Reassessing retinal pigment epithelial ketogenesis: Enzymatic assays for ketone body levels provide inaccurate results.

The retinal pigment epithelium (RPE) is omnivorous and can utilize a wide range of substrates for oxidative phosphorylation. Certain tissues with high mitochondrial metabolic load are capable of ketogenesis, a biochemical pathway that consolidates acetyl-CoA into ketone bodies. Earlier work demonstrated that the RPE expresses the rate-limiting enzyme for ketogenesis, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), and that the RPE indeed produces ketone bodies, including beta-hydroxybutyrate (ß-HB). Prior work, based on detecting ß-HB via enzymatic assays, suggested that differentiated cultures of primary RPE preferentially export ß-HB across the apical membrane. Here, we compare the accuracy of measuring ß-HB by enzymatic assay kits to mass spectrometry analysis. We found that commercial kits lack the sensitivity to accurately measure the levels of ß-HB in RPE cultures and are prone to artifact. Using mass spectrometry, we found that while RPE cultures secrete ß-HB, they do so equally to both apical and basal sides. We also find RPE is capable of consuming ß-HB as levels rise. Using isotopically labeled glucose, amino acid, and fatty acid tracers, we found that carbons from both fatty acids and ketogenic amino acids, but not from glucose, produce ß-HB. Altogether, we substantiate ß-HB secretion in RPE but find that the secretion is equal apically and basally, RPE ß-HB can derive from ketogenic amino acids or fatty acids, and accurate ß-HB assessment requires mass spectrometric analysis.

Rethinking Oncologic Facial Nerve Reconstruction in the Acute Phase Through Classification of the Level of Injury.

Early facial nerve reconstruction should be offered in every patient with oncological resections of the facial nerve due to the debilitating functional and psychosocial consequences of facial nerve palsy. Oncologic pathology or oncologic resection accounts for the second most common cause of facial nerve palsy. In the case of these acute injuries, selecting an adequate method for reconstruction to optimize functional and psychosocial well-being is paramount. Authors advocate consideration of the level of injury as a framework for approaching the viable options of reconstruction systematically. Authors breakdown oncologic injuries to the facial nerve in three levels in relation to their nerve reconstruction methods and strategies: Level I (intracranial to intratemporal), Level II (intratemporal to extratemporal and intraparotid), and Level III (extratemporal and extraparotid). Clinical features, common clinical scenarios, donor nerves available, recipient nerve, and reconstruction priorities will be present at each level. Additionally, examples of clinical cases will be shared to illustrate the utility of framing acute facial nerve injuries within injury levels. Selecting donor nerves is critical in successful facial nerve reconstruction in oncological patients. Usually, a combination of facial and nonfacial donor nerves (hybrid) is necessary to achieve maximal reinnervation of the mimetic muscles. Our proposed classification of three levels of facial nerve injuries provides a selection guide, which prioritizes methods for function nerve reconstruction in relation of the injury level in oncologic patients while prioritizing functional outcomes.

Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes.

The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, but its role in disease pathogenesis is unknown. Here, we show alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We find that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also show that one of the arginine-rich DPRs (PR) could directly contribute to glucose metabolism and metabolic stress by inhibiting glucose uptake in neurons. Our findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model with potential opportunities for therapeutic intervention.

Rising Inpatient Utilization and Costs of Cannabis Hyperemesis Syndrome Hospitalizations in Massachusetts After Cannabis Legalization.

GOALS: We described the demographics, inpatient utilization, and cost of services among patients hospitalized for putative cannabinoid hyperemesis syndrome (CHS) predating and postdating cannabis legalization in Massachusetts. BACKGROUND: As the recreational use of cannabis has been widely legalized nationally, the resulting shifts in clinical presentation, health care utilization, and estimated costs of CHS hospitalizations remain unclear in the postlegalization era. STUDY: We performed a retrospective cohort study among patients admitted to a large urban hospital between 2012 and 2021, before and after the date of cannabis legalization in Massachusetts (Dec 15, 2016). We examined the demographic and clinical characteristics of patients admitted for putative CHS, the utilization of hospital services, and estimated inpatient costs pre and postlegalization. RESULTS: We identified a significant increase in putative CHS hospitalizations pre and post-cannabis legalization in Massachusetts (0.1% vs 0.02% of total admissions per time period, P < 0.05). Across 72 CHS hospitalizations, patient demographics were similar pre and postlegalization. Hospital resource utilization increased postlegalization, with increased length of stay (3 d vs 1 d, P < 0.005), and need for antiemetics ( P < 0.05). Multivariate linear regression confirmed that postlegalization admissions were independently associated with increased length of stay ( Β = 5.35, P < 0.05). The mean cost of hospitalization was significantly higher postlegalization ($18,714 vs $7460, P < 0.0005), even after adjusting for medical inflation ($18,714 vs $8520, P < 0.001) with intravenous fluid administration and endoscopy costs increased ( P < 0.05). On multivariate linear regression, hospitalization for putative CHS during postlegalization predicted increased costs ( Β = 10,131.25, P < 0.05). CONCLUSIONS: In the postlegalization era of cannabis in Massachusetts, we found increased putative CHS hospitalizations, with a concomitant increased length of hospital stay and total cost per hospitalization. As cannabis use increases, the recognition and costs of its deleterious effects are necessary to incorporate into future clinical practice strategies and health policy.

