Left Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study.

BACKGROUND: Left ventricular dysfunction in potential donors meeting brain death criteria often results in nonuse of donor hearts for transplantation, yet little is known about its incidence or pathophysiology. Resolving these unknowns was a primary aim of the DHS (Donor Heart Study), a multisite prospective cohort study. METHODS: The DHS enrolled potential donors by neurologic determination of death (n=4333) at 8 organ procurement organizations across the United States between February 2015 and May 2020. Data included medications administered, serial diagnostic tests, and transthoracic echocardiograms (TTEs) performed: (1) within 48 hours after brain death was formally diagnosed; and (2) 24±6 hours later if left ventricular (LV) dysfunction was initially present. LV dysfunction was defined as an LV ejection fraction <50% and was considered reversible if LV ejection fraction was >50% on the second TTE. TTEs were also examined for presence of LV regional wall motion abnormalities and their reversibility. We assessed associations between LV dysfunction, donor heart acceptance for transplantation, and recipient 1-year survival. RESULTS: An initial TTE was interpreted for 3794 of the 4333 potential donors by neurologic determination of death. A total of 493 (13%) of these TTEs showed LV dysfunction. Among those donors with an initial TTE, LV dysfunction was associated with younger age, underweight, and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and troponin levels. A second TTE was performed within 24±6 hours for a subset of donors (n=224) with initial LV dysfunction; within this subset, 130 (58%) demonstrated reversibility. Sixty percent of donor hearts with normal LV function were accepted for transplant compared with 56% of hearts with reversible LV dysfunction and 24% of hearts with nonreversible LV dysfunction. Donor LV dysfunction, whether reversible or not, was not associated with recipient 1-year survival. CONCLUSIONS: LV dysfunction associated with brain death occurs in many potential heart donors and is sometimes reversible. These findings can inform decisions made during donor evaluation and help guide donor heart acceptance for transplantation.

Neighbourhood factors and tuberculosis incidence in Cape Town: A negative binomial regression and spatial analysis.

OBJECTIVES: Although the link between poverty and tuberculosis (TB) is widely recognised, limited studies have investigated the association between neighbourhood factors and TB incidence. Since the factors influencing different episodes of TB might be different, this study focused on the first episode of TB disease (first-episode TB). METHODS: All first episodes in previously linked and geocoded TB notification data from 2007 to 2015 in Cape Town, South Africa, were aggregated at the neighbourhood level and merged with the 2011 census data. We conducted an ecological study to assess the association between neighbourhood incidence of first-episode TB and neighbourhood factors (total TB burden [all episodes] in the previous year, socioeconomic index, mean household size, mean age, and percentage males) using a negative binomial regression. We also examined the presence of hotspots in neighbourhood TB incidence with the Global Moran's I statistic and assessed spatial dependency in the association between neighbourhood factors and TB incidence using a spatial lag model. RESULTS: The study included 684 neighbourhoods with a median first-episode TB incidence rate of 114 (IQR: 0-345) per 100,000 people. We found lower neighbourhood socioeconomic index (SEI), higher neighbourhood total TB burden, lower neighbourhood mean household size, and lower neighbourhood mean age were associated with increased neighbourhood first-episode TB incidence. Our findings revealed a hotspot of first-episode TB incidence in Cape Town and evidence of spatial dependency in the association between neighbourhood factors and TB incidence. CONCLUSION: Neighbourhood TB burden and SEI were associated with first-episode TB incidence, and there was spatial dependency in this association. Our findings can inform targeted interventions to reduce TB in high-risk neighbourhoods, thereby reducing health disparities and promoting health equity.

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

Effects of Atorvastatin and Rosuvastatin on Blood Lipids in Quaker Parrots (Myiopsitta monachus).

