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We report a case of a 53-year-old male with inferolateral myocardial infarction, presenting an atypical Aslanger pattern on electrocardiogram (ECG). The ECG showed ST elevation in leads III, aVR, aVF, and posterior leads, with ST depression in II and V2-V6 with terminal positive T waves. Coronary angiography revealed total occlusion of the left circumflex artery (LCx) with significant stenosis of the left anterior descending (LAD) and right coronary artery (RCA). The LCx was successfully revascularized. This case highlights the importance of recognizing atypical Aslanger patterns, which may indicate multivessel coronary artery disease., Competing Interests: Declaration of competing interest We have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aim was to evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95 mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04 mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels (P = 0.135). Obesity was not included in the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95 mg/kg twice daily and 1.04 mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels., (© 2024. Crown.)

Key Clinical Message: Constrictive Pericarditis is a rare fibrotic conversion of the pericardium that results in non-specific clinical symptoms such as hepatomegaly, ascites, pleural effusions, and lower extremity edema. A multi-modal diagnostic approach with cardiac imaging tools, cardiac hemodynamic measurements, and tissue biopsy can be used to diagnose Constrictive Pericarditis., Abstract: Constrictive Pericarditis is a rare complication resulting in the fibrotic conversion of the pericardium secondary to idiopathic, infective, post-surgical, or post-radiation etiologies. The rigid and restrictive nature of the pericardium can result in non-specific symptoms of volume overload that can mimic liver cirrhosis or congestive heart failure. We present the case of a 73-year-old female with constrictive pericarditis who presented with vague symptoms of abdominal pain, abdominal bloating, and bilateral lower extremity edema. This case report highlights the clinical manifestation, invasive, and non-invasive diagnostic work-up, and management of constrictive pericarditis., Competing Interests: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper and the authors have no relevant disclosure., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: The number of bariatric operations is increasing each year. Sleeve gastrectomy is the most popular procedure; however, it often requires revision surgery because of insufficient weight loss, weight regain or gastro-oesophageal reflux disease (GORD). The most popular revisional procedures are Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB). The primary outcome of this meta-analysis was weight loss after revisional surgery following laparoscopic sleeve gastrectomy and the secondary outcomes were gastro-oesophageal reflux, BMI difference, operative time, bleeding and anastomotic leak., Methods: A systematic electronic search was undertaken using PubMed, MEDLINE, Ovid, Cochrane Library and Google Scholar following PRISMA guidelines. The initial search identified 2,546 articles. After screening, seven papers met the inclusion criteria: six retrospective studies and one randomised controlled trial., Results: In total, 802 patients met the inclusion criteria: 390 had an OAGB and a further 412 had an RYBG. All patients previously had a sleeve gastrectomy for weight loss. The length of follow-up was 12 months for our primary outcome. We found no statistically significant difference in excess weight loss (%EWL) between OAGB and RYGB ( p = 0.11). The incidence of postoperative reflux was statistically significantly higher in the OAGB group (16% vs 10.1%, p < 0.003). Operative time was statistically significantly lower in the OAGB group ( p = 0.04)., Conclusions: This meta-analysis showed no statistically significant difference between the two revision bariatric surgery procedures for %EWL. RYGB was superior to OAGB in reducing the incidence of symptomatic GORD, whereas OAGB had a significant shorter operative time.

Background: Data on the impact of chronic thrombocytopenia (CT) on outcomes following chronic total occlusion (CTO) percutaneous coronary interventions (PCI) is limited. Most studies are case reports and focused on postprocedural thrombocytopenia. The purpose of this present study is to assess the impact of CT (> one year) on health resource utilization (HRU), in-hospital outcomes, and cost following CTO PCI., Methods: We used discharge data from the 2016-2018 National Inpatient Sample and propensity score-weighted approach to examine the association between CT and HRU among patients undergoing CTO PCI. HRU was measured as a binary indicator defined as a length of stay greater than seven days and/or discharge to a non-home setting. The cost was measured as total charges standardized to 2018 dollars. Both outcomes were assessed using generalized linear models adjusted for survey year, and baseline characteristics., Results: Relative to its absence, the presence of CT following CTO PCI was associated with a 4.8% increased probability of high HRU (Population Average Treatment Effect (PATE) estimate = 0.048; 95% Confidence Interval (CI) = 0.041-0.055; P<0.001) and approximately $18,000 more in total hospital charges (PATE estimate = +$18,297.98; 95% CI = $15,101.33-$21,494.63, P<0.001)., Conclusion: Among chronic total occlusion patients undergoing percutaneous coronary intervention, those with chronic thrombocytopenia had higher resource use, including total hospital charges, and worse in-hospital outcomes when compared with those without chronic thrombocytopenia., Competing Interests: None., (AJCD Copyright © 2024.)

