CT-guided pretreatment biopsy diagnosis in patients with thymic epithelial tumours: diagnostic accuracy and risk of seeding.

AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.

Mechanical Control of Polaritonic States in Lead Halide Perovskite Phonons Strongly Coupled in THz Microcavity.

We demonstrate the generation and control of polaritonic states in perovskite phonon polaritons, which are strongly coupled in the middle of a flexible Fabry-Perot cavity. We fabricated flexible perovskite films on a microporous substrate coated with graphene oxide, which led to a virtually free-standing film incorporated into the microcavity. Rabi splitting was observed when the cavity resonance was in tune with that of the phonons. The Rabi splitting energy increased as the film thickness increased, reaching 1.9 meV, which is 2.4-fold higher than the criterion for the strong coupling regime. We obtained dispersion curves for various perovskite film thicknesses exhibiting two polariton branches; clear beats between the two polaritonic branches were observed in the time domain. Flexible cavity devices with perovskite phonons enable macroscopic control over the polaritonic energy states through bending processes, which add an additional degree of freedom in the manipulation of polaritonic devices.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Terahertz thermal curve analysis for label-free identification of pathogens.

In this study, we perform a thermal curve analysis with terahertz (THz) metamaterials to develop a label-free identification tool for pathogens such as bacteria and yeasts. The resonant frequency of the metasensor coated with a bacterial layer changes as a function of temperature; this provides a unique fingerprint specific to the individual microbial species without the use of fluorescent dyes and antibodies. Differential thermal curves obtained from the temperature-dependent resonance exhibit the peaks consistent with bacterial phases, such as growth, thermal inactivation, DNA denaturation, and cell wall destruction. In addition, we can distinguish gram-negative bacteria from gram-positive bacteria which show strong peaks in the temperature range of cell wall destruction. Finally, we perform THz melting curve analysis on the mixture of bacterial species in which the pathogenic bacteria are successfully distinguished from each other, which is essential for practical clinical and environmental applications such as in blood culture.

OPTN/SRTR 2020 Annual Data Report: Living Donor Collective

The first successful solid organ transplant was a living donor kidney transplant in 1954. Since then, living donation has been an important source of organs for kidney and liver transplants in the United States. Unfortunately, the demand for organs has not kept pace with the supply, and unlike deceased donor transplant, there has been little growth in the number of living donor transplants over the past decade. To better understand possible barriers to living donation and long-term risks attributable to donation, the Health Resources and Services Administration (HRSA) directed the Scientific Registry of Transplant Recipients (SRTR) to establish a national registry of all living donor candidates and donors evaluated at US transplant programs to acquire lifetime follow-up information. Other goals include understanding the factors associated with candidate approval and variation in approval practices across centers. A pilot program was conducted from June 2018 through September 2020 to inform baseline data collection and registration processes. In September 2020, the registry began recruiting additional sites evaluating candidates for living donation. Here, we describe candidates registered at participating living donor kidney and liver programs, from June 2018 through the end of 2020. Not all programs submitted data throughout the whole period. Data for kidney and liver living donor candidates are presented separately.

OPTN/SRTR 2020 Annual Data Report: Heart.

As we enter the third year of the new adult heart allocation policy, we are faced with the new challenges of the COVID-19 pandemic. In 2020, new listings (adult and pediatric) decreased slightly, with 4000 new listings in 2020, compared with 4087 in 2019; however, the number of adult heart transplants performed continued to increase, to 3715 in 2020. The number of pediatric heart transplants declined from 509 in 2019 to 465 in 2020. One-year and six-month posttransplant mortality rates in adult recipients have increased slightly since 2015 but have not significantly changed over the past decade. Overall, posttransplant mortality rates for adult recipients were 7.4% at six months and 9.4% at one year for transplants in 2019, 14.0% at three years for transplants in 2017, and 19.1% at five years for transplants in 2015. Although shorter-term posttransplant mortality rates have slightly increased, there has been a steady downward trend in longer-term mortality. Mortality rates for pediatric recipients were 5.7% at six months and 8.1% at one year for transplants in 2019, 11.6% at three years for transplants in 2017, and 15.2% at five years for transplants in 2015.

Adjuvant durvalumab for esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a placebo-controlled, randomized, double-blind, phase II study.

