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To investigate the association between ankylosing spondylitis (AS) and alopecia.In this cohort study, data from over 1 000 000 patients in the Taiwan Longitudinal Health Insurance Database were extracted. We selected newly diagnosed (outpatient department visit three or more times or admission at least once) patients with AS (ICD-9-CM = 720.0) from 2000 to 2012. For the non-AS comparison group, patients never diagnosed with AS were chosen from 1999 to 2013. In all, 3640 AS patients and 14 560 non-AS controls were selected. Cox proportional hazard model and Kaplan-Meier analysis were used to present the results. The adjusted hazard ratio (HR) in the Cox proportional hazard model was adjusted for age, sex, hypertension, hyperlipidemia, diabetes, atopic dermatitis, and mental disorder.No increased risk of alopecia in AS patients was shown in the Cox proportional hazard model (crude HR 1.16, P = 0.595; adjusted HR 1.16, P = 0.599). Negative results are found as well in subgroup analysis of different age, sex (age 20-40 y: HR 1.03, P = 0.925; Age ≥40 y: HR 1.49, P = 0.406; Female: HR 1.17, P = 0.759; Male: HR 1.15, P = 0.667), and phenotypes of alopecia (androgenetic alopecia: HR 1.19, 95% confidence interval [CI] 0.58-2.41; alopecia areata: HR 0.98, 95% CI 0.37-2.62). A significant positive correlation is found between atopic dermatitis and alopecia (adjusted HR 8.05, P = 0.039).In this population-based cohort study, we found no association of risk of alopecia and AS.

Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that Errγ2 may play a crucial role in ion uptake. In situ hybridization showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl− transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl− cotransporter (Ncc), the number of Ncc ionocytes, Na+/Cl− influxes of ionocytes, and whole-body Na+/Cl− contents. In FW with low Na+ and low Cl−, the expression levels of mRNA for Na+/H+ exchanger 3 (Nhe3) and Ncc were both decreased in Errγ2 morphants. Treating embryos with DY131, an agonist of Errγ, increased the whole-body Na+/Cl− contents and ncc mRNA expression in Errγ2 morphants. As such, medaka Errγ2 may control Na+/Cl− uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

Background Many children with autism cannot receive timely in-person diagnosis and therapy, especially in situations where access is limited by geography, socioeconomics, or global health concerns such as the current COVD-19 pandemic. Mobile solutions that work outside of traditional clinical environments can safeguard against gaps in access to quality care. Objective The aim of the study is to examine the engagement level and therapeutic feasibility of a mobile game platform for children with autism. Methods We designed a mobile application, GuessWhat, which, in its current form, delivers game-based therapy to children aged 3 to 12 in home settings through a smartphone. The phone, held by a caregiver on their forehead, displays one of a range of appropriate and therapeutically relevant prompts (e.g., a surprised face) that the child must recognize and mimic sufficiently to allow the caregiver to guess what is being imitated and proceed to the next prompt. Each game runs for 90 seconds to create a robust social exchange between the child and the caregiver. Results We examined the therapeutic feasibility of GuessWhat in 72 children (75% male, average age 8 years 2 months) with autism who were asked to play the game for three 90-second sessions per day, 3 days per week, for a total of 4 weeks. The group showed significant improvements in Social Responsiveness Score-2 (SRS-2) total (3.97, p Conclusion The results support that the GuessWhat mobile game is a viable approach for efficacious treatment of autism and further support the possibility that the game can be used in natural settings to increase access to treatment when barriers to care exist.

Mesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs’ high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies’ inferior solubility or affinity/specificity to the target antigen.

Background: Colorectal cancer is curable if diagnosed early and treated properly. Black and Hispanic patients with colorectal cancer are more likely to experience treatment delays and/or receive lower standards of care. Socioeconomic deprivation may contribute to these disparities, but this has not been extensively quantified. We studied the interrelationship between patient race/ethnicity and neighborhood socioeconomic status (nSES) on receipt of timely appropriate treatment among patients with colorectal cancer in California. Methods: White, Black, and Hispanic patients (26,870) diagnosed with stage I–III colorectal cancer (2009–2013) in the California Cancer Registry were included. Logistic regression models were used to examine the association of race/ethnicity and nSES with three outcomes: undertreatment, >60-day treatment delay, and >90-day treatment delay. Joint effect models and mediation analysis were used to explore the interrelationships between race/ethnicity and nSES. Results: Hispanics and Blacks were at increased risk for undertreatment [Black OR = 1.39; 95% confidence interval (CI) = 1.23–1.57; Hispanic OR = 1.17; 95% CI = 1.08–1.27] and treatment delay (Black/60-day OR = 1.78; 95% CI = 1.57–2.02; Hispanic/60-day OR = 1.50; 95% CI = 1.38–1.64) compared with Whites. Of the total effect (OR = 1.15; 95% CI = 1.07–1.24) of non-white race on undertreatment, 45.71% was explained by nSES. Conclusions: Lower nSES patients of any race were at substantially higher risk for undertreatment and treatment delay, and racial/ethnic disparities are reduced or eliminated among non-white patients living in the highest SES neighborhoods. Racial and ethnic disparities persisted after accounting for neighborhood socioeconomic status, and between the two, race/ethnicity explained a larger portion of the total effects. Impact: This research improves our understanding of how socioeconomic deprivation contributes to racial/ethnic disparities in colorectal cancer.

While prior studies have largely focused on family communication of diagnostic single-gene test results or specific types of cancer testing results, far less work has investigated family communication of cancer-related genetic results that include multi-gene panels, a broad array of cancer types/stages, and participants without family history of cancer. The study we report here examined individuals' anticipated barriers and benefits to sharing genetic information with family members. An 80+ gene panel was performed on participants recruited from Mayo Clinic, diagnosed with different cancer types, who did not have a family history suggestive of an inherited risk. Participants completed a 49-item survey before receiving genetic test results. Family variant testing was provided to family members at no cost, allowing factors influencing intent to share to be examined in the absence of financial burdens. In all, 1721 of 2984 individuals who received genetic testing completed the survey (57.7% completion rate). Participants' intent to share with parents, siblings, and children was inversely related to the number of anticipated barriers to sharing and directly related to the number of anticipated benefits to sharing. Of those participants who did not intend to share with parents, siblings, and adult children, 64.8%, 30.3%, and 67.6% reported that there were no barriers, while 17.1%, 24.5%, and 40.2.% reported there were no benefits. Findings indicate that barriers to sharing genetic information with family members vary across family member types, and an inability to identify at least one benefit of sharing with family members is a predictor of intent not to share.

