Comparative specialization of intrinsic cardiac neurons in humans, mice, and pigs.

Intrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exists. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs, and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry, and ultrastructure of these cells across species. The densely packed, smaller ICNs of mouse lacked dendrites, formed axosomatic connections, and had high synaptic efficacy constituting an obligatory synapse. At Pig ICNs, a convergence of subthreshold cholinergic inputs onto extensive dendritic arbors supported greater summation and integration of synaptic input. Human ICNs were tonically firing, with synaptic stimulation evoking large suprathreshold excitatory postsynaptic potentials like mouse, and subthreshold potentials like pig. Ultrastructural examination of synaptic terminals revealed conserved architecture, yet small clear vesicles (SCVs) were larger in pigs and humans. The presence and localization of ganglionic neuropeptides was distinct, with abundant VIP observed in human but not pig or mouse ganglia, and little SP or CGRP in pig ganglia. Action potential waveforms were similar, but human ICNs had larger after-hyperpolarizations. Intrinsic excitability differed; 93% of human cells were tonic, all pig neurons were phasic, and both phasic and tonic phenotypes were observed in mouse. In combination, this publicly accessible, multimodal atlas of ICNs from mice, pigs, and humans identifies similarities and differences in the evolution of ICNs.

Gastroesophageal Reflux Disease.

Symptoms potentially attributable to gastroesophageal reflux disease are among those most commonly reported to primary care providers in the outpatient setting. In this review, we discuss clinical approaches to the evaluation and management of these symptoms, including proton pump inhibitor trials as well as specific indications or clinical settings that warrant referral to Gastroenterology specialists.

The role of ketamine-induced beta activity in the treatment of refractory status epilepticus. Is the EEG useful to determine responder's rate? A retrospective study.

INTRODUCTION: Multiple investigations have been done to evaluate the possible effect of ketamine in the treatment of status epilepticus (SE). OBJECTIVES: To evaluate the electrographic effect of ketamine on EEG, and its clinical utility following-up refractory and super refractory status epilepticus (SRSE). METHODS: Retrospective review of 24 patients with SE. Clinical record and Video-electroencephalogram (video-EEG) of all included patients were reviewed. The patients' EEGs were then monitored for any immediate changes after administration of the first dose of ketamine as well as at the time patients would be predicted to have peak serum concentration of ketamine. Patients with cessation of electrographic seizures and no SE recurrence within the same admissions were categorized as "Responders". Statistical differences between qualitative variables were analyzed using chi square test. Differences between median were analyzed by Mann-Whitney U test. Difference between groups were considered significant when p < 0.05. RESULTS: We identified 24 patients with SE. Twelve out of 24 (50%) had SRSE and 12 out of 24 (50%) had refractory status epilepticus (RSE). The appearance of superimposed beta activity after ketamine was initiated was associated with a higher responder rate (100% versus 33.3% in the responder group versus the non-responder group respectively). Notably, the presence of a burst suppression pattern had no significant association with one group compared to the other (41.6% versus 33.3%, in the responder group vs the non-responder group respectively). CONCLUSIONS: Background superimposed beta activity induced by ketamine is an early and reliable EEG finding associated with status epilepticus termination.

Management of Mandible Fracture in 150 Children Across 7 Years in a US Tertiary Care Hospital.

