Mixed Cryoglobulinemia Syndrome Associated with Non-HCV B-Cell Lymphoproliferative Disorder Presenting with Gangrene and Peripheral Neuropathy.

Mixed cryoglobulinemia is a rare disorder characterized by gangrene, weakness, and arthralgias with variable organ involvement. It is often associated with hepatitis C, HIV, and immunological disorders. Diagnosis is based on clinical features and laboratory testing with serology detecting cryoglobulins. Our patient, a 64-year-old female, presented with weakness, fatigue, and discoloration of her fingers and toes. Physical examination showed upper- and lower-extremity skin changes with dry gangrene. Serology showed a non-hepatitis C status, positive cryoglobulin test with a positive rheumatoid factor, and monoclonal IgM-kappa, confirming the diagnosis of mixed cryoglobulinemia. She was treated with intravenous immunoglobulins, glucocorticoids, multiple cycles of rituximab, cyclophosphamide, and plasma exchange. Following a significant event of exacerbation and relapse requiring a below-knee amputation, this case report aims to raise awareness among clinicians to consider this as a rare cause of gangrene and peripheral neuropathy in an elderly adult.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature.

BACKGROUND: Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions. METHODS: We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients". RESULTS: Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary. CONCLUSION: Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Angiocardiographic findings in patients with biphasic T-wave inversion in precordial leads.

OBJECTIVE: To determine the angiocardiographic findings in patients with unstable angina showing biphasic inversion of T-waves in precordial leads on electrocardiogram, commonly referred to as the Wellen's syndrome. METHODS: The descriptive, cross-sectional study was carried out at the National Institute of Cardiovascular Diseases, Karachi, between February and November, 2010. Using convenience sampling, the first 100 consecutive patients showing the characteristic electrocardiogram pattern with a history of chest pain indicative of unstable angina and undergoing coronary angiography were included. Data was collected with the aid of a questionnaire to assess the coronary risk factors, and angiographic findings were recorded during cardiac catherisation of the patients. All the data collected was sorted and analysed on SPSS version 16 for statistical analysis. RESULTS: Biphasic T-wave inversion was seen most commonly in leads v2-v3 in 26 (26%) patients, and in leads v2-v4 in 25 (25%) patients. Angiographic findings revealed that 50 (50%) patients had coronary artery stenosis in the proximal part of the left anterior descending artery, while 22 (22%) showed the occlusion in the middle segment. Right coronary artery established the dominance of heart in 75 (75%) of the patients and the two-vessel disease was most commonly observed during cardiac catherisation. CONCLUSION: The classical pattern of biphasic T-wave inversion on electrocardiogram was seen associated with stenosis in the proximal as well as middle part of the left anterior descending coronary artery. This electrocardiogram pattern may not be well defined during the symptomatic phase of acute ischaemia and, hence, maybe overlooked. Prompt recognition and early intervention may significantly reduce morbidity and mortality in such patients.

Long-standing Sporadic Pancreatic Insulinoma: Report of a Rare Case.

Insulinomas are rare, functional pancreatic neuroendocrine tumors arising from the pancreatic multipotent stem cells or neuroendocrine islet, occurring with a higher proportion in females. Majority of insulinomas have a sporadic etiology; however, only 5%-10% develop as a part of multiple endocrine neoplasm type 1 syndrome. They usually present with symptoms of hypoglycemia including disturbance in orientation, tremors, diaphoresis, altered mental state, seizures and visual changes among others. The diagnosis is based on appreciation of the classic Whipple triad, i.e. neuroglycopenic symptoms and sympathetic drive along with low serum glucose levels (<50 mg/dL) and a complete reversibility of these symptoms with prompt administration of glucose. The gold standard treatment for insulinoma involves complete surgical excision (i.e. enucleation), which is curative in 90% of the patients. Health care physicians should have a high index of suspicion for this tumor in patients presenting with neurological and sympathetic symptoms, particularly if they are resolved after eating. Here, we report the case of a 48-year-old female with the history of multiple episodes of hypoglycemic symptoms for the past two years which improved on glucose intake. Furthermore, we also summarized the discussion regarding diagnosis and management of pancreatic insulinoma.

Post-splenectomy Sepsis: A Review of the Literature.

