Factor XI/XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism: A narrative review.

During the past decade, direct oral anticoagulants (DOACs) have advanced and simplified the prevention and treatment of venous thromboembolism (VTE). However, there remains a high incidence of bleeds, which calls for agents that have a reduced risk of bleeding. Factor XI (FXI) deficiency is associated with lower rates of venous thrombosis and stroke compared to the general population with a lower risk of bleeding. In conjunction with this, phase 2 studies have demonstrated safety and the potential for reduced thrombotic events with FXI inhibitors as compared to currently available medications. The aim of this review is to summarize key data on the clinical pharmacology of FXI, the latest developments in clinical trials of FXI inhibitors, and to describe the efficacy and safety profiles of FXI inhibitors for the prevention of venous and arterial thromboembolism.

Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism.

Direct oral anticoagulants (DOACs) have become the standard of care for acute and long-term therapy for venous thromboembolism (VTE) due to their efficacy and safety profiles. The 2021 International Society on Thrombosis and Haemostasis guidelines recommend using standard DOAC dosages in patients with BMI >40 kg/m2 or weight >120 kg. Use of DOACs remains uncertain in morbidly obese patients with VTE, including acute PE. A morbidly obese woman in her 30s who presented with acute worsening of dyspnea was diagnosed with acute intermediate-high risk acute pulmonary embolism and concomitant proximal deep vein thrombosis, constituting a clinically challenging scenario for treating her with rivaroxaban. Standard doses of rivaroxaban for acute and extended phase treatment of venous thromboembolism in individuals with morbid obesity at BMI>70 kg/m2 may be effective, and safe.

Devido à sua eficácia e aos seus perfis de segurança, os anticoagulantes orais diretos (DOACs) tornaram-se o padrão de cuidado para a terapia aguda e de longo prazo de tromboembolismo venoso (TEV). As diretrizes da Sociedade Internacional de Trombose e Hemostasia de 2021 recomendam o uso de dosagens padrão de DOACs em pacientes com índice de massa corporal (IMC) > 40 kg/m2 ou peso > 120 kg. O uso de DOACs em pacientes com obesidade mórbida e TEV, incluindo embolia pulmonar aguda, ainda não foi esclarecido. Uma mulher com obesidade mórbida na faixa dos 30 anos que apresentou piora aguda da dispneia foi diagnosticada com embolia pulmonar aguda de risco intermediário-alto e trombose venosa profunda proximal concomitante, com o cenário clínico desafiador de tratá-la com rivaroxabana. Doses padrão de rivaroxabana para tratamento e recorrência de tromboembolismo venoso em indivíduos com obesidade mórbida e IMC > 70 kg/m2 podem ser eficazes e seguras.

The perceived global impact of the COVID-19 pandemic on doctors' medical and surgical training: An international survey.

INTRODUCTION: The COVID-19 pandemic has resulted in a significant burden on healthcare systems causing disruption to the medical and surgical training of doctors globally. AIMS AND OBJECTIVES: This is the first international survey assessing the perceived impact of the COVID-19 pandemic on the training of doctors of all grades and specialties. METHODS: An online global survey was disseminated using Survey Monkey® between 4th August 2020 and 17th November 2020. A global network of collaborators facilitated participant recruitment. Data were collated anonymously with informed consent and analysed using univariate and adjusted multivariable analyses. RESULTS: Seven hundred and forty-three doctors of median age 27 (IQR: 25-30) were included with the majority (56.8%, n = 422) being male. Two-thirds of doctors were in a training post (66.5%, n = 494), 52.9% (n = 393) in a surgical specialty and 53.0% (n = 394) in low- and middle-income countries. Sixty-nine point two percent (n = 514) reported an overall perceived negative impact of the COVID-19 pandemic on their training. A significant decline was noted amongst non-virtual teaching methods such as face-to-face lectures, tutorials, ward-based teaching, theatre sessions, conferences, simulation sessions and morbidity and mortality meetings (P ≤ .05). Low or middle-income country doctors' training was associated with perceived inadequate supervision while performing invasive procedures under general, local or regional anaesthetic. (P ≤ .05). CONCLUSION: In addition to the detrimental impact of the COVID-19 pandemic on healthcare infrastructure, this international survey reports a widespread perceived overall negative impact on medical and surgical doctors' training globally. Ongoing adaptation and innovation will be required to enhance the approach to doctors' training and learning in order to ultimately improve patient care.

