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.
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.
Background: Eosinophils constitute 1%–5% of peripheral blood leukocytes, less in the presence of acute infections (referred to as eosinopenia). Studies indicate that eosinopenia can be used as a prognostic predictor for chronic obstructive pulmonary disease exacerbation, sepsis, or acute myocardial infarction disease. There are only a few studies about predicting mortality in emergency departments and intensive care units (ICUs). Prognostic studies about patients in ICUs are generally carried out using different scoring systems. We aimed to analyze if the eosinophil count can estimate the prognosis among non-traumatic patients who underwent cardiopulmonary resuscitation and were hospitalized in ICU thereafter.
Methods: The data were evaluated of 865 non-traumatic adult patients (>18 years of age) who were admitted with cardiopulmonary arrest or developed cardiopulmonary arrest during clinical follow-ups. Admission venous blood sample tests, complete blood count, and biochemical laboratory results were recorded. Arterial blood gas results were also evaluated. The mean results of the recorded laboratory results were compared between the surviving and non-surviving patients groups.
Results: There was a significant difference between the two groups in regard to platelet, eosinophil count, pH, PaO2, SaO2, and HCO3- (P<0.001 for all). In the multiple linear regression analysis, eosinophil counts were found to be an independent factor (odds ratio=0.03, 95% confidence interval 0.33–0.56, P<0.001) associated with the mortality after cardiopulmonary resuscitation.
Conclusion: Because admission eosinophil counts can be measured easily, they are inexpensive biomarkers that can be used for predicting the prognosis among the patients who have return of spontaneous circulation and are treated in ICUs.
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.
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.
Background and Objective: Medical cannabis is becoming an acceptable treatment modality in medicine, especially for pain relief. Concurrently, cannabis use is becoming more prevalent worldwide, a public demand-driven trend despite the lack of established scientific basis. This observational open-label study sought to investigate the effectiveness of cannabis therapy for alleviating low back pain symptoms.
Methods: Two types of cannabis treatment modalities were sequentially administered to chronic low back pain patients. After an initial 1-month washout period (WO1), the first modality was cannabidiol (CBD)-rich sublingual extract treatment administered for 10 months. Following another washout period, the second modality, Δ⁹-tetrahydrocannabinol (THC)-rich smoked inflorescence (whole dried cannabis flowers) was administered for 12 months.
Results: Enrolled in the study were 24 patients whose advanced imaging studies (i.e. computerized tomography or magnetic resonance imaging of the lumbar spine) revealed disc herniation or spinal stenosis. Three patients dropped out of extract therapy treatment but resumed study participation to receive THC-rich smoking therapy. After a minimum of 2 years, cannabis therapy had reduced lower back pain symptoms, as assessed by Oswestry Disability Index, the SF-12 patient-reported outcome questionnaire, and the visual analogue scale. Pain reduction was not significant during the extract treatment part of the study; however, pain reduction was significant during the inhaled therapy part of the study.
Conclusions: Our findings indicate that inhaled THC-rich therapy is more effective than CBD-rich sublingual extract therapy for treating low back pain and that cannabis therapy is safe and effective for chronic low back pain.
Objective: To compare the results of treating patients with common bile duct (CBD) stones by endoscopic sphincterotomy (ES), surgical exploration, or a combination of ES and surgical CBD exploration (the rendezvous technique).
Methods: A narrative review of the literature.
Summary of Data: Before 1990, 17 cohort studies indicated that ES cleared CBD stones in 92.0% of patients, with a mortality rate of 1.5%. Surgery removed CBD stones in 90.2% of patients, with a 2.1% mortality rate. A single randomized controlled trial in 1987 showed that ES removed CBD stones in 91% of 55 patients, with a 3.6% mortality rate and a 27% complication rate, whereas surgical CBD exploration removed CBD stones in 92%, with a 1.8% mortality rate and a 22% complication rate. Since 1991, 26 randomized controlled trials have shown that laparoscopic–ES rendezvous is as effective as ES alone and laparoscopic surgery alone but is associated with fewer complications, a reduced need for additional procedures, and a shorter hospital stay.
