-term outcomes following one- and two-stage dual-innervated gracilis FFMTs. Methods Included were adult patients with facial paralysis who underwent either one- (one-stage group) or two-stage (two-stage group) dual-innervated gracilis FFMT with ≥1 year of postoperative follow-up. Facial measurements were obtained from standardized photographs of patients in repose, closed-mouth smile, and open-mouth smile taken preoperatively, 1 year postoperatively, and 3 years postoperatively. Symmetry was calculated from the absolute difference between the paralyzed and healthy hemiface; a lower value indicates greater symmetry. Results Of 553 facial paralysis patients, 14 were included. Five and nine patients were in the one- and two-stage groups, with mean follow-up time, respectively, being 2.5 and 2.6 years. Within-group analysis of both groups, most paralyzed-side and symmetry measurements significantly improved over time with maintained significance at 3 years postoperatively in closed and open-mouth smile (all p ≤ 0.05). However, only the two-stage group had maintained significance in improvements at 3 years postoperatively in paralyzed-side and symmetry measurements in repose with commissure position (median change [interquartile range, IQR], 7.62 [6.00–10.56] mm), commissure angle (median change [IQR], 8.92 [6.18–13.69] degrees), commissure position symmetry (median change [IQR], −5.18 [−10.48 to −1.80] mm), commissure angle symmetry (median change [IQR], −9.78 [−11.73 to −7.32] degrees), and commissure height deviation (median change [IQR], −5.70 [−7.19 to −1.64] mm; all p ≤ 0.05). In the between-group analysis, all measurements were comparable in repose, closed-mouth smile, and open-mouth smile (all p > 0.05). Conclusion Long-term outcomes demonstrate that both one- and two-stage dual-innervated gracilis FFMTs significantly improve excursion, but only two-stage reconstruction significantly improves resting tone. [ABSTRACT FROM AUTHOR]

Summary: Few studies have reported the real‐world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO‐RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO‐RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO‐RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment‐free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO‐RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO‐RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO‐RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO‐RAs had similar efficacy and safety profiles to those reported in clinical studies. [ABSTRACT FROM AUTHOR]

Background: Urinary CXCL10/creatinine (uCXCL10/Cr) is proposed as an effective biomarker of subclinical rejection in pediatric kidney transplant recipients. This study objective was to model implementation in the clinical setting. Methods: Banked urine samples at a single center were tested for uCXCL10/Cr to validate published thresholds for rejection diagnosis (>80% specificity). The positive predictive value (PPV) for rejection diagnosis for uCXCL10/Cr‐indicated biopsy was modeled with first‐positive versus two‐test‐positive approaches, with accounting for changes associated with urinary tract infection (UTI), BK and CMV viremia, and subsequent recovery. Results: Seventy patients aged 10.5 ± 5.6 years at transplant (60% male) had n = 726 urine samples with n = 236 associated biopsies (no rejection = 167, borderline = 51, and Banff 1A = 18). A threshold of 12 ng/mmol was validated for Banff 1A versus no‐rejection diagnosis (AUC = 0.74, 95% CI = 0.57–0.92). The first‐positive test approach (n = 69) did not resolve a clinical diagnosis in 38 cases (55%), whereas the two‐test approach resolved a clinical diagnosis in the majority as BK (n = 17/60, 28%), CMV (n = 4/60, 7%), UTI (n = 8/60, 13%), clinical rejection (n = 5/60, 8%), and transient elevation (n = 18, 30%). In those without a resolved clinical diagnosis, PPV from biopsy for subclinical rejection is 24% and 71% (p =.017), for first‐test versus two‐test models, respectively. After rejection treatment, uCXCL10/Cr level changes were all concordant with change in it‐score. Sustained uCXCL10/Cr after CMV and BK viremia resolution was associated with later acute rejection. Conclusions: Urinary CXCL10/Cr reliably identifies kidney allograft inflammation. These data support a two‐test approach to reliably exclude other clinically identifiable sources of inflammation, for kidney biopsy indication to rule out subclinical rejection. [ABSTRACT FROM AUTHOR]

Clostridial dermatitis (CD), caused by Clostridium septicum, is an emerging disease of increasing economic importance in turkeys. Currently, there are no effective vaccines for CD control. Here, two non-toxic domains of C. septicum alpha toxin, namely ntATX-D1 and ntATX-D2, were identified, cloned, and expressed in Escherichia coli as recombinant subunit proteins to investigate their use as potential vaccine candidates. Experimental groups consisted of a Negative control (NCx) that did not receive C. septicum challenge, while the adjuvant-only Positive control (PCx), ntATX-D1 immunization (D1) and ntATX-D2 immunization (D2) groups received C. septicum challenge. Turkeys were immunized subcutaneously with 100 μg of protein at 7, 8 and 9 weeks of age along with an oil-in-water nano-emulsion adjuvant, followed by C. septicum challenge at 11 weeks of age. Results showed that while 46.2% of birds in the PCx group died post-challenge, the rate of mortality in D1- or D2-immunization groups was 13.3%. The gross and histopathological lesions in the skin, muscle and spleen showed that the disease severity was highest in PCx group, while the D2-immunized birds had significantly lower lesion scores when compared to PCx. Gene expression analysis revealed that PCx birds had significantly higher expression of pro-inflammatory cytokine genes in the skin, muscle and spleen than the NCx group, while the D2 group had significantly lower expression of these genes compared to PCx. Peripheral blood cellular analysis showed increased frequencies of activated CD4+ and/or CD8+ cells in the D1 and D2-immunized groups. Additionally, the immunized turkeys developed antigen-specific serum IgY antibodies. Collectively, these findings indicate that ntATX proteins, specifically the ntATX-D2 can be a promising vaccine candidate for protecting turkeys against CD and that the protection mechanisms may include downregulation of C. septicum-induced inflammation and increased CD4+ and CD8+ cellular activation. [ABSTRACT FROM AUTHOR]

