Defining Ultra-Massive Transfusion through a Systematic Review.

Background: Despite the widespread use of ultra-massive transfusion (UMT) as an intervention for trauma patients in hemorrhagic shock, no standard definition exists. We performed a systematic review to determine a consensus definition for UMT. Methods: A search was performed from 1979-2022. The authors screened studies defining UMT and associated outcomes as defined by our prespecified PICO questions. The PRISMA guidelines were used. Results: 1662 articles met criteria for eligibility assessment, 17 for full-text review and eight for data extraction. Only two studies demonstrated a consensus definition of UMT, which used ≥20 units of red blood cell product within 24hrs. Parameters associated with increased mortality included lower blood pressure, lower pulse and lower Glasgow Coma Score at the time of presentation and a higher injury severity score and undergoing a resuscitative thoracotomy. Conclusions: The absence of a consensus definition for UMT raises challenges from clinical, research and ethical perspectives. Based on our findings, the authors advocate for the feasibility of standardizing the definition of UMT as ≥20 units of red blood cell product within 24hrs.

Expanding the access to kidney transplantation: Strategies for kidney transplant programs.

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient-centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre-emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant.

Walking Ability and Brain Natriuretic Peptide Are Highly Predictive of Kidney Transplant Waiting List Removal.

Kidney transplant waitlist management is complex because waiting time is long, and the patients have significant comorbidities. Identification of patients at highest risk for waiting list removal for death and medical complications could allow better outcomes and allocation of resources. Methods: Demographics, functional and frailty assessment' and biochemical data were retrospectively analyzed on 313 consecutive patients listed for kidney transplant. Troponin, brain natriuretic peptide, components of the Fried frailty metrics, pedometer activity, and treadmill ability were measured at the time of transplant evaluation and at subsequent re-evaluations. Cox proportional hazards models were used to identify factors associated with death or waiting list removal for medical reasons. Multivariate models were created to identify significant predictor sets. Results: Among 249 patients removed while waitlisted, 19 (6.1%) died and 51 (16.3%) were removed for medical reasons. Mean follow-up duration was 2.3 y (±1.5 y). 417 sets of measurements were collected. Significant (P < 0.05) non-time-dependent variables associated with the composite outcome identified on univariate analysis included N-terminal probrain natriuretic peptide (BNP), treadmill ability, pedometer activity, diagnosis of diabetes and the Center of Epidemiological Studies Depression Scale question asking how many days per week could you not get going. Significant time-dependent factors included BNP, treadmill ability, Up and Go, pedometer activity, handgrip, 30 s chair sit-stand test, and age. The optimal time-dependent predictor set included BNP, treadmill ability, and patient age. Conclusions: Changes in functional and biochemical markers are predictive of kidney waitlist removal for death and medical reasons. BNP and measures of walking ability were of particular importance.

Sarcoidosis Causing Complete Nasal Obstruction.

Our case demonstrates the rare presentation of sinonasal sarcoidosis causing severe nasal obstruction. While the patient had a remote history of pulmonary sarcoidosis, she was in remission and had no prior history of sinonasal involvement. Sarcoidosis should be considered in a patient with nasal obstruction especially when there is a history of systemic sarcoid disease.

COVID-19 & differential effects in twins: Insights from Placenta Pathology.

INTRODUCTION: COVID-19 has been associated with several adverse pregnancy outcomes, including perinatal loss. Differential effects of COVID-19 in a twin pregnancy may provide unique insights into virus-placental interactions. We present a case of perinatal loss of a female fetus with survival of the male co-twin in a pregnancy complicated by COVID-19 and premature delivery. METHODS: Viral detection methods recommended by the NICHD task force were used to identify SARS-CoV-2 and its viral receptors in the placentas and fetal tissue (Antoun et al., 2020) [1] RESULTS: Compared with the surviving twin, we found a more severe intervillous necrosis and a relatively low detection of ACE2 membranous expression in the syncytiotrophoblasts of the female twin that succumbed. DISCUSSION: The interactions of SARS-CoV-2 and ACE2 at the maternal fetal interface within the placenta may play a significant role in perinatal loss, and the effects of fetal sex and gestational age at time of infection need to be explored further.

Psychosocial characteristics of patients evaluated for kidney transplant and associations with functional and frailty metrics at a veterans affairs hospital.