Naturally occurring fluorescence protects the eutardigrade Paramacrobiotus sp. from ultraviolet radiation.

Naturally occurring fluorescence has been observed in multiple species ranging from bacteria to birds. In macroscopic animals such as birds, fluorescence provides a visual communication signal. However, the functional significance of this phenomenon is unknown in most cases. Though photoprotection is attributed to fluorescence under ultraviolet (UV) light in some organisms, it lacks direct experimental evidence. Here, we demonstrate naturally occurring fluorescence under UV light in a eutardigrade belonging to the genus Paramacrobiotus. Using a natural variant that lacks fluorescence, we show that the fluorescence confers tolerance to lethal UV radiation. Remarkably, the fluorescent extract from Paramacrobiotus sp. could protect the UV-sensitive tardigrade Hypsibius exemplaris and nematode Caenorhabditis elegans from germicidal UV radiation. We propose that Paramacrobiotus sp. possess a protective fluorescent shield that absorbs harmful UV radiation and emits harmless blue light.

Evaluation of Four Validated Risk Scores to Predict Outcomes in Hispanic Patients With Acute Pulmonary Embolism.

Risk stratification plays an essential role in the management of acute pulmonary embolism (PE). Several risk scores have been studied to support risk stratification and management. While ethnic differences in acute PE risk factors exist, current risk scores lack validation for Hispanic patients. Therefore, the present study retrospectively investigated the performance of the pulmonary embolism severity index (PESI), simplified PESI (sPESI), the European Society of Cardiology risk assessment (ESC), and the Bova score, to predict 30-day mortality in Hispanic patients presenting with an acute PE. Among 437 patients admitted with acute PE, 30-day mortality was 10.8%; 30-day mortality in low-risk groups ranged from 0% (sPESI, ESC) to 0.2% (PESI, Bova), and 3.0% (Bova) to 5.7% (PESI) in the highest risk groups, respectively. All four scores produced statistically significant discrimination between different risk strata. However, no single scoring system was able to identify all patients with 30-day mortality. The findings of the present study suggest that PESI, sPESI, ESC, and Bova scores provide important information about 30-day mortality in Hispanic in-patients presenting with acute PE. However, additional clinical information could further improve predictability that is not provided by a single scoring system.

Portal vein thrombosis in cirrhosis: A literature review.

Portal Vein Thrombosis (PVT), a common complication of advanced liver disease, is defined as an obstruction of the portal vein due to thrombus formation that can extend to the superior mesenteric and splenic veins. It was believed that PVT occurred predominantly due to prothrombotic potential. However, recent studies have shown that decreased blood flow related to portal hypertension appears to increase PVT risk as per Virchow's triad. It is well known that there is a higher incidence of PVTs in cirrhosis with a higher MELD and Child Pugh score. The controversy for management of PVTs in cirrhotics lies in the individualized assessment of risks versus benefits of anticoagulation, since these patients have a complex hemostatic profile with both bleeding and procoagulant propensities. In this review, we will systematically compile the etiology, pathophysiology, clinical features, and management of portal vein thrombosis in cirrhosis.

Vancomycin-Induced Thrombocytopenia in a 35-Year-Old Female With Pneumonia: A Case Report.

