Predictive factors of difficult biliary cannulation: An experience of a tunisian tertiary center.

Introduction: Selective biliary cannulation is a prerequisite for a successful endoscopic retrograde cholangiopancreatography (ERCP). However, conventional biliary access can be difficult. The aims of our study were to determine the prevalence of difficult biliary cannulation (DBC) and its associated factors and to describe the efficiency and safety of used standard and advanced cannulation techniques. Methods: We conducted a single-center retrospective study including all patients with naïve papilla who had an ERCP procedure in Gastroenterology department of Mohamed Taher Maamouri Hospital from June 2019 to December 2021. Efficiency was defined as successful selective deep biliary cannulation. DBC was defined based on the presence of one or more of the European Society of Gastrointestinal Endoscopy (ESGE) criteria (5-5-1): more than five cannulation attempts, more than 5 min before cannulation and more than one accidental passage in the wirsung. Prevalence was measured using ESGE 5-5-1 cutoffs and chinese set cutoffs 15-10-2. Predictors of DBC were sought by univariate and multivariate analysis (SPSS software, p significant if < 0.05). Results: We included 664 patients (mean age 62 years and sex ratio M/W = 0.8). Main indication for ERCP was choledocholithiasis (67%, n = 442) followed by malignant biliary stenosis (21%, n = 138). Based on ESGE criteria, prevalence of DBC was 42.62% (n = 283). Prevalence was 21.15% when 15-10-2 cutoffs are applied in trainee-involved procedure. Cumulative biliary success rate was 96.46%. Standard cannulation method achieved access in 98.2% while advanced methods permitted success in 92.2% in fistulotomy, 94.1% in papillotomy and 77.3% in transpancreatic sphincterotomy. Independent predictive factors of DBC in multivariate analysis were: Trainee presence OR 1.80 [1.24-2.65], SOD OR 4.71 [1.11-19.88], biliary stenosis found on imaging examinations (OR 2.53 [1.63-3.92], small papilla OR 4.09 [1.82-9.17] and difficult orientation of the papilla OR 14.90 [3.28-67.62]. Conclusion: DBC is a frequent endoscopic situation. Predictors of DBC can be related to trainee involvement in the procedure, anatomical and clinical factors. A thorough understanding of these factors can actively contribute to ERCP management plans.

High efficacy of a characterized lytic bacteriophage in combination with thyme essential oil against multidrug-resistant Staphylococcus aureus in chicken products.

BACKGROUND: The emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) in the food industry have led to using alternative natural bioagents for controlling S. aureus in food. AIMS: The current work aimed to isolate and characterize a lytic phage specific to S. aureus and evaluate its efficacy with thyme essential oil for controlling S. aureus growth in chicken fillets. METHODS: Twenty S. aureus strains previously isolated from ready-to-eat chicken products were tested for antimicrobial susceptibility and used for phage isolation. RESULTS: All S. aureus strains were multidrug-resistant (MDR). The isolated phage (vB_SauM_CP9) belonged to the family Myoviridae and maintained its stability at pH (4-9) and temperature (30-70°C). The phage showed lytic activity on ten S. aureus strains and had a burst size (228 PFU/infected cell), latent period (45 min), and rise period (15 min). A combination of S. aureus phage multiplicity of infection (MOI) 10 + thyme oil 1% caused a higher significant reduction in S. aureus growth (87.22%) in artificially inoculated chicken fillets than individual treatment with bacteriophage or thyme essential oil. CONCLUSION: To our knowledge, this is the first report to evaluate the efficacy of bacteriophage and thyme oil for controlling the growth of MDR S. aureus in chicken products and recommending application of S. aureus phage and thyme oil combination in the food industry to achieve food safety goals and consumer protection as well as mitigate the antimicrobial resistance crisis.

Aortic Valve Replacement in 8 Adults with Anomalous Aortic Origin of Coronary Artery.

