The porphyrias are a group of rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme. Neurovisceral porphyrias are characterized by acute attacks, in which excessive heme production is induced following exposure to a trigger. An acute attack usually presents with severe abdominal pain, vomiting, and tachycardia. Other symptoms which could appear include hypertension, hyponatremia, peripheral neuropathy, and mild mental symptoms. In severe attacks there could be severe symptoms including seizures and psychosis. If untreated, the attack might become very severe, affecting the peripheral, central, and autonomic nervous system, leading to paralysis, respiratory failure, hyponatremia, coma, and even death. From the biochemical point of view, acute attacks are involved with increased levels of precursors in the heme biosynthetic pathway, up to the deficient step. Of these precursors, aminolevulinic acid (ALA) is considered to be neurotoxic. Treatment is directed to reduce ALA production by reducing the activity of the enzyme aminolevulinate synthase (ALAS)—most effectively by heme therapy. Cutaneous symptoms are a consequence of elevated porphyrins in the blood stream. These porphyrins react to light; therefore sun-exposed areas are affected, producing fragile erosive skin lesions in porphyria cutanea tarda (PCT) or non-scarring stinging and burning symptoms in erythropoietic protoporphyria (EPP). Unlike the most common neurovisceral porphyria, acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) can have cutaneous symptoms as well. Differentiating them from other cutaneous porphyrias is essential for accurate diagnosis, treatment, and patient recommendations.
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.
BACKGROUND: The energy crisis hypothesis, which is a widely accepted model for the pathogenesis of myofascial pain, has been corroborated by experimental observations. However, the nature of the insult leading to the energy crisis remains elusive. A commonly cited model for this insult is the Cinderella hypothesis, suggesting that hierarchical recruitment of motor units leads to a disproportional load on small units, thus driving them towards an energy crisis. New findings cast doubt on this model, showing that in postural muscles motor units are recruited in rotation, rather than in a hierarchical order, precluding the formation of the so-called Cinderella units.
OBJECTIVE: To explore the influence of common myofascial predisposing factors such as muscle load and muscle strength on the relaxation time of postural muscle motor units, assuming they are recruited in rotation.
METHODS: A stochastic model of a postural skeletal muscle was developed which integrates the energy crisis model and motor unit rotation patterns observed in postural muscles. Postulating that adequate relaxation time is essential for the energetic replenishment of motor units, we explored the influence of different parameters on the relaxation time of individual motor units under varying conditions of muscle loads and muscle strengths.
RESULTS: The motor unit relaxation/contraction time ratio decreases with elevated muscle loads and with decreased total muscle strength.
Conclusions: In a model of a postural muscle, in which motor units are recruited in rotation, common predisposing factors of myofascial pain, such as increased muscle load and decreased muscle force, lead to shortened motor unit relaxation periods.
Today medical imaging is an essential component of the entire health-care continuum, from wellness and screening, to early diagnosis, treatment selection, and follow-up. Patient triage in both acute care and chronic disease, imaging-guided interventions, and optimization of treatment planning are now integrated into routine clinical practice in all subspecialties. This paper provides a brief review of major milestones in medical imaging from its inception to date, with a few considerations regarding future directions in this important field.
Background: Neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NACRT) have been demonstrated to improve survival compared to surgery alone in esophageal carcinoma, but the evidence is scarce on which of these therapies is more beneficial, particularly with regard to resectability rates, postoperative morbidity and mortality, and histological responses.
Objective: This study compares the resectability, pathological response rates, and short-term surgical outcomes in patients with carcinoma of the esophagus or gastroesophageal junction receiving NACT or NACRT prior to surgery.
Methods: Patients with resectable carcinoma of the esophagus or gastroesophageal junction adenocarcinoma, squamous cell carcinoma, and adenosquamous histologies were enrolled in this well-matched prospective non-randomized study. Thirty-five patients were given NACT, and 35 NACRT. In the NACT group, 25 patients received three cycles of three-weekly carboplatin and paclitaxel, and 10 received three cycles of cisplatin/5-fluorouracil, while all the patients in the NACRT group received 41.4 Gy of radiotherapy concomitant with five cycles of weekly paclitaxel and carboplatin-based chemotherapy.
Results: Twenty-two patients in the NACT group and 33 patients in NACRT group had resection (P value = 0.0027). The percentage of microscopically margin-negative resection (R0 resection) was similar in both the groups (86% versus 88%). The incidences of surgical and non-surgical complications were similar in both the groups (P=0.34). There was no 30-day mortality. There was a trend toward more pathological complete regression in the NACRT group (P=0.067). The percentage of patients achieving complete tumor regression at the primary site (pT0) was significantly higher in the NACRT group. The down-staging effect on nodal status was similar in both the groups (P=0.55). There was a statistically significant reduction in tumor size in the NACRT group. The median numbers of nodes harvested and positive nodes were similar in both the groups.
