Epidemiology, risk factors, and outcomes of Clostridium difficile infection in kidney transplant recipients.

BACKGROUND: We sought to describe the epidemiology and risk factors for Clostridium difficile infection (CDI) among kidney transplant recipients (KTR) between 1 January 2008 and 31 December 2010. METHODS: A single-institution retrospective study was conducted among all adult KTR with CDI, defined as a positive test for C. difficile by a cell cytotoxic assay for C. difficile toxin A or B or polymerase chain reaction test for toxigenic C. difficile. RESULTS: Among 603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37 (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs. 25 (of 475; 5.3%, P = 0.08) standard-risk patients. The overall rate of CDI increased from 3.7% in 2008 to 9.4% in 2010 (P = 0.05). The median time to CDI diagnosis was 9 days, with 27 (73.0%) patients developing CDI within the first 30 days after their transplant, and 14 (51.8%) developing CDI within 7 days. A case-control analysis of 37 CDI cases and 74 matched controls demonstrated the following predictors for CDI among KTR: vancomycin-resistant Enterococcus colonization before transplant (odds ratio [OR]: 3.6, P = 0.03), receipt of an organ from Centers for Disease Control high-risk donor (OR: 5.9, P = 0.006), and administration of high-risk antibiotics within 30 days post transplant (OR: 6.6, P = 0.001). CONCLUSIONS: CDI remains a common early complication in KTR, with rates steadily increasing during the study period. Host and transplant-related factors and exposure to antibiotics appeared to significantly impact the risk for CDI among KTR.

Subclinical rejection in stable positive crossmatch kidney transplant patients: incidence and correlations.

We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the long-held belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function.

Sequence and expression patterns of a human EMAP-related protein-2 (HuEMAP-2).

Until recently, the microtubule-associated protein, EMAP, was identified only in echinoderms such as sea urchin, starfish and sand dollar. Sea urchin EMAP localizes to the mitotic apparatus in vivo and modifies the assembly dynamics of microtubules in vitro. To identify domains important for EMAP function, we cloned and sequenced cDNAs for an EMAP-related protein in human. The nucleotide sequence of a human EMAP-related protein-2 (HuEMAP-2) encodes a protein of 649 amino acids in length. The translated polypeptide sequence and domain structure of sea urchin EMAP and HuEMAP-2 are highly conserved, with greater than 57% identity and 77% similarity at the translated amino acid level. Southern blot analysis is consistent with the presence of a single HuEMAP-2 gene in the human genome. Moreover, HuEMAP-2 is a member of a larger protein family with at least four HuEMAP sequences in the NCBI databases. One of these, HuEMAP-1, is identified as the candidate gene for the Usher syndrome 1 a locus (Genomics 43:104-106, 1997). Northern blot analysis indicates that HuEMAP-1, and HuEMAP-2 are expressed in different human tissues. In addition, these RNA blots indicate that HuEMAP-2 transcripts may be differentially spliced in neuronal tissues.

Biochemical and functional characterization of soluble multivalent MHC L(d)/Fc gamma 1 and L(d)/Fc mu chimeric proteins loaded with specific peptides.

Central to the specificity of the immune system is the interaction between the T cell receptor and the major histocompatibility complex (MHC)-peptide ligand complex. To better understand the nature of this interaction, and to investigate possible avenues for specific therapeutic intervention, we have produced soluble recombinant molecules that can modulate antigen-specific T cells. Our approach involved the construction of recombinant murine genes composed of the MHC class I gene H-2L(d) and the Fc portion of immunoglobulin (Ig) heavy chain genes mu or gamma1. Stable transfectants of these L(d)/Fc gamma1 and L(d)/Fc mu genes generated correctly spliced transcripts and were capable of secreting chimeric protein. Immunoprecipitation analyses demonstrated the presence of chimeric L(d)/ Fc gamma1 and L(d)/Fc mu monomers of approximately 69 kDa and 90 kDa, respectively, as well as chimeric dimers under nonreducing conditions. The capacity of L(d)/Ig molecules to bind specific peptide ligands was demonstrated using radiolabeled peptides or with monoclonal reagents that specifically identify peptide-induced conformational changes in the L(d) ligand binding site. Soluble divalent L(d)/Fc gamma1 molecules were loaded with the murine cytomegalovirus-derived peptide and other L(d)-specific peptide ligands and subsequently isolated and purified. Peptide-loaded L(d)/Fc gamma1 molecules were capable of inhibiting the response of class I-restricted T cells in vitro in a peptide-specific fashion. The development of soluble multivalent chimeric proteins that possess unique properties of both the MHC class I and Ig molecules provides a valuable reagent for the study of potential mechanisms of in vitro and in vivo immune modulation.