Maintaining tissue perfusion in sepsis depends on vascular integrity provided by the endothelial glycocalyx, the critical layer covering the luminal surface of blood vessels. The glycocalyx is composed of proteoglycans, glycosaminoglycans, and functional plasma proteins that are critical for antithrombogenicity, regulating tone, controlling permeability, and reducing endothelial interactions with leukocytes and platelets. Degradation of the glycocalyx in sepsis is substantial due to thromboinflammation, and treatments for sepsis and septic shock may exacerbate endotheliopathy via additional glycocalyx injury. As a result, therapeutic strategies aimed at preserving glycocalyx integrity should be considered, including modifications in fluid volume resuscitation, minimizing catecholamine use, controlling hyperglycemia, and potential use of corticosteroids and anticoagulants. In this review, we explore treatment strategies aligned with the recommendations outlined in the Surviving Sepsis Campaign Guidelines 2021 with a special emphasis on evidence regarding glycocalyx protection. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. Objectives: This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. Methods: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. Results: Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077–2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4–4.96), international normalized ratio (OR 0.21, 95% CI: 0.05–0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53–0.94), and intensive therapy (OR 2.05, 95% CI: 1.07–3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. Conclusion: We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis. Essentials: Acute myeloid leukemia patients are at increased risk of venous thromboembolism (VTE). Predictive model for VTE development in acute myeloid leukemia patients was created. Six parameters were included in the model: male sex, prior history of thrombotic events, international normalized ratio (iNR), Eastern Cooperative Oncology Group performance status and intensive therapy approach. This model could identify patients whose VTE risk is high enough to warrant thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Background: Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. Methods: An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. Results: All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Conclusions: Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a hypercoagulable state caused by antiphospholipid antibodies (aPL). APS clinically manifests with arterial or venous or microvascular thrombi and/or pregnancy complications. It is well-known that the development of aPL can be a transient phenomenon and thus the current diagnostic criterion for APS requires repeat laboratory testing several weeks apart before a definitive diagnosis is made. However, transient presence of aPL may also be pathogenic. In this article, we attempt to give historical and clinical evidence for the importance of these antibodies, even when transient, and call for further research into mechanisms by which these antibodies may promote thrombosis and pregnancy morbidities. [ABSTRACT FROM AUTHOR]

Russell Viper Venom (RVV) is widely used as a diagnostic test for antiphospholipid syndrome (APS). But the history of how this venom came to be discovered is well known. Dr Patrick Russell is responsible for the identification of the venom during his work on snake bites in India while Dr Robert Macfarlane used it to staunch bleeding in persons with haemophilia. The ability to directly activate factor X led RVV to the laboratory diagnosis of APS. More recently, it has come back to clinical world with a potential for an engineered factor X activator from RVV to be used in the treatment of haemophilia. [ABSTRACT FROM AUTHOR]

This article provides guidelines for the diagnosis and management of heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet count caused by an immune response to heparin. It discusses different types of HIT, the incidence of the condition, and the presentation and assessment of HIT. The article also provides recommendations for platelet monitoring and laboratory diagnosis of HIT, as well as management strategies including the use of alternative anticoagulants and therapies such as intravenous immunoglobulin and plasma exchange. The recommendations are evidence-based and aim to assist healthcare professionals in managing HIT. [Extracted from the article]

