Synergistic Combination for Chemoprevention of Hepatocellular Carcinoma: An In Silico and In Vitro Approach

Combination therapy is one of the best methods to manage the fatality rate in hepatocellular carcinoma (HCC). This study aimed to formulate a synergistic combination of synthetic and herbal compounds for the treatment of HCC as well as to elucidate a possible signalling mechanism. MTT and enzymatic assay were performed to determine the synergistic effect of drug combination (sorafenib, vitamin K1 and trans‐chalcone) on HepG2 cell lines after intoxication with H₂O₂. Protein–protein interaction and docking studies were performed using Pathwaylinker2.0 and Schrödinger's software application to find out the mechanism of action and major targets for drug combination. The overall in vitro result showed that combination of trans‐chalcone, vitamin K1 and sorafenib (10, 5 and 5 μM concentration, respectively) enhanced the resistance against oxidative stress generated by H₂O₂. The interaction studies helped in identification of few targets for docking of ligands (trans‐chalcone, vitamin K1 and sorafenib). The study reports the synergistic effects of the formulation that can protect the cells from oxidative stress and restore normal levels of cellular enzymes in HepG2 cell line. We were able to determine the mechanism of action of herbal and synthetic formulation through in silico studies. Finally, docking studies confirmed potential targets for inhibition of hepatocarcinogenesis.     

Non‐HLA‐matched 3rd party vascular allograft in renal transplant may lead to sensitization against donor HLA

3rd party donor vessels are often used for vascular reconstruction in organ transplantation. While current practice ensures that 3rd party vessels are blood group matched, HLA matching to the non‐intended recipient is not performed. This practice potentially sensitizes the recipient and may reduce their future chance of renal transplant from a larger pool of donors. We examined our cohort of renal transplant recipients who received non‐HLA‐matched 3rd party vessels for the de‐novo development of donor‐specific HLA antibodies. Our institution's Human Tissue Authority (HTA) blood vessel registers were examined to identify stored donor vessels and their non‐intended recipients. Donor vessel HLA status was cross‐referenced with the recipient HLA status. Between 2004 and 2014, five patients were identified that received 3rd party non‐HLA‐matched vessels for vascular reconstruction during renal transplantation. Three patients (60%) subsequently developed donor‐specific HLA antibodies. These data provide evidence that use of non‐HLA‐matched stored 3rd party vascular grafts may lead to sensitization in the recipient. Where time permits, HLA matching should be performed to avoid this allogeneic response. Laboratories monitoring DSA should be aware of any patient receiving a non‐HLA‐matched 3rd party vascular graft, and recipients may benefit from increased post‐transplant immunological vigilance.     

Can postoperative renal dysfunction be predicted by measuring intraoperative glomerular filtration rate in patients undergoing coronary artery bypass grafting without cardiopulmonary bypass? A pilot study

Objective

Currently, there is no effective paradigm to identify patients who are at risk for renal dysfunction following cardiac surgery. The specific mechanisms of renal injury during surgery are incompletely understood. The aim of the study was to evaluate whether postoperative renal dysfunction can be predicted from intraoperative glomerular filtration rate (GFR).

Design

This is a prospective study.

Setting

The study was conducted in a tertiary care multi-specialty hospital.

Participants and interventions

GFR was measured in 24 patients (mean age 56.6 ± 11.09 years, 20 male) undergoing elective off-pump coronary artery bypass grafting during preoperative period, intraoperative period, 24 h after surgery (ICU GFR), and on the fifth postoperative day (final GFR ).

Measurements and main results

Patients were divided into two groups depending upon changes in intraoperative GFR. Group 1 (n = 10): who had a rise in intraoperative GFR in comparison with preoperative baseline measurement. All these 10 (41.7 %) patients with a rise in intraoperative GFR had an uneventful hospital course and achieved an improvement in final GFR. Group 2 (n = 14): 14 (58.3 %) patients had a fall in intraoperative GFR (mean 36.4 %) in comparison with preoperative baseline value. Of these 14 patients, 1 patient required dialysis support and 3 patients required ionotropic support. Among these 14 patients in group two, 7 had deterioration in final GFR (mean 28.7 %), when compared to preoperative baseline value.

Conclusion

Postoperative renal dysfunction can be predicted from intraoperative GFR. Patients who have a rise in intraoperative GFR do not develop postoperative renal dysfunction, and only patients with intraoperative fall in GFR are at risk of postoperative renal dysfunction.

     

Recurrent cutaneous metaplastic synovial cyst

Orofacial granulomatosis (OFG) is a granulomatous disease of the orofacial region. This clinicopathological entity describes patients with oral lesions characterized by persistent and/or recurrent labial enlargement, ulcers, and a variety of other orofacial features, which on biopsy have lymphedema and noncaseating granulomas. The cause is idiopathic but appears to represent an abnormal immune reaction. This may be a manifestation of Crohn's disease (CD) since some patients with oral lesions develop typical bowel symptoms of CD in ensuing months to years; tooth-associated infections, sarcoidosis, food or contact allergies, and viruses have also been implicated in causing OFG. Clinical features of OFG are highly variable and sometimes so insidious that signs and symptoms are frequently not severe enough to cause alarm. The lips are most commonly involved and demonstrate a nontender, persistent swelling. Because of the relatively nonspecific clinical findings associated with granulomatous diseases, a microscopic diagnosis of granulomatous inflammation often presents a diagnostic dilemma for clinicians. We report a case of OFG of the lower lip and cheek and describe its management to add to the current body of literature on the subject.     

Pregnancy associated spontaneous coronary artery dissection: A case report and review of literature

BACKGROUNDPregnancy-associated spontaneous coronary artery dissection (PSCAD) is an important cause of chest pain and acute myocardial infarction in pregnant and postpartum women. Pregnancy is considered an isolated risk factor for spontaneous coronary artery dissection. The etiology, pathogenesis, and incidence of PSCAD are not known.CASE SUMMARYWe present a case of a 33-year-old postpartum female who presented with sudden onset chest pain and was diagnosed with spontaneous coronary artery dissection and needed urgent catheterization revealing left anterior descending coronary artery dissection. She underwent emergent coronary artery bypass graft surgery with good post-operative recovery.CONCLUSIONMost patients with PSCAD can be managed conservatively with medical management and have good outcomes. Patients with high-risk presentations benefit from the invasive approach. Coronary artery bypass graft may be required in select few patients based on angiography findings. Due to the risk of recurrent spontaneous coronary artery dissection, subsequent pregnancies are discouraged.