Palliative interventional pulmonology procedures in the incarcerated population with cancer: a case series.

RATIONALE: Cancer is the second most common cause of death in incarcerated population and lung cancer is the most common cause of cancer death in this group. Inmates are excluded from most published surveys and research,thus the effectiveness of lung cancer palliation in this population is not known. OBJECTIVE: To report the feasibility and safety of palliative interventional pulmonary procedures in inmates with cancer. STUDY DESIGN: Retrospective review of registry data from a single center. MATERIALS AND METHODS: Inmate data on prospectively enrolled data registry (2009­2012) from the interventional pulmonology procedural registry at Virginia Commonwealth University was extracted and analyzed for safety and efficacy. Inmates with lung cancer and advanced malignancies with pleural or airway metastasis requiring airway debulking (mechanical/thermal), airway stenting, and tunneled pleural catheter (TPC) placement were included in the analysis. RESULTS: A total of 16 procedures were performed in 12 incarcerated patients. These included six TPC placements in six patients. Ten procedures were performed in seven patients with airway obstruction. These procedures included rigid and flexible bronchoscopy with mechanical (rigid and balloon dilation) and thermal (laser, argon plasma coagulation, and cautery) tumor debulking and dilation,airway stenting, and tracheostomy in one case. All six TPCpatients had immediate symptomatic relief and improved lung aeration on chest radiograph. Three of six patients had successful auto-pleurodesis. In the seven patients with airway obstruction, three patients reported symptomatic relief and one had resolution of post-obstructive pneumonia. No immediate- or long-term procedure-related complications were reported. CONCLUSION: Incarcerated patients with advanced malignancy may benefit from interventional pulmonology procedures with low complications. Palliative interventional pulmonology procedures in inmates should not be withheld solely on their incarceration status.

Artificial neural network is highly predictive of outcome in paediatric acute liver failure.

Current prognostic models in PALF are unreliable, failing to account for complex, non-linear relationships existing between multiple prognostic factors. A computational approach using ANN should provide superior modelling to PELD-MELD scores. We assessed the prognostic accuracy of PELD-MELD scores and ANN in PALF in children presenting to the QLTS, Australia. A comprehensive registry-based data set was evaluated in 54 children (32M, 22F, median age 17 month) with PALF. PELD-MELD scores calculated at (i) meeting PALF criteria and (ii) peak. ANN was evaluated using stratified 10-fold cross-validation. Outcomes were classified as good (transplant-free survival) or poor (death or LT) and predictive accuracy compared using AUROC curves. Mean PELD-MELD scores were significantly higher in non-transplanted non-survivors (i) 37 and (ii) 46 and transplant recipients (i) 32 and (ii) 43 compared to transplant-free survivors (i) 26 and (ii) 30. Threshold PELD-MELD scores ≥27 and ≥42, at meeting PALF criteria and peak, gave AUROC 0.71 and 0.86, respectively, for poor outcome. ANN showed superior prediction for poor outcome with AUROC 0.96, sensitivity 82.6%, specificity 96%, PPV 96.2% and NPV 85.7% (cut-off 0.5). ANN is superior to PELD-MELD for predicting poor outcome in PALF.

Risk factors for rejection and infection in pediatric liver transplantation.

Rejection and infection are important adverse events after pediatric liver transplantation, not previously subject to concurrent risk analysis. Of 2291 children (<18 years), rejection occurred at least once in 46%, serious bacterial/fungal or viral infections in 52%. Infection caused more deaths than rejection (5.5% vs. 0.6% of patients, p < 0.001). Early rejection (<6 month) did not contribute to mortality or graft failure. Recurrent/chronic rejection was a risk in graft failure, but led to retransplant in only 1.6% of first grafts. Multivariate predictors of bacterial/fungal infection included recipient age (highest in infants), race, donor organ variants, bilirubin, anhepatic time, cyclosporin (vs. tacrolimus) and era of transplant (before 2002 vs. after 2002); serious viral infection predictors included donor organ variants, rejection, Epstein-Barr Virus (EBV) naivety and era; for rejection, predictors included age (lowest in infants), primary diagnosis, donor-recipient blood type mismatch, the use of cyclosporin (vs. tacrolimus), no induction and era. In pediatric liver transplantation, infection risk far exceeds that of rejection, which causes limited harm to the patient or graft, particularly in infants. Aggressive infection control, attention to modifiable factors such as pretransplant nutrition and donor organ options and rigorous age-specific review of the risk/benefit of choice and intensity of immunosuppressive regimes is warranted.

