Deep pericardial stitch enables hemodynamically stable exposure of beating heart

The use of a deep pericardial stitch to obtain optimal exposure for precise distal anastomoses was assessed in 51 patients (mean age, 56.5 +/- 9.1 years) undergoing off-pump coronary artery bypass grafting. Hemodynamic data were recorded after sternotomy, before, and after each of the 120 distal anastomosis. Most hemodynamic parameters did not change throughout the procedures. During exposure of the circumflex artery, there were significant decreases in systolic arterial pressure from 106.0 +/- 15.5 to 87.7 +/- 13.6 mm Hg, mean systemic arterial pressure from 83.9 +/- 11.7 to 68.5 +/- 17.0 mm Hg, stroke volume from 68.5 +/- 23.3 to 50.5 +/- 18.3 mL, and stroke index from 34.4 +/- 11.5 to 24.3 +/- 8.7 mL x m(-2). Cardiac function was not affected when other coronary arteries were bypassed. On completion of all anastomoses, hemodynamics returned to baseline status. It was concluded that the deep pericardial stitch enabled stable and safe exposure of the heart for off-pump coronary artery grafting.     

First Experience With the Synergy Micro‐Pump in Patients in INTERMACS Class 1–2 as a Bridge to Transplantation: Pushing the Limits?

The Synergy Micro‐pump is the smallest implantable left ventricular assist device (LVAD) and provides partial flow support up to 4.25 L/min. It was shown that early intervention with this device can provide substantial benefits to patients with severe heart failure not yet sick enough for a full‐support LVAD. However, as it can be inserted via small incisions with no need for sternotomy or cardiopulmonary bypass, it might be beneficial for selected high‐risk patients. The aim of this study was to evaluate the efficacy of the Synergy Micro‐pump in patients in INTERMACS class 1–2. From February 2012 to August 2013, 13 patients with severe heart failure were supported with the Synergy Pocket Micro‐pump. Patients were divided into two groups according to INTERMACS class: the high‐risk group (INTERMACS class 1–2) and the low‐risk group (INTERMACS class 3–4). There were seven patients in INTERMACS class 1–2 and six in INTERMACS class 3–4. Patient demographics, perioperative characteristics, and postoperative outcomes were compared. There were no statistically significant differences in patient demographics, and mean support time was 108 ± 114 days in the high‐risk group and 238 ± 198 days in the low‐risk group. Also, there were no significant differences in perioperative characteristics or in the rate of postoperative adverse events. The overall survival was comparable between the two groups (one late death in each group, log‐rank P = 0.608). Two patients from the high‐risk group were upgraded to a full‐support LVAD (P = 0.462) after 65 ± 84.9 days of mean support. One patient from the high‐risk group and two patients from the low‐risk group were successfully transplanted (P = 0.559). The use of the Synergy Micro‐pump in INTERMACS 1–2 patients is feasible and is associated with similar postoperative outcome as in patients in INTERMACS 3–4. Carefully selected patients with severe heart failure could benefit due to the small size of the pump; however, further studies and medium‐term follow‐up are required.     

Distal Limb Perfusion: Achilles' Heel in Peripheral Venoarterial Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a temporary mechanical circulatory assist method that offers circulatory as well as respiratory support efficiently via peripheral access; however, it is liable to complications. Limb ischemia is one of the notorious complications of ECMO but can be avoided utilizing a proper distal limb perfusion method. A retrospective study of patients undergoing peripheral venoarterial (VA) ECMO for various reasons between June 2010 and December 2012 was performed. All patients were evaluated by our multidisciplinary team for suitability as candidates for ECMO. A peripheral VA‐ECMO circuit was implanted via groin: inflow cannula in the femoral vein, an outflow cannula and distal‐perfusion cannula, or an introducer sheath in the femoral artery. During the study period, 83 patients underwent various types of ECMO; 45 received peripheral VA‐ECMO. Distal limb perfusion was achieved with an introducer sheath (6–8 Fr) in 13 cases and with a distal‐perfusion cannula (10–12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. One patient required a below‐knee amputation. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly higher for the introducer sheath compared with the cannula (30.6 vs. 15.6% and 15.4 vs. 6.25%, respectively). Moreover, the patients supported on ECMO with a distal‐perfusion cannula spent a significantly longer time on ECMO compared with the ones in whom an introducer sheath was used (11.9 ± 9.1 vs. 7.7 ± 4.3 days). The mean cannula size was significantly greater than the mean introducer sheath size (11.1 ± 1.3 vs. 7.0 ± 1.1 Fr). Use of a distal‐perfusion cannula is a most reliable method of limb perfusion in peripheral VA‐ECMO. The cannula can ensure adequate and smooth perfusion of the limb owing to its large caliber, its less turbulent flow, the ability it provides to monitor the flow, and the option to attach a side port.     

