On May 28, 2014, colleagues from the Mayo Clinic visited Rambam Health Care Campus to gather and exchange ideas and knowledge. American and Israeli caregivers and scientists shared with each other the daily challenges of their practice in many and varied settings. This issue is dedicated to the presentations given and the collaborative efforts we are building as a result of that visit. We hope this issue will serve as an example of the fruitfulness of international collaboration to enhance and propagate medical knowledge worldwide.
Whilst painting the vault of the Sistine Chapel, Michelangelo Buonarroti left an autographical sketch that revealed a prominence at the front of his hyper-extended neck. This image was recently diagnosed as goiter. The poet Michelangelo in a sonnet dated 1509 described himself as being afflicted by goiter similarly to the cats in the northern Italian Lombardy, a region with endemic goiter. Several narratives extended this sonnet into a pathological theory. The analyses of Michelangelo’s works, however, his portraits and self-portraits, of poems and major biographies, have not indicated the likelihood of goiter. This investigation makes an attempt to assess the diagnosis on clinical as well as iconographical grounds.
Surgical Apgar Score is a simple, 10-point scoring system in which a low score reliably identifies those patients at risk for adverse perioperative outcomes. Surgical techniques and anesthesia management should be directed in such a way that the Surgical Apgar Score remains higher to avoid postoperative morbidity and mortality.
The purpose of this review was to investigate what type of exercises can potentially prevent osteoporosis (OP) and its associated fractures in high-risk populations. MEDLINE was searched for work relevant to various types of exercises used to prevent osteoporotic fractures in high-risk population, from the year 1995 onwards. Twelve articles were identified, and, from them, four were deemed suitable to the objective. The studies reviewed show that various types of exercise are effective and safe in preventing the onset of OP. For example, high-intensity progressive resistance training (HiPRT) has been shown to increase vertebral height and femoral neck bone mineral density (BMD), in addition to improving functional performance. Additional studies reviewed suggested that bone reabsorption levels may be positively impacted by low-impact exercise, such as walking. This review provides insight into the effectiveness of various types of exercise to combat and possibly prevent OP for high-risk individuals, which include postmenstrual Caucasian females, people with multiple comorbidities, individuals who smoke or consume alcohol, and the frail elderly population. The prevention of OP should reduce both the social (emotional) and economic burdens faced by patients, caregivers, and health-care systems. Moving forward, research that identifies and bridges pharmaceutical treatment and exercise should be conducted, in addition to the comparison of passive versus active forms of exercise to determine which treatment best prevents OP in high-risk populations.
Diabetes and hyperglycemia are present in over one-third of inpatients in internal medicine units and are associated with worse prognosis in multiple morbidities. Treatment of inpatient hyperglycemia is usually with basal bolus insulin in a dose calculated by the patient’s weight, with lower doses recommended in patients who are at a higher risk for hypoglycemia. Other antihyperglycemic medications and insulin regimens can be used in selected patients. There are no adequately powered studies on the effect of improving glycemic control on hospitalization outcomes in non-critically ill patients in internal medicine units, and in most patients a modest glucose target of 140–180 mg/dL is recommended. A structured discharge plan should intensify antihyperglycemic treatment as needed and include an outpatient follow-up appointment shortly after discharge.
Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis.
Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test.
Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%.
Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.
Background: The ratio between the fetal umbilical artery pulsatility index (UA-PI) and the middle cerebral artery pulsatility index (MCA-PI) is termed the cerebroplacental ratio (CPR). The CPR represents fetal blood flow redistribution at the early stages of placental insufficiency; moreover, it has predictive value for adverse intrapartum and neonatal outcomes. However, internationally accepted reference ranges for CPR are lacking.
Objective: This study sought to establish UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester of pregnancy.
Methods: A retrospective cohort cross-sectional study was performed in the obstetrics ultrasound unit of a university hospital in Israel. We reviewed all fetal and maternal electronic records of pregnant women referred for ultrasound assessment during the third trimester between January 2014 and January 2019. We included only singleton pregnancies with normal anatomy scans and a normal third-trimester estimated fetal weight. The UA-PI, MCA-PI, and CPR reference ranges were reconstructed for each of the vessels for each gestational age between 29 and 41 weeks.
Results: A total of 560 pregnancies met the inclusion criteria. Satisfactory waveforms and measurements were obtained in all cases. At least 18 women enrolled at each gestational week. The MCA-PI and CPR val-ues showed a similar parabolic curve during the third trimester of pregnancy, with a peak value at 32 and 33 gestational weeks, respectively. The UA-PI showed a linear and gradual decrease over the gestational age.
Conclusions: In this study we established UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester based on the Israeli population.
Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF)-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC) is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP) upon binding of nitric oxide (NO) to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs) are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK) inhibitor which targets multiple TKs, in SSc.
The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destruc¬tive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, oto¬laryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients.
The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to pre¬viously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection.