The use of percutaneous mechanical circulatory support (MCS) devices, including Impella and Intra-aortic balloon pump (IABP), in patients with cardiogenic shock has increased in recent times. We aimed to evaluate the impact of the choice of an MCS device on healthcare resource utilization. We queried the National Inpatient Sample registry between October 2016 and December 2018 to identify adults admitted for acute coronary syndrome-related cardiogenic shock and who received percutaneous coronary intervention (PCI). The study population was segregated into Impella and IABP groups using ICD 10 diagnosis codes. The primary endpoint was high healthcare resource utilization (HRU), while secondary outcomes included periprocedural complications. Propensity scoring matching was used to determine which patients in the Impella cohort had similar health to IABP patients. During the study period, 439,610 patients were admitted who received hemodynamic support using, Impella or IABP on account of acute coronary syndrome complicated by cardiogenic shock (CS). The median age (years) of the Impella cohort and IABP cohorts were similar (64.1 vs 65.1, P = 0.08). Gender distribution of the Impella CS patients was like IABP patients with female majorities in both groups, (71.9% vs 67.9%, P = 0.05). Impella CS patients had a higher representation of those with hypertension (P = 0.002), smoking (P = 0.040), obesity (P = 0.034), diabetes mellitus (P = 0.009), CHF (P = 0.030), COPD (P = 0.034), chronic liver disease (P = 0.028), and chronic kidney disease (P = 0.031). 1:1 Propensity score matching identified 2620 Impella patients' comparable severity index with the IABP patients. Patients with hemodynamic support using Impella had higher healthcare resource utilization, (HRU), the surrogate of length of stay (LOS) ≥7 or nonhome disposition at discharge, when compared with those with IABP (57.41% vs 42.76%, P < 0.0001). Impella CS patients had higher in-hospital mortality as compared to the IABP patients (55.45% vs 45.86%, P < 0.0001). Impella CS patients developed more periprocedural complications, including vascular injury (4.8% vs 1.4%, P < 0.0001), acute kidney injury (58.36% vs 41.64%, P < 0.0001), end-stage renal disease requiring dialysis (8.75% vs 1.25%, P = 0.002) when compared to the IABP patients. Among patients with ACS undergoing PCI and receiving MCS devices, those receiving Impella demonstrated higher healthcare resource utilization, higher LOS ≥7 days, and more nonhome disposition at discharge compared to patients receiving IABP. Further investigation is warranted to elucidate factors associated with these findings., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest or financial disclosure to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study sought to investigate health and healthcare disparities in the management of severe mitral regurgitation with transcatheter edge-to-edge repair using MitraClip and how racial differences impact resource utilization and costs., Methods: We retrospectively analyzed the National Inpatient Sample (NIS) for patients who underwent Transcatheter Edge-to-Edge Repair (TEER) using MitraClip between 2016 and 2018. The patients were stratified into four racial cohorts and study outcomes included high resource utilization (HRU), periprocedural complications, and total procedural costs. High resource utilization (HRU) was defined as length of stay (LOS) ≥7 days or a nonhome disposition at discharge. Multivariate logistic regression models were utilized to determine independent predictors of HRU., Results: 17,100 weighted TEER patients were segregated by race: Caucasian (n = 13,270), others (n = 1510), African Americans, AA (n = 1245) and Hispanics (n = 1075). More African Americans and Hispanics had TEER at Urban facilities (P < 0.001), which were teaching hospitals as well (P < 0.001) but were less likely to be covered by public insurance options -Medicare or Medicaid (P < 0.001). More AA (52.2 %) and Hispanics (27.6 %) were likely to be in the lowest median annual income quartile versus Caucasians (19.2 %) (P = 0.003). AA and Hispanics had higher resource utilization (HRU), prolonged length of stay, nonhome disposition at discharge, higher procedural costs and periprocedural complications versus Caucasians. The logistic regression model revealed acute kidney injury (AKI) and actual procedural costs as independent predictors of HRU in both African American and Hispanic groups., Conclusion: Significant Health and healthcare disparities do exist among underrepresented, racial minority patients undergoing transcatheter edge-to-edge repair in the US. These disparities were associated with higher resource utilization and actual costs in patients with mitral regurgitation treated with TEER., Competing Interests: Declaration of competing interest The authors declare no actual or potential conflicts of interest relevant to the conduct of this research and its subsequent publication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In response to the increasing demand for voice, data, and multimedia applications, the next generation of wireless communication systems is projected to provide faster data rates and better service quality to customers. Techniques such as Multiple-Input-Multiple-Output (MIMO) and diversity are being studied and implemented to meet the needs of next-generation wireless communication systems. Embedding multiple antennas into the same antenna system is seen as a promising solution, which can improve both the system's channel capacity and the communication link's quality. However, for small handheld and portable devices, embedding many antennas into a single device in a small area and at the same time providing good isolation becomes a challenge. Hence, designing a shared antenna system with multiple feed ports with equivalent or better performance characteristics as compared to the approach of multiple antennas with multiple feed ports is a promising advantage which can reduce the size and cost of manufacturing. This paper intends to provide an in-depth review of different MIMO antenna designs with common radiators covering various antenna design aspects such as isolation techniques, gain, efficiency, envelope correlation coefficient, and size, etc. There is also a discussion of the mathematical concepts of MIMO and different isolation techniques, as well as a comparative analysis of different shared radiator antenna designs. The literature review shows that only very few antennas' design with common radiator have been suggested in the available literature at present. Therefore, in this review paper, we have endeavored to study different antennas' designs with common radiator. A comparison is provided of their performance improvement techniques in a holistic way so that it can lead to further develop the common radiator multiport antenna systems and realize the promising advantages they offer.

