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  • The Maimonides Model for a Regimen of Health: A Comparison with the Contemporary Scenario

    Rabbi Moses Ben Maimon, known as Maimonides, or The “Rambam” (a Hebrew acronym for his name), was one of the greatest arbiters of all times on matters of Jewish law, one of the greatest philosophers of the Middle Ages, a scientist, and a researcher. In addition, he was a court physician to the Egyptian Sultan. In addition to his monumental work on Jewish law and ethics, his writings on medicine have been considered classics over the generations. The aim of this paper is to assess Maimonides’ health regimen and to compare his dietary recommendations with contemporary dietary regimens. To this end, Maimonides’ recommendations were compared to the modern guidelines of the United States, the Netherlands, and the World Health Organization (WHO), as well as to the Mediterranean diet, which is popular worldwide. Both marked similarities and contrasts were noted between Maimonides’ and modern recommendations. Most of Maimonides’ medical recommendations remain relevant more than 800 years later.
  • Screening to Detect Precursor Lesions of Pancreatic Adenocarcinoma in High-risk Individuals: A Single-center Experience

    Objective of the work: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer. Research aim: Pancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer. Methods: Between 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described. Results: Three patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings. Conclusions: Adherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.
  • Clinical Characteristics and Prognosis of Idiopathic Acute Pancreatitis

    Objective: Acute pancreatitis is a serious diagnosis with an increasing incidence in the Western world. In this study we sought to investigate the incidence of idiopathic AP and to compare clinical and prognostic characteristics of idiopathic cases with cases of AP with known etiology. Methods: In this retrospective study of adult hospitalized patients diagnosed with acute pancreatitis between 2012 and 2015, a comparison was made between admissions of patients with known etiology and those for whom no cause was found. Primary outcome was defined as composite outcome of 30-day mortality and complications. Results: Among 560 admissions of 437 patients with a primary diagnosis of acute pancreatitis, the main factors identified were gallstones (51.2%) and idiopathic pancreatitis (35.9%), with alcohol ranked third at only 4.8%. Mortality rate within 30 days of hospitalization was 2.9% and within one year was 7.1%. Use of lipid-lowering, anti-hypertensive, and anti-diabetic medications was more frequent among patients with “idiopathic” disease (70%, 68%, and 33% versus 59%, 56%, and 27%, respectively). Patients admitted with idiopathic AP, in comparison to patients with known AP etiology, had milder disease with shorter hospital stay (3 days versus 4, respectively), and less re-admission in 30 days (7.5% versus 21.2%). Idiopathic AP patients had better prognosis in terms of 30-day death and complication (HR 0.33, 95% CI 0.08–0.40, P<0.001). Conclusion: Idiopathic disease is common among acute pancreatitis patients; the two study groups differed in severity of disease and prognosis. Common use of medications with doubtful value suggests possible under-diagnosis of drug-induced acute idiopathic pancreatitis.
  • Impact of an Integrated Yoga Therapy Protocol on Insulin Resistance and Glycemic Control in Patients with Type 2 Diabetes Mellitus

    Objective: Diabetes mellitus (DM), characterized by chronic hyperglycemia, is attributed to relative insulin deficiency or resistance, or both. Studies have shown that yoga can modulate parameters of insulin resis¬tance. The present study explored the possible beneficial effects of integrated yoga therapy with reference to glycemic control and insulin resistance (IR) in individuals with diabetes maintained on standard oral medical care with yoga therapy, compared to those on standard oral medical care alone. Methods: In this study, the subjects on yoga intervention comprised 35 type 2 diabetics, and an equal number of volunteers constituted the control group. Subjects ranged in age from 30 to 70 years, with hemoglobin A1c (HbA1c) test more than 7%, and were maintained on diabetic diet and oral hypoglycemic agents. Blood samples were drawn prior to and after 120 days of integrated yoga therapy intervention. Fasting blood glucose (FBG), post-prandial blood glucose (PPBG), HbA1c, insulin, and lipid profile were assessed in both the intervention and control groups. Results: The intervention group revealed significant improvements in body mass index (BMI) (0.7 kg/m2 median decrease; P=0.001), FBG (20 mg/dL median decrease; P<0.001), PPBG (33 mg/dL median decrease; P<0.001), HbA1c (0.4% median decrease; P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (1.2 median decrease; P<0.001), cholesterol (13 mg/dL median decrease, P=0.006), triacylglycerol (22 mg/dL median decrease; P=0.027), low-density lipo¬protein (6 mg/dL median decrease; P=0.004), and very-low-density lipoprotein levels (4 mg/dL median decrease; P=0.032). Increases in high-density lipoprotein after 120 days were not significant (6 mg/dL median increase; P=0.15). However, when compared to changes observed in patients in the control group, all these improvements proved to be significant. Conclusion: Administration of integrated yoga therapy to individuals with diabetes leads to a significant improvement in glycemic control, insulin resistance, and key biochemical parameters.
  • Factors Associated with Catch-up Growth in Term, Asymmetrical Small-for-Gestational Age Infants in the First Year of Life

