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Objective: To determine the influence of operating room familiarity on surgeon stress., Background: Regulating surgeon stress may improve patient safety. This study evaluated how assisting surgeon and operating room familiarity influence intraoperative heart rate variability among surgeons., Methods: Attending surgeons from seven specialties within four university hospitals in France were enrolled from 11/01/20-12/31/21. Vagal tone, an indicator of stress derived from heart rate variability, was assessed during the first five minutes after incision using the root mean square of successive differences (RMSSD). Higher RMSSD values indicate greater vagal tone. Team familiarity was quantified as the cumulative time the attending and assisting surgeons had operated together in the past, while operating rooms in which the surgeon conducted >10% of their operations were termed familiar. The effect of each on the RMSSD was assessed via a linear mixed-effect model adjusting for the random effect of the surgeon and possible confounders., Results: Overall, 643 surgeries performed by 37 surgeons were included. Median surgeon age was 49 years, 29(78.4%) were male, and 22(59.5%) were professors. Surgeons spent an average of 21.2 hours with the assisting surgeon prior to surgery and conducted 585(91.0%) of their operations in a familiar operating room. For every 10 additional hours spent operating together, ln(RMSSD) significantly increased by 0.018 (95%CI: 0.003 to 0.033, P=0.016). Familiar operating rooms also tended to increase surgeon ln(RMSSD) [0.098 (95%CI: -0.007 to 0.203, P=0.068)]., Conclusion: Familiar assisting surgeons, and potentially operating rooms, increased surgeon vagal tone. Maintaining a stable operating room environment may improve surgeon stress and patient care., Competing Interests: Disclosures/Conflicts of Interest: The authors report no disclosures or financial conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Epidemiological data predicts that sub-Saharan Africa will have the largest increase in type 2 diabetes (T2D) prevalence over the next two decades. Metabolomics studies have identified biomarkers that could improve T2D diagnosis and follow-up. However, no studies have characterized the metabolome of people from sub-Saharan Africa. Plasma samples from Senegalese individuals with T2D ( n = 31) or without T2D ( n = 34) were compared using measures of oxidative stress damage and plasma antioxidant enzyme activity and mass-spectrometry-based metabolomics analyses. Results showed that glucose, lactate, and tricarboxylic acid metabolites (fumarate, malate, and succinate) were increased in the T2D group, suggesting alterations in glycolysis and mitochondrial dysfunction. Several amino acids (leucine, isoleucine, valine, and tryptophan) and long-to-very-long-chain fatty acids were higher in the T2D group. Finally, elevated levels of ketone bodies and acylcarnitines were observed along with increased levels of oxidative stress damage and antioxidant activity. In conclusion, the T2D group exhibited modifications in metabolites previously shown to be associated with T2D risk in populations from other areas of the world. Future studies should seek to test whether these metabolites could be used as predictors for T2D-related complications in people from sub-Saharan Africa.

