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To summarize our experience in the application of radiofrequency ablation (RFA) and microwave ablation (MWA) for selective fetal reduction in complicated monochorionic pregnancies and compare the perinatal outcome of the two techniques.This was a retrospective study of data from a consecutive cohort of all monochorionic twin pregnancies that underwent selective fetal reduction with RFA or MWA at Peking University Third Hospital, Beijing, China from January 2012 to December 2018. All surviving cotwins were followed up to assess their neurodevelopment using the Ageamp; Stage Questionnaire, Chinese version. Perinatal and neurodevelopmental outcomes were compared between the RFA and MWA groups. We also fitted multivariable models to test the association between procedure-related factors and the main perinatal outcomes, including preterm birth (PTB)lt; 37 weeks' gestation, intrauterine fetal death (IUFD) of the cotwin, adverse outcome (defined as occurrence of IUFD of the cotwin, termination of pregnancy or PTBlt; 28 weeks) and overall survival.In total, 45 cases (42 twin and three triplet pregnancies) underwent RFA and 126 cases (105 twin and 21 triplet pregnancies) underwent MWA. The overall survival rates in monochorionic diamniotic twin pregnancies were similar between the RFA and MWA groups (61.0% vs 67.0%; P = 0.494). However, pregnancies whose indication for fetal reduction was selective intrauterine growth restriction or twin reversed arterial perfusion had higher overall survival rates (75.5% and 82.6%, respectively) compared with those in other indication groups. A total of 104 children were followed up (20 in the RFA group and 84 in the MWA group); four (20.0%) and eight (9.5%) children were assessed as having overall developmental delay in the RFA and MWA groups, respectively, with no significant difference between the two groups. Multivariable analyses showed that procedure indication, number of ablation cycles and gestational age at procedure were associated significantly with the main perinatal outcomes.RFA and MWA for selective fetal reduction in complicated monochorionic pregnancies can achieve similar overall survival rate and neurodevelopmental outcome, but MWA is associated with a lower risk of preterm birth. Moreover, procedure-related factors are associated significantly with perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Objectives: Health economic (HE) models are routinely used to support health policy and resource allocation decisions but are often considered “black boxes” that may be prone to error and bias. Open source models (OSMs) have been advocated to increase the transparency, credibility, and reuse of HE models. Previous studies have demonstrated interest in OSMs among the health economics and outcomes research community, but the number of OSMs remains low. Methods: We conducted an online survey of ISPOR (the leading professional society for health economics and outcomes research) members’ perspectives on the usefulness of OSMs and barriers to their development and implementation. Results: Respondents (N = 230) included academics (27%), pharmaceutical (or related) industry representatives (23%), health research or consulting representatives (21%), governmental or nonprofit agency representatives (10%), and others (19%). Respondents were generally not familiar with barriers to the development and adoption of OSMs. Most agreed that OSMs would improve transparency (92%), efficiency (76%), and HE model reuse (86%) and promote confidence in using HE models (75%). The use of OSMs by health technology assessment authorities was considered a very important indicator of the usefulness of OSMs by 49% of respondents. Three-quarters of respondents perceived legal concerns and the ability to transfer data as important barriers to the development and use of OSMs. Conclusions: Respondents believe that OSMs could increase the transparency, efficiency, and credibility of HE models, but that several barriers hamper their widespread adoption. Our results suggest that fundamental changes may be needed across the health economics and outcomes research community if OSMs are to become widely adopted.

Objectives Examine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants

Objectives Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin. Methods A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective. Results For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs. Conclusions Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

免疫检查点抑制剂（ICI）相关性心肌炎是一种少见的免疫相关不良反应，但死亡率高达39.7%~50%。该文报道1例肝癌患者在首次使用ICI后20 d出现右侧眼睑下垂，用药后26 d出现肌钙蛋白I、肌酸激酶、肌酸激酶同工酶、肌红蛋白明显升高，但无心血管相关症状，心电图、超声心动图无异常改变，排除其他原因引起的酶谱升高，临床诊断为无症状性ICI相关性心肌炎，伴免疫性肌炎。通过大剂量糖皮质激素治疗，肌钙蛋白I在4 d后降至正常，右侧眼睑下垂于7 d后恢复正常。随访至今，患者仍存活，无任何后遗症。ICI用药后通过主动监测心肌损伤标志物，有助于早期诊断心肌炎，激素治疗可明显改善患者预后。.

ObjectiveThe use of therapeutic hypothermia (TH) for mild hypoxic–ischaemic encephalopathy (HIE) remains controversial and inconsistent. We analysed trends in TH and maternal and infant characteristics associated with short-term outcomes of infants with mild HIE.DesignRetrospective cohort analysis of the California Perinatal Quality Care Collaborative database 2010–2018. E-value analysis was conducted to determine the potential impact of unmeasured confounding.SettingCalifornia neonatal intensive care units.Patients1364 neonates with mild HIE.InterventionsSupportive care versus TH.Main outcome measuresFactors associated with TH and mortality.ResultsThe proportion of infants receiving TH increased from 46% in 2010 to 79% in 2018. TH was more likely in the setting of singleton birth (OR 2.69, 95% CI 1.21 to 5.39), no major birth defects (OR 2.18, 95% CI 1.42 to 3.30), operative vaginal delivery (OR 3.04, 95% CI 1.80 to 5.10) and 5-minute Apgar score ≤5 (OR 3.17, 95% CI 2.43 to 4.13). Mortality was associated with small for gestational age (OR 5.79, 95% CI 1.90 to 18.48), ConclusionsVariation in management of mild HIE persists, but therapeutic drift has become more prevalent over time. Further studies are needed to assess long-term outcomes alongside resource utilisation to inform evidence-based practice.

Background The COVID-19 pandemic has resulted in negative impacts on the economy, population health, and health-related quality-of-life (HRQoL). Objective To assess the impact of COVID-19 on US population HRQoL using the EQ-5D-5L. Design We surveyed respondents on physical and mental health, demographics, socioeconomics, brief medical history, current COVID-19 status, sleep, dietary, financial, and spending changes. Results were compared to online and face-to-face US population norms. Predictors of EQ-5D-5L utility were analyzed using both standard and post-lasso OLS regressions. Robustness of regression coefficients against unmeasured confounding was analyzed using the E-Value sensitivity analysis. Subjects Amazon MTurk workers (n=2776) in the USA. Main Measures EQ-5D-5L utility and VAS scores by age group. Key Results We received n=2746 responses. Subjects 18–24 years reported lower mean (SD) health utility (0.752 (0.281)) compared with both online (0.844 (0.184), p=0.001) and face-to-face norms (0.919 (0.127), p

BACKGROUND: Opioid analgesia is often avoided in infants undergoing pyloromyotomy. Previous studies highlight an association between opioid use and prolonged hospitalization after pyloromyotomy. However, the impact of opioid use on healthcare resource utilization cost is unknown. We hypothesized that use of opioids after pyloromyotomy is associated with increased resource utilization and costs. METHODS: A retrospective cohort study was conducted identifying healthy infants

The purpose was to discuss the infection status of human parainfluenza virus type 3 (HPIV-3) in children with acute respiratory tract infection(ARTI) in Qingdao, Shandong province, and to analyze the gene characteristics of HPIV-3 hemagglutinin-neuraminidase protein (HN). This study was a cross-sectional study. A total of 1 674 throat swab samples were collected randomly from children with ARTI, in the three hospitals (Qingdao Women and Children's Hospital, West Coast Branch of Affiliated Hospital of Qingdao University, Laoshan Branch of Affiliated Hospital of Qingdao University) from January 2018 to December 2019. Multiplex real-time fluorescence RT-PCR was performed to screen HPIV-3 positive specimens. For HPIV-3 positive specimens, nested PCR was used to amplify the full-length HN gene of HPIV-3. The HN gene was sequenced and compared with the representative strains of HPIV-3 in GenBank, and the phylogenetic tree was established. As results, this study collected 1 674 samples, in which there were 90 HPIV-3 positive samples showed and the detection rate was 5.37%. Among positive specimens, the number of samples from children under 6 years old was 88, accounting for 97.78%. HPIV-3 positive cases were mainly distributed in spring and summer. The full-length sequences of 44 HPIV-3 HN genes were obtained by nested PCR method. Sequence alignment and evolutionary analysis showed that the HPIV-3HN gene belonged to the C3a and C3b branches of C3 genotype, with 30 strains of subtype C3a and 14 strains of subtype C3b. The nucleotide and amino acid homology of the amplified 44 strains of the HPIV-3 HN gene in Qingdao were 97.0%-100.0% and 98.5%-100.0%, respectively. In conclusion, from 2018 to 2019, the C3a and C3b branches of HPIV-3 C3 genotype were circulating prevalent in Qingdao, Shandong province. HN gene variation rate was low, but showed certain regional characteristics in evolution.探讨山东省青岛市地区急性呼吸道感染患儿人副流感病毒3型（HPIV-3）的感染情况，并分析HPIV-3血凝素-神经氨酸酶蛋白（HN）基因特征。本研究为横断面研究，青岛市妇女儿童医院、青岛大学附属医院西海岸院区及崂山院区在2018年1月至2019 年12月期间，每月随机采集急性呼吸道感染（ARTI）儿科患者的咽拭子样本，总共1 674份，采用多重实时荧光逆转录-聚合酶链反应（RT-PCR）方法，筛查HPIV-3阳性样本。采用巢式PCR方法扩增HPIV-3阳性样本HN全长基因并进行序列测定，序列结果与GenBank中HPIV-3的代表株进行对比分析，建立系统进化树。结果显示，1 674份咽拭子样本中，HPIV-3阳性有90份，检出率为5.37%，其中，6岁以下儿童占97.78%（88份）。HPIV-3阳性病例主要分布在春季和夏季。通过巢式PCR方法扩增得到44株HPIV-3 HN基因全长序列，序列比对及进化分析表明，HPIV-3 HN基因属于C3基因亚型的C3a和C3b分支，其中，C3a亚型有30株，C3b亚型有14株。44株青岛分离株之间的核苷酸和氨基酸同源性分别为97.0%~100.0%和98.5%~100.0%。综上，2018至2019年间，HPIV-3 C3基因型的C3a和C3b分支在山东省青岛市地区循环流行，其HN基因型变异较小，进化上具有一定的地域特征。.

Colorectal cancer is the third most common cancer in the world. The treatments include surgery, chemotherapy, radiotherapy and targeted therapy. The guidelines of many tumor types have been rewritten with the advent of immune checkpoint inhibitors. There are significant differences in the efficacy of immune checkpoint inhibitors in colorectal cancer according to microsatellite status. Microsatellite instability-high (MSI-H) colorectal cancer has made a breakthrough in immunotherapy, whether in the late-line, first-line, adjuvant or neoadjuvant therapy. The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer. The NICHE study, which used immunotherapy as neoadjuvant treatment of colorectal cancer, has made exciting achievements in MSI-H colorectal cancer. For microsatellite stability (MSS) colorectal cancer, many studies are ongoing, and immunotherapy is still unable to challenge the status of traditional treatment. In this paper, we review the clinical trials related to immune checkpoint inhibitors of colorectal cancer, expecting to provide references for the development of colorectal cancer immunotherapy.结直肠癌是全球第三大肿瘤，治疗手段包括手术、化疗、放疗和靶向治疗等。免疫检查点抑制剂的出现改写了许多瘤种的诊治指南。免疫检查点抑制剂在不同微卫星状态结直肠癌中有着显著的疗效差别，微卫星高度不稳定（MSI-H）结直肠癌无论是在后线、一线、辅助还是新辅助治疗方面，均取得了突破。KEYNOTE-177研究已经成功地改写了指南，帕博利珠单抗成为一线MSI-H晚期结直肠癌的标准治疗。NICHE研究将免疫治疗用于结直肠癌的新辅助治疗，在MSI-H结直肠癌中也取得了令人振奋的成绩。而对于微卫星稳定（MSS）结直肠癌，许多研究正在进行，免疫治疗尚不能挑战传统治疗的地位。本文就免疫检查点抑制剂治疗结直肠癌的相关临床研究进行梳理，期望为结直肠癌免疫治疗的发展提供参考。.

Background Online longitudinal surveys may be subject to potential biases due to sample attrition. This study was designed to identify potential predictors of attrition using a longitudinal panel survey collected during the COVID-19 pandemic. Methods Three waves of data were collected using Amazon Mechanical Turk (MTurk), an online crowd-sourced platform. For each wave, the study sample was collected by referencing a US national representative sample distribution of age, gender, and race, based on US census data. Variables included respondents’ demographics, medical history, socioeconomic status, COVID-19 experience, changes of health behavior, productivity, and health-related quality of life (HRQoL). Results were compared to pre-pandemic US norms. Measures that predicted attrition at different times of the pandemic were identified via logistic regression with stepwise selection. Results 1467 of 2734 wave 1 respondents participated in wave 2 and, 964 of 2454 wave 2 respondents participated in wave 3. Younger age group, Hispanic origin (p ≤ 0.001) and higher self-rated survey difficulty (p ≤ 0.002) consistently predicted attrition in the following wave. COVID-19 experience, employment, productivity, and limited physical activities were commonly observed variables correlated with attrition with specific measures varying by time periods. From wave 1, mental health conditions, average daily hours worked (p = 0.004), and COVID-19 impact on work productivity (p Conclusions Attrition in this longitudinal panel survey was not random. Besides commonly identified demographic factors that contribute to panel attrition, COVID-19 presented novel opportunities to address sample biases by correlating attrition with additional behavioral and HRQoL factors in a constantly evolving environment. While age, ethnicity, and survey difficulty consistently predicted attrition, other factors, such as COVID-19 experience, changes of employment, productivity, physical health, mental health, and financial situation impacted panel attrition during the pandemic at various degrees.

BACKGROUND AND OBJECTIVES Describe the financial burden and worry that families of preterm infants experience after discharge from the neonatal intensive care unit (NICU). METHODS We surveyed 365 parents of preterm infants in a cross-sectional study regarding socio-demographics, supplemental security income (SSI), and financial worry. We completed a multivariable logistic regression model to examine the adjusted association of financial worry with modifiable factors. RESULTS We found that 53% of participants worried about healthcare costs after NICU discharge. After adjusting for socio-demographic and infant characteristics, we identified that, aOR (95% CI), out-of-pocket costs from the NICU index hospitalization, 3.51 (1.7, 7.26) and durable medical equipment use, 2.41 (1.11, 5.23) was associated with increased financial worry while enrollment in SSI, 0.38 (0.19, 0.76) was associated with decreased financial worry. CONCLUSIONS We identified factors that could contribute to financial burden after NICU discharge that may advise future work to target financial support systems.

We explore the treatment of bone metastases in advanced non-small cell lung cancer (NSCLC).We reported a 76-year-old female patient, who was diagnosed with NSCLC with bone metastasis eight years ago (stage IVA). Due to unbearable diarrhea, she refused chemotherapy, and we adopted local treatment, including local radiotherapy 50 Gy and bone cement to lumbar spinal metastases, 62 Gy local radiotherapy of primary lung tumor, TKI inhibitor gefitinib and zoledronic acid.She survived more than eight years and is still in follow-up.The median survival time for NSCLC patients with bone metastases is often less than 1 year. We reported the patient with more than eight years of survival, showed that some special cases can adopt the methods of local treatment including bone cement, treatment benefit patients, radiation therapy and targeted therapy in clinic to expand the survival.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project’s Kids’ Inpatient Database from 1997–2012. Neonates (infants

患儿女，9岁，因“进食排骨后出现吞咽困难1 d”于2018年1月21日就诊于聊城市人民医院耳鼻咽喉头颈外科。患儿自幼多次进食梗阻，既往有食道异物史。入院诊断为食道异物。患儿当日在全身麻醉下胃镜取出异物后，探查发现食道中下段食管蹼。患儿术后1 d出院，之后接受内镜下食管扩张治疗，随访2年，症状明显改善。.

Background Our objectives were (1) to describe Care Transitions Measure (CTM) scores among caregivers of preterm infants after discharge from the neonatal intensive care unit (NICU) and (2) to describe the association of CTM scores with readmissions, enrollment in public assistance programs, and caregiver quality of life scores. Methods The study design was a cross-sectional study. We estimated adjusted associations between CTM scores (validated measure of transition) with outcomes using unconditional logistic and linear regression models and completed an E-value analysis on readmissions to quantify the minimum amount of unmeasured confounding. Results One hundred sixty-nine parents answered the questionnaire (85% response rate). The majority of our sample was Hispanic (72.5%), non-English speaking (67.1%) and reported an annual income of p = 0.01), 1.02 (1, 1.05) for enrollment in early intervention, 1.03 (1, 1.05) for enrollment in food assistance programs, and a unit change (95% CI) 0.41 (0.27, 0.56) in the Multicultural Quality of Life Index score (p Conclusion The CTM may be a useful screening tool to predict certain outcomes for infants and their families after NICU discharge. However, further work must be done to identify unobserved confounding factors such as parenting confidence, problem-solving and patient activation.

BackgroundHaving a preterm newborn and the experience of staying in the neonatal intensive care unit (NICU) has the potential to impact a mother’s mental health and overall quality of life. However, currently there are few studies that have examined the association of acute post-traumatic stress (PTS) and depression symptoms and infant and maternal outcomes in low-income populations.Design/ methodsIn a cross-sectional study, we examined adjusted associations between positive screens for PTS and depression using the Perinatal Post-traumatic stress Questionnaire (PPQ) and the Patient Health-Questionnaire 2 (PHQ-2) with outcomes using unconditional logistic and linear regression models.ResultsOne hundred sixty-nine parents answered the questionnaire with 150 complete responses. The majority of our sample was Hispanic (68%), non-English speaking (67%) and reported an annual income of p p p = 0.01) respectively.ConclusionsMore than one-third of the mothers in this sample screened positively for PTS and depression symptoms. Screening scores positive for stress and depression symptoms were associated with a negative change in some infant development scores and maternal quality of life scores. Thoughtful screening programs for maternal stress and depression symptoms should be instituted.

To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD).We used a decision tree-Markov hybrid to model neonatal intensive care unit (NICU)-related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted.Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES.Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

Objectives Throughout the coronavirus disease 2019 pandemic, susceptible-infectious-recovered (SIR) modeling has been the preeminent modeling method to inform policy making worldwide. Nevertheless, the usefulness of such models has been subject to controversy. An evolution in the epidemiological modeling field is urgently needed, beginning with an agreed-upon set of modeling standards for policy recommendations. The objective of this article is to propose a set of modeling standards to support policy decision making. Methods We identify and describe 5 broad standards: transparency, heterogeneity, calibration and validation, cost-benefit analysis, and model obsolescence and recalibration. We give methodological recommendations and provide examples in the literature that employ these standards well. We also develop and demonstrate a modeling practices checklist using existing coronavirus disease 2019 literature that can be employed by readers, authors, and reviewers to evaluate and compare policy modeling literature along our formulated standards. Results We graded 16 articles using our checklist. On average, the articles met 6.81 of our 19 categories (36.7%). No articles contained any cost-benefit analyses and few were adequately transparent. Conclusions There is significant room for improvement in modeling pandemic policy. Issues often arise from a lack of transparency, poor modeling assumptions, lack of a system-wide perspective in modeling, and lack of flexibility in the academic system to rapidly iterate modeling as new information becomes available. In anticipation of future challenges, we encourage the modeling community at large to contribute toward the refinement and consensus of a shared set of standards for infectious disease policy modeling.

Objectives Area under the time–concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. Methods A cost–benefit analysis from the institutional perspective was conducted using a decision tree to model the probabilities and costs of acute kidney injury (AKI) associated with vancomycin administered over 48 hours up to 21+ days. Costs included vancomycin concentrations, Bayesian software and AKI hospitalization costs, and probabilities were obtained from primary literature. Robustness was assessed via both one-way and probabilistic sensitivity analyses. Results In the base-case model, two-sample AUC versus trough dosing saved an average of US$ 846 per patient encounter, and single-sample Bayesian AUC versus trough dosing saved an average of US$ 2065 per patient encounter. This translates into annual cost-savings of US$ 846 810 and US$ 2 065 720 for two-sample and single-sample Bayesian methods versus trough dosing, respectively, assuming 1000 vancomycin-treated patients per year. Assuming a budget of US$ 100 000 per year for Bayesian software, an institution would need to treat ≥41 patients with vancomycin for at least 48 hours to break even. Conclusions There are significant institutional cost benefits using two-sample AUC or single-sample Bayesian methods over trough dosing, even after accounting for the annual costs of Bayesian programs. The potential to decrease rates of AKI, improve clinical outcomes and reduce costs to the institution strongly warrants consideration of improved dosing methods for vancomycin.

Immune checkpoint inhibitor (ICI) has been emerged as a major breakthrough in tumor immunotherapy, but its unique mechanism of action has also led to a number of immune-related adverse events (irAE). Type 1 diabetes mellitus (T1DM) is one of the rarest irAEs. This paper reports a case of advanced malignant liver tumor-induced T1DM who received second-line anti-PD-1 therapy and showed initial symptoms of hyperosmolar coma and hyperglycemia. In addition, the relevant literature at home and abroad was collected and reviewed, and the clinical characteristics of T1DM induced by anti-PD-1 therapy were summarized with a view to achieve early detection, diagnosis and treatment.免疫检查点抑制剂(ICI)的出现是肿瘤免疫治疗的重大突破，但其独特的作用机制也带来了许多免疫相关不良反应（irAE）。1型糖尿病（T1DM）是极为罕见的irAE之一，通过报道一例晚期肝恶性肿瘤患者在接受二线抗PD-1治疗后出现以血糖升高及高渗昏迷为初发症状的T1DM病例，并搜集回顾国内外相关文献，总结抗PD-1治疗诱发的T1DM的临床特征，以期达到早发现、早诊断、早治疗。.

Purpose A novel value-based approach to evaluate costly specialty drugs for formulary addition was developed. Summary In February 2016, Stanford Health Care launched the specialty drug subcommittee (SDSC), a subcommittee of the pharmacy and therapeutics committee, responsible for the formulary review of specialty pharmaceuticals. A process was developed for value-based review that includes not only consideration of clinical trial data and institutional acquisition costs but also internal patient outcomes and a cost-effectiveness model using internal financial data. A Markov model was developed to assess the value of trabectedin, which was approved for formulary addition in April 2016, relative to the addition of dacarbazine. The economic model and internal patient outcome analysis were presented to the prescribing oncologist and the SDSC for review. Internal data revealed that fewer patients than had been estimated received trabectedin, with outcomes significantly worse than those observed in the clinical trial leading to Food and Drug Administration approval. In the cost-effectiveness model, trabectedin had higher costs and poorer outcomes compared with dacarbazine. Based on the economic model, low utilization, and real-world outcomes, trabectedin was removed from formulary and a restrictive treatment pathway for nonformulary use, developed by the primary prescriber, was implemented. This process has since been applied to 11 more specialty drugs. Conclusion Internal cost-effectiveness models in combination with real-world patient outcomes data can be effective formulary management tools. Engagement and collaboration with the requesting provider are key to developing thoughtful treatment pathways.

Objective To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. Methods Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. Results Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from −0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). Conclusions A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

Protein phosphorylation plays a key role in tumorigenesis and progression. However, little is known about the phosphoproteome profiles of growth hormone-secreting pituitary adenomas (GH-PAs). The aim of this study was to identify critical biomarkers and signaling pathways that might play important roles in GH-PAs and may, therefore, represent potential therapeutic targets. The differential phosphoprotein expression patterns involved in GH-PAs were investigated by nano-LC–MS/MS in a group of samples. The phosphoprotein expression data were analyzed by bioinformatics. The expression levels of the candidate phosphorylated AMPK (ser496) and ATF2 (ser112) were validated by Western blot analysis in another group of samples. A total of 1213 phosphorylated protein sites corresponding to 667 proteins were significantly different between GH-PAs and healthy pituitary glands. Among these phosphorylated sites, 871 exhibited lower levels of phosphorylation in GH-PAs. Moreover, 140 novel phosphosites corresponding to 93 proteins were differentially phosphorylated between GH-PAs and healthy pituitary glands, 101 of which showed decreased phosphorylation in GH-PAs. The majority of differentially expressed phosphorylated proteins were significantly enriched in glycolysis and the AMPK signaling pathway in GH-PAs. The AMPK signaling pathway was demonstrated to be inhibited in GH-PAs by pathway activity analysis (z score = − 2.324). Notably, the phosphorylated levels of AMPK (ser496) and ATF2 (ser112) were significantly lower in GH-PAs than in healthy pituitary glands. These findings suggest that decreased phosphorylation of the AMPK/ATF2 pathway may be critical for glucose metabolism and tumorigenesis in GH-PAs.

Background:The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.Methods:Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.Results:We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).Conclusion:Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.

目的 研究未甲基化胞嘧啶鸟嘌呤二核苷酸寡脱氧核苷酸（DSP30）和IL-2在慢性淋巴细胞白血病（CLL）常规染色体检测中的价值。 方法 DSP30联合IL-2刺激CLL细胞增殖，CLL细胞培养72 h后进行染色体制备，采用R显带法进行核型分析。对85例患者进行FISH检测，与同期核型结果进行比较。 结果 89例CLL患者中，无分裂象者5例，84例（94.38%）患者染色体分析成功，51例检测出染色体异常，异常检出率为60.71%（51/84），复杂核型者占52.94%（27/51）。对85例CLL患者进行了FISH检测，FISH探针为D13S25、RB1、P53、ATM、cen12。FISH检测结果显示74例异常，异常检出率为87.06%（74/85），其中复杂核型2例，占2.70%（2/74）。85例进行FISH检测的CLL患者中，50例常规染色体核型分析异常，30例核型正常，5例无分裂象，异常检出率为62.50%（50/80）；其中FISH检测异常而核型正常者25例，核型异常而FISH检测正常者4例，两者结合检测出异常者78例，异常检出率91.76%。FISH检测到的13q−异常率明显高于常规核型分析（69.41%对16.67%，P0.05）。常规核型分析对复杂异常的检出率（50.98%）高于FISH（2.70%）。另外，根据FISH结果进行预后分层的11例低危和9例中危患者均为复杂核型，根据核型结果被归为高危组。 结论 DSP30联合IL-2可以提高CLL患者常规染色体异常的检出率，对复杂异常核型的检测更为有效。FISH异常检出率高于常规核型分析方法，对缺失片段较小的13q−异常更为敏感，两者结合不仅将染色体异常检出率提高至91.76%，还可对CLL患者进行更为准确的预后分层，为临床提供更多信息。

We used the epidemic data of COVID-19 published on the official website of the municipal health commissions in Anhui province to map the spatiotemporal changes of confirmed cases, fit the epidemic situation by the population growth curve at different stages and analyze the epidemic situation in Anhui Province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7 with a change from J-shaped curve to S-shaped curve. As the reporting time of cases might be 3-5 days later than the actual onset time, the number of new cases in Anhui province actually began to decline around February 2 to February 4, 2020.利用安徽省各地市卫生健康委员会官方网站公布的新型冠状病毒肺炎（简称新冠肺炎）疫情数据，绘制安徽省确诊病例数时空分布地图，运用种群增长曲线拟合安徽省不同阶段疫情变化曲线，对全省和各地市疫情进行统计描述与分析。截至2020年2月18日，安徽省新冠肺炎累积发病率为1.56/10万，且安徽省报告新冠肺炎疫情在2月7日后呈现下降趋势，并由J型曲线变化到S型曲线，因病例报告时间比实际发病时间可能推迟3~5 d，安徽省新增病例实际于2020年2月2—4日前后开始下降。.

Congenital heart defects (CHD) represent a growing burden of illness among adults. We estimated the lifetime health, education, labor, and social outcomes of adults with CHD in the USA using the Future Adult Model, a dynamic microsimulation model that has been used to study the lifetime impacts of a variety of chronic diseases. We simulated a cohort of adult heads of households 25 years old derived from the Panel Survey of Income Dynamics who reported a childhood heart problem as a proxy for CHD and calculated life expectancy, disability-free and quality-adjusted life years, lifetime earnings, education attainment, employment, development of chronic disease, medical spending, and disability insurance claiming status. Total burden of disease was estimated by comparing to a healthy cohort with no childhood heart problem. Eighty-seven individuals reporting a childhood heart problem were identified from the PSID and were used to generate the synthetic cohort simulated in the model. Life expectancy, disability-free, quality-adjusted, and discounted quality-adjusted life years were an average 4.6, 6.7, 5.3, and 1.4 years lower than in healthy adults. Lung disease, cancer, and severe mental distress were more common compared to healthy individuals. The CHD cohort earned $237,800 less in lifetime earnings and incurred higher average total medical spend by $66,600 compared to healthy individuals. Compared to healthy adults, the total burden of CHD is over $500K per adult. Despite being among the healthiest adults with CHD, there are significant decrements in life expectancy, employment, and lifetime earnings, with concomitant increases in medical spend.

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin's lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.结外NK/T细胞淋巴瘤（ENKTCL）是一组比较少见的高度侵袭性的非霍奇金淋巴瘤。该病临床进展迅速、恶性程度高、预后较差，传统的放化疗方案并没有显示出良好的疗效。近几年来，肿瘤的免疫治疗迅猛发展，目前已在多种实体肿瘤如非小细胞肺癌、前列腺癌、黑色素瘤、肾癌的治疗中展示出了强大的治疗活性，多个肿瘤免疫治疗药物已经获得美国食品药品监督管理局批准上市并应用于临床。本文综述了近年来ENKTCL的新型免疫治疗方案，希望能够改变这种恶性疾病的治疗模式。.

We hope it will provide a reference for early detection, early diagnosis, and early treatment of atypical Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-typical autonomic dysfunctions as the first symptom.We present a 15-year-old girl with the repetition of conscious disturbance at different levels, but no abnormal movements. Initially, there were no positive findings on routine electroencephalography (EEG) and dynamic video-electroencephalography (V-EEG), but the head-up tilt test (HTT) suggested neurocardiogenic syncope (vascular rejection type), which seemed to be the final diagnosis. However, the patient later experienced several episodes of disturbance of consciousness with unexplained abdominal pain. Abnormalities were discovered on EEG, which indicated the possibility of "epileptic seizures with autonomic-gastrointestinal features". Based on these findings, we finally tested the autoimmune encephalitis-related antibodies for the patient after the literature search and review.The patient was finally diagnosed with anti-NMDAR encephalitis. Her symptoms were fully controlled after glucocorticoid and gamma globulin treatment, and she left the hospital with complete recovery.Although autonomic nervous dysfunction occurred in our patient, her prognosis was good because she did not have respiratory or (and) circulatory failure. Exclusive diagnosis and early treatment are important in patients with anti-NMDAR encephalitis. Abdominal pain with positive HTT may be a manifestation of autonomic dysfunction in this disease.

The objective of this analysis was to update trends in LOS and costs by survivorship and ECMO use among neonates with hypoplastic left heart syndrome (HLHS) undergoing stage 1 palliation surgery using 2016 data from the Healthcare Cost and Utilization Project Kids’ Inpatient Database. We identified neonates ≤ 28 days old with HLHS undergoing Stage 1 surgery, defined as a Norwood procedure with modified Blalock–Taussig (BT) shunt, Sano modification, or both. Multivariable regression with year random effects was used to compare LOS and costs by hospital region, case volume, survivorship, and ECMO vs. no ECMO. An E-value analysis, an approach for conducting sensitivity analysis for unmeasured confounding, was performed to determine if unmeasured confounding contributed to the observed effects. Significant differences in total costs, LOS, and mortality were noted by hospital region, ECMO use, and sub-analyses of case volume. However, other than ECMO use and mortality, the maximum E-value confidence interval bound was 1.71, suggesting that these differences would disappear with an unmeasured confounder 1.71 times more associated with both the outcome and exposure (e.g., socioeconomic factors, environment, etc.) Our findings confirm previous literature demonstrating significant resource utilization among Norwood patients, particularly those undergoing ECMO use. Based on our E-value analysis, differences by hospital region and case volume can be explained by moderate unobserved confounding, rather than a reflection of the quality of care provided. Future analyses on surgical quality must account for unobserved factors to provide meaningful information for quality improvement.

急性胰腺炎是消化系统常见疾病，尤其重症胰腺炎可并发多器官功能衰竭。胃促生长素（ghrein）参与调节食欲、胃肠动力、炎症反应等多种病理生理过程，其在急性胰腺炎病理生理机制中的保护作用及外源性ghrelin的治疗作用成为近年来研究热点。现就ghrelin在急性胰腺炎炎症反应、胃肠动力、胰腺血流改变、细胞再生等方面的保护及治疗作用做一综述。.

本文报道一例女性74岁阴道后穹窿破裂伴盆腔多脏器脱出患者，于2017年4月10日收治于武汉大学中南医院，经行Hartmann术+子宫附件切除+阴道后穹窿修补+阴道残端骶岬悬吊+阴道后壁修补术后恢复良好，无便秘和肛门失禁症状。本病例为一种少见急诊，常发生于子宫切除术后。既往无盆腔手术史的病例较罕见，临床上易漏诊和误诊。正确认识该病的病因、临床特点，并早期诊断治疗，对患者预后具有重要意义。.

ObjectivesTo investigate the prevalence, clinical characteristics, and prognosis of thrombocytopenia (TP) in Chinese patients with systemic lupus erythematosus (SLE).MethodsThe study was conducted based on the Chinese SLE Treatment and Research group (CSTAR) registry. Thrombocytopenia was defined as the platelet countResultsOf 2104 patients with SLE, 342 patients (16.3%) were diagnosed with thrombocytopenia. The prevalence of neuropsychiatric SLE, vasculitis, myositis, nephritis, mucocutaneous lesions, pleuritis, fever, leukocytopenia and hypocomplementemia were significantly higher in patients with thrombocytopenia (pConclusionsThrombocytopenia was a common manifestation of SLE and was associated with leukocytopenia, nephritis and severe disease activity. Severe thrombocytopenia tended to occur in long-term and relatively inactive SLE. Patients with SLE-related thrombocytopenia has a decreased long-term survival rate. Long disease duration was an independent risk factor of mortality in patients with thrombocytopenia.