External Validation of Obese/Critically Ill Vancomycin Population Pharmacokinetic Models in Critically Ill Patients Who Are Obese.

Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population the pharmacokinetics of antimicrobials vary significantly, making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in patients who are critically ill or obese for a cohort of critically ill patients who are obese. This was a multi-center retrospective study conducted at 2 hospitals. Adult patients with a body mass index of ≥30 kg/m2 were included. PubMed was searched for published population pharmacokinetic studies in patients who were critically ill or obese. External validation was performed using Monolix software. A total of 4 models were identified in patients who were obese and 5 models were identified in patients who were critically ill. In total, 138 patients who were critically ill and obese were included, and the most accurate models for these patients were the Goti and Roberts models. In our analysis, models in patients who were critically ill outperformed models in patients who were obese. When looking at the most accurate models, both the Goti and the Roberts models had patient characteristics similar to ours in terms of age and creatinine clearance. This indicates that when selecting the proper model to apply in practice, it is important to account for all relevant variables, besides obesity.

Monkeypox Disease (MPOX) Perceptions among Healthcare Workers versus General Population during the First Month of the WHO Alert: Cross-Sectional Survey in Saudi Arabia.

Background: Monkeypox disease (MPOX) recently re-emerged in May 2022, causing international outbreaks in multiple non-endemic countries. This study demonstrates a novel comparison between the knowledge and perceptions of Saudi healthcare workers (HCWs) and the general public regarding MPOX. Methods: An online survey, conducted from 27 May to 5 June 2022, assessing participants' MPOX and monkeypox virus (MPV) knowledge in terms of transmission, vaccination, isolation precautions, and their attitudes toward seeking more information. Results: A total of 1546 members of the public and 1130 HCWs completed the survey. Briefly, 61.3% of the public and 74.2% of HCWs showed interest in seeking more information about MPOX. Both groups had average overall mean MPOX knowledge scores. Members of the public holding university degrees and those showing high levels of worry regarding MPOX had significantly higher knowledge scores. However, HCWs showed a poor vaccination knowledge score, while only 57% recognized that MPOX can present similarly to COVID-19 in the early stages. Female HCWs and those with high self-rated MPOX awareness had significantly high knowledge scores. HCWs in secondary and tertiary centers had significantly higher knowledge scores. Conclusion: Both groups showed a decent attitude in terms of seeking more MPOX knowledge, which correlated positively with their worry about and awareness of the disease. These observations are mostly as a consequence of the ongoing COVID-19 pandemic, which encouraged the public and HCW to acquire more information about any novel emerging disease. Policymakers should make the most of this attitude in their awareness campaigns to prevent the spread of the disease and encourage vaccination in cases where it is needed. The knowledge gaps among HCWs were most evident in terms of clinical presentation and vaccinations; this problem needs addressing if we are to avoid further emerging MPOX cases.

Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia.

BACKGROUND: Meropenem is commonly used in the ICU to treat gram-negative infections. Due to various pathophysiological changes, critically ill patients are at higher risk of having subtherapeutic concentrations and hence have a higher risk of treatment failure-especially in regions where gram-negative drug resistance is increasing, such as Saudi Arabia. No studies have evaluated the pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Our primary objective is to assess the percentage of patients achieving the therapeutic target for meropenem. METHODS: This prospective observational study was conducted in the ICUs of King Khalid University Hospital. Patient were included if >18 years-of-age and received meropenem for a clinically suspected or proven bacterial infection. The primary outcome was to assess the percentage of patients who achieved the pharmacokinetic/pharmacodynamic (PKPD) therapeutic target of a free trough concentration four times the MIC. The secondary outcome was to estimate the pharmacokinetics of meropenem. Pharmacokinetic analysis was performed using Monolix Suite 2020R1 (Lixoft, France). RESULTS: Trough concentrations were highly variable and ranged from <0.5 µg/mL to 39 µg/mL, with a mean ± SD trough concentration of 8.5 ± 8 µg/mL. Only 46% of patients achieved the therapeutic target. The only significant predictor of failing to achieve the PKPD target was augmented renal clearance. CONCLUSION: In conclusion, more than half of our patients did not achieve the PKPD target. Thus, there is a need for better dosing strategies of meropenem in critically ill patients in Saudi Arabia such as extended and continuous infusion.

Assessment of anti-factor Xa activity in critically ill COVID-19 patients receiving three different anticoagulation regimens.

