Right ventricular remodeling and clinical outcomes following transcatheter tricuspid valve intervention.

AIMS: Characterize the impact of residual tricuspid regurgitation (TR) on right ventricle (RV) remodeling and clinical outcomes after transcatheter tricuspid valve intervention. METHODS: We performed a single-center retrospective analysis of transcatheter tricuspid valve repair (TTVr) or replacement (TTVR) patients. The primary outcomes were longitudinal tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure (PASP), and RV dimensions (RVd). We used multivariable linear mixed models to evaluate association with replacement versus repair and degree of TR reduction with changes in these echo measures over time. Multivariable Cox regression was used to identify associations between changes in these echo measures and a composite clinical outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention. RESULTS: We included a total of 61 patients; mean age was 77.5 ± 11.7 and 62% were female. TTVR was performed in 25 (41%) and TTVr in 36 (59%). Initially, 72% (n = 44) had ≤ severe TR and 28% (n = 17) had massive or torrential TR. The median number of follow up echos was 2: time to 1st follow-up was 50 days (interquartile range [IQR]: 20, 91) and last follow-up was 147 (IQR: 90, 327). Median TR reduction was 1 (IQR: 0, 2) versus 4 (IQR: 3, 6) grades in TTVr versus TTVR (p < 0.0001). In linear mixed modeling, TTVR was associated with decline in TAPSE and PASP, and TR reduction was associated with decreased RVd. In multivariable Cox regression, greater RVd was associated with the clinical outcome (hazard ratio: 9.27, 95% confidence interval: 1.23-69.88, p = 0.03). CONCLUSION: Greater TR reduction is achieved by TTVR versus TTVr, which is in turn associated with RV reverse remodeling. RV dimension in follow-up is associated with increased risk of a composite outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention.

Unplanned hospital readmissions following HeartMate 3 implantation: Readmission rates, causes, and impact on survival.

BACKGROUND: Hospital readmissions following left ventricular assist device (LVAD) remain a frequent comorbidity, associated with decreased quality of life and increased resources utilization. This study sought to determine causes, predictors, and impact on survival of hospitalizations during HeartMate 3 (HM3) support. METHODS: All patients implanted with HM3 between November 2014 to December 2019 at Columbia University Irving Medical Center were consecutively enrolled in the study. Demographics and clinical characteristics from the index admission and the first outpatient visit were collected and used to estimate 1-year and 900-day readmission-free survival and overall survival. Multivariable analysis was performed for subsequent readmissions. RESULTS: Of 182 patients who received a HM3 LVAD, 167 (92%) were discharged after index admission and experienced 407 unplanned readmissions over the median follow up of 727 (interquartile range (IQR): 410.5, 1124.5) days. One-year and 900-day mean cumulative number of all-cause unplanned readmissions was 0.43 (95%CI, 0.36, 0.51) and 1.13 (95%CI, 0.99, 1.29). The most frequent causes of rehospitalizations included major infections (29.3%), bleeding (13.2%), device-related (12.5%), volume overload (7.1%), and other (28%). One-year and 900-day survival free from all-cause readmission was 38% (95%CI, 31-46%) and 16.6% (95%CI, 10.3-24.4%). One-year and 900-day freedom from 2, 3, and ≥4 readmissions were 60.7%, 74%, 74.5% and 26.2%, 33.3%, 41.3%. One-year and 900-day survival were unaffected by the number of readmissions and remained >90%. Male sex, ischemic etiology, diabetes, lower serum creatinine, longer duration of index hospitalization, and a history of readmission between discharge and the first outpatient visit were associated with subsequent readmissions. CONCLUSIONS: Unplanned hospital readmissions after HM3 are common, with infections and bleeding accounting for the majority of readmissions. Irrespective of the number of readmissions, one-year survival remained unaffected.

Continuous near-infrared reflectance spectroscopy monitoring to guide distal perfusion can minimize limb ischemia surgery for patients requiring femoral venoarterial extracorporeal life support.

