Leveraging machine learning to enhance postoperative risk assessment in coronary artery bypass grafting patients with unprotected left main disease - A retrospective cohort study.

BACKGROUND: Risk stratification for patients undergoing coronary artery bypass surgery (CABG) for left main coronary artery (LMCA) disease is essential for informed decision-making. This study explored the potential of machine learning (ML) methods to identify key risk factors associated with mortality in this patient group. METHODS: This retrospective cohort study was conducted on 866 patients from the Gulf Left Main Registry who presented between 2015 and 2019. The study outcome was hospital all-cause mortality. Various machine learning models [logistic regression, random forest (RF), k-nearest neighbor, support vector machine, naïve Bayes, multilayer perception, boosting] were used to predict mortality, and their performance was measured using accuracy, precision, recall, F1 score, and area under the receiver operator characteristic curve (AUC). RESULTS: Nonsurvivors had significantly greater EuroSCORE II values (1.84 (10.08-3.67) vs. 4.75 (2.54-9.53) %, P<0.001 for survivors and nonsurvivors, respectively). The EuroSCORE II score significantly predicted hospital mortality (OR: 1.13 (95% confidence interval: 1.09-1.18), P<0.001), with an AUC of 0.736. RF achieved the best ML performance (accuracy=98, precision=100, recall=97 and F1 score=98). Explainable artificial intelligence using SHAP demonstrated the most important features as follows: preoperative lactate level, emergency surgery, chronic kidney disease (CKD), NSTEMI, nonsmoking status, and sex. QLattice identified lactate and CKD as the most important factors for predicting hospital mortality this patient group. CONCLUSION: This study demonstrates the potential of ML, particularly the Random Forest, to accurately predict hospital mortality in patients undergoing CABG for LMCA disease and its superiority over traditional methods. The key risk factors identified, including preoperative lactate levels, emergency surgery, chronic kidney disease, NSTEMI, nonsmoking status, and sex, provide valuable insights for risk stratification and informed decision-making in this high-risk patient population. Additionally, incorporating newly identified risk factors into future risk scoring systems can further improve mortality prediction accuracy.

Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

Single Versus Dual Antiplatelet Therapy After Coronary Artery Bypass Grafting for Unprotected Left-Main Coronary Disease.

BACKGROUND: The use of dual antiplatelet therapy (DAPT) after coronary revascularization for left-main disease is still debated. The study aimed to characterize patients who received dual versus single antiplatelet therapy (SAPT) after coronary artery bypass grafting (CABG) for unprotected left-main disease and compare the outcomes of those patients. RESULTS: This multicenter retrospective cohort study included 551 patients who were grouped into 2 groups: patients who received SAPT (n = 150) and those who received DAPT (n = 401). There were no differences in age ( P = 0.451), gender ( P = 0.063), smoking ( P = 0.941), diabetes mellitus ( P = 0.773), history of myocardial infarction ( P = 0.709), chronic kidney disease ( P = 0.615), atrial fibrillation ( P = 0.306), or cerebrovascular accident ( P = 0.550) between patients who received SAPT versus DAPT. DAPTs were more commonly used in patients with acute coronary syndrome [87 (58%) vs. 273 (68.08%); P = 0.027], after off-pump CABG [12 (8%) vs. 73 (18.2%); P = 0.003] and in patients with radial artery grafts [1 (0.67%) vs. 32 (7.98%); P < 0.001]. While SAPTs were more commonly used in patients with low ejection fraction [55 (36.67%) vs. 61 (15.21%); P < 0.001] and in patients with postoperative acute kidney injury [27 (18%) vs. 37 (9.23%); P = 0.004]. The attributed treatment effect of DAPT for follow-up major adverse cerebrovascular and cardiac events was not significantly different from that of SAPT [ß, -2.08 (95% confidence interval (CI), -20.8-16.7); P = 0.828]. The attributed treatment effect of DAPT on follow-up all-cause mortality was not significantly different from that of SAPT [ß, 4.12 (CI, -11.1-19.32); P = 0.595]. There was no difference in bleeding between groups ( P = 0.666). CONCLUSIONS: DAPTs were more commonly used in patients with acute coronary syndrome, after off-pump CABG, and with radial artery grafts. SAPTs were more commonly used in patients with low ejection fraction and acute kidney injury. Patients on DAPT after CABG for left-main disease had comparable major adverse cerebrovascular and cardiac events and survival to patients on SAPT, with no difference in bleeding events.

