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Introduction: There is limited data concerning concomitant cardiac and lung surgery outcomes during lung transplantation (LTx). While some evidence suggests that cardiac surgery during LTx has no significant impact on surgical outcomes, scarce data examines the role of concomitant lung surgery (CLS). This study compares the survival outcomes of concomitant cardiac and lung surgeries during LTx., Methods: A retrospective analysis of all single and double LTx patients from March 2012 to June 2023 at a single center was performed (n = 1099). Patients were stratified into three concomitant surgical groups: concomitant cardiac surgery (CCS), CLS, and no concomitant surgeries. Groups were compared on recipient demographics, diagnosis, and surgical intervention using analysis of variance and chi-square tests. Survival (5 y) was analyzed using Kaplan-Meier curves, log-rank test, and univariable Cox proportional hazard model where P value <0.05 was considered significant., Results: In total, 1099 patients were analyzed in this study; 965 had no concomitant surgery, 100 had CCS (mode: coronary artery bypass grafting, n = 75), and 34 had CLS (mode: lung volume reduction surgery, n = 14). Between the three surgical groups, there was no significant difference in body mass index (P = 0.091), total ischemic time (P = 0.194), induction (P = 0.140), or cause of death (P = 0.240). Lung allocation score and length of stay were significantly higher in the concomitant surgical groups, especially the CLS group when compared to the no concomitant surgery group (P = 0.002, P = 004). Patients with no concomitant surgery had a higher incidence of single LTx and off-pump utilization than concomitant surgical groups (P < 0.001). Kaplan-Meier curves and log-rank tests found no significant difference in survival between groups (P = 0.849). This result is supported by Cox proportional hazard model with no significant difference in mortality risk between the CCS group (P = 0.522) and CLS group (P = 0.936) compared to no concomitant surgery during LTx., Conclusions: Our study provides promising data indicating that individuals undergoing concomitant heart or lung surgery during LTx have similar survival outcomes to those exclusively undergoing LTx. These results highlight the potential advantages of utilizing LTx to address concurrent thoracic surgical needs, such as coronary revascularization. This holds implications for optimizing patient care and decision-making when complex thoracic interventions are necessary., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has expanded considerably, though evidence-based selection criteria and long-term outcome data are lacking. The purpose of this study was to evaluate whether risk factors often used to exclude patients from ECMO BTT-specifically older age and not yet being listed for transplant-are validated by long-term outcomes., Methods: To ensure minimum 5-year follow-up, a retrospective cohort study was performed of adult patients actively listed for lung transplantation at a high-volume center and bridged on ECMO between January 2012 and December 2017. Data was collected through January 1, 2023., Results: Among 50 patients bridged on ECMO, 25 survived to transplant. Median age at listing was 58 (interquartile range [IQR], 42-65) in the transplanted group and 65 (IQR, 56.5-69) in the deceased group (P = 0.051). One-year, 3-year, and 5-year survival were 88% (22/25), 60% (15/25), and 44% (11/25), respectively, with eight patients still living at the time of review. Median time spent at home during the year post-transplant was 340 days (IQR, 314-355). Older age at listing was a negative predictor of survival on ECMO to transplant (odds ratio 0.92 [95% confidence interval, 0.86-0.99], P = 0.01). Thirteen patients were placed on ECMO prior to being listed and three were listed the same day as ECMO cannulation, with 10/16 transplanted. No significant difference in post-transplant survival was found between patients placed on ECMO prior to listing (n = 10) and those already listed (n = 15) (P = 0.93, log-rank). Serial post-transplant spirometry up to 5 years and surveillance transbronchial biopsy demonstrated good allograft function and low rates of cellular rejection., Conclusions: In one of the oldest cohorts of ECMO BTT patients described, favorable survival outcomes and allograft function were observed up to 5 years irrespective of whether patients were previously listed or bridged to decision. Despite inherent limitations to this retrospective, single-center study, the data presented support the feasibility of ECMO BTT in older and not previously listed advanced lung disease patients., (© 2024. The Author(s).)