Conclusions: A laparoscopic–ES rendezvous appears to be the optimal approach to the treatment of CBD stones in younger and fit patients. The choice between ES alone and laparoscopic–ES rendezvous in older or high-risk patients remains uncertain.
Pancytopenia is defined as a reduction in red blood cells, white blood cells, and platelets, and can pose as a diagnostic challenge due to the multitude of causes. Myxedema coma is the manifestation of severe untreated hypothyroidism. This case report presents a rare instance of myxedema coma-associated pancytopenia in a 53-year-old man with a history of untreated hypothyroidism. The patient presented with altered mental status and vital instability, and on further workup was found to have pancytopenia. During his hospital stay his symptomatic hypothyroidism was identified, and he was treated with intravenous levothyroxine, hydrocortisone, and supportive care. The patient’s clinical status improved gradually, with normalized blood counts upon discharge. This case underscores the significance of considering myxedema coma in the differential diagnosis of pancytopenia, especially in older patients with limited healthcare access. Increased awareness of this association can aid clinicians in timely diagnosis and management, preventing potential complications associated with untreated hypothyroidism.
Objective: Early identification of atherosclerosis using a non-invasive tool like ankle–brachial index (ABI) could help reduce the risk for cardiovascular disease among long-term hemodialysis patients. The study objective was to assess the frequency and impact of abnormal ABI as a marker of subclinical peripheral artery disease (PAD) in chronic hemodialysis patients.
Methods: This was a historic cohort study of kidney failure patients on long-term hemodialysis for at least 6 months. The ABI, measured with two oscillometric blood pressure devices simultaneously, was used to assess subclinical atherosclerosis of low limb extremities. Abnormal ABI was defined as ABI <0.9 or >1.3 (PAD present). Survival was defined as time to death. Independent factors associated with abnormal ABI were assessed using multiple logistic regression analysis. Kaplan–Meier method (log-rank test) was used to compare cumulative survival between the two groups; a P value <0.05 was statistically significant.
Results: Abnormal ABI was noted in 50.6% (n=43) of the 85 kidney failure patients included in the study; 42.4% (n=36) had a low ABI, and 8.2% (n=7) had a high ABI. Factors associated with PAD present were cholesterol (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01–1.04; P=0.019), inflammation (AOR, 9.44; 95% CI, 2.30–18.77; P=0.002), phosphocalcic product (AOR, 6.25; 95% CI, 1.19–12.87; P=0.031), and cardiac arrhythmias (AOR, 3.78; 95% CI, 1.55–7.81, P=0.009). Cumulative survival was worse among patients with PAD present (log-rank; P=0.032).
Conclusion: The presence of PAD was a common finding in the present study, and associated with both traditional and emerging cardiovascular risk factors as well as a worse survival rate than patients without PAD.
Objective: In patients with acute hepatic porphyria (AHP), prolonged fasting is a known trigger of AHP attacks. Despite this, some Jewish AHP patients—mainly hereditary coproporphyria (HCP) and variegate porphyria (VP) patients—fast for 25 consecutive hours during the traditional Jewish holy day known as Yom Kippur. In this study, we evaluated the effect of the fast on these patients.
Methods: A retrospective study and survey of AHP patients in Israel was carried out. Patients were asked whether they have fasted and whether any symptoms were induced by this fast. Patients’ medical records were reviewed for an emergency department (ED) visit following YK between 2007 and 2019. Only 3 acute intermittent porphyria (AIP) patients reported fasting; they were excluded from analysis.
Results: A total of 21 HCP patients and 40 VP patients completed the survey; 30 quiescent patients reported they fast, while 31 did not fast. The majority of fasting patients (96.67%) reported no symptoms following a fast. We found no statistically significant association between ED visits 1 week (0.26% in both fasting and non-fasting patients) or 1 month (2.1% visits in non-fasting versus 0.78% in fasting patients) following Yom Kippur. Of the symptomatic ED visits following a fast, none were defined as severe attacks.
Conclusion: A 25-hour fast in stable HCP and VP patients did not increase the risk of an acute attack and can probably be regarded as safe.
