Early mortality and overall survival in acute promyelocytic leukemia: do real-world data match results of the clinical trials?

Acute promyelocytic leukemia (APL) boasts overall survival (OS) of >90% at 3 years and early mortality of <5% in recent clinical trials. Using a large National Cancer Database, we performed analysis of 7190 adults with APL to determine whether one-month mortality and OS of patients with APL treated in real-world practices mirror outcomes noted in clinical trials. Only 64% of total patients received multi-agent therapy; 32% received either single-agent therapy or no therapy at all. One-month mortality was 6% for patients ≤18 years, 6% for 19-40 years, 10% for 41-60 years, and 21% for >60 years. OS at 1- and 3-year were 81% and 75%, respectively. In a multivariate analysis, age ≤ 40 years, treatment at academic center, use of multi-agent therapy, and diagnosis after 2009 conferred better OS. In this largest database study in APL till date, we demonstrated an overall improvement in OS over time but challenges still exist in translating successes of clinical trials to real-world practices.

Perforation of Anterior Mitral Valve Leaflet Aneurysm: Complication of Enterococcus Faecalis Infective Endocarditis.

Infective endocarditis (IE) is a potentially fatal disease if untreated and transesophageal echocardiogram should be performed in all suspected cases. We report a complicated case of infective (Enterococcal faecalis) endocarditis in an elderly man who recently had a genitourinary procedure. He presented with decompensated congestive heart failure due to valvular insufficiency and was found to have multiple vegetations on aortic and mitral valves with aneurysm and perforation of the anterior mitral valve leaflet. He was appropriately treated with antibiotics and surgery. Echocardiography plays central role in risk stratification, evaluation, diagnosis and management.

A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants.

Anticoagulation carries a tremendous therapeutic advantage in reducing morbidity and mortality with venous thromboembolism and atrial fibrillation. For over six decades, traditional anticoagulants like low molecular weight heparin and vitamin K antagonists like warfarin have been used to achieve therapeutic anticoagulation. In the past decade, multiple new direct oral anticoagulants have emerged and been approved for clinical use. Since their introduction, direct oral anticoagulants have changed the landscape of anticoagulants. With increasing indications and use in various patients, they have become the mainstay of treatment in venous thromboembolic diseases. The safety profile of direct oral anticoagulants is better or at least similar to warfarin, but several recent reports are focusing on spontaneous hemorrhages with direct oral anticoagulants. This narrative review aims to summarize the incidence of spontaneous hemorrhage in patients treated with direct oral anticoagulants and also offers practical management strategies for clinicians when patients receiving direct oral anticoagulants present with bleeding complications.

Interstitial lung disease and diabetes.

Diabetes mellitus (DM) is a chronic metabolic disease and its prevalence has been steadily increasing all over the world. DM and its associated micro and macrovascular complications result in significant morbidity and mortality. The microvascular complications are usually manifested as retinopathy, neuropathy, nephropathy and macrovascular complications generally affect the cardiovascular system. In addition to these complications, DM also affects the lungs because of its rich vascularity and abundance in connective tissue (collagen and elastin). DM has been found to cause microvascular complications and proliferation of extracellular connective tissue in the lungs, leading to decline in lung function in a restrictive pattern. Interstitial lung disease (ILD) includes a diverse group of disease conditions characterized by different degrees of inflammation and fibrosis in the pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is one of the common type of idiopathic interstitial pneumonia with a high mortality rate. IPF is characterized by chronic progressive fibrosis leading to progressive respiratory failure. In this review we focus on lung as the target organ in DM and the association of DM and ILD with special emphasis on IPF.

Qualifying Patients for Noninvasive Positive Pressure Ventilation Devices on Hospital Discharge.

When and how do I qualify inpatients with acute on chronic hypercapnic respiratory failure for home noninvasive positive-pressure ventilation at the time of discharge? A 44-year-old woman with morbid obesity (BMI, 48) was brought to the hospital by her boyfriend for 1 day of confusion and reduced alertness. She had a history of chronic dyspnea on exertion and 10-pack-years of smoking. She also had history of well-treated diabetes and hypertension. In the ER, she was found to be somnolent but arousable and following commands appropriately. Her oxygen saturation was 86% on room air, and arterial blood gases indicated a pH of 7.16 with a Paco2 of 87 mm Hg, a Pao2 of 60 mm Hg, and a bicarbonate of 42 mEq/L. Chest radiograph showed mild pulmonary vascular congestion. She was started on continuous bilevel positive airway pressure and medical therapy, with clinical improvement.

A Fatal Case of Coronavirus Disease 2019 (COVID-19) in a Patient With Idiopathic Pulmonary Fibrosis.

