Significant Risk Factor For Development Research Articles

Predictors of functional tricuspid regurgitation after successful left-sided valve surgery

Tricuspid regurgitation (TR) is probably the most common and anticipated complication of left-sided heart valve pathology, especially MV disease. Whether preoperative functional TR will regress or progress after successful left-sided valve surgery is unknown. The aim of this study was to identify the predictors of significant TR after successful left-sided valve surgery. A retrospective analysis was performed on a total of 56 patients who underwent left-sided valve surgery (mitral or mitro-aortic-valve surgery). We have excluded patients who had organic TR. All patients had complete clinical examination and echocardiographic studies preoperatively and clinical and echocardiographic follow-up postoperatively. Mean operative age of patients was 49.3 ± 13.7 years with a sex-ratio of 0,8. Tricuspid annuloplasty was associated to left-sided valve surgery in 18 (32%) patients. Postoperatively, significant TR was found in 13 patients (23%) with a mean follow-up of 20.5 ± 33 months. Patients with significant postoperative TR were more often female (83% vs. 48%, P = 0.03), had more often a previous mitral commissurotomy (58% vs. 23%, P = 0.02) and showed a higher prevalence of significant preoperative TR (69% vs. 42%, P = 0.04). Postoperatively, residual pulmonary hypertension ( P = 0.04), dilatation of left atrium ( P = 0.02) and dilatation of right cardiac cavities ( P = 0.01) were significant risk factors for development or progression of TR after surgery. Late onset or progression of functional TR after successful left-sided valve surgery is a significant clinical entity as it displays a great impact on patient prognosis. So, the identification of clinical and echocardiographic predictors of late TR allows an adequate screening of patients that will require tricuspid valve repair at the time of initial left-sided valve surgery.

Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up.

Background:Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection. This study explores the association of hepatic steatosis among CHB-infected individuals in HCC development.Methods:This is a retrospective study on a cohort of patients with CHB who underwent liver biopsy between January 2000 and December 2014. They were stratified according to presence and severity of histologically proven hepatic steatosis and subsequently followed up to evaluate the association between hepatic steatosis and HCC development.Results:Among 289 patients with a median follow-up of 111.1 months, hepatic steatosis was present in 185 patients (64.0%). In all, 27 patients developed HCC on follow-up and 21 of them had hepatic steatosis. Univariate Cox analysis showed that age (hazard ratio [HR] = 1.08, 95% CI = 1.042-1.12), type 2 diabetes mellitus (T2DM) (HR = 4.00, 95% CI = 1.622-9.863), and Ishak score (HR = 1.221, 95% CI = 1.014-1.472) were associated with HCC development, whereas multivariate Cox analysis demonstrated that age and T2DM (HR = 2.69, 95% CI = 1.072-6.759) were significant risk factors for development of HCC.Conclusions:Concurrent hepatic steatosis in patients with CHB infection is not a risk factor for hepatocellular carcinoma formation.

Radiomics of 18F Fluorodeoxyglucose PET/CT Images Predicts Severe Immune-related Adverse Events in Patients with NSCLC.

To investigate the performance of pretreatment fluorine 18 (18F) fluorodeoxyglucose PET/CT radiomics in predicting severe immune-related adverse events (irSAEs) among patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy, which is important in optimizing treatment plans and alleviating future complications with early interventions. The retrospective arm of this study included 146 patients with histologically confirmed stage IIIB-IV NSCLC who were treated with immune checkpoint blockade between June 2011 and December 2017 and who were split into training (n = 97) and test (n = 49) cohorts. A prospective validation arm enrolled 48 patients before initiation of immunotherapy between January 2018 and June 2019 as an independent test cohort. Radiomics features extracted from baseline (preimmunotherapy treatment) PET, CT, and PET/CT fusion images were used to generate a radiomics score (RS) to quantify patient risk for developing irSAEs by an improved least absolute shrinkage and selection operator method. Weighted multivariable logistic regression analysis was then used to develop a nomogram model to predict irSAEs, which was assessed by its calibration, discrimination, and clinical usefulness. The radiomics nomogram, incorporating the RS, type of immune checkpoint blockade, and dosing schedule, was able to predict patients with and without irSAEs with area under the receiver operating characteristic curve of 0.92 (95% confidence interval [CI]: 0.86, 0.98), 0.92 (95% CI: 0.86, 0.99), and 0.88 (95% CI: 0.78, 0.97) in the training, test, and prospective validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram model had the highest overall net benefit. A high RS is a significant risk factor for development of irSAEs, demonstrating the value of PET/CT images in predicting irSAEs. By the identification, at baseline, of patients with NSCLC most likely to have irSAEs, treatment plans can be optimized before initiation of immunotherapy.Supplemental material is available for this article.© RSNA, 2020See also the commentary by Yousefi.

