Cutaneous leishmaniasis in Tabuk, Saudi Arabia: epidemiological trends from 2006 to 2021.

Introduction: cutaneous leishmaniasis (CL) is a vector-borne protozoan skin disease that affects all human ages and can pose extreme social and psychological impacts. This study aimed to reveal the epidemiological trends of CL in the Tabuk region, the Kingdom of Saudi Arabia (KSA), during the period from 2006 to 2021. Methods: patients with CL, who were detected and registered at the regional Vector-borne Diseases Control Unit of the Tabuk province, between January 2006 and December 2021, were analyzed in this retrospective study. The patients´ data included their nationality, gender, and age, and their annual and month-by-month recorded patterns. Results: a total of 1575 CL patients were reported during the said period. They were 53.1% Saudis and 46.9% non-Saudi expatriates with a ratio around 1.1: 1.0; and they were re-categorized as 83.17% males and 16.83% females with a ratio of 4.9: 1.0 (p <0.5). Additionally, the majority (1002/1575; 63.6%) of these CL patients were in age group of 15-45 years (p <0.5), and the lowest number was in age group of <5 years. Most importantly, there was a continuous annual and month-by-month record of these patients; reflecting CL endemicity in the Tabuk region of KSA. Conclusion: the present findings imply that CL is endemic in the Tabuk region of KSA. As there is a recent increase in human immigration to this region, sustainable monitoring of CL and improving its control measures is warranted.

Regulating the Electron Depletion Layer of Au/V2O5/Ag Thin Film Sensor for Breath Acetone as Potential Volatile Biomarker.

Human exhaled breath has been utilized to identify biomarkers for diseases such as diabetes and cancer. The existence of these illnesses is indicated by a rise in the level of acetone in the breath. The development of sensing devices capable of identifying the onset of lung cancer or diabetes is critical for the successful monitoring and treatment of these diseases. The goal of this research is to prepare a novel breath acetone sensor made of Ag NPs/V2O5 thin film/Au NPs by combining DC/RF sputtering and post-annealing as synthesis methods. The produced material was characterized using X-ray diffraction (XRD), UV-Vis, Raman, and atomic force microscopy (AFM). The results revealed that the sensitivity to 50 ppm acetone of the Ag NPs/V2O5 thin film/Au NPs sensor was 96%, which is nearly twice and four times greater than the sensitivity of Ag NPs/V2O5 and pristine V2O5, respectively. This increase in sensitivity can be attributed to the engineering of the depletion layer of V2O5 through the double activation of the V2O5 thin films with uniform distribution of Au and Ag NPs that have different work function values.

Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study.

Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer's disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3ß, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B-protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B-protein complexes.

Antimicrobial efficacy and topographical alterations of photodynamic therapy versus conventional antimicrobials on contaminated zirconia ceramic in vitro.

PURPOSE: The aim of this in vitro study was to assess the efficacy of antimicrobial photodynamic therapy (aPDT), neodymium-doped yttrium aluminium garnet (Nd:YAG) laser, and two other disinfecting agents against P. gingivalis and T. forsythia that colonized over zirconia ceramics and to evaluate if the disinfecting protocols result in zirconia surface alteration. MATERIALS AND METHODS: The experiment was conducted on pre-sintered, commercially available Yttria Stabilized Zirconia (Y-TZP) ceramic blocks. The bacterial strains of P. gingivalis and T. forsythia were used to contaminate the zirconia specimens. The infected zirconia specimens were randomly divided into 4 groups (n=20/group): aPDT, Nd:YAG laser, hydrogen peroxide (H2O2), and chlorhexidine groups. The viability of bacteria was assayed using the MTT protocol. The surface roughness (Ra) of all zirconia specimens was estimated using a profilometer and a drop-shape analyzer was used to evaluate the contact angle using a special sessile drop method. RESULTS: A statistically significant reduction by the aPDT group is noticed for P. gingivalis and T. forsythia species compared to other disinfection methods (p<0.05). The second highest reduction was seen for chlorhexidine followed by Nd:YAG laser. The least reduction was demonstrated for the hydrogen peroxide group. Statistically, there was no significant difference in Ra scores between the four groups. However, the contact angles were significantly reduced from the zirconia specimens after the aPDT method which indicates a hydrophilicity increase compared to other groups. The SFE scores of all decontamination protocols from highest to lowest were aPDT (41.68), chlorhexidine (39.83), Nd:YAG (34.52), and H2O2 (29.88). CONCLUSIONS: Antimicrobial photodynamic therapy demonstrated a high antibacterial efficacy over zirconia ceramic surface without altering surface topography.

