Review of Medical Management of Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with presumed autoimmune etiology. Current treatment options include ursodeoxycholic acid, obeticholic acid, and fibrate, which target mainly cholestasis. There is no effective therapy against autoimmune or hepatic fibrosis components. We can still achieve adequate biochemical response with monotherapy or a combination of medications in non-cirrhotic and compensated cirrhotic PBC patients. Several criteria are available for risk stratification and assess treatment response. Liver stiffness measurement by transient elastography is also a useful tool for evaluating disease progression. Lack of treatment or inadequate response are predictors of poor outcome. There is a strong need for additional therapies for PBC.

Modes of death and clinical outcomes in adult patients with hypertrophic cardiomyopathy in Thailand.

BACKGROUND: There are limited data about modes of death and major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM) in South East Asian population. The aim of the study was to examine modes of death and clinical outcomes in Thai patients with HCM. METHODS: Between January 1, 2009 and December 31, 2013, 166 consecutive patients with HCM diagnosed in our institution were evaluated. Five patients were excluded because of non-Thai ethnic groups (n = 3) and diagnosis of myocardial infarction at initial presentation documented by coronary angiography (n = 2). The final study population consisted of 161 patients with HCM. HCM-related deaths included: (1) sudden cardiac death (SCD) - death due to sudden cardiac arrest or unexpected sudden death; (2) heart failure - death due to refractory heart failure; or (3) stroke - death due to embolic stroke associated with atrial fibrillation. MACEs included: (1) SCD, sudden unexpected aborted cardiac arrest, fatal, or nonfatal ventricular arrhythmia (ventricular fibrillation or sustained ventricular tachycardia); (2) heart failure (fatal or non-fatal), or heart transplantation; or (3) stroke - fatal or non-fatal embolic stroke associated with atrial fibrillation. RESULTS: One hundred and sixty-one Thai patients with HCM (age 66 ± 16 years, 58% female) were enrolled. Forty-two patients (26%) died over a median follow-up period of 6.8 years including 25 patients (16%) with HCM-related deaths (2%/year). The HCM-related deaths included: heart failure (52% of HCM-related deaths; n = 13), SCD (44% of HCM-related deaths; n = 11), and stroke (4% of HCM-related deaths, n = 1). The SCDs occurred in 6.8% of patients (1%/year). Eighty-four major MACEs occurred in 65 patients (41, 5%/year). The MACEs included: 40 heart failures in which 2 patients underwent heart transplants; 22 SCDs and nonfatal ventricular arrhythmias; and 22 fatal or nonfatal strokes. CONCLUSIONS: The most common mode of death in adult patients with HCM in Thailand was heart failure followed by SCD. About one-third of the patients experiencing heart failure died during the 6.8 years of follow-up. SCDs occurred in 7% of patients (1%/year), predominantly in the fourth decade or later.

Cholecystokinin Receptor-Targeted Polyplex Nanoparticle Inhibits Growth and Metastasis of Pancreatic Cancer.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) remains the most aggressive malignancy with the lowest 5-year survival rate of all cancers in part owing to the lack of tumor-specific therapy and the rapid metastatic nature of this cancer. The gastrointestinal peptide gastrin is a trophic peptide that stimulates growth of PDAC in an autocrine fashion by interaction with the cholecystokinin receptor that is overexpressed in this malignancy. METHODS: We developed a therapeutic novel polyplex nanoparticle (NP) that selectively targets the cholecystokinin receptor on PDAC. The NP was characterized in vitro and stability testing was performed in human blood. The effects of the target-specific NP loaded with gastrin small interfering RNA (siRNA) was compared with an untargeted NP and with an NP loaded with a scrambled siRNA in vitro and in 2 orthotopic models of PDAC. A polymerase chain reaction metastasis array examined differentially expressed genes from control tumors compared with tumors of mice treated with the targeted polyplex NP. RESULTS: The polyplex NP forms a micelle that safely delivers specific gastrin siRNA to the tumor without off-target toxicity. Consistent with these findings, cellular uptake was confirmed only with the targeted fluorescently labeled NP by confocal microscopy in vitro and by IVIS fluorescent based imaging in mice bearing orthotopic pancreatic cancers but not found with untargeted NPs. Tumor uptake and release of the gastrin siRNA NP was verified by decreased cellular gastrin gene expression by quantitative reverse-transcription polymerase chain reaction and peptide expression by immunohistochemistry. Growth of PDAC was inhibited in a dose-related fashion in cell culture and in vivo. The targeted NP therapy completely blocked tumor metastasis and altered tumor-specific genes. CONCLUSIONS: Our polyplex nanoparticle platform establishes both a strong foundation for the development of receptor-targeted therapeutics and a unique approach for the delivery of siRNA in vivo, thus warranting further exploration of this approach in other types of cancers.