Correlates of picky eating behaviour in children and its effect on growth

Background: Picky eating is common in preschool-aged children. Children’s picky eating behaviour has been linked both to being overweight and underweight. Authors objectives was to study the factors associates of picky eating behaviour on growth and nutritional status of children.Methods: A Cross-sectional study done in 200 parents of children between 1-5 year age visiting outpatient department. Picky eating behaviours were assessed using questions from children eating behaviour questionnaire.Results: In the study, the estimated prevalence rate was 25%, maximum 38% at 49 to 60 months. 26% of subjects with picky eating behaviour had height for age <-3SD (severely stunted) 38% of subjects with picky eating behaviour had weight for height <-3SD (severely wasted) as compared to only 4% in non-picky eating behaviour subjects. Low birth weight and exclusive breast feeding for less than 6 month, were found to be significant risk factor for development of picky eating behaviour, while no significant association was seen with the time of introduction of semisolid complimentary feeds.Conclusions: Picky eating is major parental concern and impacts growth of children. The children with picky eating behaviours need to be monitored for growth.

Factors Correlated with Post Endoscopic Retrograde Cholangiopancreatography Hyperamylasemia: A Single Center Study

Background and aim of the work: Identifying patient at risk for post ERCP hyperamylasemia which may progress to pancreatitis is essential to minimize morbidity and mortality by suitable procedural or pharmacological intervention. In this study hyperamylasemia following ERCP were recorded and correlated with different patient or procedure related risk factors. Patients and methods: The data of all patients who met the inclusion criteria of the study and underwent endoscopic retrograde cholangiopancreatography (ERCP) in Al-Hada Armed Force Hospital, Taif, Saudi Arabia from January 2015 to March 2016, were collected through a review of their hospital and data base records. Results: There were 138 patients (86 females and 52 males) with mean age of 63.7±15.3 years. Hyperamylasemia was developed in 29.7% of them; 16.8% were recorded as asymptomatic hyperamylasemia and post ERCP pancreatitis in the remaining 13%. Multivariate analysis confirmed that, the gender, precut sphincterotomy and pancreatic duct cannulation were significant risk factors for development of non symptomatic hyperamylasemia and confirmed also the significance of precut sphincterotomy and pancreatic duct cannulation for post ERCP pancreatitis. Conclusion: This study confirmed the correlation of precut sphincterotomy and pancreatic duct cannulation with post ERCP hyperamylasemia and pancreatitis and in such conditions preventive measures are recommended.

Factors Correlated with Post Endoscopic Retrograde Cholangiopancreatography Hyperamylasemia: A Single Center Study

Background and aim of the work: Identifying patient at risk for post ERCP hyperamylasemia which may progress to pancreatitis is essential to minimize morbidity and mortality by suitable procedural or pharmacological intervention. In this study hyperamylasemia following ERCP were recorded and correlated with different patient or procedure related risk factors. Patients and methods: The data of all patients who met the inclusion criteria of the study and underwent endoscopic retrograde cholangiopancreatography (ERCP) in Al-Hada Armed Force Hospital, Taif, Saudi Arabia from January 2015 to March 2016, were collected through a review of their hospital and data base records. Results: There were 138 patients (86 females and 52 males) with mean age of 63.7±15.3 years. Hyperamylasemia was developed in 29.7% of them; 16.8% were recorded as asymptomatic hyperamylasemia and post ERCP pancreatitis in the remaining 13%. Multivariate analysis confirmed that, the gender, precut sphincterotomy and pancreatic duct cannulation were significant risk factors for development of non symptomatic hyperamylasemia and confirmed also the significance of precut sphincterotomy and pancreatic duct cannulation for post ERCP pancreatitis. Conclusion: This study confirmed the correlation of precut sphincterotomy and pancreatic duct cannulation with post ERCP hyperamylasemia and pancreatitis and in such conditions preventive measures are recommended.

INVASIVE PULMONARY ASPERGILLOSIS SUPERINFECTION IN A CRITICALLY ILL PATIENT WITH INFLUENZA A AND LIMITED CORTICOSTEROID EXPOSURE

