Live Donor Partial Hepatectomy for Liver Transplantation: Is There a Learning Curve?

Background: Donor safety is the first priority in living donor liver transplantation (LDLT). Objective: To determine the characteristics and outcome of live liver donors who underwent donor hepatectomy from January, 1997 to May, 2007 at Massachusetts General Hospital. Methods: 30 patients underwent LDLT between January, 1997 and May, 2007 at our institution. Results: The type of graft was the right lobe (segments 5-8) in 14, left lobe (segments 2-4) in 4, and left lateral sector (segments 2 and 3) in 12 patients. The mean donor age was 36 (range: 26-57) years. The mean follow-up was 48 (range: 18-120) months. No deaths occurred. Overall, 8 (26.6%) patients experienced a total of 14 post-operative complications. Donor complications based on graft type were as follows: left lateral sector (16.7%), left lobe (25%), and right lobe (35.7%). The experience was divided into two periods 1997-2001 (n=15) and 2002-2007 (n=15). Overall complications during 2 periods were 40% and 13.3%, respectively (p<0.001). The incidence of grade III complication also significantly decreased; 66.7% vs 33.3% (p<0.01). Conclusion: Partial hepatectomy in living donors has a learning curve which appears to be approximately 15 cases. This learning curve is not restricted to the surgeons performing the procedure but involves all aspects of patient care

Induction with Rabbit Antithymocyte Globulin following Orthotopic Liver Transplantation for Hepatitis C

Background: Hepatitis C (HCV) is the most common indication for liver transplantation in the US. Objective: Since steroids are the major stimulus of viral replication, we postulated that steroid-free immunosuppression might be a safer approach. Methods: From January 1995 to October 2002, we used steroid plus calcineurin inhibitor (CNI) immunosuppression after liver transplantation for HCV (steroid group, n=81). From October 2002 to June 2007, rabbit antithymocyte globulin (RATG) induction, followed by CNI and azathioprine (RATG group, n=73) was utilized. Results: There were no differences in 1- and 3-year patient/allograft survival rates. The incidence of acute rejection rate (19% vs. 28%), of biopsy-proven HCV recurrence (70% vs. 75%), and chronic rejection (6% vs. 9%) were comparable. The mean time to develop recurrent HCV was significantly longer in the RATG group (16.2 vs. 9.2 months, p=0.008). The incidence of severe portal fibrosis appears to be lower in RATG group compared to the steroid group; 14% vs. 4% (p=0.07). Conclusions: RATG induction is safe and effective after liver transplantation for HCV, but has no impact on the incidence of HCV recurrence and patient/allograft survival. However, a significant delay in time to HCV recurrence and a trend toward less rejection and portal fibrosis was observed

RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities

With rising rates of drug-resistant infections, there is a need for diagnostic methods that rapidly can detect the presence of pathogens and reveal their susceptibility to antibiotics. Here we propose an approach to diagnosing the presence and drug-susceptibility of infectious diseases based on direct detection of RNA from clinical samples. We demonstrate that species-specific RNA signatures can be used to identify a broad spectrum of infectious agents, including bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a small set of bacterial transcripts after a brief antibiotic pulse can rapidly differentiate drug-susceptible and -resistant organisms and that these measurements can be made directly from clinical materials. Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents

apeNEXT: A Multi-Tflops LQCD Computing Project

This paper is a slightly modified and reduced version of the proposal of the {\bf apeNEXT} project, which was submitted to DESY and INFN in spring 2000. .It presents the basic motivations and ideas of a next generation lattice QCD (LQCD) computing project, whose goal is the construction and operation of several large scale Multi-TFlops LQCD engines, providing an integrated peak performance of tens of TFlops, and a sustained (double precision) performance on key LQCD kernels of about 50% of peak speed

Undergraduate Medical Education Reform in Viet Nam for a Primary Health Care Workforce

