Citations

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10−4). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.

OBJECTIVESurgery for brain aneurysms is technically demanding. In recent years, the process to learn the technical skills necessary for these challenging procedures has been affected by a decrease in the number of surgical cases available and progressive restrictions on resident training hours. To overcome these limitations, surgical simulators such as cadaver heads and human placenta models have been developed. However, the effectiveness of these models in improving technical skills is unknown. This study assessed concurrent and predictive validity of brain aneurysm surgery simulation in a human placenta model compared with a “live” human brain cadaveric model.METHODSTwo human cadaver heads and 30 human placentas were used. Twelve neurosurgeons participated in the concurrent validity part of this study, each operating on 1 human cadaver head aneurysm model and 1 human placenta model. Simulators were evaluated regarding their ability to simulate different surgical steps encountered during real surgery. The time to complete the entire aneurysm task in each simulator was analyzed. The predictive validity component of the study involved 9 neurosurgical residents divided into 3 groups to perform simulation exercises, each lasting 6 weeks. The training for the 3 groups consisted of educational video only (3 residents), human cadaver only (3 residents), and human placenta only (3 residents). All residents had equivalent microsurgical experience with superficial brain tumor surgery. After completing their practice training, residents in each of the 3 simulation groups performed surgery for an unruptured middle cerebral artery (MCA) aneurysm, and their performance was assessed by an experienced vascular neurosurgeon who watched the operative videos.RESULTSAll human cadaver heads and human placentas were suitable to simulate brain aneurysm surgery. In the concurrent validity portion of the experiment, the placenta model required a longer time (p < 0.001) than cadavers to complete the task. The placenta model was considered more effective than the cadaver model in simulating sylvian fissure splitting, bipolar coagulation of oozing microvessels, and aneurysm neck and dome dissection. Both models were equally effective in simulating neck aneurysm clipping, while the cadaver model was considered superior for simulation of intraoperative rupture and for reproduction of real anatomy during simulation. In the predictive validity portion of the experiment, residents were evaluated for 4 tasks: sylvian fissure dissection, microvessel bipolar coagulation, aneurysm dissection, and aneurysm clipping. Residents trained in the human placenta simulator consistently had the highest overall performance scores when compared with those who had trained in the cadaver model and those who had simply watched operative videos (p < 0.001).CONCLUSIONSThe human placenta biological simulator provides excellent simulation for some critical tasks of aneurysm surgery such as splitting of the sylvian fissure, dissection of the aneurysm neck and dome, and bipolar coagulation of surrounding microvessels. When performing surgery for an unruptured MCA aneurysm, residents who had trained in the human placenta model performed better than residents trained with other simulation scenarios/models. In this age of reduced exposure to aneurysm surgery and restrictions on resident working hours, the placenta model is a valid simulation for microneurosurgery with striking similarities with real surgery.

AbstractBackgroundVascularized lymph node (VLN) transfer for lymphedema treatment has shown promising results. Optimal donor and recipient sites remain a matter of debate. We describe the technique and outcomes of a laparoscopically harvested extended gastroepiploic VLN flap with two levels of inset.Patients and MethodsBetween 2014 and 2015, four‐patients with upper limb breast cancer‐related lymphedema and three‐patients with lower limb pelvic cancer‐related lymphedema who underwent VLN transfers were included. After harvest, the gastroepiploic VLN flap was divided into two halves that were separately inset at the level of elbow and wrist (upper limb) or knee and ankle (lower limb). The mean patient age was 53.1 years (range, 42–65 years).ResultsThe average flap size after division was 6.3 cm in length (range, 5–7 cm) and 3.4 cm in width (range, 3–4 cm). The mean pedicle length was 3.2 cm (range, 2.5–4 cm). All flaps survived completely. No donor or recepient site complication was noted. At a mean follow‐up of 9.7 months (range, 8–11 months), the mean circumference reduction rate was 43.7 ± 2.5% along the entire limb (P < 0.05). No episode of infection was noted postoperatively.ConclusionsDouble gastroepiploic VLN transfers to middle and distal limb are a safe approach with very promising results. This technique may be used to improve clinical outcomes by enhancing the lymphatic drainage of the entire affected limb in a uniform fashion. In addition, the laparoscopic harvest can provide decreased donor site morbidity with a faster recovery.

AbstractBackgroundWe sought to determine whether adolescents with metastatic alveolar rhabdomyosarcoma (ARMS) or embryonal RMS (ERMS) had a different event‐free survival (EFS) compared with younger patients, and to identify treatment‐related factors (adverse events, AEs) that may be associated with differences in outcome.MethodsThe prevalence of AEs in adolescents older than 13 years was compared with that in patients less than or equal to 13 years of age (Fisher exact test) in patients enrolled onto ARST0431. EFS by age and histology was compared by log–rank test.ResultsOf 109 patients, 60 (55%) were older than 13 years; they were more likely to have nausea (17 vs. 4%, P = 0.06) and pain (20 vs. 6%, P = 0.05) compared with younger patients. Adolescents were less likely to complete therapy (63 vs. 76%) and more likely to have unplanned dose modifications outside of protocol guidelines (23 vs. 2.7%). The 3‐year EFS was 26% (95% confidence interval [CI]: 15–38) for adolescents compared with 46% (95% CI: 32–60) for those less than or equal to 13 years (P = 0.011). Forty‐two (59%) adolescents with ARMS had a 3‐year EFS of 13% (95% CI: 2–23) compared with 30% (95% CI: 10–51) for those less than or equal to 13 years (P = 0.032). EFS was comparable between older and younger patients with ERMS (64 vs. 55%, P = 0.53).ConclusionsAlthough there was a significant difference in EFS and protocol compliance by age, the differences in age‐related toxicity are unlikely to account for this. Observed differences in pain and nausea by age could be real or be dependent on patient reporting of symptoms. Future studies in RMS should include patient‐reported outcomes to better evaluate health‐related quality of life.

Acute respiratory compromise describes a deterioration in respiratory function with a high likelihood of rapid progression to respiratory failure and death. Identifying patients at risk for respiratory compromise coupled with monitoring of patients who have developed respiratory compromise might allow earlier interventions to prevent or mitigate further decompensation. The National Association for the Medical Direction of Respiratory Care (NAMDRC) organized a workshop meeting with representation from many national societies to address the unmet needs of respiratory compromise from a clinical practice perspective. Respiratory compromise may arise de novo or may complicate preexisting lung disease. The group identified distinct subsets of respiratory compromise that present similar opportunities for early detection and useful intervention to prevent respiratory failure. The subtypes were characterized by the pathophysiological mechanisms they had in common: impaired control of breathing, impaired airway protection, parenchymal lung disease, increased airway resistance, hydrostatic pulmonary edema, and right-ventricular failure. Classification of acutely ill respiratory patients into one or more of these categories may help in selecting the screening and monitoring strategies that are most appropriate for the patient's particular pathophysiology. Standardized screening and monitoring practices for patients with similar mechanisms of deterioration may enhance the ability to predict respiratory failure early and prevent its occurrence.