Valacyclovir and Acyclovir Neurotoxicity With Status Epilepticus.

We present the case of a 52-year-old man with hypertension, diastolic congestive heart failure, end-stage renal disease on hemodialysis 3 times a week and a remote history of a hemorrhagic stroke who presented to the emergency department with a vesicular rash on his left arm. The rash was observed to be in a dermatomal distribution, and a diagnosis of herpes zoster was made. The patient was discharged home on valacyclovir 1 g 3 times a day for a duration of 7 days. The patient took 2 doses of valacyclovir before presenting to the hospital again with irritability and hallucinations. Over the next several days, the patient's neurologic status declined and he became disoriented and increasingly somnolent. Because of a concern for varicella zoster virus (VZV) or herpes simplex virus (HSV) meningoencephalitis, acyclovir was initiated intravenously at 600 mg (10 mg/kg) for every 12 hours. Computed tomography and magnetic resonance imaging of the brain failed to reveal an acute process. Electroencephalogram was interpreted as seizure activity versus metabolic encephalopathy. Lumbar puncture was not suggestive for meningitis, subarachnoid hemorrhage, or HSV/VZV infection. The patient subsequently had a witnessed seizure during dialysis and was felt to have status epilepticus due to acyclovir and valacyclovir neurotoxicity. The patient underwent daily hemodialysis for removal of the drug and eventually made a full neurologic recovery. Our case highlights that acyclovir neurotoxicity can result in status epilepticus, hallucinations, and altered consciousness. Differentiating acyclovir neurotoxicity from HSV or VZV meningoencephalitis is of crucial importance because the symptoms are similar but the management is vastly different.

Retrospective cohort study of portacaval lymphadenopathy identified on multidetector CT and implications for follow-up.

PURPOSE: Portacaval lymphadenopathy (PCLA) is common in cirrhosis and chronic viral hepatitis and is frequently an incidental finding on abdominal CT scans. We aimed to detect the incidence of malignancy in organs drained by portacaval nodes in patients with PCLA associated with cirrhosis or chronic viral hepatitis, or incidentally detected PCLA. METHODS: We searched CT reports from 2005 to 2007 for the phrases "periportal node" and "portacaval node." MDCTs of patients with portacaval nodes ≥10 mm in maximal short-axis size on contrast-enhanced MDCTs, were included. Records were reviewed for presence of malignancy, liver metastases, chronic viral hepatitis, and cirrhosis. Clinical or imaging follow-up ≥6 months was performed to detect if malignancy developed in organs drained by portacaval nodes in patients with incidental PCLA, cirrhosis, or chronic viral hepatitis. RESULTS: 479 patients met inclusion criteria [298 males (62%), mean age 61.4 years]. In 285 (59.5%) patients, PCLA was explained by local pathology or systemic lymphadenopathy. PCLA was incidental in 146 (30.5%) patients. Of these, 112 (76.7%) had ≥6 months of follow-up (median 26 months). No patient with incidental PCLA developed malignancy in organs drained by these nodes. Cirrhosis or chronic viral hepatitis was present in 48 (10.0%) patients. Of these, 42 (87.5%) had ≥6 months follow-up (median 28 months), and only 1 patient developed cholangiocarcinoma (positive predictive value 2.4%). CONCLUSIONS: Development of malignancy is rare in patients with PCLA, either incidental or secondary to cirrhosis or chronic viral hepatitis. Our study suggests that no follow-up of PCLA is required in these settings.

Effect of Low (7.5 mg/day), Standard (15 mg/ day) and High (30 mg/day) Dose Pioglitazone Therapy on Glycemic Control and Weight Gain in Recently-Diagnosed Type 2 Diabetes Patients.