Background: Although COVID-19 is no longer a declared global health emergency, data remain limited on the impact of COVID-19 in lung transplant recipients., Methods: We identified lung transplant recipients who were diagnosed with COVID-19 from March 2020 through August 2022 in our institutional database and investigated clinical outcomes. We then analyzed outcomes based on date of COVID-19 diagnosis (first wave March 2020-October 2020; second wave November 2020-2021; third wave December 2021-September 2022) and compared these results., Results: Of the 210 lung transplant recipients (median age 67; 67% men) enrolled, 140 (67%) required hospital admission. Among admitted recipients, 35 (25%) were intubated and 7 (5%) were placed on extracorporeal membrane oxygenation. Overall survival was 67.1% at 1 y and 59.0% at 2 y post-COVID-19 diagnosis. COVID-19 led to mortality in all 5 patients diagnosed during their index admission for lung transplantation. Although overall survival was significantly better in recipients with COVID-19 during the third wave, in-hospital mortality remained high (first wave 28%, second wave 38%, and 28% third wave). Vaccination (partially vaccinated versus none and fully vaccinated versus none) was the only significant protective factor for hospital admission, and age 70 y and older and partially vaccinated (versus none or fully vaccinated) were independent risk factors for in-hospital mortality., Conclusions: Overall survival after COVID-19 infection in lung transplant recipients continues to improve; however, in-hospital mortality remains remarkably high. Vaccination appears to have been impactful in preventing hospital admission, but its impact on in-hospital mortality is still unclear. Further research is needed to better identify lung transplant recipients at high risk for mortality from COVID-19., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objectives: Donors with characteristics that increase risk of hepatitis B virus, hepatitis C virus, and HIV transmission are deemed increased-risk donors (IRDs) per Public Health Service guidelines. Compared with organs from standard-risk donors (SRDs), IRD organs are more frequently declined. We sought to investigate the outcomes of IRD lung transplant recipients following the 2013 guideline change., Methods: We retrospectively identified lung transplant recipients using the United Network of Organ Sharing registry (February 2014 to March 2020). Patients were divided into 2 cohorts, based on Centers for Disease Control and Prevention risk status of the donor: SRD or IRD. Demographics and clinical parameters were compared across groups. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was performed to identify variables associated with survival outcome., Results: We identified 13,205 lung transplant recipients, 9963 who received allografts from SRDs and 3242 who received allografts from IRDs. In both groups, most donors were White, male, and <30 years old. IRDs demonstrated greater rates of heavy alcohol, cigarette, and cocaine use. SRDs had greater rates of cancer, hypertension, previous myocardial infarction, and diabetes. Survival analysis demonstrated no significant difference in 90-day, 1-year, 3-year, or 5-year survival outcome between SRD and IRD recipients (P = .34, P = .67, P = .40, P = .52, respectively). Cox regression demonstrated that double-lung transplants were associated with 13% decreased mortality risk compared with single-lung (P = .0009)., Conclusions: IRD and SRD recipients demonstrated equivalent survival outcomes. Our study suggests that IRDs offer a safe approach to expand the donor pool and increase availability of lungs for transplantation., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: As life expectancies continue to increase, a greater proportion of older patients will require lung transplants (LTs). However, there are no well-defined age cutoffs for which LT can be performed safely. At our high-volume LT centre, we explored outcomes for LT recipients ≥70 vs <70 years old., Methods: This is a retrospective single-centre study of survival after LT among older recipients. Data were stratified by recipient age (≥70 vs <70 years old) and procedure type (single versus double LT). Demographics and clinical variables were compared using Chi-square test and 2 sample t-test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching., Results: A total of 988 LTs were performed at our centre over 10 years, including 289 LTs in patients ≥70 years old and 699 LTs in patients <70 years old. The recipient groups differed significantly by race (P < 0.0001), sex (P = 0.003) and disease aetiology (P < 0.0001). Older patients were less likely to receive a double LT compared to younger patients (P < 0.0001) and had lower rates of intraoperative cardiopulmonary bypass (P = 0.019) and shorter length of stay (P = 0.001). Both groups had overall high 1-year survival (85.8% vs 89.1%, respectively). Survival did not differ between groups after propensity matching (P = 0.15)., Conclusions: Our data showed high survival for older and younger LT recipients. There were no statistically significant differences observed in survival between the groups after propensity matching, however, a trend in favour of younger patients was observed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population., Methods: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating., Results: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women., Conclusion: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To investigate the impact of donor-recipient (DR) sex matches on survival after lung transplantation while controlling for size difference in the United Network of Organ Sharing (UNOS) database., Methods: We performed a retrospective study of 27,423 lung transplant recipients who were reported in the UNOS database (January 2005-March 2020). Patients were divided into groups based on their respective DR sex match: male to male (MM), male to female (MF), female to female, (FF), and female to male (FM). Kaplan-Meier curve and Cox regression with log-rank tests were used to assess 1-, 3-, 5-, and 10-year survival. We also modeled survival for each group after controlling for size-related variables via the Cox regression., Results: Kaplan-Meier curves showed overall significance at 1-, 3-, 5-, and 10-year end points ( P  < .0001). Estimated median survival time based on Kaplan-Meier analysis were 6.41 ± 0.15, 6.13 ± 0.18, 5.86 ± 0.10, and 5.37 ± 0.17 years for FF, MF, MM, and FM, respectively ( P  < .0001). After we controlled for size differences, FF had statistically significantly longer 5- and 10-year survival than all other cohorts. MF also had statistically significantly longer 5- and 10-year survival than FM., Conclusions: When variables associated with size were controlled for, FF had improved survival than other DR groups. A female recipient may experience longer survival with a female donor's lungs versus a male donor's lungs of similar size., Competing Interests: Y.T. reported clinical research and grant support from Transmedics Incorporated, Cerus Corporation ReciPe Study, and EvaHeart Incorporated. This had no relationship with the current study and has not affected the integrity of our report. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Introduction: Lung transplantation is the last option for patients with end-stage interstitial lung disease (ILD), yet organ allocation remains a challenge. This single-center study investigated the correlation of procedure type and donor and recipient age with survival outcomes in patients with ILD., Methods: We performed a retrospective study of lung recipients diagnosed with ILD who were transplanted in our center. Survival was assessed using Kaplan-Meier curves and log-rank tests according to the following variables: double lung transplant (DLT) or single lung transplant (SLT), recipient age <65 and ≥65, recipient sex, donor sex, and donor age. Cox proportional hazards regression was performed using the same variables. P values < 0.05 were considered significant., Results: Of 969 lung recipients transplanted at our center, 648 (66.8%) were diagnosed with ILD. There was no significant difference in survival for patients <65 or ≥65 when compared by DLT versus SLT. There were no significant differences in survival based on donor age. Survival at 5 y was significantly higher for recipient age <65 versus ≥65 (P = 0.0014). For DLT patients <65 or ≥65, there was no significant survival difference. However, for SLT patients, survival at 5 y was significantly higher for patients <65 (P = 0.0109)., Conclusions: Our findings suggest that donor age did not have a significant association with survival of patients with ILD posttransplant. In older patients with ILD, there was no significant difference for DLT versus SLT. However, within the SLT group, younger patients with ILD showed better survival compared to older patients., (Copyright © 2023. Published by Elsevier Inc.)