BACKGROUND: We evaluated the efficacy of adjuvant durvalumab after neoadjuvant concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: This randomized, double-blind, phase II study included patients with ESCC who underwent curative surgery after neoadjuvant CCRT. Patients were randomized to receive either durvalumab (20 mg/kg/i.v. every 4 weeks for 12 months) or placebo in a 1:1 ratio and were stratified by age and pathologic tumor stage. The primary endpoint was disease-free survival (DFS). RESULTS: Between March 2016 and June 2018, 86 patients were randomized to the durvalumab (n = 45) or placebo (n = 41) arm. The median follow-up duration was 38.7 months. There was no difference in DFS [hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.62-2.27, P = 0.61] or overall survival (HR 1.08, 95% CI 0.52-2.24, P = 0.85) between the two arms. Subgroup analysis was performed for patients for whom the post-CCRT programmed death-ligand 1 (PD-L1) expression profile could be assessed (n = 54). In the PD-L1-positive group, based on tumor proportion score ≥1%, durvalumab was associated with longer overall survival compared with the placebo (36-month survival rate: 94% versus 64%; HR 0.42, 95% CI 0.10-1.76), while in the PD-L1-negative group, it was associated with shorter overall survival (42% versus 55%; HR 1.53, 95% CI 0.48-4.83), showing the tendency of interaction between post-CCRT PD-L1 status and adjuvant durvalumab therapy for overall survival (interaction P = 0.18). CONCLUSIONS: We failed to demonstrate that adjuvant durvalumab improved survival after neoadjuvant CCRT in patients with ESCC. However, post-CCRT PD-L1 expression could predict the survival of patients who receive adjuvant durvalumab after neoadjuvant CCRT, which needs to be validated.

Light intensity dependence of organic solar cell operation and dominance switching between Shockley-Read-Hall and bimolecular recombination losses.

We investigated the variation of current density-voltage (J-V) characteristics of an organic solar cell (OSC) in the dark and at 9 different light intensities ranging from 0.01 to 1 sun of the AM1.5G spectrum. All three conventional parameters, short-circuit currents (Jsc), open-circuit voltage (Voc), and Fill factor (FF), representing OSC performance evolved systematically in response to light intensity increase. Unlike Jsc that showed quasi-linear monotonic increase, Voc and FF showed distinctive non-monotonic variations. To elucidate the origin of such variations, we performed extensive simulation studies including Shockley-Read-Hall (SRH) recombination losses. Simulation results were sensitive to defect densities, and simultaneous agreement to 10 measured J-V curves was possible only with the defect density of [Formula: see text]. Based on analyses of simulation results, we were able to separate current losses into SRH- and bimolecular-recombination components and, moreover, identify that the competition between SRH- and bimolecular-loss currents were responsible for the aforementioned variations in Jsc, Voc, and FF. In particular, we verified that apparent demarcation in Voc, and FF variations, which seemed to appear at different light intensities, originated from the same mechanism of dominance switching between recombination losses.

Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study.

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.

OPTN/SRTR 2019 Annual Data Report: Intestine.

Intestine transplant can be life-saving and can improve quality of life for patients with intestinal failure. Medical and surgical advances in treatment of intestinal failure over the past 10 to 15 years have resulted in fewer patients being added to the waiting list for intestine transplant alone or for intestine transplant in combination with liver transplant (and sometimes other organs). Consequently, fewer transplants are being performed. The numbers of listings and transplants fell to new lows in 2019. The number of programs performing transplants in at least one patient in 2019 was the lowest in the last decade, equal to 2014, at 15. Graft failure plateaued over the past decade, but early graft loss has increased in the past 2 years, notably in recipients of a combined liver and intestine allograft. Five-year patient survival for transplants in 2012-2014 varied little by graft type.

OPTN/SRTR 2019 Annual Data Report: Heart.

The new adult heart allocation policy was approved in 2016 and implemented in October 2018. This year's Annual Data Report provides early insight into the effects of this policy. In 2019, new listings continued to increase, with 4086 new candidates. Also in 2019, 3597 heart transplants were performed, an increase of 157 (4.6%) from 2018; 509 transplants occurred in children and 3088 in adults. Short- and long-term posttransplant mortality rates improved. Overall, Mortality rates for adult recipients were 6.4% at 6 months and 7.9% at 1 year for transplants in 2018, 14.4% at 3 years for transplants in 2016, and 20.1% at 5 years for transplants in 2014. Mortality rates for pediatric recipients were 6.3% at 6 months and 8.2% at 1 year for transplants in 2018, 10.3% at 3 years for transplants in 2016, and 17.8% at 5 years for transplants in 2014.

Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles.

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.

Potential anti-ageing effect of chondroitin sulphate through skin regeneration.