Objective: To study the effect of different daily doses of pioglitazone on glycemic control and weight gain in newly-diagnosed type 2 diabetes mellitus (DM) patients. Research Design and Methods: Chart reviews were performed of recently-diagnosed (<24 months) type 2 DM patients receiving oral therapy including pioglitazone. Patients were excluded if they had heart disease, liver dysfunction or renal insufficiency; or were being treated with insulin or the incretin drugs. Patients had received 7.5 mg/day (Group A), 15 mg/day (Group B) or 30 mg/day (Group C) of pioglitazone. Characteristics including demographics, weight, body mass index and glycated hemoglobin (HbA1c) were recorded at baseline and at six months. Results: At the end of six months, there was significant weight gain in all groups from baseline (P<0.01). Weight gain was greatest in Group C (2.72 kg; SD=2.97), intermediate in Group B (1.62 kg; SD=2.91) and least in Group A (0.88 kg; SD=2.77). The difference was statistically significant between Groups A and C; and Groups B and C; but not between Groups A and B. There was no difference between HbA1c lowering in the three groups (P>0.05). Dose correlated with weight gain (r=0.254; P<0.001) but not with HbA1c reduction (r=0.012; P=0.85). There was no correlation between HbA1c reduction and BMI increase (r = -0.024; P=0.72). Conclusions: The glycemic effect of pioglitazone is preserved even at lower doses, while the propensity to cause weight gain increases with dose. We suggest that low-dose pioglitazone (7.5 mg/day) should be the preferred dose at which to initiate therapy in recently-diagnosed patients. Pioglitazone is an extremely useful agent in the treatment of type 2 diabetes mellitus (DM) through its actions on alleviating insulin resistance.

Resolution of whipple disease-induced pulmonary hypertension following antibiotic therapy.

Whipple disease is a disorder caused by Tropheryma whipplei, a ubiquitous Gram-positive bacillus. In addition to gastrointestinal manifestations, many other systems may be involved in Whipple disease. Pulmonary hypertension (PH) is a rare manifestation of Whipple disease, and its clinical course is not well established. We report a case of a 45-year-old woman who presented with typical gastrointestinal manifestations of Whipple disease, which was diagnosed by duodenal biopsy. She was also noted to have elevated pulmonary arterial pressures on transthoracic echocardiography. There was no evidence of left-sided valvular disease, hypertrophy, or dyskinesis, and there was no evidence of endocarditis. The patient was started on intravenous ceftriaxone for 6 weeks and then transitioned to oral trimethoprim-sulfamethoxazole for a year. The patient demonstrated clinical improvement, endoscopic and histologic improvement, and also resolution of PH. This is the third reported case of PH that is convincingly secondary to Whipple disease that resolved after appropriate antibiotic therapy.

Serotonin syndrome, disseminated intravascular coagulation, and hepatitis after a single ingestion of MDMA in an Asian woman.

N-Methyl-3,4-methylenedioxyamphetamine (MDMA), also called "Ecstasy," is a commonly abused psychoactive drug among the American youth. We present the case of a 23-year-old Korean-American woman who presented with seizure, delirium, and rigidity after MDMA ingestion. She was febrile (38.7°C), tachycardic (188 beats/min), tachypneic (26 breaths/min) with a borderline blood pressure (95/43 mm Hg). Examination revealed generalized muscle rigidity, tremors, hyperreflexia, and ocular clonus, leading to the diagnosis of serotonin syndrome. Urine toxicology screen was only positive for amphetamines, consistent with the history of MDMA ingestion. Initial laboratory testing showed thrombocytopenia, further testing showed deranged prothrombin time, partial thromboplastin time, decreased fibrinogen, and elevated D-dimer, suggesting disseminated intravascular coagulation. Hepatic transaminases trended up dramatically reflecting acute hepatitis. The patient received supportive care and improved by hospital day 3. MDMA toxicity manifested as serotonin syndrome, hepatitis, and coagulopathy is exceedingly rare. MDMA is metabolized by the hepatic CYP2D6 enzyme. Certain populations, such as Koreans, Chinese, and Japanese have a high prevalence of a polymorphism that confers reduced enzyme activity. We discuss this hypothesis as a possible cause for this severe presentation in our patient after a single ingestion.