BACKGROUND: Patients requiring femoral venoarterial (VA) extracorporeal life support (ECLS) are at risk of distal lower limb hypoperfusion and ischemia of the cannulated leg. In the present study, we evaluated the effect of using continuous noninvasive lower limb oximetry with near-infrared reflectance spectroscopy (NIRS) to detect tissue hypoxia and guide distal perfusion catheter (DPC) placement on the rates of leg ischemia requiring surgical intervention. METHODS: We performed a retrospective analysis of patients who had undergone femoral VA-ECLS at our institution from 2010 to 2014 (pre-NIRS era) and 2017 to 2021 (NIRS era). Patients who had undergone cannulation during the 2015 to 2016 transition era were excluded. The baseline characteristics, short-term outcomes, and ischemic complications requiring surgical intervention (eg, fasciotomy, thrombectomy, amputation, exploration) were compared across the two cohorts. RESULTS: Of the 490 patients included in the present study, 141 (28.8%) and 349 (71.2%) had undergone cannulation before and after the routine use of NIRS to direct DPC placement, respectively. The patients in the NIRS cohort had had a greater incidence of hyperlipidemia (53.7% vs 41.1%; P = .015) and hypertension (71.4% vs 60%; P = .020) at baseline, although they were less likely to have been supported with an intra-aortic balloon pump before ECLS cannulation (26.9% vs 37.6%; P = .026). These patients were also more likely to have experienced cardiac arrest (22.9% vs 7.8%; P ≤ .001) and a pulmonary cause (5.2% vs 0.7%; P = .04) as an indication for ECLS, with ECLS initiated less often for acute myocardial infarction (15.8% vs 34%; P ≤ .001). The patients in the NIRS cohort had had a smaller arterial cannula size (P ≤ .001) and a longer duration of ECLS support (5 vs 3.25 days; P ≤ .001) but significantly lower rates of surgical intervention for limb ischemia (2.6% vs 8.5%; P = .007) despite comparable rates of DPC placement (49.1% vs 44.7%; P = .427), with only two patients (1.1%) not identified by NIRS ultimately requiring surgical intervention. CONCLUSIONS: The use of a smaller arterial cannula (≤15F) and continuous NIRS monitoring to guide selective insertion of DPCs could be a valid and effective strategy associated with a reduced incidence of ischemic events requiring surgical intervention.

Acute kidney injury during extracorporeal life support in cardiogenic shock: Does flow matter?

BACKGROUND: This study examines the role of extracorporeal life support flow in the development of acute kidney injury in cardiogenic shock. METHODS: We performed a retrospective analysis of 465 patients placed on extracorporeal life support at our institution between January 2015 and December 2020 for cardiogenic shock. Flow index was calculated by dividing mean flow by body surface. Stages of acute kidney injury were determined according to Kidney Disease: Improving Global Outcomes (KDIGO) organization guidelines. RESULTS: There were 179 (38.5%) patients who developed acute kidney injury, 63.1% of which were classified as Stage 3--the only subgroup associated with 1-year mortality (hazard ratio = 2.03, p < .001). Risk of kidney injury increased up to a flow index of 1.6 L/min/m2, and kidney injury was more common among patients with flow index greater than 1.6 L/min/m2 (p = .034). Those with kidney injury had higher baseline lactate levels (4.4 vs 3.1, p = .04), and Stage 3 was associated wit higher baseline creatinine (p < .001). CONCLUSIONS: In our cohort, kidney injury was common and Stage 3 kidney injury was associated with worse outcomes compared to other stages. Low flow was not associated with increased risk of kidney injury. Elevated baseline lactate and creatinine among patients with acute kidney injury suggest underlying illness severity, rather than flow, may influence kidney injury risk.

Long-term outcomes of patients bridged to recovery with venoarterial extracorporeal life support.