The purpose of the study was to assess sex-related differences in resting mechanical properties and adaptations of skeletal muscles and tendons in response to trail running races of different distances using multi-site shear wave elastography assessments of the lower limb, force capacity and blood analyses. Sex differences in resting mechanical properties of knee extensor and plantar flexor muscles and tendons were characterized by shear wave velocity (SWV) measurements in healthy males (N = 42) and females (N = 25) trained in long-distance running. Effects of running distance on muscle and tendon properties were assessed in short (<60 km, N = 23) vs. long (>100 km, N = 26) distance races. Changes in isometric maximal voluntary contraction torque, serum C-reactive protein and creatine kinase activity were also quantified after running races. Higher SWV of relaxed triceps surae muscle was detected in females as compared to males before running races (+4.8%, p = 0.006), but the significant increases in triceps surae muscle group (+7.0%, p = 0.001) and patellar tendon SWV (+15.4%, p = 0.001) after short-distance races were independent of sex. A significant decrease in triceps surae muscle SWV was found after long-distance races in the whole experimental population (-3.1%, p = 0.049). Post-races increase in C-reactive protein and creatine kinase activity were significantly correlated to the relative decreases in triceps surae and quadriceps femoris skeletal muscle SWV (ρ = -0.56, p = 0.001 and ρ = -0.51, p = 0.001, respectively). Resting mechanical properties of muscles and tendons are affected by sex, and adaptations to trail races are related to running distance. Exercise-induced changes in resting skeletal muscle mechanical properties are associated with enhanced indirect markers of inflammation and muscle damage., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To characterize quantitative studies on coaching interventions for professional surgeons to understand how surgical coaching is defined; examine how different coaching programs are designed, implemented, and evaluated; and identify any relevant research gaps., Background: Surgical coaching is gaining attention as an approach that could help surgeons optimize performance and improve overall wellbeing. However, surgical coaching programs and definitions of coaching vary widely between studies., Methods: A systematic literature search of PubMed, Scopus, Web of Science, CENTRAL, clinicaltrials.gov, and WHO ICTRP was conducted according to the PRISMA-ScR framework to identify studies and registered clinical trials written in English. Original quantitative studies on coaching interventions for professional surgeons were included. Characteristics of the coachees, coaching programs, study designs, outcomes, and findings were charted and analyzed., Results: From 2589 references, 8 studies (6 published; 2 registered trials) met inclusion criteria. Published studies targeted technical or nontechnical skills, included 2-26 surgeons as coachees, and used coaches who were surgeons. Two studies demonstrated that surgeons react positively to coaching. Studies showed inconsistent effects on technical/nontechnical skills. Only two studies measured patient adverse events and reported no significant positive impacts. The registered randomized trials targeted surgeons' physiological parameters or wellbeing and used professional coaches. These trials measure surgeon and patient outcomes., Conclusions: There is an emerging interest in coaching programs to improve surgeons' performance by targeting their professional skills and personal factors. However, more randomized trials are needed to evaluate the impact of coaching interventions on patient outcomes and surgeon wellness., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients., (© 2021 The Authors.)

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals . In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA., (Copyright © 2020 Nader, Romana, Guillot, Fort, Stauffer, Lemonne, Garnier, Skinner, Etienne-Julan, Robert, Gauthier, Cannas, Antoine-Jonville, Tressières, Hardy-Dessources, Bertrand, Martin, Renoux, Joly, Grau and Connes.)

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

Storage lesion-induced, red cell-derived microvesicles (RBC-MVs) propagate coagulation by supporting the assembly of the prothrombinase complex. It has also been reported that RBC-MVs initiate coagulation via the intrinsic pathway. To elucidate the mechanism(s) of RBC-MV-induced coagulation activation, the ability of storage lesion-induced RBC-MVs to activate each zymogen of the intrinsic pathway was assessed in a buffer system. Simultaneously, the thrombin generation (TG) assay was used to assess their ability to initiate coagulation in plasma. RBC-MVs directly activated factor XII (FXII) or prekallikrein, but not FXI or FIX. RBC-MVs initiated TG in normal pooled plasma and in FXII- or FXI-deficient plasma, but not in FIX-deficient plasma, suggesting an alternate pathway that bypasses both FXII and FXI. Interestingly, RBC-MVs generated FIXa in a prekallikrein-dependent manner. Similarly, purified kallikrein activated FIX in buffer and initiated TG in normal pooled plasma, as well as FXII- or FXI-deficient plasma, but not FIX-deficient plasma. Dual inhibition of FXIIa by corn trypsin inhibitor and kallikrein by soybean trypsin inhibitor was necessary for abolishing RBC-MV-induced TG in normal pooled plasma, whereas kallikrein inhibition alone was sufficient to abolish TG in FXII- or FXI-deficient plasma. Heating RBC-MVs at 60°C for 15 minutes or pretreatment with trypsin abolished TG, suggesting the presence of MV-associated proteins that are essential for contact activation. In summary, RBC-MVs activate both FXII and prekallikrein, leading to FIX activation by 2 independent pathways: the classic FXIIa-FXI-FIX pathway and direct kallikrein activation of FIX. These data suggest novel mechanisms by which RBC transfusion mediates inflammatory and/or thrombotic outcomes.