Background Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. Methods This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. Results A total of 135 patients were included. Median age at diagnosis was 53 years old (19–84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0–1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka‐Koga system, overall survival (OS) at five‐years was 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1–7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3–12.7]; p = 0.016) were significantly associated with increased risk of death. Conclusions Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control., Here, we report the largest analysis of clinical characteristics of thymomas and outcomes in Latin American patients. Out of 135 patients included in the study, 21.5% (n = 29) concurrently presented myasthenia gravis. Relapse‐free survival rates at five‐years were 58.5% for stage I–II, and 35.4% for stage III. Five‐year overall survival rates were 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively.

OBJECTIVE Intravenous iloprost improves Raynaud's phenomenon (RP) and promotes healing of digital ulcers in systemic sclerosis (SSc; scleroderma). Despite a short half-life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE-cadherin clustering between endothelial cells (ECs), regulate endothelial properties including barrier function, endothelial-to-mesenchymal transition (EndoMT), and angiogenesis. We undertook this study to investigate the hypothesis that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions. METHODS Dermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative polymerase chain reaction. RESULTS Adherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE-cadherin and increased permeability in SSc ECs (P < 0.05). Iloprost increased VE-cadherin clustering at junctions and restored junctional levels of VE-cadherin in SSc ECs (mean ± SD 37.3 ± 4.3 fluorescence units) compared to normal ECs (mean ± SD 29.7 ± 3.4 fluorescence units; P < 0.05), after 2 hours of iloprost incubation. In addition, iloprost reduced permeability of monolayers, increased tubulogenesis, and blocked EndoMT in both normal and SSc ECs (n ≥ 3; P < 0.05). The effects in normal ECs were inhibited by a function-blocking antibody that prevents junctional clustering of VE-cadherin. CONCLUSION Our data suggest that the long-lasting effects of iloprost reflect its ability to stabilize adherens junctions, resulting in increased tubulogenesis and barrier function and reduced EndoMT. These findings provide a mechanistic basis for the use of iloprost in treating SSc patients with RP and digital ulcers.

The management of persistent postsurgical pain and neuropathic pain remains a challenge in the clinic. Local anesthetics have been widely used as simple and effective treatment for these two disorders, but the duration of their analgesic effect is short. We here reported a new poly lactic-co-glycolic acid (PLGA)-coated ropivacaine that was continuously released in vitro for at least 6 days. Peri-sciatic nerve injection of the PLGA-coated ropivacaine attenuated paw incision-induced mechanical allodynia and heat hyperalgesia during the incisional pain period, and spared nerve injury-induced mechanical and cold allodynia for at least 7 days post-injection. This effect was dose-dependent. Peri-sciatic nerve injection of the PLGA-coated ropivacaine did not produce detectable inflammation, tissue irritation, or damage in the sciatic nerve and surrounding muscles at the injected site, dorsal root ganglion, spinal cord or brain cortex, although the scores for grasping reflex were mildly and transiently reduced in the higher dosage-treated groups. PERSPECTIVE: Given that PLGA is an FDA-approved medical material, and that ropivacaine is used currently in clinical practice, the injectable PLGA-coated ropivacaine represents a new and highly promising avenue in the management of postsurgical pain and neuropathic pain.

Background The purpose of this study was to determine the efficacy of a mandibular advancement device (MAD) for increasing patient safety during sedated total knee arthroplasty (TKA) and total hip replacement (THR). Methods Forty patients undergoing TKA or THR surgery in the supine or lateral recumbent positions under spinal anesthesia were enrolled. Sedation and oxygenation were administered. The MAD (Sweet Sleep Anti-Snoring Device®) was then placed after 15 min of observation. SpO2, PetCO2, blood pressure, and respiratory rate were recorded. Results Sedated patients in the decubitus position had higher saturation nadirs, shorter desaturation durations, shorter airway obstruction durations, and fewer rescue events than those in the supine position. In patients at a high risk of obstructive sleep apnea syndrome (OSAS), desaturation duration, obstruction duration, apnea duration, desaturation duration, and rescue events were significantly lower after MAD placement. However, the saturation nadir did not improve after MAD placement. Conclusion The MAD may shorten the duration of desaturation events during spontaneous breathing sedative procedures in the lateral recumbent position but not in the supine position. Breathing patterns did not change from nasal breathing to oral breathing or vice versa between pre- and post-placement of the MAD. Sedation score evaluation affects breathing pattern changes from oral breathing to nasal breathing and vice versa.

Dementia with Lewy bodies (DLB), a highly prevalent neurodegenerative disorder, causes motor and cognitive deficits. The main pathophysiologies of DLB are glutamate excitotoxicity and accumulation of Lewy bodies comprising α-synuclein (α-syn) and β-amyloid (Aβ). Amitriptyline (AMI) promotes expression of glutamate transporter-1 and glutamate reuptake. In this study, we measured the effects of AMI on behavioral and neuronal function in a DLB rat model. We used rivastigmine (RIVA) as a positive control. To establish the DLB rat model, male Wistar rats were stereotaxically injected with recombinant adenoassociated viral vector with the SNCA gene (10 μg/10 μL) and Aβ (5 μg/2.5 μL) into the left ventricle and prefrontal cortex, respectively. AMI (10 mg/kg/day, i.p.), RIVA (2 mg/kg/day, i.p.), or saline was injected intraperitoneally after surgery. From the 29th day, behavioral tests were performed to evaluate the motor and cognitive functions of the rats. Immunohistochemical staining was used to assess neuronal changes. We measured the α-syn level, number of newborn cells, and neuronal density in the hippocampus and in the nigrostriatal dopaminergic system. The DLB group exhibited deficit in object recognition. Both the AMI and RIVA treatments reversed these deficits. Histologically, the DLB rats exhibited cell loss in the substantia nigra pars compacta and in the hippocampal CA1 area. AMI reduced this cell loss, but RIVA did not. In addition, the DLB rats exhibited a lower number of newborn cells and higher α-syn levels in the dentate gyrus (DG). AMI did not affect α-syn accumulation but recovered neurogenesis in the DG of the rats, whereas RIVA reversed the α-syn accumulation but did not affect neurogenesis in the rats. We suggest that AMI may have potential for use in the treatment of DLB.

Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case–control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28–1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34–1.67], 3.47 [1.12–10.8], 1.22 [1.04–1.43], 1.60 [1.31–1.96], 2.10 [1.63–2.72], and 1.69 [1.26–2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14–1.58] and 1.50 [1.38–1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72–2.49] and 1.39 [1.28–1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.