Statin drugs are the most effective class of hypolipidemic and antiatherosclerotic drugs, with atorvastatin and rosuvastatin being the most effective. While the use of statins would be a tremendous asset in the treatment of dyslipidemia and lipid-accumulation disorders in birds, there are only limited data available regarding their use and effectiveness in psittacine species. Two consecutive randomized crossover trials on Quaker parrots (Myiopsitta monachus) were performed to study the effect of atorvastatin and rosuvastatin. Ten birds were used in an initial balanced crossover experiment with 5 oral treatments (control; atorvastatin 10 mg/kg q12h and q24h; rosuvastatin 10 mg/kg q12h and q24h) for 2 weeks each. Plasma lipidomics and lipoprotein profiling were performed after each treatment. Twelve birds were used in a second experiment consisting of 2 parallel crossover studies, each with 6 birds either fed their regular diet or a 0.3% cholesterol diet. In the 2 parallel crossover studies, the treatment group was administered atorvastatin 20 mg/kg orally q12h and the control group a placebo suspension orally q12h. Plasma lipidomics, lipoprotein profiles, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity were subsequently measured. Results were analyzed with serial linear mixed models and trends were assessed graphically. No statistically significant effect of any statin treatment was detected on plasma lipids, lipoproteins, creatinine kinase, or HMG-CoA reductase activity. In the first trial, all the rosuvastatin treatments led to some nonsignificant decreases in several triacylglycerol species, while in the second trial this was only observed in the birds on atorvastatin 20 mg/kg q12h being fed their regular diet. Quaker parrots may require much higher doses of statin drugs to show significant and clinically useful lipid-lowering effects.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.

Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya.

The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies. Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore. Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers.

Severe maternal morbidity in Scotland.

Using a cohort study design, we analysed 17 diagnoses and 9 interventions (including critical care admission) as a composite measure of severe maternal morbidity for pregnancies recorded over 14 years in Scotland. There were 762,918 pregnancies, of which 7947 (10 in 1000 pregnancies) recorded 9345 severe maternal morbidity events, 2802 episodes of puerperal sepsis being the most common (30%). Severe maternal morbidity incidence increased from 9 in 1000 pregnancies in 2012 to 17 in 1000 pregnancies in 2018, due in part to puerperal sepsis recording. The odds ratio (95%CI) for severe maternal morbidity was higher for: older women, for instance 1.22 (1.13-1.33) for women aged 35-39 years and 1.44 (1.27-1.63) for women aged > 40 years compared with those aged 25-29 years; obese women, for instance 1.13 (1.06-1.21) for BMI 30-40 kg.m-2 and 1.32 (1.15-1.51) for BMI > 40 kg.m-2 compared with BMI 18.5-24.9 kg.m-2 ; multiple pregnancy, 2.39 (2.09-2.74); and previous caesarean delivery, 1.52 (1.40-1.65). The median (IQR [range]) hospital stay was 3 (2-5 [1-8]) days with severe maternal morbidity and 2 (1-3 [1-5]) days without. Forty-one women died during pregnancy or up to 42 days after delivery, representing mortality rates per 100,000 pregnancies of about 365 with severe maternal morbidity and 1.6 without. There were 1449 women admitted to critical care, 807 (58%) for mechanical ventilation or support of at least two organs. We recorded an incidence of severe maternal morbidity higher than previously published, possibly because sepsis was coded inaccurately in our databases. Further research may determine the value of this composite measure of severe maternal morbidity.

Neonatal hyperleukocytosis and regenerative anemia in a septic puppy.