The spleen is an intraperitoneal organ that performs vital hematological and immunological functions. It maintains both innate and adaptive immunity and protects the body from microbial infections. The removal of the spleen as a treatment method was initiated from the early 1500s for traumatic injuries, even before the physiology of spleen was properly understood. Splenectomy has therapeutic effects in many conditions such as sickle cell anemia, thalassemia, idiopathic thrombocytopenic purpura (ITP), Hodgkin's disease, and lymphoma. However, it increases the risk of infections and, in some cases, can lead to a case of severe sepsis known as overwhelming post-splenectomy infection (OPSI), which has a very high mortality rate. Encapsulated bacteria form a major proportion of the invading organisms, of which the most common is Streptococcus pneumoniae. OPSI is a medical emergency that requires prompt diagnosis (with blood cultures and sensitivity, blood glucose levels, renal function tests, and electrolyte levels) and management with fluid resuscitation along with immediate administration of empirical antimicrobials. OPSI can be prevented by educating patients, vaccination, and antibiotic prophylaxis. This article summarizes the anatomy and physiology of the spleen and highlights its important functions. It primarily focuses on the pathophysiology of OPSI, its current management, and prevention strategies.

Axial Torsion and Gangrene: An Unusual Complication of Meckel's Diverticulum.

Meckel's diverticulum (MD), a congenital abnormality of the gastrointestinal tract, is usually found in the pediatric population younger than two years of age; hence, its incidence in adults is rare. Although MD is mostly clinically silent, in adults, it may present with intestinal obstruction and diverticulitis. The complications of MD include hemorrhage, perforation, enterolith formation, torsion, Littre's hernia, ulceration and neoplasm. Among these, torsion is one of the rarely reported complications of MD. MD being attached to the ileal mesentery or umbilicus, presence of mesodiverticular band, and the length, breadth and base diameter of the diverticulum contribute as a risk factor for torsion. A similar clinical picture of acute appendicitis must be excluded. We report a case of a 25-year-old male who presented with signs of intestinal obstruction in whom intraoperative finding of a torted MD with necrotic and twisted base was found upon emergency exploratory laparotomy.

Chronic Non-cirrhotic Portal Vein Thrombosis with Cavernous Transformation Secondary to Protein C and S Deficiency.

Hereditary thrombophilia (HT), including the mutation of factor V gene and the deficiency of proteins C, protein S, or antithrombin, is a risk factor for portal vein thrombosis (PVT). PVT in acute cases is usually asymptomatic, whereas chronic cases mostly present as variceal bleeding and splenomegaly. However, cavernous transformation of the portal vein secondary to a long-standing PVT is very rare. Here we present a case of a 28-year-old female who was admitted with complaints of left upper abdominal pain and swelling for four to five years. Using laboratory and radiological examinations, a confirmatory diagnosis of cavernous transformation of a thrombosed portal vein due to protein C and S deficiency was made. The patient was managed through splenectomy with splenorenal shunting along with life-long prescription of anticoagulants.

Chylomicron Retention Disease in A Male Infant: A Rare Case from Pakistan.

Chylomicron retention disease (CMRD), also known as Anderson's disease, is an autosomal recessive condition with a genetic mutation in the secretion associated Ras related GTPase 1B (SAR1B) gene, a protein coding gene. CMRD classically manifests as steatorrhea, vomiting, failure to thrive or abdominal bloating shortly after birth or in childhood. Here, we report a rare case of a 50-day-old male infant who was, at first, overseen as a case of acute gastroenteritis with sepsis owing to the non-specific symptoms i.e. multiple episodes of loose stools with a low-grade fever and failure to thrive, and was managed accordingly. However, the symptoms did not resolve; moreover, the clinical condition deteriorated. Later, lipid profile, clinical presentation and pathological features led to a presumptive diagnosis of CMRD. Our patient showed significant improvement when treated with a trial of medium- and short-chain fatty acids. We conclude that, in resource-restricted countries, a therapeutic trial with the dietary changes is essential to not only prevent the devastating complication but also support the diagnosis.

Cerebral Infarction Followed by Myocardial Infarction in a Young Adult with Protein C and S Deficiency.

Protein C (PC) and protein S (PS) are natural anticoagulants that protect the body against thrombosis, and their deficiency, either inherited or acquired, renders the body to a hypercoagulable state. This leads to venous thromboembolism manifesting as thrombosis, pulmonary embolism and superficial thrombophlebitis among other causes. The involvement of arteries is rare and has been explained by only a few studies. Hence, the presentation of PC and PS deficiencies with stroke and myocardial infarction (MI) is rarely observed, especially in young patients. We report a case of a 33-year old male with a past medical history of stroke and MI for which no underlying cause was found. He presented now with shortness of breath and left-sided chest pain and after a series of workup, eventually diagnosed as a rare case of PC and PS deficiencies.