Drug-induced taste disorders are a serious problem in an aging society. This study investigated the mechanisms underlying taste disturbances induced by diclofenac, a non-steroidal anti-inflammatory drug that reduces pain and inflammation by inhibiting the synthesis of prostaglandins by cyclooxygenase enzymes (COX-1 and COX-2). RT-PCR analyses demonstrated the expression of genes encoding arachidonic acid pathway components such as COX-1, COX-2 and prostaglandin synthases in a subset of mouse taste bud cells. Double-staining immunohistochemistry revealed that COX-1 and cytosolic prostaglandin E synthase (cPGES) were co-expressed with taste receptor type-1 member-3 (T1R3), a sweet/umami receptor component, or gustducin, a bitter/sweet/umami-related G protein, in a subset of taste bud cells. Long-term administration of diclofenac reduced the expression of genes encoding COX-1, gustducin and cPGES in mouse taste buds and suppressed both the behavioral and taste nerve responses to sweet and umami taste stimuli but not to other tastants. Furthermore, diclofenac also suppressed the responses of both mouse and human sweet taste receptors (T1R2/T1R3, expressed in HEK293 cells) to sweet taste stimuli. These results suggest that diclofenac may suppress the activation of sweet and umami taste cells acutely via a direct action on T1R2/T1R3 and chronically via inhibition of the COX/prostaglandin synthase pathway inducing down-regulated expression of sweet/umami responsive components. This dual inhibition mechanism may underlie diclofenac-induced taste alterations in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hirayama, Iwata, Oike, Kawabata, Nagasato, Takai, Sanematsu, Takahashi and Shigemura.)

Background: Coronary artery disease is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation., Methods: A retrospective analysis of all single and double lung transplant patients from Feb, 2012 to Aug, 2021 at a single center was performed (n = 880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received preoperative coronary artery bypass grafting, (3) those who received coronary artery bypass grafting during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. A p value< 0.05 was considered significant., Results: Most patients receiving LTx were male and white. Pump type (p = 0.810), total ischemic time (p = 0.994), warm ischemic time (p = 0.479), length of stay (p = 0.751), and lung allocation score (p = 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-coronary artery bypass grafting group had a higher portion of single LTx procedures (p = 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p = 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009)., Conclusions: Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Drug-induced taste disorders reduce quality of life, but little is known about the molecular mechanisms by which drugs induce taste disturbances. In this study, we investigated the short-term and long-term effects of the antiarrhythmic drug flecainide, which is known to cause taste dysfunction. Analyses of behavioral responses (licking tests) revealed that mice given a single intraperitoneal injection of flecainide exhibited a significant reduction in preference for a sour tastant (HCl) but not for other taste solutions (NaCl, quinine, sucrose, KCl and monopotassium glutamate) when compared with controls. Mice administered a single dose of flecainide also had significantly higher taste nerve responses to HCl but not to other taste solutions. Compared with controls, mice administered flecainide once-daily for 30 d showed a reduced preference for HCl without any changes in the behavioral responses to other taste solutions. The electrophysiological experiments using HEK293T cells transiently expressing otopetrin-1 (Otop1; the mouse sour taste receptor) showed that flecainide did not alter the responses to HCl. Taken together, our results suggest that flecainide specifically enhances the response to HCl in mice during short-term and long-term administration. Although further studies will be needed to elucidate the molecular mechanisms, these findings provide new insights into the pathophysiology of drug-induced taste disorders., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Kawabata et al.)

Background: We hypothesized that outcomes after 2 staged, contralateral single lung transplantation procedures (SSLTs) may be equivalent to those of double lung transplantation (DLT) by capitalizing on the known long-term survival advantages of DLT., Methods: Using the United Network for Organ Sharing data set (1987-2018), the largest national data set available, the outcomes of 278 SSLTs were retrospectively analyzed and compared with the outcomes of 21,121 standard DLTs., Results: During SSLT, the median interval between the 2 transplants was 960 days, and the indication for the second transplant was most often chronic lung allograft dysfunction (n = 148; 53.2%) or the same disease that necessitated the first transplant (n = 81; 29.1%). The patients who underwent SSLT were significantly older and had a higher baseline creatinine level than the patients who underwent DLT. Most posttransplantation short-term outcomes were equivalent between the second stage of SSLT and DLT, but renal insufficiency requiring hemodialysis was notably higher after SSLT. There were no differences in long-term survival. In multivariate analysis, baseline creatinine, O 2 support at rest, ventilator support at the time of the second transplantation, and posttransplantation renal insufficiency requiring dialysis were independent predictors of 1-year mortality after SSLT., Conclusions: Over a study period of 30 years, long-term survival after SSLT was comparable with survival after DLT. With further analysis of individual risk profiles, including the contributions of preoperative renal function and functional status, SSLT can be a valuable option for patients who would have undergone single lung transplantation to reap the long-term benefits of a second transplant., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

GPRC5C is an orphan G protein-coupled receptor (GPCR) that belongs to the class C GPCR family. Although GPRC5C is expressed in various organs, its function and ligand are still undetermined. We found that GPRC5C is expressed in mouse taste cells, enterocytes, and pancreatic α-cells. In functional imaging assays, HEK293 cells heterologously expressing GPRC5C and the chimeric G protein α subunit Gα16-gust44 showed robust intracellular Ca 2+ increases in response to monosaccharides, disaccharides, and a sugar alcohol, but not an artificial sweetener or sweet-tasting amino acid. Notably, Ca 2+ increases occurred after washout, not during stimulation. Our findings suggest that GPRC5C has receptor properties which lead to novel 'off' responses to saccharide detachment and may work as an internal or external chemosensor specifically tuned to natural sugars., (© 2023 Federation of European Biochemical Societies.)