Background Masses in the heart and valves have a broad differential diagnosis including infective and rheumatic causes as well as primary or metastatic tumours. Diagnosis involves delineating the location, shape, and origin of the mass/masses and considering the clinical context. This case outlines the work-up and approach to diagnosing a cardiac mass along with imaging findings of a unique secondary metastatic mass in the left ventricle (LV). Case summary A 69-year-old female with past medical history of metastatic lung cancer treated with radiotherapy and breast cancer treated with mastectomy presented with dyspnoea and fever. Due to concern for infective endocarditis, transthoracic echocardiogram (TTE) was performed revealing 2 cm × 0.72 cm finger-like, echo-lucent, mobile mass, appearing to originate from LV lateral wall, protruding into the LV cavity, along with valvular masses on mitral and tricuspid valves. Initial differential diagnosis included benign pathologies, but due to the clinical suspicion of malignancy, cardiac MRI was performed which revealed a broad-based mass with invasion into the LV lateral wall and delayed gadolinium enhancement, suggestive of metastatic tumour. The patient was given Aspirin to prevent embolization and eventually underwent hospice care. Discussion Atypical appearing cardiac masses can be seen on TTE. Cardiac magnetic resonance imaging (MRI) should be used for definite diagnosis in cases where clinical features do not match the echocardiographic findings. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; laboratory medicine; pandemic; SARS-CoV-2 EN COVID-19 laboratory medicine pandemic SARS-CoV-2 e235 e238 4 10/30/23 20231101 NES 231101 To the Editor, According to the World Health Organization (WHO), the European region is in a "polycrisis" and "permacrisis" that goes far beyond pandemic, climate change, and war [[1]]. Most of these laboratories performed <1 million tests per year (42.0 %), followed by laboratories performing between 1 and 4 million tests per year (32.0 %), while 15.5 % of all respondents worked in large laboratories performing more than 8 million tests per year. COVID-19, laboratory medicine, pandemic, SARS-CoV-2. [Extracted from the article]

Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Mitral valve aneurysm is a rare imaging finding most caused by infective endocarditis. The concurrent presence of an aortic valve aneurysm is unique and foretells a severe presentation that would require valve replacement during the same admission. A 42‐year‐old male patient presented with intermittent fever, night sweats, and weight loss for 2 months. TEE showed a rare finding of concurrent mitral and aortic valve aneurysms, and blood cultures grew streptococcus mutans. His infective endocarditis was successfully treated with antibiotics and placement of mechanical mitral and aortic valves. [ABSTRACT FROM AUTHOR]

Introduction: Thrombopoietin receptor agonists (TPO‐RAs) increase platelet counts (PC) in the majority of patients with chronic immune thrombocytopaenia (ITP). Platelet kinetics study (PKS) might contribute to the understanding of mechanisms that lead to durable response. Objectives: To evaluate the effects of TPO‐RAs on PKS parameters in chronic ITP patients. Methods: Fifteen chronic ITP patients, aged 59 years [range: 22–84], female/male: 10/5, splenectomised 7/15, were treated with TPO‐RAs (eltrombopag/romiplostim: 11/4). Durable response was defined as PC ≥30 × 109/L at 6 months. Autologous 111Indium‐oxinate PKS was performed before and 5 months after TPO‐RAs initiation. Accordingly, platelet survival (PS), platelet turnover, production ratio and sequestration site were assessed. Results: Durable response was achieved in 13/15 of patients (eltrombopag/romiplostim: 10/3). Pre‐treatment parameters were: PC 10 × 109/L [range: 1–110], PS 0.5 days [range: 0.1–1.7 (normal values: 7–10)], platelet turnover 30 857 Plt/μL/day [range: 944–103 500] and platelet production ratio 0.64 [range: 0.01–3.2 (normal values: 1 ± 0.2)]. Post‐treatment assessment showed significantly higher: PC 92.5 × 109/L [range: 28–260, p =.001], PS 2.2 days [range: 0.1–3.6, p =.008], platelet turnover 70 213 Plt/μL/day [range: 2800–462 236, p =.02] and platelet production ratio 1.8 [range: 0.5–37.9, p =.011] compared to the pre‐treatment values. Platelet sequestration site altered in 3/15 treated with TPO‐RAs. Conclusions: TPO‐RAs could increase PC by simultaneous increasing of platelet production and decreasing of platelet destruction. [ABSTRACT FROM AUTHOR]

A survey to gain insight into anticoagulant prescribing practice in the setting of chronic kidney disease (CKD) across the UK was disseminated via renal and haematology networks. Areas of anticoagulant use included patients with venous thromboembolism (VTE), requiring thromboprophylaxis for VTE, Atrial Fibrillation (AF) and nephrotic syndrome. An online-survey was disseminated via British Haematology Society, UK Kidney Association, and Renal Pharmacy Group over a five month period. All responses were voluntary and anonymous. Among 117 responses there were 49 nephrology doctors, 47 renal pharmacists and 20 haematology clinicians. A specialist multidisciplinary team to discuss the specific anticoagulant management of these patients was only available to 3% (4/117) respondents. Renal function estimate used for anticoagulant dosing was mainly Cockcroft-Gault for pharmacists and haematology but lab-based estimates were used by nephrology doctors. Therapeutic dose of Low Molecular Weight Heparin was mostly likely to be reduced by one-third when used for VTE treatment, with the majority of units undertaking anti-Xa monitoring in CKD stage 5 and dialysis. Direct-acting Oral Anticoagulants are being used in patients with nephrotic syndrome, those with CKD stage 5 and on dialysis for VTE and AF in the absence of license in these indications. This survey highlighted the significant differences between anticoagulant prescribing in CKD between two professional specialties and marked variation between centres in anticoagulant management strategies employed for these patients. With gaps still existing in the evidence base and answers to these not expected within the next few years, development of a best-practice guideline would be warranted to support clinicians in this field. [ABSTRACT FROM AUTHOR]