Exploring the Binding Pattern of Geraniol with Acetylcholinesterase through In Silico Docking, Molecular Dynamics Simulation, and In Vitro Enzyme Inhibition Kinetics Studies.

Acetylcholinesterase (AChE) inhibition is a key element in enhancing cholinergic transmission and subsequently relieving major symptoms of several neurological and neuromuscular disorders. Here, the inhibitory potential of geraniol and its mechanism of inhibition against AChE were elucidated in vitro and validated via an in silico study. Our in vitro enzyme inhibition kinetics results show that at increasing concentrations of geraniol and substrate, Vmax did not change significantly, but Km increased, which indicates that geraniol is a competitive inhibitor against AChE with an IC50 value 98.06 ± 3.92 µM. All the parameters of the ADME study revealed that geraniol is an acceptable drug candidate. A docking study showed that the binding energy of geraniol (-5.6 kcal mol-1) was lower than that of acetylcholine (-4.1 kcal mol-1) with AChE, which exhibited around a 12.58-fold higher binding affinity of geraniol. Furthermore, molecular dynamics simulation revealed that the RMSD of AChE alone or in complex with geraniol fluctuated within acceptable limits throughout the simulation. The mean RMSF value of the complex ensures that the overall conformation of the protein remains conserved. The average values of Rg, MolSA, SASA, and PSA of the complex were 3.16 Å, 204.78, 9.13, and 51.58 Å2, respectively. We found that the total SSE of AChE in the complex was 38.84% (α-helix: 26.57% and ß-sheets: 12.27%) and remained consistent throughout the simulation. These findings suggest that geraniol remained inside the binding cavity of AChE in a stable conformation. Further in vivo investigation is required to fully characterize the pharmacokinetic properties, optimization of dose administration, and efficacy of this plant-based natural compound.

Embilica officinalis L. inhibits the growth and proliferation of Leishmania donovani through the induction of ultrastructural changes, mitochondrial dysfunction, oxidative stress and apoptosis-like cell death.

Visceral leishmaniasis (VL) is caused by a protozoan parasite, Leishmania donovani (L. donovani). It affects around 1-2 million people around the world annually. There is an urgent need to investigate new medicament of it due to difficult method of drug administration, long period of treatment, high cost of the drug, adverse side-effects, low efficacy and development of parasite resistance to the available drugs. Medicinal plants have also been used for the treatment of different diseases in traditional system of medicines due to their holistic effects. The Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland has already started the program for identification of potential medicinal plant and plant products having antileishmanial potential. Keeping all these in consideration, we planned to study the antileishmanial activity of one of the medicinal plant, Embilica officinalis L. (EO) fruit extract. EO fruit extract inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes in dose-dependent manner. EO fruit extract induced morphological and ultrastructural changes in parasites as observed under Electron Microscope. It also induced the oxidative stress, mitochondrial dysfunction, DNA laddering and apotosis-like cell death in parasites. Here, we for the first time reported such a detailed mechanism of action of antileishmanial activity of EO fruit extract. Our results suggested that EO fruit extract could be used for the development of new phytomedicine against leishmaniasis.

High-Throughput Screening and Molecular Dynamics Simulation of Natural Product-like Compounds against Alzheimer's Disease through Multitarget Approach.

Alzheimer's disease (AD) is a progressive neurological disorder that affects 50 million people. Despite this, only two classes of medication have been approved by the FDA. Therefore, we have planned to develop therapeutics by multitarget approach. We have explored the library of 2029 natural product-like compounds for their multi-targeting potential against AD by inhibiting AChE, BChE (cholinergic pathway) MAO-A, and MOA-B (oxidative stress pathway) through in silico high-throughput screening and molecular dynamics simulation. Based on the binding energy of these target enzymes, approximately 189 compounds exhibited a score of less than -10 kcal/mol against all targets. However, none of the control inhibitors exhibited a binding affinity of less than -10 kcal/mol. Among these, the top 10 hits of compounds against all four targets were selected for ADME-T analysis. As a result, only F0850-4777 exhibited an acceptable range of physicochemical properties, drug-likeness, pharmacokinetics, and suitability for BBB permeation with high GI-A and non-toxic effects. The molecular dynamics study confirmed that F0850-4777 remained inside the binding cavity of targets in a stable conformation throughout the simulation and Prime-MM/GBSA study revealed that van der Waals' energy (ΔGvdW) and non-polar solvation or lipophilic energy (ΔGSol_Lipo) contribute favorably towards the formation of a stable protein-ligand complex. Thus, F0850-4777 could be a potential candidate against multiple targets of two pathophysiological pathways of AD and opens the doors for further confirmation through in vitro and in vivo systems.

Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region. Sterol C-24 methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3-group from S-adenosyl methionine to C-24 position of sterol side chain which makes the ergosterol different from cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan-3-ol, and parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction, gigantol showed the best lead-likeness and drug-likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that gigantol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes. Gigantol exerted its antileishmanial action through the induction of reactive oxygen species in dose-dependent manner. Our study, suggested the possible use of gigantol as antileishmanial drug after further validations to overcome leishmaniasis.

Targeting sterol alpha-14 demethylase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha-14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)-approved drugs against LdSDM to identify the potential lead-drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra-macrophagic amastigotes. Avodart-induced reactive oxygen species (ROS) in the parasites in a dose-dependent manner. ROS induced by avodart led to the induction of apoptosis-like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA-approved drug, avodart, establishing a nice example of the drug-repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 µM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-µM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.

Assessment of the Antileishmanial Potential of Cassia fistula Leaf Extract.

Cassia fistula has a wide array of biologically active and therapeutically important class of compounds. Leishmania donovani important drug targets, sterol 24-c methyltransferase (LdSMT), trypanothione reductase (LdTR), pteridine reductase (LdPTR1), and nucleoside hydrolase (LdNH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential. To confirm this, we performed in vitro antileishmanial and cytotoxicity assays. Methanolic extract of C. fistula leaves showed growth inhibition and proliferation of L. donovani promastigote with an IC50 value of 43.31 ± 4.202 µg/mL. It also inhibited the growth of intra-macrophagic amastigotes with an IC50 value of 80.76 ± 3.626 µg/mL. C. fistula extract was found cytotoxic at a very high concentration on human macrophages (CC50 = 626 ± 39 µg/mL). Annexin V/propidium iodide (PI) staining assay suggested partial apoptosis induction in parasites by C. fistula to exert its antileishmanial activity. Here, for the first time, we have shown the antileishmanial potential of C. fistula leaves. Overall, our results could open new insight for an affordable and natural antileishmanial with high efficacy and less toxicity.

Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response.

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reactive oxygen species (ROS) generation in parasites. Molecular-docking studies with key drug targets of Leishmania donovani showed significant inhibition. Out of these targets, cynaroside showed strongest affinity with uridine diphosphate (UDP)-galactopyranose mutase with -10.4 kcal/mol which was further validated by molecular dynamics (MD) simulation. The bioactivity, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, Organisation for Economic Co-operation and Development (OECD) chemical classification and toxicity risk prediction showed cynaroside as an enzyme inhibitor having sufficient solubility and non-toxic properties. In conclusion, cynaroside may be used alone or in combination with existing drug, miltefosine to control leishmaniasis with less cytotoxicity.

Students' perceptions of the educational environment at King Abdulaziz University Faculty of Dentistry (KAUFD): a cross sectional study.

BACKGROUND: Prior research studies have found that dental students' educational environment has an impact on their academic achievement. Therefore, the aim of this cross-sectional study was to assess dental students' perceptions of the educational environment at King Abdulaziz University Faculty of Dentistry (KAUFD) in Saudi Arabia. METHODS: Second-, third-, and fourth-year dental students at KAUFD, responded to the Dundee Ready Education Environment Measure (DREEM) in October 2017. It consists of five subscales: students' perceptions of learning, students' perceptions of teachers, students' academic self-perceptions, students' perceptions of the atmosphere, and students' social self-perceptions. The overall mean value was calculated. RESULTS: A total of 217 dental students responded to the questionnaire (92 males, 125 females); the response rate was 43.40%. The overall mean DREEM score was 125, which is considered "more positive than negative." The mean DREEM score was higher for females (128.73) than for males (120.13). Third-year students (137.99) obtained higher mean scores compared to fourth-year (121.42) and fifth-year students (115.94). CONCLUSIONS: Dental students' perceptions of the educational environment at KAUFD support the findings of national and international studies. Students in the preclinical dental academic year (third year) obtained the highest DREEM score, when compared to those who belonged to the clinical academic years. Therefore, a personal development program and good support systems must be emphasized for clinical-year students.

Physicians' awareness and practice toward influenza and pneumococcal vaccines for high-risk patients.