BACKGROUND: The effect of psychosocial problems on listing outcomes and potential interactions with functional metrics is not well-characterized among Veteran transplant candidates. METHODS: The results from psychosocial evaluations, frailty metrics, and biochemical markers were collected on 375 consecutive Veteran kidney transplant candidates. Psychosocial diagnoses were compared between patients listed or denied for transplant. Functional abilities were compared among patients with or without psychosocial diagnoses and then evaluated based on reason for denial. RESULTS: Eighty-four percent of patients had a psychosocial diagnosis. Common issues included substance or alcohol abuse (62%), psychiatric diagnoses (50%), and poor adherence (25%). Patients with psychiatric diagnoses, cognitive impairments, and poor adherence were more likely to be denied for transplant (P < .05). Patients with depression, PTSD, and anxiety did not have worse functional ability, but experienced more exhaustion than patients without these problems. Patients denied for medical but not purely psychosocial reasons had worse troponin and functional metrics compared with listed patients. CONCLUSION: Over 80% of patients with a psychosocial diagnosis were listed; however, poor adherence was a particularly important reason for denial for purely psychosocial reasons. Patients with psychosocial diagnoses generally were not more functionally limited than their counterparts without psychosocial diagnoses or those listed for transplant.

Feasibility, preliminary efficacy, and accessibility of a twitter-based social support group vs Fitbit only to decrease sedentary behavior in women.

BACKGROUND: Health behavior change interventions delivered by social media allow for real-time, dynamic interaction, peer social support, and experimenter-provided content. AIMS: We tested the feasibility, acceptability, and preliminary efficacy of a novel Twitter-based walking break intervention with daily behavior change strategies and prompts for social support, combined with a Fitbit, vs. Fitbit alone. METHODS: In a 2-group pilot, 45 sedentary women from a heart clinic were randomized to Twitter + Fitbit activity tracker (Tweet4Wellness, n = 23) or Fitbit-only (control, n = 22). All received a Fitbit and 13 weeks of tailored weekly step goals. Tweet4Wellness consisted of a private Twitter support group, with daily automated behavior change "tweets" informed by behavior change theory, and encouragement to communicate within the group. Feasibility outcomes included recruitment and enrollment numbers, implementation challenges, and number and type of help requests from participants throughout the study period. Preliminary efficacy outcomes provided by Fitbit data were sedentary minutes, number of hours with >250 steps, maximum sitting bout, weighted sedentary median bout length, total steps, intensity minutes (>3.0 METS), and ratio of time spent sitting-to-moving. Acceptability outcomes included level of Twitter participation within Tweet4Wellness, and Likert scale plus open-ended survey questions on enjoyment and perceived effectiveness of intervention components. Survey data on acceptability of the features of the intervention were collected at 13 weeks (end-of-treatment [EOT]) and 22 weeks (follow-up). RESULTS: The study was feasible, with addressable implementation challenges. Tweet4Wellness participants changed significantly from baseline to EOT relative to control participants on number of active hours p = .018, total steps p = .028, and ratio of sitting-to-moving, p = .014. Only sitting-to-moving was significant at follow-up (p = .047). Among Tweet4Wellness participants, each tweet sent during treatment was associated with a 0.11 increase in active hours per day (p = .04) and a 292-step increase per day (p < .001). Tweet4Wellness participants averaged 54.8 (SD = 35.4) tweets, totaling 1304 tweets, and reported liking the accountability and peer support provided by the intervention. CONCLUSION: A Twitter-delivered intervention for promoting physical activity among inactive women from a heart clinic was feasible, acceptable, and demonstrated preliminary efficacy in increasing daily active hours, daily total steps, and the ratio of sitting-to-moving from pre to post for the intervention compared with the control. Lessons learned from this pilot suggest that the next study should expand the recruitment pool, refine the intervention to increase group engagement, and select active hours, total steps, and ratio of sitting-to-movement as primary sedentary behavior measures.

Analysis of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profile in the Large Helical Device.

The analysis method of the Motional Stark Effect (MSE) diagnostic to measure the rotational transform and current profiles in the Large Helical Device has been improved. This was done by using the Variational Moments Equilibrium Code to calculate an equilibrium database for various pressure profiles and current profiles. This method looks for the radial profile of the rotational transform in the equilibrium database that gives the best fit to the polarization angle profiles measured with the MSE diagnostic. This analysis improves the measurements of rotational transform, especially near the magnetic axis, where the sensitivity of the polarization angle measurements becomes low and the uncertainty due to error in the estimation of the Pfirsch-Schlüter current becomes large. The radial profiles of the rotational transform and current profiles for Electron Cyclotron Current Drive and Neutral Beam Current Drive are obtained in the new analysis method with a sufficiently high accuracy to discuss the discrepancy of the current density profiles between the measurements and the calculations.