Vancomycin is one of the most empirically used antibiotics in severely ill patients in hospitalized settings. Vancomycin-induced thrombocytopenia (VITP) is a rare and potentially life-threatening complication that requires immediate recognition. Platelet destruction is largely immune-mediated and results in a precipitous drop in the platelet count over a short period of time. Most cases of VITP are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline to pre-exposure platelet levels. Here, we present a case of severe vancomycin-induced thrombocytopenia in a 35-year-old female with a history of multiple comorbidities who presented with pneumonia. She was undergoing treatment with vancomycin and piperacillin-tazobactam and developed thrombocytopenia within 24 hours of hospitalization. The patient was on a loading dose of 1250 mg intravenous vancomycin every 24 hours and piperacillin-tazobactam 3.375 g intravenously every six hours for presumed community-acquired pneumonia. Her other medications included ondansetron, bupropion, sertraline, tamsulosin, pantoprazole, ergocalciferol, and insulin glargine. Additionally, the patient was placed on a prophylactic dose of enoxaparin while in-patient. The patient's thrombocytopenia resolved with discontinuation of vancomycin. Clinicians should be well-informed about which medications can trigger thrombocytopenia whenever starting a medication in such cases.

Persistent Headaches in an Avid Hiker: A Case of Chronic Coccidioidal Meningitis.

The clinical presentation, diagnosis, treatment, and complications of coccidioidal meningitis caused by the dimorphic pathogenic fungus Coccidioides (Coccidioides immitis and Coccidioides posadasii) have been well documented in the literature. Despite the abundance of literature concerning this disease manifestation, it is not very commonly seen in clinical practice, delaying its diagnosis and treatment and leading to devastating neurological sequelae. Therefore, considering this disease process as a potential diagnosis in endemic areas is important for appropriate and timely treatment. We present the case of a 26-year-old male who was found to have chronic coccidioidal meningitis on further investigation. The patient presented as a transfer for an abnormal head MRI with a three-month history of progressive occipital headaches and shortness of breath. Associated symptoms included transit vision loss, upper extremity numbness, night sweats, decreased appetite, and weight loss. Relevant risk factors were being a hiker and living in the southwest of Texas. The patient was started on empiric ceftriaxone and vancomycin. A repeat MRI showed leptomeningeal enhancement and acute infarcts in the left temporal lobe and lentiform nucleus. Cerebrospinal fluid (CSF) analysis showed pleocytosis with lymphocytic predominance, the presence of eosinophils, elevated protein level, and an extremely low glucose level. Further workup ruled out syphilis and tuberculosis. Therefore, considering his clinical presentation, risk factors, and workup results, ceftriaxone and vancomycin were discontinued, and high-dose oral fluconazole was started, which produced a marked clinical response within the next 48 hours. A CT thorax showed findings suggestive of pulmonary coccidioidomycosis, and Coccidioides serology in both serum and CSF specimens returned positive.

A Rare Association Between Herpes Simplex Virus Type 1 and Miller-Fisher Syndrome.

The etiopathogenesis for Guillain-Barré syndrome (GBS) and Miller-Fisher syndrome (MFS), a variant of GBS, is well-documented in the literature. However, the association between MFS and an underlying herpes simplex virus type 1 (HSV-1) infection is very limited. We present a unique case of a 48-year-old man who developed diplopia, bilateral ptosis, and gait instability following an acute diarrheal illness and recurring cold sores. The patient was diagnosed with MFS precipitated by recurrent HSV-1 infection following a Campylobacter jejuni acute infection. The diagnosis of MFS was supported by a positive anti-GQ1b ganglioside immunoglobulin (Ig)G and abnormal MRI-enhancing lesions of the bilateral cranial nerves III and VI. Intravenous immunoglobulin and acyclovir produced a significant clinical response in the patient within the first 72 hours. Our case highlights the rare association between two pathogens and MFS and the importance of recognizing risk factors, symptomatology, and appropriate workup accompanying an atypical MFS case.

Successful Treatment With the Oral Factor Xa Inhibitor Edoxaban in Heparin-Induced Thrombocytopenia With Thrombosis.

Heparin-induced thrombocytopenia with thrombosis (HITT) is a rare immune reaction to the drug heparin that causes increased blood clotting, putting patients at risk for arterial and venous thromboembolism which can have severe consequences. We present a case of HITT successfully treated with the direct oral anticoagulant (DOAC), edoxaban. A 56-year-old man had surgery to remove a colorectal mass. After discharge, he developed chest discomfort, shortness of breath, and low oxygen levels and was diagnosed with a right-sided lobar pulmonary embolism. His platelet count dropped, his tests confirmed a diagnosis of HITT, and he was initially treated with fondaparinux. After showing clinical and laboratory improvement, he was switched to edoxaban. Despite being diagnosed with colonic adenocarcinoma during follow-up, the patient's platelet count returned to normal, and he did not experience any more blood clots or serious bleeding events. The use of DOACs like edoxaban as potential therapies for HITT is promising; further research is being conducted to evaluate their effectiveness, safety, and potential benefits for treating this acquired high-risk thrombophilia.