A compact four-port multi-input, multi-output (MIMO) antenna with good isolation is proposed for sub-6 GHz and Internet of Things (IoT) applications. Four similar L-shaped antennae are placed orthogonally at 7.6 mm distance from the corner of the FR4 substrate. The wideband characteristics and the required frequency band are achieved through the L-shaped structure and with proper placement of the slots on the substrate. To obtain good isolation between the ports, rectangular slots are etched in the bottom layer and are interconnected. The proposed antenna has total dimensions of 40 mm × 40 mm × 1.6 mm. The interconnected ground plane provides good isolation of less than -17 dB between the ports, and the impedance bandwidth obtained by the proposed four-port antenna is about 54% between the frequency range of 3.2 GHz to 5.6 GHz, thus providing a wideband antenna characteristic covering sub-6 GHz 5G bands (from 3.4 to 3.6 GHz and 4.8 to 5 GHz) and the WLAN band (5.2 GHz). The proposed design antenna is fabricated and tested. Good experimental results are achieved when compared with the simulation results. As the proposed design is compact and low profile, this antenna could be a suitable candidate for 5G and IoT devices.

Context: Germline CDKN1B pathogenic variants result in multiple endocrine neoplasia type 4 (MEN4), an autosomal dominant hereditary tumor syndrome variably associated with primary hyperparathyroidism, pituitary adenoma, and duodenopancreatic neuroendocrine tumors., Objective: To report the phenotype of 3 unrelated cases each with a unique germline CDKN1B variant (of which 2 are novel) and compare these cases with those described in the current literature., Design/methods: Three case studies, including clinical presentation, germline, and tumor genetic analysis and family history., Setting: Two tertiary University Hospitals in Sydney, New South Wales, and 1 tertiary University Hospital in Canberra, Australian Capital Territory, Australia., Outcome: Phenotype of the 3 cases and their kindred; molecular analysis and tumor p27kip1 immunohistochemistry., Results: Family A: The proband developed multiglandular primary hyperparathyroidism, a microprolactinoma and a multifocal nonfunctioning duodenopancreatic neuroendocrine tumor. Family B: The proband was diagnosed with primary hyperparathyroidism from a single parathyroid adenoma. Family C: The proband was diagnosed with a nonfunctioning pituitary microadenoma and ectopic Cushing's syndrome from an atypical thymic carcinoid tumor. Germline sequencing in each patient identified a unique variant in CDKN1B, 2 of which are novel (c.179G > A, p.Trp60*; c.475G > A, p.Asp159Asn) and 1 previously reported (c.374&#95;375delCT, p.Ser125*)., Conclusions: Germline CDKN1B pathogenic variants cause the syndrome MEN4. The phenotype resulting from the 3 pathogenic variants described in this series highlights the heterogenous nature of this syndrome, ranging from isolated primary hyperparathyroidism to the full spectrum of endocrine manifestations. We report the first described cases of a prolactinoma and an atypical thymic carcinoid tumor in MEN4., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: The MitraClip from Abbott is FDA approved intracardiac implantable device for transcatheter edge-to-edge repair (TEER). Despite a few previously published studies, there is limited safety data for its use in clinical practice, hence, we designed this study using data obtained from a safety nationwide database to demonstrate the safety profile of MitraClip., Methods: The first two of the five authors independently queried all reported adverse events from the United State Food and Drug Administration [FDA] Manufacturer and User Facility Device Experience [MAUDE] registry from January 2014 to December 2020. The primary end point was