Emerging Role of Vedolizumab in Managing Refractory Immune Checkpoint Inhibitor-Induced Enteritis.

We report a 62-year-old white woman with metastatic choroidal melanoma who developed immune checkpoint inhibitor (ICI)-induced enteritis and grade 3 diarrhea refractory to steroids and infliximab. Her diarrhea quickly resolved after infusion of vedolizumab, and the patient was able to taper down steroids. Vedolizumab's mechanism of action and its gut specificity have the potential to reverse immune-induced enterocolitis without neutralizing or reversing the therapeutic benefit of ICI on the malignancy.

Predictor of 90-Day Readmission Rate for Hepatic Encephalopathy.

OBJECTIVES: The purpose of our study was to identify clinical parameters associated with readmissions within 90 days in patients with hepatic encephalopathy (HE). METHODS: We reviewed electronic medical records of patients admitted between January 1, 2010 and September 30, 2013 at University Medical Center, Lubbock, Texas. Inclusion criteria were admission to the hospital with diagnosis of HE in patients older than 18 years. We compared the patients with readmission within 90 days with patients with no readmission using routine clinical data. RESULTS: A total of 140 admissions met inclusion criteria; 35% were white, 59.3% were Hispanic, and their mean age was 55.6 ± 10.5 years. The median admission Model for End-Stage Liver Disease score was 15.5 (4-38). Univariate analysis demonstrated that a history of diabetes mellitus, a history of hypertension, prior transjugular intrahepatic portosystemic shunt placement, a history of prior HE, and the use of lactulose posthospitalization were associated with increased readmission rates and the presence of gastrointestinal bleeding was associated with decreased readmission rates (P < 0.05 for each factor). Multivariate logistic regression demonstrated that history of hypertension (P = 0.02) predicted an increased readmission rate. CONCLUSIONS: Our study demonstrates that hypertension increased the risk of readmission in patients with HE. More intensive interventions in these patients may decrease readmission rates and improve outcomes.

A rare case of low-solute hyponatremia in a nonalcoholic person.

Low-solute hyponatremia is a relatively uncommon entity of euvolemic hyponatremia. Classic cases were described in alcoholics as beer potomania, which is characterized by hyponatremia in the setting of low-solute intake due to heavy beer drinking. We report a case of low-solute hyponatremia in a nonalcoholic person who was given a solute load, and, subsequently, had excessive diuresis with the resultant rapid increase in serum sodium concentration.

Carcinoma of the lungs causing enlarged kidneys.

Bilateral enlarged kidneys can be caused by a number of conditions. Renal metastasis is included in the differential diagnosis. We report a case of a 67-year-old woman with a 6-month history of productive cough and unintentional weight loss. Cavitary pulmonary lesions and bilateral enlarged kidneys were noted on imaging studies. Hematuria, azotemia, and proteinuria were present. Renal biopsy showed squamous carcinoma cells invading normal-appearing glomeruli and atrophic tubules. The invasive squamous cells stained negative for CK7 and CK 20. Lung biopsy confirmed squamous cell carcinoma. Our case shows that in patients with renal enlargement, even with the absence of a focal mass, renal metastasis should be considered, especially in those with suspected or diagnosed malignancy elsewhere.

Postextubation Dysphagia.

Postextubation dysphagia (PED) is a common problem in critically ill patients with recent intubation. Although several risk factors have been identified, most of them are nonmodifiable preexisting or concurrent conditions. Early extubation, small endotracheal tube size, and small bore of nasogastric tube potentially decrease the risk of PED. The majority of patients receive treatment based on only bedside swallow evaluations, which has an uncertain diagnostic accuracy as opposed to gold standard instrumental tests. Therefore, the treatment decision for patients may not be appropriately directed for each individual. Current treatments are mainly focused on dietary modifications and postural changes/compensatory maneuvers rather than interventions, but recent studies have shown limited proven benefits. Direct therapies in oromotor control, such as therapeutic exercises and neuromuscular stimulations, should be considered as potential effective treatments.

Diverticulitis in the young.