Background Nonintubated video-assisted thoracic surgery (VATS) is widely used due to its acceptable postoperative outcomes. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) has been successfully applied in cases of prolonged difficult intubation and intensive respiratory care in patients receiving VATS lobectomy. Thopaz Digital Chest Drainage System (THOPAZ) provides regulated negative pressure close to the patient's chest, optimizing drainage of the pleural and mediastinum. We explored the surgical outcomes of nonintubated VATS lung wedge resection and traditional wedge resection with a double-lumen endotracheal tube. Methods Patients who received nonintubated VATS lung wedge resection (group A, n = 81) and traditional wedge resection with double-lumen endotracheal tube (group B, n = 79) during the period of November 2015 to April 2018 were enrolled in the study. Demographic data and operation outcomes were obtained and analyzed from review of patient medical charts. Results Group B had significantly longer mean induction and operative times than group A. Similarly, group B suffered greater intraoperative blood loss, longer postoperative hospital stays, and increased chest tube retention times than group A. Group A had higher partial pressure of carbon dioxide levels in both the pre-one-lung and during one-lung ventilation periods than group B. Furthermore, group A showed lower serum pH levels during one-lung ventilation period. However; group A had significantly higher partial pressure of oxygen levels during one-lung ventilation than group B, although the differences in peripheral oxygen saturation were not statistically significant. Conclusion Our study demonstrated that nonintubated VATS using THRIVE and THOPAZ in lung wedge resection provides measurable benefits to patients.

Appendectomy is a frequently performed surgical procedure; however, long-term consequences have not been fully explored. We used a nationwide population-based cohort to determine whether patients undergoing appendectomy are at an increased risk of sepsis. Overall, 252,688 patients undergoing appendectomy and 252,472 matched controls were identified from the National Health Insurance Research Database in Taiwan. A propensity score analysis was used for matching age, sex, index year and comorbidities at a ratio of 1:1. Multiple Cox regression and stratified analyses were used to estimate the adjusted hazard ratio (aHR) of developing sepsis. Patients undergoing appendectomy had a 1.29 times (aHR: 1.29; 95% confidence interval [CI], 1.26–1.33) higher risk of developing sepsis than those not undergoing. Patients aged 20–49 years had a 1.58-fold higher risk of sepsis in the appendectomy cohort (aHR; 95% CI, 1.50–1.68). Also, having undergone appendectomy, patients had a higher likelihood of sepsis, regardless of sex and with or without comorbidities. Patients with

Self-management helps patients understand their illnesses and learn about disease-related skills so they can better manage their situation. However, published studies on the effectiveness of self-management for chronic obstructive pulmonary disease (COPD) are heterogeneous. Quasi-experimental design was used to investigate the effectiveness of a self-management program in self-care efficacy and quality of life in patients with COPD. Sixty participants who had experienced COPD were assigned to control group (usual care) or experimental group (self-care program) (1:1 ratio) according to a purposeful sampling at a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale, the Clinical COPD Questionnaire were used to analyze data. The Medical Research Council dyspnea scale was more significant improvement in the 2 months after discharge in the experimental group than in the control group. The COPD Self-Efficacy Scale and Clinical COPD Questionnaire scores in the experimental group within 3 months after discharge were significantly improved compared with the control group. These findings demonstrate the application and initial effect of this self-management program.

Refracture of cemented vertebrae occurs commonly after vertebroplasty (VP) for osteoporotic vertebral compression fracture (OVCF). It can result in severe pain or neurological deficit, but no preventive medication is available. Owing to the bone anabolic benefits of teriparatide (TP), this study was aimed to compare the outcomes of cemented vertebrae with TP to those without TP. Patients who received VP for OVCF with at least 1 year follow-up were included. The anterior body height (ABH) and middle body height (MBH) and kyphotic angle (KA) were measured before VP and 1 week and at least 1 year after VP. Refracture was defined as a 15% decrease in ABH or MBH and 8° decrease in KA compared with those at postoperative 1 week. The clinical outcomes were evaluated. 35 VP procedures in 21 patients treated with TP (TP group), and, matched to that, 29 out of 133 patients treated with VP alone (VP group) were included. One year after VP, ABH and MBH were significantly greater, except KA, in the TP group (VP group vs. TP group: KA − 4.97° ± 12.1 vs. −2.85° ± 12.21°, p = 0.462, ABH 1.56 ± 0.48 cm vs. 1.84 ± 0.56 cm, p = 0.027, MBH 1.49 ± 0.39 cm vs. 1.73 ± 0.41 cm, p = 0.017). The refracture rates of KA, ABH, and MBH were significantly lower in the TP group (VP group vs. TP group: KA 42.11% vs.8.57%, p p p

Objective The loading force applied in infant external chest compression (ECC) has not been determined. The objective of this crossover study was to quantify the actual force involved in two-thumb (TT)-encircling hands and two-finger (TF) methods during infant cardiopulmonary resuscitation. Methods A total of 42 emergency medical professionals performed lone rescuer infant external chest compression (ECC) with TF and TT methods. The order of two methods was arranged randomly, with an interval of 30 min in between. The force was collected by MatScan as primary outcomes. The secondary outcomes, quality of chest compressions, and fatigue level were also recorded by SkillReporter and perceived exertion scale. Results Using the TT method, the rescuers performed cardiopulmonary resuscitation (CPR) with higher ECC quality, but more incomplete recoil than they did using the TF method. The mean compression forces delivered in the first and second minutes were 3.53 ± 1.27 kg and 3.22 ± 1.11 kg (P = 0.012) for TF and 4.11 ± 1.80 kg and 4.04 ± 1.83 kg (P = 0.568) for TT, respectively. Pairwise comparison indicates that the compression force delivered through the TF method during the first and second minute of ECC were inferior to that delivered through the TT method. The TF method involved greater perceived exertion than the TT method (5.27 ± 4.69 vs. 4.02 ± 2.31; P = 0.007). The median perceived exertions for the TF and TT methods were 5 and 4, respectively. Conclusion For infant CPR, the TT method involved greater loading force, lower fatigue, and higher overall ECC quality than the TF method. The optimal compression force is about 3.8-4.3 kg.

