Acute Decompensated Heart Failure in the Elderly: An Observational Study in a Regional Victorian Hospital.

Objective This study aimed to evaluate the frequency, triggers, clinical management, and outcomes of acute decompensated heart failure (ADHF) episodes in the elderly population of a regional Victorian town, along with analysing long-term outcomes, including rehospitalization rates, functional status, and mortality. Methods In this single-centre retrospective study, approved by the Research Governance Unit of Goulburn Valley Health, we analysed data from patients over 65 years of age discharged with a primary diagnosis of heart failure (HF) between July 2022 and June 2023. The study included 174 episodes from 148 patients, examining demographic and clinical profiles, investigations, outcome measures, and hospital admission risk program (HARP) involvement. Results The study highlighted a high prevalence of heart failure with preserved ejection fraction (HFpEF), especially in patients over 85 years. No significant association between sex and ejection fraction categories was observed. The average length of stay was 5.9 days, with longer stays noted for females. Non-invasive ventilation emerged as a significant predictor of extended hospitalization. A 30-day readmission rate of 6.67% was noted, lower than some existing studies. Conclusion The findings underscore the complexity of ADHF management in the elderly, suggesting the need for region-specific, gender-focused strategies and indicating the potential benefits of enhanced HARP program engagement. These insights contribute to a nuanced understanding of HF management in elderly populations in regional settings.

Understanding the Clinical Profile and Hospitalisation Patterns of Residents From Aged Care Facilities: A Regional Victorian Hospital Study.

Introduction Residents of residential aged care facilities (RACFs) are typically frailer than their community-dwelling counterparts. They often present to the emergency department (ED) with varied health issues, frequently leading to hospital admissions. These admissions can exacerbate patient frailty and strain the healthcare system. Despite global efforts to reduce ED presentations from RACFs, effective strategies still need to be discovered. This study examines the clinical profile and hospitalisation patterns of RACF residents in a regional Victorian town. Aims The study aimed to assess the prevalence of ED presentations and representations from RACFs, investigate the causes and outcomes of hospital admissions stemming from these presentations, and evaluate the prevalence of documented (advanced care directives) ACDs within this patient cohort. Methods Following ethical approval, we conducted a retrospective analysis of 467 ED presentations from 310 RACF patients admitted to Goulburn Valley Health's (GVH) ED from January to June 2022. We collected and examined data on demographics, ACD existence, ED presentation characteristics, and hospital admissions, classifying admission reasons into eleven groups. Statistical analysis was performed with GraphPad Prism and IBM SPSS, using inferential tests and logistic regression to assess readmission odds at a significance threshold of p<0.05. Results Our study encompassed 310 patients from multiple RACFs, yielding 467 ED presentations. These constituted 2.28% of total ED visits and 9.85% of those aged 65 and above. Most of the cohort were females (59.4%), aged between 79 and 91. About 98 patients presented multiple times, and 48.2% of presentations led to hospital admissions, with 6.2% of admitted patients succumbing during the hospital stay. A documented ACD was absent in 42.9% of the cohort. Statistically significant results include a correlation between male sex and an increased frequency of ED representations (p=0.0422) and a longer ED stay duration for admitted patients (p<0.0001). No significant associations were found between ACD presence and ED representations, ACD and sex, or between age and duration of stay in the ED. Age did not differ significantly among patients with single or multiple presentations or between patients with or without ACD. Regarding fall-related presentations, no significant sex-based difference in admission rates was found. The duration of stay between surgical and medical admissions was also statistically indifferent. Conclusion Our study highlights the significant utilisation of ED services by RACF residents, mainly males. The substantial percentage of these presentations resulting in hospital admissions underlines the critical nature of these visits. The absence of ACD in a significant portion of the cohort and the lack of its influence on the frequency of representations signal the need for further exploration. The results underline the ongoing challenge of meeting the complex healthcare needs of RACF residents and emphasise the importance of gender-specific interventions and efficient hospital utilisation strategies to optimise healthcare delivery in this population. Future studies should further investigate the underlying reasons for these findings to inform targeted strategies for reducing unnecessary ED visits and hospital admissions. Furthermore, fall-related presentations necessitate comprehensive ED assessments and integrated management approaches.