This paper reports a case of neonatal hyperleukocytosis in a dog due to a bacterial infection. A 3-week-old, mixed-breed dog was brought to a veterinary college referral center with a history of weight loss despite a good appetite. Clinical and laboratory examinations included: physical examination, complete blood (cell) count (CBC), serum biochemistry profile, abdominal ultrasound examination, and cytology of liver and bone marrow aspirates. The CBC showed hyperleukocytosis of 158.0 × 109/L (RI: 2.1 to 21.2 × 109/L) and hematocrit of 0.19 L/L (RI: 0.21 to 0.34 L/L). The strong leukemoid reaction was comprised of neutrophils, monocytes, and lymphocytes. The dog was diagnosed with Staphylococcus pseudointermedius liver infection based on liver aspirates and culture. Amoxicillin-clavulanic acid was prescribed. A recheck abdominal ultrasound and CBC repeated 4 wk after initial examination were unremarkable. Neonatal hyperleukocytosis is well-described in human medicine but veterinary studies in small animal neonates are scarce. Key clinical message: Hyperleukocytosis in adult dogs may be caused by leukemia or leukemoid reactions. Generalized sepsis is a leading cause of leukemoid reactions in adult dogs and cats. In puppies, neoplasia is less likely, and other causes should be investigated. Similar to human neonates, puppies can mount a strong leukemoid reaction during an infection, even if it is not a generalized septic process.

Hyperleucocytose néonatale et anémie régénérative chez un chiot septique. Cet article rapporte un cas d'hyperleucocytose néonatale chez un chien dû à une infection bactérienne. Un chien de race mixte âgé de 3 semaines a été amené dans un centre de référence d'une école vétérinaire avec des antécédents de perte de poids malgré un bon appétit. Les examens cliniques et de laboratoire comprenaient : examen physique, numération globulaire complète (CBC), profil biochimique sérique, examen échographique abdominal et cytologie des aspirations du foie et de la moelle osseuse.Le CBC montrait une hyperleucocytose de 158,0 × 109/L (RI : 2,1 à 21,2 × 109/L) et un hématocrite de 0,19 L/L (RI : 0,21 à 0,34 L/L). La forte réaction leucémique était composée de neutrophiles, de monocytes et de lymphocytes. Le chien a été diagnostiqué avec une infection hépatique à Staphylococcus pseudointermedius sur la base d'aspirations et de cultures de foie. L'amoxicilline-acide clavulanique a été prescrit. Une échographie abdominale de contrôle et un CBC répété 4 semaines après l'examen initial étaient sans particularité. L'hyperleucocytose néonatale est bien décrite en médecine humaine mais les études vétérinaires chez les nouveau-nés de petits animaux sont rares.Message clinique clé :L'hyperleucocytose chez les chiens adultes peut être causée par une leucémie ou des réactions leucémiques. La septicémie généralisée est l'une des principales causes de réactions leucémiques chez les chiens et les chats adultes. Chez les chiots, la néoplasie est moins probable et d'autres causes doivent être recherchées. Semblables aux nouveaunés humains, les chiots peuvent développer une forte réaction leucémique lors d'une infection, même s'il ne s'agit pas d'un processus septique généralisé.(Traduit par Dr Serge Messier).

Survey of public attitudes towards imminent death donation in the United States.

Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. Although IDD was ethically justified by United Network for Organ Sharing, the concept remains controversial due to presumed lack of public support. The aim of this study was to evaluate the public's attitudes towards IDD. A cross-sectional survey was conducted of US adults age >18 years (n = 2644). The survey included a case scenario of a patient with a devastating brain injury. Responses were assessed on a 5-point Likert scale. Results showed that 68% - 74% of participants agreed or strongly agreed with IDD when posed as a general question and in relation to the case scenario. Participants were concerned about "recovery after a devastating brain injury" (34%), and that "doctors would not try as hard to save a patient's life" (33%). Only 9% of participants would be less likely to trust the organ donation process. In conclusion, our study demonstrates strong public support for IDD in the case of a patient with a devastating brain injury. Notably, participants were not largely concerned with losing trust in the organ donation process. These results justify policy change towards imminent death donation.

Parents' experiences of care and support after stillbirth in rural and urban maternity facilities: a qualitative study in Kenya and Uganda.