Key content: Thromboembolism is a major cause of preventable morbidity and mortality. Hospital acquired thrombosis (HAT) accounts for 50–60% of all thromboembolic events.As well as effects on patient safety, there are considerable cost implications to both prophylaxis and treatment.While guidance exists on thromboprophylaxis for patients in obstetrics and those undergoing general surgery, there is a paucity of guidance relating to gynaecological practice.Increasing prevalence of risk factors and multimorbidity is paralleled by higher risk of thromboembolic events.Gynaecological surgery presents some unique risk factors for thrombosis. Learning objectives: To understand the basic pathophysiology of thrombosis in relation to risk factors particularly relevant to gynaecology and pelvic surgery.To know the current evidence in key areas relevant to gynaecological practice: early pregnancy; day case surgery; minimally invasive gynaecological surgery; open and complex benign gynaecology and gynaecological oncology.To be aware of proposed guidance on risk assessment and prophylaxis in thrombosis as relevant to the gynaecologist based on current evidence. Ethical issues: Problems with thromboprophylaxis in high‐risk patients include noncompliance and refusing animal products/injections.Clinicians may be reluctant to institute thromboprophylaxis, most times because of the possible risks of bleeding. [ABSTRACT FROM AUTHOR]

Prescribing of anticoagulation is increasing worldwide. This is partly reflective of an aging population with cardiovascular comorbidities such as arrhythmias and prosthetic heart valves, alongside improvements in cancer treatments and survival. In this review, we discuss three common challenges faced by clinicians. These concern the management of patients with thrombosis and thrombocytopenia, resumption of anticoagulation in patients with a history of gastrointestinal or intracranial haemorrhage, and how to approach and treat a patient with recurrent thrombosis on anticoagulation. We consider the available evidence including relevant published recommendations and propose practical management suggestions to aid clinicians faced with these dilemmas. [ABSTRACT FROM AUTHOR]

Background and Objectives: Enabling universal access to safe blood components should be a key component of every country's national healthcare strategy. This study aimed to assess the current status of infrastructure and resources of blood transfusion services (BTS) in low‐ and middle‐income countries. Materials and Methods: A cross‐sectional survey was designed to gather information on blood donations, components, redistribution, testing resources and quality management systems (QMSs). The survey was distributed to the International Society of Blood Transfusion members between October 2021 and November 2021. Results: A total of 54 respondents from 20 countries responded to the survey. This included hospital‐based BTS/blood centres (46%), national blood centres (11%)and national and regional blood services (11%). Voluntary non‐remunerated, replacement and paid donors accounted for 94.2%, 84.6% and 21.1% of donations, respectively. Apheresis donation was available in 59.6% of institutions. National/regional criteria for redistribution of blood components were reported by 75.9% of respondents. Blood components incurred payment charges in 81.5% of respondents' institutions, and payments were borne by patients in 50% of them. Testing methods, such as manual (83%), semi‐automated (68%) or fully automated (36.2%), were used either alone or in combination. QMSs were reported in 17 institutions, while accreditation and haemovigilance were reported in 12 and 8 countries, respectively. Conclusion: QMS was implemented in most of the countries despite the common use of paid donations and the lack of advanced testing. Efforts to overcome persistent challenges and wider implementation of patient blood management programmes are required. [ABSTRACT FROM AUTHOR]

Disseminated intravascular coagulation (DIC) has been understood as a consumptive coagulopathy. However, impaired hemostasis is a component of DIC that occurs in a progressive manner. The critical concept of DIC is systemic activation of coagulation with vascular endothelial damage. DIC is the dynamic coagulation/fibrinolysis disorder that can proceed from compensated to decompensated phases, and is not simply impaired hemostasis, a misunderstanding that continues to evoke confusion among clinicians. DIC is a critical step of disease progression that is important to monitor over time. Impaired microcirculation and subsequent organ failure due to pathologic microthrombi formation are the pathophysiologies in sepsis-associated DIC. Impaired hemostasis due to coagulation factor depletion from hemodilution, shock, and hyperfibrinolysis occurs in trauma-associated DIC. Overt-DIC diagnostic criteria have been used clinically for more than 20 years but may not be adequate to detect the compensated phase of DIC, and due to different underlying causes, there is no "one-size-fits-all criteria." Individualized criteria for heterogeneous conditions continue to be proposed to facilitate the diagnosis. We believe that future research will provide therapeutics using new diagnostic criteria. Finally, DIC is also classified as either acute or chronic, and acute DIC results from progressive coagulation activation over a short time and requires urgent management. In this review, we examine the advances in research for DIC. [ABSTRACT FROM AUTHOR]

Summary: Myeloproliferative neoplasms can be associated with bleeding manifestations which can cause significant morbidities. Although haematologists are aware of the likelihood of this complication in the setting of myeloproliferative neoplasms, it may often be overlooked especially in patients with no extreme elevation of blood counts and those with myelofibrosis. Acquired von Willebrand syndrome and platelet dysfunction are the two common diagnoses to be considered in this regard. In this review article, we discuss the mechanisms for the development of these rare bleeding disorders, their diagnosis and practical management. [ABSTRACT FROM AUTHOR]

Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease. Objectives: (1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001–2017. The study population was divided into three groups: (1) comparison group (n = 207,266 deliveries); (2) HELLP syndrome without DIC (n = 320); (3) HELLP syndrome with DIC (n = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (p-value <.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (p-value <.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (p-value <.001). (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome. [ABSTRACT FROM AUTHOR]

D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mammary and salivary glands, which ensures smooth flow of arising fluids where any blood contamination could be immediately lysed. In addition, healthy individuals can also regularly sustain minor injuries, often unbeknown to them, and wound healing follows clot formation in these situations. D-dimers can also arise in anxiety and following exercise, and are also markers of inflammation. Lung inflammation (triggered by microbes or foreign particles) is perhaps also particularly relevant, since the hemostasis system and fibrinolysis help to trap and remove such debris. Lung inflammation in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to D-dimer levels additive to thrombosis in patients with COVID-19 (coronavirus disease 2019). Indeed, severe COVID-19 can lead to multiple activation events, including inflammation, primary and secondary hemostasis, and fibrinolysis, all of which may contribute to cumulative D-dimer development. Finally, D-dimer testing has also found a role in the diagnosis and triaging of the so-called (COVID-19) vaccine-induced thrombotic thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistance in companion animals poses significant risks to animal and human health. Prolonged antimicrobial drug (AMD) treatment in animals is a potential source of selection pressure for antimicrobial resistance (AMR) including in the gastrointestinal microbiota. We performed a prospective study of dogs treated for septic peritonitis, pyometra, or bacterial pneumonia and collected repeated fecal samples over 60 days. Bacterial cultures and direct molecular analyses of fecal samples were performed including targeted resistance gene profiling. Results: Resistant Escherichia coli increased after 1 week of treatment (D1:21.4% vs. D7:67.9% P < 0.001) and returned to baseline proportions by D60 (D7:67.9% vs D60:42.9%, P = 0.04). Dogs with septic peritonitis were hospitalized significantly longer than those with pneumonia or pyometra. Based on genetic analysis, Simpson's diversity index significantly decreased after 1 week of treatment (D1 to D7, P = 0.008), followed by a gradual increase to day 60 (D1 and D60, P = 0.4). Detection of CTX-M was associated with phenotypic resistance to third-generation cephalosporins in E. coli (OR 12.1, 3.3–68.0, P < 0.001). Lincosamide and macrolide-resistance genes were more frequently recovered on days 14 and 28 compared to day 1 (P = 0.002 and P = 0.004 respectively). Conclusion: AMR was associated with prescribed drugs but also developed against AMDs not administered during the study. Companion animals may be reservoirs of zoonotic multidrug resistant pathogens, suggesting that veterinary AMD stewardship and surveillance efforts should be prioritized. [ABSTRACT FROM AUTHOR]

Radiation-induced normal tissue toxicity is a common acute and chronic outcome of radiotherapy (RT) for prostate cancer (PCa). There are currently no existing pre-assessments before treatment to predict acute and late RT-induced toxicity. Novel predictive blood biomarkers in radiation oncology may improve treatment decision-making and therapeutic monitoring for patients with PCa. A comprehensive systematic search of microRNA (miRNA/miR) profiling studies published in PubMed, Science Direct and Google Scholar was performed. The present systematic review, supported by meta-analysis, summarises key findings and discusses the results of prospective clinical studies investigating miRNA expression levels and their association with RT-induced toxicity in PCa. Out of seven clinical studies, six highlighted levels of 10 miRNAs changing in plasma, serum or peripheral blood mononuclear cells during RT. The post-RT expression levels of miRNA-132-5p, miRNA-1-3p, miRNA-410 and miRNA-221 were increased, and miRNA-23a-3p expression was decreased among patients with low-grade RT-induced toxicity. Furthermore, in patients with high-grade RT toxicity, miRNA-197-3p, miRNA-151a-5p, miRNA-18b-5p, miRNA-99a and miRNA-21 expression was increased, while miRNA-132-5p expression was decreased. The present miRNA meta-analysis could be the focus of future studies to identify their potential clinical value as PCa biomarkers and therapeutic mediators in RT-induced toxicity. The variations in miRNA levels post-RT could be used as predictive biomarkers of RT-induced toxicity. However, further extensive validation is required to establish the relationship between miRNA expression levels and RT-induced toxicity in PCa and to confirm their predictive value. [ABSTRACT FROM AUTHOR]

In the study of electoral politics and political behavior in the developing world, India is often considered to be an exemplar of the centrality of contingency in distributive politics, the role of ethnicity in shaping political behavior, and the organizational weakness of political parties. Whereas these axioms have some empirical basis, the massive changes in political practices, the vast variation in political patterns, and the burgeoning literature on subnational dynamics in India mean that such generalizations are not tenable. In this article, we consider research on India that compels us to rethink the contention that India neatly fits the prevailing wisdom in the comparative politics literature. Our objective is to elucidate how the many nuanced insights about Indian politics can improve our understanding of electoral behavior both across and within other countries, allowing us to question core assumptions in theories of comparative politics. [ABSTRACT FROM AUTHOR]

