Conservative management of iatrogenic oesophageal perforations--a viable option.

OBJECTIVE: Iatrogenic Oesophageal perforations are a dreaded complication and there is no consensus as to their best management. The aim of our study was to assess the results of conservative management in these cases. METHODS: Twenty-six patients with iatrogenic perforations of the oesophagus treated over a 10-year period were reviewed retrospectively. They were managed conservatively by keeping them nil by mouth on intravenous fluids and intravenous antibiotics. Out of these 26, nine were patients of carcinoma of the oesophagus while the remaining 17 had benign pathologies. Twenty-two were diagnosed within 6h, while the remaining four were diagnosed over 24h after perforation. Twenty-three of the 26 were caused by oesophageal dilatations. RESULTS: Twenty-two (84.6%) of the 26 survived on this regimen. Out of the four that died, two had advanced carcinomas and died of chest complications, one died of a myocardial infarction and the fourth was an old debilitated man who died of renal failure. All four who died had extension of the leak into the pleural cavity. Early diagnosis and treatment is of critical importance and is only possible by maintaining a high index of suspicion. CONCLUSIONS: Conservative management when applied to cases of iatrogenic oesophageal perforations gives results comparable to or better that those reported in series where early surgical intervention was practised. Extension of the leak into the pleura carries a worse prognosis.     

Interventions to Increase Multivitamin Use Among Women in the Interconception Period: An IMPLICIT Network Study

Maternal and Child Health Journal - Each year, 3% of infants in the Unites States (US) are born with congenital anomalies, including 3000 with neural tube defects. Multivitamins (MVIs) including...     

Age-dependent rate of anaplastic transformation in low-grade astrocytoma

Age and histologic grade are interrelated characteristics of diffuse fibrillary astrocytomas, because the peak age incidence rises with increasing grade. The relationship between age and grade may be explained if age determines the rate of anaplastic progression in astrocytomas. The authors tested this hypothesis by determining the interval between diagnosis of low-grade astrocytoma and progression to high-grade astrocytoma in patients of various ages. A two-way scatterplot of age at initial diagnosis versus interval to anaplastic progression demonstrated a strong negative correlation (n = 24; Pearson correlation coefficient = -0.83; Spearman correlation coefficient = -0.79; p < 0.001 for both values). It was concluded that the rate of anaplastic progression in low-grade astrocytoma is directly correlated with patient age.     

Systematic review of the application of virtual reality to improve balance,gait and motor function in patients with Parkinson’s disease

Background:Virtual reality (VR) is an advanced technique used in physical rehabilitation of neurological disorders, however the effects of VR on balance, gait, and motor function in people with Parkinson’s (PD) are still debated. Therefore, the systematic review aimed to determine the role of VR on motor function, balance and gait in PD patients.Methods:A comprehensive search to identify similar randomised controlled trials was conducted targeting 5 databases including Web of Science, PubMed, CINHAL, Cochrane Library, and Physiotherapy Evidence Database. A total of 25 studies were found eligible for this systematic review, and the methodological assessment of the quality rating of the studies was accomplished using the physiotherapy evidence database scale by 2 authors.Results:Out of the 25 included studies, 14 studies reported on balance as the primary outcome, 9 studies were conducted to assess motor function, and 12 assessed gait as the primary outcome. Most studies used the Unified Parkinson disease rating scale UPDRS (part-III) for evaluating motor function and the Berg Balance Scale as primary outcome measure for assessing balance. A total of 24 trials were conducted in clinical settings, and only 1 study was home-based VR trainings. Out of 9 studies on motor function, 6 reported equal improvement of motor function as compared to other groups. In addition, VR groups also revealed superior results in improving static balance among patient with PD.Conclusion:This systemic review found that the use of VR resulted in substantial improvements in balance, gait, and motor skills in patients with PD when compared to traditional physical therapy exercises or in combination with treatments other than physical therapy. Moreover, VR can be used as a supportive method for physical rehabilitation in patients of PD. However, the majority of published studies were of fair and good quality, suggesting a demand for high quality research in this area.     

The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment–induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment–related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

Cancer survival times have increased annually owing to advances in early detection and treatment that prolong patient survival. However, increasing survivorship has underscored the observation that cancer survivors develop age-related diseases prematurely, which cause significant morbidity, health expenditures, and mortality. Many cancer survivors have been exposed to chemotherapy, radiotherapy, or both; despite eradicating cancer cells, these therapies also damage normal cells to accelerate biologic aging, such that a discrepancy exists between their biologic and chronologic age (1). Considerable data exist regarding the phenotypes of accelerated aging. However, mechanical and molecular uncertainties have limited the study of these manifestations in a clinical context. Our Review discusses accelerated aging phenotypes in cancer survivors and the cellular mechanisms underpinning these phenomena. We then discuss the translational evidence on how accelerated aging phenotypes, mainly related to senescence, are being targeted while highlighting areas of uncertainty for future research to address.     

