Mind and heart: Heart rate variability in major depressive disorder and coronary heart disease - a review and recommendations

Objective: There is a reciprocal association between major depressive disorder (MDD) and coronary heart disease (CHD). These conditions are linked by a causal network of mechanisms. This causal network should be quantitatively studied and it is hypothesised that the investigation of vagal function represents a promising starting point. Heart rate variability (HRV) has been used to investigate cardiac vagal control in the context of MDD and CHD. This review aims to examine the relationship of HRV to both MDD and CHD in the context of vagal function and to make recommendations for clinical practice and research. Methods: The search terms 'heart rate variability', 'depression' and 'heart disease' were entered into an electronic multiple database search engine. Abstracts were screened for their relevance and articles were individually selected and collated. Results: Decreased HRV is found in both MDD and CHD. Both diseases are theorised to disrupt autonomic control feedback loops on the heart and are linked to vagal function. Existing theories link vagal function to both mood and emotion as well as cardiac function. However, several factors can potentially confound HRV measures and would thus impact on a complete understanding of vagal mechanisms in the link between MDD and CHD. Conclusions: The quantitative investigation of vagal function using HRV represents a reasonable starting point in the study of the relationship between MDD and CHD. Many psychotropic and cardiac medications have effects on HRV, which may have clinical importance. Future studies of HRV in MDD and CHD should consider antidepressant medication, as well as anxiety, as potential confounders.     

Anti-Cancer Effect of Moroccan Cobra Naja haje Venom and Its Fractions against Hepatocellular Carcinoma in 3D Cell Culture

Hepatocellular carcinoma (HCC) is the most common primary liver cancer in adults, the fifth most common malignancy worldwide and the third leading cause of cancer related death. An alternative to the surgical treatments and drugs, such as sorafenib, commonly used in medicine is necessary to overcome this public health problem. In this study, we determine the anticancer effect on HCC of Moroccan cobra Naja haje venom and its fraction obtained by gel filtration chromatography against Huh7.5 cancer cell line. Cells were grown together with WI38 human fibroblast cells, LX2 human hepatic stellate cell line, and human endothelial cells (HUVEC) in MCTS (multi-cellular tumor spheroids) models. The hepatotoxicity of venom and its fractions were also evaluated using the normal hepatocytes cell line (Fa2N-4 cells). Our results showed that an anti HCC activity of Moroccan cobra Naja haje venom and, more specifically, the F7 fraction of gel filtration chromatography exhibited the greatest anti-hepatocellular carcinoma effect by decreasing the size of MCTS. This effect is associated with a low toxicity against normal hepatocytes. These results strongly suggest that the F7 fraction of Moroccan cobra Naja haje venom obtained by gel filtration chromatography possesses the ability to inhibit cancer cells proliferation. More research is needed to identify the specific molecule(s) responsible for the anticancer effect and investigate their mechanism of action.     

Predictive Power of the NSQIP Risk Calculator for Early Post-Operative Outcomes After Whipple: Experience from a Regional Center in Northern Ontario

Background

NSQIP Risk Calculator was developed to allow surgeons to inform their patients about their individual risks for surgery. Its ability to predict complication rates and length of stay (LOS) has made it an appealing tool for both patients and surgeons. However, the NSQIP Risk Calculator has been criticized for its generality and lack of detail towards surgical subspecialties, including the hepatopancreaticobiliary (HPB) surgery. We wish to determine whether the NSQIP Risk Calculator is predictive of post-operative complications and LOS with respect to Whipple’s resections for our patient population. As well, we wish to identify strategies to optimize early surgical outcomes in patients with pancreatic cancer.

Methods

We conducted a retrospective review of patients who underwent elective Whipple’s procedure for benign or malignant pancreatic head lesions at Health Sciences North (Sudbury, Ontario), a tertiary care center, from February 2014 to August 2016. Comparisons of LOS and post-operative complications between NSQIP-predicted and actual ones were carried out. NSQIP-predicted complications rates were obtained using the NSQIP Risk Calculator through pre-defined preoperative risk factors. Clinical outcomes examined, at 30 days post-operation, included pneumonia, cardiac events, surgical site infection (SSI), urinary tract infection (UTI), venous thromboembolism (VTE), renal failure, readmission, and reoperation for procedural complications. As well, mortality, disposition to nursing or rehabilitation facilities, and LOS were assessed.

Results

A total of 40 patients underwent Whipple’s procedure at our center from February 2014 to August 2016. The average age was 68 (50–85), and there were 22 males and 18 females. The majority of patients had independent baseline functional status (39/40) with minimal pre-operative comorbidities. The overall post-operative morbidity was 47.5% (19/40). The rate of serious complication was 17.5% with four Clavien grade II, two grade III, and one grade V complications. One mortality occurred within 30 days after surgery. NSQIP Risk Calculator was predictive for the majority of post-surgical complication types, including pneumonia, SSI, VTE, reoperation, readmission, and disposition to rehabilitation or nursing home. Our center appears to have a higher rate of UTI than NSQIP predicted (O/E = 3.9), as well, the rate of cardiac complication (O/E = 3.1) also appears to be higher at our center. With respect to readmission rates (O/E = 0.6) and renal failure (O/E = 0), NSQIP provided overestimated rates. The average LOS was 11.9 ± 0.9 days, which was not significantly different from the average LOS of 11.5 ± 0.3 days predicted by NSQIP (p = 0.3). Overall, 80% of discharges occurred less than or within 3 days of that predicted by NSQIP.

Conclusion

NSQIP Risk Calculator is predictive of post-operative complications and LOS for patients who have undergone Whipple’s at our center. A more HPB-focused NSQIP calculator may accurately project post-operative complication in the pre-operative period. Nevertheless, the generic NSQIP has allowed us to examine our existing practice of post-operative care and has paved way to reduce cardiac and urinary complications in the future.

     

Increase of plasma neuropeptide Y-like immunoreactivity following chronic hypoxia in the rat

In an attempt to understand the changes of circulating neuropeptide Y (NPY) during hypoxia, the plasma level of NPY was investigated by radioimmunoassay. Exposure of rats to hypobaric hypoxia at an altitude of 18,000 ft for 4 weeks causes an increase of pulmonary pressure and an elevation of plasma NPY-like immunoreactivity (NPY-LI). However, the systemic blood pressure was not elevated by this chronic hypoxia. Also, plasma noradrenaline (NA) estimated by chromatographic analysis (HPLC-ECD) was not markedly raised. Failure of bretylium and guanethidine, sympathetic neuron blockers, in reducing the plasma NPY-LI level of these rats ruled out the participation of adrenergic nervous terminals. Adrenal medulla seems responsible for this elevation of plasma NPY-LI because this magnitude disappeared in adrenalectomized rats. These data suggest that chronic hypoxia induced an elevation of circulating NPY from the adrenal gland of rats.