Radial glial progenitor cells (RGPs) are the major neural progenitor cells that generate neurons and glia in the developing mammalian cerebral cortex1-4. In RGPs, the centrosome is positioned away from the nucleus at the apical surface of the ventricular zone of the cerebral cortex5-8. However, the molecular basis and precise function of this distinctive subcellular organization of the centrosome are largely unknown. Here we show in mice that anchoring of the centrosome to the apical membrane controls the mechanical properties of cortical RGPs, and consequently their mitotic behaviour and the size and formation of the cortex. The mother centriole in RGPs develops distal appendages that anchor it to the apical membrane. Selective removal of centrosomal protein 83 (CEP83) eliminates these distal appendages and disrupts the anchorage of the centrosome to the apical membrane, resulting in the disorganization of microtubules and stretching and stiffening of the apical membrane. The elimination of CEP83 also activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of RGPs, together with a subsequent overproduction of intermediate progenitor cells, which leads to the formation of an enlarged cortex with abnormal folding. Simultaneous elimination of YAP suppresses the cortical enlargement and folding that is induced by the removal of CEP83. Together, these results indicate a previously unknown role of the centrosome in regulating the mechanical features of neural progenitor cells and the size and configuration of the mammalian cerebral cortex.

Background The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein‐Barr virus (EBV) infection for NPC risk. Methods 1235 male NPC cases and 1262 hospital‐based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti‐EBV VCA IgA and anti‐EBV EA‐EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. Results 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60‐fold (95% CI = 1.30‐1.97) and former smokers a borderline significant 1.27‐fold (95% CI = 1.00‐1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack‐years of cigarette smoking but not with age at smoking initiation. Among controls, anti‐EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19‐2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti‐EBV VCA IgA. Conclusion This study confirms the association between long‐term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti‐EBV VCA IgA antibodies., Smoking duration and intensity but not age at initiation are NPC risk factors, and anti‐EBV VCA IgA seropositivity rate was higher in current than never smokers among controls. Mediation analyses show that NPC and EBV association may be explained by the interplay between smoking and EBV antibodies serostatus.

Background Surgical interventions for congenital scoliosis are challenging for spine surgeons. The coordination of 3-dimensional (3D), real-time, image-guided navigation with an ultrasonic bone cutter allows surgeons to localize the affected area of the spine accurately and remove the lesion without damaging soft tissue structures. The goal of this technical paper is to report a previously undescribed method of hemivertebrectomy that combines 3D, real-time, image-guided navigation and an ultrasonic bone cutter. We highlight the feasibility and safety of this method in spinal surgery. Methods Three patients with congenital scoliosis were treated with this technique. We present three illustrative cases comprising hemivertebrectomies for congenital scoliosis. Intraoperative photos demonstrating the technique are also provided. Results All surgeries were completed without complications. The hemivertebrae were completely removed, and marked correction of congenital scoliosis was noted. Conclusions We believe that the combination of 3D, real-time image navigation and an ultrasonic bone cutter improves hemivertebrectomy by increasing accuracy and avoiding dura laceration, major organ damage, or potential vessel damage.

PURPOSE: We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan. METHODS: We performed a prospective, multicenter, randomized controlled trial. The inclusion criteria were age ≥21 years, baseline glycated hemoglobin (HbA(1c)) level ≤9.5%, and intention to fast for ≥10 days during Ramadan. Exclusion criteria included baseline estimated glomerular filtration rate

Background. Increasing attention has been paid to the predictive power of different prognostic scoring systems for decades. In this study, we compared the abilities of three commonly used scoring systems to predict short-term and long-term mortalities, with the intention of building a better prediction model for critically ill patients. We used the data from the National Health Insurance Research Database (NHIRD) in Taiwan, which included information on patient age, comorbidities, and presence of organ failure to build a new prediction model for short-term and long-term mortalities.Methods. We retrospectively collected the medical records of patients in the intensive care unit of a regional hospital in 2012 and linked them to the claims data from the NHIRD. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Elixhauser Comorbidity Index (ECI), and Charlson Comorbidity Index (CCI) were compared for their predictive abilities. Multiple logistic regression tests were performed, and the results were presented as receiver operating characteristic curves and C-statistic.Results. The APACHE II score has the best predictive power for inhospital mortality (0.79;C−statistic=0.77−0.83) and 1-year mortality (0.77;C−statistic=0.74−0.79). The ECI and CCI alone have poorer predictive power and need to be combined with other variables to be comparable to the APACHE II score, as predictive tools. Using CCI together with age, sex, and whether or not the patient required mechanical ventilation is estimated to have a C-statistic of 0.773 (95% CI 0.744-0.803) for inhospital mortality, 0.782 (95% CI 0.76-0.81) for 30-day mortality, and 0.78 (95% CI 0.75-0.80) for 1-year mortality.Conclusions. We present a new prognostic model that combines CCI with age, sex, and mechanical ventilation status and can predict mortality, comparable to the APACHE II score.

BACKGROUND Microelectrode recording (MER) for target refinement is widely used in deep brain stimulator insertion for Parkinson disease. Signals may be influenced by anesthetics when patients receive general anesthesia (GA). This study determined the inhibitory concentration (IC) of propofol on MER signals when it was coadministered with dexmedetomidine. METHODS Patients were anesthetized with dexmedetomidine (0.5 μg·kg loading, followed by infusion at 0.4 μg·kgh) and propofol through target-controlled infusion for GA with tracheal intubation. The surgeon conducted the online scoring of the background signals, spiking frequency, amplitude, and pattern of single-unit activities by using a 0-10 verbal numerical rating scale (NRS; 0, maximal suppression; 10, minimal suppression), and responses were grouped into suppression (NRS ≤ 6) and nonsuppression (NRS > 6). The median inhibitory concentration (IC50) of propofol (as target effect-site concentrations: Ceprop) was determined using modified Dixon's up-and-down method. Probit regression analysis was further used to obtain the dose-response relationship, and IC05 and IC95 were calculated. RESULTS Twenty-three adult patients participated in this study. Under the concomitant infusion of dexmedetomidine, the predicted IC50 value (95% CI) of Ceprop for neuronal suppression during MER was 1.29 (1.24-1.34) μg·mL as calculated using modified Dixon's up-and-down method. Using probit analysis, the estimated IC05, IC50, and IC95 values (95% CIs) were 1.17 (0.87-1.23), 1.28 (1.21-1.34), and 1.40 (1.33-1.85) μg·mL, respectively. CONCLUSION Our data provided reference values of propofol for dosage adjustment to avoid interference on MER under GA when anesthetics have to be continuously infused during recording.