The Utilisation of Computed Tomography Pulmonary Angiography in a Regional Victorian Emergency Department.

BACKGROUND: Pulmonary embolism (PE) is a critical condition with various recognized risk factors. This study investigates these factors in a regional Australian population. AIMS: The primary aim is to examine the significance of traditional risk factors in the clinical decision to request a computed tomography pulmonary angiography (CTPA) scan for suspected PE within this population and assess the association between the timing of CTPA requests (office vs. after-hours) and PE occurrence. METHODS: In this single-center retrospective study, we analyzed data from 434 patients undergoing CTPA at Goulburn Valley Health's (GVH) emergency department (ED) between January and August 2022. Covariates included age, clinical indications, and medical background. Statistical tests were applied with a p-value <0.05 indicating significance. RESULTS: Pulmonary embolism was diagnosed in 39 (20.9%) males and 17 (6.9%) females, with a mean age of 65.04 years (SD: 16.11). Univariate regression indicated a positive association between age and PE. Multivariate analysis showed a significant positive association for unilateral lower limb (LL) swelling/deep vein thrombosis (DVT) (OR: 5.474, p=0.003) and a significant negative association for being female (OR: 0.308, p<0.001). Variables such as shortness of breath, tachycardia, syncope, and chest pain were not significantly associated with PE. No association was found between CTPA request time and PE (χ²=0.9535, df=1, p=0.3288). CONCLUSION: Increasing age and unilateral LL swelling/DVT are significantly associated with PE. Some signs and symptoms showed negative or positive odds but were not statistically significant. The timing of CTPA requests did not correlate with PE incidence.

Comparisons of pathologic findings and outcomes of gastric cancer patients younger and older than 40: a propensity score matching study in a single center of Korea.

Background and Aim: Gastric cancer (GC) is one of the most common cancers worldwide, with a high incidence rate in Korean men. However, comparative studies are scarce on the pathologic findings and treatment effects of GC in patients aged less than 40 years. We evaluated the characteristics and pathologic findings of GC patients aged younger and older than 40 years. Methods: We retrospectively analyzed 2307 patients diagnosed with GC between January 2010 and May 2018. Eighty-eight (3.8%) and 2219 (96.2%) patients were younger and older than 40 years, respectively. The patients were divided into younger (n = 70) and older (n = 62) age groups through propensity matching. Results: Overall, compared to the younger group, the older group (n = 2219) had a significantly higher proportion of male patients (66.7% vs 39.8%; P < 0.001) and patients who underwent endoscopic submucosal dissection (ESD) (2.3% vs 23.1%; P < 0.001). However, young patients more often underwent operations compared to older patients (78.4% vs 60.1%; P = 0.001). In the propensity-matched group, older patients more often showed differentiated carcinoma, including well-differentiated (5.7% vs 11.3%) and moderately differentiated (1.4% vs 32.3%). However, younger patients more often showed signet ring cell carcinoma (SRC) (70.0% vs 25.8%). In multivariate analysis, Helicobacter pylori infection (odds ratio, 12.643; 95% confidence interval, 1.068-1449.665; P = 0.044) independently correlated with SRC risk. Conclusions: Patients below 40 years were more likely to undergo surgery compared to ESD, and pathologic findings were more common in SRC. Therefore, more active screening and H. pylori eradication are needed even in patients aged less than 40 years.

WICOX: Weight-Based Integrated Cox Model for Time-to-Event Data in Distributed Databases Without Data-Sharing.