trend in reported fatal events obtained from this database. The secondary end points included the causes of reported nonfatal reports from the MAUDE registry. The trend of reported fatal events was assessed using the Cochran Armitage trend test over the period of the study., Results: During the study period, subjects included 3370 patients whose MitraClip-associated adverse events were reported and captured by MAUDE registry. Of these, 211 were fatal and 3159 nonfatal events. Fatal event reports resulted deaths and reported nonfatal events were from injuries and device system malfunction. This study demonstrated an initial upward trend from 2014 to 2015 then a subsequent statistically significant downward trend in reported fatal events from 2015 to 2020 (Cochran-Armitage test P = 0.039). The peak proportion of reported fatal events occurred in 2015, (n = 44; representing 1.25% of reported adverse events) and lowest proportion of reported fatal events took place in 2020 (n = 19; representing 0.56% of reported adverse events). The most reported nonfatal events were from malfunctioning of MitraClip system (n = 1170; representing 37% of reported nonfatal events), new unremarkable repolarization abnormalities on periprocedural EKG (n = 864; representing 27% of reported nonfatal events), leaflet rupture (n = 651; representing 21% of reported nonfatal events), and cardiogenic shock (n = 170; representing 5% of reported nonfatal events)., Conclusions: This analysis of the MAUDE Registry indicated, especially within the confines of this study's limitations and poor data quality of information, an apparent downward trend of reported fatal events over the study period. Even though conclusive attributions cannot be made regarding this important finding, perhaps, this points to early evidence of a potential institutional or operator learning curve with this device. However, in view of the inferior quality of the data accrued from the MAUDE Registry, more high-precision studies are needed to better understand these changes, as the utility of MitraClip, becomes more established in clinical practice., Competing Interests: Declaration of competing interest This is to state that the Author of this Manuscript titled “Adverse Events Following Transcatheter Mitral Valve Repair using MitraClip: Lessons learned from the Manufacturer and User Facility Device Experience (MAUDE) Registry” have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Heller myotomy (HM) remains the gold standard procedure for achalasia. The addition of different types of fundoplication to HM has been debated in several studies. Given the contradictory reports, this meta-analysis was undertaken to compare different outcomes after HM and HM with fundoplication (HMF)., Methods: An electronic search was performed among five major databases (PubMed, Ovid, Scopus, Cochrane Library, Google Scholar) from inception to October 2019, identifying all randomised and non-randomised studies comparing HM with HMF. Two authors searched electronic databases using the keywords 'achalasia' AND 'dysphagia' AND 'gastroesophageal reflux' and all data were pooled for random-effects meta-analysis. The primary and secondary outcomes were gastroesophageal reflux and dysphagia, respectively., Results: A total of six studies were included and involved 576 patients comparing HM and HMF. There was no statistically significant difference between gastroesophageal reflux in the HM vs HMF group (21.3% vs 22.9%, RR 1.32, 95% CI 0.60-2.88, p  = 0.49). There was a slightly higher incidence of dysphagia observed in HM vs HMF (14.8% vs 10.8%, RR 1.54, 95% CI 0.98-2.41, p  = 0.06)., Conclusions: There was no statistically significant difference in long-term outcomes between a group of patients undergoing HM and a group who underwent HM with fundoplication.