OBJECTIVE: To explore parents' lived experiences of care and support following stillbirth in urban and rural health facilities. DESIGN: Qualitative, interpretative, guided by Heideggerian phenomenology. SETTING: Nairobi and Western Kenya, Kampala and Central Uganda. SAMPLE: A purposive sample of 75 women and 59 men who had experienced the stillbirth of their baby (≤1 year previously) and received care in the included facilities. METHODS: In-depth interviews, analysed using Van Manen's reflexive approach. RESULTS: Three main themes were identified; parents described devastating impacts and profound responses to their baby's death. Interactions with health workers were a key influence, but poor communication, environmental barriers and unsupportive facility policies/practices meant that needs were often unmet. After discharge, women and partners sought support in communities to help them cope with the death of their baby but frequently encountered stigma engendering feelings of blame and increasing isolation. CONCLUSIONS: Parents in Kenya and Uganda were not always treated with compassion and lacked the care or support they needed after the death of their baby. Health workers in Kenya and Uganda, in common with other settings, have a key role in supporting bereaved parents. There is an urgent need for context and culturally appropriate interventions to improve communication, health system and community support for African parents. TWEETABLE ABSTRACT: Health-system response and community support for parents after stillbirth in Kenya and Uganda are inadequate.

Donor derived hepatitis B virus infection: Analysis of the Organ Procurement & Transplantation Network/United Network for Organ Sharing Ad Hoc Disease Transmission Advisory Committee.

Hepatitis B virus (HBV) can be transmitted from organ donor to recipient, but details of transmission events are not widely published. The Disease Transmission Advisory Committee (DTAC) evaluated 105 cases of potential donor derived transmission events of HBV between 2009-2017. Proven, probable or possible transmission of HBV occurred in 25 (23.8%) cases. Recipients of liver grafts were most commonly infected (20 of 21 exposed recipients) compared to 9 of 21 exposed non-hepatic recipients. Eleven of 25 donors were HBV core antibody (HBcAb) positive/HBV surface antigen (HBsAg) negative and infected 8/20 recipients. Of the 10 liver recipients and 1 liver-kidney recipient who received organs from these donors: six were not given antiviral prophylaxis, two developed infection after antiviral prophylaxis was discontinued, two developed HBV while on lamivudine prophylaxis, one was on antiviral prophylaxis and did not develop HBV viremia or antigenemia. One recipient of a HBcAb positive/HBsAg negative kidney developed active HBV infection. Unexpected donor-derived transmission of HBV was a rare event in reports to DTAC, but was often detected in the recipient late post-transplant. Six of 11 recipients (54.5%) of a liver from a HBcAb positive donor did not receive prophylaxis; all of these were potentially preventable with the use of anti-viral prophylaxis.

National population prevalence of antibodies to SARS-CoV-2 among pregnant women in Scotland during the second wave of the COVID-19 pandemic: a prospective national serosurvey.

OBJECTIVES: This study aimed to determine SARS-CoV-2 seroprevalence among pregnant women in the Scottish population during the second wave of the COVID-19 pandemic. STUDY DESIGN: Prospective national serosurvey. METHODS: We tested 13,428 residual samples retrieved from pregnant women participating in the first trimester combined ultrasound and biochemical screening for fetal trisomy across Scotland for SARS-CoV-2 antibodies over a 6-month period from November 2020 to April 2021. Seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. RESULTS: Seroprevalence rates in the antenatal samples significantly increased from 5.5% (95% confidence interval [CI] 4.7%-6.5%) in the 5-week period up to and including International Organization for Standardization (ISO) Week 51 (w/b Monday 14 December 2020) to 11.3% (95% CI 10.1%-12.6%) in the 5-week period up to and including ISO Week 14 (w/b Monday 5 April 2021). Increasing seroprevalence trends across the second wave were observed among all age groups. CONCLUSIONS: By the end of the second wave of the COVID-19 pandemic, approximately one in 10 women tested around the end of the first trimester of pregnancy had antibodies to SARS-CoV-2, suggesting that the vast majority were still susceptible to COVID-19 as they progressed to the later stages of pregnancy, when risks from infection are elevated for both mother and baby.

