Emicizumab for acquired hemophilia A: Report of two cases and dosing strategies.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by autoantibodies against FVIII. Severe AHA is life-threatening. Currently, licensed hemostatic agents for the treatment of severe AHA have short half-lives and require intravenous administration, leading to a need for hospitalization, higher costs, and negative effects on quality of life. We present two cases of severe AHA with high inhibitor titers where emicizumab was safely and effectively used with intensive immunosuppression. These reports suggest in vivo efficacy even in high inhibitor environments. The optimal dosing regimen (accelerated vs. standard loading, maintenance frequency) is unknown and we discuss the current approaches.

A Case Report of Cytarabine-Induced Red Ear Syndrome.

Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia which acts by inhibiting DNA synthesis and subsequently cell division. It works on rapidly dividing cells, for that reason, it affects cancer cells, bone marrow and skin cells. Cytarabine has variable cutaneous side effects, the most common one is palmar-plantar erythema which usually presents with a tingling sensation around 5-7 days after cytarabine initiation, followed by erythema and tenderness. Auricular erythema is a rare subtype involving bilateral ears which often presents as ear redness and tenderness as described in the presented case. It is unclear if the skin side effects are related to cytarabine dose or plasma concentration. Most cases of auricular erythema have a benign course and resolve spontaneously. Treatment is mainly conservative. Steroids and antihistamines can be used to speed up recovery given that the pathophysiology is thought to be immediate or due to a delayed hypersensitivity reaction to cytarabine.

The Heart of the Matter: Immune Checkpoint Inhibitors and Immune-Related Adverse Events on the Cardiovascular System.

Cancer remains a prominent global cause of mortality, second only to cardiovascular disease. The past decades have witnessed substantial advancements in anti-cancer therapies, resulting in improved outcomes. Among these advancements, immunotherapy has emerged as a promising breakthrough, leveraging the immune system to target and eliminate cancer cells. Despite the remarkable potential of immunotherapy, concerns have arisen regarding associations with adverse cardiovascular events. This review examines the complex interplay between immunotherapy and cardiovascular toxicity and provides an overview of immunotherapy mechanisms, clinical perspectives, and potential biomarkers for adverse events, while delving into the intricate immune responses and evasion mechanisms displayed by cancer cells. The focus extends to the role of immune checkpoint inhibitors in cancer therapy, including CTLA-4, PD-1, and PD-L1 targeting antibodies. This review underscores the multifaceted challenges of managing immunotherapy-related cardiovascular toxicity. Risk factors for immune-related adverse events and major adverse cardiac events are explored, encompassing pharmacological, treatment-related, autoimmune, cardiovascular, tumor-related, social, genetic, and immune-related factors. The review also advocates for enhanced medical education and risk assessment tools to identify high-risk patients for preventive measures. Baseline cardiovascular evaluations, potential prophylactic strategies, and monitoring of emerging toxicity symptoms are discussed, along with the potential of adjunct anti-inflammatory therapies.

Clinical Utility of Neutrophil to Lymphocyte Ratio in Sickle Cell Disease With Vaso-Occlusive Crisis.

BACKGROUND AND OBJECTIVES: The neutrophil-to-lymphocyte ratio represents a universally accessible value that correlates with inflammation and prognosis in several disease states; however, the role of this biomarker in sickle cell disease remains poorly explored. Hence, the objective of the present study was to determine its potential clinical utility in patients with sickle cell disease. PATIENTS: Herein, we retrospectively reviewed 143 patients with sickle cell disease who presented to the emergency department with fever and painful vaso-occlusive crisis. RESULTS: The examined cohort had a prevalence of 11% confirmed bacterial infection, with approximately two-thirds reporting the use of hydroxyurea. The neutrophil-to-lymphocyte ratio was lowest in the vaso-occlusive crisis-only group when compared with all other groups; this ratio was the highest in those with a confirmed bacterial infection. Patients with confirmed bacterial infection experienced the longest mean length of in-hospital stay, approximately 2 weeks, whereas patients with viral infections and vaso-occlusive crisis had the shortest stay (4-5 days). An elevated neutrophil-to-lymphocyte ratio on presentation correlated with confirmed bacterial infection (area under the curve 0.76); maximum specificity (76%) and sensitivity (69%) for confirmed bacterial infection were achieved using a neutrophil-to-lymphocyte ratio threshold ≥4.6. However, the neutrophil-to-lymphocyte ratio did not predict acute chest syndrome in this patient cohort. CONCLUSION: The neutrophil-to-lymphocyte ratio is a promising biomarker in sickle cell disease with diagnostic and prognostic utility.

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.

Coagulopathy following Crotaliπae snakebites in northeast Florida.

Effects of Crotalinae envenomation vary by geographical areas and research into coagulopathy and effects of antivenom are needed to optimize management. This was a single-center retrospective review with testing on presentation and 4 h after; antivenom administration was noted and data analyzed overall and comparing envenomations. One hundred and nineteen snakebites evaluated with 59 identified as Crotalinae and half receiving antivenom. PT/aPTT was elevated in 20% of water moccasin/copperhead and 21% of rattlesnake bites. DIC-like syndrome occurred in 8% water moccasin/copperhead and 6% rattlesnake bites. Antivenom did not seem to correct PT or aPTT at 4 h follow-up in most cases. Thrombotic microangiopathy was not seen. Coagulopathy was prevalent affecting one in five patients in this cohort and does seem to persist at short interval follow-up, even in those receiving antivenom. We support guidelines recommending clinical monitoring and serial coagulation profiles in such cases. Blood Coagul Fibrinolysis 30:000 - 000 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Procalcitonin as a diagnostic marker for infection in sickle cell disease.