Protein C Deficiency as a Risk Factor for Stroke in Young Adults: A Review.

Protein C (PC) is a 62-kD vitamin K dependent glycoprotein produced by the liver as a zymogen and is activated by binding to the thrombin-thrombomodulin complex, with protein S (PS) acting as a cofactor. Among its various functions, PC acts as a naturally occurring anticoagulant and its deficiency, either homozygous or heterozygous, predisposes the individual to a state of thrombosis, particularly venous thromboembolism, and mainfests as myocardial infarction (MI), deep venous thrombosis, pulmonary embolism, or stroke. This review discusses the pathophysiology of the anticoagulatory effect of PC, mode of inheritance of its deficiency, the arterial and venous involvement in patients with stroke, and its risk factors. A detailed analysis of published case reports on PC deficiency as a causative agent of stroke in young adults has also been included along with the management of such patients.

Anti-tuberculous Effects of Statin Therapy: A Review of Literature.

Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis (M. TB). It is transmitted through respiratory droplets. Increased cholesterol level is a predisposing factor for TB. M. TB uses cholesterol in the host macrophage membranes to bind and enter the macrophages. Statins are the drugs that are prescribed to hyperlipidemic patients to maintain their lipid levels in the normal range, thereby reducing the risk of stroke and cardiovascular events. Moreover, statins aid in reducing the levels of cholesterol in human macrophages. Therefore, a reduction in the membrane cholesterol minimizes the entry of TB pathogen inside macrophages. Furthermore, acting as vitamin D3 analogs and positively influencing pancreatic beta-cell function in a chronic diabetic state, statins minimize the occurrence of M. TB infection among diabetic population as well. This review aims to provide a comprehensive detail of all in vitro, in vivo, and retrospective studies that investigated the effects of statins in relation to the prevention or treatment of TB infection.

Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review.

Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.

Ivabradine in Postural Orthostatic Tachycardia Syndrome: A Review of the Literature.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder characterized by symptoms such as palpitations, dyspnea, chest discomfort, and lightheadedness affecting various systems. The pathophysiology of POTS is not completely understood due to a variety of symptoms showing that the disease is multifactorial. There is no approved uniform management strategy for POTS and hence, no drug has been approved by the United States (US) Food and Drug Administration (FDA) for it. Ivabradine is an FDA-approved drug for stable symptomatic heart failure (HF) and patients with an ejection fraction (EF) of ≤35%. Previous studies have depicted improvement in symptoms of POTS with the use of ivabradine. It is a selective inhibitor of funny sodium channels (If) in the sinoatrial (SA) node cells resulting in the prolongation of the slow diastolic depolarization (phase IV) and reduction in the heart rate (HR). Although beta-adrenoceptor blockers are commonly used to lower HR in patients with POTS, they are less ideal due to numerous adverse effects. This review aims to provide a comprehensive and up-to-date picture of all the studies and case reports that utilized ivabradine for the treatment of POTS along with a precise overview of epidemiology, pathophysiology, and types of POTS. To conclude, we recommend further research on the effectiveness of ivabradine in patients who experience symptoms of POTS. Other than stable chronic angina pectoris, its application in this setting has been proven to be effective and safe. Further evaluation by means of randomized control trials is required to encourage use of this HR-lowering agent in common disorders other than HF and stable angina, i.e. POTS.

Anthropometric Measurements and Lifestyle Characteristics of Individuals with Non-alcoholic Fatty Liver Disease.