IMPORTANCE: Pediatric mandible fractures are the most common pediatric facial fracture requiring hospitalization, but data are lacking on management methods, outcomes, and complications. OBJECTIVE: To analyze management methods, outcomes, and complications of pediatric mandible fractures at an urban academic tertiary care center. DESIGN, SETTING, AND PARTICIPANTS: Single-institution cohort study conducted at 2 urban level 1 pediatric trauma centers including all patients aged 0 to 17 years diagnosed with mandible fractures between January 1, 2010, and December 31, 2016. Fractures were treated by multispecialty surgical teams. Data were analyzed between January 1, 2018, and March 1, 2018. MAIN OUTCOMES AND MEASURES: Fracture distributions, mechanisms, treatment methods, complications, and follow-up. RESULTS: Of 150 patients with 310 total mandible fractures, the mean (SD) age was 12.8 (4.6) years; 108 (72.0%) were male; 107 (71.3%) were white; and 109 (72.7%) had 2 or more mandible fractures. There were 78 condylar or subcondylar fractures (60 patients), 75 ramus or angle fractures (69 patients), 69 body fractures (62 patients), 78 symphyseal or parasymphyseal fractures (76 patients), and 10 coronoid fractures (10 patients). The most common mechanisms of injury were assault and battery, motor vehicle collisions, falls or play, and sports-related mechanisms. Thirty-eight (25%) patients were treated with observation and a soft diet. Children 12 years and older were more likely to receive open reduction internal fixation (ORIF) (P = .02). Of 112 patients treated with surgery, 63 (56.2%) were treated with maxillomandibular fixation (MMF), 24 (21.4%) received ORIF, and 20 (17.9%) received both MMF and ORIF. Nonabsorbable plating was used in all but 1 of the ORIF procedures. Five of 44 (11.4%) patients receiving ORIF or ORIF and MMF had follow-up beyond 6 months, and 8 of the 44 (18.2%) had documented plating hardware removal; hardware was in place for a mean (SD) 180 (167) days. Sixty of the 150 patients (40.0%) had some form of follow-up, a mean (SD) 90 (113) days total after initial presentation. Thirteen patients experienced complications, for a total complication rate of 8.7%. CONCLUSIONS AND RELEVANCE: Conservative management, using MMF and a soft diet, was favored for most operative pediatric mandible fractures. Open reduction internal fixation with titanium plating was less commonly used. Outcomes were favorable despite a lack of consistent follow-up. LEVEL OF EVIDENCE: 4.

Association of Intracranial Hypertension With Calvarial and Skull Base Thinning.

OBJECTIVE: Determine if patients with increased opening pressure (OP) on lumbar puncture (LP) have thinner calvaria and skull bases. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Patients (≥18 yr of age) who had a recorded OP on LP and high-resolution computed tomography imaging of the head. Patient age, sex, body mass index were calculated. Intracranial hypertension (IH) was defined with an OP≥25 cm-H2O and low intracranial pressure with an OP<15 cm-H2O. INTERVENTION: Measurement of calvarial, zygoma, and skull base thickness when blinded to OP with three-dimensional slicer and radiologic calipers. MAIN OUTCOME MEASURES: Association of calvarial, skull base, and zygoma thickness with OP and age. RESULTS: Fifty-eight patients were included with a mean (SD) age of 53.1 (16.2) years and average (SD) body mass index of 30.1 (9.1) kg/m. Patients with IH had thinner mean (SD) calvaria (3.01 [0.81] versus 2.70 [0.58] mm; p = 0.036) and skull bases (5.17 [1.22] versus 4.60 [1.42] mm; p = 0.043) when compared with patients without IH. The mean (SD) extracranial zygoma thickness was similar between the two groups (5.09 [0.76] versus 5.00 [0.73] mm; p = 0.56). General linear model regression demonstrated advancing age was associated with increasing calvarial thickness in patients without IH and calvarial thinning in patients with IH (p = 0.038). CONCLUSION: IH is independently associated with intracranial bone (calvaria and skull base) thinning and not extracranial (zygoma) thinning. Skull thinning occurs with IH and advancing age. These findings support a possible role of increased ICP in the pathophysiologic development of spontaneous cerebrospinal fluid leaks.

Safety and efficacy of non-anesthesiologist administration of propofol sedation during esophagogastroduodenoscopy in the intensive care unit.

Background and study aims Propofol sedation is an increasingly popular method of sedation for gastrointestinal endoscopic procedures. The safety and efficacy of the non-anesthesiologist administration of propofol (NAAP) sedation has been demonstrated in the ambulatory setting. However, NAAP sedation in intensive care unit (ICU) patients has not been reported. The purpose of this study is to determine safety and efficacy of NAAP sedation in an ICU population. Methods We retrospectively reviewed esophagogastroduodenoscopies (EGD) performed with NAAP sedation in our intensive care units from June 2014 to September 2016. All EGDs were performed for evaluation of gastrointestinal bleeding. The primary end point of this study was to analyze the incidence of sedation-related adverse events (AEs). The secondary end points included successful completion of procedure and any endoscopic interventions performed. Results Two of 161 procedures (1.2 %) had sedation-related AEs requiring procedure termination. One hundred forty-six of 161 procedures (90.7 %) were successfully completed. Incomplete procedures were due to excess heme, retained food or obstructive lesions (13/161, 8.1 %). Endoscopic intervention was performed successfully in 17/24 cases (70.8 %) that had endoscopically treated lesions identified. One hundred six of 161 patients (66 %) were American Society of Anesthesiologists (ASA) classification III or IV. Conclusion Our retrospective analysis demonstrated that EGDs can be successfully completed in ICU patients using NAAP sedation. When procedures cannot be completed, it is rarely due to sedation-related AEs. NAAP sedation further allows adequate examination and successful treatment of high-risk lesions. NAAP sedation appears safe and effective for endoscopic procedures in the ICU setting.