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: It is our aim to highlight less well-recognized risk factors for invasive pulmonary aspergillosis(IPA). Early recognition of risk factors can raise clinical suspicion for Aspergillus superinfection so that appropriate and prompt therapy can be initiated potentially reducing morbidity and mortality. CASE PRESENTATION: A 69 year old female with a history of diabetes mellitus type 2, pancreatic cancer in remission status post remote Whipple procedure and COPD presented with dyspnea, wheezing and non-productive cough. She quickly deteriorated and was admitted to the ICU with hypoxic respiratory failure. One week prior to admission, she had completed a five day corticosteroid steroid burst for COPD exacerbation. CT chest demonstrated bilateral ground glass alveolar opacities on a background of stable centrilobular emphysema. Influenza A molecular assay was positive and Oseltamivir therapy was initiated. Despite receiving broad spectrum antibiotics and oseltamivir she remained febrile, required more oxygen and declined. Repeat thoracic imaging demonstrated worsening of the infiltrates and bronchoalveolar lavage specimens isolated Aspergillus fumigatus prompting immediate voriconazole therapy. DISCUSSION: Classically, IPA has been regarded as an ailment of those with weakened host immune systems such as in hematological malignancy, solid organ transplant and neutropenia. Influenza A is known to lay the framework for bacterial superinfections, but predisposing patients to invasive fungal organisms has only garnered significant attention within the last decade. Abbott et al. documented a case of invasive aspergillosis plaguing a previously immunocompetent individual acutely infected with Influenza in 1952, but it was not until 2018 that Schauwvlieghe et al identified Influenza as an independent risk factor for IPA in patients admitted to the ICU with pneumonia. Further, those receiving prolonged, high-dose glucocorticoid therapy have also been shown to be at greater risk for development of IPA, but the threshold of glucocorticoid exposure remains unclear. In 2012, Wauters et al demonstrated that steroid administration within seven days of presentation was a significant risk factor for development of Aspergillus; however, no corticosteroid dose risk relationship could be identified. Both corticosteroid exposure and Influenza A infection predispose patients to Aspergillus superinfection, on their own, but additional investigation is necessary to determine the threshold of corticosteroid exposure as well as the concurrent additive risk of Aspergillus infection when these two factors are combined. CONCLUSIONS: Knowledge of risk factors and thus the ability to identify patients at increased risk for Aspergillus superinfection, earlier in the course of hospitalization, may lead to a better determination of who warrants empiric antifungal coverage with the end result being improved morbidity and mortality. Reference #1: Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, Lagrou K, Verweij PE, Van de Veerdonk FL, Gommers D, Spronk P, Bergmans DCJJ, Hoedemaekers A, Andrinopoulou ER, van den Berg CHSB, Juffermans NP, Hodiamont CJ, Vonk AG, Depuydt P, Boelens J, Wauters J; Dutch-Belgian Mycosis study group. "Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study". Lancet Respir Med. 2018 Oct;6(10):782-792. Reference #2: Lewis R, Kontoyiannis, D. "Invasive aspergillosis in glucocorticoid-treated patients". Medical Mycology, Volume 47, Issue Supplement 1, 1 January 2009, Pages S271–S281 Reference #3: Wauters J, Baar I, Meersseman P, Meersseman W, Dams K, De Paep R, Lagrou K, Wilmer A, Jorens P, Hermans G. "Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study". Intensive Care Med. 2012 Nov;38(11):1761-8. DISCLOSURES: No relevant relationships by Median Ali, source=Web Response No relevant relationships by James Gleason, source=Web Response No relevant relationships by Aleksandra Kozlova, source=Web Response No relevant relationships by Shawn Marein, source=Web Response No relevant relationships by Avneek Singh Sandhu, source=Web Response

1135 What Causes Marginal Ulceration Following Gastric Bypass?

INTRODUCTION: The obesity epidemic affects more than one-third of the USA adult population, and over 350 000 bariatric procedures are performed annually. While bariatric surgery results in long lasting weight loss and resolution of comorbidities, complications can occur after surgery. Marginal ulceration (MU) is the most common complication following Roux-en-Y gastric bypass (RYGB), with an incidence reported to be between 1-9%. The etiology of MU is largely unknown but is believed to be secondary to technical aspects of the surgery as well as local factors such as inflammation and underlying macro and microvascular damage.The objective of this study is to investigate non-surgical factors and comorbidities that may contribute to the incidence of MU based on a national database. METHODS: After Institutional Review Board exemption was granted, we retrospectively reviewed the National Inpatient Sample database from 2003 to 2011. ICD-9 codes were used to abstract data including RYGB for obesity, gastrojejunal (GJ) ulcer, Helicobacter pyloriinfection (HPI), use of NSAIDs, use of aspirin, diabetes, hypertension, obstructive sleep apnea (OSA) and smoking. We compared groups using chi-squared and unadjusted odds ratio (OR). Multivariate logistic regression analysis was performed to adjust for confounders RESULTS: 34830 patients with GJ ulcer after RYGB for obesity were identified. In univariate analysis, OSA had the highest OR of all the variables (91.22), whereas aspirin use had the lowest (3.09). All the listed factors were associated with increased risk for MU (Table 1). During multivariate analysis, NSAID use had the highest OR (13.14) followed by HPI (5.08) and OSA (4.03). Aspirin use was not found to be associated with the development of MU in our multivariate analysis (Table 2). CONCLUSION: To our knowledge this is the largest study assessing the risk factors for MU after RYGB for obesity and the first to report that OSA strongly correlates with the presence of MU. Our analysis demonstrated that the most significant risk factors for development of MU were in decreasing order NSAID, HPI, OSA and Smoking. Studies using bariatric specific databases should examine the issue. Prospective studies are also required to determine if correction or optimization of these risk factors can prevent MU after RYGB.

