Midazolam-Induced Hiccups Reversed by Flumazenil: A Case Report.

Hiccups are a common phenomenon experienced by many people and are usually short-lived with spontaneous resolution of symptoms. Certain anesthetic medications have been associated with the development of hiccups, though the underlying pathophysiology and reflex arcs remain poorly understood. We describe a patient who developed hiccups lasting 9 days following an orthopedic surgery and again developed hiccups during a subsequent surgery after only having received midazolam; flumazenil administration led to sustained cessation of his hiccup symptoms immediately.

Parameters of cardiac symptoms in young athletes using the Heartbytes database.

Introduction: To determine clinical parameters that are related to abnormal cardiac symptoms in physically active youth. Methods: We used Simon's Heart Heartbytes National Youth Cardiac Registry to collect data from adolescent athletes in southeastern Pennsylvania. We collected age, race/ethnicity, abnormal cardiac symptoms, medical history, medication use, caffeine intake, and family history. We obtained height, weight, blood pressure, cardiac murmur findings, and ECGs. Echocardiogram was obtained if necessary. Binary logistic regression analysis was performed to identify independent associations between abnormal cardiac symptoms and collected variables. The odds ratio (OR), 95% confidence interval (95% CI), and p-values were used as statistical values. Results: Of the 887 athletes (543 males and 344 females, age = 16.9 ± 2.1 years, height = 166.9 ± 11.4 cm, weight = 62.0 ± 16.0 kg), 186 (21%) had abnormal cardiac symptoms including chest pain, passing out, difficulty breathing, extreme fatigue, and heart race. There was an independent association between abnormal symptoms and a past medical history (OR: 4.77, 95%CI: 3.18, 7.17, p = 0.001) and medication use (OR: 1.74, 95%CI: 1.08, 2.79, p = 0.022). In medical history, young athletes with asthma showed a greater propensity of abnormal cardiac symptoms (48.9%) compared to young athletes without (14.0%, p = 0.001). Additionally, young athletes with anxiety or depression demonstrated a higher proportion of abnormal cardiac symptoms (48.9%) than those without (19.5%, p = 0.001). Although the association between the presence of abnormal symptoms and African-American race (OR: 2.04, 95%CI: 0.96, 4.35, p = 0.065) and average daily consumption of at least 2 caffeine drinks (OR: 2.08, 95%CI: 0.86, 5.02, p = 0.103) were not significant, there was a trend to reach the a priori significance level. Conclusions: This study identified several clinical parameters that are associated with symptoms suggestive of abnormal cardiac conditions. Larger studies need to be done to better sort out the clinical history that may contribute to false positives to further reduce false positives at heart screenings.

Living Donor Liver Transplantation in a Paediatric Patient With Citrullinaemia Type 2.

Citrullinaemia is a urea cycle defect that results from a deficiency of the enzyme arginosuccinate synthetase. Type 1 disease is diagnosed in childhood, whereas type 2 disease is adult onset. But, we report the outcome in a boy (13 years) with citrullinaemia type 2 who received a live donor liver transplant (LDLT) at our centre. One advantage of LDLT over deceased donor liver transplantation is the opportunity to schedule surgery, which beneficially affects neurological consequences. In conclusion, transplantation should be considered to be the definitive treatment for citrullinaemia type 2 at this stage, although some issues remain unresolved.

Physician adherence to 'Seattle' and 'International' ECG criteria in adolescent athletes: An analysis of compliance by specialty, experience, and practice environment.

BACKGROUND: Screening electrocardiography (ECG) for athletes is both controversial and rapidly evolving. While identifying an abnormal ECG could detect a serious cardiovascular disease, falsely interpreting a benign ECG pattern as abnormal can lead to unnecessary testing, cost, and anxiety. Though recent refinements of athlete screening ECG criteria have significantly improved its accuracy, in clinical practice physician adherence to these criteria may vary. METHODS: We analyzed physician adherence to contemporary athlete ECG criteria in a large, national athlete screening registry. 1577 consecutive screening ECGs were independently re- interpreted to assess for physician adherence to Seattle Criteria or International Criteria, respective to the criteria in place when the screening was performed. We further determined the most common ECG interpretations that deviated from these criteria, and analyzed physician characteristics for independent predictors of adherence to published ECG criteria. RESULTS: Though overall adherence to contemporary criteria was high, 60.4% of ECGs interpreted as abnormal did not meet athlete ECG criteria for pathology when independently re- read. The most common ECG patterns misinterpreted as abnormal were isolated left ventricular hypertrophy (LVH) and non-pathologic T-wave inversions (TWI). Multivariate regression identified three independent predictors of adherence to athlete ECG criteria: participating in a screening overseen by the organization's medical leadership, electrophysiology specialists and adult cardiologists. CONCLUSION: This study highlights the need for quality control measures and continued clinician education in a controversial and rapidly evolving field. Clinician education for athlete screening ECG criteria should emphasize the recent changes in how TWI and LVH voltage criteria should be interpreted in this patient population.

