Unplanned Cesarean delivery is associated with risk for postpartum depressive symptoms in the immediate postpartum period.

PURPOSE: Postpartum depression (PPD) is a common pregnancy complication. The association between cesarean delivery (CD) and PPD has shown conflicting results in prior studies, although emergent CD appears to be a clear risk factor. Establishing PPD risk is critical and may, however, be related to the unplanned nature of the CD, rather than the surgery itself. Our objective was to determine whether women who underwent unplanned CD were more likely than those with vaginal delivery to have higher depressive symptoms and thus screen positive for PPD risk in the immediate postpartum period. MATERIALS AND METHODS: This cohort study was conducted at a community medical center using data for deliveries between 8/2015-1/2016. Women were screened in the hospital for depressive symptoms (PPD risk) using the Edinburgh Postnatal Depression Scale (EPDS) within 4 days post-delivery. Logistic regression, adjusting for maternal race/ethnicity and parity, was performed to evaluate the association between delivery route (vaginal vs planned vs unplanned CD) and PPD risk (EPDS ≥ 10). RESULTS: A total of 2094 women had complete data for analysis. Overall, 44 women (2.1%) screened positive for PPD risk. Logistic regression results showed that unplanned CD was significantly associated with PPD risk (OR = 2.28, 95% CI 1.13-4.57, p = .022), after adjusting for parity and race/ethnicity. Planned CD was not associated with PPD risk. CONCLUSION: Unplanned CD may be an independent risk factor for PPD risk in the immediate postpartum period. This finding might explain why some previous studies have demonstrated different results with regards to risk of CD where the unplanned nature of the delivery was not accounted for.

High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents.

BACKGROUND AND PURPOSE: In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents. MATERIALS AND METHODS: This was a retrospective analysis of on-site patients with brain tumors. Fifty-nine patients received only gadobutrol, and 60 patients received only linear gadolinium-based contrast agents. Linear gadolinium-based contrast agents included gadoversetamide, gadobenate dimeglumine, and gadodiamide. T1 signal intensity in the globus pallidus, dentate nucleus, and pons was measured on the precontrast portions of patients' first and seventh brain MRIs. Ratios of signal intensity comparing the globus pallidus with the pons (globus pallidus/pons) and dentate nucleus with the pons (dentate nucleus/pons) were calculated. Changes in the above signal intensity ratios were compared within the gadobutrol and linear agent groups, as well as between groups. RESULTS: The dentate nucleus/pons signal ratio increased in the linear gadolinium-based contrast agent group (t = 4.215, P < .001), while no significant increase was seen in the gadobutrol group (t = -1.422, P = .08). The globus pallidus/pons ratios followed similarly, with an increase in the linear gadolinium-based contrast agent group (t = 2.931, P < .0001) and no significant change in those receiving gadobutrol (t = 0.684, P = .25). CONCLUSIONS: Successive doses of gadobutrol do not result in T1 shortening compared with changes seen in linear gadolinium-based contrast agents.

Defining fetal growth restriction: abdominal circumference as an alternative criterion.