Internal medicine residents' perspectives on effects of 2011 ACGME work hour regulations on patient care.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) introduced new work hour limitations in July 2011. PURPOSES: The aim is to assess internal medicine residents' perspectives on the impact of these limitations on their ability to discharge patient care duties. METHODS: An anonymous survey was administered to 158 medicine residents in an urban university-affiliated internal medicine residency program. Residents' perspectives on various aspects of patient care were recorded on a 5-point Likert-type scale. RESULTS: The response rate was 62%. The majority of residents (80%) agreed that patients had adequate continuity of care. Most residents agreed that they had enough time to follow up on consult notes (64% agreed) and investigations (80% agreed) daily. Most PGY-1 residents (59%) reported having enough time to prepare sign-outs. Most (60%) residents felt that reducing handoffs would improve patient care. CONCLUSIONS: Most residents believe that the new work hour limitations would continue to uphold patient safety, but handoffs in care must be restricted.

Adjusting diffusing capacity for anemia in patients undergoing allogeneic HCT: a comparison of two methodologies.

BACKGROUND: Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint. STUDY DESIGN: This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis. RESULTS: Patients had normal spirometry (FEV1 99.7% [IQR: 89.4-109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9-94.1%) while Dinakara-DLCO 111.0% (97.3-124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV1, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20). CONCLUSION: The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.

Parsonage-Turner Syndrome and Hereditary Brachial Plexus Neuropathy.

Parsonage-Turner syndrome and hereditary brachial plexus neuropathy (HBPN) present with indistinguishable attacks of rapid-onset severe shoulder and arm pain, disabling weakness, and early muscle atrophy. Their combined incidence ranges from 3 to 100 in 100,000 persons per year. Dominant mutations of SEPT9 are the only known mutations responsible for HBPN. Parsonage and Turner termed the disorder "brachial neuralgic amyotrophy," highlighting neuropathic pain and muscle atrophy. Modern electrodiagnostic and imaging testing assists the diagnosis in distinction from mimicking disorders. Shoulder and upper limb nerves outside the brachial plexus are commonly affected including the phrenic nerve where diaphragm ultrasound improves diagnosis. Magnetic resonance imaging can show multifocal T2 nerve and muscle hyperintensities with nerve hourglass swellings and constrictions identifiable also by ultrasound. An inflammatory immune component is suggested by nerve biopsies and associated infectious, immunization, trauma, surgery, and childbirth triggers. High-dose pulsed steroids assist initial pain control; however, weakness and subsequent pain are not clearly responsive to steroids and instead benefit from time, physical therapy, and non-narcotic pain medications. Recurrent attacks in HBPN are common and prophylactic steroids or intravenous immunoglobulin may reduce surgical- or childbirth-induced attacks. Rehabilitation focusing on restoring functional scapular mechanics, energy conservation, contracture prevention, and pain management are critical. Lifetime residual pain and weakness are rare with most making dramatic functional recovery. Tendon transfers can be used when recovery does not occur after 18 months. Early neurolysis and nerve grafts are controversial. This review provides an update including new diagnostic tools, new associations, and new interventions crossing multiple medical disciplines.

Environmental improvements brought by the legal interventions in the homes of poorly controlled inner-city adult asthmatic patients: a proof-of-concept study.

OBJECTIVES: Domestic contamination with mold, cockroaches, rodents, and dust worsens asthma severity. This violates warranty of habitability laws in most of the states, but patients often find it beyond their means to remedy their housing situation. We aimed to study the effect of a medical-legal collaborative intervention to force landlords into providing better living conditions for patients with poorly controlled asthma. METHODS: We retrospectively studied charts of adult patients aged 18 years or older with poorly controlled asthma (moderate or severe persistent) despite maximum medical therapy. Additionally, patients had self-reported domestic allergen exposures such as mold, cockroaches, mice or rats, and dust. The patients received legal assistance to improve their domestic environments, including fixing leaks, exterminating pests, or providing a different apartment. Post-intervention change in peak expiratory flow rate (PEFR), asthma severity class, medications, emergency department (ED) visits, hospitalizations, and requirement for systemic steroids for symptom control was assessed. RESULTS: Data were available for 12 patients (9-12 months pre-intervention and 6-12 months post-intervention). Analysis of paired data revealed that mean PEFR rose by 38.6 LPM (95% CI: 9.9-67.3; p = .014). The number of ED visits and hospital admissions declined from 22 ED visits and 11 admissions to 2 ED visits and 1 admission (91% reduction), respectively. Of the 11 patients requiring systemic steroids, only three required these post-intervention. All patients had reductions in the dose and/or number of medications. During post-intervention, 11 (91.7%) patients dropped ≥2 classes in asthma severity. CONCLUSIONS: Medical-legal collaboration is highly effective in improving the control of inner-city asthmatics by effecting improvements in the domestic environment.