Caspase-3 gene deletion prolongs survival in polycystic kidney disease

Pan-caspase inhibition reduces tubular apoptosis and proliferation and slows progression of disease in a rat model of polycystic kidney disease (PKD). It is unknown, however, which specific caspases are involved in PKD progression. Because caspase-3 is a major mediator of apoptosis, its role in autosomal recessive PKD was determined. Mice with caspase-3 gene deletion were crossed with mice harboring the congenital polycystic kidney (cpk) mutation to generate double-mutant mice. cpk;casp3^−/− mice lived nearly 4 times longer than littermate control cpk mice (mean survival of 117 d versus 32 d, P < 0.01), and cpk;casp3^+/− mice lived slightly longer than controls (mean survival of 56 d). In addition, the kidney weight, relative to body weight, was significantly lower in the cpk;casp3^−/− mice than in the cpk and cpk;casp3^+/− mice. Despite deletion of caspase-3, however, apoptosis occurred and cysts formed; therefore, the alternative pathways of apoptosis in cystic kidneys were investigated. Caspase-7 was up-regulated and the anti-apoptotic protein Bcl-2 was down-regulated in cpk, cpk;casp3^+/−, and cpk;casp3^−/− mice compared with wild-type controls. In summary, homozygous deletion of caspase-3 markedly prolongs survival of cpk mice, but a caspase-7-mediated pathway may compensate for the deficiency of functional caspase-3. These findings suggest that pan-caspase inhibition may have a greater therapeutic effect than selective caspase inhibition in PKD.Inherited polycystic kidney disease (PKD) is one of the leading causes of end-stage kidney disease requiring dialysis and kidney transplantation in children and adults.¹ Inherited PKD includes both autosomal dominant and autosomal recessive forms. Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in one of two genes, PKD1 or PKD2. The prevalence of ADPKD varies between 1 in 400 and 1 in 1000, thus making it one of the most common hereditary diseases in the United States. ADPKD progresses to end-stage renal disease (ESRD) over a period of decades in 50% to 75% of affected people. Autosomal recessive polycystic kidney disease (ARPKD) results from a mutation in a single gene, PKHD1. ARPKD is less common, affecting about 1 in 20,000 live births and results in ESRD in childhood.²The congenital polycystic kidney (cpk) mouse is the most extensively characterized mouse model of PKD.² The inheritance, cyst localization in the kidney, and severity of kidney disease in the cpk mouse resembles ARPKD. Cys1, the cpk gene, encodes a cilia-associated protein called cystin that is disrupted in the cpk mouse.³ Increased apoptosis in polycystic kidneys has been described in cpk mice^4–8 as well as in human and other rat and mouse models of PKD.⁹ In support of a deleterious effect of apoptosis in PKD, we have recently demonstrated that pan-caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in the Han:SPRD rat model of PKD.¹⁰ The effect of caspase or apoptosis inhibition in other rat and mouse models of PKD is not known. Caspase-3 is the major mediator of apoptosis (i.e., the so-called “executioner” caspase) and caspase-1 is a pro-inflammatory caspase. However, the effect of inhibition of a specific caspase on PKD is not known. We tested the hypothesis that specific inhibition of caspase-3 would prolong life and reduce cyst formation in PKD.In the present study, we developed cpk mice that were either heterozygous or homozygous for caspase-3 deletion to determine the effect of specific caspase-3 deletion on the development of PKD.     

Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose

Purpose

The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED₉₀) undergoing elective Cesarean delivery (CD) under spinal anesthesia.

Methods

We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED₉₀. The initial dose was 10 μg, with increments/decrements of 5 μg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects.

Results

The ED₉₀ of carbetocin was 14.8 μg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%.

Conclusion

Based on our study, the ED₉₀ of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 μg. This study was registered at clinicaltrials.gov (NCT-01651130).     

Low-fidelity simulation improves mastery of the aseptic technique for labour epidurals: an observational study

Purpose

The objective of this study was to determine the impact of a low-fidelity simulation model on mastering the sterile technique during placement of epidural catheters.

Methods

Trainees, including residents and fellows, were given conventional teaching consisting of a lecture and a video demonstration on the appropriate sterile technique to apply during the placement of epidural catheters. The trainees were then provided with a one-on-one demonstration session using a low-fidelity Styrofoam? epidural model, followed by a series of simulation sessions. After conventional teaching and following each simulation session, the trainees were assessed on their performance until competence was achieved based on a 15-point checklist. The retention of competence was subsequently evaluated bi-weekly in clinical practice for four assessments.

Results

Twenty-one trainees participated in the study. The average score for the residents following conventional teaching was 6.0 out of 15 points on the checklist. Following the initial one-on-one hands-on demonstration, the average score increased to 10.8 (difference = 4.8, 95% confidence interval (CI): 3.3 to 6.2; P < 0.001). The average score for the fellows following conventional teaching was 7.9 out of 15 points on the checklist. Following the initial one-on-one hands-on demonstration the average score increased to 11.2 (difference = 3.3, 95% CI: 0.05 to 6.6; P = 0.047). During the retention of competence phase, scores ranged from 13-15 for both residents and fellows.

Conclusion

This study describes a comprehensive teaching model for mastering the sterile technique during epidural catheter placement. It suggests that low-fidelity simulation improves the learning process when used in addition to conventional teaching.