The effect of recipient-specific surgical issues on outcome of liver transplantation in biliary atresia.

Biliary atresia (BA), the most common reason for orthotopic liver transplantation (OLT) in children, is often accompanied by unique and challenging anatomical variations. This study examines the effect of surgical-specific issues related to the presence of complex vascular anatomic variants on the outcome of OLT for BA. The study group comprised 944 patients who were enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry and underwent OLT for BA over an 11-year period. 63 (6.7%) patients met the study definition of complex vascular anomalies (CVA). Patient survival, but not graft survival, was significantly lower in the CVA group, (83 vs. 93 % at 1-year post-OLT). The CVA group had a significantly higher incidence of all reoperations, total biliary tract complications, biliary leaks and bowel perforation. The most frequent cause of death was infection, and death from bacterial infection was more common in the CVA group. Pretransplant portal vein thrombosis and a preduodenal portal vein were significant predictors of patient survival but not graft survival. This study demonstrates that surgical and technical factors have an effect on the outcome of BA patients undergoing OLT. However, OLT in these complex patients is technically achievable with an acceptable patient and graft survival.

Fetal and maternal endocrine responses to reduced uteroplacental blood flow.

In clinical practice, falling or reduced maternal estrogen levels are commonly regarded as indicators of fetal distress. However, experimental studies in primate animal models demonstrate that changes in maternal estradiol concentrations vary in response to reduced uteroplacental blood flow and are elevated during fetal hypoxemic stress, suggesting an increase in fetal adrenal precursor steroids. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the fetal MCR of dehydroepiandrosterone (D; MCR-D), the fetal production rate of D (PR-D), and changes in maternal and fetal plasma concentrations of D, D sulfate, cortisol, androstenedione, estrone (E1), and estradiol (E2) and in fetal plasma ACTH, PRL, and LH. A continuous i.v. infusion of [7-3H]D was administered to fetuses in five pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min. A 50% reduction in mean distal aortic blood flow was imposed after 60 min by means of partial occlusion of the aorta with a snare device, which was released at 180 min. Maternal and fetal blood samples were collected at 10-min intervals from 30-60, 120-180, and 240-270 min. Equilibrium concentrations of [3H]D in fetal plasma were determined, and the MCR-D and PR-D were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals. Concentrations of steroid and peptide hormones in maternal and fetal plasma were determined by RIA, and arterial blood pH, pO2, and pCO2 were measured. Control fetal PR-D (mean +/- SE, 4.4 +/- 2.0 mg/day) rose significantly during aortic occlusion accompanied by fetal hypoxemia (11.8 +/- 3.1 mg/day; P less than 0.05) and remained elevated with release of the aortic constriction (13.8 +/- 2.9 mg/day). Changes in fetal MCR-D were variable and not statistically significant. Among the maternal plasma steroids, only E1 and E2 increased significantly, doubling from control values during aortic occlusion and increasing by another 50% after release (P less than 0.05). There was a significant correlation between fetal PR-D and maternal plasma E2 and E1 concentrations (r2 = 0.76 and 0.71, respectively; P less than 0.01). Fetal hypoxemia was associated with dramatic increases in fetal plasma D, D sulfate, androstenedione, E1, and E2. No significant change occurred in fetal plasma cortisol, which tended to decline throughout the study. We observed a dramatic and sustained increase in fetal plasma ACTH during the period of reduced Qda and for 90 min thereafter, but no change in PRL or LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Body composition in myelomeningocele.