The number of cases of coronavirus disease 2019 (COVID-19) has been exponentially increasing everyday. It is important to recognize the comorbidities and risk factors associated with this highly contagious and serious disease that has caused thousands of deaths worldwide. Patients with certain conditions like diabetes, hypertension, cardiovascular disease and chronic lung diseases have been reported to develop serious complications from COVID-19. Idiopathic pulmonary fibrosis (IPF) is a disease that is more prevalent in the elderly population, the same group that are more susceptible to serious complications from COVID-19. Our literature search did not reveal any review about COVID-19 in IPF patients. We report a patient with IPF who was exposed to COVID-19 from her spouse and died from its complications. This case would help to raise the awareness among IPF patients to follow the necessary precautions to reduce the risk of contracting the disease.

Abdominal compartment syndrome: Often overlooked conditions in medical intensive care units.

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome are well recognized entities among surgical patients. Nevertheless, a number of prospective and retrospective observational studies have shown that IAH is prevalent in about half of the critically ill patients in the medical intensive care units (ICU) and has been widely recognized as an independent risk factor for mortality. It is alarming to note that many members of the critical care team in medical ICU are not aware of the consequences of untreated IAH and the delay in making the diagnosis leads to increased morbidity and mortality. Frequently it is underdiagnosed and undertreated in this patient population. Elevated intra-abdominal pressure decreases the blood flow to the kidneys and other abdominal viscera and also results in reduced cardiac output and difficulties in ventilating the patient because of increased intrathoracic pressure. When intraabdominal hypertension is not promptly recognized and treated, it leads to abdominal compartment syndrome, multiorgan dysfunction syndrome and death. Large volume fluid resuscitation is very common in medical ICU patients presenting with sepsis, shock and other inflammatory conditions like pancreatitis and it is one of the major risk factors for the development of intra-abdominal hypertension. This article presents an overview of the epidemiology, definitions, risk factors, pathophysiology and management of IAH and abdominal compartment syndrome in critically ill medical ICU patients.

Treatment Strategies for Therapy-related Acute Myeloid Leukemia.

Prospective evidence for management of therapy-related acute myeloid leukemia (t-AML) is limited, with evidence extrapolated from major AML trials. Optimal treatment is challenging and needs consideration of patient-specific, disease-specific, and therapy-specific factors. Clinical trials are recommended, especially for unfit patients or those with unfavorable cytogenetics or mutations. CPX-351 as an upfront intensive chemotherapy is preferred for fit patients; venetoclax with decitabine or azacitidine is an option for patients unfit for intensive chemotherapy. Hematopoietic cell transplant, the only curative option, should be offered to eligible patients with intermediate or unfavorable t-AML or patients with good-risk AML with minimal residual disease. Ongoing clinical trials focusing on treatment of t-AML, including targeted agents and immunotherapy, bode well for the future.

Pemetrexed Induced Life-threatening Anaphylaxis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. The American Society for Clinical Oncology (ASCO) recommends platinum based regimens as the first-line of treatment for NSCLC. Pemetrexed, an antifolate agent, has been approved by the ASCO for the treatment of advanced non-squamous NSCLC and has been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup. It is administered intravenously over 10 minutes and is usually well tolerated with a very few side effects. There have been a few cases of anaphylaxis reported with pemetrexed use and most of the patients presented only with cutaneous manifestations. We present a patient with stage IV adenocarcinoma of the lung who developed a severe life threatening anaphylactic reaction requiring ventilatory support after administration of pemetrexed.

Metformin Use and Metformin-associated Lactic Acidosis in Intensive Care Unit Patients with Diabetes.

Metformin is a very potent anti-diabetic drug that has become the drug of choice for the treatment of type 2 diabetes. In addition to its glucose-lowering properties, it also reduces all-cause mortality through its anti-inflammatory and cardioprotective effects. Although metformin-associated lactic acidosis (MALA) is a very rare event, the mortality associated with it is close to 50%. As it is excreted through the kidney, MALA is frequently seen in patients on metformin with risk factors for developing acute kidney injury. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration, usually in the presence of a secondary event that disrupts lactate production or clearance. The incidence of acute kidney injury is very high in critically ill patients contributed by circulatory defects as well as contrast-induced nephropathy, the incidence of which is also high in this subset of the population. Because of this potential risk, metformin is frequently discontinued in diabetic patients admitted to the intensive care unit. Blood glucose variability and hypoglycemia, however, are both related to poor intensive care unit (ICU) outcomes and in order to prevent this in diabetic patients admitted to ICU, oral hypoglycemic agents are frequently switched to intravenous or subcutaneous insulin regimens, which allows for closer monitoring and better blood glucose control.