Ultrasound-Guided Injections for Treatment of Facial Paralysis Sequelae: A Randomized Study on Body Donors.

BACKGROUND: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven. METHODS: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures. RESULTS: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22). CONCLUSIONS: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis.

Preoperative assessment of depressor anguli oris to prevent myectomy failure: An anatomical study using high-resolution ultrasound.

BACKGROUND: Myectomies of the lower lip depressor muscles have unexplained high failure rates. This study aimed to examine the depressor anguli oris (DAO) muscle using high-resolution ultrasound to identify potential anatomical explanations for surgical failures and to determine the accuracy of utilizing preoperative ultrasound assessment to improve myectomies. METHODS: Anatomical features of DAO and the surrounding anatomy were examined in 38 hemifaces of human body donors using high-resolution ultrasound and dissection. RESULTS: The ultrasound and dissection measurements showed the DAO muscle width to be 16.2 ± 2.9 versus 14.5 ± 2.5 mm, respectively, and the location of the lateral muscle border 54.4 ± 5.7 versus 52.3 ± 5.4 mm lateral to the midline. In 60% of the cases, the facial artery was either completely covered by lateral DAO muscle fibers or was found to be in direct contact with the lateral border. Significant muscle fiber continuity was present between the DAO and surrounding muscles in 5% of cases, whereas continuity between the depressor labii inferioris and surrounding muscles was considerably more common and pronounced. CONCLUSIONS: High-resolution ultrasound can accurately reveal important preoperative anatomical information in myectomies. Two potential explanations for the surgical failures were discovered: an overlap of lateral DAO muscle fibers over the facial artery could lead to inadequate resections and continuity with the surrounding muscles might lead to muscle function takeover despite adequate resections. Both can be uncovered preoperatively by the surgeon through a brief, directed ultrasound examination, which may allow for modification of the surgical plan to reduce surgical failure.

Imaging Modalities for Evaluating Lymphedema.

Lymphedema is a progressive condition. Its therapy aims to reduce edema, prevent its progression, and provide psychosocial aid. Nonsurgical treatment in advanced stages is mostly insufficient. Therefore-in many cases-surgical procedures, such as to restore lymph flow or excise lymphedema tissues, are the only ways to improve patients' quality of life. Imaging modalities: Lymphoscintigraphy (LS), near-infrared fluorescent (NIRF) imaging-also termed indocyanine green (ICG) lymphography (ICG-L)-ultrasonography (US), magnetic resonance lymphangiography (MRL), computed tomography (CT), photoacoustic imaging (PAI), and optical coherence tomography (OCT) are standardized techniques, which can be utilized in lymphedema diagnosis, staging, treatment, and follow-up. Conclusions: The combined use of these imaging modalities and self-assessment questionnaires deliver objective parameters for choosing the most suitable surgical therapy and achieving the best possible postoperative outcome.

The Impact of Race and Sex on the Clinical Outcomes of Homeless Patients With Alcoholic Liver Disease: Propensity Score Matched Analysis of US Hospitals.

