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  • Editorial: Does Every Thyroid Cancer Patient Need Surgery?

    In the management of malignant thyroid disorders, the standard primary treatment is thyroidectomy, a surgical resection of the thyroid gland. This procedure has been performed for over a century. Hence, it comes as no surprise that it is not only exceedingly well-described in the literature. This issue of Rambam Maimonides Medical Journal includes an article by Chaturvedi et al. that challenges the standard widely-practiced clinical inclination toward surgery as the first and best option for all patients with early thyroid cancer. This editorial discusses the issues raised by the authors and points out the importance of ongoing research to determine when standards of care should be modified in the light of low-risk disease.
  • 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.
  • Umbilical Cord and Neonatal Transthyretin and Their Relationship to Growth and Nutrition in Preterm Infants

    Background: Transthyretin (TTR), also known as prealbumin, has been suggested as an indicator of protein and nutritional status. Objective: The aim of this study was to examine the maternal and umbilical cord (UC) TTR in relation to intrauterine growth, and the serum TTR of preterm infants in relation to nutritional status and growth. Methods: After application of exclusion criteria, 49 preterm infants (mean gestational age and birth-weight 32.9±2.9 weeks and 1822±556 g) were included in the study. Transthyretin was sampled at birth and on days 14, 28 or at discharge with growth parameters and nutritional laboratories. Results: Mean UC and maternal TTR were positively correlated (8.5±2.4 mg/dL and 20.4±7.0 mg/dL, r=0.31, P=0.07). Umbilical cord TTR was neither an index of maturity nor of intrauterine growth. Umbilical cord TTR was higher in females (9.4±2.6 versus 7.6±1.8 mg/dL, P=0.015). Maternal TTR was lower in twin pregnancies (16.8±4.9 versus 22.5±7.3 mg/dL, P=0.007). Although TTR levels gradually increased over time in correlation with post-menstrual and chronological ages (r=0.24, P=0.011 and r=0.40, P<0.001, respectively), there was no correlation to weight gain (r=0.10, P=0.41), nutritional status, protein intake, or laboratories. The only significant correlations were between TTR and glucose and triglycerides levels (r=0.51, P<0.001 for both). Conclusions: Although TTR levels increased over time, we could not demonstrate significant correlations between TTR and indices of the nutritional status in preterm infants at birth or during the neonatal course.
  • 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.
  • 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.
  • Food Security and Nutrition as the Neglected Missing Links in Cultural Evolution: The Role of the Sociotype

    Food security and nutrition were major drivers of cultural evolution by enabling sociotypic development and communal living after the Neolithic agricultural revolution some 12,000 years ago. The sociotype unites concepts from the sciences and the humanities; in concert with the genotype it determines an individual’s phenotype (observable traits and behavior), and together they advance societal culture. As such, the sociotype relates to an individual’s dynamic interactions with the surrounding social environment through¬out life and comprises three domains: the Individual, Relationships, and Context. Nutrition affects each domain, respectively, by ensuring the following dimensions of food security: utilization (metabolic fuel and health); accessibility (physical and economic); and availability (the right to nutritious food for all citi¬zens). The sociotype is influenced by multiple factors, including diet–gene interactions, allostasis, micro¬biota, oxytocin, and culturally through mate selection, family bonds, social communication, political ideol¬ogies, and values. Food security, sociotypes, and culture form a complex adaptive system to enable coping with the circumstances of life in health and disease, to achieve sustainable development, and to eradicate hunger. The current geopolitical unrest highlights the absolutely critical role of this system for global security, yet many challenges remain in implementing this paradigm for society. Therefore, sustainable food security must be considered a fundamental human right and responsibility for safeguarding the survival and progress of the sociotypes of humankind (Homo cultures) worldwide.
  • Postoperative Pain Control by Local Infiltration Analgesia and Peripheral Nerve Block in Primary Prosthetic Total Knee Arthroplasty