OBJECTIVE: Skin ageing is inevitably exposed through its typical features such as wrinkles and sagging. Therefore, skin anti-ageing is a major issue in cosmetic research to prevent and improve ageing symptoms using effective ingredients. Chondroitin sulphate (CS), a type of glycosaminoglycan, is an important structural component of the extracellular matrix (ECM) and is involved in various biological processes, such as cell proliferation, differentiation and migration. Here, we aimed to investigate the effects of CS on skin regeneration and examine its efficacy as a potential safe and effective skin anti-ageing ingredient. METHODS: We investigated the effects of CS on cell proliferation in normal human keratinocytes and fibroblasts. Then, cell migration, ECM synthesis and related signalling pathways were examined in fibroblasts through gene and protein expression analysis. Finally, the effect on skin wound healing and regeneration was validated using a full-thickness skin wound model and an aged skin model. RESULTS: Chondroitin sulphate treatment increased the proliferation of keratinocytes and fibroblasts. It also stimulated the migration and synthesis of ECM components of fibroblasts. Further analysis revealed that CS induced the expression of type I procollagen by activating the extracellular signal-regulated kinase pathway. Using a full-thickness skin wound model and an aged skin model, we confirmed that CS treatment promoted skin wound healing and regeneration. CONCLUSION: Together, our results indicated that CS has the potential to facilitate skin regeneration, implying that CS could be clinically applied to improve skin ageing.

OBJECTIF: Le vieillissement cutané est inévitable, dans ses caractéristiques intrinsèques nous trouvons l'apparition des rides et l'affaissement de la peau. Sachant cela, l'anti-âge cutané est un enjeu majeur de la recherche cosmétique où sa prévention ou son amélioration sont faites à l'aide d'ingrédients efficaces. Le sulfate de chondroïtine (CS), un type de glycosaminoglycane, est un composant structurel important de la matrice extracellulaire (ECM) et il est aussi impliqué dans les divers processus biologiques, tels que la prolifération, la différenciation et la migration cellulaire. Dans le travail présenté ici, nous avons étudié les effets du CS sur la régénération de la peau et son efficacité en tant qu'ingrédient anti-âge cutané sûr. MÉTHODES: Nous avons étudié les effets du CS sur la prolifération cellulaire des kératinocytes et fibroblastes humains normaux. Ensuite, la migration cellulaire, la synthèse de la ECM et les voies de signalisation associées ont été examinées dans les fibroblastes par l'analyse de l'expression des gènes et des protéines. Finalement, l'effet sur la cicatrisation et la régénération cutanées a été validé à l'aide d'un modèle de plaie cutanée « full thickness ¼ et d'un modèle de peau âgée. RÉSULTATS: Le traitement au sulfate de chondroïtine a augmenté la prolifération des kératinocytes et des fibroblastes. Il a également stimulé la migration et la synthèse des composants de la MEC des fibroblastes. Une analyse plus approfondie a démontré que CS induisait l'expression du procollagène du type I en activant la voie de la kinase régulée par le signal extracellulaire. En utilisant un modèle de plaie cutanée « full thickness ¼ et un modèle de peau âgée, nous avons confirmé que le traitement CS favorisait la cicatrisation et la régénération des blessures cutanées. CONCLUSION: Dans l'ensemble, nos résultats ont indiqué que le CS a le potentiel de faciliter la régénération de la peau, ce qui implique que le CS pourrait être appliqué cliniquement pour améliorer le vieillissement cutané.

Author Correction: Light Intensity-dependent Variation in Defect Contributions to Charge Transport and Recombination in a Planar MAPbI3 Perovskite Solar Cell.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Identifying different types of microorganisms with terahertz spectroscopy.

Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes. Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range. We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory. The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11. The yeasts exhibited particularly high dielectric constants reaching 5.63-5.97, which were even higher than that of water. These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials. In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment. By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water. Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and ß-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.

Light Intensity-dependent Variation in Defect Contributions to Charge Transport and Recombination in a Planar MAPbI3 Perovskite Solar Cell.

We investigated operation of a planar MAPbI3 solar cell with respect to intensity variation ranging from 0.01 to 1 sun. Measured J-V curves consisted of space-charge-limited currents (SCLC) in a drift-dominant range and diode-like currents in a diffusion-dominant range. The variation of power-law exponent of SCLC showed that charge trapping by defects diminished as intensity increased, and that drift currents became eventually almost ohmic. Diode-like currents were analysed using a modified Shockley-equation model, the validity of which was confirmed by comparing measured and estimated open-circuit voltages. Intensity dependence of ideality factor led us to the conclusion that there were two other types of defects that contributed mostly as recombination centers. At low intensities, monomolecular recombination occurred due to one of these defects in addition to bimolecular recombination to result in the ideality factor of ~1.7. However, at high intensities, another type of defect not only took over monomolecular recombination, but also dominated bimolecular recombination to result in the ideality factor of ~2.0. These ideality-factor values were consistent with those representing the intensity dependence of loss-current ratio estimated by using a constant internal-quantum-efficiency approximation. The presence of multiple types of defects was corroborated by findings from equivalent-circuit analysis of impedance spectra.