BACKGROUND Chronic pain is a common postoperative complication in patients undergoing major surgery and may significantly affect their quality of life (QOL). Whether patient-controlled analgesia (PCA) can reduce the risk of chronic postsurgical pain and promote long-term QOL is still unclear. METHODS In this prospective cohort study, we followed up patients undergoing major surgery, recorded changes in their postoperative QOL over time using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and chronic pain events, evaluated the long-term effects of distinct PCA techniques (intravenous, epidural, or none) on their QOL and risk of chronic pain, and explored relevant predictors. The patients' QOL and chronic pain events were collected preoperatively, 3, 6, and 12 months after surgery. Generalized linear mixed models were used to control for individual heterogeneity and adjust for potential confounding factors. RESULTS We included 328 patients undergoing major surgery from September 22, 2015, to December 31, 2016, in this study. Multivariate regression models showed that patients using intravenous PCA had a better QOL in physical health (adjusted coefficient 3.7, 95% CI, 0.5-8.0) compared with those receiving non-PCA treatments. Distinct PCA techniques did not significantly affect QOL in psychological, social relationship, or environmental domains of the WHOQOL-BREF scale or the risk of chronic postsurgical pain. CONCLUSION Patients using intravenous PCA had a better QOL in physical health over time after major surgery, which may have been due to factors other than pain-relieving effects.

Delta opioid receptor (DOR) is well known to be involved in heroin dependence. This study tested the hypothesis that single nucleotide polymorphisms (SNPs) in the opioid receptor delta 1 (OPRD1) gene coding region are associated with treatment responses in a methadone maintenance therapy (MMT) cohort in Taiwan. Three hundred forty-four MMT patients were recruited. Diastolic/systolic blood pressure, heart rate, methadone dosage, and plasma concentrations of methadone were recorded. Twenty-five SNPs located within the OPRD1 genetic region were selected and genotyped from the genomic DNA of all 344 participants. After pairwise tagger analyses, tagger SNP rs204047 showed a significant association with methadone dosage (P = 0.0019), and tagger SNPs rs204047 and rs797397 were significantly associated with plasma R, S-methadone concentrations (P

Background It is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis. Methods We performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission. Results A total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3–4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6–6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P

This study aimed to identify outcome determinants for extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) at our institution.This retrospective single-center study reviewed patients on ECMO between 2010 and 2018 and compared clinical characteristics between patients who underwent successful-BTT and those who did not. Additionally, we examined differences between actively versus emergently listed patients and reasons for failure-to-list. Seventy-six patients were placed on ECMO with the intent to bridge to transplant. Of those, 42 were actively on the waitlist (AWL) prior to ECMO initiation, 20 were emergently evaluated and waitlisted (EWL) after ECMO initiation, and 14 failed-to-list. Of the 62 listed patients, 42 (68%) were successfully transplanted. Risk factors of failed-BTT included right ventricular dysfunction prior to ECMO initiation, longer ECMO duration, reduced mobility status, shorter stature, higher prevalence of blood type B, worse kidney and liver function, and increased transfusion requirements. The number of patients transitioned to central VA-ECMO was higher in the failed-BTT group. Thirty-day survival post-transplantation was 98%, with 90% successfully discharged; 1-year survival conditional upon discharge was 97%. AWL and EWL groups had comparable outcomes. Reasons for failure-to-list are not readily modifiable. ECMO-BTT has become a viable option with satisfactory 1-year survival in patients with irreversible lung injury. Our results support rescue transplant for emergently evaluated and waitlisted patients on ECMO. Our data suggests that modification in national organ allocation policies especially as they pertain to high-acuity recipients with rare blood types and short stature could enhance successful outcome.

Background/purpose: Non-small cell lung cancer (NSCLC) presenting as subcentimeter lung tumor was increasing due to the popularity of low dose CT in recent years. However, the ideal surgical management is still controversial. We utilized our lung cancer surgery database to study the important issue, aiming to find the optimal treatment with VATS. Methods: From January 2010 to December 2015, we retrospectively reviewed the clinical characteristics, staging, operation methods, and outcomes of 424 patients with subcentimeter lung cancer. Three groups distinguished by surgical methods were compared. Results: There are 273, 57, and 94 undergoing VATS wedge resection, segmentectomy, and lobectomy, respectively. Of the nine recurrence or metastasis events, seven and two occurred within the wedge resection and lobectomy groups, respectively. The average follow-up time is 779 days (2.16 years). Furthermore, 97.4%, 100%, and 97.9% of patients in the wedge resection, segmentectomy, and lobectomy groups, respectively remained tumor-free during follow-up. The complication rate of approximately 1.5% did not differ significantly between the three groups. An obvious difference in disease-free survival between the three groups (p-value = 0.027; −2 log likelihood score and chi-square test). No cases of recurrence or metastasis were observed in the segmentectomy group. Conclusion: Lung cancer with subcentimeter size will be more and more encountered. VATS plays an important role in the management with good post-operative outcome, whether with wedge resection, segmentectomy and lobectomy. However, VATS segmentectomy can deliver 100% overall survival and progression-free survival in our series. Further randomized controlled trial should be conducted to prove the concept. Keywords: Non-small cell lung cancer, VATS, Outcome, Early lung cancer, Subcentimeter lung tumor

Whether epidural anesthesia and analgesia (EA) improves long-term outcomes after pancreatic cancer surgery remains controversial. We conducted this retrospective cohort study to investigate the influence of EA on cancer recurrence and overall survival after surgery for pancreatic cancer.We conducted an electronic medical chart review of patients with pancreatic cancer who underwent curative resection at our hospital from 2008 to 2017 and were followed up until December 2019. Patient demographics, anesthetic and surgical characteristics, and pathologic features were also collected. The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW) based on propensity scores to balance unequal distributions of observed covariates. For sensitivity analysis, multivariable regression modeling and quintile-stratified propensity adjustments were also used.Among the 252 included patients, the median follow-up period was 15.9 months (interquartile range 6.8-28.2 months), and 88 (35%) received EA after pancreatic cancer surgery. EA was not associated with greater cancer recurrence (IPTW adjusted HR: 0.98; 95% CI, 0.78%-1.24%; p = 0.87) or all-cause mortality (IPTW adjusted HR: 1.02; 95% CI, 0.82%-1.27%; p = 0.85) after pancreatic cancer resection. In sensitivity analysis, both the multivariable and stratified Cox regression analyses failed to demonstrate significant effects of EA on cancer recurrence and survival after surgery.There were no significant associations between EA and cancer recurrence and overall survival after curative surgery for pancreatic cancer. Prospective studies should be considered to elucidate the relationship between EA and cancer outcomes after pancreatic cancer surgery.

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease’s progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.