    Introduction: Catch-up growth (CUG) in small-for-gestational age (SGA) infants is essential for their overall development. Knowledge about the factors influencing CUG might be critical in their effective management. Hence this study was performed with the aim of identifying factors that may influence CUG in SGA infants. Methods: Asymmetrical SGA infants born at term were included in the study as per defined criteria, and their demographic details were recorded. Anthropometric data, feeding practice details, and intercurrent illnesses data were collected on follow-up at 6 weeks, 6 months, and 12–15 months of age. Catch-up growth weight was defined as improvement of weight to the normal range of -2 to +2 weight-for-age Z score (WAZ). Analysis was carried out using SPSS Expand 17 software. Chi-square test was used to find association between variables. Logistic regression analysis was used to measure effect. A P value of less than 0.05 was taken as significant. Results: Out of 324 SGA infants born at term, 119 completed 12–15-month follow-up, of which 69.7% had achieved CUG weight. Exclusive breastfeeding >4 months, continued breastfeeding until 12–15 months, and absence of diarrheal episodes were positively associated with CUG. Pregnancy-induced hypertension, gestational diabetes, and maternal overweight/obesity were negatively associated with CUG. Maternal education status, conception age, gravida status, mode of delivery, vitamin D and iron supplementation, and intercurrent respiratory infections were not associated with CUG. On multivariate analysis, continued breastfeeding and absence of diarrheal episodes were independent factors associated with CUG. Conclusion: Breastfeeding practice, especially continued breastfeeding, and the absence of diarrheal illness are the key determinants for achieving CUG weight in term SGA infants, particularly in settings where resources are limited.
  • Can Endoscopic Appearance, Selective Cytology, and Pathological Sampling During Ureteroscopy Accurately Predict Tumor Grade of Upper-Tract Urothelial Carcinoma?

    Objective: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU). Methods: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report. Results: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the “solid”-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease. Conclusions: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.
  • Population-level Outcomes of Early Thyroid Cancers: A Need to Revisit Current Practice

    Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level. Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model. Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P<0.001). Among the untreated T1a or T1b tumors, the risk of disease-specific death was 21 times lower than death due to other causes. There was no significant difference between T1a and T1b tumors nor across sex. The age-adjusted risk of death for the healthy US population was higher than the population with thyroid cancer. Dynamic categorization demonstrated worsening outcomes up to 73 years, uninfluenced by sex or tumor size. For patients over 73 years of age, only tumors >26 mm impacted outcomes. Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.
  • Anti-osteoporotic Drug Utilization Rates for Secondary Prevention Among Patients with Osteoporotic Fractures

    Objectives: Anti-osteoporotic drugs (AOD) are essential for secondary prevention of osteoporotic fracture (OF) in patients with established osteoporosis. However, data about AOD utilization rates are scarce among patients with OF. This study was therefore aimed at determining the AOD utilization rates among those particularly vulnerable patients. Materials and Methods: This cross-sectional study followed the medical records of patients with OF starting from their first OF diagnosis date. Each patient’s preventive osteoporosis treatments (vitamin D, calcium+vitamin D) and AOD utilization rate were recorded for a 12-month period following OF diagnosis. Results: A total of 210 patients (168 females, mean age: 67.8±11.9 years; 42 males, mean age 62.4±16.1 years) were enrolled in the study. Of these, 65.7% (n=138) did not use any medication for primary protection against osteoporosis before OF diagnosis. The ratio of patients not using any type of medication for secondary prevention after OF increased from 26.5% to 51% during a 12-month period. In addition, by one year following diagnosis, AOD usage rate had decreased from 62.3% to 41.3%. Conclusion: The AOD usage rates for secondary prevention of OF were insufficient, and cessation rates were high. Identification of factors associated with decreased AOD utility rates will provide important information for guiding patient follow-up in order to reduce the occurrence of OF.
  • Factors Associated with Liver Enzyme Abnormalities in HIV–HBV and/or HCV Co-infected Patients in Kinshasa, Democratic Republic of the Congo: Multicenter Cross-sectional Study