To exploit large-scale biomedical data, the application of common data models and the establishment of data networks are being actively carried out worldwide. However, due to the privacy issues, it is difficult to share data distributed among institutions. In this study, we developed and evaluated weight-based integrated Cox model (WICOX) as a privacy-protecting method without sharing patient-level information across institutions. WICOX generates a weight for each institutional model and builds an integrated model of multi-institutional data based on these weights. WICOX does not require iterative communication until the centralized parameter converges. We performed experiments to show the weight characteristic of our algorithm based on 10 hospitals (2910 intensive care unit (ICU) stays in total) from the electronic intensive care unit Collaborative Research Database to predict time to ICU mortality with eight risk factors. Compared with the centralized Cox model, WICOX showed biases from 0 to 0.68E-2, from 0.00E-2 to 4.98E-2, and from 0.74E-2 to 1.7E-2 for time-dependent AUC, log hazard ratio, and survival rate, respectively. In addition, through simulation results using real 10 hospitals, WICOX showed robust results in accuracy under any composition of hospitals. The results of the experiments highlight that WICOX has robust characteristics and provides predictive performance and statistical inference results nearly the same as those of the centralized model. WICOX is a non-iterative method using the weight of institutional model for implementing the Cox model across multiple institutions in a privacy-preserving manner.

Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study).

AIM: To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. MATERIALS AND METHODS: In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). RESULTS: After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks. CONCLUSION: In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.

Efficacy of modified radical prostatectomy technique for recovery of urinary incontinence in high-grade prostate cancer.

BACKGROUND: This study was conducted to evaluate predictive factors of urinary continence recovery after radical prostatectomy (RP) for high-grade prostate cancer (PCa). METHODS: A total of 241 patients with high-grade (Gleason Score 8 or 9) PCa who underwent RP in a single Korean center between January 2011 and May 2018 were retrospectively reviewed. Urinary continence was defined as no pads use. Urinary continence was evaluated at 1, 3, 6, and 12 months after RP. Univariate and multivariate analyses were performed to determine the predictive factors of urinary continence recovery after RP. RESULTS: The mean age was 67.6±6.4 years, and the mean PSA was 18.7±21.1 ng/dL. A total of 197 (81.7%) patients underwent nerve-sparing RP, and 198 patients (82.2%) were continent 1 year after RP. Multivariate analysis showed that the age (odds ratio [OR]=1.091 [1.015-1.172], P=0.018), Body Mass Index (BMI) (OR=1.227 [1.057-1.424], P=0.007), and modified surgical technique (OR=0.109 [0.044-0.267], P<0.001) were independent factors for predicting urinary continence recovery after RP. CONCLUSIONS: Younger age, low BMI, and modified surgery were independent predictors of urinary continence recovery after RP in patients with high-grade PCa. These findings may help surgeons to give pre- and postoperative advice to patients with high-grade PCa about urinary continence recovery after RP.

Prognosis of patients with gastric variceal bleeding after endoscopic variceal obturation according to the type of varices.

BACKGROUND AND AIMS: This study was performed to evaluate the treatment efficacy of endoscopic variceal obturation (EVO) in patients with gastric variceal bleeding (GVB) according to the type of varices. PATIENTS AND METHODS: All patients who were treated with EVO for bleeding from gastric varices (GVs) were included. Patients with a previous history of endoscopic treatment for GVB and those with accompanying portal vein invasion by hepatocellular carcinoma or other malignancy were excluded. RESULTS: Ninety-one patients with GVB were included. Mean age was 59.4±12.4 years and 72 (79.1%) patients were men. The types of varices were gastroesophageal varices (GOV) type 1 (GOV1), GOV2, and isolated gastric varices type 1 (IGV1) in 30 (33.3%), 35 (38.5%), and 26 (28.6%) patients, respectively. Hemostasis and GV obliteration were achieved in 88 (96.7%) and 81 (89.0%) patients, respectively. Among 81 patients with GV obliteration, GV recurred in 26 (32.1%) patients. The GV recurrence rate was significantly lower in patients with GOV1 than in those with GOV2 (P=0.007), while it was comparable between patients with GOV1 and IGV1 (P=0.111) and between patients with GOV2 and IGV1 (P=0.278). Variceal rebleeding occurred in 11 (13.6%) patients. GVB recurrence rate was significantly higher in patients with GOV2 than in those with GOV1 (P=0.034) and IGV1 (P=0.018), while it was comparable between patients with GOV1 and IGV1 (P=0.623). Mortality rate was comparable among the three groups. CONCLUSIONS: EVO was very effective in patients with GVB. GV recurrence and GV rebleeding were significantly lower in patients with GOV1 than in those with GOV2.

