Comparison of endoscopic third ventriculostomy versus cerebrospinal fluid shunt procedures for the treatment of pediatric hydrocephalus in Taiwan.

PURPOSE: Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS: We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. RESULTS: A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION: Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.

Salpingectomy for ectopic pregnancy reduces ovarian cancer risk-a nationwide study.

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

Purpose: To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Methods: Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). Results: A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Conclusion: Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

The landscape of investigator-initiated oncology trials conducted in mainland China during the past decade (2010-2019).

The number of clinical trials conducted in mainland China, including investigator-initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer-related IITs. We performed a comprehensive analysis of the landscape of cancer-related IITs in mainland China in the past decade. All cancer-related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer-related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double-blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer-related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015-2019 vs. 40.2% in 2010-2014, p < 0.001) and data monitoring committee use (44.5% vs. 40.0%, p = 0.001) and a decrease in randomization (51.5% vs. 62.7%, p < 0.001) and funding (36.4% vs. 56.3%, p < 0.001) between these periods. We also observed changes in intervention type (decrease in cytotoxic drug therapy [34.8% vs. 48.9%, p < 0.001]; increase in targeted therapy [17.8% vs. 14.2%, p = 0.004], immune checkpoint inhibitor therapy [6.6% vs. 0.0%, p < 0.001], and immune cell therapy [9.6% vs. 4.5%, p < 0.001]). Details of cancer-related IITs conducted during the past decade illustrate the merits of oncology research in mainland China. Although the increased quantity of IITs is encouraging, limitations remain regarding the quality of clinical trials, regional imbalances, and funding allocation.

Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies.

BACKGROUND: To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity. METHOD: The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently. RESULT: Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well. CONCLUSION: CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.

Risk Factors for Postischemic Stroke Epilepsy in Young Adults: A Nationwide Population-Based Study in Taiwan.

Background: The incidence of ischemic stroke has been increasing in the young population over the past 20 years. Poststroke epilepsy (PSE) is a common complication after stroke. However, few population-based studies with sufficient follow-up have investigated factors associated with PSE, especially factors related to comorbidities and unhealthy lifestyles in the modern young population. Accordingly, this study aimed to determine the long-term incidence and these risk factors for PSE young adults. Methods: This cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) from 2002 to 2018. All patients aged between 19 and 44 years and diagnosed with ischemic stroke from 2002 to 2015 were retrospectively enrolled with a follow-up of at least 3 years. Multivariable Cox regression models were performed to identify predictors of PSE, including patients' demographics, baseline conditions, stroke severity, etiologies, comorbidities, and unhealthy behaviors. Results: Among 6,512 ischemic stroke patients, 402 cases (6.2%) developed PSE who were with a mean follow-up period of 8.3 years (SD = 4.3 years). During the overall follow-up, stroke severity and manifestations were associated with PSE, including National Institutes of Health Stroke Scale (NIHSS) score ≥10 (aHR, 1.98; 95% CI, 1.50-2.61), seizure at first stroke admission [adjusted hazard ratio (aHR), 57.39; 95% confidence interval (CI), 43.02-76.55], length of hospital stay ≥14 days (aHR, 1.60; 95% CI, 1.26-2.02), recurrent stroke (aHR, 2.32; 95% CI, 1.85-2.90), aphasia (aHR, 1.77; 95% CI, 1.20-2.60), and malignancy (aHR, 2.05; 95% CI, 1.30-3.24). Furthermore, stroke patients with drug abuse were 2.90 times more likely to develop PSE than those without (aHR, 2.90; 95% CI, 1.53-5.50). By contrast, statin use (aHR, 0.62; 95% CI, 0.48-0.80) was associated with a lower risk of PSE. The risk factors at 1-year and 5-year PSE were similar to that of an overall follow-up. Conclusions: Stroke severity, aphasia, malignancy, and drug abuse were associated increased risk of PSE and statin use may protect against PSE in young adults. Reducing the severity of stroke, statin use and controlling unhealthy behaviors might be able to decrease the development of PSE. Since PSE is associated with poor outcomes, early identification or intervention of PSE based on the risk factors might reduce the harmful effects of PSE.

Association Between DPP-4 Inhibitors and Events of Colorectal and Liver Cancers in Patients With Diabetes Receiving Second-Line Agents: A Nested Case-Control Study.