Coercive parenting: modifiable and nonmodifiable risk factors in parents of children with developmental disabilities.

BACKGROUND: Parents of children with developmental or intellectual disabilities tend to report greater use of coercive parenting practices relative to parents of typically developing children, increasing the risk of adverse child outcomes. However, to date, there is limited research exploring the role and relative contribution of modifiable and nonmodifiable risk factors in parents of children with a disability. The present study aimed to explore the role of various modifiable and nonmodifiable parenting, family and sociodemographic factors associated with the use of coercive parenting practices in parents of children with a disability. METHODS: Caregivers (N = 1392) enrolled in the Mental Health of Young People with Developmental Disabilities (MHYPeDD) programme in Australia completed a cross-sectional survey about their parenting and their child aged 2-12 years with a disability. Measures covered a range of domains including relevant demographic and family background, use of coercive parenting practices, intensity of child behavioural difficulties and questions relating to parent and family functioning such as parental self-efficacy, adjustment difficulties and quality of family relationships. RESULTS: Parents of older children, those who were younger at the birth of their child, and parents who were co-parenting or working reported more use of coercive parenting practices. Greater intensity of child difficulties, poorer parental self-efficacy and parent-child relationships, and more parental adjustment difficulties were also significantly associated with more use of coercive parenting. Examination of the relative contribution of variables revealed parent-child relationship was a key contributing factor, followed by intensity of child behaviour problems, parent adjustment and parent confidence. CONCLUSIONS: These findings highlight a range of factors that should be targeted and modified through upstream prevention programmes and further inform our understanding of how coercive practices may be influenced through targeted parenting interventions.

Frailty measures can be used to predict the outcome of kidney transplant evaluation.

BACKGROUND: Experience incorporating frailty and functional metrics in the transplant evaluation process is limited. We hypothesized that simple tests correlate with kidney transplant listing outcomes. METHODS: Frailty metrics, treadmill ability, pedometer data, troponin T, and brain natriuretic peptide were collected on 375 consecutive kidney transplant evaluations between July 2015 and December 2018. Patients initially denied were compared with those listed or deferred. Frailty metrics included handgrip, chair sit-stand, up-and-go, chair sit-reach, and questions related to exhaustion. RESULTS: A total of 95 (25%) patients were initially denied. Those denied were older, diabetic, or had higher body mass indexes. Frailty metrics including chair sit-stand, up-and-go, chair sit-reach, grip strength, and exhaustion; biochemical markers troponin and brain natriuretic peptide; and pedometer and treadmill ability were all significantly associated with denial (P < .001). The best order three model combining parsimony and predictiveness included treadmill ability, exhaustion, and troponin. The most predictive pedometer model also included exhaustion and up-and-go. The best order three model excluding biochemical markers, pedometer, and treadmill results included up-and-go, exhaustion, and chair sit-reach. CONCLUSION: Outcomes after on-site kidney transplant evaluation strongly correlated with the results of common clinical and functional frailty metrics.

Infiltrating Kaposi sarcoma presenting as acute kidney injury: An unexpected consequence of deliberate hepatitis C-positive organ transplantation.

Kaposi sarcoma (KS) following kidney transplantation can result from recipient reactivation of latent human herpesvirus 8 (HHV-8) infection or activation of donor-acquired HHV-8 infection. Post-transplant KS typically manifests with cutaneous pathology, but rare cases of renal allograft involvement have been reported. We describe two cases of donor-derived HHV-8 infection in two hepatitis C (HCV) viremia-negative transplant recipients who each received a kidney from a donor with HCV viremia. One recipient did not develop KS while the other presented with acute kidney injury caused by extensive KS infiltration of the renal parenchyma and metastatic disease. This report reviews the literature for cases of KS involving the renal allograft and highlights an unexpected consequence of deliberate HCV-positive organ transplantation.

Development and implementation of a Telenephrology dashboard for active surveillance of kidney disease: a quality improvement project.