Patients with anomalous origin of a coronary artery during aortic valve replacement (AVR) are at risk of coronary compromise. Large case series are lacking. In this retrospective study, we review our experience with this condition. From August 2014 through June 2016, 8 adult patients (mean age, 74 ± 17.5 yr; age range, 33-86 yr; 5 men) with anomalous aortic origin of a coronary artery underwent surgical or transcatheter AVR at our institution. Six patients had aortic stenosis; 2 had aortic insufficiency, one of whom had an associated aortic root aneurysm. In 7 patients, the left anomalous coronary artery originated from the right aortic sinus, and in one, the right coronary artery arose from the left cusp. The anatomic course was revealed by means of 3-dimensional computed tomographic angiography. No patient underwent primary aortic reimplantation of the anomalous artery. Two had the artery mobilized from encircling the annulus too closely and then underwent coronary artery bypass grafting. Two high-risk patients underwent transcatheter AVR. After surgical AVR, 2 patients had perioperative myocardial infarction caused by coronary compression, so percutaneous coronary intervention was performed. One patient died of sepsis 3 months after discharge from the hospital. In our patients, AVR sometimes led to severe perioperative complications. Successful AVR depended on 3-dimensional computed tomographic angiographic findings, individual anatomic variations, and appropriate treatment choices.

Adjusting the neochords height for better leaflets coaptation following mitral valve repair.

Often times, in mitral valve repair techniques, the height of the newly placed Gore-Tex sutures needs correction to achieve better mitral valve leaflet coaptation or to correct systolic anterior motion (SAM). Herein, a less challenging "Hornet" technique to accurately adjust artificial chordal length is described. This technique describes a way to adjust/shorten the Gore-Tex chords, should they need revision. Ideally, this should not be needed, however due to the circumstances for mitral valve repair, this is sometimes necessary. With the annuloplasty band already in place, it is somewhat harder to reinsert new chords and hence, this technique may be beneficial.

An Introduction to the Mathematical Modeling in the Study of Cancer Systems Biology.

BACKGROUND: Frequently occurring in cancer are the aberrant alterations of regulatory onco-metabolites, various oncogenes/epigenetic stochasticity, and suppressor genes, as well as the deficient mismatch repair mechanism, chronic inflammation, or those deviations belonging to the other cancer characteristics. How these aberrations that evolve overtime determine the global phenotype of malignant tumors remains to be completely understood. Dynamic analysis may have potential to reveal the mechanism of carcinogenesis and can offer new therapeutic intervention. AIMS: We introduce simplified mathematical tools to model serial quantitative data of cancer biomarkers. We also highlight an introductory overview of mathematical tools and models as they apply from the viewpoint of known cancer features. METHODS: Mathematical modeling of potentially actionable genomic products and how they proceed overtime during tumorigenesis are explored. This report is intended to be instinctive without being overly technical. RESULTS: To date, many mathematical models of the common features of cancer have been developed. However, the dynamic of integrated heterogeneous processes and their cross talks related to carcinogenesis remains to be resolved. CONCLUSIONS: In cancer research, outlining mathematical modeling of experimentally obtained data snapshots of molecular species may provide insights into a better understanding of the multiple biochemical circuits. Recent discoveries have provided support for the existence of complex cancer progression in dynamics that span from a simple 1-dimensional deterministic system to a stochastic (ie, probabilistic) or to an oscillatory and multistable networks. Further research in mathematical modeling of cancer progression, based on the evolving molecular kinetics (time series), could inform a specific and a predictive behavior about the global systems biology of vulnerable tumor cells in their earlier stages of oncogenesis. On this footing, new preventive measures and anticancer therapy could then be constructed.

Replacing surveillance cystoscopy with urinary biomarkers in followup of patients with non-muscle-invasive bladder cancer: Patients' and urologic oncologists' perspectives.

INTRODUCTION: Urinary biomarkers are being developed to detect bladder cancer recurrence/progression in patients with non-muscle-invasive bladder cancer (NMIBC). We conducted a questionnaire-based study to determine what diagnostic accuracy and cost would such test(s) need for both patients and urologic oncologists to comfortably forgo surveillance cystoscopy in favour of these tests. METHODS: Surveys were administered to NMIBC patients at followup cystoscopy visit and to physician members of the Society of Urologic Oncology. Participants were questioned about acceptable false-negative (FN) rates and costs for such alternatives, in addition to demographics that could influence chosen error rates and costs. RESULTS: A total of 137 patient and 51 urologic oncologist responses were obtained. Seventy-seven percent of patients were not comfortable with urinary biomarker(s) alternatives to repeat cystoscopy, with a further 14% willing to accept such alternatives only if the FN rate were 0.5% or lower. Seventy-five percent of urologic oncologists were comfortable with an alternative urinary biomarker test(s), with 37% and 33% willing to accept FN rates of 5% and 1%, respectively. Forty-seven percent of patients were not willing to pay out-of-pocket for such tests, while 61% of urologic oncologists felt that a price range of $100-500 would be reasonable. CONCLUSIONS: This is the first survey evaluating patient and urologic oncologist perspectives on acceptable error rates and costs for urinary biomarker alternatives to surveillance cystoscopy for patients with NMIBC. Despite potential responder bias, this study suggests that urinary biomarker(s) will require sensitivity equivalent to that of cystoscopy in order to completely replace it in surveillance of patients with NMIBC.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PURPOSE: We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. MATERIALS AND METHODS: We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. RESULTS: Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. CONCLUSIONS: Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