Alterations in circulating lipidomic profile in patients with type 2 diabetes with or without non-alcoholic fatty liver disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) often coexist and drive detrimental effects in a synergistic manner. This study was designed to understand the changes in circulating lipid and lipoprotein metabolism in patients with T2DM with or without NAFLD. Methods: Four hundred thirty-four T2DM patients aged 18-60 years were included in this study. Fatty liver was assessed by FibroScan. The comprehensive metabolic lipid profiling of serum samples was assessed by using high-throughput proton NMR metabolomics. Results: Our data revealed a significant association between steatosis and serum total lipids in VLDL and LDL lipoprotein subclasses, while total lipids in HDL subclasses were negatively associated. A significant positive association was found between steatosis and concentration of lipids, phospholipids, cholesterol, and triglycerides in VLDL and LDL subclasses, while HDL subclasses were negatively associated. Furthermore, a significant, association was observed between fibrosis and concentrations of lipids, phospholipids, cholesterol, and triglycerides in very small VLDL, large, and very large HDL subclasses. Subgroup analysis revealed a decrease in the concentrations of lipids, phospholipids, cholesterol, and other lipid biomolecules in patients using antilipemic medications. Conclusion: The metabolomics results provide evidence that patients with T2DM with higher steatosis grades have altered lipid metabolomics compared to patients without steatosis. Increased lipid, phospholipids, cholesterol, and triglycerides concentration of VLDL and LDL subclasses are associated with steatosis in patients with T2DM.

Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes.

Background: Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim: To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods: This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results: In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion: In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Transient elastography for the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes: Evidence from the CORDIAL cohort study.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of NAFLD among Saudi patients with T2DM using transient elastography. Methods: A total of 490 patients with T2DM who attended diabetes and primary care clinics were recruited. Controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were obtained via FibroScan to assess steatosis and fibrosis. Results: Of the examined 490 patients with T2DM, 396 (80.8%) had hepatic steatosis (CAP ≥248 dB/m): 326 (66.5%) had severe steatosis (CAP ≥280 dB/m), while 41 (8.4%) and 29 (5.9%) had mild (CAP ≥248 to <268 dB/m) and moderate steatosis (CAP ≥268 to <280 dB/m), respectively. Of the 396 patients with steatosis, only 35 (8.8%) had LSM ≥7.9 kPa, suggesting the presence of fibrosis, while 361 (91%) had LSM <7.9 kPa, indicating the absence of fibrosis. Increased body mass index (BMI), waist circumference, systolic blood pressure (SBP), and alanine aminotransferase (ALT) were positively associated with both steatosis and fibrosis. After adjusting for age and gender, data from logistic regression analysis demonstrated BMI, waist circumference, SBP, ALT, and high-density lipoprotein (HDL) as significant independent factors for steatosis, while SBP was the only significant predictor associated with fibrosis. Conclusions: Our results demonstrate an increase in prevalence of NAFLD in Saudi patients with T2DM, based on transient elastography and CAP score. The risk of NAFLD appears to be higher in T2DM patients with abdominal obesity, elevated SBP, and increased ALT levels, which supports the screening of these conditions in patients with T2DM.

Cyber-Security Threats and Side-Channel Attacks for Digital Agriculture.

The invention of smart low-power devices and ubiquitous Internet connectivity have facilitated the shift of many labour-intensive jobs into the digital domain. The shortage of skilled workforce and the growing food demand have led the agriculture sector to adapt to the digital transformation. Smart sensors and systems are used to monitor crops, plants, the environment, water, soil moisture, and diseases. The transformation to digital agriculture would improve the quality and quantity of food for the ever-increasing human population. This paper discusses the security threats and vulnerabilities to digital agriculture, which are overlooked in other published articles. It also provides a comprehensive review of the side-channel attacks (SCA) specific to digital agriculture, which have not been explored previously. The paper also discusses the open research challenges and future directions.