On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the K ATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake., Competing Interests: The authors declare no competing financial interest.

In patients with severe acute respiratory distress syndrome caused by coronavirus 2019 (COVID-19), mortality remains high despite optimal medical management. Extracorporeal membrane oxygenation (ECMO) has been widely used to support such patients. ECMO is not a perfect solution; however, there are several limitations and serious complications associated with ECMO use. Moreover, the overall short-term mortality rate of patients with COVID-19 supported by ECMO is high (~30%). Some patients who survive severe acute respiratory distress syndrome have chronic lung failure requiring oxygen supplementation, long-term mechanical ventilation, or ECMO support. Although lung transplant remains the most effective treatment for patients with end-stage lung failure from COVID-19, optimal patient selection and transplant timing for patients with COVID-19-related lung failure are not clear. Access to an artificial lung (AL) that can be used for long-term support as a bridge to transplant, bridge to recovery, or even destination therapy will become increasingly important. In this review, we discuss why the COVID-19 pandemic may drive progress in AL technology, challenges to AL implementation, and how some of these challenges might be overcome., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Mammalian taste bud cells are composed of several distinct cell types and differentiated from surrounding tongue epithelial cells. However, the detailed mechanisms underlying their differentiation have yet to be elucidated. In the present study, we examined an Ascl1-expressing cell lineage using circumvallate papillae (CVP) of newborn mice and taste organoids (three-dimensional self-organized tissue cultures), which allow studying the differentiation of taste bud cells in fine detail ex vivo. Using lineage-tracing analysis, we observed that Ascl1 lineage cells expressed type II and III taste cell markers both CVP of newborn mice and taste organoids. However, the coexpression rate in type II cells was lower than that in type III cells. Furthermore, we found that the generation of the cells which express type II and III cell markers was suppressed in taste organoids lacking Ascl1-expressing cells. These findings suggest that Ascl1-expressing precursor cells can differentiate into both type III and a subset of type II taste cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The sweet taste receptor plays an essential role as an energy sensor by detecting carbohydrates. However, the dynamic mechanisms of receptor activation remain unclear. Here, we describe the interactions between the transmembrane domain of the G protein-coupled sweet receptor subunit, TAS1R3, and allosteric modulators. Molecular dynamics simulations reproduced species-specific sensitivity to ligands. We found that a human-specific sweetener, cyclamate, interacted with the mouse receptor as a negative allosteric modulator. Agonist-induced allostery during receptor activation was found to destabilize the intracellular part of the receptor, which potentially interfaces with the Gα subunit, through ionic lock opening. A common human variant (R757C) of the TAS1R3 exhibited a reduced response to sweet taste, in support of our predictions. Furthermore, histidine residues in the binding site acted as pH-sensitive microswitches to modulate the sensitivity to saccharin. This study provides important insights that may facilitate the prediction of dynamic activation mechanisms for other G protein-coupled receptors., (© 2023. The Author(s).)

Background: The role of lung transplantation for coronavirus disease 2019 (COVID-19)-related lung failure is evolving as the pandemic persists., Methods: From January 2021 to April 2022, 20 patients (median age 62 y; range 31-77) underwent lung transplantation for COVID-related lung failure at our institution. We reviewed their clinical and intraoperative characteristics and early outcomes including postoperative complications., Results: Eleven patients (55%) had chronic lung disease when they contracted COVID-19. All 20 patients required hospitalization for antivirus treatment. Median lung allocation score was 74.7 (33.1-94.0). Thirteen patients (65%) underwent single-lung transplants, and 7 patients (35%) underwent double-lung transplants. Concomitant coronary artery bypass graft surgery was performed in 2 (10%) patients because of severe coronary artery disease. Postoperatively, venovenous extracorporeal membrane oxygenation was needed in 3 patients (15%) because of severe primary graft dysfunction; all were eventually weaned. Ten patients (50%) experienced deep venous thrombosis, and 1 eventually developed a major pulmonary embolus. The median intensive care unit stay and hospital stays were 6.5 d (3-44) and 18 d (7-77), respectively. During a median follow-up of 201 d (47-418), we experienced 1 late mortality due to COVID-19-related myocarditis. Among the 13 patients with single-lung transplant, 5 demonstrated improvement in their native lungs., Conclusions: Lung transplantation yielded favorable early outcomes in a heterogeneous patient cohort that included older patients, obese patients, and patients with coronary artery disease or preexisting chronic lung disease. Our data also shed light on the transforming role of lung transplantation for the pulmonary sequelae of a complex multisystem COVID-19 disorder., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Little is known about the molecular mechanisms underlying drug-induced taste disorders, which can cause malnutrition and reduce quality of life. One of taste disorders is known adverse effects of bisphosphonates, which are administered as anti-osteoporotic drugs. Therefore, the present study evaluated the effects of risedronate (a bisphosphonate) on taste bud cells. Expression analyses revealed that farnesyl diphosphate synthase (FDPS, a key enzyme in the mevalonate pathway) was present in a subset of mouse taste bud and tongue epithelial cells, especially type III sour-sensitive taste cells. Other mevalonate pathway-associated molecules were also detected in mouse taste buds. Behavioral analyses revealed that mice administered risedronate exhibited a significantly enhanced aversion to HCl but not for other basic taste solutions, whereas the taste nerve responses were not affected by risedronate. Additionally, the taste buds of mice administered risedronate exhibited significantly lower mRNA expression of desmoglein-2, an integral component of desmosomes. Taken together, these findings suggest that risedronate may interact directly with FDPS to inhibit the mevalonate pathway in taste bud and tongue epithelial cells, thereby affecting the expression of desmoglein-2 related with epithelial barrier function, which may lead to alterations in behavioral responses to HCl via somatosensory nerves., (© 2022. The Author(s).)