Background: Choosing the correct Endotracheal tube (ETT) size is important in paediatric patients because an inappropriately large and small sized tube has its own disadvantages and chances of re-intubation with different size tube is high. The currently available modalities do not reflect the actual tracheal diameter for selection of endotracheal tube. Ultrasonography (USG) guided evaluation of transverse diameter at subglottic region may be helpful to estimate the proper size of ETT. We tested the hypothesis that Ultrasound guided subglottic diameter better predicts optimal ETT size than existing methods., Aims: To predict the appropriate size of ETT in pediatric patients to avoid multiple attempts of intubation and airway edema using simple noninvasive USG-guided methods., Settings and Design: Design: Prospective study., Settings: Tertiary care hospital., Materials and Methods: Institutional ethical committee clearance no. BMCRI/PS/138/2020-21 was taken. Laryngoscopy and endotracheal intubation were done in 27 pediatric patients of age 2-15 years using a predetermined-sized ETT, estimated by ultrasonography. ETT size was considered optimal when the cuff leak test was negative. If there was resistance to ETT passage into the trachea, the tube was exchanged with one that was 0.5 mm smaller. If the cuff leak test was positive, then the ETT was exchanged for one with the 0.5-mm larger tube. The comparison was done between the size of ETT calculated by USG-guided subglottic diameter, age, height-related formulas, and clinical methods to look for accuracy of prediction for proper ETT size after cuff leak test., Statistical Analysis: The data collected were entered into Microsoft Excel and analyzed using SPSS version 22. IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Appropriate parametric and nonparametric tests were applied wherever necessary., Categorical Data: Represented in the form of frequencies and proportions. Continuous data: Represented as mean and standard deviation. Paired sample test: Test to identify the mean difference between two quantitative variables. Kappa statistics: To measure the level of agreement., Results: A total of 27 children of age between 2 and 15 years were selected, out of which 15 were male and 12 were female. The accuracy of predicting appropriate ETT size is greater in ultrasound-guided subglottic diameter when compared to conventional clinical assessment and age- and height-related formula and almost the same accuracy as the clinical method., Conclusion: Ultrasound-guided subglottic diameter is an easy, effective, and noninvasive way of predicting accurate ETT size in the pediatric population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Anesthesia: Essays and Researches.)

Background and Objective: Inhalational challenge with dry mannitol powder may potentially induce cough by two mechanisms: airway bronchoconstriction or laryngeal irritation. This prospective observational study investigated laryngeal and bronchial components of cough induced by mannitol challenge., Methods: We recruited consecutive patients referred for clinical mannitol challenge. The Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) was administered. Throughout testing, coughs were audio-recorded to derive a cough frequency index per time and dose of mannitol. Relationships between cough indices, laryngeal hypersensitivity and bronchial hyperresponsiveness (BHR) were examined. Participants were classified by cough characteristics with k-means cluster analysis., Results: Of 90 patients who underwent challenge, 83 completed both the questionnaire and challenge. Cough frequency was greater in patients with abnormal laryngeal hypersensitivity (p = 0.042), but not in those with BHR. There was a moderate negative correlation between coughs per minute and laryngeal hypersensitivity score (r = -0.315, p = 0.004), with lower LHQ scores being abnormal. Cluster analysis identified an older, female-predominant cluster with higher cough frequency and laryngeal hypersensitivity, and a younger, gender-balanced cluster with lower cough frequency and normal laryngeal sensitivity., Conclusion: Cough frequency during mannitol challenge in our cohort reflected laryngeal hypersensitivity rather than BHR. Laryngeal hypersensitivity was more often present among older female patients. With the incorporation of cough indices, mannitol challenge may be useful to test for laryngeal hypersensitivity as well as BHR., (© 2021 Asian Pacific Society of Respirology.)

Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 years using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2 , TP53 , RB1 , and PTEN , resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression; however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses., (© 2019 McCabe et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: Hypophysitis develops in up to 19% of melanoma patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may avert life-threatening hypopituitarism. We aimed to assess the incidence of ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre, and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring could predict IH onset., Methods: We performed a retrospective cohort study of ipilimumab-treated patients at a quaternary melanoma referral centre in Australia. The inclusion criteria were patients with metastatic or unresectable melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements prior to ≥ 2 infusions. The main outcomes were IH incidence and TSH and cortisol patterns in patients who did and did not develop IH., Results: Of 78 ipilimumab-treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a median duration of 13.0 weeks (range 7.7-18.1) following ipilimumab initiation. All patients whose TSH fell ≥ 80% compared to baseline developed IH, and, in 5/9 patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4 TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P = 0.006). TSH fall was detected at a median time of 9.2 (range 7.7-16.4) weeks after commencing ipilimumab, and a median of 3.6 (range of - 1.4 to 9.7) weeks before IH diagnosis. There was no difference in TSH between the groups before cycles 1-3 or in cortisol before cycles 1-4., Conclusions: TSH fall ≥ 80% may be an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an inexpensive tool to expedite IH diagnosis.

