Risk modeling for ventricular assist device support in post-cardiotomy shock

BackgroundPost-cardiotomy shock (PCS) has a complex etiology. Although treatment with inotrops and intra-aortic balloon pump (IABP) support improves cardiac performance, end-organ injuries are common and lead to prolonged ICU stay, extended hospitalization and increased mortality. Early consideration of mechanical circulatory support may prevent such complications and improve outcome.MethodsBetween January 1997 and January 2002, 321 patients required IABP and inotropic support for PCS following coronary artery bypass grafting (CABG) at our institution. Perioperative variables including age, mixed venous saturation (MVO₂), inotropic requirements and LV function were analyzed using multivariate statistical methods. All explanatory variables with a univariate p value <0.10 were entered into a stepwise logistic regression model to predict hospital mortality. Odds ratios from significant variables (p < 0.05) in the regression model were used to compose a risk score.ResultsOverall hospital mortality was 16%. The independent risk factors for mortality in this population were: MVO₂ < 60% (OR = 3.2), milrinone > 0.5 μg/kg/min (OR = 3.2), age > 75 (OR = 2.7), adrenaline > 0.1 μg/kg/min (OR = 1.5). A 15-point risk score was developed based on the regression model. Hospital mortality in patients with a score >6 was 46% (n = 13/28), 3–6 was 31% (n = 9/29) and <3 was 11% (n = 29/264).ConclusionsA significant proportion of patients with PCS continue to face high mortality despite IABP and inotropic support. Advanced age, heavy inotropic dependency and poor oxygen delivery all predicted increased risk for death. Further investigation is needed to assess whether early institution of VAD support could improve outcome in this high-risk group of patients.     

Retinoic Acid-related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema

Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.     

Neo‐adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource‐poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo‐adjuvant therapy for breast cancer have been conducted in resource‐rich countries. We chose Nigeria, a resource‐poor country, as the major site for a phase II feasibility open‐label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo‐adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m² twice daily (2,000 mg/m² total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo‐adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.     

Association of suicide rates, gun ownership, conservatism and individual suicide risk

Objectives

The purpose of the study was to examine the association of suicide rates, firearm ownership, political conservatism, religious integration at the state level, and individual suicide risk. Social structural and social learning and social integration theories were theoretical frameworks employed. It was hypothesized that higher suicide rates, higher state firearm availability, and state conservatism elevate individual suicide risk.

Method

Data were pooled from the Multiple Cause of Death Files. Multilevel logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide.

Results

The state suicide rate significantly elevated individual suicide risk (AOR = 1.042, CI = 1.037, 1.046). Firearm availability at the state level was associated with significantly higher odds of individual suicide (AOR = 1.004, CI = 1.003, 1.006). State political conservatism elevated the odds of individual suicides (AOR = 1.005, CI = 1.003, 1.007), while church membership at the state level reduced individual odds of suicide (AOR = 0.995, CI = 0.993, 0.996). The results held even after controlling for socioeconomic and demographic variables at the individual level.

Conclusion

It was concluded that the observed association between individual suicide odds and national suicide rates, and firearm ownership cannot be discounted. Future research ought to focus on integrating individual level data and contextual variables when testing for the impact of firearm ownership. Support was found for social learning and social integration theories.     

The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics

The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes.     

Residents feel unprepared and unsupervised as leaders of cardiac arrest teams in teaching hospitals: a survey of internal medicine residents

OBJECTIVE: We aimed to determine internal medicine residents' perceptions of the adequacy of their training to serve as in-hospital cardiac arrest team leaders, given the responsibility of managing acutely critically ill patients and with recent evidence suggesting that the quality of cardiopulmonary resuscitation provided in teaching hospitals is suboptimal. DESIGN: Cross-sectional postal survey. SETTING: Canadian internal medicine training programs. PARTICIPANTS: Internal medicine residents attending Canadian English-speaking medical schools. INTERVENTIONS: A survey was mailed to internal medicine residents asking questions relating to four domains: adequacy of training, perception of preparedness, adequacy of supervision and feedback, and effectiveness of additional training tools. MEASUREMENTS AND MAIN RESULTS: Of the 654 residents who were sent the survey, 289 residents (44.2%) responded. Almost half of the respondents (49.3%) felt inadequately trained to lead cardiac arrest teams. Many (50.9%) felt that the advanced cardiac life support course did not provide the necessary training for team leadership. A substantial number of respondents (40%) reported receiving no additional cardiac arrest training beyond the advanced cardiac life support course. Only 52.1% of respondents felt prepared to lead a cardiac arrest team, with 55.3% worrying that they made errors. Few respondents reported receiving supervision during weekdays (14.2%) or evenings and weekends (1.4%). Very few respondents reported receiving postevent debriefing (5.9%) or any performance feedback (1.3%). Level of training and receiving performance feedback were associated with perception of adequacy of training (r(2) = .085, p < .001). Respondents felt that additional training involving full-scale simulation, leadership skills training, and postevent debriefing would be most effective in increasing their skills and confidence. CONCLUSIONS: The results suggest that residents perceive deficits in their training and supervision to care for critically ill patients as cardiac arrest team leaders. This raises sufficient concern to prompt teaching hospitals and medical schools to consider including more appropriate supervision, feedback, and further education for residents in their role as cardiac arrest team leaders.     

Modest rates and wide variation in timely access to repeat kidney transplantation in the United States

Success of transplantation is not limited to initial receipt of a donor organ. Many kidney transplant recipients experience graft loss following initial transplantation and the benefits of expedited placement on the waiting list and retransplantation extend to this population. Factors associated with access to repeat transplantation may be unique given experience with the transplant process and prior viability as a candidate. We examined the incidence, risk factors, secular changes, and center‐level variation of preemptive relisting or transplantation (PRLT) for kidney transplant recipients in the United States with graft failure (not due to death) using Scientific Registry of Transplant Recipients data from 2007 to 2018 (n = 39 557). Overall incidence of PRLT was 15% and rates of relisting declined over time. Significantly lower PRLT was evident among patients who were African American and Hispanic, males, older, obese, publicly insured, had lower educational attainment, were diabetic, had longer dialysis time prior to initial transplant, shorter graft survival, longer distance to transplant center, and resided in distressed communities. There was significant variation in PRLT by center, median = 13%, 10th percentile = 6%, 90th percentile = 24%. Cumulatively, results indicate that despite prior access to transplantation, incidence of PRLT is modest with pronounced clinical, social, and center‐level sources of variation suggesting opportunities to improve preemptive care among patients with failing grafts.