Association of Obstructive Sleep Apnea With Calvarial and Skull Base Thinning.

Importance: Spontaneous cerebrospinal fluid leaks (sCSF-L) of the temporal bone are associated with obesity, calvarial thinning, and obstructive sleep apnea (OSA), and the incidence has doubled in the past decade. It is currently unknown if OSA is independently associated with skull thinning. Objective: To determine if patients with OSA have thinner skulls than patients without OSA. Design, Setting, and Participants: A retrospective cohort study of patients who underwent a level 1 polysomnogram (PSG) and also had high-resolution computed tomographic (CT) imaging of the head from January 2010 to March 2017 at Indiana University was carried out. Patients with moderate to severe OSA (apnea-hypopnea index [AHI]≥25/h) and without OSA (AHI<5/h) were matched for age and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared). Interventions: Measurement of calvarial thickness, extracranial zygoma thickness, skull base height and tegmen dehiscence (>4 mm) when blinded to OSA status. Main Outcomes and Measures: Primary outcomes were calvarial, skull base, and zygoma thickness differences between patients with OSA vs those without OSA. Results: A total of 22 933 patients had a PSG and 1012 also had head CT imaging. Of the 1012 patients with both PSG and CT, the mean (SD) age was 50.8 (16.2) years and 624 (61.7%) were women. Those patients with moderate to severe OSA (56) and without OSA (58) were matched for mean (SD) age (50.3 [6.5] vs 49.8 [6.1] years]) and BMI (37.4 [8.1] vs 38.6 [6.8]). Patients with OSA had thinner mean (SD) calvaria (2.73 [0.67] vs 2.47 [0.52] mm; difference, -0.26 mm; 95% CI, -0.49 to -0.04; Cohen d, 0.44) and thinner skull bases (5.03 [1.40] vs 4.32 [1.28] mm; difference, -0.71; 95% CI, -1.23 to -0.19; Cohen d, 0.53). The mean (SD) extracranial zygoma thickness was the same (4.92 [0.87] vs 4.84 [0.84] mm; difference, -0.07 mm; 95% CI, -0.39 to 0.24). The tegmen mastoideum was dehiscent in nearly twice as many patients with OSA as those without (37% vs 20%; difference, 17%; 95% CI, 0.4-32). Conclusions and Relevance: Obstructive sleep apnea was independently associated with intracranial bone (calvaria and skull base) thinning and not with extracranial (zygoma) thinning. These findings support a possible role of OSA in the pathophysiologic development of sCSF-L.

Rare hereditary cause of chronic pancreatitis in a young male: SPINK1 mutation.

Hereditary chronic pancreatitis associated with a mutation in the serine protease inhibitor, Kazal Type-1 (SPINK-1 gene) is extremely rare. The SPINK1 mutation results in trypsinogen activation which predisposes to chronic pancreatitis predominately when combined with CFTR gene mutations. It presents as either chronic or recurrent acute pancreatitis. Symptom control and management of complications is important. Active surveillance with cross-sectional imaging for pancreatic malignancy in individuals with hereditary pancreatitis is advocated due to individuals being high risk. We present an unusual case of a young male who initially presented with renal colic and was incidentally diagnosed with severe chronic pancreatitis on abdominal imaging, with genetic testing confirming a homozygous SPINK1 mutation.

Role of photodynamic therapy and intraductal radiofrequency ablation in cholangiocarcinoma.

Cholangiocarcinoma comprises 3% of all gastrointestinal malignancies. Prognosis is poor as the disease is locally advanced at the time of its presentation. Biliary endoprosthesis are widely used for biliary decompression, however, they only provides temporary relief. Photodynamic therapy and Radiofrequency ablation are two innovative approaches performed endoscopically to locally destruct the malignant tissue. This chapter focuses on their application and appropriate use along with their benefits and complications.