Introduction: In 2013, the US Public Health Service (PHS) updated guidelines for high-risk donor organs and renamed the category increased risk. Project Aims: We compared survival of patients who received increased risk or non-increased risk donor lungs to determine if PHS designated increased risk donor lungs were an underutilized resource. Design: This retrospective cohort analysis compared survival and utilization rates of increased-risk and non-increased-risk donor lungs used in lung transplantation at a single institution over a period of 8 years (Feb-2012 through Mar-2020). Survival was assessed using Kaplan-Meier analysis and compared by log-rank test. Cox proportional hazards modeling was used to analyze impact on survival of variables significantly associated with risk status, including recipient ethnicity, lung allocation score (LAS), donor age, year of transplant procedure, and lung transplant type. Results: Of 744 lung transplant recipients from February 2012 through March 2020, there were 192 (26%) recipients of increased risk designated lungs. In 2012 and 2013, 6% and 0% respectively of the lungs transplanted were increased risk labeled. After the PHS guidelines were nationally implemented in February 2014, the proportion of increased risk lung transplants rose to 7% (2014), 21% (2015), 27% (2016), 35% (2017), 28% (2018), 27% (2019), and 40% (January-March 2020). Kaplan-Meier analysis and log-rank test comparison showed no significant difference in survival between patients that received increased risk versus non-increased risk labeled lungs (P = 0.47). Conclusions: Our analysis suggested the 2013 PHS increased risk designation threatened underutilization of viable donor lungs, providing further support for the 2020 PHS changes.