BACKGROUND: Kidney disease accounts for more than 49 billion dollars in healthcare expenditures annually. Early detection and intervention may reduce the burden of disease. We describe a quality improvement project to develop a telenephrology dashboard that proactively monitors kidney disease. METHODS: One hundred eighty-four thousands Veterans within the Iowa City Veterans Affairs Health Care System were eligible for telenephrology consultation. The dashboard accessed the charts of 53,085 Veterans at risk for kidney disease. We utilized Lean-Six Sigma tools and principles and the Define-Measure-Analyze-Improve-Control Framework to develop and deploy a telenephrology dashboard in 4 community-based outpatient clinics (CBOCs). The primary measure was the number of days to complete consultation. Secondary measures included number of electronic consultations per month, distance and cost of Veteran travel saved, and number of steps for completion of consult. RESULTS: The data of 1384 Veterans at the 4 CBOCs were analyzed by the telenephrology dashboard, of which 459 generated telenephrology consults. The number of days to complete any type of consultation was unchanged (48.9 days in 2019, compared to 41.6 days in 2017). The average Veteran saved between $21.60 to $63.90 per trip to Iowa City. Between March 2019 and August 2019, there were 27.3 telenephrology consults per month. The number of steps needed to complete the consult request was decreased from 13 to 9. CONCLUSIONS: Utilization of the telenephrology dashboard system contributed to an increase in consultations completed through electronic means without decreasing face-to-face consults. Electronic consults now outnumber traditional face-to-face consultations at our institution. Telenephrology consultation improved early detection and identification of kidney disease and saved time and costs for Veterans in travel, but did not decrease the average number of days to complete consultation requests.

Retail refrigerated probiotic foods and their association with evidence of health benefits.

Probiotic usage in food is widespread and growing. The objective of this study was to determine the percentage of probiotic food products sold in the refrigerated section of retail grocery stores in the Washington DC area that we could link to evidence of any health benefit. We surveyed refrigerated sections of eight large grocery stores representing five national chains for probiotic products. Based on declared probiotic composition (strain and count) for each product, we searched PubMed for controlled trials that provided evidence of any health benefit. Our assessment showed that 49% (22 out of 45 distinct probiotic foods) could be linked to evidence supporting a health benefit. All products indicating strain composition could be linked to evidence. Our study suggests that consumers have a reasonable likelihood of purchasing a refrigerated probiotic food with evidence, but room for improvement exists.

Accuracy and precision of non-invasive cardiac output monitoring by electrical cardiometry: a systematic review and meta-analysis.

Cardiac output monitoring is used in critically ill and high-risk surgical patients. Intermittent pulmonary artery thermodilution and transpulmonary thermodilution, considered the gold standard, are invasive and linked to complications. Therefore, many non-invasive cardiac output devices have been developed and studied. One of those is electrical cardiometry. The results of validation studies are conflicting, which emphasize the need for definitive validation of accuracy and precision. We performed a database search of PubMed, Embase, Web of Science and the Cochrane Library of Clinical Trials to identify studies comparing cardiac output measurement by electrical cardiometry and a reference method. Pooled bias, limits of agreement (LoA) and mean percentage error (MPE) were calculated using a random-effects model. A pooled MPE of less than 30% was considered clinically acceptable. A total of 13 studies in adults (620 patients) and 11 studies in pediatrics (603 patients) were included. For adults, pooled bias was 0.03 L min-1 [95% CI - 0.23; 0.29], LoA - 2.78 to 2.84 L min-1 and MPE 48.0%. For pediatrics, pooled bias was - 0.02 L min-1 [95% CI - 0.09; 0.05], LoA - 1.22 to 1.18 L min-1 and MPE 42.0%. Inter-study heterogeneity was high for both adults (I2 = 93%, p < 0.0001) and pediatrics (I2 = 86%, p < 0.0001). Despite the low bias for both adults and pediatrics, the MPE was not clinically acceptable. Electrical cardiometry cannot replace thermodilution and transthoracic echocardiography for the measurement of absolute cardiac output values. Future research should explore it's clinical use and indications.

Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains.

Understanding the mechanism(s) underpinning drug resistance could lead to novel treatments to reverse the increased tolerance of a pathogen. In this study, paromomycin (PMM) resistance (PMMr) was induced in three Nepalese clinical strains of Leishmania donovani with different inherent susceptibilities to antimony (Sb) drugs by stepwise exposure of promastigotes to PMM. Exposure to PMM resulted in the production of mixed populations of parasites, even though a single cloned population was used at the start of selection. PMM 50% inhibitory concentration (IC50) values for PMMr parasites varied between 104 and 481 µM at the promastigote stage and 32 and 195 µM at the intracellular amastigote stage. PMM resistance was associated with increased resistance to nitric oxide at the amastigote stage but not the promastigote stage (P < 0.05). This effect was most marked in the Sb-resistant (Sbr) PMMr clone, in which PMM resistance was associated with a significant upregulation of glutathione compared to that in its wild type (P < 0.05), although there was no change in the regulation of trypanothione (detected in its oxidized form). Interestingly, PMMr strains showed an increase in either the keto acid derivative of isoleucine (Sb intermediate PMMr) or the 2-hydroxy acids derived from arginine and tyrosine (Sb susceptible PMMr and Sbr PMMr). These results are consistent with the recent finding that the upregulation of the branched-chain amino acid aminotransferase and d-lactate dehydrogenase is linked to PMMr In addition, we found that PMMr is associated with a significant increase in aneuploidy during PMM selection in all the strains, which could allow the rapid selection of genetic changes that confer a survival advantage.