Attack of the Clones: A Patient With Untreated Aplastic Anemia Presenting With Classical Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired X-linked, clonal hematopoietic stem cell disease. Patients with PNH may complain of vague symptomatology that contributes to the challenge of its diagnosis. This is especially true in the clinical context of a coinciding hematologic disorder. Aplastic anemia (AA) is an additional immune-mediated illness that results in the destruction of hematopoietic precursors and pancytopenia. The authors encourage screening for PNH clones in patients initially diagnosed with AA, treating underlying hematologic disease to prevent clonal expansion, and further research to investigate the effectiveness of eculizumab in an unusual "classical" PNH secondary to AA with hypercellular bone marrow.

An Unusual Case of Combined Thrombosis and Amegakaryocytopenia Resembling Thrombosis With Thrombocytopenia Syndrome Following COVID-19 Infection in an Unvaccinated Patient.

As a global community, we have learned that the manifestations of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), infection, or coronavirus disease 2019 (COVID-19), extends far beyond respiratory compromise. Thrombocytopenia is thought to occur secondary to increased platelet consumption. Platelet activation and platelet-mediated immune inflammation contribute towards the thromboembolic complications seen in COVID-19 patients. In this report, the authors present the unusual case of a 75-year-old female with a history of COVID-19 infection who presented with a transient ischemic attack, thrombocytopenia, and amegakaryocytopenia.

Chronic Recurrent Multifocal Osteomyelitis: A Comprehensive Literature Review.

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious, inflammatory disorder of the bones. CRMO typically affects children, with a predisposition to females. Bone-related pain is often felt in the metaphysis of long bones, particularly of the lower extremities, but it can also target other sites at varied time intervals. Patients are likely to complain of tenderness and swelling that may cause considerable disability and adversely impact quality of life. There are three main pathophysiological mechanisms that have been hypothesized to drive CRMO including imbalanced cytokine expression, increased inflammasome activation, and enhanced osteoclast differentiation. Therapies have been based on targeting and suppressing these key players in CRMO patients. The first step in management involves pain control. Non-steroidal anti-inflammatory drugs should provide initial relief, albeit temporarily. It is imperative to initiate immunosuppressive medication that will help limit bone involvement and thereby prevent the development of fractures or leg-length discrepancies, for example. The purpose of this literature review is to study the pathophysiology of CRMO and carefully dissect the agents that have been previously employed in the management of CRMO patients. This could allow for the purposeful formulation of individualized care plans and improving the overall well-being of patients. The authors included a multitude of PubMed-indexed articles published from 2000 onwards in this review.

A Rare Case of Page Kidney With Superimposed Infection.

Page kidney (PK) is a rare renal condition characterized by external compression of the kidney, typically by a subcapsular hematoma, leading to resistant secondary hypertension due to hypoperfusion and ischemia. This hypertension is caused by the external compression of the kidney by a chronic subcapsular hematoma that activates the renin-angiotensin-aldosterone system (RAAS) system. Hematoma formation can result from external or internal trauma. The resolution of the hematoma can take months, and, in some cases, may necessitate a nephrectomy. Unresolved subcapsular hematomas can be complicated by infection, leading to sepsis, hospitalization, and the need for surgical drainage. This report presents a unique case of a 67-year-old female with a spontaneous left renal subcapsular hematoma that did not resolve with conservative measures and was complicated by superimposed infection requiring percutaneous drainage.

Brazilian Butt Lift Gone Wrong: A Case Series of Non-Tuberculous Mycobacterial Gluteal Infection After Brazilian Butt Lifts.

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient's clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

Prevalence and clinical significance of deep vein thrombosis in Hispanic patients with acute pulmonary embolism.

