Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
Introduction: Antisemitism and antisemitic incidents have been increasing in United States medical institutions since the Hamas attack of October 7, 2023. Such incidents include anecdotal reports of antisemitic displays at medical school commencements. This study examined unprofessional behavior observed at the commencement ceremonies of the 25 US medical schools top-ranked for research excellence. This issue is significant since these graduates are expected to become future leaders in the field of medicine.
Materials and Methods: Based on publicly available videotaped commencements, we assessed the number of students in the graduating classes wearing non-school-provided regalia, carrying signs, wearing protest buttons, or engaging in verbal protests related to the Israel–terror groups conflict that were either openly antisemitic or potentially offensive or insensitive.
Results: Symbols representing antisemitic themes (keffiyehs and three-part graduation stoles conveying antisemitic messages) were worn by students at just under half (12) of the medical schools. The mean number of students in each school wearing keffiyehs or non-official school stoles was 4.0 (95% confidence interval [CI] 2.2–5.8), ranging from 0%–13% of the classes, or 2.5% of the overall graduating cohort. The wearing of buttons, carrying of banners or signs, verbal protests interrupting the ceremony, or students deviating from script ranged from 0% to 22.5% of graduating students, with a mean of 2.7 per school (95% CI -0.8–6.2), or 1.7% of the medical schools graduating cohort.
Conclusions: We identified unprofessional behavior at commencements of top-ranked medical schools consisting of antisemitism and displaying offensive and insensitive symbols and messaging. There is an urgent need for medical schools in the US to educate medical trainees about the dangers of antisemitism and all forms of hate and insensitivity.
Experimental pain stimuli can be used to simulate patients’ pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests—conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.
This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non-invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain (peripheral or central), objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain.
The world is facing an epidemic rise in diabetes mellitus (DM) incidence, which is challenging health funders, health systems, clinicians, and patients to understand and respond to a flood of research and knowledge. Evidence-based guidelines provide uniform management recommendations for “average” patients that rarely take into account individual variation in susceptibility to DM, to its complications, and responses to pharmacological and lifestyle interventions. Personalized medicine combines bioinformatics with genomic, proteomic, metabolomic, pharmacogenomic (“omics”) and other new technologies to explore pathophysiology and to characterize more precisely an individual’s risk for disease, as well as response to interventions. In this review we will introduce readers to personalized medicine as applied to DM, in particular the use of clinical, genetic, metabolic, and other markers of risk for DM and its chronic microvascular and macrovascular complications, as well as insights into variations in response to and tolerance of commonly used medications, dietary changes, and exercise. These advances in “omic” information and techniques also provide clues to potential pathophysiological mechanisms underlying DM and its complications.
The fetal “programming of adult diseases” has been previously reviewed. The descriptions were comprehensive, dealing with the effects of nutritional deprivation on the development of adult metabolic and cardiovascular diseases. During the past decade, research into this “programming” also expanded to the development of osteoporosis. The present review deals with the imbalance of bone mineral metabolism, “programmed” by maternal/fetal/infantile nutritional deprivation, and is illustrated with a family history from the Budapest Ghetto.
Objectives: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma.
Methods: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes.
Results: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission.
Conclusions: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.
Oropharyngeal cancer represents a growing proportion of head and neck malignancies. This has been associated with the increase in infection of the oropharynx by oncogenic strains of human papillomavirus (HPV). Transoral robotic surgery (TORS) has opened the door for minimally invasive surgery for HPV-related and non-HPV-related oropharyngeal cancer. Compared to traditional open surgical approaches, TORS has been shown to improve functional outcomes in speech and swallowing, while maintaining good oncologic outcomes.
Background. Spermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential.
Objectives. We present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel.
Methods. Between 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post-orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically.
Results. Mean age at diagnosis was 44 years (range 30–58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5–24 months). Three patients were irradiated to the para-aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries.
Conclusions. Prognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy.
The twentieth century witnessed profound changes in medical education. All these changes, however, took place within the existing framework, suggested by Flexner a century ago. The present paper suggests that we are approaching a singularity point, where we shall have to change the paradigm and be prepared for an entirely new genre of medical education. This suggestion is based upon analysis of existing and envisaged trends: first, in technology, such as availability of information and sophisticated simulations; second, in medical practice, such as far-reaching interventions in life and death that create an array of new moral dilemmas, as well as a change in patient mix in hospitals and a growing need of team work; third, in the societal attitude toward higher education. The structure of the future medical school is delineated in a rough sketch, and so are the roles of the future medical teacher. It is concluded that we are presently not prepared for the approaching changes, neither from practical nor from attitudinal points of view, and that it is now high time for both awareness of and preparation for these changes.
