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  • Comparison of Postoperative Analgesia in Patients Undergoing Ileostomy Closure with and Without Dual Transversus Abdominis Plane (TAP) Block: A Randomized Controlled Trial

    Background and Aims: Multimodal analgesia comprising opioid, paracetamol, and non-steroidal anti-inflammatory drugs is used for managing postoperative surgical pain after ileostomy closure (IC). We investigated the efficacy of unilateral dual transversus abdominis plane (TAP) block to reduce morphine consumption in the first 24 hours along with a reduction in visual analogue score for pain and in post-operative nausea/vomiting. Methods: This was a single-center, investigator-initiated, prospective, parallel-group, placebo-controlled randomized study involving patients undergoing IC under general anesthesia. We recruited 55 patients in two groups: 28 in a TAP group and 27 in a placebo group. The TAP group patients received 30 mL of 0.375% bupivacaine: 15 mL by a posterior TAP approach and 15 mL by a subcostal approach using ultrasonography. Patients in the placebo group received 30 mL normal saline (placebo) using the same approaches. Blocks were administered at the end of surgery before extubation. To monitor for the primary outcome—24-hour morphine consumption for both groups—patients were transferred to a high-dependency unit. The secondary outcome was to compare postoperative nausea/vomiting in both groups. Results: The demographic data, gender distribution, ASA physical status, duration of surgery, and time of first morphine dose was comparable in both groups. The 24-hour morphine consumption was 3.29±2.78 mg and 9.23±2.94 mg for the TAP and placebo groups, respectively, which was statistically significant (P=0.001). Conclusion: Dual TAP block reduces opioid consumption in the first 24 hours after an IC and can facilitate early recovery with less adverse effects seen than with opioids and NSAIDs.
  • 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.
  • Fibromatoses of Head and Neck: Case Series and Literature Review

    Objective: The objective of this study was to retrospectively review clinical data, management protocols, and clinical outcomes of patients with fibromatoses of head and neck region treated at our tertiary care center. Methods: We retrospectively reviewed the medical records of 11 patients with confirmed histopathological diagnosis of fibromatosis registered in the Department of Head and Neck Surgery at Tata Memorial Centre, India, between 2009 and 2019. Various clinical and pathological features and treatment modalities were evaluated. Results: Age at diagnosis ranged between 18 and 74 years, with a median age of 36 years. The female-to-male ratio was 5:6. Supraclavicular fossa (n=4) was the most common subsite of origin in the neck (n=8). The lateral (n=2) and posterior cervical regions (n=2) were other common neck subsites. Less commonly involved sites were the mandible (n=1), maxilla (n=1), and thyroid (n=1). A total of eight patients underwent surgery at other centers before being referred to us for further management. Out of a total 11 patients, nine patients had unresectable disease at presentation. Six of the patients with unresectable disease received a combination of weekly doses of vinblastine 6 mg/m2 and methotrexate 30 mg/m2 for a median duration of 6 months (range 6–18 months) followed by hormonal therapy with tamoxifen. Three patients received metronomic chemotherapy followed by hormonal therapy. One treatment-naive patient with fibromatosis of posterior cervical (suboccipital) region underwent R2 resection (excision of bulk of the tumor with preservation of critical structures) at our center along with adjuvant radiotherapy. One pregnant patient reported to us after undergoing surgery outside and defaulting radiotherapy. During median follow-up of 29 months (range 1–77 months), six patients had stable disease, and four patients had disease reduction. Disease progression was seen in one patient. The two-year progression-free survival (PFS) was 90% (95% CI 70%–100%). Conclusion: Gross residual resection (R2) was the mainstay of surgical treatment in our series as obtaining clear surgical margins is seldom possible in these locally aggressive tumors. Radiotherapy, chemotherapy, and hormonal therapy are the other preferred and more conservative treatment modalities. The goal of surgery should be preserving function with minimal or no morbidity. As fibromatoses in the head and neck region are extremely rare, their treatment awaits the development of standard treatment protocols.
  • 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.
  • Jewish Values in Medical Decision-making for Unrepresented Patients: A Ritualized Approach

    Determining appropriate care for patients who cannot speak for themselves is one of the most challenging issues in contemporary healthcare and medical decision-making. While there has been much discussion relating to patients who left some sort of instructions, such as an advance directive, or have someone to speak on their behalf, less has been written on caring for patients who have nobody at all available to speak for them. It is thus crucial to develop clear and rigorous guidelines to properly care for these patients. The Jewish tradition offers an important perspective on caring for unrepresented patients and determining approaches to guide care providers. This article develops an understanding of fundamental Jewish principles that can provide clear guidance in navigating this challenge. It applies those values to a specific set of suggested behaviors, one of which adds a novel ritualized component to what has been recommended by bioethicists in the past.
  • Comparison of Fasting Insulin Level, Homeostatic Model of Insulin Resistance, and Lipid Levels between Patients with Primary Hypertension and Normotensive Subjects