INTRODUCTION: Critically ill COVID-19 patients are at increased risk of thrombosis with an enhanced risk of bleeding. We aimed to explore the role of anti-factor Xa levels in optimizing the high-intensity anticoagulation's safety and efficacy and finding possible associations between D-dimer levels, cytokine storm markers, and COVID-19-induced coagulopathy or thrombophilia. METHODS: Retrospective cohort study conducted on 69 critically ill COVID-19 patients who received three regimens of higher intensity anticoagulation. RESULTS: Seventeen patients (24.6%) received high-dose enoxaparin prophylaxis, 29 patients (42%) received therapeutic doses of enoxaparin, and 23 patients (33.3%) were on therapeutic unfractionated heparin infusion. Fewer than one-third of the whole cohort (n = 22; 31.8%) achieved the target range of anti-factor Xa. The patients were divided into three subgroups based on anti-factor Xa target status within each anticoagulation regimen; when compared, the only association observed among them was for interleukin-6 levels, which were significantly higher in both the "above the expected range" and "below the expected range" groups compared with the "within the expected range" group (p = 0.009). Major bleeding episodes occurred in 14 (20.3%) patients and were non-significantly more frequent in the "below the expected anti-factor Xa range group" (p = 0.415). Seven patients (10.1%) developed thrombosis. The majority of patients had anti-factor Xa levels below the expected ranges (four patients, 57.1%). CONCLUSION: Conventional anti-factor Xa ranges may not be appropriate as a predictive surrogate for bleeding in critically ill COVID-19. The clinical decision to initiate therapeutic anticoagulation preemptively may be individualized according to thrombosis and bleeding risks. Cytokine storm markers, namely, interleukin-6, may play a role in COVID-19-induced coagulopathy or thrombophilia.

Clinical, molecular and cytopathological characterization of a Newcastle disease virus from an outbreak in Baghdad, Iraq.

BACKGROUND: The frequent outbreaks of Newcastle disease virus (NDV) in Iraq pose a constant threat to commercial poultry, despite the introduction of routine vaccination programmes. Several factors, particularly stress factors and coinfections, might play a role in increasing NDV outbreaks in poultry species. OBJECTIVES: The current study was aimed to characterize an NDV isolate from an outbreak in North Baghdad, Iraq. METHODS: Clinical pathogenicity of the isolate was determined experimentally in chickens. In vitro studies included cytopathological examination, as well as molecular and phylogenetic analyses. RESULTS: Based on the clinical studies and pathogenicity indices (mean death time and intracerebral and intravenous pathogenicity indices), the isolate was characterized as velogenic (highly virulent). Reverse transcriptase polymerase chain reaction targeting the partial fusion protein gene of the NDV genome confirmed the detection. Partial sequencing of the hypervariable region of the fusion gene identified the presence of an avirulent (lentogenic) fusion protein motif (GRQGRL). Phylogenetic analysis of the new isolate along with previously known regional isolates revealed that the new isolate was related to genotype II strains. Additionally, sequence analysis indicated a distinct genetic lineage of the new isolate, which was related to some of the lineages identified in previous outbreaks in the Middle East. CONCLUSION: The current study offers essential information on the epidemiology, characteristics and diagnosis of NDV for disease control in Iraq. The isolate was found to belong to genotype II and possess an avirulent fusion protein motif.

A randomized, double-blind, placebo-controlled trial investigating the effect of ticagrelor on saphenous vein graft patency in patients undergoing coronary artery bypass grafting surgery-Rationale and design of the POPular CABG trial.

RATIONALE: An estimated 15% of saphenous vein grafts (SVGs) occlude in the first year after coronary artery bypass grafting (CABG) despite aspirin therapy. Graft occlusion can result in symptoms, myocardial infarction, and death. SVG occlusion is primarily caused by atherothrombosis, in which platelet activation plays a pivotal role. Evidence regarding the effect of stronger platelet inhibition on SVG patency after CABG is limited. The main objective of the POPular CABG trial is to determine whether dual antiplatelet therapy with aspirin plus ticagrelor improves SVG patency when compared to aspirin alone. STUDY: The POPular CABG is a randomized, double-blind, placebo-controlled, multicenter trial investigating the effect of adding ticagrelor to standard aspirin therapy on the rate of SVG occlusion. A total of 500 patients undergoing CABG with ≥ 1 SVG are randomized to ticagrelor or placebo. The primary end point is SVG occlusion rate, assessed with coronary computed tomography angiography at 1 year. Secondary end points are stenoses and occlusions in both SVGs and arterial grafts and SVG failure at 1 year, defined as a composite of SVG occlusion on coronary computed tomography angiography or coronary angiography, SVG revascularization, myocardial infarction in the territory supplied by an SVG, or sudden death. Safety end points are bleeding events at 30 days and 1 year. CONCLUSION: The POPular CABG trial investigates whether adding ticagrelor to standard aspirin after CABG reduces the rate of SVG occlusion at 1 year.