OBJECTIVES: The aim of the study is to assess the awareness of family medicine residents about influenza and pneumococcal vaccination for high-risk patients and to verify the most significant variables that might affect residents' knowledge and the tools needed to enhance their practice. MATERIALS AND METHODS: This cross-sectional study was conducted at four major hospitals in Riyadh, Saudi Arabia, during the period, October through December 2017. A pretested self-administered questionnaire was handed to 180 family residents. Descriptive statistics were used to analyze the study data. The Chi-square test was used to compare categorical variables data. The One-way ANOVA test was used to detect the significant difference. RESULTS: The overall knowledge of physicians about influenza and pneumococcal vaccines was inadequate and was more toward pneumococcal vaccine, in spite their respectable knowledge about the target population. The main reasons for non- prescribing of vaccines were forgetfulness (59.4%), the availability of vaccines (33.9%), and the patients' refusal (23.3%). The tools that might help for prescribing were the need for the presence of electronic reminder (69.4%) and the patients should follow a regular family physician (47.2%). CONCLUSION: Knowledge and practice of influenza and pneumococcal vaccination are inadequate. This is mainly because of forgetfulness owing to minimal guideline awareness, lack of vaccine availability, and patients' refusal. The important recommendations to enhance vaccination practice among physicians are the implementation of electronic reminders, regular follow-up with the same physician in addition to educational programs during residency, and patient education about the importance of vaccinations as a means of disease prevention.

Eat, Sleep, Console Approach: A Family-Centered Model for the Treatment of Neonatal Abstinence Syndrome.

BACKGROUND: The opioid epidemic in the United States has resulted in an increased number of drug-exposed infants who are at risk for developing neonatal abstinence syndrome (NAS). Historically, these infants have been treated with the introduction and slow weaning of pharmaceuticals. Recently, a new model called Eat, Sleep, Console (ESC) has been developed that focuses on the comfort and care of these infants by maximizing nonpharmacologic methods, increasing family involvement in the treatment of their infant, and prn or "as needed" use of morphine. PURPOSE: The purpose of this evidenced-based practice brief was to summarize and critically review emerging research on the ESC method of managing NAS and develop a recommendation for implementing an ESC model. METHODS: A literature review was conducted using PubMed, Cochrane, and Google Scholar with a focus on ESC programs developed for treating infants with NAS. FINDING/RESULTS: Several studies were found with successful development and implementation of the ESC model. Studies supported the use of ESC to decrease length of stay, exposure to pharmacologic agents, and overall cost of treatment.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=32&autoPlay=true.

Repurposing Glyburide as Antileishmanial Agent to Fight Against Leishmaniasis.

BACKGROUND: Leishmaniasis is caused by a protozoan parasite, Leishmania. It is common in more than 98 countries throughout the world. Due to insufficient availability of antileishmanial chemotherapeutics, it is an urgent need to search for new molecules which have better efficacy, low toxicity and are available at low cost. OBJECTIVES: There is a high rate of diabetic cases throughout the world that is why we planned to test the antileishmanial activity of glyburide, an effective sugar lowering drug used for the treatment of diabetes. In this study, glyburide showed a significant decrease in the parasite growth and survival in vitro in a dose-dependent manner. METHODS: Anti-leishmanial activity of glyburide was checked by culturing Leishmania donovani promastigotes in the presence of glyburide in a dose and time dependent manner. Docking study against Leishmania donovani-Trypanothione synthetase (LdTrySyn) protein was performed using Autodock Vina tool. RESULTS: Growth reversibility assay shows that growth of treated parasite was not reversed when transferred to fresh culture media after 7 days. Moreover, docking studies show efficient interactions of glyburide with key residues in the catalytic site of Leishmania donovani- Trypanothione synthetase (LdTrySyn), a very important leishmanial enzyme involved in parasite's survival by detoxification of Nitric Oxide (NO) species, generated by the mammalian host as a defense molecule. Thus this study proves that the drug-repurposing is a beneficial strategy for identification of new and potent antileishmanial molecules. CONCLUSION: The results suggest that glyburide binds to LdTrySyn and inhibits its activity which further leads to the altered parasite morphology and inhibition of parasite growth. Glyburide may also be used in combination with other anti-leishmanial drugs to potentiate the response of the chemotherapy. Overall this study provides information about combination therapy as well as a single drug treatment for the infected patients suffering from diabetes. This study also provides raw information for further in vivo disease model studies to confirm the hypothesis.

Maxillary sinus schwannoma.

Schwannoma (neurilemmoma) is a benign tumour that arises from the Schwann cells which cover the nerve sheaths of the peripheral or autonomic nervous system especially the sympathetic system. Reported cases of schwannoma arising from the sinonasal tract are rare. We report a case of a 28-year-old man who presented to otolaryngology-head and neck surgery clinic with left cheek swelling and left-sided nasal obstruction for 1-year period. Endoscopic examination and high-resolution CT scan revealed a homogenous expansile mass occupying the left maxillary antrum extending to the left orbit and left ethmoidal air cells. The mass was excised through endoscopic endonasal approach followed by Caldwell-Luc approach for the residual tumour. Postoperative histopathological examination revealed benign type Antoni A schwannoma.