BackgroundTraditional risk factors for chronic kidney disease (CKD) include diabetes mellitus (DM), hypertension (HTN), and metabolic syndrome, which are health conditions related to obesity. We aimed to investigate which of the three obesity indices has the strongest association with CKD and to explore whether there are gender differences in these relationships in the middle-aged and elderly Taiwanese population.MethodsThis was a cross-sectional, community-based study. It included 400 residents (141 males and 259 females, age 50–90 years) residing in a community in northern Taiwan. Each participant was asked to fill a questionnaire that collected personal information, medical history, medication use, and anthropometric measurements. The laboratory data were obtained by testing the blood and urine samples. The baseline characteristics were compared, and the obesity indices included body mass index (BMI), waist circumference (WC), and visceral adiposity index (VAI). CKD was defined as the presence of renal dysfunction (urine albumin-creatinine ratio ≥ 30 mg/g) or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. We used a multiple logistic regression model to evaluate the association between each obesity index and CKD for both genders. Further, we used the area under the receiver operating characteristic (ROC) curve (AUC) to examine the best obesity indices to predict CKD in different genders.ResultsThe average age of the subjects was 64.47 ± 8.45 years, and men were significantly older. CKD was found in 31 (22.0%) males and 50 (19.3%) females. In men, there was no significant difference between the CKD and non-CKD groups among the three obesity indices. However, in women, only VAI was significantly higher in subjects with CKD (1.9 [1.1, 3.4]) than in subjects without CKD (1.5 [1.0, 2.2]) (p-value = 0.03). The multivariate logistic regression revealed that even after adjusting for possible confounding factors, VAI was found to be an independent risk factor for CKD in women (OR: 1.32, 95% CI: 1.04-1.69, p = 0.02), but not in men (OR: 1.20, 95% CI: 0.85-1.69, p = 0.30). The AUC of VAI had a significant ability to predict CKD in women but not in men.ConclusionOur results showed that among the three obesity indices, VAI had the strongest association with CKD compared to BMI and WC in women. In addition, VAI in women should be given more importance in the screening for CKD among the middle-aged and elderly Taiwanese population.

This cross-sectional study evaluated and quantified the possible association of psychological symptoms and health status ratings on the burnout of healthcare workers from a tertiary medical center. Demographic data were obtained through a questionnaire survey. We evaluated their psychological symptoms using a 5-item Brief Symptom Rating Scale (BSRS-5) and burnout was measured using the Chinese version of the Maslach Burnout Inventory–Health Services Survey. The study began in Nov. 2018 and ended in Nov. 2020. A total of 2813 participants (men = 296, 10.5%; women = 2517, 89.5%) completed the questionnaires between December 2018 and March 2019. The response rate and complete rate were 71.7% and 93.2%. The multivariate analysis showed that, as the BSRS-5 level added, the odds ratio (OR) of burnout increased (BSRS-5 scores 6–9, 10–14, and 15–20; OR = 1.83, 3.23, and 9.15, separately; p value

Wind turbines generate low-frequency noise (LFN, 20–200 Hz), which poses health risks to nearby residents. This study aimed to assess heart rate variability (HRV) responses to LFN exposure and to evaluate the LFN exposure (dB, LAeq) inside households located near wind turbines. Thirty subjects living within a 500 m radius of wind turbines were recruited. The field campaigns for LFN (LAeq) and HRV monitoring were carried out in July and December 2018. A generalized additive mixed model was employed to evaluate the relationship between HRV changes and LFN. The results suggested that the standard deviations of all the normal to normal R–R intervals were reduced significantly, by 3.39%, with a 95% CI = (0.15%, 6.52%) per 7.86 dB (LAeq) of LFN in the exposure range of 38.2–57.1 dB (LAeq). The indoor LFN exposure (LAeq) ranged between 30.7 and 43.4 dB (LAeq) at a distance of 124–330 m from wind turbines. Moreover, households built with concrete and equipped with airtight windows showed the highest LFN difference of 13.7 dB between indoors and outdoors. In view of the adverse health impacts of LFN exposure, there should be regulations on the requisite distances of wind turbines from residential communities for health protection.

Neutrophil-mediated activation and injury of the endothelium play a role in the pathogenesis of diverse disease states ranging from autoimmunity to cancer to COVID-19. Neutralization of cationic proteins (such as neutrophil extracellular trap/NET-derived histones) with polyanionic compounds has been suggested as a potential strategy for protecting the endothelium from such insults. Here, we report that the FDA-approved polyanionic agent defibrotide (a pleiotropic mixture of oligonucleotides) directly engages histones and thereby blocks their pathological effects on endothelium. In vitro, defibrotide counteracted endothelial cell activation and pyroptosis-mediated cell death, whether triggered by purified NETs or recombinant histone H4. In vivo, defibrotide stabilized the endothelium and protected against histone-accelerated inferior vena cava thrombosis in mice. Mechanistically, defibrotide demonstrated direct and tight binding to histone H4 as detected by both electrophoretic mobility shift assay and surface plasmon resonance. Taken together, these data provide insights into the potential role of polyanionic compounds in protecting the endothelium from thromboinflammation with potential implications for myriad NET- and histone-accelerated disease states.

The global prevalence of diabetes mellitus is rapidly increasing. This disease is associated with many complications including male reproductive dysfunctions and infertility. Seahorse ( Hippocampus kuda) is a marine teleost fish well known for its beneficial effects on the reproductive system in traditional Chinese medicine books. Recently, several studies have been shown that the enzymatic hydrolysate of seahorse has multiple pharmacological activities. This study aimed to investigate the seahorse peptide hydrolysate (SH) ameliorative effects on the diabetic-induced male reproductive dysfunction in rat models. The in vivo studies were carried out with three different doses of SH (4, 8, and 20 mg/kg) and the diabetes condition was induced by administrating with streptozotocin (35 mg/kg) and fed a 40% high-fat diet. Seahorse hydrolysate (20 mg/kg) inhibited lipid peroxidation, increased antioxidant enzyme activity, and restored seminiferous tubules morphology in testis. Moreover, it improved reproductive dysfunction by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, sperm count, and motility. According to these results, we suggested that SH exhibited amelioration effects on the reproductive dysfunction.

