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.
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.
Objective: To review current medical literature on the risks and potential benefits of e-cigarette use and its permissibility under Jewish law.
Methods: A survey of current medical literature about the risks and potential benefits of e-cigarette use, and a review of existing rabbinic literature regarding both combustible and e-cigarette products.
Results: E-cigarettes contain fewer harmful materials than do combustible cigarettes. However, they are not risk-free. Their skyrocketing use among youth is of concern, as e-cigarettes lead to nicotine addiction and are a gateway to combustible cigarettes. Preliminary data indicate that e-cigarettes increase the risk of myocardial infarction, chronic obstructive pulmonary disease (COPD), and emphysema and are no more effective as aids to smoking cessation than US Food and Drug Administration (FDA)-approved interventions with acceptable safety profiles. Few halakhic decisors have opined on the permissibility of e-cigarettes, but extrapolating from halakhic discussions regarding combustible cigarettes strongly suggests that they would prohibit e-cigarettes based on government warnings and preliminary data demonstrating increased risk of cardiovascular and respiratory diseases, at the least because of possible danger (safek sakana). Among youth and pregnant women, for whom e-cigarettes are particularly dangerous and for whom the government has administered explicit warnings, a Jewish legal prohibition should be absolute. There is a unique obligation to prevent youth from obtaining these products. Jewish law might also prohibit deriving benefit from the sale or advertisement of these products.
Conclusions: Extrapolating from rabbinic literature regarding combustible cigarettes, the preliminary data establishing the dangers of e-cigarettes and the government warnings against usage would render these products prohibited under Jewish law, especially for youth and pregnant women.
Objective: The World Health Organization’s (WHO) guidelines for cancer pain management were intentionally made simple in order to be widely implemented by all physicians treating cancer patients. Referrals to pain specialists are advised if pain does not improve within a short time. The present study examined whether or not a reasonable use of the WHO guideline was made by non-pain specialists prior to referral of patients with cancer-related pain to a pain clinic.
Methods: Cancer patients referred to a pain specialist completed several questionnaires including demographics, medical history, and cancer-related pain; the short-form McGill Pain Questionnaire (SF-MPQ); and the Short Form Health Survey SF-12. Data from referral letters and medical records were obtained. Treatments recommended by pain specialists were recorded and categorized as “unjustified” if they were within the WHO ladder framework, or “justified” if they included additional treatments.
Results: Seventy-three patients (44 women, 29 men) aged 55 years (range, 25–85) participated in the study. Their pain lasted for a mean of 6 (1–192) months. Mean pain intensity scores on a 0–10 numerical rating scale were 7 (2–10) at rest and 8 (3–10) upon movement. Most patients complied with their referring physician’s recommendations and consumed opioids. Adverse events were frequent. No significant correlation was found between the WHO analgesic medication step used and mean pain levels reported. There were 63 patient referrals (85%) categorized as “unjustified,” whereas only 11 patients (15%) required “justified” interventions.
Conclusions: These findings imply that analgesic treatment within the WHO framework was not reasonably utilized by non-pain specialists before referring patients to pain clinics.
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.
United States (US) and European Union (EU) laws attempt to counterbalance the presumed discrimination of children in drug treatment and drug development. The US Food and Drug Administration (FDA)-rewarded pediatric studies with antidepressants triggered in 2004 an FDA black-box warning of suicidality in young patients. Fewer antidepressants were prescribed, and the number of completed suicides of young persons increased. The dilemma between this warning and the need to adequately treat young depressed patients remains unsolved. We analyzed the history of drug development, the evolving view of diseases in young patients, US/EU pediatric laws, and pediatric studies triggered by FDA/European Medicines Agency (EMA) in depression and other diseases on the background of developmental pharmacology; financial, institutional, and other interests; and the literature. The FDA/EMA define children administratively, not physio¬logically, as <17 (FDA)/<18 years old (EMA). But young persons mature physiologically well before their 17th/18th birthday. Depression occurs in young persons, has special characteristics, but is not fundamentally different from adult depression. Young persons are not another species. Regulatory requirements for “pediatric” studies focus on “pediatric” labels. Many “pediatric” studies, including those in depression, lacked and lack medical sense and harm patients by placebo treatment although effective drugs exist. The FDA has partially abandoned separate “pediatric” efficacy studies, but not in psychiatry. Clinicians, parents, institutional review boards, and ethics committees should become aware of questionable “pediatric” studies, should re-evaluate ongoing ones, consider to suspend them, and to reject new ones. The concept of separate “pediatric” drug approval needs to be abandoned.
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.
Objectives: To analyze, perioperatively and in follow-up, transilluminated powered phlebectomy (TIPP), a surgical technique for the treatment of varicose veins.
Method: Retrospective study in one medical institution of patients undergoing TIPP between July 2015 and December 2017. Data analyzed included demographic data, surgery, and results. Postoperatively, pain was evaluated by a 10-point visual analogue scale. The Venous Clinical Severity Score (VCSS) was assessed 5–8 weeks following surgery.
Results: Sixty-six patients with extensive varicosities who underwent TIPP were included. Postoperative pain scores were higher in patients undergoing bilateral compared to unilateral TIPP (visual analogue score 7 versus 5; P=0.031). Following surgery, the VCSS improved in 81.8% (54/66) of the patients. However, 39.7% (25/63; data missing in 3 patients) reported that they would not be willing to undergo a similar procedure in the future. Pain was the most common reason for dissatisfaction.
Conclusions: Transilluminated powered phlebectomy was associated with considerable pain and discom¬fort in many patients included in this study. For this reason, it should be reserved for a select group of patients in whom other treatment options are limited; TIPP could be considered in the following cases: patients with a large number of varicosities, reoperations, after extensive thrombophlebitis, obesity, or following bariatric surgery.
The increasing medicinal use of cannabis during recent years has largely overlooked children and pregnant women due to litigious and ethical concerns. However, over the last few years medicine has observed increasing numbers of children treated with cannabis for autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD), and pregnant women treated for hyperemesis gravidarum (HG). This review provides an account of major findings discovered through this research. Specifically, cannabis may offer therapeutic advantages to behavioral symptoms of autism spectrum disorder and fetal alcohol spectrum disorder, and to the severe nausea and vomiting in hyperemesis gravidarum. The use of medical cannabis in children and pregnant women should be further discussed and researched in this patient population.