The prevalence of concomitant deep vein thrombosis (DVT) and its impact on 30-day outcomes in Hispanic patients with acute pulmonary embolism (PE) is unknown. We retrospectively studied a cohort of Hispanic patients admitted for acute PE to determine the relationship of concomitant DVT to clot burden on chest computer tomography (CT), right heart strain, and 30-day mortality. We identified 391 patients admitted with acute PE; 168 (42.9%) had concomitant DVTs on admission; 39 patients (9.9%) died during the 30-day follow-up: 12 patients without concomitant DVT and 27 with concomitant DVT, respectively (p < .001). The presence of a proximal DVT independently predicted 30-day mortality even after adjusting for age, gender and admission PE severity index scores (PESI) (hazard ratio [HR] 2.0; 95% confidence interval [CI]: 1.4-3.0, p = .001). Proximal DVTs remained a significant predictor of 30-day mortality in patients with low and intermediate PESI scores (HR 2.5; 95% CI: 1.1-6.0, p = .035). The prevalence of concomitant DVT in Hispanic patients presenting with acute DVT is relatively lower than other ethnic groups. However, a proximal location of a DVT is of significant prognostic relevance. Hispanic patients with acute PE should routinely undergo compression doppler ultrasonography (CDUS) of the lower extremities.

Improvement in Primary Autoimmune Myelofibrosis Following a Short Course of Steroids and Intravenous Immunoglobulins.

Bone marrow fibrosis (BMF) is a histopathological finding appreciated in a multitude of conditions such as myeloproliferative diseases and malignant neoplasms, along with autoimmune disorders. Autoimmune myelofibrosis (AIMF) is a particularly uncommon etiology of benign BMF. AIMF may be primary with serologic evidence of autoantibodies or secondary to an underlying autoimmune disease. The authors aim to emphasize the importance of distinguishing between primary versus secondary causes owing to significant prognostic and therapeutic discrepancies and in hopes of expediting the diagnostic journey. Research has recommended a treatment strategy of high-dose steroids followed by a steroid taper. However, our patient responded positively to a short course of high-dose steroids and intravenous immunoglobulins (IVIG) as evidenced by an improvement in cytopenias and bone marrow fibrosis grading. This outcome warrants further research on the necessity of steroid tapers in AIMF.

A Rare Case of Phentermine-Induced Nonischemic Cardiomyopathy.

Obesity is a global epidemic with steadily increasing prevalence in most countries. Weight loss is generally challenging for patients to tackle in the face of the temptation to overeat and avoid physical activity. Hence, clinicians and patients alike are likely to steer toward the use of anorexigens. We report the case of a 33-year-old female with no significant cardiac history who presented with dyspnea, productive cough, and chest pressure for one month and was diagnosed with new-onset heart failure with a reduced ejection fraction secondary to prolonged phentermine use. The authors aim to highlight phentermine's potential for precipitating heart failure, even in a young, relatively healthy person, especially with a growing obese population. Ultimately, healthy weight loss can be achieved by implementing dietary changes and encouraging adequate physical activity, as the World Health Organization (WHO) recommended. Anorectic drugs may be employed for short-term use. Further research concerning the long-term side effects of phentermine may avert the prescriber and patient from abusing this drug.

Undifferentiated Pleomorphic Sarcoma Presenting With Cardiac Tamponade: A Case Report and Review.

Soft tissue sarcomas (STS) comprise a large group of heterogeneous malignant tumors that form approximately 1% of all adult malignancies. Most sarcomas originate from soft tissue and the rest arise from the bone. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor that usually presents as an asymptomatic subcutaneous mass that exhibits rapid growth with unremarkable skin findings. The diagnosis is usually made with histopathology or immunohistochemistry; once the diagnosis is confirmed, evaluation and workup of the primary tumor, lymph nodes, and metastasis should be made. Treatment is stage-dependent but generally involves en-bloc resection followed by a review of pathology with a discussion of the benefits of adjuvant radiation or chemotherapy. Here, we discuss a case of a 77-year-old patient who presented with a large mass over the right shoulder and echocardiographic findings of cardiac tamponade.