BACKGROUND: Colonic diverticulitis is relatively uncommon in young patients, especially those younger than 40 years. We compared demographic data, clinical presentation, management, and clinical course of diverticulitis in patients ≤40 years old compared with patients >40 years old. METHODS: This study included all patients who presented to the emergency department with a diagnosis of diverticulitis between October 1, 2009 and September 30, 2010. Patients were divided into 2 groups: group 1 (≤40 years old) and group 2 (>40 years old). Demographic characteristics, clinical presentation and management, and short-term outcomes were compared. RESULTS: Ninety-four patients were included in the study (37 patients in group 1 and 57 patients in group 2). A higher percentage of obese and Hispanic men was found in group 1 (P > .05). The rate of discharge from the emergency department was significantly higher in group 1 (56.8% in group 1 vs 7.0% in group 2, P < .01). Group 2 patients had a shorter median length of stay than group 1 patients (3.1 vs 5.7 days, P = .16). There were no differences in vital signs, laboratory data (including complete blood count and basic metabolic panel), and in-hospital mortality rates between the 2 groups. CONCLUSIONS: This study demonstrates that young Hispanic men develop diverticulitis and that this diagnosis needs to be considered when they present to emergency rooms with abdominal symptoms. A longitudinal study is needed to determine the long-term outcomes in these patients and to investigate the pathogenesis.

Factors influencing the length of hospital stay in patients with acute exacerbations of chronic obstructive pulmonary disease admitted to intensive care units.

BACKGROUND: The cost of hospital admissions for acute exacerbations of COPD (AECOPD) accounts for 70% of total costs for the treatment of COPD patients. We wanted to identify clinical parameters associated with a longer length of stay (LOS) in these patients. METHODS: We reviewed electronic medical records of patients with AECOPD admitted between January 1, 2006, and December 31, 2010. The inclusion criteria were age 45 years or older, the diagnosis of AECOPD by GOLD (Global Initiative for Chronic Obstructive Lung Disease) guideline criteria, and admission to an intensive care unit. We compared the quartile with the longest LOS group with the other 3 quartiles using routine clinical data. RESULTS: 217 patients met inclusion criteria. The mean age was 67.4 ± 10.9 years, 47% were male, the mean FEV1s (forced expiratory volume in 1 second) was 42.4% ± 17.4% of predicted, and the mean LOS was 9.0 ± 6.0 days. Univariate analysis demonstrated that nursing home status, low albumins, the presence of pleural effusions, intubation, and high APACHE II scores were associated with increased LOS (P < .05 for each factor). Multivariate logistic regression demonstrated that the need for intubation (P < .001) predicted an increased LOS. CONCLUSIONS: Our study demonstrates that intubation for mechanical ventilation increased the LOS in patients with AECOPD. More intensive interventions in these patients might decrease the LOS and improve outcomes.

Chiari syndrome and respiratory failure: a literature review.

BACKGROUND: Patients with failed extubation requiring reintubation have increased morbidity and mortality. This situation may reflect the severity of the underlying disorder or may reflect an undiagnosed condition that was not apparent at the time of the initial intubation. METHODS: Case report and literature review. RESULTS: A 49-year-old man developed acute hypercapneic respiratory failure during an episode of community-acquired pneumonia. This patient failed extubation 4 times. Routine neurological evaluation, including computed tomography of the head, was within normal limits. A magnetic resonance imaging revealed a severe Chiari malformation type I. The patient eventually required tracheostomy and prolonged mechanical ventilation. We identified 28 cases with Chiari malformations (CM) in the medical literature, who presented with respiratory failure. The mean age was 29.5 years, 46% of the cases were male, 50% had an associated syringomyelia, and 64% required a decompressive surgery. Twenty-five percent had recurrent symptoms postsurgery. CONCLUSIONS: Patients with CMs can have repeated extubation failures. Some of these patients have normal neurological examinations and studies and are not identified until they have an MRI study. Clinicians need to consider this possibility in patients who are difficult to wean.

Meningitis-retention syndrome as a presentation of west nile virus meningitis.

A 26-year-old previously healthy man presented with fever, urinary retention, nuchal rigidity, and hyperreflexia but with a clear sensorium. His initial spinal fluid results were consistent with aseptic meningitis from West Nile virus infection, and this was confirmed by serological studies on blood and cerebrospinal fluid. Computed tomography and magnetic resonance imaging studies were unremarkable. He received supportive care and urinary catheterization to prevent bladder injury from overdistension. He was discharged home without recurrence of urinary retention after five days of hospitalization. Therefore, this case report describes the first case of West Nile virus meningitis in a patient with the meningitis-retention syndrome.

