Perinatal bacterial colonization and neonatal early-onset sepsis: A case-control study.

BACKGROUND: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS). OBJECTIVE: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. METHODS: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status. RESULTS: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]. CONCLUSION: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

The trend of percutaneous and open surgical procedures for peripheral arteriovenous malformations in the National Health Service England.

INTRODUCTION: This study aimed to assess the trend of percutaneous and open surgical procedures for peripheral arteriovenous malformations (AVMs) performed in NHS hospitals in England between 2012 and 2018. METHODS: Hospital Episode Statistics (HES) is a freely available data warehouse that represents the whole population of England served by the NHS. Data from the HES database was obtained and analysed for all hospital episodes between 2012 and 2018 for the total number and trend of 'primary diagnosis', and 'primary procedures and interventions' identified for peripheral AVMs. RESULTS: Over the period studied, there was an increase in the total number of admissions for peripheral AVMs; total primary diagnosis increased from 2242 to 2857 per year. Open surgery remained more commonly performed than percutaneous procedures throughout the studied period. However, the overall percentage of primary procedures and interventions being percutaneous in this period increased from 29.8% to 41.0% per year. The increase in the number of percutaneous procedures per year seemed to occur in both children (from 43 to 124) and adults (from 408 to 492) over the course of the study period. CONCLUSIONS: This study concluded that open surgery remained the most commonly performed primary procedure for peripheral AVMs, although there was an increasing trend for percutaneous procedures in NHS hospitals in England. The increase in the number and percentage of percutaneous procedures for peripheral AVMs was likely to have significant resource implications for the provision of care for patients with peripheral AVMs in NHS hospitals.

Facilitators and Barriers to Post-partum Diabetes Screening Among Mothers With a History of Gestational Diabetes Mellitus-A Qualitative Study From Singapore.

Introduction: Gestational Diabetes Mellitus (GDM) affects one in six births worldwide. Mothers with GDM have an increased risk of developing post-partum Type-2 Diabetes Mellitus (T2DM). However, their uptake of post-partum diabetes screening is suboptimal, including those in Singapore. Literature reports that the patient-doctor relationship, mothers' concerns about diabetes, and family-related practicalities are key factors influencing the uptake of such screening. However, we postulate additional factors related to local society, healthcare system, and policies in influencing post-partum diabetes screening among mothers with GDM. Aim: The qualitative research study aimed to explore the facilitators and barriers to post-partum diabetes screening among mothers with GDM in an Asian community. Methods: In-depth interviews were carried out on mothers with GDM at a public primary care clinic in Singapore. Mothers were recruited from those who brought their child for vaccination appointments and their informed consent was obtained. Both mothers who completed post-partum diabetes screening within 12 weeks after childbirth and those who did not were purposively recruited. The social ecological model (SEM) provides the theoretical framework to identify facilitators and barriers at the individual, interpersonal, organizational, and policy levels. Results: Twenty multi-ethnic Asian mothers with GDM were interviewed. At the individual and interpersonal level, self-perceived risk of developing T2DM, understanding the need for screening and the benefits of early diagnosis, availability of confinement nanny in Chinese family, alternate caregivers, emotional, and peer support facilitated post-partum diabetes screening. Barriers included fear of the diagnosis and its consequences, preference for personal attention and care to child, failure to find trusted caregiver, competing priorities, and unpleasant experiences with the oral glucose tolerance test. At the organizational and public policy level, bundling of scheduled appointments, and standardization of procedure eased screening but uptake was hindered by inconvenient testing locations, variable post-partum care practices and advice in the recommendations for diabetes screening. Conclusion: Based on the SEM, facilitators and barriers towards post-partum diabetes screening exist at multiple levels, with some contextualized to local factors. Interventions to improve its uptake should be multi-pronged, targeting not only at personal but also familial, health system, and policy factors to ensure higher level of success.

Wilms tumour with poor response to pre-operative chemotherapy: A report of 2 cases.

INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy. CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up. DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.

Comorbidities Can Predict Mortality of Kidney Transplant Recipients: Comparison With the Charlson Comorbidity Index.