Optimization of Detergent-Mediated Reconstitution of Influenza A M2 Protein into Proteoliposomes.

We report the optimization of detergent-mediated reconstitution of an integral membrane-bound protein, full-length influenza M2 protein, by direct insertion into detergent-saturated liposomes. Detergent-mediated reconstitution is an important method for preparing proteoliposomes for studying membrane proteins, and must be optimized for each combination of protein and membrane constituents used. The purpose of the reconstitution was to prepare samples for site-directed spin-labeling electron paramagnetic resonance (SDSL-EPR) studies. Our goals in optimizing the protocol were to minimize the amount of detergent used, reduce overall proteoliposome preparation time, and confirm the removal of all detergent. The liposomes were comprised of (1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) and 1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG), and the detergent octylglucoside (OG) was used for reconstitution. Rigorous physical characterization was applied to optimize each step of the reconstitution process. We used dynamic light scattering (DLS) to determine the amount of OG needed to saturate the preformed liposomes. During detergent removal by absorption with Bio-Beads, we quantified the detergent concentration by means of a colorimetric assay, thereby determining the number of Bio-Bead additions needed to remove all detergent from the final proteoliposomes. We found that the overnight Bio-Bead incubation used in previously published protocols can be omitted, reducing the time needed for reconstitution. We also monitored the size distribution of the proteoliposomes with DLS, confirming that the size distribution remains essentially constant throughout the reconstitution process.

Stereoisomers of the Bacterial Volatile Compound 2,3-Butanediol Differently Elicit Systemic Defense Responses of Pepper against Multiple Viruses in the Field.

The volatile compound 2,3-butanediol, which is produced by certain strains of root-associated bacteria, consists of three stereoisomers, namely, two enantiomers (2R,3R- and 2S,3S-butanediol) and one meso compound (2R,3S-butanediol). The ability of 2,3-butanediol to induce plant resistance against pathogenic fungi and bacteria has been investigated; however, little is known about its effects on induced resistance against viruses in plants. To investigate the effects of 2,3-butanediol on plant systemic defense against viruses, we evaluated the disease control capacity of each of its three stereoisomers in pepper. Specifically, we investigated the optimal concentration of 2,3-butanediol to use for disease control against Cucumber mosaic virus and Tobacco mosaic virus in the greenhouse and examined the effects of drench application of these compounds in the field. In the field trial, treatment with 2R,3R-butanediol and 2R,3S-butanediol significantly reduced the incidence of naturally occurring viruses compared with 2S,3S-butanediol and control treatments. In addition, 2R,3R-butanediol treatment induced the expression of plant defense marker genes in the salicylic acid, jasmonic acid, and ethylene signaling pathways to levels similar to those of the benzothiadiazole-treated positive control. This study reports the first field trial showing that specific stereoisomers of 2,3-butanediol trigger plant immunity against multiple viruses.

Clinicopathologic characteristics of double primary endometrial and colorectal cancers in a single institution.

AIM: To investigate the clinicopathologic and genetic correlations between double primary endometrial and colorectal cancer related to Lynch syndrome and to analyze germline mutations in mismatch repair genes in endometrial cancer patients in Korea. METHODS: Thirteen patients diagnosed with pathologically endometrial and colorectal cancer between January 2005 and November 2016 in a single institution were enrolled in the study. The medical records were retrospectively analyzed. The genetic mutational information of endometrial cancer in Korea was retrieved from the literature review. RESULTS: Endometrial cancer was diagnosed first in eight (62%) patients, and one patient was diagnosed with colorectal cancer first. Endometrioid adenocarcinoma was reported in 10 of 13 (77%) endometrial cancer patients. Endometrial cancer was found at the low uterine segment in three patients. Three of four patients had high microsatellite instability. The loss of mismatch repair proteins was confirmed in 7 of 11 cases using immunohistochemistry. Four patients fulfilled clinical criteria based on a family history of cancer. Overall, the incidence of suspected Lynch syndrome was 77% (10/13). Four of them underwent genetic testing and three were found to have a pathogenic germline mutation. A possible founder mutation, c.1757_1758insC in MLH1, was observed in 21 germline mutation information from literature review. CONCLUSION: The present study describes the clinicopathologic data of double primary endometrial and colorectal cancer patients and supports that these patients should undergo closed approach for Lynch syndrome. Moreover, a possible founder mutation in Korean endometrial cancer patients was identified.