Endoscopic retrograde cholangiopancreatography is not always successful even with needle knife precut sphincterotomy (NKPS). How to manage these patients with initial NKPS failure has not been well studied. We report the outcomes of patients who received endoscopic and non-endoscopic rescue treatment after the initial NKPS failure. During the 15 years from 2004 to 2018, 87 patients with initial NKPS failure received interval endoscopic treatment (IET group, n = 43), percutaneous transhepatic biliary drainage (PTBD group, n = 25), or bile duct surgery (BDS group, n = 19) were retrospectively studied. Compared with the PTBD group, the prevalence of choledocholithiasis was higher (69.8% vs. 16.0%, p

Supplemental Digital Content is available in the text., Objectives: For children to understand the emotional behavior of others, the first two steps involve emotion encoding and emotion interpreting, according to the Social Information Processing model. Access to daily social interactions is prerequisite to a child acquiring these skills, and barriers to communication such as hearing loss impede this access. Therefore, it could be challenging for children with hearing loss to develop these two skills. The present study aimed to understand the effect of prelingual hearing loss on children’s emotion understanding, by examining how they encode and interpret nonverbal emotional cues in dynamic social situations. Design: Sixty deaf or hard-of-hearing (DHH) children and 71 typically hearing (TH) children (3–10 years old, mean age 6.2 years, 54% girls) watched videos of prototypical social interactions between a target person and an interaction partner. At the end of each video, the target person did not face the camera, rendering their facial expressions out of view to participants. Afterward, participants were asked to interpret the emotion they thought the target person felt at the end of the video. As participants watched the videos, their encoding patterns were examined by an eye tracker, which measured the amount of time participants spent looking at the target person’s head and body and at the interaction partner’s head and body. These regions were preselected for analyses because they had been found to provide cues for interpreting people’s emotions and intentions. Results: When encoding emotional cues, both the DHH and TH children spent more time looking at the head of the target person and at the head of the interaction partner than they spent looking at the body or actions of either person. Yet, compared with the TH children, the DHH children looked at the target person’s head for a shorter time (b = −0.03, p = 0.030), and at the target person’s body (b = 0.04, p = 0.006) and at the interaction partner’s head (b = 0.03, p = 0.048) for a longer time. The DHH children were also less accurate when interpreting emotions than their TH peers (b = −0.13, p = 0.005), and their lower scores were associated with their distinctive encoding pattern. Conclusions: The findings suggest that children with limited auditory access to the social environment tend to collect visually observable information to compensate for ambiguous emotional cues in social situations. These children may have developed this strategy to support their daily communication. Yet, to fully benefit from such a strategy, these children may need extra support for gaining better social-emotional knowledge.

Researchers have conducted many studies about the relationships between peri-cardiovascular fat, nonalcoholic fatty liver disease (NAFLD), waist circumference, and cardiovascular disease (CVD). Nevertheless, the relationship between NAFLD and pericardial fat (PCF)/thoracic peri-aortic adipose tissue (TAT) phenotypes was still unknown. This study aimed to explore whether PCF/TAT was associated with NAFLD/abdominal obesity (AO) phenotypes in different high-sensitivity C-reactive protein (hs-CRP) levels. We consecutively studied 1655 individuals (mean age, 49.44 ± 9.76 years) who underwent a health-screening program. We showed a significant association between PCF/TAT and NAFLD/AO phenotypes in the cross-sectional study. We observed that the highest risk occurred in both abnormalities’ groups, and the second highest risk occurred in the AO-only group. Subjects with AO had a significantly increased risk of PCF or TAT compared to those with NAFLD. Notably, the magnitude of the associations between PCF/TAT and NAFLD/AO varied by the level of systemic inflammatory marker (hs-CRP level). We suggested that people with AO and NAFLD must be more careful about changes in PCF and TAT. Regular measurement of waist circumference (or AO) can be a more accessible way to monitor peri-cardiovascular fat (PCF and TAT), which may serve as a novel and rapid way to screen CVD in the future.

Background. The pedicle screw is one of the main tools used in spinal deformity correction surgery. Robotic and navigated surgeries are usually used, and they provide superior accuracy in pedicle screw placement than free-hand and fluoroscopy-guided techniques. However, their high cost and space limitation are problematic. We provide a new solution using 3D printing technology to facilitate spinal deformity surgery. Methods. A workflow was developed to assist spinal deformity surgery using 3D printing technology. The trajectory and profile of pedicle screws were determined on the image system by the surgical team. The engineering team designed drill templates based on the bony surface anatomy and the trajectory of pedicle screws. Their effectiveness and safety were evaluated during a preoperative simulation surgery. The surgery consisted in making a pilot hole through the drill template on a computed tomography- (CT-) based, full-scale 3D spine model for every planned segment. Somatosensory evoke potential (SSEP) and motor evoke potential (MEP) were used for intraoperative neurophysiological monitoring. Postoperative CT was obtained 6 months after the correction surgery to confirm the screw accuracy. Results. From July 2015 to November 2016, we performed 10 spinal deformity surgeries with 3D printing technology assistance. In total, 173 pedicle screws were implanted using drill templates. No notable change in SSEP and MEP or neurologic deficit was noted. Based on postoperative CT scans, the acceptable rate was 97.1% (168/173). We recorded twelve pedicle screws with medial breach, six with lateral breach, and five with inferior breach. Medial breach (12/23) was the main type of penetration. Lateral breach occurred mostly in the concave side (5/6). Most penetrations occurred above the T8 level (69.6%, 16/23). Conclusion. 3D printing technology provides an effective alternative for spinal deformity surgery when expensive medical equipment, such as intraoperative navigation and robotic systems, is unavailable.

Background Although animal studies have shown that pain can suppress host immunity and promote tumor metastasis, few clinical studies have evaluated the association between acute pain and long-term outcomes after cancer surgery. Methods Patients undergoing colorectal cancer resection at a medical center between November 2010 and December 2014 were collected. Pain intensity was recorded using a numeric rating scale at 12, 24, 36, 48, 72, 96, and 120 hours postoperatively. Group-based modeling of longitudinal pain scores was used to categorize pain trajectories. Recurrence-free survival and overall survival were analyzed using Cox proportional hazards models. Results A total of 2401 patients with 13 931 pain score observations were analyzed. The trajectory model identified three groupings of inpatient postsurgical pain, including 70.3% with mild pain dropping to low (group 1), 20.0% with moderate/severe pain dropping to mild (group 2), and 9.7% with moderate pain rebounding to severe (group 3). Univariate models showed that pain trajectories were significantly associated with recurrence-free survival (group 2 vs 1: hazard ratio [HR], 1.23; 95% CI, 1.02-1.47 and group 3 vs 1: HR, 1.63; 95% CI, 1.30-2.04) and overall survival (group 2 vs 1: HR, 1.36; 95% CI, 1.05-1.77 and group 3 vs 1: HR, 1.81; 95% CI, 1.31-2.51). However, the associations disappeared after adjusting for other significant risk factors. Conclusion Abnormal pain resolution identified by pain trajectory analysis and resulting from complex interactions among disease progression, surgery, and analgesia may be considered as an indicator of an inferior prognosis following colorectal cancer resection.