Objective: Plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. Until now, whether DPP4is therapy affects the progression of liver cancer and colorectal cancer in patients with T2DM has not been well investigated. We investigated the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes. Materials and Methods: We identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan's National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is. Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32-0.75; P=0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32-2.61; P<0.001). No association between DPP4is use and liver cancer risk was observed. Conclusions: This nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. Therefore, the effects of long-term DPP4is use on colorectal cancer risk warrant further study.

Risk Factors for Spine Reoperation and Joint Replacement Surgeries after Short-Segment Lumbar Spinal Surgeries for Lumbar Degenerative Disc Disease: A Population-Based Cohort Study.

BACKGROUND: Short-segment lumbar spinal surgery is the most performed procedure for treatment of degenerative disc disease. However, population-based data regarding reoperation and joint replacement surgeries after short-segment lumbar spinal surgery is limited. METHODS: The study was a retrospective cohort design using the Taiwan National Health Insurance Research Database for data collection. Patients selected were diagnosed with lumbar degenerative disc disease and undergone lumbar discectomy surgery between 2002 and 2013. The Kaplan-Meier method was used to estimate the incidence of 1-year spine reoperation and joint replacement surgeries, and the Cox proportional hazard regression was used to examine risk factors associated with the outcomes of interest. RESULTS: A total of 90,105 patients were included. Incidences of 1-year spine reoperation and joint replacement surgeries for the hip and knee were 0.27, 0.04, and 0.04 per 100 people/month. Compared to fusion with the fixation group, fusion without fixation and the non-fusion group had higher risks of spine reoperation. Risk factors associated with spine reoperation included fusion without fixation, non-fusion surgery, age ≥ 45 years old, male gender, diabetes, a Charlson Comorbidity Index = 0, lowest social economic status, and steroid use history. Spine surgeries were not risk factors for joint replacement surgeries. CONCLUSIONS: Non-fusion surgery and spinal fusion without fixation had higher risks for spine reoperation. Spine surgeries did not increase the risk for joint replacement surgeries.

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo.

Exploring the mechanism through which berberine (Ber) reverses the multidrug resistance (MDR) of breast cancer is of great importance. Herein, we used the methyl thiazolyl tetrazolium assay to determine the drug resistance and cytotoxicity of Ber and doxorubicin (DOX) alone or in combination on the breast cancer cell line MCF-7/DOXFluc. The results showed that Ber could synergistically enhance the inhibitory effect of DOX on tumor cell proliferation in vitro, and the optimal combination ratio was Ber/DOX = 2:1. Using a luciferase reporter assay system combined with the bioluminescence imaging technology, the efflux kinetics of d-luciferin potassium salt in MCF-7/DOXFluc cells treated with Ber in vivo was investigated. The results showed that Ber could significantly reduce the efflux of d-luciferin potassium salt in MCF-7/DOXFluc cells. In addition, western blot and immunohistochemistry experiments showed that the expression of P-glycoprotein (P-gp/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) in MCF-7/DOXFluc cells was downregulated upon Ber treatment. Finally, high-performance liquid chromatography was used to investigate the effect of Ber on DOX tissue distribution in vivo, and the results showed that the uptake of DOX in tumor tissues increased significantly when combined with Ber (P < 0.05). Thus, the results illustrated that Ber can reverse MDR by inhibiting the efflux function of ATP-binding cassette transporters and downregulating their expression levels.

Association of frailty with in-hospital outcomes in elderly patients with heart failure.

BACKGROUND: Frailty is prevalent in elderly patients with cardiovascular diseases. However, the association between frailty and in-hospital outcomes for elderly patients with heart failure and reduced ejection (HFrEF) remains unknown. AIM: To evaluate the predictive efficacy of frailty, compared with pre-frailty, for adverse events in these patients. METHODS: Elderly patients (≥ 60 years) with HFrEF were assessed. Frailty was evaluated with the Fried phenotype criteria, and physical performance was evaluated based on handgrip strength and the short physical performance battery (SPPB). The composite incidence of adverse events, including all-cause death, multiple organ failure, cardiac shock, and malignant arrhythmia, during hospitalization was recorded. RESULTS: Overall, 252 elderly individuals with HFrEF [mean age: 69.4 ± 6.7 years, male: 169 (67.0%)] were included. One hundred and thirty-five (53.6%) patients were frail and 93 (36.9%) were pre-frail. Frail patients were older, more likely to be female, to have a lower blood pressure, and to present with left ventricular thrombosis (P all < 0.05). Frail patients with HFrEF had a higher incidence of in-hospital mortality (11.9% vs 4.3%, P = 0.048). Multivariate analyses showed that female gender (OR = 0.422), aging (OR = 1.090), poor cardiac functional class (OR = 2.167), frailty (OR = 2.379), and lower handgrip strength (OR = 1.106) were independent predictors of in-hospital adverse events (P all < 0.05). CONCLUSION: Frailty may be associated with poor in-hospital outcomes for elderly patients with HFrEF. The influence of frailty on long-term prognosis in these patients deserves further investigation.