BACKGROUND: Among patients with alcoholic liver disease (ALD), homelessness poses significant medical and psychosocial risks; however, less is known about the effects of race and sex on the hospital outcomes of admitted homeless patients with ALD. METHODS: The National Inpatient Sample database from 2012 to 2017 was used to isolate homeless patients with ALD, and the cohort was further stratified by race and sex for comparisons. Propensity score matching was utilized to minimize covariate confounding. The primary endpoints of this study include mortality, hospital length of stay, and hospital costs; secondary endpoints included the incidence of liver complications. RESULTS: There were 3972 females/males postmatch, as well as 2224 Blacks/Whites and 4575 Hispanics/Whites postmatch. In multivariate, there were no significant differences observed in mortality rate, length of stay, and costs between sexes. Comparing liver outcomes, females had a higher incidence of hepatic encephalopathy [adjusted odds ratio (aOR) 1.02, 95% CI: 1.01-1.04, P<0.001]. In comparing Blacks versus Whites, Black patients had higher hospitalization costs (aOR 1.13, 95% CI: 1.03-1.24, P=0.01); however, there were no significant differences in mortality, length of stay, or liver complications. In comparing Hispanics versus Whites, Hispanic patients had longer length of hospital stay (aOR 1.12, 95% CI: 1.06-1.19, P<0.001), greater costs (aOR 1.15, 95% CI: 1.09-1.22, P<0.001), as well as higher prevalence of liver complications including varices (aOR 1.04, 95% CI: 1.02-1.06, P<0.001), hepatic encephalopathy (aOR 1.03, 95% CI: 1.02-1.04, P<0.001), and hepatorenal syndrome (aOR 1.01, 95% CI 1.00-1.01, P=0.03). However, there was no difference in mortality between White and Hispanic patients. CONCLUSIONS: Black and Hispanic ALD patients experiencing homelessness were found to incur higher hospital charges; furthermore, Hispanic patients also had greater length of stay and higher incidence of liver-related complications compared with White counterparts.

Efficacy and safety of paliperidone palmitate 6-monthly long-acting injectable in reduction of relapses in patients with schizophrenia: An Asian subgroup analysis of phase 3, randomized study.

BACKGROUND: Evaluate efficacy and safety of paliperidone palmitate 6-monthly (PP6M) for patients with schizophrenia in the Asian subgroup of a global, multicenter, noninferiority phase-3 study (NCT03345342). METHODS: Patients received paliperidone palmitate 1-monthly (PP1M, 100/150 mg eq.) or paliperidone palmitate 3-monthly (PP3M, 350/525 mg eq.) during the maintenance phase and entered a 12-month double-blind (DB) phase, wherein they were randomized (2:1) to PP6M (700/1000 mg. eq.) or PP3M (350/525 mg eq.). Subgroup analysis was performed for 90 (12.7%) patients from Asia region (India, Taiwan, Malaysia, Hong Kong, and Korea). Primary endpoint was time-to-relapse during DB phase (Kaplan-Meier estimates). Secondary endpoints were changes from baseline in Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale score. RESULTS: In Asian subgroup, 91.9% (82/90) of patients completed DB phase (PP6M: 54/62 [87%]; PP3M: 28/28 [100%]). Median time-to-relapse was "not-estimable" due to low relapse rates in both groups. Estimated difference (95% confidence interval [CI]) between relapse-free patients in PP6M and PP3M groups of Asian subgroup was -0.1% [-8.5%, 8.4%] (global study population: -2.9% [-6.8%, 1.1%]). Mean change from baseline in secondary efficacy parameters was comparable between both groups, similar to the global study population. The incidence of extrapyramidal symptoms was higher in the Asian subgroup than in the global study population. CONCLUSION: Consistent with the global study population, PP6M was noninferior to PP3M in preventing relapse in patients with schizophrenia from the Asia region. Findings suggest the possibility of switching from PP1M/PP3M to twice-yearly PP6M without loss of efficacy and with no unexpected safety concerns.

A Nonconserved Histidine Residue on KRAS Drives Paralog Selectivity of the KRASG12D Inhibitor MRTX1133.

MRTX1133 is the first noncovalent inhibitor against the KRASG12D mutant that demonstrated specificity and potency in preclinical tumor models. Here, we used isogenic cell lines expressing a single RAS allele to evaluate the selectivity of this compound. In addition to KRASG12D, MRTX1133 showed significant activity against several other KRAS mutants as well as wild-type KRAS protein. In contrast, MRTX1133 exhibited no activity against both G12D and wild-type forms of HRAS and NRAS proteins. Functional analysis revealed that the selectivity of MRTX1133 toward KRAS is associated with its binding to H95 on KRAS, a residue that is not conserved in HRAS and NRAS. Reciprocal mutation of amino acid 95 among the three RAS paralogs resulted in reciprocal change in their sensitivity toward MRTX1133. Thus, H95 is an essential selectivity handle for MRTX1133 toward KRAS. Amino acid diversity at residue 95 could facilitate the discovery of pan-KRAS inhibitors as well as HRAS and NRAS paralog-selective inhibitors. SIGNIFICANCE: The nonconserved H95 residue on KRAS is required for the selectivity of the KRASG12D inhibitor MRTX1133 and can be exploited for the development of pan-KRAS inhibitors.

