A Difficult and Rare Case of Warfarin Refractory Antiphospholipid Syndrome Presenting With Catastrophic Antiphospholipid Syndrome Complicated by Gastrointestinal Bleeding.

Antiphospholipid syndrome (APS) is managed with warfarin for secondary prophylaxis in patients who have had a thrombotic event in the past. Warfarin has been deemed superior to novel oral anticoagulants in preventing venous and arterial thrombosis in conjunction with aspirin. The catastrophic variant of APS (CAPS) is very rarely reported, especially in those who have been on a therapeutic dose of warfarin therapy. We present a rare case of CAPS in a patient with a history of APS who had been on a therapeutic dose of warfarin along with aspirin therapy. The patient is a 70-year-old male with APS diagnosed 30 years prior when he presented with a pulmonary embolism; aspirin was added to warfarin two years ago when he had a cerebrovascular accident (CVA). He presented to the hospital with acute onset right-sided weakness and aphasia, left lower extremity pain. He had ischemic CVA, acute deep vein thrombosis (DVT), acute renal failure with a creatinine of 2.8, anemia with hemoglobin of 3.8, gastrointestinal bleed (GIB) on EGD, with INR of 3.48 cardiolipin IgM of >140g/L. He was transfused packed red blood cells, fresh frozen plasma, and provided Vit K. Subsequently, he had a cardiac arrest and was intubated and placed on a mechanical ventilator. Given simultaneous multiorgan involvement, acute arterial and venous thrombosis, the patient was diagnosed with CAPS. The patient was started on high-dose dexamethasone, intravenous immunoglobulin (IVIG), and underwent plasma exchange with significant improvement in symptoms, laboratory parameters; and was extubated with near normalization of his speech and motor deficits. He was discharged on enoxaparin and prednisone with sustained clinical improvement two months following discharge. This patient was on the recommended treatment for APS. However, he had presented with a CAPS. This is the first reported case of warfarin refractory CAPS. This case highlights that there might be a subgroup of the population in whom warfarin is not an effective form of treatment modality for an unknown cause, and in fact, it could potently expose a patient to the adverse events related to warfarin therapy as it did in our patient who had significant GIB. This case also highlights the uncommon scenario of spontaneous CAPS with no inciting event as previously reported in the literature, such as infection, recent surgeries, or trauma.

Unique presentation of occult breast cancer with uterine cervix metastasis.

We are reporting a case of occult breast cancer (OBC) diagnosed via biopsy of an asymptomatic cervical mass. While non-OBC has occasionally been reported as metastatic to the uterine cervix, OBC never has, to our knowledge. Awareness of this presentation can be beneficial for a more expedite diagnosis and treatment.

A Rare Concurrence of Leiomyomatosis Peritonealis Disseminata, Leiomyosarcoma of the Pelvis and Leiomyomatous Nodule of the Liver.

Leiomyomatosis peritonealis disseminata (LPD) is a rare entity that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface mimicking a malignant process. LPD follows a benign course in general, and it is often found incidentally during abdominal surgery. There have been reported cases of LPD with malignant degeneration although the association is uncertain. Concurrent finding of LPD and leiomyosarcoma of the pelvis is very rare that could be coincidental, malignant transformation of LPD to leiomyosarcoma, or progression of undetected primary leiomyosarcoma. There are only a few previously reported cases in the literature. Herein, we report a case of 56-year-old woman with a history of leiomyoma of uterus who presented with progressive abdominal swelling secondary to mass lesions in the pelvis. The patient underwent exploratory laparotomy and debulking of the tumors, and the histologic examination of the tumors revealed coexistence of LPD and leiomyosarcoma. After recovery from the operation, core needle biopsy of the superficial, residual liver mass was obtained to investigate potential liver metastasis, and the histopathologic findings are consistent with leiomyoma which represents the first simultaneous occurrence of LPD, leiomyosarcoma, and leiomyomatous nodule of the liver.

Management of locally advanced or unresectable head and neck cancer.

The treatment of patients with locoregionally advanced or unresectable squamous cell carcinoma of the head and neck is complex and associated with significant toxicities. During the past 30 years, there has been an ongoing shift in what is perceived as the best treatment approach. Differing radiation techniques have been employed, and chemotherapy has been incorporated in both sequential and concomitant strategies. In this article, we will review the available data regarding many of the advances that have been achieved. We will also discuss the most relevant recent clinical trials, as well as ongoing trials that will hopefully answer some of the questions that remain as we attempt to best treat this patient population

Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart.

Impulse-conducting Purkinje fibers differentiate from myocytes during embryogenesis. The conversion of contractile myocytes into conduction cells is induced by the stretch/pressure-induced factor, endothelin (ET). Active ET is produced via proteolytic processing from its precursor by ET-converting enzyme 1 (ECE1) and triggers signaling by binding to its receptors. In the embryonic chick heart, ET receptors are expressed by all myocytes, but ECE1 is predominantly expressed in endothelial cells of coronary arteries and endocardium along which Purkinje fiber recruitment from myocytes takes place. Furthermore, co-expression of exogenous ECE1 and ET-precursor in the embryonic heart is sufficient to ectopically convert cardiomyocytes into Purkinje fibers. Thus, localized expression of ECE1 defines the site of Purkinje fiber recruitment in embryonic myocardium. However, it is not known how ECE1 expression is regulated in the embryonic heart. The unique expression pattern of ECE1 in the embryonic heart suggests that blood flow-induced stress/stretch may play a role in patterning ECE1 expression and subsequent induction of Purkinje fiber differentiation. We show that gadolinium, an antagonist for stretch-activated cation channels, downregulates the expression of ECE1 and a conduction cell marker, Cx40, in ventricular chambers, concurrently with delayed maturation of a ventricular conduction pathway. Conversely, pressure-overload in the ventricle by conotruncal banding results in a significant expansion of endocardial ECE1 expression and Cx40-positive putative Purkinje fibers. Coincident with this, an excitation pattern typical of the mature heart is precociously established. These in vivo data suggest that biomechanical forces acting on, and created by, the cardiovascular system during embryogenesis play a crucial role in Purkinje fiber induction and patterning.

Induction and patterning of the Purkinje fibre network.

Impulse-conducting Purkinje cells differentiate from myocytes during embryogenesis. In the embryonic chicken heart, this conversion of contractile myocytes into conduction cells occurs subendocardially and periarterially. The unique sites of Purkinje fibre differentiation suggest that a shear stress-induced paracrine signal from the endocardium and arterial beds may induce adjacent myocytes to differentiate into conduction cells. Consistent with this model, Purkinje fibre marker genes can be induced in cultured embryonic myocytes by endothelin (ET), an endothelial cell-derived signalling peptide. This inductive response is, however, gradually lost from myocytes as embryos develop, and mature myocytes express only genes characteristic of hypertrophy in response to ET. In vivo, active ET is produced, through proteolytic processing, from its precursor by ET-converting enzyme 1 (ECE1) and triggers signalling by binding to its receptors, ETA and ETB. In the embryonic heart, the expression of these ET signalling components changes dynamically, defining the site and timing of Purkinje fibre differentiation within the ventricular myocardium during chick embryogenesis.