Corrected formula for rectangular area ratio (RAR), a parameter used to quantify airflow limitation on expiratory flow-volume curves.

Quantification of expiratory flow limitation during exercise has been demonstrated using computerized breath-by-breath analysis of the flow-volume curve. One of the parameters used in quantitation of airflow limitation is the rectangular area ratio (RAR) described in this journal by Ma et al. (2010). Upon closer review of the formula utilized in this paper, it is noted that the formula does not accurately capture the RAR, and the formula may underestimate the true RAR due to errors in various terms contained within the numerator and the denominator. A correct version of the formula is presented in this report. The correct formula does not require re-measurement of new variables but uses the existing variables in the correct mathematical and geometric context. This study has implications for validity of the data contained in the original paper as well as several other studies utilizing the same formula that have been published since the original publication. All future research using the RAR should use the correct formula, as contained in this paper.

Isolated Elevation in Lung Residual Volume Is Associated With Airway Diseases.

BACKGROUND: Residual volume (RV) is a derived lung compartment that correlates with air trapping in the context of air flow obstruction on spirometry. The significance of an isolated elevation in RV in the absence of other pulmonary function test (PFT) abnormalities is not well defined. We sought to assess the clinical and radiologic findings associated with isolated elevation in RV. METHODS: We searched our out-patient PFT database at Mayo Clinic (Rochester, Minnesota) from 2016-2018 for adult patients with isolated elevation in RV. We defined isolated elevation in RV as RV ≥ upper limit of normal or ≥ 130% predicted with normal total lung capacity (TLC), spirometry, and diffusion capacity of the lung for carbon monoxide (DLCO). We then matched this high-RV group by age and sex to an equal number of individuals with normal RV, TLC, spirometry, and DLCO (normal-RV group). RESULTS: We identified 169 subjects with isolated elevation in RV on PFTs, with a median age of 73 y; 55.6% were female, and median body mass index was 26.8 (vs 29.8 in the normal-RV group). The median RV was 3.08 L (134% predicted, interquartile range [IQR] 130-141) in the high-RV group and 2.26 L (99% predicted, IQR 90-109) in the normal-RV group (P < .001). Subjects with high RV were more likely to have smoked (54% vs 40%, P = .01) and almost twice as likely to have a maximum voluntary ventilation < 30 times the FEV1 (21% vs 12%, P = .02). Clinically, asthma (21% vs 11%, P = .01) and non-tuberculous mycobacterial lung infections (12% vs 2%, P = .001) were more prevalent in the high-RV group. On chest computed tomography, bronchiectasis (31% vs 15%, P = .008), bronchial thickening or mucus plugging (46% vs 22%, P < .001), and emphysema (13% vs 5%, P = .046) were more common in the high-RV group. CONCLUSIONS: Isolated elevation in RV on PFTs is a clinically relevant abnormality associated with airway-centered diseases.

Nodal recurrences after stereotactic body radiotherapy for early stage non-small-cell lung cancer.