Acute HIV-1 infection presenting with fulminant encephalopathy.

Human immunodeficiency virus (HIV)-1 directly affects the nervous system, causes distinct neurological symptoms, and indirectly results in opportunistic infections, which include herpes virus simplex (HSV)-1, HSV-2, varicella zoster virus, and cytomegalovirus encephalitis caused by immunodeficiency. Early HIV-1 invasion of the central nervous system is also possible, and acute encephalopathy is a potentially lethal complication. We encountered a case of fulminant encephalopathy as a primary presentation of acute HIV-1 infection, in which highly active antiretroviral treatment resulted in a full clinical recovery. This case highlights the importance of considering acute HIV-1 infection in the differential diagnosis of reversible encephalopathy.

Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain.

Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development.

Outcome of extensive descending aorta repair adopting present concepts of spinal cord preservation.

BACKGROUND: Preoperative radiological identification of the Adamkiewicz artery and intraoperative neurologic monitoring are known to be helpful for preventing paraplegia after thoracoabdominal aorta replacement. To answer whether they should be used routinely, we investigated the incidence of spinal cord ischemia after extensive descending aortic repair without using such modalities. METHODS: We retrospectively reviewed the outcome of 95 patients who underwent extensive descending thoracic (DTA) or thoracoabdominal aorta (TAA) repair without the Adamkiewicz artery identification or neurologic monitoring from 2006 through 2010. Spinal cord protection strategy consisted of distal aortic perfusion, cerebrospinal fluid drainage, mild hypothermia, and maintenance of hypertension (systolic≥120mmHg) through the second postoperative day. A few segmental arteries were empirically selected for reimplantation based on the size and the amount of backbleeding; overall 1.4 per patient, 0.3 for DTA, 1.4 for type I, 2.4 for type II, 0.9 for type III, and 0 for type IV TAA. RESULTS: Two patients died early after surgery. All the remaining patients awoke without paraplegia or paraparesis. Delayed deficit occurred in 7 patients (7.4%) after hypotensive events caused by sedation, bleeding, respiratory distress, or cardiac dysfunction. Three patients (3.2%) became permanently paraplegic and the other four recovered completely within 48 hours after cerebrospinal fluid drainage and elevation of systemic blood pressure. CONCLUSION: Even without the Adamkiewicz artery identification and neuromonitoring, the incidence of immediate paraplegia could be kept low by applying the strategy based on the modern concept of cord perfusion. The relatively high incidence of delayed deficit suggests the importance of postoperative hemodynamic management and prevention of cardiopulmonary complications.

Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications.

AIM: Diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon variant of PTC, and its prognostic significance remains controversial. The aim of this study was to investigate the major genetic alterations of DSV-PTC and their prognostic implications. METHODS AND RESULTS: We included 37 patients with DSV-PTC who underwent thyroid surgery and had formalin-fixed paraffin-embedded samples. We tested for a panel of genetic alterations, including BRAF(V) (600E) , NRAS codon 61, HRAS codon 12/13/61 and KRAS codon 12/13 point mutations as well as RET/PTC1, RET/PTC3 and PAX8/PPARγ rearrangements using reverse transcription real-time polymerase chain reaction (PCR). All genetic alterations found on PCR were confirmed by Sanger sequencing. Associations between the identified genetic alterations and clinicopathological characteristics were evaluated. Among 37 cases of DSV-PTC, 17 were positive for RET/PTC1 (46%), six for RET/PTC3 (16%) and nine for BRAF(V) (600E) (24%). All mutations/rearrangements were mutually exclusive. The remaining five cases had none of the above genetic alterations. DSV-PTC with RET/PTC3 rearrangement was associated with advanced-stage disease, including T4 and distant metastasis (P < 0.05). Patients with RET/PTC3 showed a higher frequency of persistent disease (P < 0.01). In contrast, DSV-PTC with RET/PTC1 was associated with a higher prevalence of disease remission (P < 0.05) and coexistent Hashimoto's thyroiditis (P < 0.01). CONCLUSION: Taken together, RET/PTC rearrangement was the major genetic alteration seen in patients with DSV-PTC, and the RET/PTC3 rearrangement was associated with advanced stage at diagnosis and poor clinical outcome.