BACKGROUND: Comorbid conditions are important in the survival of kidney transplant recipients. The weights assigned to comorbidities to predict survival may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in renal allograft recipients (mCCI-KT), thereby improving risk stratification for mortality. METHODS: A total of 3765 recipients in a multicenter cohort were included to develop a comorbidity score. The weights of the comorbidities, per the CCI, were recalibrated using a Cox proportional hazards model. RESULTS: Peripheral vascular disease, liver disease, myocardial infarction, and diabetes in the CCI were selected from the Cox proportional hazards model. Thus, the mCCI-KT included 4 comorbidities with recalibrated severity weights. Whereas the CCI did not discriminate for survival, the mCCI-KT provided significant discrimination for survival using the Kaplan-Meier method and Cox regression analysis. The mCCI-KT showed modest increases in c-statistics (0.54 vs 0.52, P = .001) and improved net mortality risk reclassification by 16.3% (95% confidence interval, 3.2-29.4; P = .015) relative to the CCI. CONCLUSION: The mCCI-KT stratifies the risk for mortality in renal allograft recipients better than the CCI, suggesting that it may be a preferred index for use in clinical practice.

Deep Venous Procedures Performed in the National Health Service in England between 2005 and 2015.

OBJECTIVES: Recent advances in imaging technology and endovenous interventions have revolutionised the management of specific groups of patients with deep venous pathology. This study aimed to examine data published by Hospital Episode Statistics (HES) to assess trends in the number of endovascular and open surgical deep venous procedures performed in National Health Service (NHS) hospitals in England between 2005 and 2015. MATERIALS AND METHODS: The main diagnosis of deep venous thrombosis (DVT), and total number of primary open and percutaneous procedures for deep venous pathology for patients admitted to the NHS hospitals in England from 2005 to 2015 were retrieved from the HES database and analysed. RESULTS: An overall declining trend in the annual number of admissions for a primary diagnosis of DVT was observed (linear regression r2 = 0.9, p < .0001). The number of open surgical procedures for removal of thrombus remained largely unchanged (range 26-70); the frequency of percutaneous procedures increased steadily over the study period (range 0-311). The number of open surgical procedures relating to the vena cava fell between 2005 and 2009, and remained around 50 per year thereafter. Annual numbers of cases of deep venous bypass (range 17-33) and venous valve surgery (range 8-47) remained similar in trend over this period. The number of vena cava stent (range 0-405), other venous stent (range 0-316), and percutaneous venoplasty (range 0-972) procedures increased over the first 5 years of the study period. CONCLUSIONS: There is an increasing trend in relation to endovenous procedures but not open surgery, being carried out for deep venous pathology in the last decade in NHS hospitals in England. Despite a number of limitations with HES, the increase in the number of endovenous procedures shown is likely to have significant implications for the provision of care and healthcare resources for patients with deep venous pathology.

Comparison of microbubble presence in the right heart during mechanochemical and radiofrequency ablation for varicose veins.

Objective Mechanochemical ablation is a novel technique for ablation of varicose veins utilising a rotating catheter and liquid sclerosant. Mechanochemical ablation and radiofrequency ablation have no reported neurological side-effect but the rotating mechanism of mechanochemical ablation may produce microbubbles. Air emboli have been implicated as a cause of cerebrovascular events during ultrasound-guided foam sclerotherapy and microbubbles in the heart during ultrasound-guided foam sclerotherapy have been demonstrated. This study investigated the presence of microbubbles in the right heart during varicose vein ablation by mechanochemical abaltion and radiofrequency abaltion. Methods Patients undergoing great saphenous vein ablation by mechanochemical abaltion or radiofrequency ablation were recruited. During the ablative procedure, the presence of microbubbles was assessed using transthoracic echocardiogram. Offline blinded image quantification was performed using International Consensus Criteria grading guidelines. Results From 32 recruited patients, 28 data sets were analysed. Eleven underwent mechanochemical abaltion and 17 underwent radiofrequency abaltion. There were no neurological complications. In total, 39% (11/28) of patients had grade 1 or 2 microbubbles detected. Thirty-six percent (4/11) of mechanochemical abaltion patients and 29% (5/17) of radiofrequency ablation patients had microbubbles with no significant difference between the groups ( p=0.8065). Conclusion A comparable prevalence of microbubbles between mechanochemical abaltion and radiofrequency ablation both of which are lower than that previously reported for ultrasound-guided foam sclerotherapy suggests that mechanochemical abaltion may not confer the same risk of neurological events as ultrasound-guided foam sclerotherapy for treatment of varicose veins.