Body composition and measures of obesity were evaluated in 59 subjects with myelomeningocele (MMC), aged 0.3-29 y, by anthropometry and measures of body cell mass (BCM) and intra- and extracellular water (ICW and ECW), derived from total body potassium and deuterium-isotope dilution; these results were compared with reference data. Body composition was normal in preambulatory children with MMC. Beyond ages 3-4 y there was significant depletion of BCM and total body water, with maldistribution of water (increased ECW and decreased ICW) and increased percentage body fat above that expected for age and sex. These findings were more pronounced in females and in those with high lesions, and were less pronounced in those who remained ambulatory. These changes may result in metabolic and nutritional maladaption during stress. The relation of BCM, total body water depletion and increased ECW to decreasing ambulatory activity suggests that early nutritional and mobility programs warrant further study.

Short-term nutritional supplementation during management of pulmonary exacerbations in cystic fibrosis: a controlled study, including effects of protein turnover.

Effects of nutritional supplements on minimizing weight loss and abnormalities of protein turnover during pulmonary exacerbations in cystic fibrosis (CF) were studied by controlled trial. Patients received pulmonary therapy and either standard diet (n = 10) or adjunctive enteral supplements (n = 12). Initial protein turnover, measured by [15N]glycine kinetics, showed alterations of protein synthesis (P Syn) and catabolism (P Cat), which correlated with the degree of underweight, and negligible net protein deposition (P Dep). With treatment both groups had significant increases in mean body weight and forced expiratory volume in 1 s, expressed as percent predicted value for height (FEV1) by 3 wk, but a significant correlation between initial underweight and subsequent weight gain was observed only in supplemented patients. Mean P Syn and P Dep increased significantly (p less than 0.001) only in the supplemented group. Pulmonary exacerbations in CF have important adverse effects on body-protein metabolism, similar to changes in protein-energy malnutrition and infection. These effects are reversed by short-term nutritional support. Strategic nutritional intervention should thus be considered in management, especially in malnourished patients.

Altered body composition and muscle protein degradation in nutritionally growth-retarded children with cystic fibrosis.

To investigate nutritional growth retardation and the adaptive response to malnutrition in cystic fibrosis (CF), body composition and muscle protein catabolism were studied in nine malnourished CF children and eight healthy controls by anthropometry, measurement of whole body potassium, urinary creatinine excretion, creatinine height index, and urinary 3-methylhistidine excretion, an index of myofibrillar protein catabolism. CF children had a significant deficit of body mass (p less than 0.001), derived from both the body fat and the fat-free compartments, including a deficit in muscle mass (p less than 0.005). A deficit of muscle mass in CF was also reflected by a lower creatinine height index (mean +/- 1 SEM = 0.66 +/- 0.04 in CF, versus 0.85 +/- 0.5 in controls, p less than 0.02). Urinary 3-methylhistidine excretion was elevated in CF children and the mean (+/- 1 SEM) rate of muscle protein catabolism was 0.82 +/- 0.06 versus 0.53 +/- 0.04 kg-1 24 h-1 in CF and controls, respectively (p less than 0.01). 3-Methylhistidine excretion rates did not correlate with severity of disease as assessed by clinical score. We conclude that nutritional growth retardation in CF is characterized by a protein energy deficit resembling that of protein-energy malnutrition, but that in contrast to the normal adaptive response to protein-energy malnutrition, muscle protein catabolism is markedly increased. These data may have important implications regarding the clinical course and prognosis of CF and the design of optimal therapy.

Whole body protein turnover in malnourished cystic fibrosis patients and its relationship to pulmonary disease.