BACKGROUND: Patients with sickle cell disease (SCD) are at increased risks of infection. Fever often occurs with vaso-occlusive crisis (VOC), posing a diagnostic challenge in SCD. Procalcitonin (PCT) is an infectious biomarker validated in the general population but with limited data on use in SCD. METHODS: We performed a retrospective single-center study (n = 145) with primary objective of assessing ability of PCT to differentiate infection from VOC in SCD presenting with fever. Subgroups included confirmed bacterial infection (CBI), suspected bacterial infection, viral infection, and VOC. A secondary objective examined the association of PCT with acute chest syndrome. Clinical characteristics and data were collected and analyzed to assess the diagnostic performance of PCT and associated variables. RESULTS: Of the cohort, 16% had CBI and 8% had viral infection. PCT was able to discriminate CBI from viral infection [AUC = 0.89 (95%CI, 0.78-0.99)] and VOC [AUC = 0.87 (95%CI, 0.78-0.97)]. PCT had an association with ACS but poor diagnostic performance [AUC = 0.69 (95% CI, 0.54-0.84)]. CONCLUSION: PCT has utility in distinguishing confirmed bacterial infection from VOC or viral infection and is a promising biomarker when investigating fever in SCD.

Sinonasal renal cell-like adenocarcinoma arising in von Hippel Lindau (VHL) syndrome.

Sinonasal renal cell-like adenocarcinoma (SNRCLA) is a rare and relatively novel diagnosis. Hereditary and somatic genomic signatures are not well defined in this disease. We report the case of a 35-year-old African-American male with von Hippel Lindau (VHL) syndrome who developed SNRCLA. He underwent surgical resection followed by adjuvant radiation and has no recurrence one year from diagnosis. A review of the literature yielded two similar cases in the setting of VHL. In our case with associated VHL syndrome, next generation sequencing detected MST1R mutation, a possible driver. SNRCLA is an emerging tumor associated with VHL syndrome and it is hoped that future studies shed light on the underlying biology of this unique tumor.

Novel splicing (c.6529-1G>T) and missense (c.1667G>A) mutations causing factor V deficiency.

Congenital factor V deficiency (FVD) is a rare bleeding disorder. In this study, we investigated the genetic basis in an African American patient with factor V activity 3%. Custom sequence capture and targeted next-generation (NGS) sequencing of the F5 gene were undertaken followed by PCR and Sanger sequencing. Two novel variants were identified. In silico analyses correlated clinically with the patient's factor V activity and hemorrhagic tendency. A review of the literature regarding these genomic alterations is presented. We described two novel mutations causing moderate FVD. The first, Chr1:g.169483698C>A with cDNA change (F5):c.6529-1G>T, occurred in a conserved nucleotide at the canonical acceptor splice site of intron 24. The second, Chr1:g.169515775C>T with cDNA change (F5):c.1667G>A, was a missense variant of exon 11, affecting a highly conserved amino acid in the A2 domain. Further research into the mechanisms of F5 mutations leading to FVD and residual factor V expression are needed.

Renal artery stenosis presenting as preeclampsia.

BACKGROUND: Renal artery stenosis is a notorious cause of secondary hypertension which classically presents as chronic refractory hypertension, recurrent flash pulmonary edema or renal insufficiency after initiation of an angiotensin converting enzyme inhibitor. Rarely, there have been reported cases of pregnant patients presenting with new onset or superimposed preeclampsia secondary to renovascular hypertension. In this subset of patients, renovascular hypertension carries significantly higher risks including obstetric, fetal and medical emergencies and death. Prompt treatment is required. However, the teratogenic risks of radiological investigations and antihypertensive medications limit diagnostic and management options thus posing quite a dilemma. CASE PRESENTATION: A 38-year-old female, at 33 weeks of gestation, was hospitalized for preeclampsia with severe features. A viable neonate had been expeditiously delivered yet the patient's post-partum blood pressures remained severely elevated despite multi-class anti-hypertensive therapy. Renal artery dopplers revealed greater than 60% stenosis of the proximal left renal artery and at least 60% stenosis of the right renal artery. Renal angiography showed 50% stenosis of the left proximal renal artery for which balloon angioplasty and stenting was performed. The right renal artery demonstrated less than 50% stenosis with an insignificant hemodynamic gradient, thus was not stented. Following revascularization, the patient's blood pressure improved within 48 h, on dual oral antihypertensive therapy. CONCLUSIONS: Preeclampsia that is refractory to multi-drug antihypertensive therapy should raise suspicion for renal artery stenosis. Suspected patients can be screened safely with Doppler ultrasonography which can be then followed by angiography. Even if renal artery stenosis does not seem severe, early renal revascularization may be considered in patients with severe preeclampsia who do not respond to antihypertensive management.

Metastatic ductal adenocarcinoma of the breast presenting with pericardial effusion-Challenges in the diagnosis of breast cancer.

Breast cancer is a common entity that can be difficult to diagnose. This case demonstrates the limitations of breast cancer diagnostics. Particularly, how the available imaging techniques and even biopsy can potentially miss a malignancy. It exemplifies the role immunohistochemistry staining plays in the diagnosis of cancers of unclear origin.