Attributes of a Good Microsurgeon-A Brief Counsel to the Up-and-Coming Prospects.

Microsurgery, which deservedly sits on top of the reconstruction ladder, has been a boon to plastic surgery. It is because of this marvelous tool that plastic surgeons the world over have been able to tackle many reconstructive dilemmas, which were once considered to be an improbability. Microsurgery-aided revolutions have rendered a new meaning to all forms of reconstruction-whether it is postoncological, posttraumatic, or postlymphedema reconstruction. As the most advanced reconstructive medium at our disposal that has broadened the horizons of plastic surgery exponentially, it is but obvious that many budding plastic surgeons are drawn toward this subspecialty. In lieu of the aforementioned facts, it is necessary to sensitize all such aspiring surgeons about the various intricacies concerning the field of microsurgery. This article with its focus on the six desirable microsurgical attributes of "Clarity, Curiosity, Perseverance, Passion, An Open Mindset and Action," is meant to be a modest attempt on part of the authors to share their microsurgical insights, procured through their respective journeys, with budding aspirants, hoping to sensitize as well as motivate them for the challenging path that lies ahead.

Clinical implications of gender and race in patients admitted with autoimmune hepatitis: updated analysis of US hospitals.

Background: Autoimmune hepatitis (AIH) can result in end-stage liver disease that requires inpatient treatment of the hepatic complications. Given this phenomenon, it is important to analyse the impact of gender and race on the outcomes of patients who are admitted with AIH using a national hospital registry. Methods: The 2012-2017 National Inpatient Sample database was used to select patients with AIH, who were stratified using gender and race (Hispanics and blacks as cases and whites as reference). Propensity score matching was employed to match the controls with cases and compare mortality, length of stay and hepatic complications. Results: After matching, there were 4609 females and 4609 males, as well as 3688 blacks and 3173 Hispanics with equal numbers of whites, respectively. In multivariate analysis, females were less likely to develop complications, with lower rates of cirrhosis, ascites, variceal bleeding, hepatorenal syndrome, encephalopathy and acute liver failure (ALF); they also exhibited lower length of stay (adjusted OR, aOR 0.96 95% CI 0.94 to 0.97). When comparing races, blacks (compared with whites) had higher rates of ALF and hepatorenal syndrome related to ALF, but had lower rates of cirrhosis-related encephalopathy; in multivariate analysis, blacks had longer length of stay (aOR 1.071, 95% CI 1.050 to 1.092). Hispanics also exhibited higher rates of hepatic complications, including ascites, varices, variceal bleeding, spontaneous bacterial peritonitis and encephalopathy. Conclusion: Males and minorities are at a greater risk of developing hepatic complications and having increased hospital costs when admitted with AIH.

Chronic Fistulas of Thigh Presenting Unusually in an Operated Patient of Carcinoma Rectum. More Than What Meets the Eye!

Chronic skin lesions of the thigh (wounds, fistulas etc) are relatively uncommon, vis-à-vis, their notorious cousins over the distal limb. Even when present, the cause is usually obvious, mostly as trauma or a systemic affliction. We present an unusual case of chronic fistulas over the right thigh in a patient of carcinoma rectum for which anterior resection and an end colostomy was done 4 years earlier. Postsurgical pelvic abscesses finding their way into the thigh are a known entity, but they are usually accompanied by systemic/local features and their presentation is within a shorter time span. The novelty of our case lies in its manifestation (as a cluster of chronic fistulas and not a frank abscess), its late presentation as well as in the absence of any systemic/local inflammatory signs. Our primary objective is to educate wound physicians about the origin of such fistulas whenever they deal with patients who have had a preceding surgical intervention of the abdomen. In our humble opinion, this will ease out many diagnostic and management dilemmas, that such patients can potentially pose.

Selective ansa cervicalis nerve transfer to the marginal mandibular nerve for lower lip reanimation: An anatomical study in cadavers and a case report.