PURPOSE: The purpose of this study is to determine if using abdominal circumference percentile (AC) to define fetal growth restriction (FGR) improves ultrasound at ≥36 weeks as a screening test for small for gestational age (SGA). MATERIALS AND METHODS: All non-anomalous singletons undergoing ultrasound at a single center at ≥36 weeks during 12/2008-5/2014 were included. FGR was defined as (estimated fetal weight) estimated fetal weight (EFW) and/or abdominal circumference (AC) < 10 for gestational age (GA). The primary outcome was SGA (birthweight ≤10th percentile for GA). Data were stratified by maternal race/ethnicity and BMI. Sensitivity, specificity, false-positive rate (FPR), positive- and negative-predictive values (positive-predictive value (PPV), negative-predictive value (NPV)), and areas under the receiver-operating characteristic (ROC) curve (AUC were calculated. RESULTS: There were 1594 ultrasounds. Median (IQR) ultrasound GA was 37.3 (36.6-38.0), days to delivery 10.6 (5.0-18.4), and delivery GA 39.29 (38.6-39.9). EFW <10 had the following characteristics: sensitivity 50.6%, FPR 2.0%, PPV 83.8%, and AUC 0.743. Using AC <10, these were 64.0, 2.9, 81.3, and 0.806, respectively. Using AC or EFW <10, these were 67.5, 3.3, 80.3, and 0.821, respectively; this criterion has the largest AUC (p < .008). This finding persisted when stratified by maternal race/ethnicity and BMI. CONCLUSIONS: AC <10 is more sensitive and has a similar PPV compared with EFW <10 for SGA. Using AC <10 or EFW <10 has the best balance of sensitivity and specificity as a screening test and has a low FPR. AC may be a reasonable alternative criterion to EFW for FGR diagnosis.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Similar Mortality and Morbidity of Orthotopic Heart Transplantation for Patients 70 Years of Age and Older Compared With Younger Patients.

BACKGROUND: The upper age limit of heart transplantation remains controversial. The goal of the present study was to investigate the mortality and morbidity of orthotopic heart transplantation (HT) for recipients ≥70 compared with those <70 years of age. METHODS: Of 704 adults who underwent HT from December 1988 to June 2012 at our institution, 45 were ≥70 years old (older group) and 659 were <70 years old (younger group). Survival, intraoperative blood product usage, intensive care unit (ICU) and hospital stays, and frequency of reoperation for chest bleeding, dialysis, and >48 hours ventilation were examined after HT. RESULTS: The older group had 100% 30-day and 60-day survival compared with 96.8 ± 0.7% 30-day and 95.9 ± 0.8% 60-day survival rates in the younger group. The older and younger groups had similar 1-year (93.0 ± 3.9% vs 92.1 ± 1.1%; P = .79), 5-year (84.2 ± 6.0% vs 73.4 ± 1.9%; P = .18), and 10-year (51.2 ± 10.7% vs 50.2 ± 2.5%; P = .43) survival rates. Recipients in the older group had higher preoperative creatinine levels, frequency of coronary artery disease, and more United Network for Organ Sharing status 2 and fewer status 1 designations than recipients in the younger group (P < .05 for all). Pump time and intraoperative blood usage were similar between the 2 groups (P = NS); however, donor-heart ischemia time was higher in the older group (P = .002). Older recipients had higher postoperative creatinine levels at peak (P = .003) and at discharge (P = .007). Frequency of postoperative complications, including reoperation for chest bleeding, dialysis, >48 hours ventilation, pneumonia, pneumothorax, sepsis, in-hospital and post-discharge infections, were similar between groups (P = NS for all comparisons). ICU and hospital length of stays were similar between groups (P = .35 and P = .87, respectively). In Cox analysis, recipient age ≥70 years was not identified as a predictor of lower long-term survival after HT. CONCLUSIONS: HT recipients ≥70 years old had similar 1, 5, and 10-year survival rates compared with younger recipients. Both patient groups had similar intra- and postoperative blood utilization and frequencies of many postoperative complications. Older and younger patients had similar morbidity and mortality rates following HT. Carefully selected older patients (≥70 years) can safely undergo HT and should not be excluded from HT consideration based solely on age.

Adult Heart Transplantation Following Ventricular Assist Device Implantation: Early and Late Outcomes.