Potential Impact of the Proposed Revised UNOS Thoracic Organ Allocation System.

The current United States heart allocation system faces 2 main challenges: an evolving landscape of device therapy in advanced heart failure and a rapidly increasing transplant waiting list. The proposed new heart allocation system involves expansion of the 3 tiers and enables greater distinction between different types of mechanical circulatory support devices. In this review, we discuss how the proposed revision reconciles key concerns of the current system to create a more fair and equitable allocation of hearts in the United States.

Intraoperative thermographic imaging to assess myocardial distribution of Del Nido cardioplegia.

We describe the intraoperative non-invasive use of an infrared (IR) camera to monitor Del Nido cardioplegia delivery in patients undergoing cardiac surgery. Thermal pictures were taken pre- and post-cardioplegia and at timed points after arrest, and compared to readings from a transseptal temperature probe. There was good concordance between the transseptal probe and the IR camera temperature readings. This non-invasive technique, which assesses cardioplegic distribution, may help to determine when additional doses of Del Nido cardioplegia are required during periods of cardioplegic arrest.

Assessment of Proliferative Potential of Odontogenic Keratocyst and Dentigerous Cyst using Podoplanin: An Immunohistochemical Study.

INTRODUCTION: Odontogenic cysts are commonly encountered lesions among head and neck pathologies. Odontogenic keratocyst (OKC) has unique features of recurrence and local aggressiveness. Podoplanin (PDP) is a lymphatic endothelial marker and is shown to be expressed in a variety of tissues. Hence, we planned to assess the significance of PDP in OKC and dentigerous cyst (DC). MATERIALS AND METHODS: The present study included assessment of immunoexpression of PDP in OKC and DC. Twenty specimens each of OKC and DC were included in the present study and were stained with D2-40 antibody. All the sections were analyzed and were categorized as negative staining, weakly positive staining, and strongly positive staining. All the results were analyzed by Statistical Package for the Social Sciences (SPSS) software. RESULTS: We detected PDP-positive staining in the cell membrane and cytoplasm of the cells of basal cell layer and supra-basal cell layers. In DC cases, we observed positive staining only in cases associated with inflammation. CONCLUSION: Podoplanin does play a significant role in enhancing the local invasive and neoplastic properties of OKC. CLINICAL SIGNIFICANCE: Podoplanin expression in OKC is potentially associated with moderate invasive nature of the neighboring structures.

Arterioenteric Fistulae Due to Pseudoaneurysms of the Right Common Iliac and Splanchnic Vessels Presenting as Upper GI Bleed.

Arterial pseudoaneurysms are relatively rare complications of the vascular system. Many cases may remain asymptomatic for a lifetime only to be discovered incidentally, whereas others may cause fatal hemorrhage. Majority of cases present with local compressive symptoms. Rarely, it has been implicated as an etiology for gastrointestinal (GI) bleed by eroding into an adjacent bowel, with splanchnic pseudoaneurysm being more commonly responsible as compared to peripheral ones. Although rare, they are an important consideration because of the high mortality rate. They require a high index of suspicion with prompt diagnosis and expedient treatment, either surgical or endovascular. In this study, we report a case series of a right iliacoduodenal and 2 splanchnic pseudoaneurysms presenting as upper GI bleeding. These 3 cases presented with occult source of hematemesis due to the formation of arterioenteric fistula. Also discussed are the diagnostic approach used and successful treatment methods, which included placing endoprosthesis in the aorta and common iliac artery and endovascular coiling for respective cases. To the best of our knowledge, such a case of common iliac pseudoaneurysm presenting with massive hematemesis due to fistulization into duodenum has never been reported previously.

Life-threatening upper gastrointestinal bleeding due to gastric Dieulafoy's lesion: Successful minimally-invasive management.

Dieulafoy's lesion (DL) is a relatively rare, but potentially life-threatening condition. It accounts for 1-2% of acute gastrointestinal bleedings. Its serious nature makes it necessary for early diagnosis and treatment. This is a case report of a patient who presented with life-threatening haematemesis due to gastric Dieulafoy's that was successfully treated laparoscopically after failed endotherapy.

Cryo-EM Analysis of the Conformational Landscape of Human P-glycoprotein (ABCB1) During its Catalytic Cycle.

The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug pharmacokinetics and contributing to the development of multidrug resistance. Structural information about the conformational changes in human P-gp during the ATP hydrolysis cycle has not been directly demonstrated, although mechanistic information has been inferred from biochemical and biophysical studies conducted with P-gp and its orthologs, or from structures of other ATP-binding cassette transporters. Using single-particle cryo-electron microscopy, we report the surprising discovery that, in the absence of the transport substrate and nucleotides, human P-gp can exist in both open [nucleotide binding domains (NBDs) apart; inward-facing] and closed (NBDs close; outward-facing) conformations. We also probe conformational states of human P-gp during the catalytic cycle, and demonstrate that, following ATP hydrolysis, P-gp transitions through a complete closed conformation to a complete open conformation in the presence of ADP.