How do cancer cells replenish their fuel supply?

BACKGROUND: Multiple genetic changes, availability of cellular nutrients and metabolic alterations play a pivotal role in oncogenesis AIMS: We focus on cancer cell's metabolic properties, and we outline the cross talks between cellular oncogenic growth pathways in cancer metabolism. The review also provides a synopsis of the relevant cancer drugs targeting metabolic activities that are at various stages of clinical development. METHODS: We review literature published within the last decade to include select articles that have highlighted energy metabolism crucial to the development of cancer phenotypes. RESULTS: Cancer cells maintain their potent metabolism and keep a balanced redox status by enhancing glycolysis and autophagy and rerouting Krebs cycle intermediates and products of ß-oxydation. CONCLUSIONS: The processes underlying cancer pathogenesis are extremely complex and remain elusive. The new field of systems biology provides a mathematical framework in which these homeostatic dysregulation principles may be examined for better understanding of cancer phenotypes. Knowledge of key players in cancer-related metabolic reprograming may pave the way for new therapeutic metabolism-targeted drugs and ultimately improve patient care.

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.

Cancer Rates in Adults After Cardiac Interventions: A Preliminary Observational Report.

BACKGROUND: The postprocedural state after cardiac revascularization interventions is characterized by intense inflammation and activation of inflammatory cytokines due to myonecrosis and ischemia/reperfusion injury. Involvement of similar processes also participates in cellular malignant transformation. In this study, the association between cardiac interventions and subsequent cancer risk development was therefore evaluated. METHODS: The 5-year cumulative incidence of cancer was examined in 2 cardiac care cohorts: all patients undergoing either open heart surgery or percutaneous coronary interventions (PCI) at hospitals in the commonwealth of Massachusetts. The observed cases of cancer were compared with the number of expected cases based on the state cancer rates, adjusting for sex and 5-year age groups. The standardized morbidity ratio (SMR) was used for this comparison. RESULTS: Of 10,301 patients in the surgical cohort, 804 (7.8%) incident cancers developed over 5 years of follow-up, whereas 245.7 incident cancers were expected. This yielded an SMR of 3.27 (95% CI, 3.05-3.51; P<0.0001). In the PCI cohort comprising 13,001 patients, 1029 (7.9%) incident cancers developed over 5 years, resulting in an SMR of 3.53 (95% CI, 3.32-3.75; P<0.0001). Excluding respiratory cancers from the analysis (to limit smoking-related cancers) reduced risk estimates only slightly. For the surgical cohort: SMR=2.80; 95% CI, 2.59-3.01; P<0.0001. For the PCI cohort: SMR=2.97; 95% CI, 2.78-3.18; P<0.0001. CONCLUSIONS: Undergoing heart revascularization procedures was associated with increased rate of cancer development as compared with the state general population. This cohort may warrant increased monitoring.

Endovascular Closure of an Aortic Pseudoaneurysm Complicated by Aorto-Pulmonary Fistula.

Aorto-pulmonary fistula (APF) due to an eroding pseudoaneurysm of the ascending aorta (AOP) is rare and can be life threatening. We report an 83-year-old male with multiple comorbidities who presented with an AOP, which was successfully treated with an endovascular exclusion device. doi: 10.1111/jocs.12758 (J Card Surg 2016;31:453-455).

A Technique for Avoiding Patient-Prosthesis Mismatch in the Small Aortic Root.