C5aR deficiency attenuates the breast cancer development via the p38/p21 axis.

Emerging evidence has shown activation of the complement component C5 to C5a in cancer tissues and C5aR expression in breast cancer cells relates to the tumor development and poor prognosis, suggesting the involvement of complement C5a/C5aR pathway in the breast cancer pathogenesis. In this study, we found that as compared to the non-tumoral tissues, both C5aR and MAPK/p38 showed an elevated expression, but p21/p-p21 showed lower expression, in the tumoral tissues of breast cancer patients. Mice deficient in C5aR or mice treated with the C5aR antagonist exhibited attenuation of breast cancer growth and reduction in the p38/p-p38 expression, but increase in p21/p-p21 expression, in the tumor tissues. Pre-treatment of the breast cancer cells with recombinant C5a resulted in reduced p21 expression, and MAPK/p38 inhibitors prevented C5a-induced reduction in p21 expression, suggesting the involvement of the MAPK/p38 signaling pathway in the C5a/C5aR-mediated suppression of p21/p-p21 expression. These results provide evidence that breast cancer development may rely on C5a/C5aR interaction, for which MAPK/p38 pathway participate in down-regulating the p21 expression. Inhibition of C5a/C5aR pathway is expected to be helpful for the treatment of patients with breast cancer.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease / Características Clínicas e Eventos Adversos em Pacientes com Síndrome Coronariana Aguda e História de Doença Arterial Periférica

Abstract Background: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. Objective: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). Methods: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. Results: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. Conclusion: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Resumo Fundamento: Na observação clínica, os pacientes com síndrome coronariana aguda com doença arterial periférica têm prognóstico ruim, portanto, a relação entre as doenças e as características clínicas precisa ser mais explorada. Objetivos: Este estudo tem o objetivo de investigar características clínicas e fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda e história de doença arterial periférica (DAP). Métodos: Foram incluídos no estudo 5682 pacientes com síndrome coronariana aguda. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de DAP prévia: grupo DAP (n = 188) e grupo sem DAP (n = 5494, grupo controle). Em seguida, foram analisadas características clínicas e a incidência de eventos adversos hospitalares nesses grupos; um p < 0,05 foi considerado estatisticamente significativo. Resultados: A idade dos pacientes com DAP foi maior que a idade do grupo controle (65,5 ± 10,3 anos vs. 58,6 ± 11 anos, p < 0,001), e a proporção de pacientes com história de diabetes ou acidente vascular cerebral foi maior no grupo DAP que no grupo controle [73 (39%) vs. 1472 (26,8%), p = 0,018; 36 (19,3%) vs. 396 (7,2%), p < 0,001). A análise de regressão logística multivariada para eventos adversos hospitalares mostrou que história de DAP (OR = 1,791, p = 0,01), história de diabetes (OR = 1,223, p = 0,001), e idade >65 anos de idade (OR = 4,670, p < 0,001) foram fatores de risco independentes para eventos adversos hospitalares. Conclusão: DAP prévia, idade avançada, e história de diabetes são fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda.

Case report: primary resistance to osimertinib in erlotinib-pretreated lung adenocarcinoma with EGFR T790 M mutation.

BACKGROUND: Among non-small cell lung cancer (NSCLC) patients with acquired T790 M mutation resistance to first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), 71% are likely to benefit from osimertinib. There have been several reports about the secondary resistance to osimertinib treatment in T790 M-positive patients, while primary resistance to osimertinib has been rarely reported. CASE PRESENTATION: A 62-year-old Asian male never smoker who presented with stage IV EGFR L858R-positive adenocarcinoma developed EGFR T790 M mutation after 14 months of treatment with erlotinib combined with thoracic radiotherapy as first-line therapy. The patient was initiated on osimertinib treatment with T790 M mutation detected (14.4%), but disease progressed 2 months later. CONCLUSION: The mechanism of primary resistance to osimertinib remains unclear. There may be an association between T790 M mutation disappearance, TP53 mutation and radiotherapy, but further researches are needed to confirm this.