Conclusion: Patients receiving NACRT had better resectability rates and pathological response rates, but similar postoperative morbidity compared to the NACT group.
Glaucoma is a chronic neurodegenerative optic nerve disease. Treatment is intended to prevent the development and progression of optic nerve damage by lowering intraocular pressure (IOP). Current therapy options include topical/systemic drugs that increase aqueous humor outflow or decrease its production, laser therapy that targets the trabecular meshwork and ciliary body, and incisional surgery. Trabeculectomy as well as glaucoma drainage devices are often performed, given their high efficacy in lowering IOP. However, the significant risk profile with potential sight-threatening complications has motivated glaucoma experts to create alternative surgeries to treat glaucoma. Minimally invasive glaucoma surgery (MIGS) is defined by: micro-invasive approach, minimal tissue trauma, high safety profile, and rapid recovery. The new devices might promote an earlier transition from medical/laser therapy to surgery, and therefore decrease the side effects associated with long-term use of topical medications as well as deal with the limited adherence of patients to their regimens. This review presents the surgical options available for glaucoma patients and their evolution over the past 25 years.
Background: The importance of emotional intelligence (EI) to the success of health professionals has been increasingly acknowledged. Concurrently, medical schools have begun integrating non-cognitive measures in candidate selection processes. The question remains whether these newly added processes correctly assess EI skills.
Objectives: Measuring EI levels among medical students; examining the correlations between participants’ EI levels and their scores on the non-cognitive MOR test; and exploring students’ attitudes regarding the importance of EI in medical practice.
Methods: The study included 111 first-year and sixth-year students at the Faculty of Medicine at the Technion, Haifa, Israel. Emotional intelligence was assessed by the Bar-On EQ-i 2.0, and MOR evaluation scores were provided by the faculty. An additional questionnaire was designed to rate students’ attitudes toward the importance of EI to the success of medical doctors (MDs).
Results: No significant correlations were found between MOR test scores and EI evaluation scores. Of the 15 EI competencies evaluated, mean scores for flexibility, problem-solving, and independence were lowest for both the first-year and the sixth-year study groups. No differences in EI levels between first-year and sixth-year students were found. Both groups of students considered EI to be highly important to their success as MDs.
Conclusions: While further studies of the links between MOR tests and EI are required, the current findings indicate that MOR test scores may not be predictive of medical students’ EI levels and vice versa. As previous evidence suggests that EI contributes to professional success and to better outcomes in the field of medicine, integrating it into selection processes for medical students and into the curricula in medical schools is recommended.
Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are inte¬grated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunc¬tional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.
Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in India. The aggressiveness of OSCC is analyzed not only based on the dysplastic features and tumor infiltration pattern, but also by means of the stromal changes that pave the way for an invasion into the connective tissue. The role of elastic fibers in the progression of OSCC is still unknown because of sparse literature and the masking effect of overlying inflammatory cells and the lower number of elastic fibers in the lamina propria. The present study provides further insight into the qualitative assessment of elastic fibers in various grades of dysplasia and OSCC.
Objectives: To analyze the morphological changes exhibited by the elastic fibers in epithelial dysplasia and OSCC.
Materials and methods: Two sections were cut from each of 60 samples of varying grades of OSCC and 60 samples of varying grades of epithelial dysplasia followed by staining with hematoxylin and eosin and Verhoeff–Van Gieson stain.
Results: Statistically significant results were obtained for qualitative analysis of elastic fibers. A change in density and orientation to overlying epithelium and tumor islands was seen on progressing from well-differentiated to poorly differentiated OSCC and in progressing grades of dysplasia.
Conclusion: The uniqueness of this study lies in the exploration of elastic fibers in dysplasia and well-differentiated OSCC, a less explored field. The study of the connective tissue stromal changes can be used as an adjunct to histological grading.
Objectives: To study mortality changes in Greece prior to and during the financial crisis.
Study design: Analysis of data by the Hellenic Statistical Authority (1955–2013).
Results: During the crisis, mortality increased from 9.76/1000 in 2009 to 10.52/1000 in 2012 and to 11.16/1000 in 2015, driven by an increase in the number of deaths and a decrease in the estimated population. The annual increase of the expected mortality accelerated during the crisis; in contrast, age-adjusted mortality continued to decrease up to 2014 and increased in 2015. The subpopulations that seemed to be affected more during the crisis were the elderly (especially those over 70 years), women, and citizens in southern Greece. The common denominator of all these subgroups was older age. Mortality due to heart diseases continued to decline at an accelerated pace, due to neoplasia continuing to increase at an accelerated pace and due to a reversal in the rate of stroke (from decline to increment).
Conclusions: The increment of crude mortality during the financial crisis in Greece should be attributed to the increase in deaths, only in part due to the aging population, the reduction in births, and the increase in emigration that contracted the population.