PURPOSE: The impact of prior implantation of a ventricular assist device (VAD) on short- and long-term postoperative outcomes of adult heart transplantation (HTx) was investigated. METHODS: Of the 359 adults with prior cardiac surgery who underwent HTx from December 1988 to June 2012 at our institution, 90 had prior VAD and 269 had other (non-VAD) prior cardiac surgery. RESULTS: The VAD group had a lower 60-day survival when compared with the Non-VAD group (91.1% ± 3.0% vs 96.6% ± 1.1%; P = .03). However, the VAD and Non-VAD groups had similar survivals at 1 year (87.4% ± 3.6% vs 90.5% ± 1.8%; P = .33), 2 years (83.2% ± 4.2% vs 88.1% ± 2.0%; P = .21), 5 years (75.7% ± 5.6% vs 74.6% ± 2.9%; P = .63), 10 years (38.5% ± 10.8% vs 47.6% ± 3.9%; P = .33), and 12 years (28.9% ± 11.6% vs 39.0% ± 4.0%; P = .36). The VAD group had longer pump time and more intraoperative blood use when compared with the Non-VAD group (P < .0001 for both). Postoperatively, VAD patients had higher frequencies of >48-hour ventilation and in-hospital infections (P = .0007 and .002, respectively). In addition, more VAD patients had sternal wound infections when compared with Non-VAD patients (8/90 [8.9%] vs 5/269 [1.9%]; P = .005). Both groups had similar lengths of intensive care unit (ICU) and hospital stays and no differences in the frequencies of reoperation for chest bleeding, dialysis, and postdischarge infections (P = .19, .70, .34, .67, and .21, respectively). Postoperative creatinine levels at peak and at discharge did not differ between the 2 groups (P = .51 and P = .098, respectively). In a Cox model, only preoperative creatinine ≥1.5 mg/dL (P = .006) and intraoperative pump time ≥210 minutes (P = .022) were individually considered as significant predictors of mortality within 12 years post-HTx. Adjusting for both, pre-HTx VAD implantation was not a predictor of mortality within 12 years post-HTx (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.77-1.97; P = .38). However, pre-HTx VAD implantation was a risk factor for 60-day mortality (HR, 2.86; 95% CI, 1.07-7.62; P = .036) along with preoperative creatinine level ≥2 mg/dL (P = .0006). CONCLUSIONS: HTx patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery. VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival following HTx. Long-term (1-, 2-, 5-, 10-, and 12-year) survival did not differ significantly in HTx patients with prior VAD or non-VAD cardiac surgery.

Insulin-dependent diabetes and serious trauma.

PURPOSE: Trauma patients with diabetes mellitus (DM) represent a unique population as the acute injury and the underlying disease may both cause hyperglycemia that leads to poor outcomes. We investigated how insulin-dependent DM (IDDM) and noninsulin-dependent DM (NIDDM) impact mortality after serious trauma without brain injury. METHODS: The National Trauma Data Bank (NTDB) version 7.0 was queried for all patients with moderate to severe traumatic injury [injury severity score (ISS) >9]. Patients were excluded if missing data, age <10 years, severe brain injury [head abbreviated injury scale (AIS) >3], dead on arrival or any AIS = 6. Logistic regression modeled the association between DM and mortality as well as IDDM, NIDDM and mortality. RESULTS: Overall 166,103 trauma patients without brain injury were analyzed. Mortality was 7.6 and 4.4 % in patients with and without DM, respectively (p < 0.01). Mortality was 9.9 % for patients with IDDM and 6.7 % for NIDDM (p < 0.01). The increased mortality associated with DM was only significantly higher for DM patients in their forties (5.6 vs. 3.3 %, p < 0.01). Regression analyses demonstrated that DM (AOR 1.14, p = 0.04) and IDDM (AOR 1.46, p < 0.01) were predictors of mortality compared to no DM, but NIDDM was not (AOR 1.02, p = 0.83). CONCLUSIONS: While DM was a predictor for higher mortality after serious trauma, this increase was only observed in IDDM and not NIDDM. Our findings suggest IDDM patients who present after serious trauma are unique and attention to their hyperglycemia and related insulin therapy may play a critical role in recovery.

JC polyomavirus viremia and progressive multifocal leukoencephalopathy in human leukocyte antigen-sensitized kidney transplant recipients desensitized with intravenous immunoglobulin and rituximab.

