Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

BackgroundThe aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature.MethodsMedline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis.ResultsFifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes.ConclusionQuality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery.     

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction

Objectives. Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied.Methods. Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 μg of subcutaneous recombinant EGF on a daily basis after UUO.Results. Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clusterin gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma.Conclusions. These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Extracellular Enzyme Activities by Basidiobolus and Conidiobolus Isolates on Solid Media./Extrazelluläre Enzymaktivitäten bei Basidiobolus- und Condiobolus-Isólaten auf festen Medien

Summary: Fifty-seven isolates of Basidiobolus from reptiles and amphibians, and 7 other obtained from the American Type Culture Collection (ATCC) in Maryland were studied for their extracellular enzyme activities on solid media. The Conidiobolus isolates studied included 4 recovered from Nigerian soil and additional 4 obtained from the ATCC All these isolates produced active extracellular lipase and protease and failed to exhibit amylase, deoxyribonuclease and ribonuclease activities. The significance of the findings is discussed.
Zusammenfassung: Fünfundsiebzig Basidiobolus-Isolate aus Reptilien und Amphibien und sieben weitere aus der American Type Culture Collection (ATCC) in Maryland wurden auf Aktivtäten extrazellulärer Enzyme auf festen Medien untersucht Die untersuchten Conidiobolus-Isolate schlossen vier aus nigerianischen Böden und vier weitere aus der ATCC ein. Alle Isolate zeigten extrazellulär Lipase- und Proteaseaktivität Amylase-, Desoxyribonuclease- und Ribonucleaseaktivität war jedoch nicht nachzuweisen. Die Bedeutung dieser Befunde wird diskutiert.