The COVID-19 impact on air condition usage: a shift towards residential energy saving.

The enforcement of the Movement Control Order to curtail the spread of COVID-19 has affected home energy consumption, especially HVAC systems. Occupancy detection and estimation have been recognized as key contributors to improving building energy efficiency. Several solutions have been proposed for the past decade to improve the precision performance of occupancy detection and estimation in the building. Environmental sensing is one of the practical solutions to detect and estimate occupants in the building during uncertain behavior. However, the literature reveals that the performance of environmental sensing is relatively poor due to the poor quality of the training dataset used in the model. This study proposed a smart sensing framework that combined camera-based and environmental sensing approaches using supervised learning to gather standard and robust datasets related to indoor occupancy that can be used for cross-validation of different machine learning algorithms in formal research. The proposed solution is tested in the living room with a prototype system integrated with various sensors using a random forest regressor, although other techniques could be easily integrated within the proposed framework. The primary implication of this study is to predict the room occupation through the use of sensors providing inputs into a model to lower energy consumption. The results indicate that the proposed solution can obtain data, process, and predict occupant presence and number with 99.3% accuracy. Additionally, to demonstrate the impact of occupant number in energy saving, one room with two zones is modeled each zone with air condition with different thermostat controller. The first zone uses IoFClime and the second zone uses modified IoFClime using a design-builder. The simulation is conducted using EnergyPlus software with the random simulation of 10 occupants and local climate data under three scenarios. The Fanger model's thermal comfort analysis shows that up to 50% and 25% energy can be saved under the first and third scenarios.

Greater concentrations of IGF-1 are associated with increasing pregnancy rate in melatonin implanted anestrous Barki ewes.

The present study was conducted to determine if increases in IGF-1 concentration, associated with treatment of ewes with melatonin, has beneficial effects on pregnancy rates when there is induction of estrus in anestrous ewes. A total of 120 multiparous lactating ewes were assigned to three groups (n = 10/group). Ewes of Group 1 were treated with a melatonin implant for 42 days followed by insertion of a controlled internal drug release (CIDR) device for 14 days with administration of equine chorionic gonadotropin (eCG) at day of CIDR removal. The ewes of Group 2 were treated with a CIDR and eCG at the same times as ewes of Group 1 and ewes of Group 3 were assigned to an be untreated control group. Melatonin implantation resulted in an increase in IGF-1 concentrations and lesser estradiol (E2) and triiodothyronine (T3) concentrations. Ewes of Groups 1 and 2 had the greatest progesterone (P4) concentration compared ewes of Group 3. The E2:P4 ratio was less in ewes of Group 1 compared Group 3. Melatonin implantation of ewes resulted in a greater pregnancy rate compared to treatment with the CIDR and eCG which, in turn, had a greater rate than ewes of the control group. In conclusion, melatonin implantation modulates the hormonal milieu including P4, E2, T3 and IGF-1 in seasonally anestrous ewes. Increased IGF-1concentrations, as a result of melatonin treatment, are associated with a greater percentage pregnancy rate when there is treatment of anestrous ewes to induce onset of estrus.

Microbial dysbiosis in irritable bowel syndrome: A single-center metagenomic study in Saudi Arabia.

BACKGROUND: The focus of this study was to explore potential differences in colonic mucosal microbiota in irritable bowel syndrome (IBS) patients compared to a control group utilizing a metagenomic study. METHODS: Mucosal microbiota samples were collected from each IBS patient utilizing jet-flushing colonic mucosa in unified segments of the colon with distilled water, followed by aspiration, during colonoscopy. All the purified dsDNA was extracted and quantified before metagenomic sequencing using an Illumina platform. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota, which were obtained during screening colonoscopies. RESULTS: The microbiota data on 50 IBS patients (31 females), with a mean age 43.94 ± 14.50 (range19-65), were analyzed in comparison to 50 controls. Satisfactory DNA samples were subjected to metagenomics study, followed by comprehensive comparative phylogenetic analysis. Metagenomics analysis was carried out, and 3.58G reads were sequenced. Community richness (Chao) and microbial structure in IBS patients were shown to be significantly different from those in the control group. Enrichment of Oxalobacter formigenes, Sutterella wadsworthensis, and Bacteroides pectinophilus was significantly observed in controls, whereas enrichment of Collinsella aerofaciens, Gemella morbillorum, and Veillonella parvula Actinobacteria was observed significantly in the IBS cohort. CONCLUSION: The current study has demonstrated significant differences in the microbiota of IBS patients compared to controls.