OBJECTIVE: Our study examines the long-term outcomes of patients discharged from the hospital without heart replacement therapy (HRT) after recovery from cardiogenic shock using venoarterial extracorporeal life support (VA-ECLS). METHODS: We retrospectively reviewed 615 cardiogenic shock patients who recovered from VA-ECLS at our institution between January 2015 and July 2021. Of those, 166 patients (27.0%) who recovered from VA-ECLS without HRT were included in this study. Baseline characteristics, discharge labs, vitals, electrocardiograms and echocardiograms were assessed. Patients were contacted to determine vital status. The primary outcome was post-discharge mortality. RESULTS: Of 166 patients, 158 patients (95.2%) had post-discharge follow-up, with a median time of follow-up of 2 years (IQR: [1 year, 4 years]). At discharge, the median ejection fraction (EF) was 52.5% (IQR: [32.5, 57.5]). At discharge, 92 patients (56%) were prescribed ß-blockers, 28 (17%) were prescribed an ACE inhibitor, ARB or ARNI, and 50 (30%) were prescribed loop diuretics. Kaplan-Meier analysis showed a 1-year survival rate of 85.6% (95% CI: [80.1%, 91.2%]) and a 5-year survival rate of 60.6% (95% CI: [49.9%, 71.3%]). A Cox regression model demonstrated that a history of congestive heart failure (CHF) was strongly predictive of increased mortality hazard (HR = 1.929; p = 0.036), while neither discharge EF nor etiology of VA-ECLS were associated with increased post-discharge mortality. CONCLUSIONS: Patients discharged from the hospital after full myocardial recovery from VA-ECLS support without HRT should have close outpatient follow-up due to the risk of recurrent heart failure and increased mortality in these patients.

Incidence and predictors of cardiogenic shock following surgical or transcatheter tricuspid valve intervention.

OBJECTIVE: The objective of this study was to evaluate the incidence of and risk factors associated with cardiogenic shock (CS) following surgery versus transcatheter tricuspid valve intervention (TTVI) for tricuspid regurgitation (TR). BACKGROUND: Surgical therapy for TR is associated with high rates of CS. Postprocedural shock has not been studied following TTVI. METHODS: We performed a single-center retrospective analysis of isolated tricuspid valve (TV) surgery or TTVI for TR. The primary outcome was postprocedural class D or E CS according to Society for Cardiovascular Angiography and Interventions (SCAI) CS classification scheme, and secondary outcome was in-hospital mortality. Multivariable logistic regression modeling was performed for primary and secondary outcomes. Support vector machine analysis was performed for sensitivity analysis. RESULTS: From 2008 to 2020, a total of 122 patients underwent isolated TV surgery (n = 58, 14 TV repair, and 44 TV replacement) or TTVI (n = 64, 36 TV repair, and 28 TV replacement). Surgical patients were significantly younger than TTVI patients (67.5 vs. 80 years, p < 0.0001). Multivariable modeling revealed an association between the primary outcome and surgery (odds ratio [OR]: 8.75, 95% confidence interval [CI]: 2.83, 27.03, p = 0.0002), as well as baseline central venous pressure (CVP, OR: 1.12, 95% CI: 1.02, 1.22, p = 0.016). Additionally, class DE CS was independently associated with in-hospital mortality (OR: 5.21, 1.35, 20.09, p = 0.016). CVP and surgery were found to have highest importance indices in support vector machine analysis. CONCLUSION: In patients undergoing TV intervention for TR, surgery versus TTVI and elevated CVP are associated with advanced postprocedural CS. Patients developing advanced CS are at increased risk of in-hospital mortality.

Three-year survival of transcatheter versus surgical aortic valve replacement in dialysis.

To highlight the trends of surgical (open) aortic valve replacement (SAVR) as well as to compare the outcome between transcatheter aortic valve replacement (TAVR) and SAVR in elderly dialysis patients. TAVR has evolved as an effective alternative to surgery (SAVR) for aortic stenosis. We identified dialysis-dependent patients who underwent SAVR or TAVR from 2000 to 2015 from the United States Renal Data System using ICD-9 codes. We defined high-risk surgical patients as age over 70 or older. The primary endpoint was survival at 3 years and we compared the outcome between SAVR and TAVR groups using inverse probability of treatment weighting (IPTW). A total of 4332 and 1280 dialysis patients underwent SAVR and TAVR, respectively, during the study period. Among SAVR cohort, 3312 patients underwent SAVR before June 2012 and 1020 after June 2012. In-hospital mortality was significantly worse before 2012 (14.6% vs. 11.3% after 2012, p = 0.007) as well as estimated 3-year mortality (69.1% vs. 60.3% after 2012, p < 0.001). After June 2012, the TAVR cohort was older and had more comorbidities including coronary artery disease and congestive heart failure compared to the SAVR cohort. After IPTW, in-hospital mortality was significantly lower after TAVR versus SAVR (odds ratio 0.38 [95% confidence interval [CI], 0.27-0.52], p < 0.001). However, TAVR had a significantly higher risk of 3-year mortality than SAVR (hazard ratio 1.24 [95% CI 1.1-1.39], p < 0.001). TAVR may be a reasonable and potentially preferable alternative to SAVR in the elderly dialysis population in the short-term period.

Predictors of 1-year outcome after cardiac re-transplantation: Machine learning analysis.

BACKGROUND: As cardiac re-transplantation is associated with inferior outcomes compared with primary transplantation, allocating scarce resources to appropriate re-transplant candidates is important. The aim of this study is to elucidate the factors associated with 1-year mortality in cardiac re-transplantation using the random forests algorithm for survival analysis. METHODS: We retrospectively reviewed the United Network for Organ Sharing registry and identified all adult (> 17 years old) recipients who underwent cardiac re-transplantation between January 2000 and March 2020. The random forest algorithm on Cox modeling was used to calculate the variable importance (VIMP) of independent variables for contributing to 1-year mortality. RESULTS: A total of 1294 patients underwent cardiac re-transplantation. Of these, 137 patients were re-transplanted within 1 year of their first transplant, while 1157 patients were re-transplanted more than 1 year after their first transplant. One-year mortality was significantly higher for patients receiving early transplantation compared with those receiving late transplantation (Early 40.6% vs. Late 13.6%, log-rank P < .001). Machine learning analysis showed that total bilirubin (> 2 mg/dl) (VIMP, 2.99%) was an independent predictor of 1-year mortality after early re-transplant. High BMI (> 30.0 kg/m2 ) (VIMP, 1.43%) and ventilator dependence (VIMP, 1.47%) were independent predictors of 1-year mortality for the late re-transplantation group. CONCLUSION: Machine learning showed that optimal 1-year survival following cardiac re-transplantation was significantly related to liver function in early re-transplantation, and to obesity and preoperative ventilator dependence in late re-transplantation.

Impact of UNOS allocation policy changes on utilization and outcomes of patients bridged to heart transplant with intra-aortic balloon pump.

OBJECTIVE: Intra-aortic balloon pump (IABP) support may improve the hemodynamic profiles of patients in cardiogenic shock and bridge patients to heart transplant. In 2018, the United Network for Organ Sharing (UNOS) introduced new heart allocation criteria that increased the waitlist status of patients with IABPs to Status 2. This study assesses the impact of this change on IABP use and outcomes of patients with IABPs. METHODS: We queried the UNOS database for first adult heart transplant candidates with IABPs listed or transplanted before and after the UNOS policy changes (October 18, 2016-October 17, 2018, or October 18, 2018-September 4, 2020). We compared post-transplant survival and waitlist outcomes using Kaplan-Meier and Fine-Gray analyses. RESULTS: Two thousand three hundred fifty-eight patients met inclusion criteria. Utilization of IABPs for hemodynamic support increased by 338% in the two years after the policy change. Patients with IABPs listed after the policy change were more likely to receive a transplant and were transplanted more quickly (p < .001). Posttransplant survival was comparable before and after the policy change (p = .056), but non-transplanted patients were more likely to be delisted post-policy change (p < .001). CONCLUSION: The UNOS allocation criteria have benefited patients bridged with an IABP, given the higher transplant rate and shorter time to transplant.

Deep vein thrombosis and pulmonary embolism after heart transplantation.

INTRODUCTION: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in-hospital VTE after heart transplantation and its association with clinical outcomes. METHOD: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post-transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies. RESULTS: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60-days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in-hospital mortality (P = .010), and worse 5-year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE. CONCLUSION: The incidence of VTE in heart transplant recipients is high. Post-transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted.

Stroke patterns and cannulation strategy during veno-arterial extracorporeal membrane support.

