Interferon Gamma ELISPOT Testing as a Risk‐Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT‐01 Multicenter Study

Previous studies suggest that quantifying donor‐reactive memory T cells prior to kidney transplantation by interferon gamma enzyme‐linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation‐01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6‐ or 12‐month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell‐depleting, rabbit anti‐thymocyte globulin (ATG). Within the no‐ATG subset, IFNγELISPOT^neg subjects had higher 6‐ and 12‐month eGFRs than IFNγELISPOT^pos subjects, independent of biopsy‐proven AR, peak PRA, human leukocyte antigen mismatches, African‐American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor‐reactive memory T cells.     

Surgical treatment for hypertrophic obstructive cardiomyopathy

INTRODUCTION AND OBJECTIVES: Five percent of the patients with hypertrophic obstructive cardiomyopathy (HOCM) have symptoms unresponsive to medical treatment and are candidates for invasive therapy. The objective of this study was to analyze our results with surgical treatment of HOCM during the last 10 years. PATIENTS AND METHOD: Between July 1993 and January 2004 26 patients with HOCM refractory to drug therapy were operated on. An extended septal myectomy was performed, in combination with anterior mitral leaflet plication in 19 cases (73%) and with mitral valve replacement in 5 (19%). Evolution of the grade of dyspnea, left ventricle outflow tract gradient (LVOTG), mitral regurgitation, and systolic anterior motion after surgery was analyzed. RESULTS: Mean follow-up was 63 (37) months. After surgery, a significant reduction in LVOTG (from 96.5 to 19.5 mmHg; P<.001), grade of mitral regurgitation (from 2.54 to 0.69; P<.001) and systolic anterior motion (from 2.92 to 0.23; P<.001) was achieved, which led to improvement in functional class. Hospital mortality and need for pacemaker implantation due to complete heart block after surgery was 3.8% (n=1). There were no cases of iatrogenic ventricular septal defect or mitro-aortic valve injury. Actuarial survival at 5 years was 96% (4%). CONCLUSIONS: Surgery in patients with HOCM yields great clinical improvements with low morbidity and mortality. Simultaneous intervention for both myocardial and valvular components of the disease allows not only reduction in the LVOTG but also correction of mitral regurgitation and abolition of systolic anterior motion.     

Robotic and Laparoscopic Surgery for Treatment of Colorectal Diseases

PURPOSE In the last ten years, several robotic systems have been developed to overcome the loss of the three-dimensional view and dexterity characteristic of laparoscopic surgery. The aim of this study was to compare the traditional laparoscopic approach and robotic techniques in the treatment of colorectal diseases.METHODS The study compares a consecutive series of patients treated surgically for colorectal disease from June 2001 to May 2003 with the da Vinci robotic system (Intuitive Surgical^®) and a matched number of patients who underwent conventional laparoscopy during the same time interval. The factors analyzed were the time required to prepare the patient and the room, total time of surgery, length of specimens, number of lymph nodes retrieved, blood loss, complications, and postoperative results.RESULTS The study included 106 patients (53 in each group). No differences were observed in total time of surgery (laparoscopic group, 222 ± 77 minutes vs. robotic group, 240 ± 61 minutes), specimen length (laparoscopic group, 29 ± 11 cm vs. robotic group, 27 ± 13 cm), or number of lymph nodes retrieved (laparoscopic group, 16 ± 9 vs. robotic group, 17 ± 10). It took significantly longer to prepare the operating room and patient in the robotic group (24 ± 12 minutes) than in the laparoscopic group (18 ± 7 minutes). There were three conversions to laparotomy in the laparoscopic group; in the robotic group, two cases were converted to laparoscopy and three to hand-assisted laparoscopy. No significant differences were observed between the two groups in terms of recovery of bowel function and postoperative hospital stay.CONCLUSIONS Robot-assisted surgery proved to be as safe and effective as laparoscopic techniques in the treatment of colorectal diseases. Because of its dexterity and three-dimensional view, the da Vinci system was particularly useful in specific stages of the procedure, e.g., takedown of the splenic flexure, dissection of a narrow pelvis, identification of nervous plexus, and handsewn anastomosis. The cost-effectiveness of the procedure still needs to be evaluated.     

Extra-abdominal infections due to Gemella species.

OBJECTIVES: To understand the role of Gemella species as a pathogen causing extra-abdominal infections in the Hospital General Universitario Gregorio Mara?ón. MATERIALS AND METHODS: Between 1994 and 1998, one or more isolates of Gemella sp. were found in 128 patients. The 113 patients with isolates from nonsignificant specimens or representing intra-abdominal infections were excluded. The clinical records of the remaining 15 patients were reviewed as well as the more recent literature. RESULTS: Mean age of patients was 41 years. The underlying conditions most frequently noted were intravenous drug users (n=6; 3 positive for human immunodeficiency virus), alcoholism (n=2), cardiovascular disease (n=2), chronic lung disease (n=2), diabetes (n=1), kidney transplant (n=1). The extra-abdominal infections were skin and soft tissue abscess (n=5), empyema (n=4), brain abscess (n=2), primary bacteremia (n=1), lung abscess (n=1), septic thrombophlebitis (n=1), complicated urinary tract infection (n=1). The infection was monomicrobial in six and polymicrobial in nine cases. Surgical drainage and betalactam antibiotics were used. The outcome was favorable in almost all cases. CONCLUSIONS: Gemella sp. should be included as a cause of localized soft-tissue abscesses, empyema, and bloodstream infection. No case of infective endocarditis was found. Although it is susceptible to several antibiotics, Gemella sp. requires a careful microbiologic diagnosis and a subtle clinical interpretation.     

Tuberculosis recurrences: reinfection plays a role in a population whose clinical/epidemiological characteristics do not favor reinfection

BACKGROUND: Tuberculosis (TB) recurrences can be due to either reactivation by the same strain (standard assumption) or reinfection by a new strain. Reinfection has mainly been studied in selected populations with a high risk of reexposure to TB. Our aim was to analyze the role of reinfection in TB recurrences in unselected populations, without the clinical/epidemiological circumstances that favor the involvement of a new different strain of Mycobacterium tuberculosis in the recurrence. METHODS: A molecular typing analysis was performed with 92 sequential isolates of M tuberculosis from 43 patients with recurrent TB, during a 12-year period. The subjects were both positive and negative for the human immunodeficiency virus, most did not adhere to anti-TB therapy, and they lived in an area with a moderate incidence of TB. Recurrence was considered as being caused by reinfection when the molecular fingerprints for the strains involved in the sequential episodes of TB were different. RESULTS: In 14 (33%) of the 43 patients, different M tuberculosis strains were involved in the first and in subsequent episodes of TB. Reinfection was found for patients who were both positive and negative for the human immunodeficiency virus, and most patients did not adhere to anti-TB therapy. Differences between the reinfection and reactivation groups were not significant (P =.77) according to the time interval between episodes. CONCLUSIONS: Reinfection plays an important role in recurrent TB in a population without the clinical/epidemiological circumstances that are usually assumed to favor it. Reinfection should, thus, be considered as a cause of TB recurrences in a wider context than before.     

Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-β-d-glucan levels in serum, tissue burden reduction, and histopathology.     

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches

The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.