Objective: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only., Research Design and Methods: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) ( n = 60), T2D ( n = 52), SCT ( n = 53), and neither T2D nor SCT (control) ( n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured., Results: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this., Conclusions: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension., (© 2018 by the American Diabetes Association.)

In extracorporeal life support (ECLS), there are two main types of oxygenators in clinical use for neonates: polymethylpentene (PMP) hollow fiber and polypropylene (PP) hollow fiber. A retrospective study was performed on neonates ( n  = 44) who had undergone ECLS for noncardiac indications from 2009 to 2015. Between the two groups (PMP n  = 21, PP n  = 23), the PP oxygenators failed 91% of the time, whereas the PMP oxygenators failed 43% of the time ( p  < 0.05). Analysis suggests PMP oxygenators are less prone to failure than PP oxygenators, and they require fewer number of oxygenator changes during a neonatal ECLS.

Despite combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to have more systemic inflammation and metabolic disturbances than the general population. These risk factors for atherosclerosis and organ dysfunction may be ameliorated by statins. We retrospectively analyzed 438 cART treated PLWH from the Nutrition For Healthy Living (NFHL) cohort to determine the association between statins and myocardial infarction (MI), stroke, and all-cause mortality as a composite. We used Cox proportional hazards regression as our main analysis. The average age was 44 years, 32% were women, and 67 of the 438 subjects used statins. There was no association between statins and our composite endpoint in two separate models [1.26 (0.57-2.79) in statin history model and 0.93 (0.65-1.32) per year in statin duration model]. The composite outcome was significantly associated with CD4 count, age, and smoking status in both models. CD4 count remained significant even after exclusion of mortality from the composite (HR=0.88, p=0.02). Confounding control via propensity scoring and multiple imputations did not change the results. Statins did not have an effect on MI, stroke, and mortality. Interestingly, CD4 count appears to be an important predictor of these outcomes, even after exclusion of death from the composite.

Hypertriglyceridemia and low high-density lipoprotein (HDL)-cholesterol (HDL-C) may contribute to a presumed accelerated risk for cardiovascular disease in HIV-infected individuals. We evaluated the effect of omega-3 fatty acid treatment on triglycerides, low-density lipoprotein (LDL)-C, HDL-C, and HDL subpopulations. Forty-one HIV-seropositive subjects with hypertriglyceridemia (≥150 mg/dl) on active antiretroviral therapy were enrolled in this placebo-controlled, double-blind, randomized, crossover trial comparing the effects of omega-3 fatty acid treatment (1.9 g EPA and 1.5 g DHA) on triglycerides, LDL-C, HDL-C, and HDL subpopulations. An independent sample t-test was used to assess the study start to posttreatment change for all components. After omega-3 fatty acid treatment, triglyceride levels decreased 63.2±86.9 mg/dl (p<0.001). No significant changes in total cholesterol, LDL-C, or HDL-C were found. Within HDL subpopulations, significant changes were seen in the most atheroprotective HDL particles, α-1, which increased by 2.5±5.6 mg/dl (p<0.05), and preα-1, which increased by 0.6±1.0 mg/dl (p<0.001). Preα-3, a presumably atherogenic HDL particle, decreased by 0.5±0.9 mg/dl (p<0.01). Omega-3 fatty acid treatment significantly lowered triglyceride levels in HIV-positive patients with moderate hypertriglyceridemia. While no study-wide improvements in LDL-C or HDL-C were detected, the HDL subpopulation profile changed in a beneficial way suggesting more cardioprotection after treatment.