Stroke has potentially devastating consequences for patients receiving veno-arterial extracorporeal membrane support (VA-ECMO). Arterial cannulation sites for VA-ECMO include the ascending aorta, axillary artery, and femoral artery. However, the influence of cannulation site on stroke risk has not been well described. The purpose of this study was to investigate the association between occurrence and patterns of stroke with ECMO arterial cannulation sites. We retrospectively reviewed 414 consecutive patients who received VA-ECMO support for cardiogenic shock between March 2007 and May 2018. Patients were categorized by cannulation strategy. The rates, subtype and location of strokes as assessed by neuroimaging during and after VA-ECMO support were analyzed. Median age was 61 years (IQR 50-69); 67% were men. 77 patients were cannulated via the ascending aorta (17%), 31 via the axillary artery (7%), and 306 (69%) via the femoral artery. In total, 26 patients (6.3%) developed 30 stroke lesions at a median of 6.0 (IQR 3.1-8.7) days after ECMO cannulation. Ischemic stroke was the most common subtype (64%), followed by hemorrhagic transformation (20%) and hemorrhagic stroke (16%). Location by CT was right hemispheric in 38%, left hemispheric in 24%, bilateral in 21%, and vertebrobasilar in 17%. The incidence of stroke was similar across cannulation strategies: aorta (n = 5, 6.5%), axillary artery (n = 2, 6.5%), and femoral artery (n = 19, 6.2%), (p = 0.99). Incidence of stroke does not appear to differ among patients cannulated via the ascending aorta, axillary artery, or femoral artery. Ischemic stroke was the most common subtype of stroke.

Diabetes workshops for providers improve glucose control in coronary artery bypass grafting patients.

OBJECTIVES: Postoperative hyperglycemia occurs in up to 80% of cardiac surgery patients and is associated with poor outcomes. We sought to determine if case-based diabetes workshops for providers would improve postoperative glycemic control and outcomes in patients undergoing coronary artery bypass grafting  (CABG). METHODS: Healthcare providers taking care of patients in the cardiothoracic step-down unit underwent 30-min weekly case-based diabetes workshops over 6 months. Workshops focused on initiation of insulin treatment, titration of insulin dosing, and transitioning from insulin drips to subcutaneous insulin. Isolated-CABG patients were recorded during 29-month periods before (Jan 2013-June 2015) and after training (Jan 2016-June 2018). Glycemic control and outcomes were compared between groups balanced for preoperative risk factors using inverse probability treatment weights. RESULTS: A total of 938 and 1032 patients were included in pre- and posttraining groups, respectively. Compared to the pretraining period, the posttraining period had a lower median of mean patient day glucose levels (151 vs. 144 mg/dl, p < .001) and percentage of patient days with a glucose level >250 mg/dl (20% vs. 14%, p < .001). The percentage of patient days with mean glucose values in the target range (80-180 mg/dl) increased from 71% to 77% (p < .001). The incidence of hypoglycemic events did not significantly change after training (p = .15). The incidence of sepsis was significantly lower in the posttraining period (1.7% vs. 0.2%, p < .001). CONCLUSIONS: Weekly diabetes workshops for healthcare providers were associated with improved glycemic control and reduced postoperative sepsis among isolated CABG patients.

Changes in waitlist and posttransplant outcomes in patients with adult congenital heart disease after the new heart transplant allocation system.

OBJECTIVE: In 2018, the United Network for Organ Sharing (UNOS) introduced new criteria for heart allocation. This study sought to assess the impact of this change on waitlist and posttransplant outcomes in adult congenital heart disease (ACHD) recipients. METHODS: Between January 2010 and March 2020, we extracted first heart transplant ACHD patients listed from the UNOS database. We compared waitlist and post-transplant outcomes before and after the policy change. RESULTS: A total of 1206 patients were listed, 951 under the old policy and 255 under the new policy. Prior to transplant, recipients under the new policy era were more likely to be treated with extracorporeal membrane oxygenation (P = .018), and have intra-aortic balloon pumps (P < .001), and less likely to have left ventricular assist devices (P = .027).Compared to patients waitlisted in the pre-policy change era, those waitlisted in the post policy change era were more likely to receive transplants (P = .001) with no significant difference in waiting list mortality (P = .267) or delisting (P = .915). There was no difference in 1-year survival post-transplant between the groups (P = .791). CONCLUSION: The new policy altered the heart transplant cohort in the ACHD group, allowing them to receive transplants earlier with no changes in early outcomes after heart transplantation.