Mechanical Cardiopulmonary Resuscitation In and On the Way to the Cardiac Catheterization Laboratory.

Cardiac arrest, though not common during coronary angiography, is increasingly occurring in the catheterization laboratory because of the expanding complexity of percutaneous interventions (PCI) and the patient population being treated. Manual chest compression in the cath lab is not easily performed, often interrupted, and can result in the provider experiencing excessive radiation exposure. Mechanical cardiopulmonary resuscitation (CPR) provides unique advantages over manual performance of chest compression for treating cardiac arrest in the cardiac cath lab. Such advantages include the potential for uninterrupted chest compressions, less radiation exposure, better quality chest compressions, and less crowded conditions around the catheterization table, allowing more attention to ongoing PCI efforts during CPR. Out-of-hospital cardiac arrest patients not responding to standard ACLS therapy can be transported to the hospital while mechanical CPR is being performed to provide safe and continuous chest compressions en route. Once at the hospital, advanced circulatory support can be instituted during ongoing mechanical CPR. This article summarizes the epidemiology, pathophysiology and nature of cardiac arrest in the cardiac cath lab and discusses the mechanics of CPR and defibrillation in that setting. It also reviews the various types of mechanical CPR and their potential roles in and on the way to the laboratory. (Circ J 2016; 80: 1292-1299).

Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery.

Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near-atomic resolution structures for well-ordered protein complexes with sizes ≥ ∼200 kDa. Whether cryo-EM methods are equally useful for high-resolution structural analysis of smaller, dynamic protein complexes such as those involved in cellular metabolism remains an important question. Here, we present 3.8 Å resolution cryo-EM structures of the cancer target isocitrate dehydrogenase (93 kDa) and identify the nature of conformational changes induced by binding of the allosteric small-molecule inhibitor ML309. We also report 2.8-Å- and 1.8-Å-resolution structures of lactate dehydrogenase (145 kDa) and glutamate dehydrogenase (334 kDa), respectively. With these results, two perceived barriers in single-particle cryo-EM are overcome: (1) crossing 2 Å resolution and (2) obtaining structures of proteins with sizes < 100 kDa, demonstrating that cryo-EM can be used to investigate a broad spectrum of drug-target interactions and dynamic conformational states.

2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition.

p97 is a hexameric AAA+ adenosine triphosphatase (ATPase) that is an attractive target for cancer drug development. We report cryo-electron microscopy (cryo-EM) structures for adenosine diphosphate (ADP)-bound, full-length, hexameric wild-type p97 in the presence and absence of an allosteric inhibitor at resolutions of 2.3 and 2.4 angstroms, respectively. We also report cryo-EM structures (at resolutions of ~3.3, 3.2, and 3.3 angstroms, respectively) for three distinct, coexisting functional states of p97 with occupancies of zero, one, or two molecules of adenosine 5'-O-(3-thiotriphosphate) (ATPγS) per protomer. A large corkscrew-like change in molecular architecture, coupled with upward displacement of the N-terminal domain, is observed only when ATPγS is bound to both the D1 and D2 domains of the protomer. These cryo-EM structures establish the sequence of nucleotide-driven structural changes in p97 at atomic resolution. They also enable elucidation of the binding mode of an allosteric small-molecule inhibitor to p97 and illustrate how inhibitor binding at the interface between the D1 and D2 domains prevents propagation of the conformational changes necessary for p97 function.

Evaluation of knowledge and experience among oral and maxillofacial surgeons about cardiopulmonary resuscitation.

OBJECTIVE: This study was undertaken to assess the level knowledge and experience about CPR among oral and maxillofacial surgeons. MATERIALS AND METHODS: In a cross-sectional study, a total of 96 professionals (31-PGs, 65-MDS staff) were surveyed using a self-administered structured questionnaire pretested through a pilot survey. The data was analyzed using the SPSS version 15.0. The Student's t-test and ANOVA test were used as test of significance. The level of significance was set at p ≤ 0.05. RESULTS: In the present study, 78% of oral surgeons had received training about CPR but only 52.0% have proper practical knowledge of performing it. As there were some cases due to CPA in dental practice even then half of the participants take history of patients regarding this. A significant difference was found according to designation with PGs having lower mean scores. A positive linear correlation was found between years of experience and knowledge about CPR (Pearson's correlation, r = 0.613, p = 0.00). CLINICAL SIGNIFICANCE: The present findings showed that practical knowledge of performing CPR is still low and half of them still do not take history regarding this. So there is need for more knowledge about CPR through CDE programs.