Sequential double-guidewire technique and transpancreatic precut sphincterotomy for difficult biliary cannulation.

BACKGROUND/AIMS: The double-guidewire technique (DGT) and transpancreatic precut sphincterotomy (TPS) are introduced as alternative biliary cannulation techniques for difficult biliary cannulation. This study aimed to evaluate the sequential use of DGT and TPS compared with a needle-knife precut papillotomy (NK). PATIENTS AND METHODS: Six hundred and thirty-five consecutive patients with naοve papilla and who underwent endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation from March 2010 to April 2014 in a single institute were analyzed. When standard techniques were unsuccessful, DGT or NK was performed. TPS was sequentially performed if DGT failed. RESULTS: DGT and NK were attempted in 65 and 58 patients, respectively. A sequential DGT-TPS was performed in 38 patients after a failed DGT. Biliary cannulations were successful in 42%, 74%, and 66% of the DGT, sequential DGT-TPS, and NK patients, respectively (P = 0.002). The cannulation rate was higher in the DGT ± TPS patients (85%) than in the NK patients (P = 0.014). Post-ERCP pancreatitis (PEP) developed in 26% of the successful DGT patients, 37% of the sequential DGT-TPS patients, and 10% of the NK patients (P = 0.008). Of the sequential DGT-TPS patients, the incidence of PEP was significantly reduced in patients with a pancreatic duct (PD) stent compared with patients without a PD stent (24% vs. 62%, P = 0.023). CONCLUSIONS: Sequential DGT-TPS is a useful alternative method compared with NK for patients in whom biliary cannulation is difficult. In the sequential DGT-TPS patients, the incidence of PEP was significantly reduced with the use of a PD stent.

'Neonatal' Nav1.2 reduces neuronal excitability and affects seizure susceptibility and behaviour.

Developmentally regulated alternative splicing produces 'neonatal' and 'adult' isoforms of four Na(+) channels in human brain, NaV1.1, NaV1.2, NaV1.3 and NaV1.6. Heterologously expressed 'neonatal' NaV1.2 channels are less excitable than 'adult' channels; however, functional importance of this difference is unknown. We hypothesized that the 'neonatal' NaV1.2 may reduce neuronal excitability and have a seizure-protective role during early brain development. To test this hypothesis, we generated NaV1.2(adult) mice expressing only the 'adult' NaV1.2, and compared the firing properties of pyramidal cortical neurons, as well as seizure susceptibility, between the NaV1.2(adult) and wild-type (WT) mice at postnatal day 3 (P3), when the 'neonatal' isoform represents 65% of the WT NaV1.2. We show significant increases in action potential firing in NaV1.2(adult) neurons and in seizure susceptibility of NaV1.2(adult) mice, supporting our hypothesis. At postnatal day 15 (P15), when 17% of the WT NaV1.2 is 'neonatal', the firing properties of NaV1.2(adult) and WT neurons converged. However, inhibitory postsynaptic currents in NaV1.2(adult) neurons were larger and the expression level of Scn2a mRNA was 24% lower compared with the WT. The enhanced seizure susceptibility of the NaV1.2(adult) mice persisted into adult age. The adult NaV1.2(adult) mice also exhibited greater risk-taking behaviour. Overall, our data reveal a significant impact of 'neonatal' NaV1.2 on neuronal excitability, seizure susceptibility and behaviour and may contribute to our understanding of NaV1.2 roles in health and diseases such as epilepsy and autism.