Measurement of 24-h urine-free cortisol is frequently employed as a first-line screening and disease-monitoring test in Cushing's syndrome (CS). The quest for 'cortisol specificity' has seen the emergence of mass spectrometry (MS) based assays, particularly liquid chromatography/tandem mass spectrometry. In contrast to traditional immunoassays, liquid chromatography/tandem mass spectrometry 'free cortisol' measurement is less susceptible to 'interference' from cortisol precursors and metabolites. However, detection of these conjugates is important in mild CS and therefore, missed by MS if cortisol alone is measured. MS assays nevertheless are capable of measuring broad steroid profiles, including the potential to distinguish benign from malignant adrenal-based CS and detection of exogenous glucocorticoids. Until this is routine practice, we recommend against abandoning immunoassays measurement of urine-free cortisol.

Genomic insights and analyses of Mendelian hypertension (HTN) syndromes and Genome-Wide Association study (GWAS) on essential hypertension have contributed to the depth of understanding of the genetics origins of hypertension. Mendelian syndromes are important for the field, since such knowledge leads to specific insights about disease pathogenesis and the potential for precision medicine. The clinical impact of findings of on essential hypertension is continuously evolving, and the insights accrued will refine efforts to combat the societal impact of hypertension. Comprehensive identification of all genomic variants of hypertension, along with their individual associated mechanisms, is paving the way forward in the era of personalized medicine. The overriding challenge for care providers is to reduce health inequities through improved compliance and, perhaps, new paradigms for implementation science that incorporate genomic medicine., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The optimal treatment of diabetes in pregnancy requires accurate measurement of blood glucose levels, in order to minimize adverse outcomes for both mother and neonate. Self-monitoring of blood glucose is routinely used to measure glycemic control and to assess whether treatment targets are being met; however, the accuracy of blood glucose meters in pregnancy is unclear., Materials and Methods: Pregnant women with gestational, type 1, or type 2 diabetes mellitus were eligible to participate. Nonfasting capillary blood glucose levels were measured in duplicate using the BGStar(®) (Sanofi, Sydney, Australia) and FreeStyle Lite(®) (Abbott, Sydney) blood glucose meters. Venous blood samples were collected and analyzed for plasma glucose, hematocrit, and glycated hemoglobin. Capillary blood glucose was compared with plasma glucose and further assessed according to International Organization for Standardization (ISO) 15197:2013 standards., Results: One hundred ten women were recruited, providing 96 samples suitable for analysis. The mean ± SD laboratory plasma glucose level was 4.6 ± 1.4 mmol/L; the BGStar and FreeStyle Lite capillary blood glucose values were 5.3 ± 1.4 mmol/L and 5.0 ± 1.3 mmol/L, respectively. Both meters showed a positive bias (0.42 mmol/L for the FreeStyle Lite and 0.65 mmol/L for the BGStar). Furthermore, neither meter fulfilled the ISO 15197:2013 standards, and there was a nonsignificant improvement in meter performance at blood glucose levels of ≤4.2 mmol/L. Hematocrit did not affect the results of either blood glucose meter. Clarke Error Grid analysis demonstrated that approximately 70% of the results of both meters would lead to appropriate clinical action., Conclusions: The BGStar and FreeStyle Lite blood glucose meters did not meet ISO 15197:2013 recommendations for blood glucose monitoring systems when assessed in a population of women with diabetes in pregnancy. Clinicians should consider this difference in blood glucose readings when making diabetes-related treatment decisions.