Molecular Epidemiology of Bovine Papillomatosis and Identification of Three Genotypes in Central Iraq.

OBJECTIVE: This study aims to provide a molecular and epidemiological characterization of bovine papillomavirus (BPV) infections in Iraq. METHODS: The present study focuses on identifying BPV based on clinical and epidemiological manifestations, histopathological examinations, and polymerase chain reactions (PCR). Samples were collected from 163 animals suffering from cutaneous bovine papillomatosis, including 129 females (79.14%) with an age range of 16-40 months and 34 males (20.85%) with an age range of 17-29 months. RESULTS: The incidence rate was significantly higher in females than in males. The most commonly affected sites were the teats and neck, though warts were found in other areas of the body. Histological sections were diagnosed as fibropapilloma. PCR results showed that 80.13% of the extracted papilloma DNA samples corresponded to the BPV-1 genotype. Furthermore, 7.94% of the samples showed a mixed infection of BPV-1 and BPV-13. While, 40.63% of the extracted DNA blood samples showed 2 DNA fragments corresponding to both genotypes BPV-1 and BPV-2. CONCLUSIONS: This study confirmed the presence of BPV-1, BPV-2, and BPV-13, which belong to the Deltapapillomavirus genera, for the first time in the DNA of Iraqi cattle. Understanding BPV diversity and epidemiology is of critical importance for starting prevention strategies.

Molecular and Phylogenetic Analysis of Bovine Papillomavirus Type 1: First Report in Iraqi Cattle.

This study aimed to provide the first molecular characterization of bovine papillomavirus type 1 (BPV-1) in Iraq. BPV is a widely spread oncogenic virus in Iraqi cattle and is associated with the formation of both benign and malignant lesions, resulting in notable economic losses in dairy and beef cattle. In the current study, 140 cutaneous papilloma specimens were collected from cattle in central Iraq. These samples were submitted to histopathological examination, PCR, and sequencing analysis. The histopathology revealed that the main lesion type among the specimens was fibropapilloma. BPV-1 DNA was detected in 121 of the samples (86.42%) in Iraqi cattle as the main causative agent for the disease. A partial sequence for the E2, L2 genes, and complete sequence for the E5 gene were deposited in GenBank. Phylogenetic analysis confirmed the presence of BPV-1 and showed that the origin of infection may be imported European cattle. Obtaining a complete E5 gene sequence enabled us to perform structural predictions. This study presents the first report of BPV-1 infection in the Iraqi cattle and contributes to extending the knowledge of the origin of the spread of this disease. The results of this study will aid in the development of appropriate control measures and therapeutic strategies.

Anomalous Left Anterior Descending Coronary Artery Arising from Pulmonary Artery in a 63 Year-old Male Patient: Case Report and Literature Review.

To present a case of a rare congenital coronary anomaly in an adult patient, which was not reported before in Palestine, review the literature, and compare with previously reported cases.

Frequency and prognosis of new bundle branch block induced by surgical aortic valve replacement.

OBJECTIVES: Recently, transcatheter aortic valve implantation has been introduced, but one of its complications is left bundle branch block (LBBB), a conduction disturbance that has been associated with increased mortality. We investigated the incidence and fate of both right bundle branch block (RBBB) and LBBB after aortic valve replacement (AVR) using a retrospective analysis. We also studied the predictive value of both disorders for all-cause mortality. METHODS: All patients who underwent AVR, with or without concomitant coronary artery bypass grafting surgery, between 2002 and 2010 in our centre were included. All-cause mortality was compared between patients who did and those who did not develop persistent new bundle branch block (BBB) within 7 days postoperatively. Patients were not eligible if one of their electrocardiogram (ECG) recordings prior to AVR showed a BBB or pacemaker activity. A postoperative period of 3-12 months was used to collect follow-up ECGs. RESULTS: Of the 2279 AVR patients, 2033 patients were eligible for analysis. After excluding patients lacking baseline or follow-up ECG (n = 269), 1764 patients remained for analysis. Early LBBB and RBBB occurred in 71 (4.0%) and 92 (5.2%) patients, respectively. At follow-up, LBBB was persistent in 29 patients (1.6%) and RBBB in 74 patients (4.2%). During a median follow-up of 4.5 (2.4-6.5) years, the mortality rate was 16.3% (n = 271) in patients without BBB, 24.1% (n = 7) in patients with persistent LBBB and 18.9% (n = 14) in patients with persistent RBBB (log-rank P = 0.49). Though, in univariate analysis, the hazard ratio for mortality was 1.54 and 1.10 for LBBB and RBBB, respectively, the small numbers precluded identifying AVR-induced LBBB and RBBB as a predictor of mortality. CONCLUSIONS: In the current practice of AVR, persistent postoperative LBBB and RBBB occur infrequently (∼ 5% of cases), a percentage less than half of that in current transcatheter aortic valve implantation procedures. Given the adverse effects of LBBB, the lower prevalence of procedure-induced LBBB in AVR should be taken into account while deciding which valve replacement procedure is chosen for a patient.