Objectives: Data on the health burden of COVID-19 among Asian American people of various ethnic subgroups remain limited. We examined COVID-19 outcomes of people of various Asian ethnic subgroups and other racial and ethnic groups in an urban safety net hospital system. Methods: We conducted a retrospective analysis of 85 328 adults aged ≥18 tested for COVID-19 at New York City's public hospital system from March 1 through May 31, 2020. We examined COVID-19 positivity, hospitalization, and mortality, as well as demographic characteristics and comorbidities known to worsen COVID-19 outcomes. We conducted adjusted multivariable regression analyses examining racial and ethnic disparities in mortality. Results: Of 9971 Asian patients (11.7% of patients overall), 48.2% were South Asian, 22.2% were Chinese, and 29.6% were in other Asian ethnic groups. South Asian patients had the highest rates of COVID-19 positivity (30.8%) and hospitalization (51.6%) among Asian patients, second overall only to Hispanic (32.1% and 45.8%, respectively) and non-Hispanic Black (27.5% and 57.5%, respectively) patients. Chinese patients had a mortality rate of 35.7%, highest of all racial and ethnic groups. After adjusting for demographic characteristics and comorbidities, only Chinese patients had significantly higher odds of mortality than non-Hispanic White patients (odds ratio = 1.44; 95% CI, 1.04-2.01). Conclusions: Asian American people, particularly those of South Asian and Chinese descent, bear a substantial and disproportionate health burden of COVID-19. These findings underscore the need for improved data collection and reporting and public health efforts to mitigate disparities in COVID-19 morbidity and mortality among these groups. [ABSTRACT FROM AUTHOR]

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what neural response a given MiSt will produce and possibly allow the development of natural "sensation." To date, our optimization has been conducted in the rodent model and simulations. Here, we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we used MiSt in the VPL of macaques, which have a somatosensory system more like humans, as compared to our previous rat work (Li et al., 2014; Choi et al., 2016). We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post-stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt toward producing a somatosensory neuroprosthesis in humans. [ABSTRACT FROM AUTHOR]

Objective: To determine the short- and long-term outcomes of triple semicircular canal occlusion as a potential alternative for patients with intractable Ménière's disease. Methods: A retrospective case series was performed in university settings, enrolling patients with intractable Ménière's disease with previous maximum treatment, who underwent transmastoid, triple semicircular canal occlusion. The study documented: pre- and post-operative Dizziness Handicap Inventory scores at six weeks and one year post-treatment, pure tone audiometry, and surgical aspects. Results: Two female patients, aged 42 and 65 years, underwent unilateral three-semicircular-canal occlusion. Their respective Dizziness Handicap Inventory scores improved from 88 to 68 and 54 to 30 at six weeks post-operatively, with scores of 66 and 0 at one year post-treatment. The one patient with pre-existing functional hearing maintained her hearing threshold post-operatively. Conclusion: Triple semicircular canal occlusion is a safe, hearing-preserving, extracranial alternative technique that can control rotatory vertigo in patients with intractable Ménière's disease, when other measures have failed. [ABSTRACT FROM AUTHOR]

Nonovert disseminated intravascular coagulation (DIC) is a subclinical hemostatic dysfunction that has not yet reached the decompensation stage. The detection of pregnant patients at this stage may assist in the identification of those who will develop severe obstetrical hemorrhage, as it is one of the leading causes for preventable maternal mortality. Currently, nonovert DIC is diagnosed by a scoring system based on nonpregnant patients, originally generated by the International Society on Thrombosis and Hemostasis (ISTH), which does not address the physiologic changes of the hemostatic system during pregnancy. (1) To develop a pregnancy-specific nonovert DIC score, (2) to determine the diagnostic performance of this score in detecting women at risk for obstetrical hemorrhage requiring blood product transfusion, and (3) to compare it to the existing ISTH nonovert DIC score. This retrospective study has longitudinal and cross-sectional components and includes three steps: (1) characterization of the longitudinal changes in the components of modified ISTH nonovert DIC scores, including these parameters – fibrinogen, antithrombin III, protein C, prothrombin time (PT), platelets, thrombin-antithrombin (TAT) complex, and D-dimer – during gestation in a group of normal pregnancies (n = 50); (2) development of a pregnancy-specific nonovert DIC score in a cross-sectional design of high-risk (n = 152) and control (n = 50) pregnancies, based on the predictive performance of each analyte for the detection of women at risk for obstetrical hemorrhage requiring blood product transfusion and a logistic regression model; and (3) comparison between the diagnostic performance of the pregnancy-specific nonovert DIC score and the modified ISTH nonovert DIC score to detect, upon admission, women who are at increased risk for subsequent development of obstetrical hemorrhage requiring blood product transfusion. (1) The study cohort included 202 patients, of which 21 (10%) had obstetrical hemorrhage that required blood product transfusion and were considered to have nonovert DIC; (2) using the nonpregnant ISTH nonovert DIC score, 92% of the patients had a D-dimer concentration above the 0.5 mg/L threshold, and only 2% were identified to have a low fibrinogen concentration (<100 mg/dL); thus, this scoring system was unable to identify any of the patients with nonovert DIC based on the suggested cutoff of a score of ≥5; (3) the parameters included in the pregnancy-specific nonovert DIC score were selected based on their contribution to the performance of the model for the prediction of women at risk for obstetrical hemorrhage requiring blood product transfusion; as a result, we excluded the PT difference parameter from the score and the TAT complex concentration was added; and (4) a pregnancy-specific nonovert DIC score of ≥3 had a sensitivity of 71.4% and a specificity of 77.9% to identify patients at risk for obstetrical hemorrhage requiring blood product transfusion. We propose (1) a pregnancy-specific nonovert DIC score adjusted for the physiologic changes in the hemostatic system during gestation; and (2) that the pregnancy-specific nonovert DIC score can be a useful tool for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion. [ABSTRACT FROM AUTHOR]

