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AbstractBackgroundMany serologic and radiographic modalities are used for monitoring multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal neuroendocrine tumors (PNETs). We compared serum markers and imaging studies obtained preoperatively with the gross pathology and immunohistochemical findings and correlated preoperative testing with postoperative outcome.MethodsFrom 2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19–74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies] for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide (HPP), gastrin, and glucagon] and imaging [CT, 111In pentetreotide scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic findings. Postoperative serum markers and survival were followed.ResultsHuman pancreatic polypeptide had the highest agreement between an elevated serum level and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67% agreement for glucagon). Preoperative CT had 81% sensitivity and positive predictive value (PPV) of 97% for PNETs. 111In pentetreotide scintigraphy had 84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had 100% sensitivity and PPV, with close correlation (rs = 0.93) between the largest lesion seen on EUS and pathology. Median follow‐up was 4.3 years (range = 0.1–10.9 years). Overall survival was 89% at 5‐year follow‐up.ConclusionsOur study substantiates EUS as providing the highest preoperative sensitivity and PPV in assessing the presence of PNETs in MEN 1 patients. CT and octreotide scintigraphy can yield both false‐positive and false‐negative results. HPP, gastrin, and glucagon were the most commonly measured tumor markers in our series but did not always correlate with immunostaining. With an aggressive surgical approach, satisfactory rates of biochemical improvement and long‐term survival were observed.

Objective Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence‐based recommendations for the diagnosis, management, and follow‐up of patients who present with SHL. The guideline primarily focuses on sudden sensorineural hearing loss (SSNHL) in adult patients (aged 18 and older). Prompt recognition and management of SSNHL may improve hearing recovery and patient quality of life (QOL). Sudden sensorineural hearing loss affects 5 to 20 per 100,000 population, with about 4000 new cases per year in the United States. This guideline is intended for all clinicians who diagnose or manage adult patients who present with SHL. Purpose The purpose of this guideline is to provide clinicians with evidence‐based recommendations in evaluating patients with SHL, with particular emphasis on managing SSNHL. The panel recognized that patients enter the health care system with SHL as a nonspecific, primary complaint. Therefore, the initial recommendations of the guideline deal with efficiently distinguishing SSNHL from other causes of SHL at the time of presentation. By focusing on opportunities for quality improvement, the guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. Results The panel made strong recommendations that clinicians should (1) distinguish sensorineural hearing loss from conductive hearing loss in a patient presenting with SHL; (2) educate patients with idiopathic sudden sensorineural hearing loss (ISSNHL) about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy; and (3) counsel patients with incomplete recovery of hearing about the possible benefits of amplification and hearing‐assistive technology and other supportive measures. The panel made recommendations that clinicians should (1) assess patients with presumptive SSNHL for bilateral SHL, recurrent episodes of SHL, or focal neurologic findings; (2) diagnose presumptive ISSNHL if audiometry confirms a 30‐dB hearing loss at 3 consecutive frequencies and an underlying condition cannot be identified by history and physical examination; (3) evaluate patients with ISSNHL for retrocochlear pathology by obtaining magnetic resonance imaging, auditory brainstem response, or audiometric follow‐up; (4) offer intratympanic steroid perfusion when patients have incomplete recovery from ISSNHL after failure of initial management; and (5) obtain follow‐up audiometric evaluation within 6 months of diagnosis for patients with ISSNHL. The panel offered as options that clinicians may offer (1) corticosteroids as initial therapy to patients with ISSNHL and (2) hyperbaric oxygen therapy within 3 months of diagnosis of ISSNHL. The panel made a recommendation against clinicians routinely prescribing antivirals, thrombolytics, vasodilators, vasoactive substances, or antioxidants to patients with ISSNHL. The panel made strong recommendations against clinicians (1) ordering computerized tomography of the head/brain in the initial evaluation of a patient with presumptive SSNHL and (2) obtaining routine laboratory tests in patients with ISSNHL.

Although the two-kidney, one-clip (2K1C) model is widely used as a model of human renovascular hypertension, mechanisms leading to the development of fibrosis and atrophy in the cuffed kidney and compensatory hyperplasia in the contralateral kidney have not been defined. Based on the well-established role of the transforming growth factor (TGF)-β signaling pathway in renal fibrosis, we tested the hypothesis that abrogation of TGF-β/Smad3 signaling would prevent fibrosis in the cuffed kidney. Renal artery stenosis (RAS) was established in mice with a targeted disruption of exon 2 of the Smad3 gene (Smad3 KO) and wild-type (WT) controls by placement of a polytetrafluoroethylene cuff on the right renal artery. Serial pulse-wave Doppler ultrasound assessments verified that blood flow through the cuffed renal artery was decreased to a similar extent in Smad3 KO and WT mice. Two weeks after surgery, systolic blood pressure and plasma renin activity were significantly elevated in both the Smad3 KO and WT mice. The cuffed kidney of WT mice developed renal atrophy (50% reduction in weight after 6 wk, P < 0.0001), which was associated with the development of interstitial fibrosis, tubular atrophy, and interstitial inflammation. Remarkably, despite a similar reduction of renal blood flow, the cuffed kidney of the Smad3 KO mice showed minimal atrophy (9% reduction in weight, P = not significant), with no significant histopathological alterations (interstitial fibrosis, tubular atrophy, and interstitial inflammation). We conclude that abrogation of TGF-β/Smad3 signaling confers protection against the development of fibrosis and atrophy in RAS.

Seizures are often the first manifestation of central nervous system dysfunction and are common in many inborn errors of metabolism, especially in neonates, infants, and children. A high index of suspicion is required to diagnose inborn errors of metabolism as the cause of seizures. It is also important to recognize these metabolic disorders early, as specific disease-modifying treatments are available for some with favorable long-term outcomes. This review discusses the classification of metabolic disorders as a cause of seizures based on pathogenesis and age and proposes a tiered approach for cost-effective diagnosis of metabolic disorders.

ABSTRACT Introduction Peyronie’s disease (PD) is characterized by fibrotic plaque formation within the tunica albuginea, leading to penile deformity, angulation, painful erections, and often, erectile dysfunction. There is limited knowledge of its etiology and pathophysiology. Currently, there is no standardization for reporting the evaluation and treatment outcomes. No consensus exists on the ideal management of PD. Aim The aim of this study is to review the use of radiation therapy (RT) for the treatment of PD. Methods This study used a review of the literature and informed expert opinion. Main Outcome Measures The main outcome measures are the reported improvement with regard to pain, curvature, plaque size, and erectile function as well as a review of the safety profile of RT. Results Radiation has been used for the empirical treatment of PD with mixed results throughout the literature. Low-dose RT in the early stages of PD seems to be effective in patients with painful erections not improving with time or with the use of oral or intralesional therapies. Comparison with other current medical therapies is difficult due to the absence of criteria for therapeutic success and the absence of randomized, controlled trials. Multiple studies have demonstrated varied results in terms of curvature reduction, plaque volume, and sexual functioning. The absence of the use of validated means of measuring penile deformity and sexual function, the limited relevance of plaque and pain improvement combined with the potential negative consequences of radiation on erectile tissue structure and function lead us to make a recommendation that RT not be used for the management of PD. Conclusions In clinical practice, mixed success for RT has led to the recommendation against its use as a treatment modality for PD.