What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography?

OBJECTIVES: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. METHODS: Follow-up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (> or =12). RESULTS: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients.     

Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to examine the effect of peri-operative red blood cell (RBC) transfusion on 30-day and 1-year mortality following coronary artery bypass grafting (CABG). METHODS: We retrospectively analysed 3024 consecutive patients who underwent isolated CABG between January 1999 and December 2001. Patient records were linked to the National Strategic Tracing Service, which records all mortality in the UK. Thirty-day and 1-year mortality were derived from Kaplan-Meier curves. Confounding variables were controlled for by constructing a propensity score for the probability of receiving a transfusion from core patient characteristics including the lowest recorded laboratory haemoglobin (LL Hb) from a clinical chemistry database (C statistic 0.81). The propensity score and the comparison variable (transfusion versus no transfusion) were included in a Cox proportional hazards analysis, allowing calculation of adjusted hazard ratios (HR) and Kaplan-Meier survival curves. RESULTS: Nine hundred and forty (31.1%) patients received RBC transfusion during or within 72h of surgery. Predictors of the need for transfusion were LL Hb and lower body mass index, use of cardiopulmonary bypass, female sex, number of grafts, renal dysfunction, increased age, extent of disease, and prior CABG; these factors were all included in the propensity score. After 1-year of follow-up, 122 (4.03%) deaths occurred. The crude HR for 1-year mortality in patients transfused was 3.0 (P<0.001). After adjusting for the propensity score, re-operation for bleeding, peri-operative blood loss and post-operative complications, the adjusted 30-day mortality was 1.9% in transfused patients compared to 1.1% in patients not transfused (P<0.05). The adjusted HR for 1-year mortality in patients transfused was 1.88 (P<0.01). CONCLUSIONS: Peri-operative RBC transfusion after CABG is associated with an increased risk of mortality during a 1-year follow-up period, with a large proportion of deaths occurring within 30-days.     

Anatomical study of the obturator internus, gemelli and quadratus femoris muscles with special reference to their innervation

The manner of innervation of the obturator internus, superior and inferior gemelli, and the quadratus femoris in humans (101 pelvic halves) and in rhesus monkeys (Macaca mulatta: 8 pelvic halves) were investigated. In most specimens, the inferior gemellus originated from the lateral surface of the ischial tuberosity and also from the medial surface (intrapelvic origin) just beneath the obturator internus and was covered by the falciform process of the sacrotuberous ligament. The superior gemellus was frequently innervated by the nerve to the obturator internus and the nerve to the quadratus femoris (60.4%), and the inferior gemellus was innervated by the obturator internus nerve in two specimens. The quadratus femoris nerve originated from more cranial segments than the obturator internus nerve, however these nerves had various communication patterns inside and outside the muscles. According to the intramuscular nerve distribution, in some specimens the branches to the superior gemellus from the quadratus femoris nerve extended to the inferior gemellus, and the branches to the inferior gemellus were distributed to the obturator internus. The present findings revealed that the positional relationships among the branches to the obturator internus and gemelli muscles are relatively constant, although the branching patterns and innervation patterns were varied. The various patterns and routes are considered to reflect the variability of the differentiation patterns of the anlage of the muscles. A possible schematic model of the positional relationships between the muscles and the nerves is proposed.     

Gastrointestinal haemorrhage from a jejunal gangliocytic paraganglioma.

A case of jejunal gangliocytic paraganglioma is reported in a 54 year old woman who presented with brisk melaena. The tumour was not encapsulated, involved the mucosa and submucosa, and was composed of epithelial nests, spindle cells, and ganglion cells. These cells were mixed, giving carcinoid-like, paraganglioma-like, and ganglioneuroma-like patterns in different areas of the tumour. The lesion was excised locally and recovery was uneventful. Only four previous cases have been reported at this site.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.     

Correlation of tensile strength with bursting pressure in the evaluation of intestinal anastomosis

BACKGROUND: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. MATERIAL AND METHODS: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. RESULTS: During the lag phase (days < or = 4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day > or = 5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. CONCLUSION: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.     

Mast cell desensitization to IgE fails to induce a parallel adenosine receptor desensitization

Desensitization induced by challenge of mast cells with antigen is specific for IgE-dependent signals. During the secretory process mast cells release adenosine, which can induce a desensitization of adenosine receptors. To determine whether adenosine receptors may de desensitized from a previous antigen challenge, mast cells were sensitized with anti-DNP IgE antibody, challenged with DNP-BSA antigen, returned to culture overnight, resensitized, and rechallenged. Previously challenged cells exhibited increased spontaneous -hexosaminidase release, but adenosine retained its ability to augment -hexosaminidase release. Adenosine enhanced A23187-stimulated release of -hexosaminidase in control and previously challenged cells. Leukotriene C₄ generation followed a similar pattern. Mastoparan, a direct G protein activator and mast cells secretogogue, produced a doubling of -hexosaminidase release in previously challenged cells. Results using other G protein activators were equivocal. Degranulation alone is insufficient to induce adenosine receptor hyposensitization. Whether the hyperresponsiveness to mastoparan is a consequence of uncoupling of IgE receptors from G proteins remains uncertain.     

Metachronous skeletal osteosarcoma in patients treated with adjuvant and neoadjuvant chemotherapy for nonmetastatic osteosarcoma.

PURPOSE: The prognosis for patients who develop metachronous skeletal osteosarcoma (OS) has been considered grave compared with that for patients with relapse limited to the lungs. We investigated the incidence and outcome of metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer Center (New York, NY) between February 1973 and May 2000 developed metachronous skeletal OS. Initial therapy included combination chemotherapy and surgery. Treatment of subsequent relapses consisted of chemotherapy or radiation alone or surgery with or without additional individualized chemotherapy. RESULTS: The median time from the diagnosis of primary OS to the development of metachronous OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95% confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%), respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4 years). For 11 patients who developed metachronous OS 24 months or more from initial diagnosis, 5-year postmetachronous survival rate for patients receiving combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95% CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who developed late metachronous OS, combined-modality therapy with surgery and aggressive chemotherapy may result in long-term postmetachronous survival. This implies that principles used in treatment of primary OS may be applied to patients with late metachronous skeletal OS.