Anti-N-methyl-D-aspartate receptor encephalitis.

A case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with an atypical finding of transient increased intracranial pressure is reported. Anti-NMDAR encephalitis is an underrecognized, novel and treatable form of encephalitis being increasingly identified as an explanation of encephalitis in young adults. Management of these patients requires a multidisciplinary approach involving neurologists, internists, nursing and rehabilitation staff. It is important for internists to recognize this condition and consider it in the differential diagnosis of encephalopathy. Internists also need to be familiar with the clinical manifestations and the treatment of the disease as they have an important role in the care of these patients during their prolonged stay in the hospital. Increased intracranial pressure is an atypical and underrecognized finding that has been only noted in a previous review on this disorder. It may present a diagnostic or management challenge in patients with anti-NMDAR encephalitis.

Reactive Thrombocytosis Associated with Acute Myocardial Infarction following STEMI with Percutaneous Coronary Intervention.

The etiology of thrombocytosis can be classified into reactive and essential forms. The rate of thromboembolic events is higher in essential thrombocytosis, and these events include strokes, transient ischemic attacks, retinal artery or retinal vein occlusions, digital ischemia, and acute coronary syndrome. In a study of 732 medical and surgical patients with thrombocytosis, 88% had reactive thrombocytosis. Patients with reactive thrombocytosis do not require cytoreductive medications or antiplatelet treatment. We report a healthy 40-year-old man without any medical problems who developed a new episode of myocardial infarction associated with thrombocytosis after an episode of myocardial infarction followed by percutaneous coronary intervention. He had thrombocytosis, and his platelet function test did not reveal adequate inhibition. To treat his acute coronary syndrome, therapeutic enoxaparin was added, and clopidrogel was substituted with ticagrelor. We decided to start hydroxyurea to reduce platelets counts. Enoxaparin and hydroxyurea were discontinued when platelet count returned to baseline. JAK-2 and BCR/ABL mutations were negative. This case report highlights a clinical dilemma (reactive thrombocytosis), which is challenging in terms of management and pathophysiology.

Obscure Severe Infrarenal Aortoiliac Stenosis With Severe Transient Lactic Acidosis.

A 57-year-old man presented with sudden onset of leg pain, right-sided weakness, aphasia, confusion, drooling, and severe lactic acidosis (15 mmol/L). He had normal peripheral pulses and demonstrated no pain, pallor, poikilothermia, paresthesia, or paralysis. Empiric antibiotics, aspirin, full-dose enoxaparin, and intravenous fluid were initiated. Lactic acid level decreased to 2.5 mmol/L. The patient was subsequently extubated and was alert and oriented with no complaints of leg or abdominal pain. Unexpectedly, the patient developed cardiac arrest, rebound severe lactic acidosis (8.13 mmol/L), and signs of acute limb ischemia. Emergent computed tomography of the aorta confirmed infrarenal aortoiliac thrombosis. Transient leg pain and transient severe lactic acidosis can be unusual presentations of severe infrarenal aortoiliac stenosis. When in doubt, vascular studies should be implemented without delay to identify this catastrophic diagnosis.

Renal infarction as a presentation of Austrian syndrome: thromboembolic phenomenon of pneumococcal endocarditis.

A 52-year-old unvaccinated and splenectomized man presented with fever, altered sensorium, bilateral flank pain and chest discomfort accompanied with paroxysmal atrial fibrillation with a rapid ventricular response. An abdominal computed tomography scan was performed, which revealed a right renal infarct and splenosis. Transthoracic echocardiography was performed, which demonstrated an echodense structure on the mitral valve with mitral regurgitation and a vegetation on the aortic valve with aortic regurgitation. Subsequently, he was found to have pneumococcal infective endocarditis, pneumococcal pneumonia and bacterial meningitis, namely Austrian syndrome. He underwent an early aortic valve and mitral valve repair but still had a poor clinical outcome. Renal infarction has a mortality of approximately 13.2%, which is strongly influenced by the underlying diseases and infectious complications. Medical and surgical treatment initiated in a timely manner is often inadequate. The authors report the first case of Austrian syndrome presenting with renal infarction as a clue to an embolic event associated with infective endocarditis in this study.