Cardiac transplantation in adult congenital heart disease with prior sternotomy.

BACKGROUND: Adult congenital heart disease (ACHD) patients who require orthotopic heart transplantation are surgically complex due to anatomical abnormalities and multiple prior surgeries. In this study, we investigated these patients' outcomes using our institutional database. METHODS: ACHD patients who had prior intracardiac repair and subsequent heart transplant were included (2008-2018). Adult patients without ACHD were extracted as a control. A comparison of patients with functional single ventricular (SV) and biventricular (BV) hearts was performed. RESULTS: There were 9 SV and 24 BV patients. The SV group had higher central venous pressure/pulmonary capillary wedge pressure (P = .028), hemoglobin concentration (P = .010), alkaline phosphatase (P = .022), and were more likely to have liver congestion (P = .006). Major complications included infection in 16 (48.5%), temporary dialysis in 12 (36.4%), and graft dysfunction requiring perioperative mechanical support in 7 (21.2%). Overall in-hospital mortality was 15.2%. Kaplan-Meier analysis showed a higher, but not statistically significant, survival after 10 years between the ACHD and control groups (ACHD 84.9% vs. control 67.5%, P = .429). There was no significant difference in 10-year survival between SV and BV groups (78% vs. 88%, P = .467). CONCLUSIONS: Complex ACHD cardiac transplant recipients have a high incidence of early morbidities after transplantation. However, long-term outcomes were acceptable.

Early venoarterial extracorporeal membrane oxygenation improves outcomes in post-cardiotomy shock.

Post-cardiotomy shock (PCS) is associated with substantial morbidity and mortality. We reviewed our 12-year experience of venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy for PCS. Between July 2007 and June 2018, 156 consecutive patients underwent VA-ECMO for PCS. We retrospectively investigated patient characteristics, indications, and management to determine factors affecting outcomes. Secondary analysis was performed by dividing the cohort into Era 1 (2007-2012, n = 52) and Era 2 (2013-2018, n = 104) for comparison. After a median of 4.70 days (interquartile range [IQR] 2.76-8.53) of ECMO support, 72 patients (46.1%) survived to discharge. In-hospital mortality decreased in Era 2 from 75 to 43.3% (P < 0.001). Survivors were cannulated at lower serum lactate (5.3 [IQR 2.8-8.2] versus 7.5 [4.7-10.7], P = 0.003) and vasoactive-inotropic score (22.7 [IQR 11.3-35.5] versus 28.1 [IQR 20.8-42.5], P = 0.017). Patients in Era 2 were more frequently cannulated intraoperatively (63.5% versus 34.6%, P = 0.002), earlier in their hospital course, and at lower levels of serum lactate and vasoactive-inotropic score than in Era 1. Independent risk factors for mortality included increased age (odds ratio [OR] 1.06, P = 0.002), serum lactate at cannulation (OR 1.17, P = 0.009), and vasoactive-inotropic score (OR 1.04, P = 0.009). Bleeding and limb ischemia were less common in Era 2. Overall, outcomes of ECMO for PCS improved over the study period. The survival benefit appears to be associated with earlier ECMO initiation before prolonged hypoperfusion occurs.

Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis-Human Immunodeficiency Virus Coinfection in South Africa.

Background: Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone. Methods: This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Results: Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6). Conclusions: Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

Delivery of risperidone from gels across porcine skin in vitro and in vivo in rabbits.