Effects of microbial feed additives on feed utilization and growth performance in growing Barki lambs fed diet based on peanut hay.

The effects of supplementing diet of growing lambs with microbial feed additive mixture (direct-fed microbial; DFM) based on Saccharomyces cerevisiae, lactic acid bacteria and exogenous enzymes on feed intake, nutrient digestibility, nitrogen (N) utilization, ruminal fermentation, blood chemistry and growth performance were studied. The study was a completely randomized design with 12 growing Barki lambs divided into two groups of six lambs per treatment. Lambs were offered a control diet of peanut hay and concentrates (1:1 dry matter (DM) basis) or the control diet supplemented with DFM at 0.5 g/day (Bactozyme treatment) for 16 weeks. There was no effect on feed efficiency but Bactozyme lambs had increased (p = 0.009) feed intake, average daily gain (p = 0.042) and final body weight (p = 0.047). Bactozyme treatment had greater neutral detergent fiber (p = 0.020) and acid detergent fiber (p = 0.034) digestibility compared with the control treatment. Metabolism experiment showed that the feed additive mixture increased (p<0.05) N intake and N retention. Bactozyme treatment had greater blood total protein (p = 0.027), and globulin (p = 0.025) concentrations compared with the control treatment. It is concluded that supplementing growing Barki lambs with DFM at 0.5 g daily enhanced final body weight gain and fiber digestion without affecting feed efficiency.

Microbial dysbiosis in inflammatory bowel diseases: results of a metagenomic study in Saudi Arabia.

BACKGROUND: The intestinal microbiota plays an essential role in the pathogenesis of ulcerative colitis (UC)and Crohn disease (CD). METHODS: Metagenomic studies were used to study microbiota in the diagnosed cases of UC and CD at King Fahad Medical City, Riyadh, Saudi Arabia. Each segment of the colon was flushed with distilled water during colonoscopy, and the material was aspirated, immediately frozen for the study. The patients attending for screening colonoscopies were taken as age-matched healthy controls. The UC patients were followed clinically for any signs of exacerbation relapse, and CD patients were followed for any complications. RESULTS: The metagenomic data on 46 (24 females) patients with CD were analyzed along with a group of age and gender-matched controls. Their age ranged from 14 to 65 years, mean age 25.19±10.67 years. There were 50 UC patient (28 females) mean age of 34.42±12.58, and their age ranged from 13-58 years. This study identified enrichment of 19 genera in the control group (Abiotrophia, Anaerofustis, Butyrivibrio, Campylobacter, Catenibacterium, Coprococcus, Dorea, Eubacterium, Facklamia, Klebsiella, Lactococcus, Oscillibacter, Paenibacillus, Parabacteroides, Parasutterella, Porphyromonas, Prevotella, Ruminococcus, Treponema). There was a significant enrichment of 14 genera in our CD cohort (Beggiatoa, Burkholderia, Cyanothece, Enterococcus, Escherichia, Fusobacterium, Jonquetella, Mitsuokella, Parvimonas, Peptostreptococcus, Shigella, Succinatimonas, ThermoanaerobacterVerrucomicrobiales, Vibrio). There was a significant enrichment of 7 genera in UC cohort (Beggiatoa, Burkholderia, Parascardovia, Parvimonas, Pseudoflavonifractor, Thermoanaerobacter, Verrucomicrobiales). CONCLUSIONS: A significant dysbiosis was found in UC and CD patients compared to controls.

Position statement on the diagnosis and management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.

Involvement of Quebracho tannins in diet alters productive and reproductive efficiency of postpartum buffalo cows.