Obstetrical hemorrhage and especially DIC (disseminated intravascular coagulation) is a leading cause for maternal mortality across the globe, often secondary to underlying maternal and/or fetal complications including placental abruption, amniotic fluid embolism, HELLP syndrome (hemolysis, elevated liver enzymes and low platelets), retained stillbirth and acute fatty liver of pregnancy. Various obstetrical disorders can present with DIC as a complication; thus, increased awareness is key to diagnosing the condition. DIC patients can present to clinicians who may not be experienced in a variety of aspects of thrombosis and hemostasis. Hence, DIC diagnosis is often only entertained when the patient already developed uncontrollable bleeding or multi-organ failure, all of which represent unsalvageable scenarios. Beyond the clinical presentations, the main issue with DIC diagnosis is in relation to coagulation test abnormalities. It is widely believed that in DIC, patients will have prolonged prothrombin time (PT) and partial thromboplastin time (PTT), thrombocytopenia, low fibrinogen, and raised D-dimers. Diagnosis of DIC can be elusive during pregnancy and requires vigilance and knowledge of the physiologic changes during pregnancy. It can be facilitated by using a pregnancy specific DIC score including three components: 1) fibrinogen concentrations; 2) the PT difference – relating to the difference in PT result between the patient's plasma and the laboratory control; and 3) platelet count. At a cutoff of ≥ 26 points, the pregnancy specific DIC score has 88% sensitivity, 96% specificity, a positive likelihood ratio (LR) of 22, and a negative LR of 0.125. Management of DIC during pregnancy requires a prompt attention to the underlying condition leading to this complication, including the delivery of the patient, and correction of the hemostatic problem that can be guided by point of care testing adjusted for pregnancy. [ABSTRACT FROM AUTHOR]

Our brain's ability to represent vast amounts of information, such as continuous ranges of reward spanning orders of magnitude, with limited dynamic range neurons, may be possible due to normalization. Recently our group and others have shown that the sensorimotor cortices are sensitive to reward value. Here we ask if psychological affect causes normalization of the sensorimotor cortices by modulating valence and motivational intensity. We had two non-human primates (NHP) subjects (one male bonnet macaque and one female rhesus macaque) make visually cued grip-force movements while simultaneously cueing the level of possible reward if successful, or timeout punishment, if unsuccessful. We recorded simultaneously from 96 electrodes in each the following: caudal somatosensory, rostral motor, and dorsal premotor cortices (cS1, rM1, PMd). We utilized several normalization models for valence and motivational intensity in all three regions. We found three types of divisive normalized relationships between neural activity and the representation of valence and motivation, linear, sigmodal, and hyperbolic. The hyperbolic relationships resemble receptive fields in psychological affect space, where a unit is susceptible to a small range of the valence/motivational space. We found that these cortical regions have both strong valence and motivational intensity representations. [ABSTRACT FROM AUTHOR]

Background: : Kidney transplant recipients(KTRs) are at an increased risk of venous thromboembolism (VTE) and atrial fibrillation(AF). Direct oral anticoagulants (DOACs) have shown important advantages over vitamin K antagonists; however, in KTRs, concerns regarding interactions and use in severe kidney disease may limit their use. This evaluation describes a large UK kidney transplant center's experience of DOACs in KTRs with CrCl > 15 mL/min. Methods: Electronic records were reviewed for all adult KTRs at Manchester University Foundation Trust Hospitals taking DOACs between January 2018 and October 2020 with VTE or AF. The primary outcome was trough and peak DOAC levels within the expected reference ranges and secondary outcomes included bleeding and thrombotic events. Results: In 31 KTRs taking DOACS, eight patients had a CrCl < 30 mL/min. Overall, 94% (62/66) of DOAC levels were within the recommended ranges. There were no thrombotic events and four bleeding events (two major and two clinically relevant non‐major bleeds). The overall bleeding rate was 6.9 per 100 patient‐years at risk. Conclusions: There was no evidence of a significant interaction of apixaban or rivaroxaban with CNIs based on expected DOAC and CNI levels. Their use was found to be safe and effective with no VTE events and bleeding episodes similar to published trial data. [ABSTRACT FROM AUTHOR]