Management of long-standing cardiocutaneous fistulas after resection of left ventricular aneurysms.

Cardiocutaneous fistulas arising from pledgets used in the closure of resected left ventricular aneurysms are rare but have serious implications. The case histories of four patients, each managed in a somewhat different manner, are presented. From this experience we recommend an aggressive approach to remove the infected pledgets once scar formation is complete and before erosion of the pledgets into the left ventricular cavity can occur.

Surgery for congenital heart disease in the adult.

A total of 205 adults with a variety of congenital heart lesions underwent operation for total correction of their defects. Operative and long-term mortality were 3 and 4 percent, respectively. There has been only one operative death in the past five years (85 patients). While most defects were repaired with good hemodynamic and symptomatic improvement, the three lesions associated with the worst results were cyanotic tetralogy of Fallot, severe pulmonic stenosis complicated by atrial septal defect, and ostium primum atrial septal defect. Myocardial failure due to end-stage myocardial fibrosis was the major cause of operative mortality. Myocardial fibrosis and irreversible pulmonary changes seemed to be the two factors limiting operative correctio

Open-heart surgery in von Willebrand's disease.

The case is presented of a hemophilia carrier, also affected by von Willebrand's disease, who underwent aortic valve replacement. The clinical and laboratory findings of von Willebrand's disease (prolonged bleeding time, low factor VIII, and abnormal platelet activity) are discussed, and a protocol for management of patients with low factor VIII levels (such as hemophilia carriers and subjects with hemophilia A or von Willebrand's disease) undergoing open-heart surgery is proposed. Our case proves that corrective cardiac surgery in similar circumstances is feasible so long as adequate levels of factor VIII are maintained.

Left ventricular myotomy. Physiologic approach to surgical therapy for IHSS.

Twenty patients were operated on for idiopathic hypertrophic subaortic stenosis (IHSS) between 1966 and 1980. All were in New York Heart Association functional class 3 or 4, and 17 had overt congestive failure. The mean resting gradient across the left ventricular (LV) outflow tract preoperatively was 78 mm Hg. Seventeen patients underwent transaortic LV myotomy, one had mitral valve replacement (MVR), and two patients with rheumatic mitral insufficiency (MI) and IHSS underwent myotomy and MVR. There was one operative death (5 percent). Mean follow-up was 5.8 years. Eighteen of 19 survivors were improved to class 1 or 2. One patient whose gradient and symptoms were not relieved by myotomy was improved by myectomy and MVR. The MI was abolished or reduced by myotomy in ten of 13 patients. There were six late deaths, five of which are known or assumed to be cardiac related. We concluded that LV myotomy is a safe and effective technique for surgical management of IHSS. Left ventricular myectomy, MVR, or both are indicated in selected cases.

Effect of intra-aortic balloon pumping on nutrient coronary flow in normal and ischemic myocardium.

The effects of intra-aortic balloon pumping (IABP) on myocardial flow distribution were studied in 50 dogs. Cardiac output was controlled by right heart bypass. In each dog the following parameters were measured with and without IABP during normal coronary perfusion and after regional ischemia was induced by anterior descending coronary vein flow by timed collection, and endocardial/epicardial flow ratios by a previously reported thermal washout technique. In nonischemic myocardium, IABP significantly (p less than 0.05) increased mean coronary sinus flow 11.5 percent +/- 5.8 percent (S.D.) and the mean endocardial/epicardial ratio, 17.3 percent +/- 0.28 percent. In the regionally ischemic myocardium, IABP significantly (p less than 0.05) increased mean segmental coronary vein flow 13.9 percent +/- 1.23 percent but decreased the endocardial/epicardial ratio 29.9 percent +/- 1.1 percent. We conclude that in the dog, IABP enhances subendocardial blood flow in perfused but not in ischemic myocardium. Contrary to common suppositions, the increase in collateral blood flow with IABP preferentially supplies epicardial layers in segmental ischemic zones, but may be shunted from the subendocardium.

Reduction of blood usage in open heart surgery.

A series of 142 adult patients undergoing open-heart surgery were studied. All known blood-conservativing methods were utilized in an attempt to use as little blood as possible. Hemodilution, autologous transfusion, prevention of wasting of blood, and management of postoperative anemia were the measures employed. An average of 2.66 units of blood were given per patient during the entire hospital stay. Twenty patients were not given any blood at all. The patients were removed from cardiopulmonary bypass without difficulty when the hematocrit reading was in the high teens or low twenties. Later in the postoperative period the patients seemed to progress without difficulty with hematocrit readings of 22 to 25 percent.