The purpose of this study was to develop and evaluate a transdermal delivery system for RIS using hydrogels. First, the effects of different concentrations of hydroxypropyl methylcellulose and Carbomer 934 (CBR) on RIS permeation were investigated in porcine skin. The optimized formulation was chosen as the base gel to screen for penetration enhancers. The pharmacokinetics of the optimized RIS formulation was then studied in vitro in rabbits. A formulation with 0.5% CBR showed the highest RIS permeation and was selected as the base gel. RIS permeation was further increased by incorporation of Azone, lauryl alcohol, or menthol, and the enhancing effects of the three were dose-dependent. When each enhancer combined with propylene glycol (PG) a synergistic effect was found. A combination of 6% menthol and 6% PG exhibited highest RIS in vitro penetration rate and showed a high efficiency in vivo, with a relative bioavailability of 131.53% compared with intragastric administration. These findings showed that 1% RIS in 0.5% CBR, containing a combination of 6% menthol and 6% PG, can deliver doses of RIS that are therapeutically relevant for treating patients with schizophrenia.

Recent incarceration and buprenorphine maintenance treatment outcomes among human immunodeficiency virus-positive patients.

BACKGROUND: Opioid use disorder is a common cause of morbidity and mortality among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Buprenorphine maintenance treatment (BMT) is an effective means of therapy, but patients with recent criminal justice involvement may need more support during BMT than other patients. The authors hypothesized that recently incarcerated BMT patients who initiated treatment in primary care would have poorer treatment outcomes than those who were not recently incarcerated. METHODS: Investigators analyzed data from a multisite cohort study of BMT integrated into HIV care. Patients were stratified by self-reported incarceration in the 30 days before initiation of BMT. The outcomes of interest were 6- and 12-month treatment retention and self-reported opioid use. Investigators used multivariable logistic regression and hierarchical linear model, respectively, to evaluate the association between recent incarceration and these outcomes while adjusting for potential confounding variables. RESULTS: Among 305 BMT patients living with HIV/AIDS, 39 (13%) reported recent incarceration. Patients with recent incarceration (vs. without) were more likely to be homeless, unemployed, and previously diagnosed with mental illness. Recent incarceration was not significantly associated with differences in 6-month (odds ratio [OR] = 0.95; 95% confidence interval [CI] = 0.46-1.98) and 12-month (OR = 0.57; 95% CI = 0.27-1.18) treatment retention or in self-reported opioid use (OR = 0.99; 95% CI = 0.51-1.92) after adjustment for potential confounding variables. CONCLUSIONS: Those with incarceration in the 30 days prior to BMT initiation were more likely to be homeless, unemployed, and previously diagnosed with mental illness than those without recent incarceration. However, no significant difference in self-reported opioid use or 6-month or 12-month retention in treatment was detected between those with and without recent incarceration. Future studies should confirm these findings with larger sample sizes. Encouraging formerly incarcerated individuals with opioid use disorder to initiate evidence-based treatments, including BMT, should be part of efforts to confront the opioid addiction epidemic in the United States.

Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian.

The aim of this study was to evaluate the skin permeability of anemonin, which was extracted from the Chinese herb weilingxian, and its potency of relieving the inflammation caused by rheumatoid arthritis (RA). To optimize the formulation, the solubility of anemonin in water and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation of drug were investigated. Finally, the anti-inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema. The results showed that the solubility and transdermal permeation of anemonin in ethanol-water vehicles linearly depended on the ethanol concentration. The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was 48.85%. The results indicated that transdermal administration of anemonin is a potential modality for combating inflammation caused by RA.

Minimal diversity of drug-resistant Mycobacterium tuberculosis strains, South Africa.

Multidrug- (MDR) and extensively drug-resistant tuberculosis (XDR TB) are commonly associated with Beijing strains. However, in KwaZulu-Natal, South Africa, which has among the highest incidence and mortality for MDR and XDR TB, data suggest that non-Beijing strains are driving the epidemic. We conducted a retrospective study to characterize the strain prevalence among drug-susceptible, MDR, and XDR TB cases and determine associations between strain type and survival. Among 297 isolates from 2005-2006, 49 spoligotype patterns were found. Predominant strains were Beijing (ST1) among drug-susceptible isolates (27%), S/Quebec (ST34) in MDR TB (34%) and LAM4/KZN (ST60) in XDR TB (89%). More than 90% of patients were HIV co-infected. MDR TB and XDR TB were independently associated with mortality, but TB strain type was not. We conclude that, although Beijing strain was common among drug-susceptible TB, other strains predominated among MDR TB and XDR TB cases. Drug-resistance was a stronger predictor of survival than strain type.