Background Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder caused by the deposition of lipids and fats in the hepatocytes, in individuals who consume little or no alcohol, which eventually progresses to cirrhosis and carcinoma. Apart from the known risk factors like obesity, metabolic syndrome (MS), and lack of physical activity (PA), diet also plays a major role in the development of NAFLD. A high body mass index (BMI) and waist circumference (WC) have positive associations with NAFLD. The aim of this study was to find the prevalence of risk factors of hepatic steatosis in NAFLD population and to raise public awareness about the condition. Method We conducted a cross-sectional study from October to December 2019 with a sample size of 98 subjects determined by using a confidence interval (CI) of 99.9%. Patients presenting to Essa Laboratory, Karachi for abdominal ultrasound (US) were scanned for fatty changes in the liver, after obtaining consent, and were then assessed for risk factors by administering a 20-item questionnaire along with registering their BMI and WC measurement. The collected data was analyzed using the Statistical Package for Social Sciences (SPSS), version 22 (IBM, Armonk, NY). The independent sample t-test was applied for the exploration of variables and a p-value <0.05 was considered significant. Result Our study included 96 participants, of which 49 (51%) were male and 47 (49%) female. Mean BMI in females was slightly greater (30.58) than in males (27.98), whereas WC (in inches) was almost equal in males (40.796) and females (40.383). Among the people that had any comorbidities (n = 60, 62.5%), hypertension (HTN) was the most common one (n = 37, 38.5%) followed by diabetes mellitus (DM) type 2 (n = 26, 27.1%). A significant majority (n = 63, 65.5%) never consumed any fruits or vegetables in their meal nor did they perform any sort of physical exercise (n = 46, 47.9%). Conclusion Obesity (high BMI), lack of PA, lower consumption of fruits and vegetables along with a carbohydrate- and fat-rich diet play a vital role in the development of hepatic steatosis. Moreover, HTN and DM, as components of MS, exhibit a significant association with NAFLD. Screening and counseling sessions should be considered for individuals with these anthropometric measurements and lifestyle characteristics.

Inositol Supplementation in the Prevention of Gestational Diabetes Mellitus.

Inositol, an emerging novel therapy for the treatment of gestational diabetes mellitus (GDM), is a cyclic polyol that has insulin-like effects and plays an important role in glucose homeostasis. The conventional treatment of GDM with insulin and oral antihyperglycemic drugs usually comes with side effects, paving the way for and shedding spotlight on clinical trials involving inositol. This review analyzed a host of recent trials that involved inositol supplementation for preventing GDM and their positive outcomes in reducing the rate of GDM among obese and overweight pregnant women, as well as women with polycystic ovarian syndrome (PCOS) or a family history of type 2 diabetes mellitus.

Acute Myocardial Infarction as an Initial Presentation of Protein C and Protein S Deficiency Followed by Dilated Cardiomyopathy in a Young Male.

Protein C and protein S are vitamin K dependent anti-coagulant proteins required for the inhibition of activated protein V and VIII. In an inherited thrombophilia, hypercoagulability caused by the deficiency of protein C and protein S predisposes an individual to increased risk of thromboembolism (TE) that could herald as a venous thromboemboilsm (VTE) in the leg, pulmonary embolism (PE), stroke, or Budd-Chiari syndrome. However, very rarely does inherited thrombophilia cause coronary artery thrombosis leading to the development of myocardial infarction (MI). We report a case of a young male with combined protein C and protein S deficiency who presented with acute MI, worsened ventricular systolic function, and progressive declination of ejection fraction (EF) secondary to dilated cardiomyopathy (DCM).

Cavernous Transformation of Portal Vein in the Setting of Protein C and Anti-thrombin III Deficiency.

Cavernous transformation of the portal vein (CTPV), also known as portal cavernoma, is a sequelae of thrombosis in the portal vein causing its occlusion and portal hypertension. The etiology, however, remains unknown. Gastroesophageal variceal bleeding, splenomegaly, portosystemic collaterals, and ultimate hematologic abnormalities are among the prominent clinical features. Among the causes, predisposing an individual to CTPV is natural anticoagulant protein C and antithrombin III deficiencies. Determination of the etiology of CTPV may also give a direction toward the management plan to not only relieve the patient of the already developed complications but also to treat the primary cause of the pathology  We discuss a case of a nine-year-old male child diagnosed as CTPV secondary to protein C and antithrombin III deficiency who was treated symptomatically for anemia and varices and was referred for transjugular intrahepatic portosystemic shunt (TIPS).

Michelin Tire Baby Syndrome: A Rare Case with Review of Literature.

Michelin tire baby syndrome (MTBS) is a benign hamartomatous condition with ring-like lesions present on the limbs and trunk. MTBS is a rare genodermatosis. According to our search, only 20 cases have been reported. We present a case of a six-month-old female child, with complaints of fever and seizures. Since birth, she had asymptomatic multiple, asymmetric skin folds on all four limbs, resembling "Michelin Man" logo of the French tire manufacturer. She had microcephaly with characteristic round face hypertelorism, depressed nasal bridge, hypertrichosis with low set ears, a thin down-turned vermillion border of the upper lip, and a short neck. MRI was normal. Clinically, the diagnosis of MTBS was made. In addition, the parents were counseled about the self-limiting course of this disorder. MTBS itself might not be a single disorder but may manifest as a clinical finding associated with other disorders; therefore, a regular follow up of these patients is usually advised.