Household chaos during infancy and infant weight status at 12 months.

BACKGROUND: Infancy is a critical period for obesity prevention. Emerging evidence links household chaos to poor health outcomes, yet its impact on obesity in infancy is unknown. OBJECTIVES: We examined associations between household chaos when infants were 6 and 12 months and weight-for-length (WFL) z-score at 12 months, exploring potential mediation by infant sleep and screen time. METHODS: We examined 401 predominately Black women and infants in the southeastern United States. We conducted multivariable linear regressions examining household chaos and infant WFL z-score, assessing breastfeeding, sleep, screen time as potential mediators. RESULTS: Among infants, 69.7% were Black and 49.0% were female. Mean breasting duration was 3.7 months. Over half (50.4%) of families had annual household incomes <$20 000. After adjustment for potential confounders, household chaos was associated with infant WFL z-score (0.02; 95% CI 0.001, 0.04; p = 0.04) at 12 months. We did not observe associations between chaos and infant breastfeeding, sleep or screen time. CONCLUSIONS: Higher household chaos was associated with greater infant weight at 12 months, but there was no evidence of mediation by breastfeeding, sleep or screen time.

Growth of liver allografts over time in pediatric transplant recipients.

The liver's capacity to grow in response to metabolic need is well known. However, long-term growth of liver allografts in pediatric recipients has not been characterized. A retrospective review of pediatric recipients at a single institution identified patients who had cross-sectional imaging at 1, 5, and 10 years post-transplant. Using volumetric calculations, liver allograft size was calculated and percent SLV were compared across the different time points; 18 patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2 or more time points. Measured liver volumes increased by 59% after 5 years and 170% after 10 years. The measured liver volumes compared to calculated %SLV for these patients were 123 ± 37%, 97 ± 19%, and 118 ± 27% at 1, 5, and 10 years after transplant, respectively. Our data suggest that liver allografts in pediatric recipients increase along with overall growth, and reach SLVs for height and weight by 5 years post-transplantation. Additionally, as pediatric recipients grow, the livers appear to maintain appropriate SLV.

No country for old livers? Examining and optimizing the utilization of elderly liver grafts.

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.

Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children.

BACKGROUND/OBJECTIVE: Exposure to food advertisements may cue overeating among children, especially among those genetically predisposed to respond to food cues. We aimed to assess how television food advertisements affect eating in the absence of hunger among children in a randomized trial. We hypothesized that the fat mass and obesity-associated gene (FTO) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements. SUBJECTS/METHODS: In this randomized experiment, 200 children aged 9-10 years were served a standardized lunch and then shown a 34-min television show embedded with either food or toy advertisements. Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake. Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype. A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted. RESULTS: About 172 unrelated participants were included in this analysis. Children consumed on average 453 (s.d.=185) kcals during lunch and 482 (s.d.=274) kcals during the experimental exposure. Children who viewed food advertisements consumed an average of 48 kcals (95% confidence interval: 10, 85; P=0.01) more of a recently advertised food than those who viewed toy advertisements. There was a statistically significant interaction between genotype and food advertisement condition (P for interaction=0.02), where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele, even after controlling for body mass index percentile. CONCLUSIONS: Food advertisement exposure was associated with greater caloric consumption of a recently advertised food, and this effect was modified by an FTO genotype. Future research is needed to understand the neurological mechanism underlying these associations.

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2).

Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.

Hypothermic machine preservation facilitates successful transplantation of "orphan" extended criteria donor livers.

Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used to preserve kidneys for transplantation with improved results over static cold storage (SCS). At our center, we have used HMP in 31 adults receiving extended criteria donor (ECD) livers declined by the originating United Network for Organ Sharing region ("orphan livers"). These cases were compared to ECD SCS cases in a matched cohort study design. Livers were matched for donor age, recipient age, cold ischemic time, donor risk index and Model for End-Stage Liver Disease (MELD) score. HMP was performed for 3-7 h at 4-8 °C using our previously published protocol. Early allograft dysfunction rates were 19% in the HMP group versus 30% in the control group (p = 0.384). One-year patient survival was 84% in the HMP group versus 80% in the SCS group (p = NS). Post hoc analysis revealed significantly less biliary complications in the HMP group versus the SCS group (4 vs. 13, p = 0.016). Mean hospital stay was significantly shorter in the HMP group (13.64 ± 10.9 vs. 20.14 ± 11.12 days in the SCS group, p = 0.001). HMP provided safe and reliable preservation in orphan livers transplanted at our center.

Timing of energy intake during the day is associated with the risk of obesity in adults.