Invasive Fungal Infections in the Pediatric Intensive Care Unit.

Invasive Fungal Infections in the Pediatric Intensive Care Unit.

Renal Outcomes of Liver Transplantation Recipients Receiving Standard Immunosuppression and Early Renal Sparing Immunosuppression: A Retrospective Single Center Study.

Background.New-onset stage 4–5 chronic kidney disease (CKD) after liver transplantation (LT) is associated with high morbidity, mortality, and economic burden. In 2010, we instituted an early renal sparing immunosuppression (RSI) protocol for LT recipients with severe renal dysfunction (pre-LT dialysis/estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2 or post-LT acute kidney injury) consisting of 2 doses of basiliximab for induction and delaying tacrolimus to post-LT day 4–7. We examined the effect of early RSI on post-LT renal outcomes.Methods.Data on all adults who had LT between January 1, 2010, and December 12, 2014 were collected. We calculated the renal risk index (RRI) score for each LT recipient (https://rri.med.umich.edu). Primary outcome was new-onset post-LT stage 4–5 CKD.Results.Of 214 LT recipients, 121 (57%) received early RSI and 93 (43%) received standard immunosuppression. Cumulative incidence of new-onset stage 4–5 CKD was higher in early RSI compared with standard immunosuppression (P = 0.03). Female sex and RRI score were the significant risk factors for development of post-LT stage CKD in the entire study cohort as well as the LT recipients with RRI ≥ sixth decile (high-risk group).Conclusions.Delaying tacrolimus initiation combined with basiliximab induction did not have a durable effect on long-term renal outcomes in high-risk LT recipients. Further studies are needed to identify the effective strategies to preserve renal function by targeting patients at high risk for CKD progression.

Participation of Sphingolipids in the Pathogenesis of Atherosclerosis

Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids. Sphingolipids - a group of lipids, which include a molecule of aliphatic alcohol sphingosine. This group includes sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines and sphingosine-1-phosphate (S-1-P). Ceramides and sphingosines have pro-apoptotic properties, and S-1-P protects cells from apoptosis. Particular attention as inducer CVD attracts ceramide. It has been established that aggregated lipoproteins isolated from atherosclerotic zones are enriched with ceramides. The level of ceramide and sphingosine increases with ischemia/reperfusion of the heart, in the infarction zone and in the blood, and also in hypertensive disease. S-1-P has a pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P performs a special function in the structure of high-density lipoproteins (HDL), being one of the main lipid components of these lipoproteins, which determines their multiple functions. Recently, work has been underway to create drugs that can correct the metabolism of S-1-P. The most successful drugs are those that use the S-1-P receptor as a target, since all of its actions are carried out through receptors. Increasing ceramide and sphingosine and reducing blood plasma level of S-1-P can be an important factor in the development of atherosclerosis. It is proposed to use the determination of the level of sphingolipids in blood plasma for early diagnosis of cardiac ischemia and in arterial hypertension. Chromatography-mass spectrometry has been suggested as the main method for testing these lipids.

Risk factors for febrile neutropenia in neoadjuvant docetaxel, cisplatin, and 5-fluorouracil chemotherapy for esophageal cancer.

The aim of the present study was to evaluate the incidence and explore the risk factors of febrile neutropenia (FN) in patients with esophageal cancer receiving neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy in real-world settings. We retrospectively reviewed clinical data of 128 consecutive patients with esophageal cancer. Specifically, these patients underwent neoadjuvant DCF chemotherapy with prophylactic antibiotic administration at our institution between July 2009 and January 2015. Two FN-related endpoints were set as follows: definite FN (dFN) defined as grade 4 neutropenia at the onset of fever and clinically suspected FN (csFN), which included both patients with dFN and patients without grade 4 neutropenia but with deteriorating grade 3 neutropenia at the onset of fever who were clinically diagnosed with FN for which they underwent treatment. The risk factors for dFN and csFN were evaluated based on patients' characteristics. A total of 72 (56.3%) patients developed grade 3 or grade 4 neutropenia and 26 (20.3%) developed csFN including 14 (10.9%) with dFN. Multivariate analysis revealed that older age (OR 3.57, CI 1.27-10.1, P = 0.016) and living alone (OR 5.17, 95% CI 1.26-21.3, P = 0.023) were statistically significant risk factors for csFN development. As to dFN, no statistically significant risk factors were identified. Older age and living alone are significant risk factors for developing FN, and thus, particularly for patients with risk factors for FN, G-CSF should be considered instead of prophylactic antibiotics with careful observation.

