“Open” approach to aortic arch aneurysm repair

Aortic arch aneurysm is a relatively rare entity in cardiac surgery. Repair of such aneurysms, either in isolation or combined with other cardiac procedures, remains a challenging task. The need to produce a relatively bloodless surgical field with circulatory arrest, while at the same time protecting the brain, is the hallmark of this challenge. However, a clear understanding of the topic allows a better and less morbid approach to such a complex surgery.Literature has shown the advantage of selective cerebral perfusion techniques in comparison with only circulatory arrest. Ability to perfuse the brain has allowed circulatory arrest temperatures at moderate hypothermia without the need for deep hypothermia. Even though cannulation site selection appears to be a minor issue, literature has shown that the subclavian/axillary route has the best outcomes and that femoral cannulation should only be reserved for no access patients. Although different techniques for arch anastomosis have been described, we routinely perform the distal first technique as we find it to be less cumbersome and easiest to reproduce.In this review our aim is to outline a systematic approach to aortic arch surgery. Starting with indications for intervention and proceeding with approaches on site of cannulation, approaches to brain protection with hypothermia and selective cerebral perfusion and finally surgical steps in performing the distal and arch vessels anastomosis.     

Rationale and design of the Kidney Precision Medicine Project

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Validation of the language component of the Addenbrooke's Cognitive Examination – Revised (ACE‐R) as a screening tool for aphasia in stroke patients

Aim: Several tests are available for aphasia screening following stroke. However, some of them have shortcomings such as need of specialist knowledge, low sensitivity and/or specificity and lengthy administration time. Our study aims to evaluate the language component of the Addenbrooke's Cognitive Examination – Revised (ACE‐R) as a screening tool for aphasia in stroke patients. Methods: The language component of ACE‐R was administered to consecutive patients admitted to a post‐acute stroke unit. Patients who were medically unstable or had a significant history of sensory impairment or mental health issues were excluded. The test was administered by two junior doctors with basic training in ACE‐R administration. Patients recruited were also assessed by an experienced speech and language therapist (SLT). The results of the two assessments were documented by a different member of the team and the SLT results were used as the benchmark to calculate the ACE‐R language component sensitivity and specificity. Results: Fifty‐nine participants were recruited and 27 of them were women. The mean age was 72 (SD 11.9). Thirty‐four participants had left and 11 right hemisphere stroke. Fourteen had bilateral affection. Six participants were left handed. A cut‐off value of 22/26 of ACE‐R language component showed 100% specificity and 83.1% sensitivity, while a cut‐off value of 16/26 had 88.2% specificity and 100% sensitivity. Conclusion: Our results suggest that the language component of ACE‐R has a satisfactory sensitivity and specificity compared with other screening tests used in strokes. It is easy to administer and free to use.     

Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population

CONTEXT: Genetic aberration in phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been detected in numerous and diverse human cancers. PIK3CA, which encodes for the catalytic subunit of p110alpha of PI3K, is amplified in some cases of papillary thyroid cancer (PTC). Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC. OBJECTIVE: The objective of the study was to investigate genetic alterations like PIK3CA gene mutation, PIK3CA amplification, RAS, and RAF mutations and to further explore the relationship of these genetic alterations with various clinicopathological characteristics in Middle Eastern PTC. DESIGN: We used the fluorescence in situ hybridization technique for analysis of PIK3CA amplification from 536 PTC cases, and selected amplified samples were further validated by real-time quantitative PCR. Mutation analysis was done by direct DNA sequencing of PIK3CA, N2-RAS, and BRAF genes. RESULTS: PIK3CA amplification was seen in 265 of 499 PTC cases analyzed (53.1%); PIK3CA gene mutations in four of 207 PTC (1.9%); N2-RAS mutations in 16 of 265 PTC (6%); and BRAF mutations in 153 of 296 PTC (51.7%). N-RAS mutations were-associated with an early stage (P = 0.0465) and lower incidence of extrathyroidal extension (P = 0.027), whereas BRAF mutations were-associated with metastasis (P = 0.0274) and poor disease-free survival (P = 0.0121) in PTCs. CONCLUSION: A higher incidence of PIK3CA alterations and the possible synergistic effect of PIK3CA alterations and BRAF mutations suggest their major role in Middle Eastern PTC tumorigenesis and argue for therapeutic targeting of PI3K/AKT and MAPK pathways.     

Once-weekly epoetin alfa improves anemia and facilitates maintenance of ribavirin dosing in hepatitis C virus-infected patients receiving ribavirin plus interferon alfa

OBJECTIVE: The aim of this study was to determine the efficacy of epoetin alfa in alleviating anemia and minimizing ribavirin (RBV) dose reductions in patients with chronic hepatitis C virus (HCV) infection receiving combination RBV/interferon alfa (IFN) therapy. METHODS: HCV-infected patients who had Hb levels of 12 g/dl or less during the first 24 wk of combination RBV/IFN therapy (n=64) were randomized to treatment with epoetin alfa (40,000 units) s.c. q.w. or to standard of care (SOC) for anemia management (RBV dose reduction or discontinuation, transfusions). Primary and secondary efficacy endpoints were changes in Hb level and RBV dosage, respectively, from baseline to week 16 of epoetin alfa therapy.Based on intent-to-treat analysis, the mean changes from baseline Hb levels at week 16 were +2.8 g/dl for epoetin alfa versus +0.4 g/dl for SOC (p<0.0001), and the mean changes in RBV dosage were -34 mg/day for epoetin alfa versus -146 mg/day (p=0.060) for SOC. The mean Hb level at week 16 in the epoetin alfa group (13.8 g/dl) was significantly (p<0.0001) higher than that of the SOC group (11.4 g/dl). At week 4 and subsequently, significantly more patients in the epoetin alfa group did not have RBV dosage reductions (p<0.011). At study end, 83% of epoetin alfa-treated patients maintained RBV dosages of at least 800 mg/day, compared with 54% of patients receiving SOC (p=0.022). Epoetin alfa was well tolerated. CONCLUSIONS: In anemic HCV-infected patients treated with RBV/IFN, epoetin alfa increases Hb levels and maintains RBV dosing. Based on these results, epoetin alfa seems to be promising in the treatment of HCV treatment-related anemia. Further research is warranted to determine the potential impact on outcomes, including quality of life and sustained viral response rate.