Absolute assessment of aortic valve stenosis by planimetry using cardiovascular magnetic resonance imaging: comparison with transesophageal echocardiography, transthoracic echocardiography, and cardiac catheterisation

OBJECTIVE: The aims of this study were to investigate absolute assessment of aortic valve area (AVA), before surgery for aortic stenosis, using cardiovascular magnetic resonance (CMR) in comparison with transesophageal echocardiography (TEE) and with effective AVA indirectly obtained by routine techniques i.e. transthoracic echocardiography (TTE) and cardiac catheterisation. MATERIALS AND METHODS: Absolute AVA planimetry was performed by TEE and CMR steady state free precession sequences obtained through the aortic valvular plane. Effective AVA was calculated by the continuity equation in TTE and by cardiac catheterisation (Gorlin formula). RESULTS: Thirty-nine patients with aortic valve stenosis, mean age 71.7 +/- 7.6 years, with a mean AVA of 0.93 +/- 0.31 cm2 as measured by TEE, were enrolled in the study. Mean differences were: between CMR and TEE planimetry: d = 0.01 +/- 0.14 cm2, between CMR and cardiac catheterisation: d = 0.05 +/- 0.13 cm2, between CMR and TTE: d = 0.10 +/- 0.17 cm2, between TTE and TEE: d = 0.10 +/- 0.18 cm2, between TTE and cardiac catheterisation: d = 0.06 +/- 0.16 cm2, and between TEE and cardiac catheterisation: d = 0.07 +/- 0.13 cm2. Mean intraobserver and interobserver differences of CMR planimetry were d = 0.02 +/- 0.07 cm2 and d = 0.03 +/- 0.14 cm2, respectively. CONCLUSION: CMR planimetry of the AVA is a noninvasive and reproducible technique to evaluate stenotic aortic valves and can be used as an alternative to echocardiography or cardiac catheterisation.     

The value of 16-slice multidetector computed tomographic angiography in preoperative appraisal of vascular anatomy in potential living renal donors

Background

Comprehensive preoperative appraisal of potential living renal donors is the key for selecting a proper donor and a suitable kidney.

Objective

To prospectively assess the diagnostic value of 16-slice multidetector computed tomography (MDCT) in preoperative appraisal of vascular anatomy in potential living renal donors.

Materials and methods

Preoperative angiography using a 16-slice MDCT scanner was performed in 68 consecutive potential living renal donors. The MDCT angiography included unenhanced and contrast-enhanced multiphasic scans. The MDCT images were reviewed for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with the actual anatomy at the open donor nephrectomy as the diagnostic standard of reference.

Results

The sensitivity and the specificity of MDCT angiography for the detection of various anatomic variants of renal arteries as well as renal venous anomalies were 100%. The anatomic variants of renal arteries included accessory arteries (n = 7) and early arterial branching (n = 10). Whereas, the detected venous anomalies were of major category of the circumaortic left renal vein anomaly (n = 2). No minor renal venous anomaly was identified in any subject.

Conclusion

16-Slice MDCT angiography is highly accurate for preoperative assessment of diverse anomalies of the renal vascular anatomy in potential living renal donors; in consequence, it markedly affects the surgical planning.     

Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors

Purpose

LY2334737 is an oral gemcitabine prodrug. This Phase I study assessed the safety and tolerability of LY2334737 in Japanese patients with solid tumors and evaluated pharmacokinetics (PK), pharmacodynamics, and antitumor activity.

Methods

Patients with advanced/metastatic solid tumors received escalating doses of LY2334737 once daily for 14 days, followed by a 7-day drug-free period. Cycles were repeated until discontinuation criteria were met.

Results

Of 13 patients treated, 3 received 20 mg/day, 6 received 30 mg/day, 4 received 40 mg/day. On the 40 mg dose, 3 patients experienced dose-limiting toxicities (DLTs): hepatic toxicities (e.g., Grade [G]3/4 transaminase and G1–3 bilirubin elevation) and G4 thrombocytopenia; all 3 showed features of disseminated intravascular coagulation. One additional DLT occurred on the 30 mg dose (G3 transaminase elevation). Exploratory pharmacogenetic analyses identified a genetic variation in the CES2 gene potentially associated with these DLTs. PK data showed no clear relationship between the AUC of gemcitabine and its incorporation into leukocyte DNA; 2 of the 3 DLT patients had high incorporation. Two patients (30 mg/day) achieved stable disease with progression-free survival lasting 135 and 155 days.

Conclusions

LY2334737 was tolerated by Japanese patients up to 30 mg/day. The toxicities observed at the 40 mg dose may require the development of alternative dosing schedules.     

Effect of a Perioperative Nutritional Supplementation with Oral Impact® in Patients undergoing Hepatic Surgery for Liver Cancer: A Prospective,Placebo-Controlled,Randomized, Double-Blind Study

Perioperative nutrition with supplements containing l-arginine, ω3-polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact® in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean ± SD) was 70 ± 27% and 79 ± 25% (P = 0.409) 3 days after surgery and 90 ± 30% and 106 ± 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, γ-glutamyl transferase, α-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer.     

Disease prioritarianism: a flawed principle

Disease prioritarianism is a principle that is often implicitly or explicitly employed in the realm of healthcare prioritization. This principle states that the healthcare system ought to prioritize the treatment of disease before any other problem. This article argues that disease prioritarianism ought to be rejected. Instead, we should adopt ‘the problem-oriented heuristic’ when making prioritizations in the healthcare system. According to this idea, we ought to focus on specific problems and whether or not it is possible and efficient to address them with medical means. This has radical implications for the extension of the healthcare system. First, getting rid of the binary disease/no-disease dichotomy implicit in disease prioritarianism would improve the ability of the healthcare system to address chronic conditions and disabilities that often defy easy classification. Second, the problem-oriented heuristic could empower medical practitioners to address social problems without the need to pathologize these conditions. Third, the problem-oriented heuristic clearly states that what we choose to treat is a normative consideration. Under this assumption, we can engage in a discussion on de-medicalization without distorting preconceptions. Fourth, this pragmatic and de-compartmentalizing approach should allow us to reconsider the term ‘efficiency’.