Background: Although double lung transplant is recommended in patients with severe secondary pulmonary hypertension (SPH), our institutional experiences suggest a role for single lung transplant in these patients. Here, we review our experience prioritizing single lung transplant in patients with SPH to minimize their surgical burden., Methods: We conducted a retrospective review of our lung transplant database to identify patients with SPH who underwent single lung transplant. Patients were stratified as either mild SPH (mean pulmonary artery pressure 25-40 mm Hg) or severe SPH (mean pulmonary artery pressure >40 mm Hg). Singe lung recipients without PH transplanted over the same time were also examined., Results: Between January 2017 and December 2019, 318 patients underwent single lung transplantation; 217 had mild SPH (68%), and 59 had severe SPH (18.5%). Forty-two patients without PH underwent single lung transplant. When the groups were compared, significantly higher pulmonary vascular resistance was noted in the severe SPH group, and obesity was noted in both the mild and severe SPH groups. Although the severe SPH group required more intraoperative cardiopulmonary support (37.3% versus 10.3% versus 4.7%, P < 0.05), there were no significant differences in most major postoperative parameters, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Survival 1 y posttransplant was not significantly different among the groups (93.2% versus 89.4% versus 92.9%, P = 0.58)., Conclusions: Our experience supports the option of single lung transplantation with appropriate intraoperative mechanical circulatory support in patients with SPH. This strategy is worth pursuing, especially with ongoing donor lung shortages., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Postoperative bronchial anastomotic complications are not uncommon in lung transplant recipients. We investigated 2 surgical techniques (continuous and interrupted sutures) during bronchial anastomosis, comparing survival and postoperative bronchial complications., Methods: We retrospectively analyzed 421 patients who were transplanted in our center (February 2012 to March 2018). Patients were divided according to bronchial anastomotic technique (continuous or interrupted). Demographics and clinical parameters were compared for significance (P < .05). Comparison of postoperative morbidity included bronchial complications, venovenous extracorporeal membrane oxygenation support, and intervention requirements. Survival was assessed using Kaplan-Meier curve and log-rank tests (P < .05)., Results: Of the 421 patients, 290 underwent bronchial anastomoses with continuous suture; 44 of these patients had postoperative bronchial complications (15.2%). Contrarily, 131 patients underwent the interrupted suture technique; 9 patients in this group had postoperative bronchial complications (6.9%). Demographics and clinical parameters included age, sex, ethnicity, etiology, lung allocation score, body mass index, donor age, lung transplant type, cardiopulmonary bypass usage, surgical approaches, and median length of stay. Postoperative complications (continuous vs interrupted) were bronchial complications (P = .017), venovenous extracorporeal membrane oxygenation support (P = .41), venoarterial extracorporeal membrane oxygenation support (P = .38), and complications requiring dilatation with stent placement (P = .09). Kaplan-Meier curve showed better survival in the interrupted group (P = .0002)., Conclusions: Our study demonstrated the comparable postoperative results between the continuous and interrupted technique., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Currently, standard practice is to use the continuous suturing technique on the bronchial anastomosis during lung transplantation. This study used a large cohort to investigate and contrast continuous and interrupted suturing techniques, comparing survival outcomes and occurrence of postoperative bronchial complications to examine if utilization of interrupted suturing has merit., Methods: Survival outcomes of 740 single-center lung transplant recipients over 8 y (February 2012-March 2020) were compared by suturing techniques: either continuous or interrupted at the bronchial anastomosis. Clinical parameters and demographics were compared between two suturing groups, with P values < 0.05 considered significant. The groups were compared for postoperative morbidity, including need for bronchial interventions. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox regression analysis was run with statistically significant variables to study association with survival., Results: Of the 740 patients, 462 received the continuous suturing technique and 278 received the interrupted suturing technique. Most demographic and clinical data were not statistically significant between the two groups, and those that were significant were not associated with worse survival outcomes, with the exception of the variable diagnosis. Bronchial complications were comparable between the continuous and interrupted groups (12.6% versus 10.4%, P = 0.382). Extracorporeal membrane oxygenation (ECMO) use did not differ significantly between the two groups (P = 0.12). The Kaplan-Meier curve showed comparable survival between groups (P = 0.98), and Cox regression analysis showed that only diagnosis, bronchial complications, and ECMO utilization were associated with different survival outcomes. Chronic obstructive pulmonary disorder was shown to be associated with more favorable survival outcomes as opposed to idiopathic pulmonary fibrosis and the category "other". The need for ECMO and the occurrence of a bronchial complication were also associated with worse survival outcomes., Conclusions: Both techniques showed reasonable post-transplant outcomes, as our study demonstrated similar survival outcomes and bronchial complication rates., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Anastomosis management is the main challenge of airway resection and reconstruction, and postoperative anastomotic complications, including ischemia, stenosis, dehiscence, and separation may lead to severe outcomes and a poor prognosis. The anastomotic buttress is vital in airway reconstruction, but the selection of surgical buttress and reinforcement remains controversial. We aimed to demonstrate and evaluate the buttress options of anastomosis, including their preoperative characteristics, the intraoperative process, and the incidence of postoperative complications to help address the controversy regarding anastomosis management., Methods: This retrospective study was conducted at a single institution. Patients who underwent airway reconstruction with anastomotic wrapping from Jan. 2019 to Sep. 2021 were enrolled in this study and preoperative characteristics and operational features were collected. All patients were carefully followed up by telephone and outpatient. Their postoperative complications and postoperative status after 6 months were recorded. The surgical procedures and clinical characteristics of the buttress options of anastomosis were assessed., Results: A total of 62 patients undergoing either cervical tracheal, thoracic tracheal, carinal, or secondary carinal and main bronchus resection and reconstruction were evaluated. The anastomotic buttress used included mediastinal pleural flap (24/62, 38.7%), anterior cervical muscle (14/62, 22.6%), sternocleidomastoid (2/62, 3.2%), thymus flap (12/62, 19.4%), intercostal muscle flap (2/62, 3.2%), biological patch (2/62, 3.2%), prepericardial fat (1/62, 1.6%), thyroid gland (1/62, 1.6%), pectoralis major flap (2/62, 3.2%), and omental flap (2/62, 3.2%). All procedures produced satisfactory results without short-term anastomotic complications. A follow-up for 6 months was conducted and all patients were alive postoperatively. Tracheomalacia stenosis postoperatively occurred in 3 patients and they were subsequently treated with an endotracheal stent. One patient had tumor recurrence 3 months after surgery and received adjuvant chemotherapy., Conclusions: Various anastomotic wrapping materials are used in airway reconstruction. Different utilizations of buttress are selected according to the anatomic characteristics and the reconstruction method used. This study indicated that appropriate surgical buttresses for wrapping anastomoses are legitimate alternatives to reduce the risk of anastomotic complications., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-406/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Backgroud: Idiopathic pulmonary fibrosis (IPF) accounts for a marked proportion of diagnoses on the US lung transplant (LTx) list. The effects of single (SLT) versus double LTx (DLT) and lung donor age on survival in IPF remain unclear and were investigated in this study., Methods: We retrospectively assessed survival of LTx recipients with IPF at a single institution from February 2012-March 2020. Survival was analyzed and compared between LTx types (SLT and DLT), donor ages, and the combined groups (LTx type & donor age) using Kaplan-Meier survival analysis and compared by log-rank test. P-values less than 0.05 were considered significant., Results: Of 744 LTx patients at our institution, 307 (41.3%) were diagnosed with IPF, of which 208 (67.8%) were SLT, and 97 (31.6%) were DLT (2 excluded patients underwent heart-lung transplantation). There was no significant difference in survival due to LTx type (P = 0.41) or for patients with donor age <50 or ≥50 y (P = 0.46). Once stratified by both LTx type and donor age, analysis showed no significant difference in survival between the four groups (P = 0.69)., Conclusions: With ethical consideration for organ allocation, as the average age of the US population increases, donor lungs aged ≥50 are an increasingly useful resource in LTx. Our findings suggest donor age and LTx type do not significantly affect survival. Therefore, SLT, and donor lungs aged ≥50 ought to be more readily considered as non-inferior options for LTx in patients with IPF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation., Methods: We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants., Results: The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity., Conclusions: Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist., (© 2021. The Author(s).)

Objectives: Debate continues on whether a bilateral (BLT) or a single lung transplantation (SLT) is preferred for patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study is to examine the interplay between patient age and transplant type on survival outcomes., Methods: We performed a retrospective study of lung transplants for COPD at our centre from February 2012 to March 2020 (n = 186). Demographics and clinical parameters were compared between patients based on their age (≤65 vs >65 years old) and type of transplant (single vs bilateral). Cox proportional hazards regression was also performed. P-values <0.05 were considered significant., Results: Of the 186 patients with COPD who received lung transplants, 71 (38.2%) received BLTs and 115 (61.8%) received SLTs. There was no significant difference in survival outcomes when looking at patients with single versus BLTs (P = 0.870). There was also no difference in survival between the 2 age groups ≤65 versus > 65 years (P = 0.723). The Cox model itself also did not show a statistically significant improvement in survival outcomes (P = 0.126)., Conclusions: Lung transplant outcomes in patients with end-stage COPD demonstrated non-inferior results in patients with an SLT compared to patients with a BLT. When we compared the age groups, neither transplant type showed superior survival benefits, suggesting there may be some utility in an SLT in younger recipients., (Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery 2021.)