Comparison of two new generation influenza rapid diagnostic tests with instrument-based digital readout systems for influenza virus detection.

INTRODUCTION: Influenza rapid diagnostic tests (RDTs) have been developed to supply scientists with more sensitive and specific techniques. Newly developed digital reader-based techniques require test evaluations before their clinical application. METHODS: Two types of digital influenza RDTs using a digital readout system and one conventional RDT were compared using 314 nasopharyngeal swabs of influenza. The swabs originated from symptomatic individuals suspected of influenza infection, and the presence of influenza was confirmed with influenza real-time polymerase chain reaction (PCR) testing and influenza subtyping. Methods were the Sofia® Influenza A + B Fluorescence Immunoassay (FIA), which uses a portable fluorescence analyser, the BD Veritor™ System Flu A + B, which uses a colorimetric immunochromatographic method with a reflectance-based measurement digital device, and the SD Bioline assay, which is based on a traditional immunochromatographic method. RESULTS: The Sofia® Influenza A + B system, the BD Veritor™ System Flu A + B and the SD Bioline assay showed sensitivities in relative real-time PCR results of 74.2, 73.0 and 53.9%, respectively, for influenza A, and 82.5, 72.8 and 71.0%, respectively, for influenza B. All three RDTs showed 100% specificities for influenza A and influenza B. The Sofia® Influenza A + B Fluorescence Immunoassay showed sensitive and specific results for the detection of influenza B in contrast to the BD Veritor™ System Flu A + B. The two digital RDTs showed higher sensitivity and specificity than the conventional RDT in the detection of the influenza H3 subtype. CONCLUSIONS: Digital-based readout systems for the detection of the influenza virus can be applied for more sensitive diagnosis in clinical settings than conventional RDTs.

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

BACKGROUND: There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. RESULTS: A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF. CONCLUSION: External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).

Modified Sandwich-graft Technique Employing Aorfix and Viabahn Stent-grafts to Preserve Hypogastric Flow in Cases of Complex Aortoiliac and Isolated Common Iliac Artery Aneurysms Including the Internal Iliac Artery Ostium.

OBJECTIVE: The aim was to assess the early and mid-term safety and clinical outcomes of a modified sandwich-graft technique (MSGT) that employed the Aorfix and Viabahn stent-grafts to preserve hypogastric flow in cases of complex aortoiliac and isolated common iliac artery (CIA) aneurysms including internal iliac artery (IIA) ostium who were not suitable for an iliac branch device (IBD). METHODS: A review of prospective collected data of all consecutive cases of treatment of complex aortoiliac or isolated CIA aneurysms including IIA ostium using the MSGT to preserve the hypogastric flow in three European centres between April 1, 2010, and December 31, 2013, was performed. All patients included were unfit for open repair and not suitable for an IBD. RESULTS: During the study period, 21 patients met the study criteria and had 25 MSGTs. The mean follow-up duration was 17.2 months. The technical success rate was 100%, with no perioperative mortality and stent-graft or MSGT-treated IIA occlusions. There were two cases with Type Ib endoleaks and one Type III endoleaks intraoperatively that were successfully managed. There was also no reported early and late pelvic ischaemia. The primary patency rate was 90.5%, and two cases of MGST treated IIA occlusions with no reported symptoms of pelvic ischaemia during follow-up. CONCLUSIONS: MSGT was a safe and feasible strategy to preserve hypogastric flow in cases of complex aortoiliac and isolated CIA aneurysms including IIA ostium and who were not suitable for IBD, with encouraging early and mid-term outcomes.