Strong primary health care (PHC) systems require a robust PHC workforce. Traditionally, medical education takes place in academic medical centres that favour subspecialty care rather than PHC settings. This may undervalue primary care as a career and contribute to a shortage of PHC workers. However, designing undergraduate medical education curricula that incorporate early experiences in clinical care delivery at PHC sites remains a challenge, including in many low- and middle-income countries (LMICs). This paper describes how a collaboration between Harvard Medical School and five medical schools in Vietnam, and in-country collaborations among the Vietnamese medical schools, facilitated curricular innovation and co-creation of coursework relevant to PHC through the development of a Practice of Medicine (POM) course. The collaboration implemented a technical assistance strategy consisting of in-person workshops, focused virtual consultations, on-site ‘office hours’, site visits and observations to each of the five medical universities, and immersion trips to support the creation and implementation of the POM course. A pilot program was started at a single site and then scaled nationally using local customisation, experience, and expertise utilising a train-the-trainers approach. As a result, five new POM courses have been developed by five Vietnamese institutions. Fifty Vietnamese faculty received training to lead the POM course development, and 228 community-based preceptors have been trained to teach students at PHC sites. A total of 52 new PHC and community-based clinical training sites have been added, and 3,615 students have completed or are currently going through a POM course. This experience can serve as a model for future academic collaborations to support the development of a robust PHC workforce for the 21st century

Perforated peptic ulcer (PPU) treatment: an Italian nationwide propensity score-matched cohort study investigating laparoscopic vs open approach

BackgroundPerforated peptic ulcer (PPU) remain a surgical emergency accounting for 37% of all peptic ulcer-related deaths. Surgery remains the standard of care. The benefits of laparoscopic approach have been well-established even in the elderly. However, because of inconsistent results with specific regard to some technical aspects of such technique surgeons questioned the adoption of laparoscopic approach. This leads to choose the type of approach based on personal experience. The aim of our study was to critically appraise the use of the laparoscopic approach in PPU treatment comparing it with open procedure.MethodsA retrospective study with propensity score matching analysis of patients underwent surgical procedure for PPU was performed. Patients undergoing PPU repair were divided into: Laparoscopic approach (LapA) and Open approach (OpenA) groups and clinical-pathological features of patients in the both groups were compared.ResultsA total of 453 patients underwent PPU simple repair. Among these, a LapA was adopted in 49% (222/453 patients). After propensity score matching, 172 patients were included in each group (the LapA and the OpenA). Analysis demonstrated increased operative times in the OpenA [OpenA: 96.4 +/- 37.2 vs LapA 88.47 +/- 33 min, p = 0.035], with shorter overall length of stay in the LapA group [OpenA 13 +/- 12 vs LapA 10.3 +/- 11.4 days p = 0.038]. There was no statistically significant difference in mortality [OpenA 26 (15.1%) vs LapA 18 (10.5%), p = 0.258]. Focusing on morbidity, the overall rate of 30-day postoperative morbidity was significantly lower in the LapA group [OpenA 67 patients (39.0%) vs LapA 37 patients (21.5%) p = 0.002]. When stratified using the Clavien-Dindo classification, the severity of postoperative complications was statistically different only for C-D 1-2.ConclusionsBased on the present study, we can support that laparoscopic suturing of perforated peptic ulcers, apart from being a safe technique, could provide significant advantages in terms of postoperative complications and hospital stay

Gastro-intestinal emergency surgery: Evaluation of morbidity and mortality. Protocol of a prospective, multicenter study in Italy for evaluating the burden of abdominal emergency surgery in different age groups. (The GESEMM study)

Gastrointestinal emergencies (GE) are frequently encountered in emergency department (ED), and patients can present with wide-ranging symptoms. more than 3 million patients admitted to US hospitals each year for EGS diagnoses, more than the sum of all new cancer diagnoses. In addition to the complexity of the urgent surgical patient (often suffering from multiple co-morbidities), there is the unpredictability and the severity of the event. In the light of this, these patients need a rapid decision-making process that allows a correct diagnosis and an adequate and timely treatment. The primary endpoint of this Italian nationwide study is to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18. Secondary endpoints will be to evaluate to analyze the prognostic role of existing risk-scores to define the most suitable scoring system for gastro-intestinal surgical emergency. The primary outcomes are 30-day overall postoperative morbidity and mortality rates. Secondary outcomes are 30-day postoperative morbidity and mortality rates, stratified for each procedure or cause of intervention, length of hospital stay, admission and length of stay in ICU, and place of discharge (home or rehabilitation or care facility). In conclusion, to improve the level of care that should be reserved for these patients, we aim to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18, to analyze the prognostic role of existing risk-scores and to define new tools suitable for EGS. This process could ameliorate outcomes and avoid futile treatments. These results may potentially influence the survival of many high-risk EGS procedure

History of clinical transplantation

How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening