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As many people with intellectual disabilities (ID) live longer, the need for access to quality palliative care (PC) rises. People with ID realize significant barriers and inequities in accessing health care and PC. The need for integrated disability and PC services with extensive collaboration is great. The following tips are for PC clinicians caring for people with ID, their families, caregivers, and the community. While patient-centered care is difficult to distill into "tips," this article, written by an interdisciplinary team of PC and ID specialists, offers resources and references to improve the care provided to people with ID and serious illnesses.

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.原发性免疫缺陷病（primary immunodeficiency diseases，PID）是由免疫系统相关的单基因胚系突变导致的先天性疾病。PID患者存在免疫过程失调，对感染性疾病、自身免疫病、自身炎症性疾病、过敏性疾病和恶性肿瘤的易感性增加。部分PID患者以可疑过敏表现（如湿疹样皮损）为首发症状，或因严重的过敏性疾病就诊于变态反应科。如何在有可疑表现的过敏患者中识别并诊断出PID、减少诊断延误、预防疾病加重，是变态反应科、儿科及相关临床科室医生需要掌握的能力。本文总结归纳过敏患者中提示PID的警示征象和过敏合并PID的机制，同时概述过敏患者中常见的PID类型、PID伴发过敏患者的评估、治疗及预防。.

ObjectiveThe objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.MethodPart 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.ResultsPart 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M= 8/10). Results showed immediate post-intervention improvements in anxiety (d= −0.41), peritraumatic distress (d= −0.24), and experiential avoidance (d= −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d= −0.94), depression (d= −0.23), anxiety (d= −0.29), and experiential avoidance (d= −0.30).Significance of resultsPreliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.

Context: The COVID-19 pandemic resulted in a surge of critically ill patients that strained health care systems throughout New York City in March and April of 2020. At the peak of the crisis, consults for palliative care increased four- to sevenfold at NewYork-Presbyterian (NYP), an academic health care system with 10 campuses throughout New York City. We share our challenges, solutions, and lessons learned to help peer institutions meet increased palliative care demands during future crises and address pre-existing palliative care subspecialist shortages during nonpandemic times. Methods: In response to the increased demand, palliative care physician and administrative leadership at NYP piloted multiple creative care models to expand access to palliative care outpatient and inpatient services. The care models included virtual outpatient management of existing patients, embedded palliative care staff, education for providers, multidisciplinary family support, hospice units (which allowed for family visitation), and team expansion through training other disciplines (primarily psychiatry) and deploying an ePalliative Care service (staffed by out-of-state volunteers). Conclusion: Our comprehensive response successfully expanded the palliative care team's reach, and, at the height of the pandemic, allowed our teams to meet the increased demand for palliative care consults. We learned that flexibility and adaptability were critical to responding to a rapidly evolving crisis. Physician and family feedback and preliminary data suggest that virtual outpatient visits, embedded staff, hospice units, and team expansion through training other disciplines and deploying ePalliative Care services were impactful interventions.

Background: Burnout during residency may be a function of intense professional demands and poor work/life balance. With the onset of the COVID-19 pandemic, NYC hospital systems were quickly overwhelmed, and trainees were required to perform beyond the usual clinical duties with less supervision and limited education. Objective: The present longitudinal study examined the effects of COVID-19 caseload over time on burnout experienced by resident physicians and explored the effects of demographic characteristics and organizational and personal factors as predictors of burnout severity. Methods: This study employed a prospective design with repeated measurements from April 2020 to June 2020. Participants were surveyed about their well-being every 5 days. Predictors included caseload, sociodemographic variables, self-efficacy, hospital support, perceived professional development, meaning in work, and postgraduate training level. Results: In total, 54 resident physicians were recruited, of whom 50% reported burnout on initial assessment. Periods of higher caseload were associated with higher burnout. PGY-3 residents reported more burnout initially but appeared to recover faster compared to PGY-1 residents. Examined individually, higher self-efficacy, professional development, meaningful work, and hospital support were associated with lower burnout. When all four predictors were entered simultaneously, only self-efficacy was associated with burnout. However, professional development, meaningful work, and hospital support were associated with self-efficacy. Conclusion: Burnout among residency is prevalent and may have implications for burnout during later stages of a physician’s career. Self-efficacy is associated with lower burnout and interventions to increase self-efficacy and the interpersonal factors that promote self-efficacy may improve physician physical and emotional well-being.

IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with chronic fibroinflammatory lesions that can affect nearly any organ. IgG4-related hepatobiliary and pancreatic diseases are IgG4-RD involving the hepatobiliary and pancreatic system, which is characterized with elevated serum IgG4 concentrations, large numbers of IgG4 positive lymphoplasma cells infiltration in affected organs, storiform fibrosis, and imaging changes of organ morphology. Due to the lack of reliable biomarkers, histopathology is still an important basis for diagnosis. The pathogenesis of IgG4-related hepatobiliary and pancreatic diseases has not been clarified. This review focuses on the recent advances in intestinal microecology-immunology, host genetics-immunity and recurrence monitoring of IgG4-related hepatobiliary and pancreatic diseases.免疫球蛋白（Ig）G4相关疾病是一种免疫介导的累及多个器官的慢性纤维炎性疾病。IgG4相关肝胆胰疾病是IgG4相关疾病在肝胆胰系统中的表现，以血清IgG4滴度升高、病变组织中大量IgG4阳性浆细胞浸润、组织纤维化、影像学器官形态改变等为主要特点，因缺乏可靠的生物标志物，组织病理学仍是诊断的重要依据。IgG4相关肝胆胰疾病发病机制尚未完全明确，现重点报道IgG4相关肝胆胰疾病近年来在肠道微生态-免疫学、宿主遗传-免疫及复发监测领域的进展。.

According to Jewish law/ethics, continuous life-sustaining therapy may not be withdrawn after its introduction, unless the patient has improved and no longer has a medical indication for the treatment. We report the case of an 88-year-old Orthodox Jewish patient, on invasive mechanical ventilation, with severe anoxic brain injury after multiple cardiac arrests. Although the patient's son informed the palliative care team that his father did not want to be in pain or to linger in a vegetative state when terminally ill, the mechanical ventilation was keeping him alive with a poor neurological prognosis. Additionally, the patient had previously stated his wish to observe Orthodox Jewish principles regarding end-of-life care. After extensive discussion, the family Rabbi clarified that it would be acceptable to withdraw mechanical ventilation if there were a “reasonable expectation” he would breathe on his own for a “reasonable amount of time.” Thus, if the patient's death were to occur, it would not be an immediate consequence the normal ventilator weaning process. Following intermediation by the hospital Rabbi, the definition of what would be a “reasonable expectation” and “reasonable amount of time” was established by the family Rabbi as “over 50%” and “on the order of hours,” respectively. Following pulmonary consultation, the patient underwent palliative extubation and, 12 hours after the procedure, died comfortably surrounded by the family. In conclusion, the collaborative and interdisciplinary work among the family Rabbi, hospital Rabbi, and the various medical teams allowed the development of a plan that met all of the patient's personal and religious wishes and beliefs.

Takayasu's arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.大动脉炎（TAK）为累及主动脉及其主要分支的慢性进展性、非特异性大血管炎。我国为TAK高发地区，但其规范化诊疗的普及尚显不足。中华医学会风湿病学分会组织专家，在借鉴国内外诊治经验和指南的基础上，制定了本规范，旨在规范TAK的诊断、疾病活动度和疾病严重度的评估、内科治疗的合理制定及外科干预的时机选择，以保护TAK患者重要脏器功能，改善患者预后。.

罕见遗传病的诊断和治疗延误十分常见。筛查是快速诊断、发现新患者的重要手段，包括新生儿筛查、高危筛查以及家系筛查。通过家系筛查能够帮助罕见遗传病（如法布雷病）先证者家庭中的潜在患者尽早获得诊断，及时接受针对性治疗。本文以法布雷病为例，分别从家系筛查的意义、方法、所面临的困难和挑战出发，介绍目前我国法布雷病家系筛查的现状，并基于国外先进实践经验提出改善建议，旨在促进我国罕见遗传病家系筛查的推广和实施。.

A young male patient with abdominal pain and fever was diagnosed as acute hyper-triglyceridemicpancreatitis is clear. During the recovery of pancreatitis, the patient developed acute acalculous cholecystitis, as well as carbapenem-resistant Enterobacter infection and Cytomegaloviremia, and had anaphylaxis for several times after the use of antibiotics, which cannot be completely explained by drug allergy. This paper analyzes the possible causes of multiple diseases in the same patient in detail.本文报道1例以腹痛、发热起病的青年男性患者，临床诊断高甘油三酯血症性急性胰腺炎明确。在胰腺炎恢复过程中，患者出现急性非结石性胆囊炎、耐碳青霉烯类抗生素的大肠杆菌感染及巨细胞病毒血症，并在使用抗生素后多次发生严重过敏反应，但亦不能完全以药物过敏解释。本文通过对同一患者中出现多种疾病的病程进行详细分析，分析相互之间的可能原因。.

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.随着社会老龄化进程，我国心血管疾病（cardiovascular diseases，CVD）患病率处于持续上升阶段，伴CVD的口腔患者逐渐增加。关于口腔医师应如何规范进行CVD患者的治疗前评估和围手术期风险防范，国内尚缺乏有针对性的指南和规范，是目前有待解决的问题。中华口腔医学会第五届全科口腔医学专业委员会专家组联合心内科领域专家组成共识专家组，根据当前国内诊治CVD患者的临床经验，结合国际相关指南及研究，从CVD与口腔疾病之间的关系，心力衰竭、高血压及抗血栓治疗患者口腔诊疗等方面进行系统性总结，形成专家共识，希望逐步实现CVD患者口腔诊疗的规范化与标准化，降低诊疗风险，减少并发症的发生，提高我国口腔医师对CVD患者的诊疗水平。.

BackgroundHispanics often have disparities at the end of life. They are more likely to die full code and less likely to have discussions regarding prognosis and do not resuscitate (DNR)/do not intubate (DNI), despite studies showing Hispanic values comfort over the extension of life. Barriers to patient-centered care include language,socioeconomic status and health literacy.ContextWe evaluated the impact of palliative care (PC) consults on the change of code status and hospice referrals, comparing seriously ill Hispanic and non-Hispanic white patients.MethodA retrospective cohort study of all white and Hispanic patients referred to the PC service of a county hospital from 2006 to 2012. We evaluated ethnicity, language, code status at admission and after PC consult, and hospice discharge. Chi-squared tests were used to analyze characteristics among three groups: non-Hispanic white, English-speaking Hispanic, and Spanish-speaking Hispanic patients.ResultsOf 925 patients, 511 (55%) were non-Hispanic white, 208 (23%) were English-speaking Hispanic, and 206 (22%) were Spanish-speaking Hispanic patients. On admission, there was no statistically significant difference in code status among the three groups (57%, 64%, and 59% were full code, respectively, p = 0.5). After PC consults, Spanish-speaking Hispanic patients were more likely to change their code status to DNR/DNI when compared with non-Hispanic white and English-speaking Hispanic patients (44% vs. 32% vs. 28%, p = 0.05). Spanish-speaking Hispanic patients were more likely to be discharged to hospice when compared with English-speaking Hispanics and non-Hispanic whites (33%, 29%, and 23%, respectively, p = 0.04).Significance of resultsSpanish-speaking Hispanic patients were more likely to change from full code to DNR/DNI compared with non-Hispanic white and English-speaking Hispanic patients, despite similar code status preferences on admission. They were also more likely to be discharged to hospice. PC consults may play an important role in helping patients to align their care with their values and may prevent unwanted aggressive interventions at the end of life.

Chordoma is a rare tumor of the skeletal system that is characterized by a high recurrence rate and treatment resistance. Given the common finding of immune dysregulation in chordoma, immunotherapy has emerged as potential treatment option. As an important immune checkpoint regulator, we evaluated cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression and its prognostic significance for patients with chordoma of the spine. CTLA-4 expression was analyzed immunohistochemically in 32 chordoma tissues and 14 nucleus pulposus tissues to examine the specificity of CTLA-4 expression in chordoma. Univariate log-rank analysis was used to evaluate the association of CTLA-4 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) with survival. Cox multivariate analysis was used to identify independent factors of survival. Positive CTLA-4 expression was observed in all of the TILs and tumor cell cytoplasm, and partial in the membrane or in both the membrane and nucleus, with a markedly higher positivity rate than that observed in normal nucleus tissues. Higher CTLA-4 expression in the tumor but not in TILs was significantly associated with shorter continuous disease-free survival (CDFS) and overall survival (OS). CTLA-4 expression in tumor cells and TILs were independent predictors for CDFS, whereas only tumor cell expression was a significant predictor of OS. Furthermore, the combination of CTLA-4 expression in the tumor and TILs had higher prognostic value. Targeting CTLA-4 may be a potential novel therapeutic strategy for chordoma patients.

Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibit...

Long-term control of SARS-CoV-2 outbreaks depends on the widespread coverage of effective vaccines. In Australia, two-dose vaccination coverage of above 90% of the adult population was achieved. However, between August 2020 and August 2021, hesitancy fluctuated dramatically. This raised the question of whether settings with low naturally derived immunity, such as Queensland where less than 0.005 % of the population is known to have been infected in 2020, could have achieved herd immunity against 2021’s variants of concern. To address this question, we used the agent-based model C ovasim . We simulated outbreak scenarios (with the Alpha, Delta and Omicron variants) and assumed ongoing interventions (testing, tracing, isolation and quarantine). We modelled vaccination using two approaches with different levels of realism. Hesitancy was modelled using Australian survey data. We found that with a vaccine effectiveness against infection of 80%, it was possible to control outbreaks of Alpha, but not Delta or Omicron. With 90% effectiveness, Delta outbreaks may have been preventable, but not Omicron outbreaks. We also estimated that a decrease in hesitancy from 20% to 14% reduced the number of infections, hospitalizations and deaths by over 30%. Overall, we demonstrate that while herd immunity may not be attainable, modest reductions in hesitancy and increases in vaccine uptake may greatly improve health outcomes. This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.

Many randomized controlled clinical trials have reported that implant overdentures provided edentulous people with better retention, stability, and masticatory performance than conventional complete dentures did. The design of implant overdentures for edentulous jaws should be based on comprehensive consideration of factors such as anatomic structure, alveolar bone resorption, inter-arch distance, choice of implant number/distribution and suprastructure. During the clinical procedure, timing of attachment connection, choice of impression technique, methods of maxilla-mandibular relationship registration, wax-up try-in, and prostheses delivery should be determined according to the type of implant overdentures. The appropriate choices and conduction of the above-mentioned procedures can guarantee the long-term success of the prostheses. This review elaborates on the clinical significance, treatment design, key steps in clinical procedure of implant overdenture, and summarizes follow-up and maintenance following denture delivery.多项大样本量随机对照临床研究证实，牙列缺失采用种植覆盖义齿修复，比常规全口义齿能提高义齿的固位与稳定，并可提供更高的咀嚼效率；无牙颌种植覆盖义齿的设计应综合考虑患者的解剖条件、牙槽骨吸收程度、颌间距离等因素，选择适合的种植体数目、分布及上部附着体。在覆盖义齿的临床操作过程中，应针对不同类型的覆盖义齿，在适当的时机戴入上部附着体，并合理选择适用的印模技术、颌位关系记录、试牙排牙及戴牙方法，才能保证修复效果的长期稳定。本文对种植覆盖义齿的临床意义、治疗设计、临床操作流程中的关键步骤与义齿戴入后的复查与维护等方面进行详细阐述。.

International medical graduates (IMGs) comprise a quarter of the United States (US) physician workforce but are a diminishing minority among dermatologists. Studies on IMGs in other specialties have demonstrated their importance in addressing provider shortage in rural and medically underserved areas (MUAs), but this trend has not been systematically explored within dermatology. This study aims to assess the state-by-state distribution of IMG dermatologists in the US as compared to US medical graduates (USMGs) with focus on provider density in rural settings and MUAs. A national cross-sectional study was performed on actively practicing dermatologists who submitted Medicare claims within 1 year of July 2020; rural and MUA-serving status were determined based on federally designated rural-urban Continuum Codes and Census Bureau data. Nationally, the density of dermatologists has increased from 3.4 per 100,000 persons in 2016 to 3.66 per 100,000 persons in 2020. However, 70% of US states continue to have fewer than 4 dermatologists per 100,000 persons, the estimated minimum necessary to adequately care for a population. Among 12,009 dermatologists, only 576 (4.8%) are IMGs, with disparate distribution across the US: Kansas has the greatest percentage of IMGs with the latter comprising 8.3% of its state dermatology workforce, whereas 8 states have no IMGs. Notably, a significantly greater percentage of IMG dermatologists (43.9%) work in areas designated as MUAs compared to USMGs (37.4%) (P 0.01). In contrast, a lower percentage of IMG dermatologists (2.8%) work in rural settings compared to USMGs (4.8%) (P = 0.03). Interestingly, no significant difference was observed when rural dermatologists were further stratified by MUA-serving status. These findings corroborate the importance of IMGs in providing greater access to dermatological care in areas with healthcare provider shortage. Further studies on the underlying causes of the decline of IMGs within dermatology are needed.

This study included 93 patients with renal masses who underwent standard partial nephrectomy or tumor enucleation. After surgery, parenchymal mass loss caused by devascularization resulted in more damage to renal function than excised parenchymal mass loss. Surgeons should seek better techniques to decrease devascularization during reconstruction.To evaluate the importance of devascularized parenchymal mass(DPM) and excised parenchymal mass(EPM) in functional preservation after standard partial nephrectomy(SPN).Forty-one patients who underwent pure tumor enucleation(TE) and 52 patients who underwent SPN with necessary data were included. As no EPM was lost in TE, the TE samples were used to estimate the degree of volume shrinkage that occurred when the measurements were performed in vivo with blood flow versus ex vivo without, and the shrinkage ratio was calculated as specimen volume divided by tumor volume in vivo. In SPN, the specimen volume comprised tumor volume plus EPM. The EPM was calculated as specimen volume divided by shrinkage ratio minus tumor volume in vivo. The DPM was defined as total ipsilateral parenchymal mass loss minus EPM. T tests, χThe mean sizes of devascularized and excised parenchymal masses were 13.6 cmThe DPM comprises most of parenchymal mass loss after SPN and plays a more important role than EPM on functional outcomes. Surgeons should pay more attention to reducing devascularization during partial nephrectomy.

Background: Near-death awareness (NDA) refers to visions and dreams commonly experienced by terminally ill individuals within months to hours before death. Methods: A case report of a 68-year-old Jamaican male diagnosed with advanced cholangiocarcinoma, who experienced visions of his deceased mother during hospitalization. Results: This article discusses how to differentiate NDA from delirium, core components for determining decisional capacity, and how clinicians can use a cultural guide to optimize patient-centered care. Conclusion: Improved recognition of NDA may promote cultural humility/competency and help to differentiate NDA from an underlying medical/psychiatric condition. It may assist the clinician in understanding the significance of NDA and the comfort and meaning these experiences may hold for both the individual and their family.

OBJECTIVE: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infection in vitro and explore the molecular mechanism. METHODS: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Circular dichroism spectroscopy was used to examine the structural characteristics of HR1 and HR2 regions of SARS-CoV-2 S protein, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of Sal-B on virus-cell membrane fusion. Flow cytometry was carried out to analyze the effect of Sal-B on the binding of SARS-CoV-2 RBD to hACE2 receptor. RESULTS: The median effective concentrations (EC(50)) of Sal-B and ZDDY against SARSCoV-2 infection in Vero-E6 cells were 55.47 μmol/L and 36.07 μg/mL, respectively. Both Sal-B and ZDDY successfully inhibited the entry of SARS-CoV-2 pseudovirus into the cells that stably expressed human ACE2 (ACE2/293T), with half maximal inhibitory concentrations (IC(50)) of 1.69 μmol/L and 24.81 μg/mL, respectively. Sal-B showed a binding affinity of -8.2 kcal/mol to the 6-helix bundle (6-HB) of SARS-CoV-2 S protein. Molecular dynamics simulation showed stable binding between Sal-B and the 6-HB of SARS-CoV-2 S protein at the predicted binding site. Sal-B disturbed the formation of the secondary structure of 6-HB in HR1P/HR2P mixture, resulting in a significantly lowered α-helicity (P < 0.05). Sal-B dose-dependently inhibited SARS-CoV-2 S protein-mediated cell-cell fusion, with an IC(50) of 3.33 μmol/L. Sal-B showed no effect on RBD-Fc protein binding to the ACE2 receptor. CONCLUSION: Sal-B and its magnesium salt ZDDY can inhibit the entry of SARS-CoV-2 in Vero-E6 cells in vitro by blocking SARS-CoV-2 spike protein-mediated virus-cell membrane fusion.

本文报道2例伴不典型EWSR1信号的滑膜肉瘤。低分化滑膜肉瘤仅通过形态学及免疫组织化学常常难以确诊，须借助分子病理学手段辅助诊断。然而分子病理检测也存在陷阱，出现不典型信号时还需谨慎解读。.

Sezary syndrome (SS) is an extremely rare form of cutaneous T-cell lymphoma (incidence 0.01 cases/100,000 person-years) associated with debilitating morbidity and poor overall prognosis.1,2 For patients with relapsed or treatment-refractory SS, traditional therapies are limited and predominantly palliative.1 Multiple prior single-center studies suggest allogeneic hematopoietic stem-cell transplantation (HSCT) with total-skin electron beam (TSEB) may offer durable remission to a subset of these patients.

Context: A paucity of literature describes the growing Chinese American community’s end-of-life (EOL) priorities and preferences. Objective: Develop a culturally-tailored advance care planning (ACP) tool to understand the EOL preferences of this underserved minority group. Methods: Informed by the Cultural Appropriateness Theory, the Chinese American Coalition for Compassionate Care (CACCC) developed Heart to Heart (HTH) Cards using a 3-step approach. First, CACCC created and refined a list of bilingual, culturally relevant EOL issues. Next, CACCC organized the EOL issues into a card deck. Finally, CACCC developed a unique playstyle of the cards—the HTH Café. From 2014-2019, CACCC recruited Chinese American volunteers and participants for HTH Cafés. Following each Café, participants completed an anonymous survey describing their sociodemographics, top 3 cards, and café evaluation. Results: The 54 HTH Cards were organized into 4 suits (spiritual, physical, financial/legal, and social). Each card displayed a culturally-tailored EOL issue in English and Chinese. Playstyles included one-on-one and group formats (ie. HTH Café). CACCC volunteers conducted 316 HTH Cafés for 2,267 Chinese American adults. Most participants were female (61.6%), between 18-50 years old (56.7%), lived in California (80.2%) and born in Asia (74.3%). The top priority (25.5%) was “If I’m going to die anyway, I don’t want to be kept alive by machines.” Participants thought the session was pleasant (99.5%) and expressed intent to complete advance directives (86.5%). Conclusion: HTH Cards represents the first, theory-driven, culturally-tailored ACP tool for Chinese Americans. More research is needed to establish its impact on ACP conversations and outcomes.

Background:Dementia is a leading cause of death among US older adults. Little is known about end-of-life care intensity and do-not-resuscitate orders (DNRs) among patients with dementia who die in hospital.Aim:Examine the relationship between dementia, DNR timing, and end-of-life care intensity.Design:Observational cohort study.Setting/Participants:Inpatient electronic health record extraction for 2,566 persons age 65 and older who died in 2 New York City hospitals in the United States from 2015 to 2017.Results:Multivariable logistic regression analyses modeled associations between dementia diagnosis, DNR timing, and 6 end-of-life care outcomes. 31% of subjects had a dementia diagnosis; 23% had a DNR on day of hospital admission. Patients with dementia were 18%-40% less likely to have received 4 of 6 types of intensive care (mechanical ventilation AOR: 0.82, 95%CI: 0.67 -1.00; intensive care unit admission AOR: 0.60, 95%CI: 0.49-0.83). Having a DNR on file was inversely associated with staying in the intensive care unit (AOR: 0.57, 95%CI: 0.47-0.70) and avoiding other intensive care measures. DNR placement later during the hospitalization and not having a DNR were associated with more intensive care compared to having a DNR upon admission.Conclusions:Having dementia and a do-not resuscitate order upon hospital admission are associated with less intensive end-of-life care. Additional research is needed to understand why persons with dementia receive less intensive care. In clinical practice, encouraging advance care planning prior to and at hospital admission may be particularly important for patients wishing to avoid intensive end-of-life care, including patients with dementia.

Hydrophobic molecules may be toxic when present in excess. When dissolved in membranes, hydrophobic molecules disrupt membrane function. Studies on the effects of free fatty acids (FFA) on cultured cells contradict each other. Here we describe the effects of FFA on various human cells in culture. The addition of long-chain FFA (oleic, palmitic, linoleic, linolenic, etc.) to cultured cells led to lipid accumulation in hepatocytes and muscle cells, initiation of autophagy, and uncoupling of oxidative phosphorylation. Although treated cells increase their oxygen consumption, metabolic shifts in favor of glycolysis were observed. All these effects were expressed to varying degrees in different cells and with the addition of different FFAs. The mechanisms of these FFA effects are discussed, as well their practical implications.

OBJECTIVE: To compare the clinical efficacy of a kind of complete dentures fabricated using computer aided design/computer aided manufacturing (CAD/CAM) workflow with that of the complete denture fabricated using conventional workflow. METHODS: Twenty edentulous patients were included in this prospective, single-blind, self-controlled clinical trial. Two pairs of complete dentures were fabricated for each participant: one using the functional suitable denture (FSD) system with CAD/CAM, and the other using conventional fabrication workflow. In the final delivery appointment, the conventional dentures worn by the participant for 3 months at first. Then the participant swapped to wear digital denture for another 3 months. The patients' satisfaction and oral health related quality of life (OHRQoL) were measured using the visual analogue scale (VAS) and oral health impact profile (OHIP-20E) at baseline, 2 weeks, 1 month, 2 months, and 3 months following denture delivery. In addition, the masticatory efficiency of each pair of dentures was measured after three months adaptation period for each type of dentures. RESULTS: The VAS scores of the twenty patients in FSD denture group on general satisfaction, ease of cleaning, ability to speak, esthetics, stability and oral health status on these six domains were higher than that of conventional denture group 3 months after delivery. While the VAS cores in FSD denture group on comfort, ability to chew and ability to chew up were the same as those of conventional denture group. But there was no significant difference (P>0.05). The VAS score on each domain in FSD denture group was higher than that of conventional denture group 3 months after delivery, three domains of which reached statistical significance (P < 0.05), involving functional limitation, psychological discomfort and total. The masticatory performance of the FSD denture (1.20±0.54) was slightly higher than that for the conventional denture (1.16±0.53), but the difference did not reach statistical significance (P=0.691). CONCLUSIONS: The clinical efficacy of the FSD complete denture is comparable to that of the conventional complete denture. As for patient satisfaction and oral health related quality of life, FSD dentures received comparable scores as conventional complete dentures did.

Background Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). Patients and Methods This retrospective study of the Flatiron Health EHR-derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, through June 30, 2018). Patient characteristics and treatment patterns were characterized. Real-world progression-free survival (rwPFS) and time to discontinuation were calculated using the Kaplan-Meier method. Results First-line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second-line ALK TKI therapy to 254 patients post crizotinib (45.7% had brain metastasis on or prior to second-line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first-line ALK TKI therapy. For second-line ALK TKI post crizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48–8.32) months for first-line and 7.30 (5.72–8.42) months for second-line ALK TKI. Median (95% CI) rwPFS was significantly longer among first-line ALK TKI patients without than with brain metastasis (8.52 [7.57–10.59] vs. 4.97 [3.75–5.99] months; p Conclusion Median rwPFS in patients with advanced ALK+ NSCLC was

Introduction The treatment landscape for anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC) primarily involves ALK-directed tyrosine kinase inhibitors (TKIs). Although therapy with immune checkpoint inhibitors (ICIs) is a treatment option in NSCLC, the efficacy of ICI is inconclusive in ALK-positive NSCLC as a result of limited data. This retrospective real-world study sought to describe the characteristics of ALK-positive NSCLC patients treated with ICI and to assesses treatment outcomes in US oncology practices. Patients and Methods This analysis used the Flatiron Health electronic health record–derived deidentified database and included adult (18 years and older) ALK-positive advanced NSCLC patients with receipt of one or more ICIs after January 1, 2015. Median time to ICI discontinuation and real-world progression-free survival (rwPFS) were estimated by Kaplan-Meier methods. Results Of 83 patients with ALK-positive NSCLC treated with ICIs, 50.6% (n = 42) received ICI without a prior ALK TKI. Median time to ICI discontinuation was 2.17 months (95% confidence interval, 1.41, 3.32). The median rwPFS was 2.34 months (95% confidence interval, 1.55, 3.09); in patients who received an ICI without prior ALK TKI, it was 3.9 months, and in patients who received ICI therapy after an ALK TKI, it was 1.5 months. Conclusions Real-world effectiveness (rwPFS) of ICIs in ALK-positive NSCLC patients, whether provided before or after TKIs, was limited, underscoring the relative lack of efficacy of ICI in this patient population, particularly compared to approved ALK TKIs.

Respiratory symptoms are common in patients living with serious illness, both in cancer and nonmalignant conditions. Common symptoms include dyspnea (breathlessness), cough, malignant pleural effusions, airway secretions, and hemoptysis. Basic management of respiratory symptoms is within the scope of primary palliative care. There are pharmacologic and nonpharmacologic approaches to treating respiratory symptoms. This article provides clinicians with treatment approaches to these burdensome symptoms.