Background: Nucleosomes and neutrophil extracellular traps (NETs) are important in the pathophysiology of disseminated intravascular coagulation (DIC). Fibrinogen, as an acute phase reactant, may be protective by engaging neutrophils. We hypothesize that DIC can occur when NET formation becomes uncontrolled in relation to low fibrinogen levels. Patients/method: The ratio of both circulating nucleosomes and human neutrophil elastase alpha‐1‐antitrypsine complexes (HNE‐a1ATc) to fibrinogen was correlated to thrombocytopenia, DIC and organ failure in 64 critically ill coagulopathic patients. Results: A high nucleosome to fibrinogen ratio correlated with thrombocytopenia and organ failure (ρ −0.391, p 0.01 and ρ 0.556, p 0.01, respectively). A high HNE‐a1ATc to fibrinogen ratio correlated with thrombocytopenia, DIC and organ failure (ρ −0.418, p 0.01, ρ 0.391, p 0.01 and ρ 0.477, p 0.01 respectively). Conclusion: These findings support the hypothesis that fibrinogen is protective against DIC by counterbalancing excessive neutrophil activation. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is an autoimmune disorder in which a combination of defective platelet production and enhanced clearance leads to thrombocytopenia. The primary aim for therapy in patients with this condition is the prevention of bleeding. However, more recently, increased rates of venous and arterial thrombotic events have been reported in ITP, even in the context of marked thrombocytopenia. In this review we discuss the epidemiology, aetiology and management of thrombotic events in these patients. We consider the impact of ITP therapies on the increased thrombotic risk, in particular the use of thrombopoietin‐receptor agonists (TPO‐RAs), as well as factors inherent to ITP itself. We also discuss the limited evidence available to guide clinicians in the treatment of these complex cases. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that ABO blood group may play a role in the immunopathogenesis of SARS‐CoV‐2 infection, with group O individuals less likely to test positive and group A conferring a higher susceptibility to infection and propensity to severe disease. The level of evidence supporting an association between ABO type and SARS‐CoV‐2/COVID‐19 ranges from small observational studies, to genome‐wide‐association‐analyses and country‐level meta‐regression analyses. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues (notably endothelium). There are several hypotheses to explain the differences in SARS‐CoV‐2 infection by ABO type. For example, anti‐A and/or anti‐B antibodies (e.g. present in group O individuals) could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell infection. The SARS‐CoV‐2 virus and SARS‐CoV spike (S) proteins may be bound by anti‐A isoagglutinins (e.g. present in group O and group B individuals), which may block interactions between virus and angiotensin‐converting‐enzyme‐2‐receptor, thereby preventing entry into lung epithelial cells. ABO type‐associated variations in angiotensin‐converting enzyme‐1 activity and levels of von Willebrand factor (VWF) and factor VIII could also influence adverse outcomes, notably in group A individuals who express high VWF levels. In conclusion, group O may be associated with a lower risk of SARS‐CoV‐2 infection and group A may be associated with a higher risk of SARS‐CoV‐2 infection along with severe disease. However, prospective and mechanistic studies are needed to verify several of the proposed associations. Based on the strength of available studies, there are insufficient data for guiding policy in this regard. [ABSTRACT FROM AUTHOR]

Mirror Neurons (MNs) respond similarly when primates make or observe grasping movements. Recent work indicates that reward expectation influences rostral M1 (rM1) during manual, observational, and Brain Machine Interface (BMI) reaching movements. Previous work showed MNs are modulated by subjective value. Here we expand on the above work utilizing two non-human primates (NHPs), one male Macaca Radiata (NHP S) and one female Macaca Mulatta (NHP P), that were trained to perform a cued reward level isometric grip-force task, where the NHPs had to apply visually cued grip-force to move and transport a virtual object. We found a population of (S1 area 1–2, rM1, PMd, PMv) units that significantly represented grip-force during manual and observational trials. We found the neural representation of visually cued force was similar during observational trials and manual trials for the same units; however, the representation was weaker during observational trials. Comparing changes in neural time lags between manual and observational tasks indicated that a subpopulation fit the standard MN definition of observational neural activity lagging the visual information. Neural activity in (S1 areas 1–2, rM1, PMd, PMv) significantly represented force and reward expectation. In summary, we present results indicating that sensorimotor cortices have MNs for visually cued force and value. [ABSTRACT FROM AUTHOR]

The role of D-dimers in the management of venous thromboembolism is well established and testing for D-dimers has become common in most acute settings. Although it has been validated for the purpose of excluding venous thromboembolism, the test is increasingly ordered to 'diagnose' venous thromboembolism. Furthermore, in the COVID-19 pandemic, heavy reliance has been put on this test with the inclusion of D-dimers to guide treatment pathways. This review summarises the appropriateness of D-dimer tests in these different clinical settings. [ABSTRACT FROM AUTHOR]