    Background and Objective: Postoperative (post-op) pain control has an important impact on post-op rehabilitation. The logistics of its maintenance challenge the effect of peripheral nerve block on post-op pain control, with the risk for post-op complications. We hypothesized that perioperative use of local infiltration analgesia (LIA) is comparable to post-op pain control by peripheral nerve block. Materials and Methods: We evaluated three groups of patients treated with primary total knee arthroplasty (TKA) due to symptomatic end-stage osteoarthritis with post-op pain control by LIA (LIA group, n=52), femoral plus sciatic nerve block (FSNB) (FSNB group, n=54), and without local or regional analgesia as controls (Control group, n=53). The primary outcome variable was the post-op pain level intensity as measured by the visual analog scale (VAS). Secondary outcome variables were knee function measured by the Knee Society Score (KSS) and the quadriceps muscle strength recovery profile. Results: Up to 4 hours post-op, pain intensity was significantly lower in FSNB patients (P<0.05). This effect of the peripheral nerve block on the pain level disappeared 6 hours post-op. The LIA and FSNB patients showed a significant decrease in pain intensity on days 2 and 3 post-op (P<0.05) with no mutual differences (P>0.05). This effect disappeared on day 4 post-op (P>0.05). The KSS score showed similar significant improvement of functional abilities (P<0.001) in all three groups. There was no difference in KSS scores among the groups 6 months after surgery (P>0.05). Quadriceps muscle recovery profile was similar in the LIA and Control groups, but significantly poorer in the FSNB group (P<0.001). Conclusion: The value of very short-term and improved pain relief of post-op FSNB over LIA of the surgical wound should be carefully weighed against its cost, logistics, and potential complication threat.
  • Biomarkers in External Apical Root Resorption: An Evidence-based Scoping Review in Biofluids

    Background: External apical root resorption (EARR), an unwanted sequela of orthodontic treatment, is difficult to diagnose radiographically. Hence, the current scoping review was planned to generate critical evidence related to biomarkers in oral fluids, i.e. gingival crevicular fluid (GCF), saliva, and blood, of patients showing root resorption, compared to no-resorption or physiologic resorption. Methods: A literature search was conducted in major databases along with a manual search of relevant articles in the library, and further search from references of the related articles in March 2021. The initial search was subjected to strict inclusion and exclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: Following PRISMA guidelines, 20 studies were included in the final review. The studies included human clinical trials and cross-sectional and prospective studies with/without control groups with no date/ language restriction. Various biomarkers identified in EARR included dentinal proteins, enzymes, cytokines, and salivary proteins. Severe resorption had higher dentin sialoprotein (DSP) and resorption protein concentrations as well as lower granulocyte-macrophage colony-stimulating factor (GM-CSF) as compared with mild resorption. Increased DSP and dentin phosphophoryn (DPP) expression was found in physiologic resorption. Compared to controls, resorbed teeth showed a higher receptor activator of nuclear factor kappa B ligand/ osteoprotegerin (RANKL/OPG) ratio. In contrast, levels of anti-resorptive mediators (IL-1RA, IL-4) was significantly decreased. Differences in force levels (150 g and 100 g) showed no difference in resorption, but a significant rise in biomarkers (aspartate transaminase [AST] and alkaline phosphatase [ALP]) for 150 g force. Moderate to severe resorption in young patients showed a rise in specific salivary proteins, requiring further validation. Limitations of the studies were heterogeneity in study design, biomarker collection, sample selection, and confounding inflammatory conditions. Conclusions: Various biomarkers in biofluids indicate active resorption, while resorption severity was associated with DSP and GM-CSF in GCF, and a few salivary proteins. However, a robust study design in the future is mandated.
  • Secondary Prevention of Osteoporosis: If Not Now, When?

    The time has come for us to work together in a concerted effort to decrease the related suffering and consequences of osteoporotic fractures. And if not now, when?