Objective: To evaluate changes in cardiovascular disease risk surrogate markers in a longitudinal cohort of HIV-infected adults over 6 years., Design: Internal carotid artery (ICA) and common carotid artery (CCA) intima-media thickness (IMT), coronary artery calcium (CAC), vascular, and HIV risk factors were prospectively examined over 6 years in HIV-infected adults from 2002 to 2010., Setting: Longitudinal cohort study with participants from urban center and surrounding communities., Subjects/participants: Three hundred forty-five HIV-infected participants were recruited from a longitudinal cohort study. Two hundred eleven participants completed the study and were included in this analysis., Main Outcome Measures: Total and yearly ICA and CCA IMT change; CAC score progression., Results: Participants were 27% female and 49% nonwhite; mean age at start was 45 ± 7 years. The median change in ICA and CCA over 6 years was 0.15 mm (0.08, 0.28) and 0.12 mm (0.09, 0.15), respectively. Age, baseline triglycerides ≥150 mg/dL, and pack-years smoking were associated with ICA IMT change; age, cholesterol, nadir CD4 count, and protease inhibitor use were associated with CCA IMT change. Diabetes, HIV viral load, and highly active antiretroviral therapy duration were associated with CAC progression., Conclusions: Carotid IMT and CAC progressed in this HIV-infected cohort. Some HIV-specific characteristics were associated with surrogate marker changes, but the majority of risk factors continue to be traditional. Aggressive identification and management of modifiable risk factors may reduce progression of cardiovascular disease risk in this population.

Background/purpose: There are few studies comparing venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO) in pediatric noncardiac sepsis patients., Methods: Following approval, we reviewed the Extracorporeal Life Support Organization registry data from 1990 to 2008 for patients 0 to 18 years with a diagnosis of sepsis and without diagnosis of congenital heart disease. Survival to discharge was compared between VA and VV ECMO using χ(2) analysis and multivariable logistic regression., Results: Four thousand three hundred thirty-two ECMO runs were reviewed, 3256 VA (75%) and 1076 VV (25%). A majority of VA modality was noted in each decade studied. Overall survival was 68% and was higher in VV (79%) than in VA ECMO (64%, P < .001). Survival decreased with increasing age (73% in newborns ≤ 1 month, 40% in children 1 month to 12 years, and 32% in adolescents >12 years, P < .001). VA ECMO had increased mortality risk after adjustment for age, use of vasoactive agents, and advanced respiratory support (odds ratio, 2.06; 95% confidence interval, 1.74-2.44; P < .001)., Conclusions: These data demonstrate improved survival in VV vs. VA ECMO in select pediatric septic patients without congenital heart disease. When technically feasible, physicians should consider VV ECMO as first therapeutic choice in this patient population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Progression of carotid intima-media thickness (c-IMT) and coronary artery calcium (CAC) are increasingly used as surrogates for vascular risk. We assessed the predictors of c-IMT and CAC progression in a large longitudinal cohort of HIV-infected adults., Methods: c-IMT, CAC scores, and vascular and HIV risk factors were evaluated at baseline and at 3-year follow-up in 255 HIV-infected adults. Multivariate regression was used to determine the predictors of atherosclerotic progression., Results: The mean change in c-IMT per year of follow-up was 0.016 mm for the common and 0.020 mm for the internal. Significant predictors of yearly progression were age, systolic blood pressure, triglycerides, and insulin for common c-IMT and triglycerides >=150 mg/dL, glucose >126 mg/dL, use of glucose-lowering medications, quantitative insulin sensitivity check index, high waist circumference, and current smoking for internal c-IMT. Twenty-eight percent had CAC progression. Of those with zero CAC at baseline, 32% had detectable scores at follow-up. Of those with detectable CAC at baseline, 26% had progression at follow-up. For CAC score, quantitative insulin sensitivity check index, apolipoprotein B, and triglycerides predicted progression. Those with abnormal surrogate markers at baseline were more likely to have the metabolic syndrome reversed and be started on antihypertensive medications over the 3-year follow-up period than those who had no abnormalities at baseline., Conclusions: Although c-IMT and CAC progression rates in HIV-infected patients appear higher than expected for this age and risk groups, traditional cardiovascular risk factors remain the strongest determinants of carotid and coronary atherosclerotic disease progression in HIV-infected patients. Aggressive cardiovascular risk reduction is effective at slowing the atherosclerotic progression in those with preexisting disease.