Lobectomy is considered the standard of care for early stage non-small-cell lung cancer. However, for those patients who remain unfit to undergo surgery due to advanced age, poor performance status, comorbidities, poor pulmonary reserve or a combination of these are now treated with stereotactic body radiation therapy (SBRT). Due to its noninvasive nature, lower cost, lower toxicity, reduced recovery time and equivalent efficacy, even medically operable patients are attracted to the option of SBRT despite the lack of level I evidence. Thus, studying the incidence and patterns of recurrence after SBRT help in understanding the magnitude of the problem, risk factors associated with the different patterns of recurrence, and aid in devising strategies to prevent them in future. Nodal recurrences are not uncommon after SBRT and can potentially lead to further seeding for distant metastases and ultimately poor survival. This review is aimed at reviewing the published data on the incidence of nodal recurrences after SBRT and compare it to surgery, identify potential risk factors for recurrence, salvage treatment options and prevention strategies.

Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial.

BACKGROUND: Periintubation hypotension is associated with poor outcomes in the critically ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes postdrug administration. METHODS: Emergent-use, stratified (shock status and unit type), multiunit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture (0.5 mg/kg of ketamine and propofol each) or reduced dose etomidate (0.15 mg/kg) for emergent intubation. RESULTS: One hundred sixty participants were randomized, and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes postdrug administration (treatment difference [ketamine/propofol admixture-etomidate]: -2.1 mm Hg; 95% confidence interval, -6.9 mm Hg to +2.7 mm Hg; p = 0.385). In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 minutes and 15 minutes postdrug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non-red blood cell transfusions (16 [22%] vs. 8 [10%], p = 0.046). For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027). Serious adverse events were rare, 2 (3%) (cardiac arrest, hypotension) in ketamine/propofol admixture and 4 (5%) (hypertension, hypotension) in etomidate (p = 0.430). CONCLUSION: In a heterogeneous critically ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically ill. LEVEL OF EVIDENCE: Therapeutic/Care Management, level II. TRIAL REGISTRY: ClinicalTrials.gov, NCT02105415, Ketamine/Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB 13-000506, Trial Registration: March 31, 2014.

An epidemiological review of mobile telephones and cancer.

Mobile telecommunication technology became commercially available about 20-25 years ago in different countries around the world. The industry has grown exponentially over the years and, currently, the number of mobile phone users is estimated to be over 3.8 billion, more than half the world's population. Thus, because of such a large population-at-risk, any health hazard from these devices promises to have a large epidemiological impact. Intense speculation and investigation into the relationship between mobile phone usage and cancer has led to the publication of numerous, often contradictory, reports on this subject. This review aims to provide a large body of reported evidence to help medical professionals disseminate evidence-based information to their patients.

Health hazards of mobile phones: an Indian perspective.

The mobile phone industry has been one of the fastest growing industries in modern history. Today, India has million mobile phone users, and mobile phones account for 88% of all telecommunication users. The rural sector accounts for more than 25% of all wireless phone users and this proportion is bound to grow as affordability of mobile phones continues to increase. In the years ahead, an ever-increasing number exposed for long periods of time to radiation from mobile phones. In 2008, the Telecom Commission (the policy-making body of the Department of Telecommunicatics, Government of India) adopted the emission guidelines prescribed by the International Commission on Non-Protection (ICNIRP). Studies have demonstrated that usage behaviours, such as duration of usage and predominant, one-sided use of mobile phones are some of the chief risks that increase likelihood of hazards resulting from mobile phone use. This article attempts to present the basic biophysics of these devices and explain the health hazards of electromagnetic radiation exposure in terms of thermal and non-thermal effects. We also present some preventive measures that can reduce the risk of these hazards.

Disorders of potassium homeostasis: pathophysiology and management.

Disorders of potassium homeostasis are common electrolyte abnormalities encountered in hospitalized patients. Hypokalemia and hyperkalemia have been estimated to occur in about 21% and 3% of hospitalized patients, respectively; though the morbidity and mortality associated with the latter is significantly higher. Potassium is a predominantly intracellular ion and the understanding of its dynamics between intra- and extracellular fluid milieus, along with its handling by the kidneys, is important in the diagnosis and treatment of potassium disorders. This article aims to provide a clinically relevant update on management of potassium disorders for internists.