Personalized precision medicine in extreme preterm infants with transient neonatal diabetes mellitus.

Although hyperglycemia is common in neonates, especially preterm infants, a diagnosis of neonatal diabetes mellitus (NDM) is rarely made. NDM can be permanent (45%), transient (45%) or syndromic (10%). Of the 95% of identifiable mutations for NDM, methylation defects in 6q24, KCNJ11, ABCC8, and INS account for the majority. Two cases of transient NDM in extremely preterm, 24 weeks' gestational age (GA) triplets, due to a missense mutation c.685G>A in the KCNJ11 gene are presented. Both patients were successfully transitioned from insulin to Glyburide (Glibenclamide) at 2 months of age. Comprehensive genetic testing with targeted next-generation sequencing and 6q24 methylation analysis helps identify monogenic diabetes early, thereby improving metabolic and glycemic control when patients with potassium channel mutations are started on sulfonylurea (SU) treatment.

Simple fundoplication versus additional vagotomy and pyloroplasty in neurologically impaired children--a single centre experience.

BACKGROUND AND AIMS: Gastrooesophageal reflux disease (GERD) is a significant problem in children with neurological impairment (NI) with high failure rates for fundoplication. Fundoplication with vagotomy and pyloroplasty (FVP) can improve the outcome by altering the sensory or motor dysfunction associated with the reflux. We report our comparative outcomes for simple fundoplication (SF) and FVP in NI children. METHODS: Case records of all patients having fundoplication under a single consultant at a tertiary UK paediatric surgical centre between January 1997 and December 2012 were retrospectively assessed for recurrent symptoms and redo surgery. The data were collected using a Microsoft Excel database and analysed on Graphpad prism software program. Data are median (range). P value<0.05 was considered significant. RESULTS: Data were available for 244 out of 275 patients who underwent fundoplication during this period (157 SF and 87 FVP). Neurological disease or known syndromes were recorded in 158 patients. Thirty-five children had congenital anatomical abnormalities. Laparoscopic fundoplication was done in 37 cases. Revisional surgery for recurrent symptoms was performed in 22 patients. In the neurologically normal children, all of whom had SF, the revision rate was 6.5%. In the NI children the revision rates were 18.5% for SF and 3.9% for FVP, respectively (Fisher's exact, P<0.05). The median time to redo surgery was 10 (1-63) months, and the median time to follow up was 19.5 (2-177) months. CONCLUSIONS: There appears to be a significantly lower need for redo surgery following FVP than SF in children with NI.

Recurrence of biliary disease following non-operative management in elderly patients.

INTRODUCTION: The purpose of this study was to determine the proportion of symptomatic recurrence following initial non-operative management of gallstone disease in the elderly and to test possible predictors. METHODS: This is a single institution retrospective chart review of patients 65 years and older with an initial hospital visit (V1) for symptomatic gallstone disease, over a 4-year period. Patients with initial "non-operative" management were defined as those without surgery at V1 and without elective surgery at visit 2 (V2). Baseline characteristics included age, sex, Charlson comorbidity index (CCI), diagnosis, and interventions (ERCP or cholecystostomy) at V1. Outcomes assessed over 1 year were as follows: recurrence (any ER/admission visit following V1), surgery, complications, and mortality. A survival analysis using a Cox proportional hazards model was performed to assess predictors of recurrence. RESULTS: There were 195 patients initially treated non-operatively at V1. Mean age was 78.3 ± 7.8 years, 45.6% were male, and the mean CCI was 2.1 ± 1.9. At V1, 54.4% had a diagnosis of biliary colic or cholecystitis, while 45.6% had a diagnosis of cholangitis, pancreatitis, or choledocholithiasis. 39.5% underwent ERCP or cholecystostomy. Excluding 10 patients who died at V1, 31.3% of patients had a recurrence over the study period. Among these, 43.5% had emergency surgery, 34.8% had complications, and 4.3% died. Median time to first recurrence was 2 months (range 6 days-4.8 months). Intervention at V1 was associated with a lower probability of recurrence (HR 0.3, CI [0.14-0.65]). CONCLUSION: One-third of elderly patients will develop a recurrence following non-operative management of symptomatic biliary disease. These recurrences are associated with significant rates of emergency surgery and morbidity. Percutaneous or endoscopic therapies may decrease the risk of recurrence.