Domain swapping and SMYD1 interactions with the PWWP domain of human hepatoma-derived growth factor.

The human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal PWWP domain capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancers. We report the first crystal structures of the human HDGF PWWP domain (residues 1-100) in a complex with SMYD1 of 10 bp at 2.84 Å resolution and its apo form at 3.3 Å, respectively. The structure of the apo PWWP domain comprises mainly four ß-strands and two α-helices. The PWWP domain undergoes domain swapping to dramatically transform its secondary structures, altering the overall conformation from monomeric globular folding into an extended dimeric structure upon DNA binding. The flexible loop2, as a hinge loop with the partially built structure in the apo PWWP domain, notably refolds into a visible and stable α-helix in the DNA complex. The swapped PWWP domain interacts with the minor grooves of the DNA through residues Lys19, Gly22, Arg79 and Lys80 in varied ways on loops 1 and 4 of the two chains, and the structure becomes more rigid than the apo form. These novel structural findings, together with physiological and activity assays of HDGF and the PWWP domain, provide new insights into the DNA-binding mechanism of HDGF during nucleosomal functions.

Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver.

Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome. We identified 2,190 S-palmitoylated peptides corresponding to 883 S-palmitoylated proteins. After normalization using the membrane proteome with TMT10-plex labelling, 400 (31%) of S-palmitoylation sites on 254 proteins were down-regulated in Zdhhc13-deficient mice, representing potential ZDHHC13 substrates. Among these, lipid metabolism and mitochondrial dysfunction proteins were overrepresented. MCAT and CTNND1 were confirmed to be specific ZDHHC13 substrates. Furthermore, we found impaired mitochondrial function in hepatocytes of Zdhhc13-deficient mice and Zdhhc13-knockdown Hep1-6 cells. These results indicate that ZDHHC13 is an important regulator of mitochondrial activity. Collectively, our study allows for a systematic view of S-palmitoylation for identification of ZDHHC13 substrates and demonstrates the role of ZDHHC13 in mitochondrial function and metabolism in liver.

The Design and Validation of a Child Developmental e-Screening System.

An effective screening test could significantly impact identification of developmental delays at an early age. However, many studies have shown that delay screenings still use text-based screening survey questionnaires. Unfortunately, the traditional text-based screening method tends to be fairly passive. In addition, the advantages of using an interactive system and animation have been shown to lead to positive effects on learning in medical research. Therefore, a multimedia screening system is necessary. This study constructs a system architecture to develop an e-screening system for child developmental delays. To validate the system after development, this study conducted an experiment and employed a questionnaire to survey users. Five experts and 120 subjects participated in the experiment. After the experiment, the results of the system evaluation revealed excellent agreement between the text-based and multimedia version of Taipei II. A total of 118 (98%) participants preferred the multimedia version or had no preference, and only 2 (2%) preferred the paper version. Regular text-based screening sometimes excludes those with low literacy and those whose native language is different from the text. In addition, text-based screening tools lose users' attention easily. The current study successfully developed a multimedia text-based screening system. Feedback from the participants showed that the e-screening system was well accepted and more easily accessible than the original. In this study, a child developmental delays e-screening system was developed. After the experiment, the subjects indicated that the developmental delay e-screening system increased their comprehension and kept them interested in the screening.

Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis.

Atopic dermatitis is a complex chronic inflammatory skin disorder that results from intimate interactions among genetic predisposition, host environment, skin barrier defects, and immunological factors. However, a clear genetic roadmap leading to atopic dermatitis remains to be fully explored. From a genome-wide mutagenesis screen, deficiency of ZDHHC13, a palmitoylacyl transferase, has previously been associated with skin and multitissue inflammatory phenotypes. Here, we report that ZDHHC13 is required for skin barrier integrity and that deficiency of ZDHHC13 renders mice susceptible to environmental bacteria, resulting in persistent skin inflammation and an atopic dermatitis-like disease. This phenotype is ameliorated in a germ-free environment and is also attenuated by antibiotic treatment, but not by deletion of the Rag1 gene, suggesting that a microbial factor triggers inflammation rather than intrinsic adaptive immunity. Furthermore, skin from ZDHHC13-deficient mice has both elevated levels of IL-33 and type 2 innate lymphoid cells, reinforcing the role of innate immunity in the development of atopic dermatitis. In summary, our study suggests that loss of ZDHHC13 in skin impairs the integrity of multiple barrier functions and leads to a dermatitis lesion in response to microbial encounters.