BACKGROUND: Desensitization (DES) with intravenous immunoglobulin (IVIG) + rituximab is effective, safe, and increases the transplantation rate in human leukocyte antigen-sensitized patients. However, reports of progressive multifocal leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV) in autoimmune patients treated with rituximab is concerning. Here, we report on the JCPyV viremia and PML status in kidney transplant patients with/without DES (non-DES). METHODS: In total 1195 and 699 DNA samples from plasma in 117 DES (78% lymphocyte-depleting [LyD] induction) and 100 non-DES patients (45% LyD), respectively, were submitted for JCPyV-polymerase chain reaction. Results were compared in both groups. RESULTS: No patients in either DES or non-DES developed PML or presented with any neurological symptoms. The JCPyV viremia rate was similar in DES and non-DES patients (3/117 vs. 9/100, P = 0.07). The JCPyV levels were low (median peak levels, 1025 copies/mL) and JCPyV viremia was observed only once during the study period in most patients. All 3 DES patients with JCPyV(+) received 1 dose rituximab and no DES patients with >1 dose rituximab showed JCPyV(+). All 3 JCPyV(+) DES patients received LyD induction, while only 2 of 9 JCPyV(+) non-DES patients did so, and the remaining 7 received non-LyD or no induction. JCPyV in leukocyte was mostly negative in DES and non-DES patients. Immunosuppression in patients with or without JCPyV(+) was similar. BK polyomavirus viremia was observed more commonly in patients with JCPyV(+) than in those without (P < 0.02). CONCLUSIONS: Patients with IVIG + rituximab DES followed by transplantation with LyD induction and additional rituximab rarely show JCPyV viremia and appear at low risk for PML.

Prior sternotomy increases the mortality and morbidity of adult heart transplantation.

BACKGROUND: This study investigated the effect of prior sternotomy (PS) on the postoperative mortality and morbidity after orthotopic heart transplantation (HTx). METHODS: Of 704 adults who underwent HTx from December 1988 to June 2012 at a single institution, 345 had no PS (NPS group) and 359 had ≥ 1 PS (PS group). Survival, intraoperative use of blood products, intensive care unit (ICU) and hospital stays, frequency of reoperation for bleeding, dialysis, and >48-hour ventilation were examined. RESULTS: The NPS and PS groups had similar 60-day survival rates (97.1 ± 0.9% vs 95.3 ± 1.1%; P = .20). However, the 1-year survival was higher in the NPS group (94.7 ± 1.2% vs 89.7 ± 1.6%; hazard ratio [HR], 1.98; 95% CI, 1.12-3.49; P = .016). The PS group had longer pump time and more intraoperative blood use (P < .0001 for both). Postoperatively, the PS group had longer ICU and hospital stays, and higher frequencies of reoperation for bleeding and >48-hour ventilation (P < .05 for all comparisons). Patients with 1 PS (1PS group) had a higher 60-day survival rate than those with ≥ 2 PS (2+PS group; 96.7 ± 1.1% vs 91.1 ± 3.0%; HR, 2.70; 95% CI, 1.04-7.01; P = .033). The 2+PS group had longer pump time and higher frequency of postoperative dialysis (P < .05 for both). Patients with prior VAD had lower 60-day (91.1 ± 3.0% vs 97.1 ± 0.9%; P = .010) and 1-year (87.4 ± 3.6% vs 94.7 ± 1.2%; P = .012) survival rates than NPS group patients. Patients with prior CABG had a lower 1-year survival than NPS group patients (89.0 ± 2.3% vs 94.7 ± 1.2%; P = .018). CONCLUSION: The PS group had lower 1-year survival and higher intraoperative blood use, postoperative length of ICU and hospital stays, and frequency of reoperation for bleeding than the NPS group. Prior sternotomy increases morbidity and mortality after HTx.

Quality of life in major depressive disorder before/after multiple steps of treatment and one-year follow-up.

