The Use of Pediatric Ventricular Assist Devices in Children's Hospitals From 2000 to 2010: Morbidity, Mortality, and Hospital Charges.

OBJECTIVE: The use of ventricular assist devices has increased dramatically in adult heart failure patients. However, the overall use, outcome, comorbidities, and resource utilization of ventricular assist devices in pediatric patients have not been well described. We sought to demonstrate that the use of ventricular assist devices in pediatric patients has increased over time and that mortality has decreased. DESIGN: A retrospective study of the Pediatric Health Information System database was performed for patients 20 years old or younger undergoing ventricular assist device placement from 2000 to 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred seventy-five pediatric patients were implanted with ventricular assist devices during the study period: 69 in 2000-2003 (era 1), 135 in 2004-2006 (era 2), and 271 in 2007-2010 (era 3). Median age at ventricular assist device implantation was 6.0 years (interquartile range, 0.5-13.8), and the proportion of children who were 1-12 years old increased from 29% in era 1 to 47% in era 3 (p = 0.002). The majority of patients had a diagnosis of cardiomyopathy; this increased from 52% in era 1 to 72% in era 3 (p = 0.003). Comorbidities included arrhythmias (48%), pulmonary hypertension (16%), acute renal failure (34%), cerebrovascular disease (28%), and sepsis/systemic inflammatory response syndrome (34%). Two hundred forty-seven patients (52%) underwent heart transplantation and 327 (69%) survived to hospital discharge. Hospital mortality decreased from 42% in era 1 to 25% in era 3 (p = 0.004). Median hospital length of stay increased (37 d [interquartile range, 12-64 d] in era 1 vs 69 d [interquartile range, 35-130] in era 3; p < 0.001) and median adjusted hospital charges increased ($630,630 [interquartile range, $227,052-$853,318] in era 1 vs $1,577,983 [interquartile range, $874,463-$2,280,435] in era 3; p < 0.001). Factors associated with increased mortality include age less than 1 year (odds ratio, 2.04; 95% CI, 1.01-3.83), acute renal failure (odds ratio, 2.1; 95% CI, 1.26-3.65), cerebrovascular disease (odds ratio, 2.1; 95% CI, 1.25-3.62), and extracorporeal membrane oxygenation (odds ratio, 3.16; 95% CI, 1.79-5.60). Ventricular assist device placement in era 3 (odds ratio, 0.3; 95% CI, 0.15-0.57) and a diagnosis of cardiomyopathy (odds ratio, 0.5; 95% CI, 0.32-0.84), were associated with decreased mortality. Large-volume centers had lower mortality (odds ratio, 0.55; 95% CI, 0.34-0.88), lower use of extracorporeal membrane oxygenation, and higher charges. CONCLUSIONS: The use of ventricular assist devices and survival after ventricular assist device placement in pediatric patients have increased over time, with a concomitant increase in resource utilization. Age under 1 year, certain noncardiac morbidities, and the use of extracorporeal membrane oxygenation are associated with worse outcomes. Lower mortality was seen at larger volume ventricular assist device centers.

Analysis of significant decrease in platelet count and thrombocytopenia, graded according to NCI-CTC, as prognostic risk markers for mortality and morbidity.

BACKGROUND: In adult intensive care unit, both thrombocytopenia (TP) and ≥30% decrease in platelet count are associated with increased mortality, morbidity, and length of stay (LOS). The above mentioned observations have not been well reported in pediatric population. National Cancer Institute (NCI) common terminology criteria (CTC) is mainly used to report the adverse effects of cancer therapy, but not for grading TP. METHOD: Retrospective review of medical records was done for 204 patients. TP was graded according to the NCI-CTC. Each grade of TP and significant decrease (≥30%) in platelet count were studied for their association with LOS, mortality, and morbidity such as hospital-acquired pneumonia and positive blood culture. Four study groups were formed according to presence and/or absence of TP and significant decrease in platelet count. These groups were also studied for their association with mortality and LOS. RESULTS: Both ≥30% decrease in platelets and TP (58.3% and 25% of patients, respectively) were associated with higher mortality and longer LOS (P<0.0001). Both have association also with infection. There was a trend of increased mortality with higher TP grade. Grade 4 TP was significantly associated with increased LOS (P=0.0001). When compared with neither group, groups with positive significant decrease were associated with higher mortality and LOS, even in the absence of TP. CONCLUSIONS: We can use the NCI-CTC for classification of TP, which would enable the standardization of TP grading system. A ≥30% decrease in platelet count, even without TP, is a prognostic risk marker for mortality, morbidity, and LOS.

Preferences of Type 1 Diabetic Patients on Devices for Islet Transplantation.

Transplantation of pancreatic islets within a biomaterial device is currently under investigation in clinical trials for the treatment of patients with type 1 diabetes (T1D). Patients' preferences on such implants could guide the designs of next-generation implantable devices; however, such information is not currently available. We surveyed the preferences of 482 patients with T1D on the size, shape, visibility, and transplantation site of islet containing implants. More than 83% of participants were willing to receive autologous stem cells, and there was no significant association between implant fabricated by one's own stem cell with gender (χ2 (1, n = 468) = 0.28; P = 0.6) or with age (χ2 (4, n = 468) = 2.92; P = 0.6). Preferred location for islet transplantation within devices was under the skin (52.7%). 48.3% preferred microscopic disks, and 32.3% preferred a thin device (like a credit card). Moreover, 58.4% preferred the implant to be as small as possible, 25.4% did not care about visibility, and 16.2% preferred their implants not to be visible. Among female participants, 81% cared about the implant visibility, whereas this number was 64% for male respondents (χ2 test (1, n = 468) = 16.34; P < 0.0001). 22% of those younger than 50 years of age and 30% of those older than 50 did not care about the visibility of implant (χ2 test (4, n = 468) = 23.69; P < 0.0001). These results suggest that subcutaneous sites and micron-sized devices are preferred choices among patients with T1D who participated in our survey.

Hydrogen oxidising bacteria for production of single-cell protein and other food and feed ingredients.

Using hydrogen oxidising bacteria to produce protein and other food and feed ingredients is a form of industrial biotechnology that is gaining traction. The technology fixes carbon dioxide into products without the light requirements of agriculture and biotech that rely on primary producers such as plants and algae while promising higher growth rates, drastically less land, fresh water, and mineral requirements. The significant body of scientific knowledge on hydrogen oxidising bacteria continues to grow and genetic engineering tools are well developed for specific species. The scale-up success of other types of gas- fermentation using carbon monoxide or methane has paved the way for scale-up of a process that uses a mix of hydrogen, oxygen, and carbon dioxide to produce bacteria as a food and feed ingredients in a highly sustainable fashion.

Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity.

Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 microM in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 microM in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (>80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

7'-substituted benzothiazolothio- and pyridinothiazolothio-purines as potent heat shock protein 90 inhibitors.

We report on the discovery of benzo- and pyridino- thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2-ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H- purin-6-ylamine).