BACKGROUND: Donor nerve options for lower lip reanimation are limited in patients undergoing oncological resection of the facial nerve. The ansa cervicalis nerve (ACN) is an advantageously situated donor with great potential but has not been examined in detail. In the current study, the anatomical technical feasibility of selective ACN to marginal mandibular nerve (MMN) transfer for restoration of lower lip tone and symmetry was explored. A clinical case is presented. METHODS: Dissections were conducted in 21 hemifaces in non-embalmed human cadavers. The maximal harvestable length of ACN was measured and transfer to MMN was simulated. A 28-year-old male underwent ACN-MMN transfer after parotidectomy (carcinoma) and was evaluated 12 months post-operatively (modified Terzis' Lower Lip Grading Scale [25 observers] and photogrammetry). RESULTS: The harvestable length of ACN was 100 ± 12 mm. A clinically significant anatomical variant ("short ansa") was present in 33% of cases (length: 37 ± 12 mm). Tensionless coaptation was possible in all cases only when using a modification of the surgical technique in "short ansa" cases (using an infrahyoid muscle nerve branch as an extension). The post-operative course of the clinical case was uneventful without complications, with improvement in tone, symmetry, and function at the lower lip at 12-month post-operative follow-up. CONCLUSIONS: Selective ACN-MMN nerve transfer is anatomically feasible in facial paralysis following oncological ablative procedures. It allows direct nerve coaptation without significant donor site morbidity. The clinical case showed good outcomes 12 months post-operatively. A strategy when encountering the "short ansa" anatomical variant in clinical cases is proposed.

Detection of Transgene Location in the CYP2A13/2B6/2F1-transgenic Mouse Model using Optical Genome Mapping Technology.

Most transgenic mouse models are generated through random integration of the transgene. The location of the transgene provides valuable information for assessing potential effects of the transgenesis on the host and for designing genotyping protocols that can amplify across the integration site, but it is challenging to identify. Here, we report the successful utility of optical genome mapping technology to identify the transgene insertion site in a CYP2A13/2B6/2F1-transgenic mouse model, which produces three human cytochrome P450 (P450) enzymes (CYP2A13, CYP2B6, and CYP2F1) that are encoded by neighboring genes on human chromosome 19. These enzymes metabolize many drugs, respiratory toxicants, and chemical carcinogens. Initial efforts to identify candidate insertion sites by whole genome sequencing was unsuccessful, apparently because the transgene is located in a region of the mouse genome that contains highly repetitive sequences. Subsequent utility of the optical genome mapping approach, which compares genome-wide marker distribution between the transgenic mouse genome and a reference mouse (GRCm38) or human (GRCh38) genome, localized the insertion site to mouse chromosome 14, between two marker positions at 4451324 base pair and 4485032 base pair. A transgene-mouse genome junction sequence was further identified through long-polymerase chain reaction amplification and DNA sequencing at GRCm38 Chr.14:4484726. The transgene insertion (∼2.4 megabase pair) contained 5-7 copies of the human transgenes, which replaced a 26.9-33.4 kilobase pair mouse genomic region, including exons 1-4 of Gm3182, a predicted and highly redundant gene. Finally, the sequencing results enabled the design of a new genotyping protocol that can distinguish between hemizygous and homozygous CYP2A13/2B6/2F1-transgenic mice. SIGNIFICANCE STATEMENT: This study characterizes the genomic structure of, and provides a new genotyping method for, a transgenic mouse model that expresses three human P450 enzymes, CYP2A13, CYP2B6, and CYP2F1, that are important in xenobiotic metabolism and toxicity. The demonstrated success in applying the optical genome mapping technology for identification of transgene insertion sites should encourage others to do the same for other transgenic models generated through random integration, including most of the currently available human P450 transgenic mouse models.

Long-term Use of Wearable Health Technology by Chronic Pain Patients.

OBJECTIVES: People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be associated with improvements in key patient outcomes. METHODS: A 12-month study of WHT use among people with chronic pain was conducted, consisting of iPhone and Apple Watch applications to measure movement, sleep, and self-reported pain. Clinical outcomes among 105 patients enrolled in a multidisciplinary pain program that included WHT use were compared with 146 patients in the same program but without WHT, and to 161 patients receiving medical pain management without WHT. RESULTS: Participants used the WHT on average 143.0 (SD: 117.6) out of 365 days. Mixed-effects models revealed participants who used WHT had decreases in depression scores (-7.83, P <0.01) and prescribed morphine milligram equivalents (-21.55, P =0.04) over 1 year. Control groups also showed decreases in depression scores (-5.08, P =0.01; -5.68, P <0.01) and morphine milligram equivalents (-18.67, P =0.01; -10.99, ns). The estimated slope of change among the WHT was not statistically different than control groups. DISCUSSION: Patients who used WHT as part of their pain management program demonstrated a willingness to do so for extended periods of time despite living with chronic pain and other comorbidities. Data trends suggest that WHT use may positively impact depression and prescribed medication. Additional research is warranted to investigate the potential of WHT to improve the negative consequences of chronic pain.