OBJECTIVE: This study examines the impact of major depressive disorder (MDD) and its treatment on quality of life (QOL). METHOD: From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, we analyzed complete data of 2280 adult MDD out-patients at entry/exit of each level of antidepressant treatments and after 12 months of entry to follow-up. QOL was measured using the QOL Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The proportions of patients scoring 'within-normal' QOL (within 10% of Q-LES-Q community norms) and those with 'severely impaired' QOL (>2 SD below Q-LES-Q community norms) were analyzed. RESULTS: Before treatment, no more than 3% of MDD patients experienced 'within-normal' QOL. Following treatment, statistically significant improvements were detected; however, the proportion of patients achieving 'within-normal' QOL did not exceed 30%, with >50% of patients experiencing 'severely impaired' QOL. Although remitted patients had greater improvements compared with non-remitters, 32-60% continued to experience reduced QOL. 12-month follow-up data revealed that the proportion of patients experiencing 'within-normal' QOL show a statistically significant decrease in non-remitters. CONCLUSION: Symptom-focused treatments of MDD may leave a misleading impression that patients have recovered when, in fact, they may be experiencing ongoing QOL deficits. These findings point to the need for investigating specific interventions to ameliorate QOL in MDD.

Left ventricular assist device in patients with body mass index greater than 30 as bridge to weight loss and heart transplant candidacy.

INTRODUCTION: In obese patients with heart failure, weight reduction may be difficult due to physical restrictions, but may be necessary to achieve heart transplant candidacy. We report the outcomes of obese patients who underwent implantation of a left ventricular assist device (LVAD) using a pulsatile (HeartMate XVE [XVE]) or continuous flow (HeartMate II [HMII]) design and the effect on body mass index (BMI). METHODS: Of 37 patients with BMI >30 kg/m(2) who underwent LVAD implantation, 29 survived at least 30 days and were followed for weight change. In the 30-day survivors, end points of the study were continued LVAD support, heart transplant, or death. One patient underwent gastric bypass surgery and was excluded. RESULTS: In the 28 patients who met inclusion criteria, BMI was 35.6 ± 4.4 kg/m(2) at baseline, and at follow-up was 33.1 ± 5.5 kg/m(2) (mean BMI change -2.5 kg/m(2); P = .063), with a mean follow-up time of 301.6 ± 255.5 days. The XVE group showed a significant BMI reduction of 3.9 kg/m(2) (P = .016 vs baseline); however, the HMII group showed 0.1 kg/m(2) increase in BMI. BMI <30 kg/m(2) at follow-up was achieved in 6 patients (21%), 5 of 19 (26%) in XVE group, and 1 of 9 (11%) in HMII group. In the 14 patients (12 XVE, 2 HMII) or 50% who received a heart transplant, the mean decrease in BMI was 4.6 kg/m(2) (P = .003). CONCLUSIONS: LVAD placement in patients with BMI >30 kg/m(2) provided significant weight loss in the pulsatile XVE group, but not in recipients of the continuous flow HMII. In patients successfully bridged to a heart transplant after LVAD insertion, mean reduction in BMI was 4.6 kg/m(2) (P = .003). LVAD implantation provides a period of hemodynamic support for obese patients with advanced heart failure, during which time opportunity may be available for weight loss. Pulsatile devices appear to be associated with greater weight loss than nonpulsatile continuous flow devices. Additional therapies may be necessary to achieve significant weight loss in recipients of the continuous flow LVAD.

Heart transplantation with and without prior sternotomy: analysis of the United Network for Organ Sharing database.