Perceived stress and coping strategies among candidates for heart transplantation during the organ waiting period.

The effectiveness of the transplantation team in diffusing stress during the pretransplantation period is increasingly important the longer the patient remains on the transplant waiting list. This study describes the stressors and coping strategies of heart transplant candidates during the waiting period. Thirty-nine candidates on the active list for heart transplantation from four mid-East Coast transplantation centers participated. With a possible stress score of 0 to 243, the mean score for this sample was a low 72.84 (standard deviation = 37.47). The three most common stressors were (1) requiring a heart transplant, (2) having terminal heart disease, and (3) worrying family members. The three most common coping strategies were (1) thinking positively, (2) using humor, and (3) trying to keep life as normal as possible. The finding of low stress levels was surprising but may reflect the presence of hope or the patient's desire to spare family members worry--a concern commonly cited by patients. Another explanation is that patients desiring to be perceived as ideal transplant recipients may have underreported their stress. This suggests that the transplantation team should support positive coping strategies when possible and that both patient and family coping should be closely monitored throughout the waiting period.

Topical myocardial cooling. An intensive laboratory investigation.

To better understand efficacy of topical cooling in myocardial protection, three groups of 12 dogs each were studied. Group 1 dogs had systemic cooling to 30 C; group 2 had cooling to 30 C and outside cooling of left ventricle; group 3 was cooled in the same way as group 2 was but also had inside of left ventricle topically cooled. Measurements were taken of left ventricular function curves, regional blood flow distribution to the subendocardium, sequential pH, PCO2, PO2, and lactate and serum glutamic oxaloacetic transaminase (SGOT) levels. Lower midseptal and subendocardial temperature (means, 11 and 7 C, respectively) in group 3 correlated with higher survival and greater preservation of left ventricular function. Lower levels of SGOT and lactate in coronary sinus efflux, and higher regional flow to subendocardium postoperatively, also correlated with minimal evidence of subendocardial necrosis in group 3 dogs. Rapid of cooling of subendocardium was noted as achieving maximum preservation of left ventricular function.

Coronary artery surgery without global ischemia.

A simple technique for local occlusion of the coronary artery without aortic cross-clamping during the distal anastomosis has been developed. The use of this internal coronary artery occluder, which we developed, represents another step forward in myocardial protection during coronary bypass procedures.

A comparative synchronous coronary surgery survival study.

Utilizing patient criteria published by the Veterans Administration Cooperative (VAC) Study, a cohort of 229 surgically treated patients was retrieved from the Milwaukee Cardiovascular Data Registry. These patients were all operated on by one surgeon during 1972 to 1974. Four-year survival of this group was compared with that of the medically treated cohort of 310 patients from the VAC Study. Operative mortality was included in all surgical groups. The cumulative 4-year survival of both groups revealed a 95 to 85% advantage for surgical therapy. In patients with three-vessel disease, the cumulative survival favored surgical therapy--94% compared with 80% in the medically terated cohort--and in patients with triple-vessel disease and a normal left ventricle, surgical therapy again showed better results: 100% compared with 88%. Patients with two-vessel disease and a normal left ventricle who underwent surgical intervention had slightly better 4-year survival than those who had medical treatment--100% versus 95%--and those with two-vessel disease and an abnormal left ventricle had a 93% survival after surgical treatment compared with 84% for those with medical treatment. For patients with single-vessel disease, there was no difference in survival between the surgical and medical cohorts.

Late evaluation of patients undergoing valve replacement with the Björk-Shiley prosthesis.

This study analyzes 484 patients who survived mitral, aortic, or mitral and aortic valve replacement using the Björk-Shiley prosthesis from January, 1970, through December 31, 1974. Long-term follow-up of 1 1/2 to 6 1/2 years (mean, 3.67 yr) was done on 435 patients (98.2%). Eighty to 85% of the patients have improved noticeably. Thromboembolic problems occurred in 6.9%, representing 1.5 emboli per 1,000 patient-months. Anticoagulant bleeding problems occurred in 6.4% of the patients; late mortality was 15%. Actuarial survival curves showed patients at risk to 6 years having a 79% chance of survival. The same analysis according to preoperative New York Heart Association Functional Classification showed a striking reduction in survival in class IV patients. The Björk-Shiley prosthesis is a good choice for valve replacement today. Earlier diagnosis and treatment are needed to obtain better long-term survival.