Unipedal postural stability in nonathletes with core instability after intensive abdominal drawing-in maneuver.

CONTEXT: The exact neuromechanical nature and relative contribution of the abdominal drawing-in maneuver (ADIM) to postural instability warrants further investigation in uninjured and injured populations. OBJECTIVE: To determine the effects of the ADIM on static core and unipedal postural stability in nonathletes with core instability. DESIGN: Controlled laboratory study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 19 nonathletes (4 women: age = 22.3 ± 1.3 years, height = 164.0 ± 1.7 cm, mass = 56.0 ± 4.6 kg; 15 men: age = 24.6 ± 2.8 years, height = 172.6 ± 4.7 cm, mass = 66.8 ± 7.6 kg) with core instability. INTERVENTION(S): Participants received ADIM training with visual feedback 20 minutes each day for 7 days each week over a 2-week period. MAIN OUTCOME MEASURES(S): Core instability was determined using a prone formal test and measured by a pressure biofeedback unit. Unipedal postural stability was determined by measuring the center-of-pressure sway and associated changes in the abdominal muscle-thickness ratios. Electromyographic activity was measured concurrently in the external oblique, erector spinae, gluteus medius, vastus medialis oblique, tibialis anterior, and medial gastrocnemius muscles. RESULTS: All participants initially were unable to complete the formal test. However, after the 2-week ADIM training period, all participants were able to reduce the pressure biofeedback unit by a range of 4 to 10 mm Hg from an initial 70 mm Hg and maintain it at 60 to 66 mm Hg with minimal activation of the external oblique (t(18) = 3.691, P = .002) and erector spinae (t(18) = 2.823, P = .01) muscles. Monitoring of the pressure biofeedback unit and other muscle activations confirmed that the correct muscle contraction defining the ADIM was accomplished. This core stabilization was well maintained in the unipedal-stance position, as evidenced by a decrease in the center-of-pressure sway measures (t(18) range, 3.953-5.775, P < .001), an increased muscle-thickness ratio for the transverse abdominis (t(18) = -2.327, P = .03), and a reduction in external oblique muscle activity (t(18) = 3.172, P = .005). CONCLUSIONS: We provide the first evidence to highlight the positive effects of ADIM training on core and postural stability in nonathletes with core instability.

Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities.

OBJECTIVES: To determined the pathogen-specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008-2009 influenza season and assess temporal characteristics of respiratory illness related to infection. METHODS: 3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. RESULTS: One hundred forty-nine participants had laboratory-confirmed influenza, and 595 had at least one episode of laboratory-confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children<5 years. CONCLUSIONS: A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.

Pharmacokinetic effect of voriconazole on cyclosporine in the treatment of aspergillosis after renal transplantation.

Azole antifungal agents are essential drugs in the treatment of fungal infections in renal transplant patients. As azoles, these antifungal agents are inhibitors of CYP3A4 and P-glycoprotein (P-gp); and thus therapeutic drug monitoring is important. We evaluated a patient with cutaneous and pulmonary aspergillosis who was successfully treated with voriconazole and a low cyclosporine trough level (3.2 - 27.9 ng/ml) for 3 months. During that period, the patient showed good allograft function with the co-administration of voriconazole and cyclosporine. We measured the patient's genotype of MDR1, CYP3A4, CYP3A5 and CYP2C19 enzymes in addition to the intracellular concentration of cyclosporine in peripheral blood mononuclear cells (PBMCs). The intracellular concentration of cyclosporine in PBMC is 3.2 times higher with no functionally defected alleles in MDR1, CYP3A4, CYP3A5 or CYP2C19 enzymes when cyclosporine is co-administered with voriconazole ex vivo. Although other confounding factors causing immunological modulation may exist, it is plausible that low serum and high intracellular cyclosporine concentrations, due to the inhibition of P-gp activity by voriconazole, also contribute to an immunosuppressive state.