Prenatal effects of maternal nutritional stress and mental health on the fetal movement profile.

PURPOSE: Prenatal sub-optimal nutrition and exposure to maternal stress, anxiety and depression in pregnancy have been linked to increased postnatal morbidity and mortality. Fetal growth is most vulnerable to maternal dietary deficiencies, such as those evident in hyperemesis gravidarum (HG), early in pregnancy. The purpose of this pilot study was to examine the effects of HG on fetal movement profiles as a measure of fetal healthy development in the 3rd trimester of pregnancy, and to assess whether nutritional stress on the mother can be evaluated using isotopic analysis of hair. METHOD: We analyzed fetal movement profiles using 4D ultrasound scans at 32- and 36-weeks' gestation. Fetuses of women (N = 6) diagnosed with HG, having lost more than 10% of their body weight in the first trimester of pregnancy were compared to a healthy group (N = 6), controlling for stress, depression and anxiety. We tested carbon and nitrogen isotope ratios in maternal hair as a measure of both diet and nutritional changes due to catabolism of body proteins and fats. RESULTS: HG and catabolism were significantly correlated (p = 0.02). Furthermore, at 32-weeks' gestation movement profiles of fetuses of mothers with HG differed significantly from the movement profiles of fetuses of healthy mothers. Fetuses of mothers suffering from HG showed a significantly increased ratio of fine-grained movements at 32 weeks (p = 0.008); however, there were no significant differences detectable at 36-weeks' gestation. CONCLUSION: The effect of HG on fetal development as expressed by variations in fetal movement profiles in this pilot study suggest that prenatal effects of HG can be measured using movement profiles. Isotope analysis of hair can supplement this with information on nutritional imbalances early in pregnancy.

Renal cell carcinoma suspected at time of organ donation 2008-2016: A report of the OPTN ad hoc Disease Transmission Advisory Committee Registry.

All 179 reports to the OPTN of potential renal cell carcinoma (RCC) transmission from 1/1/2008 through 12/31/2016 were reviewed. Cases were divided into those with donor tumor known or suspected at time of transplant (N = 147 donors), and those in which tumor was initially found after transplant (N = 32). We sought to understand the risk of transplanting either the affected kidney, the contralateral kidney or non-renal organs from donors with a suspected/confirmed unilateral RCC. In the case of RCC found prior to transplant, transplantation of 21 kidneys following excision of tumor, 47 contralateral kidneys and 198 non-renal organs was performed. No cases of RCC transmission were documented in this population. An additional six cases of live donor kidney transplantation involving resection of RCC were reported, also without transmission. Six of 9 other recipients in whom the diagnosis of RCC became available after implantation underwent allograft nephrectomy and 3 received tumor resection. No recurrent RCC was documented. Given the low rate of transmission and available treatment options, consideration should be given to judicious use of organs from donors with small solitary RCC.

The humanistic burden associated with caring for patients with advanced non-small cell lung cancer (NSCLC) in three European countries-a real-world survey of caregivers.

PURPOSE: This study evaluated the humanistic burden on caregivers of patients with advanced non-small cell lung cancer (aNSCLC) as the disease progresses. METHODS: Data were drawn from a cross-sectional study of patients with aNSCLC and their caregivers conducted in France, Germany, and Italy between 2015 and 2016. Data were collected by medical chart review and patient and caregiver questionnaires. The EuroQol five-dimension three-level (EQ-5D-3L) was used to evaluate patient and caregiver health status. Caregivers also completed the Work Productivity and Activity Impairment (WPAI) questionnaire and Zarit Burden Interview (ZBI). RESULTS: The population for the analysis consisted of 427 caregivers (mean age 53.5 years; 72.6% female; 54.9% spouse; 36.2% in full-time employment) and 427 matched patients (mean age 66.2 years; 68.6% male). Most (69.5%) patients were receiving first-line therapy for advanced disease. Patients' caregivers provided a mean of 29.5 h of support per week. Significant differences in EQ-5D-3L scores were observed between caregivers of patients receiving first and later lines of therapy in France (0.87 vs. 0.78; p = 0.0055). Among employed caregivers, overall work impairment was considerable and ranged from 21.1% in Germany to 30.4% in France and 29.7% in Italy. Caregivers of patients receiving later lines of therapy in France rated their own health status as significantly worse than did those caring for patients receiving first-line therapy (82.7 vs. 72.9; p = 0.0039). CONCLUSIONS: Informal caregivers provided the majority of support for patients with advanced NSCLC and their caregiving activities impose a significant humanistic burden.