To investigate the effect of pulmonary disease in cystic fibrosis (CF), total body protein synthesis and catabolism were determined in eight CF children with acute exacerbations of pulmonary infection at the time of study (CF I), a group of CF children (n = 7) with chronic but stable pulmonary disease (CF II) and a group (n = 8) of healthy children. Protein synthesis was determined by the method of Waterlow et al (1978) using a single oral dose of 15N glycine and protein catabolism derived from nitrogen balance. Protein synthesis was markedly decreased (p less than 0.001) in the CF I group (1.01 +/- 0.10 g kg-1 10 h-1) compared with that of controls (2.02 +/- 0.08) and with CF children with chronic but stable pulmonary disease (CF II) (2.36 +/- 0.17). Protein catabolism was increased (p less than 0.01) in the CF II group compared with both controls and CF I. These findings contrast strongly to studies in normal children and those with mild protein-energy malnutrition (PEM) and infection, where infection increased protein synthesis, but are consistent with the observed decrease in protein turnover where severe PEM is accompanied by infection. We conclude that repeated pulmonary infection can adversely affect protein-energy balance and that adequate nutritional support should be considered in management during and after each episode.

Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement.

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation.

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Value of total body potassium in assessing the nutritional status of children with end-stage liver disease.

Malnutrition is a common problem in children with end-stage liver disease (ESLD), and accurate assessment of nutritional status is essential in managing these children. In a retrospective study, we compared nutritional assessment by anthropometry with that by body composition. We analyzed all consecutive measurements of total body potassium (TBK, n = 186) of children less than 3 years old with ESLD awaiting transplantation found in our database. The TBK values obtained by whole body counting of 40K were compared with reference TBK values of healthy children. The prevalence of malnutrition, as assessed by weight (weight Z score < -2) was 28%, which was significantly lower (chi-square test, p < 0.0001) than the prevalence of malnutrition (76%) assessed by TBK (< 90% of expected TBK for age). These results demonstrated that body weight underestimated the nutritional deficit and stressed the importance of measuring body composition as part of assessing nutritional status of children with ESLD.

Serial beta-hCG measurements in the early detection of ectopic pregnancy.

We investigated the sensitivity and specificity of serial serum hCG assays to diagnose early ectopic pregnancy in 50 asymptomatic women at risk. The initial two hCG values obtained at 2-5-day intervals were used to calculate doubling time and percentage increase. Twenty-five women had a viable intrauterine pregnancy, 14 an ectopic gestation, ten a spontaneous abortion, and one a molar pregnancy. A normal percentage increase and/or doubling time was observed in 64% of women who eventually proved to have an ectopic pregnancy. Ultimately, 85% of our patients demonstrated abnormal values when subsequent hCG pairs were analyzed. The sensitivity of these tests to diagnose asymptomatic ectopic pregnancy was 36%, with a specificity of 63-71%. We conclude that a normal rise in hCG production does not reliably differentiate an ectopic from an intrauterine pregnancy in the asymptomatic patient.

Comparison of two oral rehydration solutions in children with gastroenteritis in Australia.

An open-label inpatient study is in progress to compare the efficacy and safety of two oral rehydration solutions in children and infants with acute diarrhea and mild to moderate dehydration. One solution (ORS-60) contains 60 mmol/L of sodium and 1.8% glucose, with a total osmolality of 240 mosm/kg; the other (ORS-26) contains 26 mmol/L of sodium, 2.7% glucose, and 3.6% sucrose, with a total osmolality of 340 mosm/kg. An outcome analysis of 28 children with gastroenteritis indicated that ORS-60 (n = 13) reduced stool volume during the first eight hours after admission to a significantly greater (P less than 0.05) extent than did ORS-26 (n = 15). Diarrhea had ceased by 24 hours in 64% of ORS-60 patients but in only 31% of ORS-26 patients, and the patients' clinical condition was improved at eight hours in 84% of ORS-60 patients versus 60% of ORS-26 patients. Differences between treatments in degree of dehydration at each follow-up point, total duration of diarrhea, and duration of hospital stay were not detected. No adverse drug reactions occurred. Four patients received intravenous rehydration therapy, but none was considered a treatment failure. We conclude that the lower osmolar solution, ORS-60, conferred earlier recovery and reduced continuing fluid losses in the management of gastroenteritis.

A rapid, sensitive method for accurate analysis of individual bile acids in biological fluids by high performance thin-layer chromatography and densitometry.

