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.
Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentari¬um of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compro¬mise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardio¬vascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from pre¬vention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotox¬icity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae.
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.
Background: United States (US) and European Union (EU) legislation attempts to counterbalance the presumed discrimination in pediatric drug treatment and development.
Methods: We analyzed the history of drug development, US/EU pediatric laws, and pediatric studies required by US/EU regulatory authorities and reviewed relevant literature.
Results: The US and EU definitions of a child are defined administratively (rather than physiologically) as being aged <17 years and <18 years, respectively. However, children mature physiologically well before their seventeenth or eighteenth birthdays. The semantic blur for these differing definitions may indicate certain conflicts of interest.
Conclusions: Pediatric healthcare today is better than ever. Regulatory-related requirements for “pediatric” studies focus on labeling. Most of these studies lack medical usefulness and may even harm pediatric patients through administration of placebo and/or substandard treatment, despite the resultant publications, networking, patent extensions, and strengthened regulatory standing. Clinicians, parents, and ethics committees should be aware of these issues. New rules are needed to determine new pharmaceutical dose estimates in prepubescent patients, and when/how to clinically confirm them. Internet-based structures to divulge this information should be established between drug developers, clinicians, and regulatory authorities. A prerequisite for the rational use of pharmaceuticals in children would be to correct the flawed concept that children are discriminated against in drug treatment and development, and to abandon separate pediatric drug approval processes.
Background: The use of electric bicycles (E-bikes) has dramatically increased over the last decade. E-bikes offer an inexpensive, alternative form of transport, but also pose a new public health challenge in terms of safety and injury prevention.
Objective: The aim of this study was to describe the epidemiology and severity of E-bike related injuries among children treated in the emergency department (ED) and to compare these to manual bicycle related injuries.
Methods: A retrospective observational study of all pediatric patients presenting to the ED between December 2014 and November 2015 with an injury related to E-bike or manual bicycle use. Data including demographics, diagnosis, injury severity score (ISS), and outcome were compared.
Results: A total of 196 cyclist injuries presented to the ED; 85 related to E-bike use and 111 to manual bicycle riders. The mean age of E-bikers was 13.7 years (7.5–16 years) and of manual bicycle riders was 9.9 years (3–16 years). Injuries to the head and the extremities were common in both groups. E-bikers had significantly more intra-abdominal organ injury (P=0.047). Injury severity scores were low overall, but injuries of higher severity (ISS>9) only occurred among the E-bikers.
Conclusions: Pediatric E-bike injuries tend to be more severe than those sustained during manual bicycle riding. Further research into bicycle and other road and pavement users could lead to enhanced regulation regarding E-bike usage.
Objectives: We hypothesized that preoperative (pre-op) ultrasound (US)-guided posterior transversus abdominis plane block (TAP) and US-guided ilioinguinal and iliohypogastric nerve block (ILI+IHG) will produce a comparable analgesia after Lichtenstein patch tension-free method of open inguinal hernia repair in adult men. The genital branch of the genitofemoral nerve will be blocked separately.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 166 adult men were randomly assigned to one of three groups: a pre-op TAP group, a pre-op ILI+IHG group, and a control group. An intraoperative block of the genital branch of the genitofemoral nerve was performed in all patients in all three groups, followed by postoperative patient-controlled intravenous analgesia with morphine. The pain intensity and morphine consumption immediately after surgery and during the 24 hours after surgery were compared between the groups.
Results: A total of 149 patients completed the study protocol. The intensity of pain immediately after surgery and morphine consumption were similar in the two “block” groups; however, they were significantly decreased compared with the control group. During the 24 hours after surgery, morphine consumption in the ILI+IHG group decreased compared with the TAP group, as well as in each “block” group versus the control group. Twenty-four hours after surgery, all evaluated parameters were similar.
Conclusion: Ultrasound-guided ILI+IHG provided better pain control than US-guided posterior TAP following the Lichtenstein patch tension-free method of open inguinal hernia repair in men during 24 hours after surgery. (ClinicalTrials.gov number: NCT01429480.)
Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
Background: The PROSPECT (Procedure-Specific Postoperative Pain Management) Group recommended a single injection femoral nerve block in 2008 as a guideline for analgesia after total knee arthroplasty. Other authors have recommended the addition of sciatic and obturator nerve blocks. The lateral femoral cutaneous nerve is also involved in pain syndrome following total knee arthroplasty. We hypothesized that preoperative blocking of all four nerves would offer superior analgesia to femoral nerve block alone.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 107 patients were randomly assigned to one of three groups: a femoral nerve block group, a multiple nerve block group, and a control group. All patients were treated postoperatively using patient-controlled intravenous analgesia with morphine. Pain intensity at rest, during flexion and extension, and morphine consumption were compared between groups over three days.
Results: A total of 90 patients completed the study protocol. Patients who received multiple nerve blocks experienced superior analgesia and had reduced morphine consumption during the postoperative period compared to the other two groups. Pain intensity during flexion was significantly lower in the “blocks” groups versus the control group. Morphine consumption was significantly higher in the control group.
Conclusions: Pain relief after total knee arthroplasty immediately after surgery and on the first postoperative day was significantly superior in patients who received multiple blocks preoperatively, with morphine consumption significantly lower during this period. A preoperative femoral nerve block alone produced partial and insufficient analgesia immediately after surgery and on the first postoperative day. (Clinical trial registration number (NIH): NCT01303120)
Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems.
Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs) that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.