The clinical implications of pre-liver transplant diabetes on post-liver transplant outcomes in patients with NASH: analysis of the UNOS database.

BACKGROUND AND AIMS: The presence of perioperative diabetes may lead to increased mortality risks following liver transplant (LT) in patients with non-alcoholic steatohepatitis (NASH). This risk factor was evaluated using a UNOS-STAR national database. METHODS: The UNOS-STAR liver transplant registry 2005-2019 was used to select patients with NASH (including cryptogenic liver disease). The following populations were excluded: those younger than 18 years old and those with living donors/dual transplants. Selected patients were stratified into those with and without pre-LT diabetes and compared to the individual mortality endpoints using iterative Cox analyses. RESULTS: 6324 recipients with and 8251 without diabetes were selected. The median follow-up time was 3.07 years. Those with diabetes were older (58.50 vs. 54.50 years, p < 0.001), were more likely to be Hispanic or Asian, and had higher BMI than the non-diabetics (31.10 vs. 29.70 kg/m2 p < 0.001); however, there was no difference in gender (female 41.9 vs. 43.1% p = 0.170). Compared to non-diabetics, recipients with diabetes had a higher rate of all-cause mortality (61.68 vs. 47.80 per 1000 person-years). In multivariate iterations, pre-LT diabetes was associated with all-cause mortality (aHR 1.19 95% CI 1.11-1.27) as well as deaths due to cardiac (p = 0.014 aHR 1.24 95% CI 1.04-1.46) and renal causes (p = 0.039 aHR 1.38 95% CI 1.02-1.87). CONCLUSION: The presence of pre-LT diabetes is associated with all-cause mortality and deaths due to cardiac and renal causes following LT. The findings warrant an early preoperative screening procedure to ensure that patients with diabetes have their metabolic risk factors optimized prior to LT.

The Clinical Impact of Advanced Age on the Postoperative Outcomes of Patients Undergoing Gastrectomy for Gastric Cancer: Analysis Across US Hospitals Between 2011-2017.

PURPOSE: This study systematically evaluated the implications of advanced age on post-surgical outcomes following gastrectomy for gastric cancer using a national database. MATERIALS AND METHODS: The 2011-2017 National Inpatient Sample was used to isolate patients who underwent gastrectomy for gastric cancer. From this, the population was stratified into those belonging to the younger age cohort (18-59 years), sexagenarians, septuagenarians, and octogenarians. The younger cohort and each advanced age category were compared in terms of the following endpoints: mortality following surgery, length of hospital stay, charges, and surgical complications. RESULTS: This study included a total of 5,213 patients: 1,366 sexagenarians, 1,490 septuagenarians, 743 octogenarians, and 1,614 under 60 years of age. Between the younger cohort and sexagenarians, there was no difference in mortality (2.27 vs. 1.67%; P=0.30; odds ratio [OR], 1.36; 95% confidence interval [CI], 0.81-2.30), length of stay (11.0 vs. 11.1 days; P=0.86), or charges ($123,557 vs. $124,425; P=0.79). Compared to the younger cohort, septuagenarians had higher rates of in-hospital mortality (4.30% vs. 1.67%; P<0.01; OR, 2.64; 95% CI, 1.67-4.16), length of stay (12.1 vs. 11.1 days; P<0.01), and charges ($139,200 vs. $124,425; P<0.01). In the multivariate analysis, septuagenarians had higher mortality (P=0.01; adjusted odds ratio [aOR], 2.01; 95% CI, 1.18-3.43). Similarly, compared to the younger cohort, octogenarians had a higher rate of mortality (7.67% vs. 1.67%; P<0.001; OR, 4.88; 95% CI, 3.06-7.79), length of stay (12.3 vs. 11.1 days; P<0.01), and charges ($131,330 vs. $124,425; P<0.01). In the multivariate analysis, octogenarians had higher mortality (P<0.001; aOR, 4.03; 95% CI, 2.28-7.11). CONCLUSIONS: Advanced age (>70 years) is an independent risk factor for postoperative death in patients with gastric cancer undergoing gastrectomy.

Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival.

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.