Background: Venous thromboembolism (VTE) post lung transplantation is common and has been associated with worse post transplant survival. We report a comprehensive single center review of VTE incidence in the first post transplant year, investigate modifiable risk factors and assess impact on short term outcomes., Methods: Retrospective review of all lung transplant recipients between August 2016 to 2018 at Temple University Hospital. Patients were followed for 1 year post transplant. All patients were screened for deep venous thrombosis (DVT) within the first 2 weeks with a venous duplex study. Pre transplant, intra operative, post operative variables, and peri-operative practice patterns were compared between VTE positive and VTE negative groups. Logistic regression modeling was used to identify risk factors for early VTE (VTE within 30 days after transplant)., Results: A total of 235 patients were included in the study, 58 patients (24.7%) developed a VTE in the first post transplant year. Median time to diagnosis was 17 days. Of the patients with VTE, 76% had an isolated DVT, 13.5 % had an isolated pulmonary embolism (PE), and 10.3% had concomitant DVT and PE. In a multivariate logistic regression model, cardiopulmonary bypass (CPB) (OR 1.93 p = 0.015) and interruption of VTE prophylaxis (OR 4.42 p < 0.0001) were predictive of early VTE., Conclusion: VTE post lung transplant is common despite the use of prophylactic anticoagulation. CPB use and interruption of DVT prophylaxis are risk factors for early post transplant VTE. Measures to ensure consistent and uninterrupted prophylaxis may help decrease VTE incidence after lung transplantation., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: A difference in the lower body to upper body ratio between similarly heighted individuals could lead to inadequately matched transplants. There has been a perception in clinical circles that body ratio varies between people of different races, and investigating this supposition would prove useful in increasing transplant match accuracy. The investigation's purpose was to derive an equation with a greater correlation to lung length than height alone., Methods: Lung transplantation donor data for 480 adult patients was obtained and divided by ethnicity-Caucasian, African American, and Hispanic. Height, weight, age, sex, right and left lung length were evaluated for significance. The R 2 value of the multiple linear regression with these variables vs. lung length was determined and tested in a separate dataset of 100 patients., Results: Only the distribution of height was significant between the 3 ethnicities ( P = 0.041). None of the ANCOVAs were significant ( P < 0.05) or near significant ( P < 0.10). For the strongest correlation model with lung length, height had a linear fit, weight had a cubic fit, and age had a logistic fit. Multiple regression models were successfully created for right lung (R 2 = 0.202) and left lung (R 2 = 0.213). Independent testing showed a correlation of 0.131 and 0.136, respectively., Conclusion: Using demographic information from the donor and recipient as proxies for estimating lung size should only serve as a rough guide due to their weak correlation with lung length. As a result, for greater accuracy, donor-recipient matching should be individualized by taking donor and recipient chest X-Rays and/or TLC into consideration.

Careful donor quality assessment and size match can impact long-term survival in lung transplantation. With this article, we review the conceptual and practical aspects of the preoperative donor lung quality assessment and size matching., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2021.)

Taste buds are complex sensory organs embedded in the epithelium of fungiform papillae (FP) and circumvallate papillae (CV). The sweet, bitter, and umami tastes are sensed by type II taste cells that express taste receptors (Tas1rs and Tas2rs) coupled with the taste G-protein α-gustducin. Recent studies revealed that the taste response profiles of α-gustducin-expressing cells are different between FP and CV, but which genes could generate such distinctive cell characteristics are still largely unknown. We performed a comprehensive transcriptome analysis on α-gustducin-expressing cells in mouse FP and CV by single-cell RNA sequencing combined with fluorescence-activated cell sorting. Transcriptome profiles of the α-gustducin-expressing cells showed various expression patterns of taste receptors. Our clustering analysis defined the specific cell populations derived from FP or CV based on their distinct gene expression. Immunohistochemistry confirmed the specific expression of galectin-3, encoded by Lgals3, which was recognized as a differentially expressed gene in the transcriptome analysis. Our work provides fundamental knowledge toward understanding the genetic heterogeneity of type II cells, potentially revealing differential characterization of FP and CV taste bud cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R 2  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients., (© 2020 Wiley Periodicals LLC.)

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.