Intra-procedural pain score in a randomised controlled trial comparing mechanochemical ablation to radiofrequency ablation: The Multicentre Venefit™ versus ClariVein® for varicose veins trial.

OBJECTIVE: Endovenous techniques are, at present, the recommended choice for truncal vein treatment. However, the thermal techniques require tumescent anaesthesia, which can be uncomfortable during administration. Non-tumescent, non-thermal techniques would, therefore, have potential benefits. This randomised controlled trial is being carried out to compare the degree of pain that patients experience while receiving mechanochemical ablation or radiofrequency ablation. The early results of this randomised controlled trial are reported here. METHODS: Patients attending for the treatment of primary varicose veins were randomised to receive mechanochemical ablation (ClariVein®) or radiofrequency ablation (Covidien® Venefit™). The most symptomatic limb was randomised. The primary outcome measure was intra-procedural pain using a validated visual analogue scale. The secondary outcome measures were change in quality of life and clinical scores, time to return to normal activities and work as well as the occlusion rate. RESULTS: One-hundred and nineteen patients have been randomised (60 in the mechanochemical ablation group). Baseline characteristics were similar. Maximum pain score was significantly lower in the mechanochemical ablation group (19.3 mm, standard deviation ±19 mm) compared to the radiofrequency ablation group (34.5 mm ± 23 mm; p < 0.001). Average pain score was also significantly lower in the mechanochemical ablation group (13.4 mm ± 16 mm) compared to the radiofrequency ablation group (24.4 mm ± 18 mm; p = 0.001). Sixty-six percent attended follow-up at one month, and the complete or proximal occlusion rates were 92% for both groups. At one month, the clinical and quality of life scores for both groups had similar improvements. CONCLUSION: Early results show that the mechanochemical ablation is less painful than the radiofrequency ablation procedure. Clinical and quality of life scores were similarly improved at one month. The long-term data including occlusion rates at six months and quality of life scores are being collected.

Clinical outcomes in Asian elderly kidney transplant recipients: a multicenter cohort study.

BACKGROUND: The kidney transplantation rate in elderly patients is increasing rapidly. However, the clinical outcomes of kidney transplantation in elderly patients have not yet been thoroughly evaluated. METHODS: This multicenter cohort study included adult kidney transplant recipients (KTRs) admitted to five major tertiary hospitals in Korea between 1997 and 2012. A total of 3,565 adult participants were enrolled. Patient survival, allograft survival, and biopsy-proven acute rejection (BPAR) of 242 elderly recipients (≥ 60 years) were assessed and compared with those of a younger population. RESULTS: Patients were divided into five groups according to age at time of transplantation. The proportion of elderly patients was 6.7 % (mean age, 63.1 ± 2.7 years; n = 242). The numbers of male patients (69.4%), those with diabetes mellitus history (36.3%), and those with pretransplantation ischemic heart disease history (17.7%) were significantly higher in the elderly group than in the younger age groups. Elderly patients were more likely to receive a cadaveric kidney, and overall mortality rates were significantly higher in the elderly patients (1-year survival 93.3%, 5-year survival 91.3%). However, death-censored allograft survival rate and BPAR were not affected by patient age (P = .104 and .501, respectively). Among the elderly, BPAR and female donors were independent risk factors for allograft loss. CONCLUSION: The overall survival rate of the elderly KTRs was significantly lower than that of younger KTRs. However, the death-censored allograft survival rate did not differ between groups. Kidney transplantation should not be stagnated especially in elderly patients with end-stage renal disease.