Introduction: An inanimate technical skills trainer for laparoscopic pyloromyotomy (LP) has not been described. A middle fidelity model, reproducing the three consistent steps in LP, was developed as a component of a teaching module for surgical residents, and tested on medical students, residents, and pediatric surgeons., Materials and Methods: In the first phase of the study, a cohort of 29 pediatric surgeons used the LP model and completed questionnaires about the model's realism and accuracy. Descriptive statistics were used to analyze questionnaire responses. Chi-square tests were performed to determine if level of experience influenced responses. For the second phase of the study, medical students and surgical residents individually participated in the training of cognitive knowledge about hypertrophic pyloric stenosis and skills acquisition for LP. Subject testing consisted of simulator task performance and multiple-choice quiz administration immediately after training and repeated at 8 weeks after training. Data were analyzed by using paired sample t-tests and one-way analyses of variance (ANOVA)., Results: The pediatric surgeons agreed that the model accurately simulated essential components of the pyloromyotomy, and that the model would be an excellent tool to introduce surgeons to LP. A total of 26 students and early surgical residents completed the training and testing. Knowledge-based test performance improved from pre- to postinstruction by 17.45 [standard error of the mean (SEM) + 3.5] (P < 0.001) and from preinstruction to 8 weeks by 4.54 (SEM = 3.2) (P = 0.17). Mean improvement in time of simulator task performance was 85.2 +/- 75.4 seconds. Based on a one-way ANOVA, higher level of training was associated with decreased mean times (P = 0.04)., Conclusions: Face and content validities of the simulation were demonstrated by the pediatric surgeons. An effective training experience was demonstrated with medical students and residents. At 2 months, simulator task-completion rates and task-performance times showed technical skills were retained, whereas, based on test scores, cognitive knowledge was not as well retained.

Background: Elevated serum triglyceride and low HDL-cholesterol concentrations have been reported in persons with HIV., Objective: The effect of a dietary intervention plus n-3 (omega-3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated., Design: Fifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n-3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk., Results: Triglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P

Extracorporeal life support (ECLS) denotes the use of prolonged extracorporeal cardiopulmonary bypass in patients with acute, reversible cardiac or respiratory failure. As technology has advanced, organ support functions other than gas exchange, such as liver, renal, and cardiac support, have been provided by ECLS, and others, such as immunologic support, will be developed. The future of ECLS will include improvements in devices accompanied by circuit simplification and auto-regulation. Such enhancements in technology will allow application of ECLS to populations currently excluded from such support; for example, thromboresistant circuits will eliminate the need for systemic anticoagulation and lead to the use of this technique in premature newborns. As the ECLS technique becomes safer and simpler, and as morbidity and mortality are minimized, criteria for application of ECLS will be relaxed. New approaches to ECLS, such as pumpless arteriovenous bypass, the artificial placenta, arteriovenous CO(2) removal (AVCO(2)R), and intravenous oxygenators (IVOX), will become more commonly applied. Such advances in technology will allow broader and more routine application of ECLS for lung and other organ system failure.

Objective: To compare oxandrolone (OX) or strength training with nutrition alone (NA) for AIDS wasting., Subjects: Fifty patients with AIDS; 47 completing the study., Interventions: Randomization to (1) NA with placebo pills, (2) nutrition with 10 mg of OX administered orally twice a day, or (3) nutrition with progressive resistance training (PRT) for 12 weeks., Main Outcome Measures: Midthigh cross-sectional muscle area (CSMA), physical functioning (PF), costs, and cost-effectiveness in dollars/quality-adjusted life-years (dollars/QALYs)., Results: The OX and PRT subjects had increases in CSMA (7.0% +/- 2.5%, P = 0.01; 5.0% +/- 2.0%, P = 0.04, respectively), although these increases did not differ significantly from the NA arm (NA: 1.0% +/- 1.0%; OX vs. NA: P = 0.09; PRT vs. NA: P = 0.26). Only PRT caused significant improvements in PF (mean +/- SE: 10.4 +/- 3.8 points on a 100-point scale) and 7 measures of strength (P values: 0.04 to <0.001). There were no overall differences between groups in PF change. Among patients with impaired baseline PF, however, OX was significantly less effective than NA and PRT was significantly better than NA. All treatments led to increases in protein intake and performance; NA and PRT also increased caloric intake. The institutional costs per subject in this trial were 983 dollars for NA, 3772 dollars for OX, and 3189 dollars for PRT. At a community-based level of intensity, the institutional costs per QALY were 45,000 dollars (range: 42,000 dollars-64,000 dollars) for NA, 147,000 dollars (range: 147,000 dollars-163,000 dollars) for OX, and 31,000 dollars (range: 21,000 dollars-44,000 dollars) for PRT., Conclusions: OX and PRT induce similar improvements in body composition, but PRT improves quality of life more than nutrition or OX, particularly among patients with impaired PF. PRT was the most cost-effective intervention, and OX was the least cost-effective intervention.

Objective: The aim of this study was to determine the prevalence of gastrointestinal dysfunction in the era of improved treatment of HIV infection., Methods: Gastrointestinal function was studied cross-sectionally in 671 persons with HIV. Absorptive function was measured by a 25-g D-xylose test, a Sudan-III stain for fecal fat on a 100-g fat diet, and serum levels of micronutrients., Results: Eighty-eight percent had at least one abnormality of gastrointestinal function: 47.7% had low D-xylose absorption; 40.3% had a history of liver disease; 38.9% had diarrhea; 28.3% had chronic diarrhea; 22.5% had borderline or low serum vitamin B12 levels; 12.2% had stool pathogens; and 7.2% were hypoalbuminemic. Men were more likely to have low D-xylose absorption, diarrhea, and stool pathogens than women. Intravenous drug users (IVDUs) were more likely to have a history of liver disease and hypoalbuminemia. However, borderline or low vitamin B12 levels were less frequent in IVDUs; they tended to have less diarrhea and a lower prevalence of stool pathogens. Despite less history of liver disease, 14.1% of women were hypoalbuminemic. Differences in patterns of gastrointestinal dysfunction are unlikely to be due to severity of immunosuppression as abnormalities were seen in all risk groups with CD4 >200 cells/mm3. D-xylose absorption below 30 mg/dl, current diarrhea, and borderline levels of vitamin B12 were associated with advanced immunosuppression., Conclusions: Abnormalities of gastrointestinal function are common in the current era of HIV treatment, appear early in the course of HIV infection, and in the absence of diarrhea. Gender and IVDU are important determinants of the type and frequency of gastrointestinal abnormalities.

We examined the relationships between drug abuse, weight, body composition, and dietary intake in persons infected with HIV in a cross-sectional analysis of baseline data from a longitudinal study of nutritional status and HIV. Body composition was measured by bioelectrical impedance analysis. Dietary data were collected by 3-day food records or 24-hour recalls. We analyzed data from 39 current intravenous drug users (IVDU), 103 past intravenous drug users (past-IVDU), 239 users of nonintravenous drugs (users-NIVD), and 61 nonusers (reference category). In the men, there were no differences in weight, body mass index (BMI), or body composition among the drug-use groups. In the women, there was a trend to lower weight and BMI across the drug use categories: IVDU women had lower average weight (-13.7 kg; p = .006), BMI (-5.6 units; p = .003) and less fat mass than non-users (-9.8 kg; p = .0001). In women, drug users had higher weight-adjusted energy intakes than nonusers, whereas in the men both drug using groups, NIVD and IVDU, had higher energy intakes than nonusers. These data suggest that intravenous drug-abuse is associated with lower weight and fat mass in women with HIV infection despite adequate self-reported energy intake.

To test how large pulmonary embolism changes non-steady state CO2 kinetics, the right pulmonary artery (RPA) was occluded in 5 anesthetized, ventilated, thoracotomized dogs. By 1 min after RPA occlusion, CO2 volume exhaled per breath (VCO2,br) decreased from 9.3 +/- 2.8 to 7.0 +/- 2.6 ml and end-tidal PCO2 (PETCO2) decreased from 28.7 +/- 4.2 to 21.8 +/- 3.3 Torr. During the ensuing 70 min, VCO2,br increased back to baseline but PETCO2 was still 13% less than baseline. Both PaCO2 (41.5 +/- 1.7 to 55.1 +/- 8.1 Torr) and PvCO2 (48.2 +/- 1.9 to 62.8 +/- 6.5 Torr) steadily increased and approached equilibrium by 45 min of RPA occlusion. Cardiac output did not significantly change. In summary, RPA occlusion immediately decreased VCO2,br by 25%, due mostly to increased alveolar VD (VDalv). Then, VCO2,br recovered back to baseline as CO2 accumulated in tissues and lung. In contrast, elevated VDalv caused persistent decreased PETCO2, which did not detect recovery of VCO2,br nor increase in PaCO2 during RPA occlusion.

Patients with severe pulmonary embolism can suffer progressive hypercapnia refractory to supramaximal mechanical ventilation, and may require open-thoracic or transvenous emergency embolectomy in addition to anticoagulation and/or thrombolysis. The functional recovery of gas exchange would be signaled by an increase in pulmonary CO2 elimination and decrease in CO2 retention; such data could guide the course of operative embolectomy. Accordingly, we studied five chloralose-urethane anesthetized, mechanically ventilated dogs with open thoraces in which the right pulmonary arteries (RPAs) were reversibly occluded with cloth snares. After waiting for steady state, we abruptly released the snare to restore RPA perfusion and experimentally simulate resolution of pulmonary embolism. For 70 min we serially measure the CO2 volume exhaled per breath (VCO2,br), arterial, mixed venous, and end-tidal PCO2 (PACO2, PVCO2, PETCO2), cardiac output (QT), and the alveolar dead space fraction (VDalv/VTalv = [PaCO2 - PETCO2/PaCO2). RPA reperfusion caused VCO2,br to significantly and abruptly increase from 8.9 +/- 2.7 to 11.6 +/- 3.6 mL; 70 min later VCO2,br had returned to baseline. PaCO2 and PVCO2 steadily decreased during 70 min of RPA reperfusion. PETCO2 increased from 25 +/- 5 to 33 +/- 5 mm Hg immediately after RPA reperfusion, as VDalv/VTalv decreased from 54% +/- 10% to 32% +/- 12%, but PETCO2 was still significantly greater than baseline at 70 min of RPA reperfusion. QT did not significantly change. We conclude that intraoperative measurement of VCO2,br should immediately detect and follow the resolution of CO2 retention in the lung and peripheral tissues after RPA reperfusion. PETCO2 could not detect the decrease of VCO2,br back to baseline because PETCO2 does not measure exhaled volume or the PCO2 waveform.

Objectives: CO2 content can be determined from the Pco2 in an acidified (forces all CO2 into solution) and diluted blood sample. However, Pco2 concentrations measured in conventional blood gas analyzers are only correct for samples with a significant buffer capacity (such as whole blood), so that mixing with the Pco2 in the rinse solution and tubing walls does not significantly change the sample Pco2. This study describes a calibration method and validation data for the Radiometer Medical ABL2 CO2 electrode system to accurately measure unbuffered blood samples used in the determination of blood CO2 content (or other aqueous fluids)., Design: Prospective, criterion standard., Setting: Laboratory., Measurements and Main Results: Blood samples (0.4 mL) were acidified and diluted with 0.2 M lactic acid. After measuring Pco2, CO2 content was calculated using the CO2 solubility coefficient and the dilution factor of 20. CO2 content was determined in a series of sodium carbonate (Na2CO3) solutions spanning the physiologic range of CO2 content. Regression of the measured vs. the actual CO2 content data generated a straight line with a slope of 0.796 and y-intercept of 12.5 (r2 = .99; n = 48). These coefficients were successfully used to correct CO2 content determined in blood samples into which graduated amounts of sodium carbonate were added., Conclusions: This calibration procedure allows accurate measurement of Pco2 in aqueous samples using the Radiometer ABL2 electrode system, and should be applicable to other blood gas analyzers. Necessary syringes and chemicals are readily available, the method is fast and simple, and the sample volume is small. In the practice of critical care medicine, accurate Pco2 measurement in aqueous acidified and diluted blood provides direct determination of blood CO2 content (useful in calculations of modified Fick cardiac output or tissue CO2 production). Determinations of absolute CO2 content in blood requiring complex methodology are not necessary. In addition, accurate measurement of aqueous gastric Pco2 can help determine gastric pH, which is an important marker of tissue perfusion.

The measurement of average alveolar expired PCO2 (PAECO2) weights each PCO2 value on the alveolar plateau of the CO2 expirogram by the simultaneous change in exhaled volume. PAECO2 can be determined from a modified analysis of the Fowler anatomic dead space (VDANAT). In contrast, end-tidal PCO2 (PETCO2) only measures PCO2 in the last small volume of exhalate. In conditions such as mechanical ventilation with positive end-expiratory pressure (PEEP), where the alveolar plateau can have a significant positive slope, we questioned how much PETCO2 could overestimate PAECO2. Accordingly, in six anesthetized ventilated dogs, we digitally measured and processed tidal PCO2 and flow to determine VDANAT. We determined PETCO2 and PAECO before and after the application of 7.6 cm H2O PEEP. Alveolar dead space to tidal volume fraction (VD/VT) was determined by [arterial PCO2- alveolar PCO2]/arterial PCO2, where alveolar PCO2 was determined by either PETCO2 or PAECO2. During baseline ventilation, PETCO2 was 3.4 mm Hg (approximately 11%) greater than PAECO2. Because PEEP significantly increased the slope of the alveolar plateau from 28 to 74 mm Hg/L, the difference between PETCO2 and PAECO2 significantly increased to 6.6 mm Hg (approximately 20% difference). The concurrent increase in VDANAT during PEEP decreased alveolar tidal volume and tended to limit the overestimation of PETCO2 compared to PAECO2. When alveolar PCO2 was estimated by PETCO2, alveolar VD/VT was 18%, compared to an alveolar VD/VT of 26% when alveolar PCO2 was estimated by PAECO2. This difference was significantly magnified during PEEP ventilation. The overestimation of PAECO2 by PETCO2 can result in a falsely high assessment of overall alveolar PCO2. Moreover, the use of PETCO2 to estimate alveolar PCO2 in the determination of the alveolar dead space fraction can result in falsely low and even negative values of alveolar dead space.

The sidestream capnogram is delayed behind real time by transport delay (TD; time to aspirate gas through the sampling tubing) and by the dynamic response (DR) of the measurement cuvette. In six capnometers, we measured TD and DR by plunging the end of the sample tubing into a flask containing CO2 and then digitally analyzing the capnogram. TD ranged from 0.6 to 5.0 s and accounted for 89% or more of the total response time (TD + DR) of the capnometer. TD was generally not reported in the manufacturers' specifications. TD was further prolonged by low aspiration rates or by sampling tube extensions. During a series of quick breaths after endotracheal intubation, long TD can delay the appearance of CO2 and result in a false diagnosis of esophageal intubation. Also, long TD can prolong DR, which can result in underestimation of end-tidal PCO2 during rapid ventilation in pediatric anesthesia.

Intratracheally instilled 48V2O5 was rapidly cleared from the lung into blood, liver and bone. Approx. 40% of the recovered 48V was excreted, primarily in urine by day 3, while the skeleton accounted for 30% by day 7. The behavior of instilled 48VO2Cl was similar to that of 48V2O5. Uptake of gavaged 48V2O5 was 2.6% of administered dose. Skeleton, lung, kidney and liver are primary targets for intratracheally instilled 48V with uptake being much greater via the intratracheal route than by the oral route.