Profile of Ventilator Associated Pneumonia in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Care Center in India

Introduction: Limited literature is available on VAP in children, particularly from India.Hence this study aims to determine the incidence, clinical, laboratory, radiological and microbiological profile, risk factors, and outcomes of ventilator-associated pneumonia in pediatric patients. Methods: This is a prospective observational study which enrolled 125 children who were mechanically ventilated in the PICU of a tertiary teaching care hospital over a period of 2 years. Demographic, clinical, radiological and laboratory details were collected and CPIS was used to diagnose VAP. Endo tracheal aspirates were obtained at 48hrs and 96 hrs of initiation of mechanical ventilation and were cultured as per standard guidelines. All the demographic, clinical, radiological and micro biological details were entered in SPSS version 17.0.Standard statistical tests were used to analyze data. Results: Among the 125 ventilated children, 44 were found to have VAP as per the CPIS showing its incidence of 35.2%. In our study incidence of early VAP is 27.6% while that of late VAP is 75%. The major risk factor for the incidence of VAP in this study was the duration of ventilation. VAP occurred in 75% of patients intubated for more than 5 days. Among 63 children who were reintubated, 34(53.9%) developed VAP while the incidence of VAP was only 16.1% among those who were not reintubated (p value- 0.016). In this study out of the microorganisms isolated in patients with early VAP, 45% were Acinetobacter species, 20% Klebsiella pneumoniae and 10% Pseudomonas aeruginosa. Whereas in late onset VAP, Acinetobacter constituted 60% of all microbes while the rest comprised of Pseudomonas aeruginosa (20%) and Klebsiella pneumonia (6.6%). Conclusions: Significant risk factors in development of VAP were reintubation and duration of ventilation. The most common VAP pathogen was Acinetobacter species.Tracheostomized children have higher incidence of VAP but have higher recovery rates.

Dysglycemia after distal pancreatectomy: Results of a 10-year series using prospective endocrine evaluation

Background: Distal pancreatectomy (DP) is a commonly utilized procedure by hepatopancreatobiliary surgeons for the management of pancreatic body and tail lesions. While associated with low mortality rates, the development of postoperative diabetes represents a challenge to both patient and physician. Limited literature is available regarding the development or reversibility of impaired glucose tolerance and/or type-II diabetes mellitus (IGT/DM) in this patient population. The primary aim was to define the post-surgical clinical evolution of IGT/DM and the association with the pre-operative glycemic profile of patients following DP. Methods: In this prospective study, pre and postoperative fasting and 2-hour postprandial oral glucose challenge testing (OGTT) laboratories including plasma glucose, glycated hemoglobin (A1c), insulin, and c-peptide were measured in consecutive non-diabetic patients undergoing DP by the senior author from 2007 to 2017. Benign, pre-malignant, and malignant indications were included. Differences in postprandial chemistries from fasting values are denoted with delta (Δ) prefix. American Diabetes Association definitions were used for glycemic classifications. Univariate and multivariate risk factor analysis was performed overall and for individual diabetic classes in determining the development of IGT/DM. Kaplan-Meier survival curves were constructed for onset to endocrine and exocrine dysfunctions, and patient survival. Results: Among 216 patients included (mean age 63 ± 13.7 years, 71.3% Caucasians, 56% female, mean BMI 28.5 m/kg2); 29.6% (n = 64), 31% (n = 67), 39.5% (n = 85) were pre-operatively diagnosed with no-diabetes (No-DM), with pre-diabetes (Pre-DM), or diabetes (DM), respectively. At 120-months of follow-up, 17 (13.5%), 86 (39.0%), and 115 (53.2%) patients were classified as No-DM, Pre-DM or DM, respectively. Based on preoperative laboratories, patients with Pre-DM had 85% increased risk of developing post-op dysglycemia (RR = 1.85, CI 1.126-3.041, p = 0.021), compared to those with no-DM, while 80% (68/85) patients with preoperative DM retained there IGT/DM status postoperatively. Patients developing post-operative IGT/DM demonstrated higher preoperative fasting glucose, OGTT-glucose, and A1c (all p ≤ 0.010), and a greater Δglucose compared to those classified as Pre-DM and No-DM, respectively (Δ64.5±38.0 vs Δ32.5±37.9 vs Δ4.33 ± 6.03; p 130, Δglucose >30, A1c >6.0, HOMA-IR ≥2, and surgical pathology of chronic pancreatitis as risk factors for developing IGT/DM. In patients with No-DM preoperatively, a HOMA-IR >1 was identified as a risk factor for development of postoperative IGT/DM after adjusting for multiple co-variates. For patients classified with DM preoperatively by fasting or OGTT chemistries but whom still retained an A1c ≤ 6.4, multivariate analysis identified an A1c ≤ 6.1 and the absence of a history of smoking as predictors of these diabetics returning to euglycemia postoperatively. There was no association between advancing age, BMI, race, or pancreatic ductal adenocarcinoma and post-operative IGT/DM development. Conclusion: Approximately 40% and 53% of patients undergoing distal pancreatectomy develop post-operative IGT and DM, respectively over 10-years. Higher pre-op fasting glucose, OGTT glucose, A1c, HOMA-IR, and chronic pancreatitis are significant risk factors for development of diabetes. Alternatively, diabetics diagnosed by fasting or OGTT glucose values but non-diabetic A1c values, a preoperative A1c ≤ 6.1 and absence of a history of smoking may indicate postoperative conversion to a euglycemic state. The development of new-onset IGT/DM or persistent diabetes diagnosis following distal pancreatectomy is multifactorial and assessment of pre-operative glycemic status is paramount when counseling patients on their risk of developing postoperative IGT/DM.