INTRODUCTION: Patients with history of prior sternotomy may have poorer outcomes after heart transplantation. Quantitation of risk from prior sternotomy has not been well established. The United Network for Organ Sharing (UNOS) database was analyzed to assess early and late survival and predictors of outcome in adult heart transplant recipients with and without prior sternotomy. METHODS: Of 11,266 adults with first heart-only transplantation from 1997 to 2011, recipients were divided into 2 groups: those without prior sternotomy (first sternotomy group; n = 6006 or 53.3%) and those with at least 1 prior sternotomy (redo sternotomy group; n = 5260 or 46.7%). A multivariable Cox model was used to identify predictors of mortality. RESULTS: Survival was lower in the redo group at 60 days (92.6% vs 95.9%; hazard ratio [HR] 1.83, 95% confidence interval [CI]: 1.56-2.15; P < .001). Conditional 5-year survival in 60-day survivors was similar in the 2 groups (HR = 1.01, 95% CI 0.90-1.12, P = .90). During the first 60 days post-transplant, the redo group had more cardiac reoperations (12.3% vs 8.8%, P = .0008), a higher frequency of dialysis (8.9% vs 5.2%, P < .0001), a greater percentage of drug-treated infections (23.2% vs 19%, P = .003), and a higher percentage of strokes (2.5% vs 1.4%, P = .0001). A multivariable Cox proportional hazards model identified prior sternotomy as a significant independent predictor of mortality, in addition to age, female gender, congenital cardiomyopathy, need for ventilation, mechanical circulatory support, dialysis prior to transplant, pretransplant serum bilirubin (≥ 3 mg/dL), and preoperative serum creatinine (≥ 2 mg/dL). CONCLUSIONS: Prior sternotomy is associated with an excess 3.3% mortality and higher morbidity within the first 60 days after heart transplantation, as measured by frequency of dialysis, drug-treated infections, and strokes. Conditional 5-year survival after 60 days is unaffected by prior sternotomy. These findings should be taken into account for risk assessment of patients undergoing heart transplantation.

Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Antithymocyte globulin induction therapy adjusted for immunologic risk after heart transplantation.

INTRODUCTION: The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known. METHODS: All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection. RESULTS: Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS). CONCLUSIONS: ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.

Methane and hydrogen positivity on breath test is associated with greater body mass index and body fat.

CONTEXT: Colonization of the gastrointestinal tract with methanogenic archaea (methanogens) significantly affects host metabolism and weight gain in animal models, and breath methane is associated with a greater body mass index (BMI) among obese human subjects. OBJECTIVE: The objective of the study was to characterize the relationship between methane and hydrogen on breath test (as a surrogate for colonization with the hydrogen requiring methanogen, Methanobrevibacter smithii), body weight, and percent body fat in a general population cohort. DESIGN AND SUBJECTS: This was a prospective study (n = 792) of consecutive subjects presenting for breath testing. SETTING: The study was conducted at a tertiary care center. OUTCOME MEASUREMENTS: BMI and percent body fat were measured. RESULTS: Subjects were classified into 4 groups based on breath testing: normal (N) (methane <3 ppm and hydrogen <20 ppm at or before 90 minutes); hydrogen positive only (H+) [methane <3 ppm and hydrogen ≥20 ppm); methane positive only (M+) (methane ≥3 ppm and hydrogen <20 ppm), or methane and hydrogen positive (M+/H+) (methane ≥3 ppm and hydrogen ≥20 ppm]. There were significant differences in age but not in gender across the groups. After controlling for age as a confounding variable, M+/H+ subjects had significantly higher BMI than other groups (N: 24.1 ± 5.2 kg/m(2); H+: 24.2 ± 4.5 kg/m(2); M+: 24.0 ± 3.75 kg/m(2); M+/H+: 26.5 ± 7.1 kg/m(2), P < .02) and also had significantly higher percent body fat (N: 28.3 ± 10.0%; H+: 27.5 ± 9.0%; M+: 28.0 ± 8.9%; M+/H+; 34.1 ± 10.9%, P < .001). CONCLUSIONS: The presence of both methane and hydrogen on breath testing is associated with increased BMI and percent body fat in humans. We hypothesize that this is due to colonization with the hydrogen-requiring M smithii, which affects nutrient availability for the host and may contribute to weight gain.

Aortic valve replacement or heart transplantation in patients with aortic stenosis and severe left ventricular dysfunction.