STOP-Bang and the effect on patient outcome and length of hospital stay when patients are not using continuous positive airway pressure.

BACKGROUND: In patients undergoing surgical interventions under general anesthesia, obstructive sleep apnea syndrome (OSA) can cause serious perioperative cardiovascular or respiratory complications leading to fatal consequences, even sudden death. In this study we test the hypothesis that morbidly obese patients diagnosed by a polysomnography test and using continuous positive airway pressure (CPAP) therapy have fewer and less severe perioperative complications and a shorter hospital stay than patients who have a medical history that meets at least three STOP-Bang criteria and are not using CPAP therapy. METHODS: Postoperative hospital stay and pulmonary complications were analyzed in three groups of morbidly obese patients undergoing bariatric surgery (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) between January 2009 and November 2013 (n = 693). Group A comprised 99 patients who were preoperatively diagnosed with OSA based on polysomnography results. These patients used CPAP therapy before and after surgery. Group B consisted of 182 patients who met at least three STOP-Bang criteria but who were not diagnosed with OSA based on polysomnography results. These patients did not use CPAP. Group C, the reference group, comprised 412 patients who scored one to two items on the STOP-Bang. RESULTS: During the perioperative period, Group B patients had a significantly (p < 0.001) higher cumulative rate of pulmonary complications, worse oxygen saturation, respiratory rates, and increased length of stay in hospital. There was also two cases of sudden death in this group. CONCLUSION: Based on these results, we conclude that patients meeting at least three STOP-BANG criteria have higher postoperative complications and an increased length of hospital stay than patients using CPAP.

Circumferential disruption of the ventriculo-aortic junction due to infective endocarditis: surgical repair with custom-made, accurately sized, pericardial tube.

Repair of circumferential ventriculo-aortic annular disruption following infective endocarditis is technically challenging. We present an approach for systematic repair and describe a technique for preparation of an accurately sized pericardial tube graft.

Inactivation of [Fe-S] metalloproteins mediates nitric oxide-dependent killing of Burkholderia mallei.

BACKGROUND: Much remains to be known about the mechanisms by which O(2)-dependent host defenses mediate broad antimicrobial activity. METHODOLOGY/PRINCIPAL FINDINGS: We show herein that reactive nitrogen species (RNS) generated by inducible nitric oxide (NO) synthase (iNOS) account for the anti-Burkholderia mallei activity of IFNgamma-primed macrophages. Inducible NOS-mediated intracellular killing may represent direct bactericidal activity, because B. mallei showed an exquisite sensitivity to NO generated chemically. Exposure of B. mallei to sublethal concentrations of NO upregulated transcription of [Fe-S] cluster repair genes, while damaging the enzymatic activity of the [Fe-S] protein aconitase. To test whether [Fe-S] clusters are critical targets for RNS-dependent killing of B. mallei, a mutation was constructed in the NO-induced, [Fe-S] cluster repair regulator iscR. Not only was the iscR mutant hypersusceptible to iNOS-mediated killing, but its aconitase pool was readily oxidized by NO donors as compared to wild-type controls. Although killed by authentic H(2)O(2), which also oxidizes [Fe-S] clusters, B. mallei appear to be resilient to NADPH oxidase-mediated cytotoxicity. The poor respiratory burst elicited by this bacterium likely explains why the NADPH oxidase is nonessential to the killing of B. mallei while it is still confined within phagosomes. CONCLUSIONS/SIGNIFICANCE: Collectively, these findings have revealed a disparate role for NADPH oxidase and iNOS in the innate macrophage response against the strict aerobe B. mallei. To the best of our knowledge, this is the first instance in which disruption of [Fe-S] clusters is demonstrated as cause of the bactericidal activity of NO congeners.