The optimal surgical method for cT1N0 lung adenocarcinoma remains controversial. The aim of this study was to evaluate the differences in clinical outcomes of sublobar resection and lobectomy for cT1N0 lung adenocarcinoma patients. We included 1035 consecutive patients with cT1N0 lung adenocarcinoma who underwent surgery at our institute from January 2011 to December 2016. The surgical approach, either sublobar resection or lobectomy, was determined at the discretion of each surgeon. A propensity-matched analysis incorporating total tumor diameter, solid component diameter, consolidation-to-tumor (C/T) ratio, and performance status was used to compare the clinical outcomes of the sublobar resection and lobectomy groups. Sublobar resection and lobectomy were performed for 604 (58.4%; wedge resection/segmentectomy: 470/134) and 431 (41.6%) patients, respectively. Patients in the sublobar resection group had smaller total tumor diameters, smaller solid component diameters, lower C/T ratios, and better performance status. More lymph nodes were dissected in the lobectomy group. Patients in the sublobar resection group had better perioperative outcomes. A multivariable analysis revealed that the solid component diameter and serum carcinoembryonic antigen level are independent risk factors for tumor recurrence. After propensity matching, 284 paired patients in each group were included. No differences in overall survival (OS; p = 0.424) or disease-free survival (DFS; p = 0.296) were noted between the two matched groups. Sublobar resection is not inferior to lobectomy regarding both DFS and OS for cT1N0 lung adenocarcinoma patients. Sublobar resection may be a feasible surgical method for cT1N0 lung adenocarcinoma.

Background/Purpose: Enhanced recovery after surgery (ERAS) is a growing tendency in modern perioperative period management, but no protocol has been established for a strategy that optimally facilitates rapid recovery from anesthesia. We hypothesized that applying a total intravenous anesthesia (TIVA) method to the response surface model (RSM) would allow prediction of the emergence and endotracheal tube extubation in cases undergoing video-assisted thoracotomy surgery (VATS). Methods: Thirty patients who were scheduled to undergo VATs under TIVA were enrolled. Pharmacokinetic profiles were calculated using a Tivatrainer. Emergence from anesthesia was observed and the exact time point of the regained response (RR) was recorded. The effect of concentration was analyzed and applied to a response surface model. Results: The cumulative prediction curve of the RR was closer to the 50% probability as set by the OAA/S ≥ 4 than by the OAA/S ≥ 2 model. The median, averages, and standard deviations of the time differences were 14.5, 22.05 ± 19.23 min for the OAA/S ≥2 model and 10.4, 14.26 ± 10.40 min for the OAA/S ≥ 4 model. Conclusion: The OAA/S ≥ 4 model could identify the target concentration in propofol–remifentanil pairs that predicted the time of emergence from VATS in 10 min. Our results indicate that RSM can be used to derive an ERAS protocol for VATS under TIVA. Further studies should investigate application of RSM to predict ERAS for various types of procedures. Keywords: Enhanced recovery after surgery (ERAS), Response surface model, Total intravenous anesthesia (TIVA), Video-assisted thoracotomy surgery (VATS)

Background: We describe the relative proportions and epidemiological features of influenza B/Victoria and B/Yamagata, using data from nationwide surveillance systems. Methods: We collected respiratory samples from outpatients with influenza-like illness (ILI) and intensive care unit (ICU)-admitted patients with complications (pulmonary or neurological complications, myocarditis/pericarditis or invasive bacterial infection) for virus isolation and lineage typing. Demographics, epidemiological features, and vaccination history from ICU-admitted patients with complications were analyzed. Results: From July 2013–June 2017, 21% of 11517 influenza isolates were influenza B. B/Victoria was the predominant circulating strain in 2013–2014, accounted for 56% of all influenza B positive samples and B/Yamagata was predominant in 2014–2017 (82%, 69%, and 85%, respectively). Among all typed viruses, the proportion of B/Yamagata was higher among specimens from ICU-admitted patients with complications (77%, 154/199) than from ILI outpatients (66%, 276/418, p

Background: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. Methods: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case–control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. Results: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10−4), BRD2 (P = 1.6 × 10−3), TNFRSF19 (P = 4.0 × 10−3), and CLPTM1L/TERT (P = 5.4 × 10−3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10−4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10−3) for NPC risk. In addition, we validated four previously reported NPC risk–associated SNPs. Conclusions: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. Impact: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.

Background To determine the effect of riociguat, an oral, selective soluble guanylate cyclase stimulator, on the net digital ulcer (DU) burden in systemic sclerosis (SSc). Methods Participants with SSc-related active or painful indeterminate DUs were recruited in a multicenter, double-blind, randomized, placebo-controlled, proof-of-concept trial. Eligible participants were required to have at least one visible, active ischemic DU or painful indeterminate DU at screening, located at or distal to the proximal interphalangeal joint and that developed or worsened within 8 weeks prior to screening. Participants were randomized 1:1 to placebo or riociguat in individualized doses (maximum of 2.5 mg three times daily) during an 8-week titration period, followed by an 8-week stable dosing period. This was followed by an optional 16-week open-label extension phase for participants with active DU/reoccurrence of DUs within 1 month of the end of the main treatment phase. The primary endpoint was the change from baseline to week 16 in net ulcer burden (NUB), analyzed using ANCOVA. Other endpoints included plasma biomarkers and proportion of participants with treatment-emergent adverse events (AEs). Results Seventeen participants (eight placebo, nine riociguat) were randomized at five centers. Six participants in each group transitioned to the open-label extension. Baseline characteristics were comparable between the treatment groups, except participants randomized to placebo were older and had longer disease duration (p

Objectives: Predictors for post-sepsis myocardial infarction (MI) and stroke are yet to be identified due to the competing risk of death. Methods: This study included all hospitalized patients with sepsis from National Health Insurance Research Database of Taiwan between 2000 and 2011. The primary outcome was the first occurrence of MI and stroke requiring hospitalization within 180 days following hospital discharge from the index sepsis episode. The association between predictors and post-sepsis MI and stroke were analyzed using cumulative incidence competing risk model that controlled for the competing risk of death. Results: Among 42 316 patients with sepsis, 1012 (2.4%) patients developed MI and stroke within 180 days of hospital discharge. The leading 5 predictors for post-sepsis MI and stroke are prior cerebrovascular diseases (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.74-2.32), intra-abdominal infection (HR: 1.94, 95% CI: 1.71-2.20), previous MI (HR: 1.81, 95% CI: 1.53-2.15), lower respiratory tract infection (HR: 1.62, 95% CI: 1.43-1.85), and septic encephalopathy (HR: 1.61, 95% CI: 1.26-2.06). Conclusions: Baseline comorbidities and sources of infection were associated with an increased risk of post-sepsis MI and stroke. The identified risk factors may help physicians select a group of patients with sepsis who may benefit from preventive measures, antiplatelet treatment, and other preventive measures for post-sepsis MI and stroke.