    Background and Objective: Liver enzyme abnormalities (LEA) are extremely common and sometimes severe in individuals infected with human immunodeficiency virus (HIV), but data for this disorder are lacking in the developing countries. The objective of this study was to identify factors associated with LEA in HIV–hepatitis B virus (HBV)/hepatitis C virus (HCV) co-infected patients in Kinshasa, Democratic Republic of the Congo. Methods: This cross-sectional analytical study included 180 people living with HIV (PLWHIV) mono-infected or co-infected with HBV/HCV between November 10, 2013 and January 10, 2014 in Kinshasa. Sociodemographic, clinical, biological, serological, and immunological data were analyzed. Levels of serum glutamate oxaloacetate transferase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were determined. Antibody levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: The mean age of patients was 44.2±11.0 years; female sex was predominant (76.7%). Co-infection, mainly with HBV, but also HCV, was found in 43 (23.9%) patients. Elevated liver enzymes were found in 77 (42.8%) of the patients. No difference was found in the rate of liver enzyme abnormalities between patients with HIV mono-infection or HIV co-infection (46.7% versus 30.2%, respectively; P=0.08). Factors associated with LEA were age ≥50 years (adjusted odds ratio [OR] 2.7; 95% CI 1.4–5.5), duration of HIV infection >3 years (adjusted OR 2.7; 95% CI 1.4–5.5), and CD4 count ≤303 cells/mm³ (adjusted OR 2.2; 95% CI 1.1–4.5). Conclusions: Liver enzyme abnormalities are frequent in patients co-infected with HIV–HBV/HCV as well as in HIV patients without co-infection. Diagnosis is determined based on age, immunodeficiency, and length of illness.
  • The Antibacterial Action of Safranin and Gentian Violet

    Background: The increasing resistance of many bacterial pathogens against antibiotic measures urgently requires new or repurposing therapeutic strategies. Gentian violet is a triarylmethane dye used as a histological stain and for Gram’s method of classifying bacteria. It also exerts an antimicrobial effect against certain pathogens, especially dermatological infections. Safranin is the most popular counterstain used in medical laboratories due to its low cost and safe laboratory usage. However, few studies have been conducted on the antimicrobial activity of safranin. Objective: With the growing prevalence of multidrug-resistant bacteria, this study aimed to evaluate the antibacterial efficacy of gentian violet and safranin against multidrug-resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Methods: All tested bacteria were multidrug-resistant (MDR) bacteria isolated from skin infections (abscesses and wounds). Using gentian violet and safranin, antibacterial effects were studied using the well-diffusion method against 20 samples of clinically isolated bacteria, 10 diagnosed as S. aureus, and 10 as P. aeruginosa. Bacteria were diagnosed using the VITEK 2 automated system (bioMérieux, Marcy-l’Étoile, France). Iodine served as the control agent, since both Gram-positive and Gram-negative bacteria are sensitive to it. Results: Gentian violet dye has been shown to be 100% sensitive to both Gram-positive and Gram-negative bacterial isolates. Although safranin also had high sensitivity (100%) to S. aureus isolates, its sensitivity to P. aeruginosa was only 20%. Staphylococcus aureus was more resistant to iodine (40% sensitivity) compared to P. aeruginosa, which was 100% sensitive to iodine. Conclusions: Gentian violet and safranin are low-cost and better tolerated topical agents that have potential for use in dermatological applications. Gentian violet had good antibacterial activity against both Gram-positive and Gram-negative bacteria, making it useful for treating bacterial skin pathogens such as S. aureus and P. aeruginosa especially for MDR bacteria. While safranin has good efficacy against Gram-positive bacteria (S. aureus), its effect against Gram-negative bacteria (e.g. P. aeruginosa) is poor.