Proinflammatory and amyloidogenic S100A9 induced by traumatic brain injury in mouse model

Traumatic brain injury (TBI) represents a significant risk factor for development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The S100A9-driven amyloid-neuroinflammatory cascade occurring during primary and secondary TBI events can serve as a mechanistic link between TBI and Alzheimer’s as demonstrated recently in the human brain tissues. Here by using immunohistochemistry in the controlled cortical impact TBI mouse model we have found pro-inflammatory S100A9 in the brain tissues of all mice on the first and third post-TBI days, while 70% of mice did not show any S100A9 presence on seventh post-TBI day similar to controls. This indicates that defensive mechanisms effectively cleared S100A9 in these mouse brain tissues during post-TBI recovery. By using sequential immunohistochemistry we have shown that S100A9 was produced by both neuronal and microglial cells. However, Aβ peptide deposits characteristic for Alzheimer’s disease were not detected in any post-TBI animals. On the first and third post-TBI days S100A9 was found to aggregate intracellularly into amyloid oligomers, similar to what was previously observed in human TBI tissues. Complementary, by using Rayleigh scatting, intrinsic fluorescence and atomic force microscopy we demonstrated that in vitro S100A9 self-assembles into amyloid oligomers within minutes. Its amyloid aggregation is highly dependent on changes of environmental conditions such as variation of calcium levels, pH, temperature and reduction/oxidation, which might be relevant to perturbation of cellular and tissues homeostasis under TBI. Present results demonstrate that S100A9 induction mechanisms in TBI are similar in mice and humans, emphasizing that S100A9 is an important marker of brain injury and therefore can be a potential therapeutic target.

Nitric Oxide Donor Prevents Neonatal Isoflurane-induced Impairments in Synaptic Plasticity and Memory.

Some general anesthetics have been shown to have adverse effects on neuronal development that affect neural function and cognitive behavior.Clinically relevant concentrations of inhalational anesthetics inhibit the postsynaptic density (PSD)-95, discs large homolog, and zona occludens-1 (PDZ) domain-mediated protein-protein interaction between PSD-95 or PSD-93 and N-methyl-D-aspartate receptors or neuronal NO synthase. Neonatal PSD-95 PDZ2WT peptide treatment mimics the effects of isoflurane (~1 minimum alveolar concentration) by altering dendritic spine morphology, neural plasticity, and memory without inducing detectable increases in apoptosis or changes in synaptic density.These results indicate that a single dose of isoflurane (~1 minimum alveolar concentration) or PSD-95 PDZ2WT peptide alters dendritic spine architecture and functions important for cognition in the developing brain. This impairment can be prevented by administration of the NO donor molsidomine. In humans, multiple early exposures to procedures requiring anesthesia constitute a significant risk factor for development of learning disabilities and disorders of attention. In animal studies, newborns exposed to anesthetics develop long-term deficits in cognition. Previously, our laboratory showed that postsynaptic density (PSD)-95, discs large homolog, and zona occludens-1 (PDZ) domains may serve as a molecular target for inhaled anesthetics. This study investigated a role for PDZ interactions in spine development, plasticity, and memory as a potential mechanism for early anesthetic exposure-produced cognitive impairment. Postnatal day 7 mice were exposed to 1.5% isoflurane for 4 h or injected with 8 mg/kg active PSD-95 PDZ2WT peptide. Apoptosis, hippocampal dendritic spine changes, synapse density, long-term potentiation, and cognition functions were evaluated (n = 4 to 18). Exposure of postnatal day 7 mice to isoflurane or PSD-95 PDZ2WT peptide causes a reduction in long thin spines (median, interquartile range [IQR]: wild type control [0.54, 0.52 to 0.86] vs. wild type isoflurane [0.31, 0.16 to 0.38], P = 0.034 and PDZ2MUT [0.86, 0.67 to 1.0] vs. PDZ2WT [0.55, 0.53 to 0.59], P = 0.028), impairment in long-term potentiation (median, IQR: wild type control [123, 119 to 147] and wild type isoflurane [101, 96 to 118], P = 0.049 and PDZ2MUT [125, 119 to 131] and PDZ2WT [104, 97 to 107], P = 0.029), and deficits in acute object recognition (median, IQR: wild type control [79, 72 to 88] vs. wild type isoflurane [63, 55 to 72], P = 0.044 and PDZ2MUT [81, 69 to 84] vs. PDZ2WT [67, 57 to 77], P = 0.039) at postnatal day 21 without inducing detectable differences in apoptosis or changes in synaptic density. Impairments in recognition memory and long-term potentiation were preventable by introduction of a NO donor. Early disruption of PDZ domain-mediated protein-protein interactions alters spine morphology, synaptic function, and memory. These results support a role for PDZ interactions in early anesthetic exposure-produced cognitive impairment. Prevention of recognition memory and long-term potentiation deficits with a NO donor supports a role for the N-methyl-D-aspartate receptor/PSD-95/neuronal NO synthase pathway in mediating these aspects of isoflurane-induced cognitive impairment.

