The mechanisms that determine patterns of species dispersal are important factors in the production and maintenance of biodiversity. Understanding these mechanisms helps to forecast the responses of ...species to environmental change. Here, we used a comparative framework and genomewide data obtained through RAD‐Seq to compare the patterns of connectivity among breeding colonies for five penguin species with shared ancestry, overlapping distributions and differing ecological niches, allowing an examination of the intrinsic and extrinsic barriers governing dispersal patterns. Our findings show that at‐sea range and oceanography underlie patterns of dispersal in these penguins. The pelagic niche of emperor (Aptenodytes forsteri), king (A. patagonicus), Adélie (Pygoscelis adeliae) and chinstrap (P. antarctica) penguins facilitates gene flow over thousands of kilometres. In contrast, the coastal niche of gentoo penguins (P. papua) limits dispersal, resulting in population divergences. Oceanographic fronts also act as dispersal barriers to some extent. We recommend that forecasts of extinction risk incorporate dispersal and that management units are defined by at‐sea range and oceanography in species lacking genetic data.
Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of ...adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut‐off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best‐studied technique for assessing sarcopenia in patients with cirrhosis. Cut‐off values for sarcopenia, defined as SMI < 50 cm2/m2 in male and < 39 cm2/m2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.
To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes ...in frailty over time and their association with death/delisting in patients too sick for liver transplantation.
Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk.
We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35–3.09).
Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
Display omitted
•In patients with cirrhosis, changes in frailty were significantly associated with death/delisting.•Patients with cirrhosis who experienced improvements in frailty over time had a lower risk of death/delisting.•Our data support the longitudinal measurement of frailty in patients with cirrhosis.•This study lays the foundation for interventional work aimed at reversing frailty.
Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this ...study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition.
In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference < 23 cm and dominant handgrip strength < 30 kg. Anthropometric measurements were obtained. Appetite was assessed using the Simplified Nutrition Appetite Questionnaire (SNAQ) score. Fasting levels of serum adipokines, cytokines, and hormones were determined using Luminex assays. Logistic regression analysis was used to determine features independently associated with malnutrition.
Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition.
Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease.
Zinc and calcium ions play important roles in the biosynthesis and storage of insulin. Insulin biosynthesis occurs within the beta-cells of the pancreas via preproinsulin and proinsulin precursors. ...In the golgi apparatus, proinsulin is sequestered within Zn(2+)- and Ca(2+)-rich storage/secretory vesicles and assembled into a Zn(2+) and Ca(2+) containing hexameric species, (Zn(2+))(2)(Ca(2+))(Proin)(6). In the vesicle, (Zn(2+))(2)(Ca(2+))(Proin)(6) is converted to the insulin hexamer, (Zn(2+))(2)(Ca(2+))(In)(6), by excision of the C-peptide through the action of proteolytic enzymes. The conversion of (Zn(2+))(2)(Ca(2+))(Proin)(6)to (Zn(2+))(2)(Ca(2+))(In)(6) significantly lowers the solubility of the hexamer, causing crystallization within the vesicle. The (Zn(2+))(2)(Ca(2+))(In)(6) hexamer is an allosteric protein that undergoes ligand-mediated interconversion among three global conformation states designated T(6), T(3)R(3) and R(6). Two classes of allosteric sites have been identified; hydrophobic pockets (3 in T(3)R(3) and 6 in R(6)) that bind phenolic ligands, and anion sites (1 in T(3)R(3) and 2 in R(6)) that bind monovalent anions. The allosteric states differ widely with respect to the physical and chemical stability of the insulin subunits. Fusion of the vesicle with the plasma membrane results in the expulsion of the insulin crystals into the intercellular fluid. Dissolution of the crystals, dissociation of the hexamers to monomer and transport of monomers to the liver and other tissues then occurs via the blood stream. Insulin action then follows binding to the insulin receptors. The role of Zn(2+) in the assembly, structure, allosteric properties, and dynamic behavior of the insulin hexamer will be discussed in relation to biological function.
To assess the natural history and contemporary outcomes in pregnancies complicated by previable preterm premature rupture of membranes (PROM).
Retrospective study of all women with a singleton or ...twin pregnancy admitted to a single tertiary referral center who experienced preterm PROM between 20 and 23 6/7 weeks of gestation during 2004-2014 and underwent expectant management. Women electing termination of pregnancy and pregnancies complicated by major fetal anomalies were excluded. Severe neonatal morbidity was defined as a composite of bronchopulmonary dysplasia, severe neurologic injury, or severe retinopathy of prematurity. Long-term follow-up to a corrected age of 18-21 months was available for the majority of surviving neonates.
Of the 140 neonates born to women with previable preterm PROM during the study period, 104 were eligible for the study. Overall 51 (49.0%, 95% confidence interval CI 39.4-58.6%) newborns survived to discharge, of whom 24 (47.1%, 95% CI 33.4-60.8%) experienced severe neonatal morbidity. The overall rate of long-term morbidity among surviving neonates was 23.3% (95% CI 11.7-34.9%) and was significantly higher among neonates who previously experienced severe neonatal morbidity compared with those who did not (39.1% compared with 10.0%, P=.04). The only two factors that were significantly associated with overall survival and survival without severe neonatal morbidity were gestational age at preterm PROM of 22 weeks or greater (adjusted odds ratio OR 12.2, 95% CI 3.3-44.8 and adjusted OR 4.8, 95% CI 1.2-19.3, respectively) and a latency period of greater than 7 days (adjusted OR 10.1, 95% CI 3.2-31.6, and adjusted OR 6.7, 95% CI 2.2-21.0, respectively). Expectant management was associated with maternal risks including placental abruption (17.3%, 95% CI 10.0-24.6%) and sepsis (4.8%, 95% CI 0.7-8.9%).