In the small aortic root, extremely weakened tissue and extensive calcification predispose toward the implantation of small prostheses, anastomotic bleeding, and paravalvular leaks. We describe a procedure in which a "homemade" composite mechanical prosthesis-conduit is implanted in a supra-annular position in two patients with a small aortic root. This technique facilitates the placement of a larger prosthesis, thus avoiding patient-prosthesis mismatch. doi: 10.1111/jocs.12741 (J Card Surg 2016;31:309-310).

Estimated Effects of Different Alcohol Taxation and Price Policies on Health Inequalities: A Mathematical Modelling Study.

INTRODUCTION: While evidence that alcohol pricing policies reduce alcohol-related health harm is robust, and alcohol taxation increases are a WHO "best buy" intervention, there is a lack of research comparing the scale and distribution across society of health impacts arising from alternative tax and price policy options. The aim of this study is to test whether four common alcohol taxation and pricing strategies differ in their impact on health inequalities. METHODS AND FINDINGS: An econometric epidemiological model was built with England 2014/2015 as the setting. Four pricing strategies implemented on top of the current tax were equalised to give the same 4.3% population-wide reduction in total alcohol-related mortality: current tax increase, a 13.4% all-product duty increase under the current UK system; a value-based tax, a 4.0% ad valorem tax based on product price; a strength-based tax, a volumetric tax of £0.22 per UK alcohol unit (= 8 g of ethanol); and minimum unit pricing, a minimum price threshold of £0.50 per unit, below which alcohol cannot be sold. Model inputs were calculated by combining data from representative household surveys on alcohol purchasing and consumption, administrative and healthcare data on 43 alcohol-attributable diseases, and published price elasticities and relative risk functions. Outcomes were annual per capita consumption, consumer spending, and alcohol-related deaths. Uncertainty was assessed via partial probabilistic sensitivity analysis (PSA) and scenario analysis. The pricing strategies differ as to how effects are distributed across the population, and, from a public health perspective, heavy drinkers in routine/manual occupations are a key group as they are at greatest risk of health harm from their drinking. Strength-based taxation and minimum unit pricing would have greater effects on mortality among drinkers in routine/manual occupations (particularly for heavy drinkers, where the estimated policy effects on mortality rates are as follows: current tax increase, -3.2%; value-based tax, -2.9%; strength-based tax, -6.1%; minimum unit pricing, -7.8%) and lesser impacts among drinkers in professional/managerial occupations (for heavy drinkers: current tax increase, -1.3%; value-based tax, -1.4%; strength-based tax, +0.2%; minimum unit pricing, +0.8%). Results from the PSA give slightly greater mean effects for both the routine/manual (current tax increase, -3.6% [95% uncertainty interval (UI) -6.1%, -0.6%]; value-based tax, -3.3% [UI -5.1%, -1.7%]; strength-based tax, -7.5% [UI -13.7%, -3.9%]; minimum unit pricing, -10.3% [UI -10.3%, -7.0%]) and professional/managerial occupation groups (current tax increase, -1.8% [UI -4.7%, +1.6%]; value-based tax, -1.9% [UI -3.6%, +0.4%]; strength-based tax, -0.8% [UI -6.9%, +4.0%]; minimum unit pricing, -0.7% [UI -5.6%, +3.6%]). Impacts of price changes on moderate drinkers were small regardless of income or socioeconomic group. Analysis of uncertainty shows that the relative effectiveness of the four policies is fairly stable, although uncertainty in the absolute scale of effects exists. Volumetric taxation and minimum unit pricing consistently outperform increasing the current tax or adding an ad valorem tax in terms of reducing mortality among the heaviest drinkers and reducing alcohol-related health inequalities (e.g., in the routine/manual occupation group, volumetric taxation reduces deaths more than increasing the current tax in 26 out of 30 probabilistic runs, minimum unit pricing reduces deaths more than volumetric tax in 21 out of 30 runs, and minimum unit pricing reduces deaths more than increasing the current tax in 30 out of 30 runs). Study limitations include reducing model complexity by not considering a largely ineffective ban on below-tax alcohol sales, special duty rates covering only small shares of the market, and the impact of tax fraud or retailer non-compliance with minimum unit prices. CONCLUSIONS: Our model estimates that, compared to tax increases under the current system or introducing taxation based on product value, alcohol-content-based taxation or minimum unit pricing would lead to larger reductions in health inequalities across income groups. We also estimate that alcohol-content-based taxation and minimum unit pricing would have the largest impact on harmful drinking, with minimal effects on those drinking in moderation.