INTRODUCTION: The decision to perform aortic valve replacement (AVR) or heart transplantation (HTx) for aortic stenosis (AS) with severe left ventricular dysfunction is difficult and may be affected by prior myocardial infarction (MI) and coronary artery disease (CAD). METHODS: Patients who underwent AVR from 1988 to 2001 with left ventricular ejection fraction (LVEF) <30% and severe AS (aortic valve area [AVA] < 1.0 cm(2); n = 51) were assessed for operative mortality, late survival, and predictors of outcome, and were compared with HTx. Subsequently, 131 patients with LVEF ≤ 35% who underwent AVR for critical AS (AVA < 0.8 cm(2)) were evaluated. RESULTS: In the first 51 patients, 3-year survival was 100% ± 0% with no CAD, and 45% ± 10% with CAD (P < .05); 3-year survival was 88% ± 12% with no bypass, 73% ± 12% with one to two grafts, and 18% ± 11% with three grafts (P < .01). Survival with HTx was 78% at 3 years. In the subsequent analysis of 131 patients, 90-day survivors were followed for a mean 4.6 ± 3.5 years. Advanced age (P = .001) was the only predictor of long-term mortality. LVEF improved from 28.5% ± 5.2% before AVR to 45.4% ± 13.2% at 1-month postoperatively (P < .0001). New York Heart Association (NYHA) class III/IV decreased from 94.2% pre-AVR to 12.8% at 1 year (P < .0001). Predictors of LVEF recovery were no previous MI (P = .007) and higher AS gradient (P = .03). CONCLUSIONS: In severe AS and LVEF <30% with no concomitant CAD or with CAD requiring one to two bypass grafts, AVR has a survival equal to or exceeding that of HTx. In patients with CAD requiring more than two bypass grafts, survival is significantly reduced, and HTx can be considered.

Heart transplantation in patients aged 70 years and older: a two-decade experience.

OBJECTIVE: Advanced age has been viewed as a contraindication to orthotopic heart transplantation (OHT). We analyzed the outcome of OHT in patients who were aged 70 years or older and compared the results with those in younger patients during a two-decade period. METHODS: A total of 519 patients underwent first-time single-organ OHT at our institution from 1988 to 2009. Patients were divided into three groups by age: ≥70-years old (group 1, n=37), 60 to 69-years old (group 2, n=206), and ≤60-years old (group 3, n=276). Primary endpoints were 30-days, and 1-, 5-, and 10-years survival. Secondary outcomes included re-operation for bleeding, postoperative need for dialysis, and length of postoperative intubation. RESULTS: There was no significant difference in survival between the greater than or equal to 70-year-old group and the two younger age groups for the first 10 years after OHT. Survival rates at 30 days, and 1-, 5-, and 10-years, and median survival in group 1 recipients were 100%, 94.6%, 83.2%, 51.7%, and 10.9 years (CI 7.1-11.0), respectively; in group 2 those numbers were 97.6%, 92.7%, 73.8%, 47.7%, and 9.1 years (CI 6.7-10.9), respectively; and in group 3 those numbers were 96.4%, 92.0%, 74.7%, 57.1%, and 12.2 years (CI 10.7-15.4; P=NS), respectively. There was no significant difference in secondary outcomes of re-operation for bleeding, postoperative need for dialysis, and prolonged intubation among the three age groups. CONCLUSIONS: Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients. Advanced heart failure patients who are aged 70 years and older should not be excluded from transplant consideration based solely on an age criterion. Stringent patient selection, however, is necessary.

Survival and allograft rejection rates after combined heart and kidney transplantation in comparison with heart transplantation alone.

BACKGROUND: The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. METHODS: We reviewed the clinical outcomes of patients undergoing HKT (n=30) or HT (n=440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. RESULTS: There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P<.001) and a greater incidence of hypertension (P=.04). No differences were found in cardiac allograft ischemic times, including cardiopulmonary bypass or cross-clamp times. Kidney allograft ischemic time was 14.6±9 hours (mean±SD; range, 4 hours to 49 hours). Kaplan-Meier survival estimates were similar for the HKT and HT groups at 30 days (93%±4.6% versus 98%±0.7%), 1 year (87%±6.2% versus 93%±1.2%), 5 years (68%±9.0% versus 76%±2.1%), and 10 years (51%±11% versus 53%±3.0%; P=.54 for all comparisons). Follow-up serum creatinine levels were similar after HKT and HT at 30 days (1.6±1.8 mg/dL versus 1.1±0.4 mg/dL), 1 year (1.4±0.6 mg/dL versus 1.5±0.6 mg/dL), and 5 years (1.8±1.8 mg/dL versus 1.8±1.2 mg/dL; P>.05 for all comparisons). CONCLUSIONS: HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Early ultrastructural changes in renal allografts: correlation with antibody-mediated rejection and transplant glomerulopathy.