Expectant management in pregnancies complicated by previable preterm PROM between 20 and 23 6/7 weeks of gestation is associated with an overall neonatal survival rate of 49.0%, high risk of short- and long-term severe morbidity among survivors, and carries considerable maternal risks.
The COVID-19 pandemic has exacerbated and highlighted gaps in the US supply chain, including a critical shortfall of truckers (i.e., those holding a commercial driver's license CDL). In response, in ...April 2022 the White House launched a government, industry, union, and veterans service organization collaboration, Task Force Movement, to recruit 80 000 veterans into the trucking industry.1 Ten percent of employed US veterans already work as truckers, and many veterans complete their military service with the capacity and skills to succeed in the industry. As physicians for veterans, we believe that Task Force Movement's initiative to recruit new veteran truckers to improve the supply chain crisis presents an important opportunity to synchronize the effort with strong action to mitigate truckers' health risks from a second American crisis, the metabolic syndrome.The cardiovascular, endocrine, hepatic, and renal complications of the metabolic syndrome are especially prevalent and severe among truckers. Two thirds of truckers are obese, and the majority have the additional metabolic risk factors of sedentary activity; long, stressful work hours; little sleep; and high-salt, high-fat diets.2,3 The life expectancy of unionized US male truckers in 2000 was 61.3 years (vs 73.2 years for all US men), with ischemic heart disease as the leading cause of excess mortality.4 If this reported premature mortality were to remain unchanged, the 80 000 new veteran truckers being recruited today would face a loss of 952 000 life-years.To mitigate the health risks oftrucking in general, and specifically to ensure that veterans are not put at greater risk by becoming truckers, it is critical to provide them with the tools to engage in preemptive, effective risk assessment and mitigation. Risk mitigation is a welldefined and widely taught military practice that most veterans have routinely used during their service to ensure health protection and mission success.5 We believe that improved trucker health and risk mitigation require taking a series of specific actions in occupational health, public health policy, and education and advocacy.
Frailty with sarcopenia in cirrhosis causes liver transplant wait‐list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively ...assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait‐listed patients self‐assessed their performance of ordinary physical tasks using the Rosow‐Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate‐vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate‐vigorous activity was significantly associated with 9 wait‐list deaths (P = 0.004). Compared with a range of 7000‐13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow‐Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait‐listed for transplantation is highly sedentary. Self‐assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324–1332 2016 AASLD.
The Triple Aim is widely regarded as the quality improvement gold standard that enhances population health, lowers costs, and betters individual care. There have been no large-scale, sustained ...demonstrations of such improvement in healthcare. Illustrating the Triple Aim using relevant extremely premature infant outcomes might highlight interwoven proficiency and efficiency complexities that impede sustained value progress.
Ten long-term collaborating neonatal intensive care units (NICU) in the Vermont Oxford Network calculated the Triple Aim in 23
to 27
-week infants using three surrogate measures: (1) population health/x-axis-eight major morbidity rates as a composite, risk-adjusted metric; (2) cost/y-axis-total hospital length of stay; and (3) individual care/z-axis-mortality, then illustrated this relationship as a sphere within a three-dimensional cube.
Three thousand seven hundred six infants born between January 1, 2014 and December 31, 2019, with mean (standard deviation) gestational age of 25.7 (1.4) weeks and birth weight of 803 (208) grams were analyzed. Triple Aim three-axis cube positions varied inconsistently comparing NICUs. Each NICUs' sphere illustrated mixed x- and z-axis movement (clinical proficiency), and y-axis movement (cost efficiency). No NICU demonstrated the theoretically ideal Triple Aim improvement in all three axes. Backward movement in at least one axis occurred in eight NICUs. The whole-group Triple Aim sphere moved forward along the x-axis (better morbidities metric), but moved backward in the y-axis length of stay and z-axis mortality measurements.
Illustrating the Triple Aim gold standard as extreme prematurity outcomes reveals complexities inherent to simultaneous attempts at improving interwoven quality and cost outcomes. Lack of progress using relevant Triple Aim parameters from our well-established collaboration highlights the difficulties prioritizing competing outcomes, variable potentially-better-practice applications amongst NICUs, unmeasured biologic interactions, and obscured cultural-environmental contexts that all likely affect care. Triple Aim excellence, if even remotely possible, will necessitate scalable, evidence-based methodologies, pragmatism regarding inevitable trade-offs, and wise constrained-resource decisions.
· The Triple Aim gold standard is elusive. There is no demonstration of sustained, large-scale success in healthcare and our quality improvement network has previously published benchmark extreme prematuritymorbidity improvements.. · Extreme prematurity outcomes illustrated as the Triple Aim show uneven results in relevant surrogate parameters and Triple Aim achievement, if even possible, will necessitate evidence-based methodologies that are scalable.. · Pragmatism, inevitable trade-offs, and wise constrained-resource decisions are required for Triple Aim success..
PDF
