A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable Metallic Stents in Benign Extrahepatic Biliary Strictures.

BACKGROUND: Endoscopic therapy is considered first line for management of benign biliary strictures (BBSs). Placement of plastic stents has been effective but limited by their short-term patency and need for repeated procedures. Fully covered self-expandable metallic stents (FCSEMSs) offer longer-lasting biliary drainage without the need for frequent exchanges. AIMS: The aim of this study was to assess the efficacy and safety of FCSEMS in patients with BBS. METHODS: A retrospective review of all patients who underwent ERCP and FCSEMS placement at five tertiary referral US hospitals was performed. Stricture resolution and adverse events related to ERCP and/or stenting were recorded. RESULTS: A total of 123 patients underwent FCSEMS placement for BBS and 112 underwent a subsequent follow-up ERCP. The mean age was 62 years (±15.6), and 57% were males. Stricture resolution occurred in 81% of patients after a mean of 1.2 stenting procedures (mean stent dwell time 24.4 ± 2.3 weeks), with a mean follow-up of 18.5 months. Stricture recurrence occurred in 5 patients, and 3 patients required surgery for treatment of refractory strictures. Stent migration (9.7%) was the most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%), and pancreatitis (3.3%). There was one case of stent fracture during removal, and one stent could not be removed. There was one death due to cholangitis. CONCLUSIONS: Majority of BBS can be successfully managed with 1-2 consecutive FCSEMS with stent dwell time of 6 months.

Characterization of the Candiru antigenic complex (Bunyaviridae: Phlebovirus), a highly diverse and reassorting group of viruses affecting humans in tropical America.

The genus Phlebovirus of the family Bunyaviridae consists of approximately 70 named viruses, currently assigned to nine serocomplexes (species) based on antigenic similarities. Sixteen other named viruses that show little serologic relationship to the nine recognized groups are also classified as tentative species in the genus. In an effort to develop a more precise classification system for phleboviruses, we are attempting to sequence most of the named viruses in the genus with the goal of clarifying their phylogenetic relationships. In this report, we describe the serologic and phylogenetic relationships of 13 viruses that were found to be members of the Candiru serocomplex; 6 of them cause disease in humans. Analysis of full genome sequences revealed branching inconsistencies that suggest five reassortment events, all involving the M segment, and thus appear to be natural reassortants. This high rate of reassortment illustrates the inaccuracy of a classification system based solely on antigenic relationships.

Aguacate virus, a new antigenic complex of the genus Phlebovirus (family Bunyaviridae).

Genomic and antigenic characterization of Aguacate virus, a tentative species of the genus Phlebovirus, and three other unclassified viruses, Armero virus, Durania virus and Ixcanal virus, demonstrate a close relationship to one another. They are distinct from the other nine recognized species within the genus Phlebovirus. We propose to designate them as a new (tenth) serogroup or species (Aguacate virus) within the genus. The four viruses were all isolated from phlebotomine sandflies (Lutzomyia sp.) collected in Central and South America. Aguacate virus appears to be a natural reassortant and serves as one more example of the high frequency of reassortment in this genus.

Development of Fulminant Type 1 Diabetes Mellitus in a Patient with DRESS Syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease's myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.

Mobile Delivery of the Diabetes Prevention Program in People With Prediabetes: Randomized Controlled Trial.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) diabetes prevention program (DPP) has formed the foundation for Type 2 Diabetes Mellitus (T2DM) prevention efforts and lifestyle change modifications in multiple care settings. To our knowledge, no randomized controlled trial has verified the efficacy of a fully mobile version of CDC's diabetes prevention program (DPP). OBJECTIVE: This study aimed to investigate the long-term weight loss and glycemic efficacy of a mobile-delivered DPP compared with a control group receiving usual medical care. METHODS: Adults with prediabetes (N=202) were recruited from a clinic and randomized to either a mobile-delivered, coach-guided DPP (Noom) or a control group that received regular medical care including a paper-based DPP curriculum and no formal intervention. The intervention group learned how to use the Noom program, how to interact with their coach, and the importance of maintaining motivation. They had access to an interactive coach-to-participant interface and group messaging, daily challenges for behavior change, DPP-based education articles, food logging, and automated feedback. Primary outcomes included changes in weight and hemoglobin A1c (HbA1c) levels at 6 and 12 months, respectively. Exploratory secondary outcomes included program engagement as a predictor of changes in weight and HbA1c levels. RESULTS: A total of 202 participants were recruited and randomized into the intervention (n=101) or control group (n=99). In the intention-to-treat (ITT) analyses, changes in the participants' weight and BMI were significantly different at 6 months between the intervention and control groups, but there was no difference in HbA1c levels (mean difference 0.004%, SE 0.05; P=.94). Weight and BMI were lower in the intervention group by -2.64 kg (SE 0.71; P<.001) and -0.99 kg/m2 (SE 0.29; P=.001), respectively. These differences persisted at 12 months. However, in the analyses that did not involve ITT, program completers achieved a significant weight loss of 5.6% (SE 0.81; P<.001) at 6 months, maintaining 4.7% (SE 0.88; P<.001) of their weight loss at 12 months. The control group lost -0.15% at 6 months (SE 0.64; P=.85) and gained 0.33% (SE 0.70; P=.63) at 12 months. Those randomized to the intervention group who did not start the program had no meaningful weight or HbA1c level change, similar to the control group. At 1 year, the intervention group showed a 0.23% reduction in HbA1c levels; those who completed the intervention showed a 0.28% reduction. Those assigned to the control group had a 0.16% reduction in HbA1c levels. CONCLUSIONS: This novel mobile-delivered DPP achieved significant weight loss reductions for up to 1 year compared with usual care. This type of intervention reduces the risk of overt diabetes without the added barriers of in-person interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03865342; https://clinicaltrials.gov/ct2/show/NCT03865342.

Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of Ca(V)1.3 knockout mice.

Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel Ca(V)1.3 is deleted (Ca(V)1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which Ca(V)1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from Ca(V)1.3 knockout mice and wild-type littermates to explore the role of Ca(V)1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in Ca(V)1.3 knockout mice. Additionally, we found that BLA principal neurons from Ca(V)1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of Ca(V)1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear.

L-type voltage-gated calcium channels in conditioned fear: a genetic and pharmacological analysis.

Using pharmacological approaches, others have suggested that L-type voltage-gated calcium channels (L-VGCCs) mediate both consolidation and extinction of conditioned fear. In the absence of L-VGCC isoform-specific antagonists, we have begun to investigate the subtype-specific role of LVGCCs in consolidation and extinction of conditioned fear using a molecular genetics approach. Previously, we used this approach to demonstrate that the Ca(v)1.3 isoform mediates consolidation, but not extinction, of contextually conditioned fear. Here, we used mice in which the gene for the L-VGCC pore-forming subunit Ca(v)1.2 was conditionally deleted in forebrain excitatory neurons (Ca(v)1.2(cKO) mice) to address the role of Ca(v)1.2 in consolidation and extinction of conditioned fear. We demonstrate that Ca(v)1.2(cKO) mice consolidate and extinguish conditioned fear as well as control littermates. These data suggest that Ca(v)1.2 is not critical for these processes and together with our previous data argue against a role for either of the brain-expressed L-VGCCs (Ca(v)1.2 or Ca(v)1.3) in extinction of conditioned fear. Additionally, we present data demonstrating that the L-VGCC antagonist nifedipine, which has been used in previous conditioned fear extinction studies, impairs locomotion, and induces an aversive state. We further demonstrate that this aversive state can enter into associations with conditioned stimuli that are present at the time that it is experienced, suggesting that previous studies using nifedipine were likely confounded by drug toxicity. Taken together, our genetic and pharmacological data argue against a role for Ca(v)1.2 in consolidation of conditioned fear as well as a role for L-VGCCs in extinction of conditioned fear.

ELECTROCARDIOGRAM CHANGES IN ADDISON DISEASE: POTENTIAL CLINICAL MARKER FOR ADRENAL CRISIS.

OBJECTIVE: To present a unique phenomenon of a patient in addisonian crisis with electrocardiogram (ECG) anomalies that resolved following glucocorticoid therapy. METHODS: We present the case report followed by discussion with literature review. RESULTS: A 25-year-old male with Addison disease (AD) presented with a 1-week history of lightheadedness, shortness of breath, chest pain, abdominal pain, postural hypotension, and tachycardia. The patient was diagnosed with addisonian crisis and started on intravenous, high-dose glucocorticoids. An ECG showed right-heart axis deviation and T-wave inversions. In the context of ongoing chest pain, there was concern for myocardial ischemic attack and the patient underwent an extensive cardiac evaluation. Cardiac workup was negative and an echocardiogram showed an ejection fraction of 50 to 55%. The ECG abnormalities resolved 1 day into his hospital admission and his other symptoms resolved 2 days following treatment with steroids. CONCLUSION: AD is a rare, potentially lethal, and commonly misdiagnosed disease often first encountered clinically amidst an incident episode of adrenal crisis. Our AD patient was undergoing an adrenal crisis with ECG changes positive for probable cardiac ischemia. Glucocorticoid deficiency has been previously linked with decreased cardiac function and myocardial ischemia, though the underlying mechanisms are not fully clear. This patient recovered within 2 days after receiving corticosteroid supplementation. There have been similar cases previously reported. In each of these, patients underwent extensive and costly workup to evaluate cardiac function, yet all patients fully recovered with corticosteroids. Understanding the physiology and clinical presentation of adrenal crisis will be useful in establishing an earlier diagnosis, thus preventing mortality and avoiding unnecessary, expensive evaluations.