Reoperation rates of anterior cervical discectomy and fusion versus posterior laminoplasty for multilevel cervical degenerative diseases: a population-based cohort study in Taiwan.

BACKGROUND CONTEXT: The reoperation (reop) rate is a crucial indicator of the efficacy of an operation; however, studies on the reop rates of anterior cervical discectomy and fusion (ACDF) or posterior laminoplasty (LMP) for treating multilevel cervical degenerative diseases (MCDDs) are scant. PURPOSE: This study aimed to compare the reop rates and safety of ACDF and LMP for MCDD treatment. STUDY DESIGN: This is a retrospective population-based cohort study. PATIENT SAMPLE: Our sample consists of patients who underwent ACDF and LMP treatment. OUTCOME MEASURES: Reop rate, risk of pneumonia, sepsis, surgery-related complications, and death. METHODS: A total of 6,605 patients who underwent ACDF and 1,578 patients who underwent LMP for MCDD treatment from 2001 to 2011 were selected from the Taiwan National Health Insurance Research Database. Cox proportional hazard models were performed to compare the clinical outcomes of the patients who underwent ACDF with those of the patients who underwent LMP. RESULTS: Long-term reop rates (per 100 person-month) were slightly Anterior cervical discectomy and fusion; in the patients who underwent ACDF (0.04 [95% confidence interval, CI: 0.03-0.05]) than in those who underwent LMP (0.06 [95% CI: 0.04-0.08]), with adjusted hazard ratio (HR) of 1.43 (95% CI: 0.96-2.11, p=.08), although short-term reop rates were significantly higher in the LMP group (0.41 [95% CI: 0.33-0.51]) than in the ACDF group (0.09 [95% CI: 0.07-0.11]), with adjusted HR of 4.81 (95% CI: 3.46-6.69, p<.001). Patients who underwent LMP had a lower risk of pneumonia, sepsis, surgery-related complications, and death than did those who underwent ACDF within a year of follow-up. The results after adjustment for all covariates showed that osteoarthritis (adjusted HR=2.07, 95% CI: 1.40-3.06, p<.01) was associated with reop risk in the patients who underwent ACDF, and diabetes (adjusted HR=3.27, 95% CI: 1.12-9.54, p=.03) was associated with reop risk in the patients who underwent LMP. CONCLUSIONS: There was no significantly higher incidence rate of reop between the patients who underwent LMP and those who underwent ACDF after 1-year follow-up; however, ACDF was associated with a higher rate of 1-year complications and mortality compared with LMP. LMP might be considered as a treatment option for MCDD but could not be appropriate for patients with cervical kyphotic deformity.

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13(skc4) mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13(skc4) mice.

Percutaneous dilatational tracheostomy for ICU patients with severe brain injury.

OBJECTIVE: To sum up our experience in percutaneous dilatational tracheostomy (PDT) in ICU patient with severe brain injury. METHODS: Between November 2011 and April 2014, PDTs were performed on 32 severe brain injury patients in ICU by a team of physicians and intensivists. The success rate, efficacy, safety, and complications including stomal infection and bleeding, paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, as well as clinically significant tracheal stenosis were carefully monitored and recorded respectively. RESULTS: The operations took 4-15 minutes (mean 9.1 minutes ± 4.2 minutes). Totally 4 cases suffered from complications in the operations: 3 cases of stomal bleeding, and 1 case of intratracheal bloody secretion, but none required intervention. Paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, or clinically significant tracheal stenosis were not found in PDT patients. There was no procedure-related death occurring during or after PDT. CONCLUSION: Our study demonstrats that PDT is a safe, highly effective, and minimally invasive procedure. The appropriate sedation and airway management perioperatively help to reduce complication rates. PDT should be performed or supervised by a team of physicians with extensive experience in this procedure, and also an intensivist with experience in difficult airway management.