    Background: Hyperinsulinemia and insulin resistance occurs in obese patients with primary hypertension independent of diabetes and obesity. This study was aimed at assessing serum fasting insulin levels, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum lipid levels in non-obese patients with primary hypertension when compared to normotensive subjects. Methods: This observational study comprised 100 patients over 18 years of age, divided into two groups. The hypertensive group comprised non-obese patients with primary hypertension (n=50); the normotensive group comprised normotensive age- and sex-matched individuals (n=50). Patients with diabetes, impaired fasting glucose, obesity, and other causative factors of insulin resistance were excluded from the study. Serum fasting insulin levels and fasting lipid profiles were measured, and insulin resistance was calculated using HOMA-IR. These data were compared between the two groups. Pearson’s correlation coefficient was used to assess the extent of a linear relationship between HOMA-IR and to evaluate the association between HOMA-IR and systolic and diastolic blood pressures. Results: Mean serum fasting insulin levels (mIU/L), mean HOMA-IR values, and fasting triglyceride levels (mg/dL) were significantly higher in the hypertensive versus normotensive patients (10.32 versus 6.46, P<0.001; 1.35 versus 0.84, P<0.001; 113.70 versus 97.04, P=0.005, respectively). The HOMA-IR levels were associated with systolic blood pressure (r value 0.764, P=0.0005). Conclusion: We observed significantly higher fasting insulin levels, serum triglyceride levels, and HOMA-IR reflecting hyperinsulinemia and possibly an insulin-resistant state among primary hypertension patients with no other causally linked factors for insulin resistance. We observed a significant correlation between systolic blood pressure and HOMA-IR.
  • 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.
  • Quality Assurance of Undergraduate Medical Education in Israel by Continuous Monitoring and Prioritization of the Accreditation Standards

    External accreditation reviews of undergraduate medical curricula play an important role in their quality assurance. However, these reviews occur only at 4–10-year intervals and are not optimal for the immediate identification of problems related to teaching. Therefore, the Standards of Medical Education in Israel require medical schools to engage in continuous, ongoing monitoring of their teaching programs for compliance with accreditation standards. In this paper, we propose the following: (1) this monitoring be assigned to independent medical education units (MEUs), rather than to an infrastructure of the dean’s office, and such MEUs to be part of the school governance and draw their authority from university institu¬tions; and (2) the differences in the importance of the accreditation standards be addressed by discerning between the “most important” standards that have been shown to improve student well-being and/or patient health outcomes; “important” standards associated with student learning and/or performance; “possibly important” standards with face validity or conflicting evidence for validity; and “least important” standards that may lead to undesirable consequences. According to this proposal, MEUs will evolve into entities dedicated to ongoing monitoring of the education program for compliance with accreditation standards, with an authority to implement interventions. Hopefully, this will provide MEUs and faculty with the common purpose of meeting accreditation requirements, and an agreed-upon prioritization of accreditation standards will improve their communication and recommendations to faculty.
  • Controversies in Selecting Nobel Laureates: An Historical Commentary

    There is universal agreement that the Nobel Prizes, given to individuals who have made an extraordinarily notable contribution to humankind in the fields of chemistry, physics, physiology or medicine, literature, and peace, are the most prestigious prizes offered for human achievement. This commentary gives an overview of the basis for Alfred Nobel writing his third will that established the five prizes and includes a discussion of why those five fields were chosen. The commentary includes factors that influenced his choices and contains examples of controversial selections or omissions, especially in the earlier years. A few were errors of omission (e.g. Tolstoy, Tesla, Edison, Best, Gandhi, Franklin), some errors of commission (e.g. Fibiger, Moniz); but, given the complexity of the task, the error rate is small. In some cases, the conclusion that an error had been made is debatable. Such decisions are difficult. Arne Tiselius, a Nobel laureate in chemistry and President of the Nobel Foundation said that one cannot in practice apply the principle that the Nobel Prize should be given to the person who is best; it is impossible to define who is best. Hence, there is only one alternative: to try to find a particularly worthy candidate. This paper includes a brief review of the integration of the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, established in 1968, and added to the original five Nobel Prizes; the prize was first awarded in 1969. A short discussion on the absence of a Nobel Prize in mathematics is provided. Adaptations to the development of “big” science, especially in physics, may require the Nobel Foundation to extend its limit of no more than three awardees for the prize in physics and, perhaps, other scientific disciplines.
  • CRISPR Technology: A Jewish Legal Perspective

    Clustered regularly interspaced short palindromic repeats (CRISPR) gene editing is an innovative and potentially game-changing biotechnology that can potentially reverse DNA mutations in a tissue-specific manner. In addition, CRISPR is being targeted for xenotransplantation, for increasing human longevity, in animal breeding, and in plant science. However, there are many ethical challenges that emerge from CRISPR technology. This article discusses several positions that relate to these ethical challenges from a Jewish legal perspective. In addition, we present several other applications of CRISPR technology that lack a defined Jewish legal precedent and require rabbinical scholars to address and resolve them in the future.