Renal outcomes after liver transplantation in fulminant hepatitis A with acute kidney injury: comparison with hepatorenal syndrome.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). Recently, acute kidney injury (AKI) due to acute hepatitis A (HA) is increasing, but the outcome of LT is not well established. We investigated the outcomes of LT in patients with AKI due to acute HA compared with those of patients with HRS due to other causes. METHODS: We investigated the outcomes of LT in 20 patients with AKI associated with acute HA (HAV group) compared with 76 patients with hepatorenal syndrome (HRS) due to other causes (HRS group) at 3 Korea centers. RESULTS: Preoperative mean prothrombin time and serum creatinine level were higher in the HAV group than in the HRS group. But mean total bilirubin level was lower in the HAV group. There was no difference in Model for End-Stage Liver Disease scores. Post-transplantation patient and graft survival rates were similar between the 2 groups. More patients in the HAV group needed post-transplantation hemodialysis than in the HRS group (65.0% vs 38.2%; P = .043). However, post-transplantation estimated glomerular filtration rate was significantly higher in the HAV group after post-transplantation month 2 (P < .05). CONCLUSIONS: Peri-transplantation kidney function of the HAV group was poorer than that of HRS group. However, post-transplantation long-term renal outcome could be better in the HAV group.

A coiled-coil mimetic intercepts BCR-ABL1 dimerization in native and kinase-mutant chronic myeloid leukemia.

Targeted therapy of chronic myeloid leukemia (CML) is currently based on small-molecule inhibitors that directly bind the tyrosine kinase domain of BCR-ABL1. This strategy has generally been successful, but is subject to drug resistance because of point mutations in the kinase domain. Kinase activity requires transactivation of BCR-ABL1 following an oligomerization event, which is mediated by the coiled-coil (CC) domain at the N terminus of the protein. Here, we describe a rationally engineered mutant version of the CC domain, called CC(mut3), which interferes with BCR-ABL1 oligomerization and promotes apoptosis in BCR-ABL1-expressing cells, regardless of kinase domain mutation status. CC(mut3) exhibits strong proapoptotic and antiproliferative activity in cell lines expressing native BCR-ABL1, single kinase domain mutant BCR-ABL1 (E255V and T315I) or compound-mutant BCR-ABL1 (E255V/T315I). Moreover, CC(mut3) inhibits colony formation by primary CML CD34(+) cells ex vivo, including a sample expressing the T315I mutant. These data suggest that targeting BCR-ABL1 with CC mutants may provide a novel alternative strategy for treating patients with resistance to current targeted therapies.

TRPM4 inhibitor 9-phenanthrol activates endothelial cell intermediate conductance calcium-activated potassium channels in rat isolated mesenteric artery.

BACKGROUND AND PURPOSE: Smooth muscle transient receptor potential melastatin 4 (TRPM4) channels play a fundamental role in the development of the myogenic arterial constriction that is necessary for blood flow autoregulation. As TRPM4 channels are present throughout the vasculature, we investigated their potential role in non-myogenic resistance arteries using the TRPM4 inhibitor 9-phenanthrol. EXPERIMENTAL APPROACH: Pressure and wire myography were used to assess the reactivity of rat arteries, the latter in combination with measurements of smooth muscle membrane potential. Immunohistochemistry (IHC) and endothelial cell (EC) calcium changes were assessed in pressurized vessels and patch clamp measurements made in isolated ECs. KEY RESULTS: The TRPM4 inhibitor 9-phenanthrol reversibly hyperpolarized mesenteric arteries to circa EK and blocked α1 -adrenoceptor-mediated vasoconstriction. Hyperpolarization was abolished and vasoconstriction re-established by damaging the endothelium. In mesenteric and cerebral artery smooth muscle, 9-phenanthrol hyperpolarization was effectively blocked by the KCa 3.1 inhibitor TRAM-34. 9-Phenanthrol did not increase mesenteric EC [Ca(2+)]i , and Na(+) substitution with N-methyl-D-glucamine only increased the muscle resting potential by 10 mV. Immunolabelling for TRPM4 was restricted to the endothelium and perivascular tissue. CONCLUSIONS AND IMPLICATIONS: These data reveal a previously unrecognized action of the TRPM4 inhibitor 9-phenanthrol - the ability to act as an activator of EC KCa 3.1 channels. They do not indicate a functionally important role for TRPM4 channels in the reactivity of non-myogenic mesenteric arteries.