Comparative hemodynamic properties of vein and mammary artery in coronary bypass operations.

To understand better the observed differences in bypass flows between vein and internal mammary artery (IMA) grafts, a technique was devised for anastomosing both vein and IMA to the same anterior descending coronary artery in 14 patients. In the stable postperfusion state, flows in the two bypass conduits were simultaneously recorded as well as pressure relationships in both grafts and the left ventricle. The supply/demand ratio for left ventricular performance was calculated with respect to the diastolic pressure-time index/tension-time index (DPTI/TTI) for each bypass independently and simultaneously and then compared. The DPTI/TTI ratio was nearly two times greater with the vein bypass than with the IMA. This difference was further confirmed by the flow studies, in which blood flow through the vein ranged 2 to 3 times higher than IMA flow to the same coronary bed. By present criteria the DPTI/TTI ratio for IMA grafts to the left ventricle was inadequate in the majority of patients studied, and atrial pacing markedly lowered the DPTI/TTI ratio of the IMA. The choice of vein or IMA as a bypass is a critical determinant of the resultant bypass-left ventricular DPTI/TTI ratio. Vein bypasses exhibited far superior hemodynamic capability in the resting state, and the effect of atrial pacing on the DPTI/TTI ratio in IMA-vein-left ventricle bypasses confirms this point.

Ten-year follow-up in aortic valve replacement using the Björk-Shiley prosthesis.

An in-depth statistical analysis of early and late results of aortic valve replacement using the Björk-Shiley tilting-disc prosthesis is presented. Our experience with this prosthesis indicates that replacement carries a low surgical risk, a low incidence of complications (embolization, infection, or hemorrhage due to long-term use of anticoagulants), and good long-term survival. Coexisting coronary artery disease increases surgical mortality significantly, and simultaneous, complete revascularization is essential. Patients undergoing isolated aortic valve replacement did significantly better than those requiring other simultaneous procedures or those who had had previous operations. Earlier operation is imperative since progress of aortic valve disease is unpredictable by duration of symptoms, and patients in New York Heart Association Functional Class II have a low surgical risk and a greatly increased survival. It would appear from this study that additional criteria, such as increasing ventricular dilatation and hypertrophy determined by echocardiographic studies and gated nuclear studies showing deterioration of ejection fraction on exercise, should be used to help determine time of surgical intervention rather than symptomatology alone.

Prognostic considerations in the management of left ventricular aneurysms.

This report summarizes a four-year experience with 60 patients who had left ventricular aneurysm (LVA) resection and bypass of all significantly diseased coronary arteries, with an operative and late mortality of 3.3 and 8.3%, respectively. Their cardiac catheterizations were reviewed, and the only values that seemed to reflect prognosis were preoperative cardiac index and the presence of absence of septal motion. The lower the cardiac index, the less likely the patient was to do well postoperatively. There were now survivors who had lacked septal motion by left anterior oblique ventriculogram. Patients without septal motion are therefore no longer considered surgical candidates. If septal motion is present, resection of LVA carries no more risk than myocardial revascularization without LVA.

Atherosclerosis of the internal mammary artery.

To better evaluate the incidence of atherosclerosis in the internal mammary artery (IMA), 215 IMA segments from routine postmortem examinations were evaluated microscopically. Significant atherosclerotic narrowing was seen in 9 patients (4.2%). No patient had more than a 50% reduction in lumen diameter. The degree of incipient atherosclerosis correlated well with age, hypertension, diabetes, and peripheral vascular disease.

Factors predictive of perioperative myocardial infarction during coronary operations.

The diagnosis of perioperative myocardial infarction (PMI) in our patients was based upon electrocardiography, vectorcardiography, and postoperative enzyme changes. A group of 303 patients operated on between January and September, 1972, formed the basis of this study. Three groups were identified from among these patients. Group A was composed of 90 consecutive patients in whom MI was excluded by all criteria. Group B comprised 25 patients with proved MI and yielded the 8% incidence of MI among our patients. Group C included 34 patients with triple-vessel disease who did not sustain MI. Significantly more patients sustaining MI had preinfarction angina and severe coronary artery disease. The incidence of MI was also higher in patients with diffuse disease and those in whom the lesions could not be totally bypassed. A statistical correlation with longer pump runs and periods of anoxia was obtained. There was some suggestion that the preoperative location of the hypokinetic segment determined the site of MI in patients.