Intermittent energy restriction improves weight loss efficiency in obese men: the MATADOR study.

BACKGROUND/OBJECTIVES: The MATADOR (Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound) study examined whether intermittent energy restriction (ER) improved weight loss efficiency compared with continuous ER and, if so, whether intermittent ER attenuated compensatory responses associated with ER. SUBJECTS/METHODS: Fifty-one men with obesity were randomised to 16 weeks of either: (1) continuous (CON), or (2) intermittent (INT) ER completed as 8 × 2-week blocks of ER alternating with 7 × 2-week blocks of energy balance (30 weeks total). Forty-seven participants completed a 4-week baseline phase and commenced the intervention (CON: N=23, 39.4±6.8 years, 111.1±9.1 kg, 34.3±3.0 kg m-2; INT: N=24, 39.8±9.5 years, 110.2±13.8 kg, 34.1±4.0 kg m-2). During ER, energy intake was equivalent to 67% of weight maintenance requirements in both groups. Body weight, fat mass (FM), fat-free mass (FFM) and resting energy expenditure (REE) were measured throughout the study. RESULTS: For the N=19 CON and N=17 INT who completed the intervention per protocol, weight loss was greater for INT (14.1±5.6 vs 9.1±2.9 kg; P<0.001). INT had greater FM loss (12.3±4.8 vs 8.0±4.2 kg; P<0.01), but FFM loss was similar (INT: 1.8±1.6 vs CON: 1.2±2.5 kg; P=0.4). Mean weight change during the 7 × 2-week INT energy balance blocks was minimal (0.0±0.3 kg). While reduction in absolute REE did not differ between groups (INT: -502±481 vs CON: -624±557 kJ d-1; P=0.5), after adjusting for changes in body composition, it was significantly lower in INT (INT: -360±502 vs CON: -749±498 kJ d-1; P<0.05). CONCLUSIONS: Greater weight and fat loss was achieved with intermittent ER. Interrupting ER with energy balance 'rest periods' may reduce compensatory metabolic responses and, in turn, improve weight loss efficiency.

The use of omalizumab in allergen immunotherapy.

Although omalizumab (anti-IgE) is currently only approved for the treatment of asthma and chronic idiopathic urticaria, it has also been studied as an off-label treatment for numerous allergic conditions, including use as an adjunct to allergen immunotherapy in the treatment of allergic rhinitis, asthma, venom hypersensitivity and food allergy. We conducted a review of publications involving the use of omalizumab with allergen immunotherapy, by searching PubMed with key search terms of "omalizumab" and "immunotherapy." Omalizumab has been used in combination with inhalant allergen immunotherapy for the treatment of seasonal allergic rhinitis and comorbid asthma. While there have been no randomized controlled trials evaluating the addition of omalizumab to venom IT, several case reports and small patient series have been published on the use of omalizumab with venom IT. Omalizumab has been used in conjunction with oral immunotherapy for the treatment of milk, peanut and egg, as well as other foods in multi-allergen protocols. In conclusion, omalizumab used in conjunction with immunotherapy has shown promising results, especially in the reduction of adverse reactions. At this stage, larger, randomized, placebo-controlled trials are needed to better identify those patients who would benefit the most from the addition of omalizumab to immunotherapy, as well as optimal dosing strategies and duration of treatment.