Aims: To establish current acute seizure management through a review of clinical practice guidelines (CPGs) and reported physician management in the 11 largest paediatric emergency departments in Australia (n= 9) and New Zealand (n= 2) within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network, and to compare this with Advanced Paediatric Life Support (APLS) guidelines and existing evidence., Methods: (i) Review of CPGs for acute seizure management at PREDICT sites. (ii) A standardised anonymous survey of senior emergency doctors at PREDICT sites investigating management of status epilepticus (SE)., Results: Ten sites used seven different seizure CPGs. One site had no seizure CPG. First line management was with benzodiazepines (10 sites). Second line and subsequent management included phenytoin (10), phenobarbitone (10), thiopentone (9), paraldehyde (6) and midazolam infusion (5). Of 83 available consultants, 78 (94%) responded. First line management of SE without intravenous (IV) access included diazepam per rectum (PR) (49%), and midazolam intramuscular (41%) and via the buccal route (9%). First line management of SE with IV access included midazolam IV (50%) and diazepam IV (44%). The second line agent was phenytoin (88%); third line agents were phenobarbitone (33%), thiopentone and intubation (32%), paraldehyde PR (22%) and midazolam infusion (6%). Fourth line agents were thiopentone and intubation (60%), phenobarbitone (16%), midazolam infusion (13%) and paraldehyde (9%)., Conclusions: Initial seizure management by CPG recommendations and reported physician practice was broadly similar across PREDICT sites and consistent with APLS guidelines. Practice was variable for second/third line SE management. Areas of controversy would benefit from multi-centred trials.

Objective: Comparison of clinical practice guideline (CPG) recommendations and reported physician management of gastro-enteritis at Paediatric Research in Emergency Departments International Collaborative (PREDICT) network sites as a baseline for further randomised controlled trials., Methods: Two part survey comprising: (i) review of CPGs from PREDICT sites for gastro-enteritis; and (ii) survey of senior emergency department physicians regarding the management of gastro-enteritis., Results: All 11 PREDICT sites participated. Nine CPGs were available with three sites using a common CPG. For moderate dehydration, eight CPGs advocated nasogastric (NG) rehydration in preference to intravenous (IV) rehydration. The IV route was reserved for severe dehydration or failed NG rehydration. In the second component of the survey, 78 of 83 (94%) physicians responded. In moderate dehydration, 82% of respondents used NG rehydration. In severe dehydration, 86% used IV fluids; 12% used NG and 3% an initial IV bolus followed by NG fluid. Serum electrolytes were measured universally with IV fluid use and by 22% using NG rehydration. The IV fluid bolus was with normal saline (86%). Fifty-four per cent used anti-emetics 'rarely' or 'sometimes'. The commonest agents were ondansetron (60%) and metoclopramide (29%)., Conclusions: CPG recommendations and physician practice for the management of gastro-enteritis were similar across PREDICT sites with a focus on NG for moderate dehydration and IV for severe dehydration. A variety of fluids and administration rates were used. Anti-emetics were used infrequently. The efficacy and safety of newer anti-emetics should be explored in collaborative studies. Collaborative development of new CPGs should be considered to simplify fluid regimens.

Objectives: Bronchiolitis is the most frequent reason for admission in infants. We set out to compare clinical practice guideline (CPG) recommendations and physician management of bronchiolitis at Paediatric Research in Emergency Departments International Collaborative (PREDICT) sites in Australia and New Zealand as a baseline for prospective trials., Methods: (i) Review of bronchiolitis CPGs from PREDICT sites. (ii) Survey of senior pediatric emergency physicians at PREDICT sites to determine management strategies in bronchiolitis., Results: All 11 PREDICT sites participated. Ten sites used a specific bronchiolitis CPG. beta-agonists were not recommended unless the child was older or asthma was suspected. Eight sites did not and 2 sites only recommended corticosteroids for older infants in whom asthma was likely. For rehydration, 7 sites recommended intravenous (i.v.) fluids exclusively or in the acute phase, with 3 recommending nasogastric (n.g.) fluids in the recovery phase or for difficult vascular access. Two sites recommended n.g. fluids for moderate and i.v. fluids for severe bronchiolitis. Physician response rate was 78/83 (94%). No medications were used for mild (94%) or moderate (83%) bronchiolitis. Inhaled beta-agonists were used by 5% for moderate and 18% for severe bronchiolitis. Steroids were not used by any physicians for mild or moderate and was used by only 3% for severe bronchiolitis. The preferred mode of rehydration was i.v. in 45%, n.g. in 49%, and either one depending on disease severity in 6%., Conclusions: Management of bronchiolitis was similar across PREDICT sites. Practice is equally split between i.v. and n.g. rehydration. This reflects a lack of evidence which should be addressed through a multicenter comparative trial.