Transplant glomerulopathy (TG) is associated with antibody-mediated renal allograft rejection (AMR) and reduced graft survival. Histologically, TG is typically seen >1 year posttransplantation. However, ultrastructural changes including glomerular endothelial swelling, subendothelial widening and early glomerular basement membrane duplication are associated with development of TG but appear much earlier. We examined the specificity of these changes for AMR, and whether these are inevitably associated with development of TG. Of 98 for cause renal allograft biopsies carried out within 3 months of transplantation with available serologic data, 17 showed C4d-positive AMR and 16 had histologic changes of AMR and donor-specific antibodies (DSA), but no C4d. All three ultrastructural changes were seen in 11 of 17 biopsies with C4d-positive AMR, 8 of 16 with histologic changes of AMR and DSA but no C4d, and 0 of 65 without histologic changes of AMR and/or DSA (p < 0.0001 for both of the former groups vs. the latter). Twenty patients with positive DSA (18 with histologic changes of AMR and 11 C4d-positive) had ≥1 follow-up biopsy; eight developed overt TG 3.5-30 months posttransplantation. Among the 18 patients with DSA and histologic changes of AMR, 11 C4d-positive and 7 C4d-negative, treatment for AMR after the early biopsy significantly reduced subsequent development of overt TG.

Thiopurine methyltransferase activity combined with 6-thioguanine metabolite levels predicts clinical response to thiopurines in patients with inflammatory bowel disease.

BACKGROUND/AIMS: 6-Mercaptopurine and its prodrug azathioprine are effective for the treatment of inflammatory bowel disease. Thiopurine methyltransferase is important for the metabolism of thiopurines. However, there is controversy as to the clinical utility of measuring thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels. Our aim was to determine if thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide level monitoring would predict response to therapy with thiopurines in patients with inflammatory bowel disease. METHODS: Baseline thiopurine methyltransferase enzyme activity prior to initiation of therapy with either 6-mercaptopurine or azathioprine was determined in 39 patients with inflammatory bowel disease. The association between clinical response and thiopurine methyltransferase activity and 6-thioguanine nucleotide levels singly or in combination were analysed. RESULTS: Seventeen of 39 patients (44%) responded to 6-mercaptopurine or azathioprine therapy. Thiopurine methyltransferase enzyme activity below the mean of 30.5 U was significantly associated with clinical response. The thiopurine methyltransferase low phenotype was associated with response in 65% vs. 29% in individuals with thiopurine methyltransferase enzyme activity above 30.5 U (p = 0.05). There was no correlation between thiopurine methyltransferase activity and 6-thioguanine nucleotide levels. The maximal 6-thioguanine nucleotide levels did not predict clinical response. When combining thiopurine methyltransferase enzyme activity and 6-thioguanine nucleotide levels, the combination of thiopurine methyltransferase low/6-thioguanine nucleotide high was associated with response in 7/7 (100%) vs. only 2/8 (25%) with the combination of thiopurine methyltransferase high/6-thioguanine nucleotide low (p=0.01). CONCLUSIONS: Thiopurine methyltransferase activity inversely correlated with clinical response to thiopurine treatment in inflammatory bowel disease. Thiopurine methyltransferase enzyme activity below 30.5 U combined with a post-treatment 6-thioguanine nucleotide level > 230 pmol/8 x 10(8) erythrocytes was the best predictor of response.