Prevalence of Secondary Adrenal Insufficiency in Recipients of Pediatric Hematopoietic Stem Cell Transplant: A Single Center Study

Background Data on adrenal function following pediatric allogeneic hematopoietic cell transplantation (HCT) is limited. Therefore, a single-institution retrospective study was performed to determine the prevalence of secondary adrenal insufficiency (AI) and identify associated risk factors in pediatric HCT recipients. Methods All allogeneic HCT patients from January 2007 through December 2014, with a minimum of two years of post-HCT follow up were included. AI was diagnosed when testing done at either clinical presentation of AI or routine yearly screening in the long term follow up clinic, revealed a morning cortisol level Results Eighty patients (48 male, 32 female) with malignant (n=38) and non-malignant diagnoses (n=42) were included. Median age at HCT and length of follow up were 7.6 years (range 0.1- 20.5 years) and 4.1 years (range 2-10 years), respectively. Twelve (12, 15%) patients developed secondary AI at a median of 16 months post-HCT (range 2-61 months), with an equal number presenting with clinical AI (n=6) and biochemical AI (n=6) respectively. In univariate analysis (Table 1), occurrence of graft-versus-host disease (GvHD), and post-HCT corticosteroid exposure were significant risk factors for development of secondary AI. Age, gender, type of diagnosis, total body irradiation (TBI)-containing and myeloablative conditioning were not. Conclusion: GvHD, and post-HCT steroid exposure were significant risk factors for AI, with one-third patients with post-HCT corticosteroid exposure diagnosed with AI. As half of patients with AI in this cohort were asymptomatic, routine screening for AI should be performed in pediatric allogeneic HCT recipients for timely diagnosis of AI to prevent morbidity associated with this complication.

THE ROLE OF CIGARETTE SMOKING AND ALCOHOL CONSUMPTION IN PULMONARY TUBERCULOSIS DEVELOPMENT AND RECURRENCE.

SUMMARYDuring a two-year period (2001-2003), 464 patients were treated for tuberculosis at Jordanovac Department for Lung Diseases in Croatia. Besides pulmonary tuberculosis in 97.7% of patients, patients were also treated for tuberculous pleurisy (0.9%), tuberculous laryngitis (0.6%), tuberculous meningitis (0.2%), tuberculous pericarditis (0.2%) and urogenital tuberculosis (0.4%). Out of the total number of patients, 57.3% declared themselves to be active smokers (men were predominant and made up to 80.8%) and 20.9% to be active alcohol consumers. Both risk factors, i.e. smoking and alcohol consumption, were present in 15.1% of all patients. The most common comorbidities were diabetes mellitus (30.4%), cardiac diseases (11.2%) and chronic obstructive pulmonary disease (8.0%). Lung carcinoma was the most common malignant disease (n=51), with Mycobacterium tuberculosis isolated in 33% of them. Seventy-two of 464 (15.5%) patients had recurrences of tuberculosis. Of these, 30.5% had one of the risk factors (20.8% were smokers and 9.7% consumed alcohol), while 32.5% of patients had both risk factors. In conclusion, cigarette smoking was proved to be the most significant risk factor for development of pulmonary tuberculosis and its recurrence.