Validation of an ultra-high-performance liquid chromatography-mass spectrometry method for the quantification of cysteinylated aldehydes and application to malt and beer samples.

This paper describes the method validation for the simultaneous determination of seven cysteinylated aldehydes, i.e. 2-substituted 1,3-thiazolidines-4-carboxylic acids, using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Authentic reference compounds were first synthesized for identification and quantification purposes. Moreover, nuclear magnetic resonance (1H NMR and 13C NMR) was applied for verification of their structure, while ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied for estimation of the purity. The method for quantification of cysteinylated aldehydes in model solutions has been validated according to the criteria and procedures described in international standards. The synthesized compounds were successfully identified via UHPLC-MS by comparing retention time and MS spectra with the commercial reference compounds. Method validation revealed good linearity (R2 > 0.995) over the range of 0.4-2.2 µg/L to approximately 1000 µg/L, depending on the analyte. The limits of quantification varied from 0.9 to 4.3 µg/L depending on the nature of the compound. Furthermore, evaluation of the method showed good accuracy and stability of the standard solutions. Reported chromatographic recoveries ranged from 112 to 120%. Consequently, the currently described method was applied on malt and beer samples. For the first time, quantification of cysteinylated aldehydes was obtained in malt. In contrast, in fresh beers unambiguous identification of these compounds was not achieved.

BK virus histopathologic disease severity does not predict allograft outcome in renal transplant recipients.

AIMS: BK polyomavirus nephropathy (BKPyVN) is an important cause of allograft failure after renal transplantation. Despite early screening for the virus, allograft loss from BKPyVN is still experienced in up to 14% of all renal transplant recipients. The aim of this study was to investigate the association between BKPyVN histopathologic disease severity and allograft outcome at our center. METHODS: Kidney transplant recipients who had undergone transplantation between 2002 and 2014 with biopsy proven BKPyVN were eligible for this retrospective study. Each biopsy was re-evaluated by a single pathologist blinded to the clinical data and scored according to the Banff criteria for rejection and BKPyVN. Serum creatinine and BK viral load at the time of biopsy diagnosis as well as allograft outcomes to include allograft survival and serum BK viremia resolution were collected for each recipient to determine if BK virus histopathologic disease severity could predict allograft outcome. RESULTS: Twenty cases of BKPyVN were identified from 1031 total renal transplants performed. There was no statistical association between allograft loss and BKPyVN histopathology (p = 0.49). There was also no statistical association between BKPyVN histopathology and BK viral load at the time of biopsy diagnosis (p = 0.38) or serum BK viremia resolution (p = 0.16). CONCLUSIONS: BKPyVN histopathology does not appear to be useful in predicting renal allograft outcome in those recipients diagnosed with BKPyVN which is in contrast to some previously published data.

[Practice of parenting and related factors on children aged 0-5 in the urban areas of China].

Objective: To characterize the relations between the practice of parenting and associated factors on children (0-5 years old) in urban areas of China, in order to provide evidence for promoting the early development of children and to provide positive guidance and service programs on parenting. Methods: A total of 4 515 parents from 15 cities (14 provinces) were surveyed with a self-administered questionnaire. Parenting and Family Adjustment Scales (PAFAS) was used, including parameters as: consistency and coercive parenting, positive encouragement, parent-child relationship and parental emotion adjustment, family relationship and parental teamwork aspects, etc. Both single factor analysis and multiple linear regression were used to examine the associations between parenting practice, individual, parental and family factors. Results: The mean score of PAFAS was 21.00 (15.00-28.00), associated with factors as children's age, only-child family, premature delivery, father's education level, confidence on parenting, problems regarding the parental mood, annual family income, family structure and behavior on seeking professional help, etc. Results showed that there were big differences on the practice of parenting in China and influenced by variety of factors. Conclusions: The general situation of parenting was well, in the urban areas of China. The practice of parenting was associated with a series of individual, parental and family factors. Programs on improving the parenting skills and promoting the early development of children, should be highlighted.