BACKGROUND: The timing of energy intake is a modifiable behaviour that may influence energy regulation and the risk of obesity. We examined the associations of energy intake in the morning, midday and evening with body mass index (BMI) (n = 239). METHODS: Cross-sectional analyses were performed using data from the University of California, Los Angeles Energetics Study. Energy intake was assessed using three 24-h dietary recalls and stratified by time-of-day: morning (00.00 h to 11.00 h), midday (11.00 h to 17.00 h) and evening (17.00 h to 00.00 h). Sensitivity analysis was conducted among 'true-reporters', whose self-reported energy intake was ±25% of total energy expenditure measured by doubly-labelled water (n = 99). Logistic regression models were performed adjusting for age, sex, race, education, total daily energy intake and physical activity. RESULTS: Energy intake in the morning was not associated with BMI. Participants who consumed ≥33% (versus <33%) of their daily energy intake at 12.00 h were (nonsignificantly) less likely to be overweight/obese [odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.37-1.24] and this association was stronger and statistically significant among true-reporters (OR = 0.34; 95% CI = 0.12-0.95). Those who consumed ≥33% of daily energy intake in the evening were two-fold more likely overweight/obese (OR = 2.00; 95% CI = 1.03-3.89), although this association was not significant among true-reporters (OR = 2.10; 95% CI = 0.60-7.29). CONCLUSIONS: These data indicate that eating more of the day's total energy intake at midday is associated with a lower risk of being overweight/obese, whereas consuming more in the evening is associated with a higher risk. Randomised trials are needed to test whether shifting energy intake earlier in the day could have a regulatory effect with respect to reducing intake in the evening, thereby promoting weight loss and maintenance.

Using doubly labeled water to validate associations between sugar-sweetened beverage intake and body mass among White and African-American adults.

BACKGROUND: Evidence is mixed regarding sugar-sweetened beverage (SSB) intake and adiposity among adults, perhaps because of reporting bias. OBJECTIVE: The objective of this study is to determine the impact of reporting bias on any associations between increased SSB intake and overweight/obesity. DESIGN: Beverage intake and overweight/obese status (body mass index ≥ 25 kg m(-2)) were examined among adults from a dietary assessment and doubly labeled water study (n=250). Four web-based, 24-h recalls assessed dietary intake. SSB intake was categorized as no intake, 1-99 kcals per day and >99 kcals per day. Logistic regression models adjusted for total caloric intake, age, race, education and diet quality compared SSB intake with overweight/obese status. To investigate dietary self-reporting bias, analyses were replicated in a subset of 'true reporters': those with self-reported total caloric intake within 25% of total energy expenditure per doubly labeled water assessments (n=108). RESULTS: One-half of participants were overweight/obese; more overweight/obese participants consumed SSB than normal-weight participants (69% vs 47%; P<0.001). Intake of other beverages did not differ by adiposity. Less number of White participants (48%) consumed SSB compared with African-American participants (68%; P=0.002). Compared with no intake, SSB intake up to the median intake doubled the risk of being overweight/obese (odds ratio: 2.1, 95% confidence interval: 1.0-4.3; P=0.046) and SSB intake over the median more than doubled the risk (odds ratio: 2.6, 95% confidence interval: 1.2-6.0; P=0.018). When limited to true reporters, SSB intake significantly increased the risk of being overweight/obese by nearly fourfold. CONCLUSION: Underreporting of SSB intake may be attenuating true associations of SSB intake and the risk of being overweight/obese.

Totally laparoscopic full left hepatectomy for living donor liver transplantation in adolescents and adults.

In recent years different minimal access strategies have been designed in order to perform living donor liver surgery for adult recipients with less morbidity. Techniques involve shortening the length of the incision with or without previous laparoscopic mobilization of the liver. Herein we present two cases of totally laparoscopic living donor left hepatectomy, with and without removal of the middle hepatic vein, respectively. We describe in detail the anatomical and technical aspects of the procedure focusing on relevant points to enhance safety.

Prevalence of high-risk human papilloma virus among women with hepatitis C virus before liver transplantation.

BACKGROUND: We sought to assess the prevalence and risk factors for high-risk human papillomavirus (HPV) infection among female liver transplant (LT) candidates. Traditional health screening before LT listing has included Pap smear and is typically carried out by the patient's local provider. The prevalence of high-risk HPV in this population has not been studied. METHODS: With Institutional Review Board approval, 62 LT candidates received a liquid-based Pap smear with high-risk HPV testing as part of their pre-transplant evaluation by a single provider. Clinical variables included age, ethnicity, insurance status, prior Pap smear, and HPV results, HPV risk factors including age of first intercourse, number of lifetime partners, last sexual activity, smoking, birth control pill use, history of sexually transmitted infections, human immunodeficiency virus status, immunosuppressive medication, medical diagnoses, prescribed medications, and history of hepatitis A, B, C, or D. RESULTS: The 62 women had a median age of 56 years, and 39% had high-risk behavior known to be associated with HPV. Ten of 62 patients (16.1%) had high-risk HPV at baseline screening, 5 of whom had atypical cytology. All of the patients who were positive for high-risk HPV had an etiology of hepatitis C virus (HCV) as the underlying cause of liver disease, with the majority (90%) having no history of high-risk behavior for HPV. In contrast, all patients with high-risk behavior who were HCV negative were HPV negative. Fisher's exact test demonstrated a statistically significant relationship between HPV and HCV; odds ratio = 24.4, 95% confidence interval, 1.4, 438.7, P-value = 0.0013. None of the other potential risk factors were associated with HPV in this cohort. CONCLUSIONS: In this study, we provide evidence of a strong association between HCV and HPV in LT candidates, which has not been previously reported. HPV positivity was observed in non-sexually active women, suggesting a reactivation of dormant HPV. An association between hepatitis C and high-risk HPV could involve impairment of T-cell function by hepatitis C. These data support close surveillance in women's health screening for LT candidates. Further studies to characterize immune responses in these patients will be in order.

Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation.

Hypothermic machine perfusion (HMP) is in its infancy in clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls.

Multivisceral ex vivo surgery for tumors involving celiac and superior mesenteric arteries.

Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement.

The deceased organ donor with an "open abdomen": proceed with caution.

In solid organ transplantation, the disparity between donor supply and patients awaiting transplant continues to increase. The organ shortage has led to relaxation of historic contraindications to organ donation. A large percentage of deceased organ donors have been subjected to traumatic injuries, which can often result in intervention that leads to abdominal packing and intensive care unit resuscitation. The donor with this "open abdomen" (OA) presents a situation in which the risk of organ utilization is difficult to quantify. There exists a concern for the potential of a higher risk for both bacterial and fungal infections, including multidrug-resistant (MDR) pathogens because of the prevalence of antibiotic use and critical illness in this population. No recommendations have been established for utilization of organs from these OA donors, because data are limited. Herein, we report a case of a 21-year-old donor who had sustained a gunshot wound to his abdomen, resulting in a damage-control laparotomy and abdominal packing. The donor subsequently suffered brain death, and the family consented to organ donation. A multiorgan procurement was performed with respective transplantation of the procured organs (heart, liver, and both kidneys) into 4 separate recipients. Peritoneal swab cultures performed at the time of organ recovery grew out MDR Pseudomonas aeruginosa on the day after procurement, subsequently followed by positive blood and sputum cultures as well. All 4 transplant recipients subsequently developed infections with MDR P. aeruginosa, which appeared to be donor-derived with similar resistance patterns. Appropriate antibiotic coverage was initiated in all of the patients. Although 2 of the recipients died, mortality did not appear to be clearly associated with the donor-derived infections. This case illustrates the potential infectious risk associated with organs from donors with an OA, and suggests that aggressive surveillance for occult infections should be pursued.

[Necrotic skin lesions caused by pet rats in two teenagers]. / Lésions cutanées nécrotiques liées au Cowpox virus inoculé par des rats de compagnie.

We report 2 observations in young girls who, after exposure to domestic rats from the same pet shop, presented with inflammatory and necrotic skin wounds in the neck and face. Since lesions did not improve with antibiotic therapy, surgical excision of necrosis healed the wounds, with a 2nd intervention necessary in 1 patient. All bacteriological investigations appeared to be negative; finally, electron microscopy of excised subepidermal tissue and PCR characterization provided the diagnosis of cowpox virus (CPXV) infection. CPXV is part of the Orthopox virus genus, like variola virus, and is generally transmitted to humans by infected cats or rodents. CPXV infection should be kept in mind when macular, vesicular, or necrotic cutaneous wounds do not improve with antibiotics.

[Genotyping of 21,000 blood donors in Quebec and RHD analysis]. / Génotypage de 21 000 donneurs de sang au Québec et analyse du RHD.

STUDY GOAL: A repeat blood donor genotyping project was launched by Héma-Québec in October 2007. The objective was to screen 21,000 samples for 22 polymorphisms for red blood cell and platelet blood groups to build a database to easily find compatible donors. MATERIALS AND METHODS: Donors who have donated at least three times during the last year were selected. A drop of blood was spotted on FTA paper and sent to the Pharmacogenomic Centre at the Montreal Heart Institute for analysis. All genotype results were compared to the known phenotype. In parallel, the RHD gene of D negative blood donors was examined. RESULTS: Less than two years were necessary to complete the database. The genotype/phenotype concordance was 99.6% with only 165 discrepancies observed and further analysed. More than 55% of these discrepancies confirmed the initial genotype. The RHD study done on D negative samples found 13 donors positive for a variant RHD gene. Four were RHD*Ψ positive, while the other nine presented variant polymorphisms precluding a reduced expression of the D antigen. CONCLUSION: Thanks to this project, Héma-Québec is able to answer increasing demands for compatible blood more rapidly. The organisation has also demonstrated the security of its D negative inventory.