1. A rapid new micromethod for quantitative analysis of individual bile acids in duodenal juice by high performance thin-layer chromatography (HPTLC) and densitometry is described and evaluated by comparison with standard TLC and spectrophotometry. 2. Advantages of HPTLC over TLC include more rapid separation, better resolution and more sensitive detection (5 - 10 fold), without the need for prior extraction. Densitometry provides simple, direct and rapid quantitation. 3. The method is accurate and reliable over a range of bile acid concentrations. In the 0.5 mM range, recovery was greater than 89%, and coefficients of variation for within-day analysis were 2 - 12% and for between-day analysis were 6 - 18% for the individual bile acids. Twenty analyses can be performed by one worker in a single day. 4. We conclude that the method offers several advantages over most currently described techniques, is suitable for routine use and is deserving of wider application.

Children with persistent feeding difficulties: an observational analysis of the feeding interactions of problem and non-problem eaters.

This study examined the relationship between parent's feeding practices and the feeding behavior of toddlers and preschool-age children with (n = 19) or without (n = 29) persistent feeding difficulties. Specifically, patterns of parent-child interaction were assessed during standardized family mealtime observations in the clinic. Parents also kept observational records of their children's mealtime behavior at home and rated the degree of difficulty they experienced in feeding their child during each meal on a daily basis. Observational results showed that feeding-disordered children engaged in higher levels of disruptive mealtime behavior (food refusal, noncompliance, complaining, oppositional behavior, and playing with food) and lower levels of chewing during mealtime. There were several significant age effects, with younger children (under age 3) engaging in more vomiting and less aversive demanding and verbalizations. Parents of feeding-disordered children were more negative and coercive in their feeding practices and engaged in higher levels of aversive instruction giving, aversive prompting, and negative eating-related comments. There were several significant associations between coercive parental behaviors and children's food refusal and noncompliance in the sample as a whole. Measures of children's disruptiveness at mealtimes in the clinic were significantly correlated with measures of mealtime behavior in the home.

The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

Heterogeneity in the responses of clones of Giardia intestinalis to anti-giardial drugs.

Clones of two stocks of Giardia intestinalis have been tested by the [3H]thymidine uptake assay to determine their sensitivity to metronidazole, tinidazole, furazolidone and quinacrine. Each stock was not homogeneous with respect to drug sensitivity but was composed of different populations of organisms. Doubling times of lines derived from clones of a stock did not vary significantly. These findings may, in part, account for treatment failures in human giardiasis patients.

Altered uptake of metronidazole in vitro by stocks of Giardia intestinalis with different drug sensitivities.

Growth of Giardia intestinalis in TYI-S-33 medium containing a sub-lethal concentration of metronidazole over a period of 66 weeks selected a line of organisms that was over 8 times less sensitive to the drug. This resistance was unstable and the organisms reverted to their original sensitivity within 22 weeks of growth in the absence of drug. A comparison of the uptake of [14C]metronidazole by the original and selected lines showed a highly significant reduction in drug uptake by the resistant line, indicating either a defective transport mechanism across the cell membrane or decreased reduction of metronidazole to the active metabolite within the cell. There was no significant difference in the uptake of metronidazole by 9 recent isolates of G. intestinalis maintained in axenic culture.

Cryopreservation of viable Giardia intestinalis trophozoites.

A technique is described for the cryopreservation of Giardia intestinalis trophozoites. The most satisfactory results were obtained when organisms were preserved with either 7.5 or 10% dimethyl sulphoxide (Me2SO) and cooled using a liquid nitrogen controlled freezer. Under these conditions more than 70% of organisms were motile after thawing. Lower recovery rates were obtained using glycerol as the cryopreservant or when samples were placed directly into a -70 degrees C refrigerator to cool. Cultures were successfully re-established from material cooled under controlled conditions using either 7.5% Me2SO or glycerol as the cryopreservant. However, the former had an initial generation time of 12.0 hours compared to 24.5 hours for the latter.