Objective: Comparison of clinical practice guideline (CPG) recommendations and reported physician management of croup at PREDICT (Paediatric Research in Emergency Departments International Collaborative) sites as baseline for planned randomized controlled trials., Methods: Review of CPGs for croup from PREDICT sites and survey of specialist pediatric emergency physicians regarding croup management. PREDICT sites included 8 tertiary pediatric hospitals and 3 large mixed emergency departments in Australia and New Zealand., Results: Nine of the 11 sites had a CPG for croup. Response rate was 94% (78/83). Adrenaline was recommended for moderate croup (3%), severe croup (52%), and life-threatening croup by (100%). Steroid therapy was recommended for mild croup (45%), for moderate croup (97%), for severe croup (97%), and for life-threatening croup (96%). Steroid choice was oral dexamethasone (60%) and oral prednisolone (38%). In severe croup, 77% used intravenous/intramuscular dexamethasone, 10% used intravenous/intramuscular methylprednisolone, and 8% used nebulized budesonide. Commonest dosage regimens were 0.15 mg/kg dexamethasone or 1 mg/kg prednisolone. A standard volume dosage regimen for nebulized adrenaline was used by 54%, whereas 39% used a weight-based formula. Clinical practice guidelines recommended 5 mg (11%) or 10 mg (33%) for standard volume dosing, and all CPGs using weight-based dosing recommend 0.5 mg/kg with maximum doses ranging from 5 to 15 mg., Conclusions: Croup management at PREDICT emergency departments is similar, based on oral steroids and nebulized adrenaline. The steroid and adrenaline regimens used by respondents and their CPGs were not consistent. This reflects limitations of available evidence for management of this common disease, highlighting the need for definitive trials, particularly in the management of mild croup.

Objectives: To compare clinical practice guideline (CPG) recommendations and reported physician management of acute paediatric asthma in the 11 largest paediatric emergency departments, all of which have CPGs, in Australia (n = 9) and New Zealand (n = 2). All 11 sites participate in the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network., Methods: (a) A review of CPGs for acute childhood asthma from all PREDICT sites. (b) A standardised anonymous survey of senior emergency doctors at PREDICT sites investigating management of acute childhood asthma., Results: CPGs for mild to moderate asthma were similar across sites and based on salbutamol delivery by metered dose inhaler with spacer and oral prednisolone. In severe to critical asthma, differences between sites were common and related to recommendations for: ipratropium use; metered-dose inhaler versus nebulised delivery of salbutamol in severe asthma; use of intravenous aminophylline, intravenous magnesium and dosing of intravenous salbutamol in critical asthma. The questionnaire (78 of 83 doctors responded) also revealed significant differences between doctors in the treatment of moderate to severe asthma. Ipratropium was used for moderate asthma by 42%. For severe to critical asthma, nebulised delivery of salbutamol was preferred by 79% of doctors over metered dose inhalers. For critical asthma, doctors reported using intravenous aminophylline in 45%, intravenous magnesium in 55%, and intravenous salbutamol in 87% of cases. Thirty-nine different dosing regimens for intravenous salbutamol were reported., Conclusions: CPG recommendations and reported physician practice for mild to moderate paediatric asthma management were broadly similar across PREDICT sites and consistent with national guidelines. Practice was highly variable for severe to critical asthma and probably reflects limitations of available evidence. Areas of controversy, in particular the comparative efficacy of intravenous bronchodilators, would benefit from multi-centre trials. Collaborative development of CPGs should be considered.

The influence of alpha 2-adrenoceptor antagonists in animal models of anxiety is quite inconsistent, with results spanning the full range of effect from anxiogenesis to anxiolysis. In the present study, an ethological technique was used to examine the effects of yohimbine (0.5-4.0 mg/kg) on plus-maze behaviour in DBA/2 mice. Results indicated significant anxiolytic-like effects on standard spatiotemporal measures at 2.0-4.0 mg/kg, and on risk assessment measures across the entire dose range. Full-scale follow-up studies with T1 and BALB/c strains confirmed that this action of yohimbine in the murine plus-maze is not peculiar to DBA/2 mice. The more selective alpha 2-adrenoceptor antagonist, idazoxan (0.63-5.0 mg/kg), exerted much weaker behavioural effects in the maze while the alpha 2-adrenoceptor agonist, clonidine (0.01-0.1 mg/kg), produced a profile consistent with non-specific behavioural disruption. Data are discussed in relation to the possible involvement of 5-HT1A receptor mechanisms in the observed anxiolytic-like effects of yohimbine in the murine plus-maze.