Study design and hierarchy of evidence for surgical decision making

This article provides a historical overview of the hierarchy of evidence for surgical decision making and discusses key study designs in the hierarchy of evidence. This encompasses meta-analyses, randomized controlled trials, and observational studies, including cohort and case-controlled studies, case series and case reports, and basic science studies. This article also reviews the principles and importance of evidence-based plastic surgery and describes several systems to rate the strength of the scientific evidence.     

Influence of dietary fats on Ecstasy-induced hyperthermia

BACKGROUND AND PURPOSE: Studies were designed to examine the effects of dietary fats on metabolic effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). These effects included hyperthermia, expression of uncoupling protein (UCP1 and 3) in brown adipose tissue or skeletal muscle and plasma free fatty acid (FFA) levels. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were fed either a high-fat diet (HFD, 60% kcal) or a lower fat isocaloric controlled diet (LFD, 10% kcal) for 28 days before MDMA challenge. KEY RESULTS: No significant differences were observed between LFD and HFD groups in terms of body weight, plasma thyroxine (T4) levels and expression of brown fat UCP1 or skeletal muscle UCP3 protein. HFD significantly raised levels of circulating FFA and potentiated the thermogenesis induced by MDMA (10 mg kg(-1), s.c.), compared to the effects of the LFD. Moreover, 30 and 60 min after MDMA administration, plasma FFA levels decreased in HFD animals, but were markedly elevated in the LFD group. CONCLUSIONS AND IMPLICATIONS: These results indicate that high-fat feeding regulates MDMA-induced thermogenesis by augmenting the activation of UCP rather than its expression.     

Primary cutaneous aspergillosis at the site of cyanoacrylate skin adhesive in a neonate

Primary cutaneous aspergillosis is a rare but potentially life‐threatening disease. We present the case of a premature infant who developed primary cutaneous aspergillosis with Aspergillus niger at the site of a skin abrasion that had been treated with a purple‐colored cyanoacrylate product. The infection was treated successfully with gentle debridement of the cyanoacrylate product, followed by intravenous voriconazole and topical fluconazole. To our knowledge, this is the first reported case of primary cutaneous aspergillosis occurring at the site of cyanoacrylate‐based skin adhesive.     

Birt–Hogg–Dubé Syndrome Presenting as a Nevus Comedonicus–Like Lesion in an 8‐Year‐Old Boy

Birt–Hogg–Dubé syndrome is an uncommon genodermatosis characterized by hair follicle hamartomas and an increased risk of pneumothorax and renal cell carcinoma. Recognition of cutaneous manifestations is essential because it allows for early screening and management of systemic complications. We present the case of an 8‐year‐old boy with a recently described cystic and comedonal variant of the classic fibrofolliculoma, which had been present since birth.     

Rates of oropharyngeal cancer continue to rise steeply amongst Australian men

Objective

The objective was to analyse the trends in the incidence of oropharyngeal cancers (OPC) across Australia from 1982 to 2017 with implications for prevention.

Methods

Data were obtained from the Australian Cancer Database (ACD) compiled at the Australian Institute of Health and Welfare (AIHW). Joinpoint analyses are presented.

Results and discussion

There was a striking increase of age-standardised incidence rate (ASIR) of OPC by over 1.5 times; the most significant rise was between 2007 and 2017 with an annual percentage change (APC) of +5.24% (p < 0.001). Slow but gradual growth of ASIR was observed amongst women with a statistically significant APC of +1.02% (p < 0.001). Statistically significant bimodal increasing trends of APC were also observed in total ASIR of OPC. These rising trends are widely attributed to increased oral sex practices. The highest number of incident cases was found in patients aged 55–69 years attributable to continued alcohol and tobacco exposure. The most common subsites affected were base of the tongue (BOT) and ‘oropharynx’ from 1982 to 2017.

Conclusion

Oropharyngeal cancer is rising rapidly across Australia, particularly in men. Whilst the national proportion of cases driven by HPV is not known, it is evident that vaccination is yet to have an impact.     

Pre-ischemic exercise reduces matrix metalloproteinase-9 expression and ameliorates blood-brain barrier dysfunction in stroke

Exercise reduces ischemia and reperfusion (I/R) injury in the rat stroke model. We investigated whether pre-ischemic exercise ameliorates blood-brain barrier (BBB) dysfunction in stroke by reducing matrix metalloproteinase (MMP)-9 expression and strengthening basal lamina. Adult male Sprague-Dawley rats were subjected to a 30 min exercise program on a treadmill 5 days a week for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament in the exercised and non-exercised groups. Brain infarction was measured and neurological deficits were scored. BBB dysfunction was determined by examining brain edema and Evans Blue extravasation. Expression of collagen IV, the major component of basal lamina essential for maintenance of the endothelial permeability barrier, was quantitatively detected by Western blot and immunocytochemistry. Ex vivo techniques were used to compare collagen IV-labeled vessels in response to ischemic insult. Temporal relationship of expression of MMP-9 and its endogenous inhibitor, the tissue inhibitors of metalloproteinase-1 (TIMP-1), was determined by real-time PCR for mRNA and Western blot for protein during reperfusion. Brain edema and Evans Blue leakage were both significantly (P<0.01) reduced after stroke in the exercised group, in association with reduced brain infarct volume and neurological deficits. Western blot analysis indicated that exercise enhanced collagen IV expression and reduced the collagen loss after stroke. Immunocytochemistry demonstrated that collagen IV-labeled vessels were significantly (P<0.01) increased in exercised rats. In the ex vivo study, after exercised brains were incubated with ischemic brain tissue, a significantly (P<0.01) higher level of collagen IV-labeled vessels was observed as compared with non-exercised brains following the same treatment. The ex vivo study also revealed a key role of MMP-9 in exercise-strengthened collagen IV expression against I/R injury. TIMP-1 protein levels were significantly (P<0.01) increased by exercise. Our results indicate that pre-ischemic exercise reduces brain injury by improving BBB function and enhancing basal lamina integrity in stroke. This study suggests that the neuroprotective effect of physical exercise is associated with an imbalance of MMP-9 and TIMP-1 expression.     

Progesterone modulates m TOR in the hippocampus of mice after traumatic brain injury

the mechanistic target of rapamycin(m tor) is an intracellular protein kinase that functions as an energy and nutrient sensor in the cellular microenvironment of neurons. modulation of m tor is vital when nutrient and energy sources become limited. hypoxia, traumatic brain injury, cellular energy states, and growth factors all regulate the phosphorylation and total levels of m tor in cells. alterations in the microenvironment induce transduction of signals to downstream proteins by m tor allowing for cells to make the necessary adjustments to counteract stressors and survive. progesterone, a hydrophobic steroid hormone, has been shown in studies of non-neural tissue to be a suppressor of m tor and modulator of m tor phosphorylation. our study tested the effects of progesterone on m tor expression following traumatic brain injury. c57 bl/6 mice were treated with progesterone(8 mg/kg) at 1(intraperitoneal), 6(subcutaneous), 24(subcutaneous), and 48(subcutaneous) hours post closed skull traumatic brain injury. the hippocampus was then harvested 72 hours post injury and prepared for western blot analysis. we found that progesterone significantly decreased total m tor levels in all groups compared to sham treated with vehicle. this was further confirmed by immunostaining showing decreased cytoplasmic m tor levels compared to sham. our study shows progesterone is a significant modulator of m tor levels in the hippocampus of mice following traumatic brain injury.     

The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism

BACKGROUND: A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism. METHODS: Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus. RESULTS: The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 +/- 280.1 pg/mL vs. 637 +/- 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH >or=30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study. CONCLUSIONS: The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism.