Exploring Anesthesiology Management of Living Donor Liver Transplantation: Survey From the Society for the Advancement of Transplant Anesthesia and the Korean Society for Transplantation Anesthesiologists.

INTRODUCTION: While living donor liver transplantation (LDLT) serves as the predominant method of adult liver transplant (LT) in the Republic of Korea (ROK), it represents a minority of LT in the United States (US). A survey was conducted to gain insight into these nations' anesthetic management. METHODS: An electronic questionnaire was distributed to directors of LT anesthesiology overseeing LDLT programs in both countries between May 2021 and October 2021. RESULTS: The response rate was 93.0% (100% [37/37] in the US and 80% [16/20] in the ROK). Both countries mainly adhered to deceased donor LT recipient management practices, including the frequency of routine pulmonary artery catheter use, transesophageal echocardiography, and point-of-care coagulation monitoring. Differences were observed in early extubation of recipients (US vs. ROK: 39.7% vs. 14.7% of all cases), participation in donor selection meetings (88.9% [32/36] vs. 6.3% [1/16], p < 0.0001), application of the Enhanced Recovery After Surgery donor protocol (69.4% [25/36] vs. 12.5% [2/16], p < 0.0001), and cell saver usage for donors (94.4% [34/36] vs. 18.8% [3/16], p < 0.0001). More ROK programs implemented simultaneous donor/recipient anesthesia supervision by a single anesthesiologist. CONCLUSIONS: Several important differences were identified between the US and the ROK in adult LDLT anesthetic management.

Perioperative management of adult living donor liver transplantation: Part 1 - recipients.

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.

Mouse Gut Microbiome-Encoded ß-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.

Gut microbial ß-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.

Total intravenous anesthesia vs inhaled anesthetic for intraoperative visualization during endoscopic sinus surgery: a double blind randomized controlled trial.

BACKGROUND: Bleeding during endoscopic sinus surgery (ESS) can impair visualization and delay surgical progress. The role that anesthetic technique may have on the quality of surgical field during ESS has been previously studied. However, meta-analyses have deemed the current literature inconclusive and lacking methodological consistency. This study was designed with these critiques in mind to assess the effect of total intravenous anesthesia (TIVA) vs inhaled anesthetic on the quality of the surgical field during ESS. METHODS: This study was a double-blind, randomized, controlled trial of 30 patients of American Society of Anesthesiologists (ASA) class 1 or 2 undergoing bilateral ESS for the primary diagnosis of chronic rhinosinusitis. In addition to standard techniques to minimize blood loss, study patients were randomized to maintenance anesthesia with intravenous propofol or inhaled desflurane. Anesthetic depth was standardized using bispectral index (BIS). The primary outcome measured was the Wormald grading scale to assess the endoscopic surgical field. RESULTS: The use of TIVA was associated with a statistically significant reduction in mean Wormald score compared to desflurane (4.21 vs 5.53, p = 0.024). Mean Boezaart score was also lower in the TIVA arm (2.18 vs 2.76, p = 0.034). Experimental groups were homogeneous in all compared baseline characteristics. Secondary outcomes including surgical duration, time to extubation, and estimated blood loss were not found to be statistically significant between experimental groups. CONCLUSION: Even with all other factors implemented to optimize the surgical field, utilization of TIVA vs inhaled anesthetic still resulted in a statistically significant improvement in surgical field during ESS.

Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor.

Asthma is a chronic airway disease characterized by inflammation, mucus hypersecretion and abnormal airway smooth muscle (ASM) contraction. Bacterial permeability family member A1, BPIFA1, is a secreted innate defence protein. Here we show that BPIFA1 levels are reduced in sputum samples from asthmatic patients and that BPIFA1 is secreted basolaterally from healthy, but not asthmatic human bronchial epithelial cultures (HBECs), where it suppresses ASM contractility by binding to and inhibiting the Ca2+ influx channel Orai1. We have localized this effect to a specific, C-terminal α-helical region of BPIFA1. Furthermore, tracheas from Bpifa1-/- mice are hypercontractile, and this phenotype is reversed by the addition of recombinant BPIFA1. Our data suggest that BPIFA1 deficiency in asthmatic airways promotes Orai1 hyperactivity, increased ASM contraction and airway hyperresponsiveness. Strategies that target Orai1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease.

Grip strength and body composition in Turkana pastoralist children and adolescents.

OBJECTIVES: In an earlier study, age changes and sex differences in grip strength were documented for adult Turkana pastoralists of Kenya (Little and Johnson, 1986). The objective here is to characterize age changes and sex differences in grip strength of Turkana children and adolescents in the context of arm lean tissue composition, and in comparison with other African, African-American, and non-Western populations. METHODS: Anthropometric measurements, derived body composition values, and grip strength measures (maximum voluntary contraction) were taken on a sample of 232 nomadic Turkana pastoralist children (94 boys and 138 girls) aged 3 to 21 years. Relationships were tested between grip strength (in Newtons) and mid-upper arm (brachium) lean tissue cross-sectional areas. Comparisons were made among several different ethnic groups. RESULTS: Turkana children and adolescents had low arm muscle (derived lean tissue) and grip strength values when compared with U.S. NHANES percentile references. Girls' percentile rankings were greater than boys' percentile rankings for muscle and for grip strength. Both boys and girls were intermediate when compared with other non-Western populations and U.S. strength grip reference values. Correlations between grip strength and arm lean tissue areas were highly significant for both boys and girls. CONCLUSIONS: The greater relative muscle size and grip strength values of late adolescent girls compared to boys is consistent with an earlier study of adults. The difference is likely to result from greater physical subsistence activity and greater access to food in girls than in boys. Several suggestions are given to explain why Turkana youths have relatively small muscle sizes.

Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid.

The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals. Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPARα) can up-regulate the hepatic expression of Bcrp. The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPARα agonist perfluorooctanoic acid (PFOA) and the ability of PFOA to alter human BCRP function in vitro. Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL/6 mice treated with vehicle or PFOA (1 or 3mg/kg/day oral gavage) for 7 days. PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPARα target gene, cytochrome P450 4a14. Compared to vehicle-treated control mice, PFOA increased hepatic Bcrp mRNA and protein between 1.5- and 3-fold. Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA-treated mice. The kidney expression of cytochrome P450 4a14 mRNA, but not Bcrp, was increased in mice treated with PFOA. Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP-mediated transport in inverted membrane vesicles. Together, these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans.

Reducing xerostomia after chemo-IMRT for head-and-neck cancer: beyond sparing the parotid glands.

PURPOSE: To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. PATIENTS AND METHODS: In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. RESULTS: Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. CONCLUSION: The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone.

Comparison of three strategies to delineate the bowel for whole pelvis IMRT of prostate cancer.

PURPOSE: To compare three different contouring approaches of the bowel before and during whole pelvis IMRT of localized prostate cancer. MATERIALS: Nine patients were randomly selected among those treated for localized prostate cancer at UTMB from March 2004 to August 2006. On the planning CT, besides the usual organs at risk (OAR), for each patient we contoured the bowel according to three different definitions: each bowel segment ('BS'); 'BS+1', BS uniformly expanded by 1cm; intestinal cavity ('IC') or the 'container' of the bowel loops up to the pelvic/abdominal walls. For each patient we generated three rival plans each considering a different bowel definition, otherwise identical. Provided that the same target coverage and other OAR spare had been achieved, plans were compared for their ability to minimize bowel dose at planning. Furthermore, after co-registering 6 weekly CT to the initial planning CT for each patient, we investigated which of the three definitions would allow the best bowel protection also during treatment. RESULTS: All definitions provided a very similar average bowel DVH at planning. During treatment BS allowed an average approximately 20 cc more of bowel to receive at least 45 Gy over BS+1 and IC (p=0.008 and 0.029, respectively); on the contrary bowel V45 between IC and BS+1 were not significantly different (p=0.65). CONCLUSION: A definition that takes into account internal organ motion is warranted to maximize bowel protection during treatment.

Acute toxicity of whole-pelvis IMRT in 87 patients with localized prostate cancer.

PURPOSE: To assess the acute toxicity profile of whole pelvis IMRT (WP-IMRT) for localized prostate cancer. MATERIALS: Eighty seven patients treated with definitive WP-IMRT at UTMB from May 2002 to November 2006 were retrospectively reviewed. Treatment consisted of two sequential phases, WP-IMRT to 54 Gy at 1.8 Gy per fraction to the pelvic nodes and seminal vesicles and 60 Gy at 2 Gy to the prostate, and a separate external beam boost, 3DCRT or IMRT, to bring the dose to the prostate to 76 Gy. Acute toxicity was prospectively scored weekly during treatment and at 3 month follow-up according to CTC v2.0 for 10 genitourinary (GU) and gastrointestinal (GI) domains. The proportion of patients experiencing a given level of peak acute toxicity at a given point is reported. RESULTS: Treatment was feasible with delivered doses to PTVs not significantly lower than planned ones and with only two patients experiencing treatment gaps longer than 5 days. About 2/3 and 1/10 of the patients experienced peak grade 2 and grade 3 reactions at least once during RT, respectively. Frequency/urgency (Grade 2+: 37.9%) and diarrhea (36.7%) were the most prevalent symptoms followed by proctitis (21.8%) and dysuria (16.1%). GI reactions were generally shorter lasting compared to GU ones which accumulated progressively during treatment. At 3 months, almost half of the patients were asymptomatic and most of observed reactions (89.2%) were mild, with GI ones more likely to be fully resolved (92.5%) than GU ones (68.7%, chi(2), p=0.001). CONCLUSION: Our approach is dosimetrically and clinically feasible with intense, but transient, acute toxicity.

Internal initiation sites of de novo RNA synthesis within the hepatitis C virus polypyrimidine tract.

A variety of 3'-untranslated regions (UTRs) were cloned from infectious hepatitis C virus human samples and examined in NS5B polymerase de novo initiation reactions. We isolated and characterized four distinct 3'-UTRs that harbor the conserved terminal 98 nucleotides, but have poly(U/UC) tracts of 25, 93, 98, and 101 nucleotides, respectively. Reconstitution of de novo initiation by the mature NS5B with the different 3'-UTR RNA substrates revealed distinctively sized products that are consistent with internal initiation at specific sites within the polypyrimidine tract. These sites were further mapped by demonstrating that nucleotide substitutions of the cytidylate stretches within the poly(U/UC) template eliminate specific products of de novo synthesis and by showing that these products could be radiolabeled by [gamma-32P]GTP. We also examine analogs that can substitute for GTP in this reaction.