Hydrophilic Polyhedral Oligomeric Silsesquioxane,POSS(OH)32, as a Complexing Nanocarrier for Doxorubicin and Daunorubicin

A novel strategy, recently developed by us, to use polyhedral oligomeric silsesquioxanes (POSS) as an anti-cancer drug carrier is presented. Anthracycline:POSS complexes were prepared by simple co-addition of doxorubicin (DOX) or daunorubicin (DAU) with hydrophilic POSS(OH)₃₂. Co-delivery of POSS and anthracyclines led to higher anti-cancer activity towards HeLa (cervical cancer endothelial) and MCF-7 (human breast adenocarcinoma) cell lines. The obtained supramolecular hybrid complexes were characterised by nuclear magnetic resonance (NMR) spectroscopy (nuclear Overhauser effect spectroscopy [NOESY] and homonuclear correlation spectroscopy [COSY]), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The two-dimensional (2D) NOESY spectra of the complexes showed the cross-correlation peaks for hydroxyl groups of POSS (~4.3–4.8 ppm) with OH groups of DOX and DAU. FTIR showed that hydroxyl group of POSS can interact with amine and hydroxyl groups of DOX and DAU. The viability of HeLa and MCF-7 was analysed with the MTT assay to evaluate the cytotoxicity of free DOX and DAU and the relevant complexes with POSS at different molar ratios. At a low DOX concentration (2.5 µM), for molar ratios 1:1, 1:4, and 1:8 (POSS:DOX), the complexes showed two and three times higher cytotoxicity towards HeLa and MCF-7 cells, respectively, than DOX itself after both 24- and 48-h incubation. The 1 µM concentration for a 1:4 POSS:DOX molecular ratio and the 2.5 µM concentration for all complexes were more toxic towards MCF-7 cells than free DOX after 48-h incubation. In the case of POSS:DAU complexes, there was higher toxicity than that of free drug after 48-h incubation. It can be concluded that the formation of non-covalent complexes increases toxicity of anthracycline drugs towards Hela and MCF-7 cells. The novel complexes are inexpensive to prepare and more effective than free drugs at low systemic toxicity.     

Clinical Predictors and Hemodynamic Consequences of Elevated Peripheral Chemosensitivity in Optimally Treated Men With Chronic Systolic Heart Failure

AimsAugmented peripheral chemoreflex response is an important mechanism in the pathophysiology of chronic heart failure (CHF). This study characterizes prevalence and clinical predictors of this phenomenon in optimally managed male CHF patients, and seeks to describe the hemodynamic consequences of chemoreceptor hypersensitivity.Methods and ResultsThirty-four optimally managed CHF patients and 16 control subjects were prospectively studied. Hypoxic ventilatory response (HVR)—a measure of peripheral chemosensitivity—was calculated with the use of short nitrogen gas administrations. Systolic blood pressure (SBP) and heart rate (HR) following transient hypoxic challenges were recorded with a Nexfin monitor. Hemodynamic responses to hypoxia were expressed by the linear slopes between oxygen saturation (%) and SBP (mm Hg) or HR (beats/min). Elevated HVR was present in 15 (44%) of the CHF patients. Patients with elevated HVR exhibited higher levels of N-terminal pro–B-type natriuretic peptide, lower left ventricular ejection fraction, and higher prevalence of atrial fibrillation. CHF patients with elevated HVR had significantly greater SBP and HR responses to hypoxia than CHF patients with normal HVR.ConclusionsDespite comprehensive pharmacotherapy, elevated HVR is prevalent in CHF patients, related to severity of the disease and associated with augmented hemodynamic responses to hypoxia. CHF patients with elevated HVR may be prone to unfavorable hemodynamic changes.     

Treatment outcomes and secondary cancer incidence in young patients with hairy cell leukaemia

Repeated therapy of hairy cell leukaemia (HCL) with treatments that have potential long‐term toxicities has raised concerns regarding increased risk for younger patients. We compared clinical outcomes and disease complications in 63 patients with HCL aged ≤40 years at diagnosis with 268 patients >40 years treated at Memorial Sloan Kettering Cancer Center. The rate of complete remission following initial therapy was 87% and 83% (P = 0·71) and estimated 10‐year overall survival was 100% and 82% (P = 0·25) in younger and older patients, respectively. Younger patients required therapy earlier and had a significantly shorter time between first and second therapy (median: 63 months vs. 145 months) (P = 0·008). Younger patients required significantly more lines of therapy during follow‐up. The 10‐year cumulative incidence of secondary malignancies in young and old patients was 0·205 and 0·287, respectively (P = 0·22). The incidence of secondary cancers in patients aged >40 years at diagnosis increased with the number of treatments for HCL (P = 0·018). These results highlight that young patients with HCL have shorter responses to treatment and require more lines of therapy to maintain disease control, while attaining similar long‐term survival. This has implications in the design of future clinical trials given our findings that secondary malignancies increase with more chemotherapy exposure.     

Association Between Histological Type of Tumour Growth and Patient Survival in T2-T3 Lymph Node-Negative Rectal Cancer Treated with Sphincter-Preserving Total Mesorectal Excision

For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.