Predictors of Chronic Thromboembolic Pulmonary Hypertension

to elucidate predictors of development of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary artery thromboembolism (PTE). We included in this study 210 patients hospitalized withdiagnosis ofsubmassive and massive PTE from 2013 to 2017. In 1to3years after initial hospitalization these patients were invited for control examination. According to results of this examination patients were divided into two groups: with (group 1, n=45) and without (group 2, n=165) signs of CTEPH. Severity ofpulmonary artery vascular bed involvement was assessed bymultislice computed tomography (MSCT) angiography and lung scintigraphy. For detection of thrombosis in the inferior vena cava system we used ultrasound angioscanning. Examination also included echocardiography. Intheprocess of mathematical analysis, the following risk factors for the development of CTEPH embolism were determined: duration of thrombotic history (group 1 - 13.70±2.05 days, group 2- 16.16±1.13days, p=0.015), localization of venous thrombosis in the lower extremities (the most favorable- shin veins, popliteal, and common femoral veins, unfavorable- superficial femoral vein). The choice of the drug for thrombolytic and anticoagulant therapy: streptokinase and urokinase were significantly more effective than alteplase, rivaroxaban was superior to the combination of unfractionated orlow molecular weight heparins with warfarin. Also, risk factors for the development of CTEPH were the initial degree of pulmonary hypertension and tricuspid insufficiency, as well as the positive dynamics of these indicators at the background of thrombolytic oranticoagulant therapy. Of concomitant diseases, significant risk factors for development of CTEPH were grade 3 hypertensive disease, diabetes mellitus, post-infarction cardiosclerosis. Ontheother hand, age, gender, degree of severity at the time of admission, presence ofinfarction pneumonia, surgical prevention of recurrent pulmonary embolism, number of pregnancies and deliveries, history oftrauma and malignancies, cardiac arrhythmias produced nosignificant impact on the development of CTEPH.

Avascular Necrosis of the Femoral Head in Sickle Cell Disease in Egypt and Oman: A Cross Sectional Study

BACKGROUND:Avascular necrosis (AVN) especially of the femoral head has long been recognized as a morbidity of sickle cell disease (SCD). AVN might be of gradual onset and silent or run a more acute course with severe pain and limping.The clinical presentations and risk factors of this complication among Egyptian and Omani children and young adults with SCD were not fully studied. We aimed to determine the patterns of presentation, risk factors, diagnosis and management of avascular necrosis of the hip in SCD in the 2 centers.PATIENTS AND METHODS: A cross sectional study carried out at the Pediatric Hematology clinics of Ain Shams and Sultan Qaboos University Hospitals. All young SCD patients diagnosed with hip AVN during the period between Jan. 2010-Jan. 2018 were included. Age of 1st presentation with SCD, symptoms or signs of AVN, frequency of VOCs, hospital admissions and transfusion, spleen status, hydroxyurea administration (dose and compliance ), radiological findings (X-ray and MRI using FICAT and Arlet Staging) and serum ferritin were recorded. Therapeutic options included physiotherapy, autologous bone marrow stem cell injection in the affected joint, hip coring, and hip replacement.RESULTS:Sixty-eight children, adolescents and young adults with SCD and AVN; aged 8-22 years of both sexes were recruited from two centers; Egypt; n= 22, and Oman; n= 46. Twenty patients (29.4%) had hemoglobin SS while 48 (70.6%) had Sickle-βThalassemia. Thirty-seven (54%), were males with a median age of 16 years, five out of the 22 Egyptians have in addition to hip AVN, femoral shaft necrosis in one patient and 2 have lumbar vertebra necrosis. According to FICAT and Alert classification of AVN; 22 patients had stage 0, 2 patients had stage I, 13 patients had stage II, 14 had stage III and 17 patients were at stage IV; 64% of patients had stage II and above at diagnosis. Sixty percent of the studied population were on Hydroxyurea; of them 25% were non-compliant. Multivariate regression analysis didn't show a significant risk factor for development of AVN in these patients. Management was different in the 2 centers; Half of the patients in Oman were managed with physiotherapy alone; while only 25% in Egypt. Stem cell injection in the bone marrow of the affected hip was tried in 25% of Omani patients with good success while none in the Egyptian patients. Hip replacement in was performed in a total of 7 patients and Bone marrow transplantation in two.CONCLUSION:Avascular necrosis of the hip is a significant cause of morbidity in SCD in this part of the world. Majority of patients had an advanced disease at diagnosis, which emphasizes the need of early screening to avoid complications of the advanced disease. Injection of bone marrow in the affected hip might be a promising tool to prevent disease progression and improve the symptoms. DisclosuresNo relevant conflicts of interest to declare.