The unprecedented public health emergency caused by the acute viral respiratory coronavirus disease (COVID-19) has drastically changed current practices in solid organ transplantation, markedly so for transplantation of the lungs, the major target of the virus. Although national and state authorities do not recommend postponing transplant procedures, most specialists are reluctant to proceed due to substantial uncertainty and increased risks in the midst of the pandemic. There is an urgent need for evidence-based directions to move forward. Here, we offer our insights as specialists at a high-volume center located in a geographical area with high infection rates., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Lung transplantation may be a final destination therapy in lung failure, but limited donor organ availability creates a need for alternative management, including artificial lung technology. This invited review discusses ongoing developments and future research pathways for respiratory assist devices and tissue engineering to treat advanced and refractory lung disease. An overview is also given on the aftermath of the coronavirus disease 2019 pandemic and lessons learned as the world comes out of this situation. The first order of business in the future of lung support is solving the problems with existing mechanical devices. Interestingly, challenges identified during the early days of development persist today. These challenges include device-related infection, bleeding, thrombosis, cost, and patient quality of life. The main approaches of the future directions are to repair, restore, replace, or regenerate the lungs. Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems and can be used to bridge lung failure patients to transplantation. Progress in the development of microchannel-based devices has provided the concept of biomimetic devices that may even enable intracorporeal implantation. Tissue engineering and cell-based technologies have provided the concept of bioartificial lungs with properties similar to the native organ. Recent progress in artificial lung technologies includes continued advances in both engineering and biology. The final goal is to achieve a truly implantable and durable artificial lung that is applicable to destination therapy., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: Despite the benefits of ex vivo lung perfusion (EVLP) such as lung reconditioning, preservation, and evaluation before transplantation, deleterious effects, including activation of proinflammatory cascades and alteration of metabolic profiles have been reported. Although patient outcomes have been favorable, further studies addressing optimal conditions are warranted. In this study, we investigated the role of the immunosuppressant drug cyclosporine A (CyA) in preserving mitochondrial function and subsequently preventing proinflammatory changes in lung grafts during EVLP., Methods: Using rat heart-lung blocks after 1-hour cold preservation, an acellular normothermic EVLP system was established for 4 hours. CyA was added into perfusate at a final concentration of 1 μM. The evaluation included lung graft function, lung compliance, and pulmonary vascular resistance as well as biochemical marker measurement in the perfusate at multiple time points. After EVLP, single orthotopic lung transplantation was performed, and the grafts were assessed 2 hours after reperfusion., Results: Lung grafts on EVLP with CyA exhibited significantly better functional and physiological parameters as compared with those without CyA treatment. CyA administration attenuated proinflammatory changes and prohibited glucose consumption during EVLP through mitigating mitochondrial dysfunction in lung grafts. CyA-preconditioned lungs showed better posttransplant lung early graft function and less inflammatory events compared with control., Conclusions: During EVLP, CyA administration can have a preconditioning effect through both its anti-inflammatory and mitochondrial protective properties, leading to improved lung graft preservation, which may result in enhanced graft quality after transplantation.

The purpose of this study was to examine the influence of extracorporeal membrane oxygenation (ECMO) as a bridge to reoperative lung transplantation (LT) on outcomes and survival. A total of 1960 LT recipients transplanted a second time between 2005 and 2017 were analyzed using the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN). Of these recipients, 99 needed ECMO as a bridge to reoperative LT. Mean age was 50 ± 14 years, 47% were females, and the group with ECMO was younger [42 (30-59) vs. 55 (40-62) years]. In both univariate and multivariable analyses (adjusting for age and gender), the ECMO group had greater incidence of prolonged ventilation >48 h (83% vs. 40%, P < 0.001) and in-hospital dialysis (27% vs. 7%, P < 0.001). There were no differences in incidence of acute rejection (15% vs. 11%, P = 0.205), airway dehiscence (4% vs. 2%, P = 0.083), stroke (3% vs. 2%, P = 0.731), or reintubation (20% vs. 20%, P = 0.998). Kaplan-Meier survival analysis showed the ECMO group had reduced 1-year survival (66.6% vs. 83.0%, P < 0.001). After covariate adjustment, the ECMO group only had increased risk for 1-year mortality in the 2005-2011 era (HR = 2.57, 95% CI = 1.45-4.57, P = 0.001). For patients who require reoperative LT, bridging with ECMO was historically a significant predictor of poor outcome, but may be improving in recent years., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Bitter taste receptors TAS2Rs detect noxious compounds in the oral cavity. Recent heterologous expression studies reported that some compounds function as antagonists for human TAS2Rs. For examples, amino acid derivatives such as γ-aminobutyric acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-Lysine (BCML) blocked responses to quinine mediated by human TAS2R4. Probenecid inhibited responses to phenylthiocarbamide mediated by human TAS2R38. In this study, we investigated the effects of these human bitter receptor antagonists on behavioral lick responses of mice to elucidate whether these compounds also function as bitter taste blockers. In short-term (10 s) lick tests, concentration-dependent lick responses to bitter compounds (quinine-HCl, denatonium and phenylthiourea) were not affected by the addition of GABA or BCML. Probenecid reduced aversive lick responses to denatonium and phenylthiourea but not to quinine-HCl. In addition, taste cell responses to phenylthiourea were inhibited by probenecid. These results suggest some bitter antagonists of human TAS2Rs can work for bitter sense of mouse., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or perioperative revascularization on lung transplant survival outcomes is not adequately established., Methods: We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012 to 2018 (n = 468). Patients were split into 4 groups: (1) patients who received a preoperative percutaneous coronary intervention (n = 34), (2) those who received coronary artery bypass grafting (CABG) before transplantation (n = 25), (3) those that received concomitant CABG during transplantation (n = 29), and (4) those who had lung transplantation with no need for revascularization (n = 380). Groups were compared for demographics, surgical procedure, and survival outcomes., Results: The no-revascularization group was statistically younger than the rest (P = .001). The lung allocation score trended toward being higher in the concomitant coronary artery bypass group (P = .03). All groups were predominantly diagnosed with idiopathic pulmonary fibrosis. The proportion of patients with chronic obstructive pulmonary disease was greatest in the group not requiring revascularization (P = .001). Patients with previous CABG were more likely to receive a single lung transplant than a double one (21 versus 4; P = .054). Length of stay, posttransplant survival, and postoperative adverse events were similar among all groups., Conclusions: Results suggest that preoperative or intraoperative revascularization does not negatively affect survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)