Preserving a Well-Functioning 33-Year-Old Starr-Edwards Aortic Prosthesis in Repeat Aortic Root Aneurysm Repair.

We report the case of a 61-year-old obese male patient in whom we found a well-functioning 33-year-old Starr-Edwards aortic prosthesis during repeat aortic surgery. Rather than explant the prosthesis, we remodeled the aortic root, almost completely removing the aortic sinuses and leaving only a pillar of aortic tissue around the coronary ostia. The proximal end of a Hemashield tube-graft was then scalloped to accommodate the remaining aortic tissue. The patient's heart function was excellent after his weaning from cardiopulmonary bypass. Simplifying the repeat aortic root repair, by preserving a well-functioning Starr-Edwards valve, might lead to a better outcome in similar cases. We also discuss other instances of this valve's durability.

Blood transfusion and the risk of atrial fibrillation after cardiac surgery.

BACKGROUND: Red blood cell transfusion (Tx) induces a proinflammatory state. Inflammatory mediators are associated with an increased risk of postoperative atrial fibrillation (AF). Therefore, in this study we determined the association between AF and Tx after isolated coronary artery bypass graft surgery (CABG). METHOD: Between January 2008 and December 2010, a total of 879 patients underwent CABG. Of these, 815 (92.7%) had complete data extracted from our institution's Society of Thoracic Surgeons (STS) database. Predictors of AF development among four levels of Tx versus nontransfused patients were examined. Multivariable logistic regression and propensity score matching models were used. RESULTS: The mean age was 65.8 years (±10.3), 77.4% were male, and 54.4% had an STS predicted risk score (mortality/morbidity) of ≥10%. A total of 564 (69.2%) had at least one unit of Tx. Adjusting for age, sex, time on pump, congestive heart failure, stroke, creatinine level (<1.5 mg per deciliter vs. ≥1.5), STS morbidity/mortality score, perioperative myocardial infarction (MI), cross-clamp time, medications, and hemoglobin level, the odds ratio (OR) of AF increased with increasing Tx (OR, 1.36; 95% confidence interval [CI], 1.11 to 1.68; p = 0.003). The odds of AF increased 61% with each increasing level of Tx (OR, 1.61; 95% CI, 1.15 to 2.26; p = 0.006, by propensity analysis). CONCLUSIONS: Perioperative Tx may be associated with excess AF following CABG. This risk increases with increasing number of Tx.

Alternative perfusion technique without axillary artery cannulation during combined aortic root and total arch replacement.

This report describes an effective cerebral perfusion method using an additional 4th side limb graft sewn to a trifurcated graft in patients undergoing redo aortic root reconstruction combined with total aortic arch replacement. This method is useful in cases where the origin of the innominate artery is unsuitable for clamping or when axillary perfusion is not employed, and assures continuous brain protection and minimizes circulatory arrest time.

Effect of a single-piece aspheric hydrophobic acrylic intraocular lens design on centration and rotation.

PURPOSE: To assess the rotation and centration stability of the new design features of a 1-piece aspheric hydrophobic acrylic intraocular lens (IOL). SETTING: National Eye Hospital, Cairo, Egypt. DESIGN: Randomized clinical trial. METHODS: Patients in this study had implantation of a 1-piece Tecnis 1 ZCB00 IOL or a 3-piece Sensar AR40e IOL. Decentration and rotation were recorded immediately postoperatively, and 2 to 3 days and 8 weeks postoperatively. This was done using 2 slitlamp eyepieces and referring to constant corneal landmarks (ie, the limbus and the phaco incision). RESULTS: Thirty-two 1-piece IOLs and 30 3-piece IOLs were implanted. Although the 1-piece IOLs moved toward the corneal center more than the 3-piece IOLs between 3 days and 8 weeks postoperatively (P=.054), the difference was not statistically significant between 0 day and 3 days or during the entire follow-up (P=.546 and P=.367, respectively). There were no statistically significant differences in the horizontal or vertical components of this movement between the 2 groups (P=.883 and P=.636, respectively). The mean rotation was 2.5 degrees ± 9.1 (SD) in the 1-piece IOL group and 0 ± 6.5 degrees in the 3-piece IOL group, with no statistically significant difference between the groups (P=.521). CONCLUSION: The new 1-piece design showed relatively good centration and stability in the horizontal, vertical, and rotational aspects.