This study was conducted to investigate the effects of 10 weeks supplementation of Quebracho tannins (QT; 0 [control], 100 [QT100] or 200 g/[cow·d] [QT200]) to 30 multiparous postpartum buffalo cows (10 cows per group) on milk yield and composition, blood metabolites and reproductive performance. Supplementation of QT100 had no significant effect on milk yield, whereas QT200 decreased (P < 0.05) this trait. Compared with the control group, both QT levels decreased (P < 0.05) fat-corrected milk (FCM) yield, but no significant effects were found on percentages of milk fat and protein. Contrariwise, yields of milk fat, lactose and milk protein were decreased (P < 0.05) when QT200 was supplemented. The solids nonfat (SNF) percentage and yield were decreased (P < 0.05) with QT100 supplementation. Moreover, QT tended to numerically reduce total number of ovarian follicles, number of small follicles, peripheral progesterone concentration and conception rate. Supplementation of QT200 numerically increased number of large follicles, mean diameter of large follicle, number and diameters of corpora lutea. The inclusion of QT200 shortened days open (DO) and decreased number of services per conception. Contrariwise, QT did not show significant effects on serum total protein, albumin, globulin, glucose, cholesterol and triglycerides concentrations. Supplementation of QT100 caused an increase (P < 0.05) of serum urea compared with that in control and QT200 groups. Generally, QT decreased (P < 0.05) serum creatinine concentration. Therefore, the supplementation of a commercial QT to early lactating Egyptian buffalo cows displayed negative consequences on their productive and reproductive performances.

Colonic Mucosal Microbiota in Colorectal Cancer: A Single-Center Metagenomic Study in Saudi Arabia.

BACKGROUND AND AIM: Because genetic and geographic variations in intestinal microbiota are known to exist, the focus of this study was to establish an estimation of microbiota in colorectal cancer (CRC) patients in Saudi Arabia by means of metagenomic studies. METHODS: From July 2010 to November 2012, colorectal cancer patients attending our hospital were enrolled for the metagenomic studies. All underwent clinical, endoscopic, and histological assessment. Mucosal microbiota samples were collected from each patient by jet-flushing colonic mucosa with distilled water at unified segments of the colon, followed by aspiration, during colonoscopy. Total purified dsDNA was extracted and quantified prior to metagenomic sequencing using an Illumina platform. Satisfactory DNA samples (n = 29) were subjected to metagenomics studies, followed by comprehensive comparative phylogenetic analysis. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota. RESULTS: Metagenomics data on 29 patients (14 females) in the age range 38-77 years were analyzed. The majority 11 (37%) of our patients were overweight (BMI = 25-30). Rectal bleeding was the presenting symptom in 18/29 (62%), while symptomatic anemia was the presenting symptom in 11/29 (37%). The location of colon cancer was rectal in 14 (48%), while cecal growth was observed in 8 (27%). Hepatic flexure growth was found in 1 (3%), descending colonic growth was found in 2 (6%), and 4 (13%) patients had transverse colon growth. The metagenomics analysis was carried out, and a total of 3.58G reads were sequenced, and about 321.91G data were used in the analysis. This study identified 11 genera specific to colorectal cancer patients when compared to genera in the control group. Bacteroides fragilis and Fusobacterium were found to be significantly prevalent in the carcinoma group when compared to the control group. CONCLUSION: The current study has given an insight into the microbiota of colorectal cancer patients in Saudi Arabia and has identified various genera significantly present in these patients when compared to those of the control group.

Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study.

Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.

Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT.

Antifungal prophylaxis with azoles is considered standard in allogeneic hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. We identified 67 patients with hematologic malignancies who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT. Patients received sirolimus and voriconazole concurrently for a median of 113 days. The median daily dose reduction of sirolimus at the start of coadministration was 90%. The median serum sirolimus trough levels before and at steady state of coadministration were 5.8 ng/mL (range: 0-47.6) and 6.1 ng/mL (range: 1-14.2) (P=0.45), respectively. One patient with an average sirolimus level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was reported. Seventeen patients (25%) prematurely discontinued voriconazole because of the adverse events. Only two patients (3%) presented with possible invasive fungal infections at day 100. We demonstrate that sirolimus and voriconazole coadministration with an empiric 90% sirolimus dose reduction and close monitoring of sirolimus trough levels is safe and well tolerated.

Infection complications and pattern of bacterial resistance in living-donor liver transplantation: a multicenter epidemiologic study in Egypt.

INTRODUCTION: Data on the prevalence and pattern of infection after living-donor liver transplantation (LDLT) are scarce in Egypt. We therefore conducted this study to quantify the incidence, risk factors, and pattern of bacterial resistance post-LDLT in 3 hospitals in Egypt. PATIENTS AND METHODS: We conducted a retrospective, multicenter study of the medical records of 246 patients who underwent LDLT between January 2006 and April 2011 at 3 transplant centers in Egypt. RESULTS: Of 246 patients enrolled in this study, 127 (52%) developed infectious complications after LDLT, with 416 episodes of infection occurring within 3 months of transplantation. Biliary tract infection was the most common, occurring in 169 (40.6%) patients. The rate of infection with Gram-negative bacteria was higher than that of infection with Gram-positive bacteria (310 [74%] vs 87 [21%]; P < .001). Overall, 75% of Gram-negative isolates were multidrug resistant. Significant independent risk factors for infection were portal vein thrombosis (odds ratio, 2.4; P = .037) and biliary complications (odds ratio, 5.4; P < .001). CONCLUSIONS: Our data showed a high-resistance pattern of bacterial infection after LDLT in Egypt. Early biliary complications were an independent risk factor for bacterial infection.

Factors impacting stem cell mobilization failure rate and efficiency in multiple myeloma in the era of novel therapies: experience at Memorial Sloan Kettering Cancer Center.

Thalidomide, lenalidomide and bortezomib have increasingly been incorporated in first-line induction therapies for multiple myeloma. Concerns regarding the impact of these agents, especially lenalidomide, on stem cell mobilization prompted us to re-evaluate the risk factors that impact mobilization, including exposure to novel induction regimens. Among 317 patients who proceeded to stem cell collection after induction therapy between 2000 and 2009, the rate of mobilization failure, defined as the inability to collect 5 × 10(6) CD34+ cells/kg following the first collection attempt, was 13%. By multivariate analysis, independent risk factors associated with mobilization failure included older age (P=0.04), lower platelet count (P=0.002) and use of single-agent G-CSF for mobilization (P<0.0001). When considering for outcome measurement stem cell collection efficiency measured by the number of CD34+ cells yielded per pheresis performed during first collection attempt, lower platelet count, use of single-agent G-CSF and older age were also associated with lower efficiency. In this population mobilized mostly with cyclophosphamide and G-CSF, the use of lenalidomide during induction was not associated with a lower stem cell collection efficiency by multivariate analysis. The data support the current International Multiple Myeloma Working Group guidelines recommending the use of cyclophosphamide and G-CSF based mobilization for patients previously exposed to lenalidomide.

Molecular epidemiology of gonorrhoea in Wales (UK).

OBJECTIVES: After a trend of increasing incidence of gonorrhoea in the 1990s, by 2004 the incidence was declining in England, but continuing to increase in Wales. This prompted an investigation of the epidemiology of gonorrhoea in Wales to inform future prevention and control measures. METHODS: As an extension to Gonococcal Resistance to Antimicrobials Surveillance Programme, between May 2005 and September 2006, 540 consecutive gonococcal isolates were collected from three microbiology laboratories in South Wales. Isolates were typed using Neisseria gonorrhoeae Multi Antigen Sequence Typing tested for susceptibility to therapeutic agents and demographic and behavioural data were collected retrospectively from patient notes. RESULTS: 163 sequence types (STs) were identified in 475 N gonorrhoeae isolates from 502 patient episodes. The most frequently observed STs (>20 isolates) were: 2, 752, 471, 249 and 8, all of which were susceptible to the antimicrobial agents tested. A significant association between ST and sexual orientation was identified, the most frequently observed STs occurring in young (median age <25 years) heterosexuals. STs 147, 4, 1634 and 64 predominated in men who have sex with men. CONCLUSIONS: We confirm the existence of common STs across the UK, as well as identify a number of types that were novel to Wales. Discrete sexual networks were identified, the most localised being in young heterosexuals. Molecular typing provides a method for identifying local clusters of gonorrhoea, and could assist in the implementation and evaluation of targeted interventions.