Search

Purpose To highlight a case of chorioretinitis sclopetaria, with concomitant macular hole formation and orbital emphysema, caused by a commercial-grade pressure washer. Patient A 19-year-old male presented to the emergency department with a left eye injury, incurred after being sprayed with a commercial-grade pressure washer. He endorsed ipsilateral blurred vision, pain, and linear floaters. Left eye visual acuity was 20/40. Dilated fundus exam showed inferior vitreous hemorrhage, retinal whitening, and pre-, intra-, and sub-retinal hemorrhages, consistent with chorioretinitis sclopetaria. Optical coherence tomography revealed a full-thickness macular hole. Computed tomography scan of the orbits showed subcutaneous and post-septal orbital emphysema. Two months following injury, vitreous and retinal hemorrhages and macular hole resolved. Five months following injury, visual acuity improved to 20/20. Discussion Chorioretinitis sclopetaria is defined as a full-thickness chorioretinal disruption resulting from a high-velocity projectile passing adjacent to or into the orbit without penetrating the globe. Chorioretinal deformation and ocular comorbidities are influenced by the velocity of the missile and its spatial relationship to the orbit. While this pattern of injury is typically associated with indirect trauma to the globe by a BB or a bullet, this is the first report of chorioretinitis sclopetaria precipitated by a high-velocity liquid missile.

Objective To determine the diagnostic accuracy of Necrotizing Otitis Externa (NOE) based on radiologic studies. Methods The PubMed, Cochrane, Embase, Web of Science, SCOPUS, and Google Scholar databases were searched. True-positive and false-negative results were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results The included studies contained data on 37 studies diagnosed with NOE. The sensitivity of gallium-67, technetium-99m, and Magnetic Resonance Imaging (MRI) was 0.9378 (0.7688–0.9856), 0.9699 (0.8839–0.9927), and 0.9417 (0.6968–0.9913), respectively. For Computed Tomography (CT), the positive criteria consisted of bony erosion alone and bony erosion plus any soft tissue abnormality. The sensitivity of CT based only on bony erosion was 0.7062 (0.5954–0.7971); it was higher 0.9572 (0.9000–0.9823) when based on bony erosion plus any soft tissue abnormality. Conclusion The diagnostic sensitivity of technetium-99m, gallium-67, and MRI was favorable. On CT, the presence of bony erosion may be a useful diagnostic marker of NOE, but the diagnostic sensitivity will be even higher if the criterion of any soft tissue abnormality is also included; however, care should be taken when interpreting the results. Our study demonstrates the potential utility of radiology studies for diagnosing NOE, but their lack of specificity must be considered, and standardized anatomic criteria are still needed. Level of evidence 2A.

ACAN variants can manifest as various clinical features, including short stature, advanced bone age (BA), and skeletal defects. Here, we report rare clinical manifestations of ACAN defects in a 9 year, 5 month-old girl born small for gestational age (SGA), presented with short stature, and was initially diagnosed with idiopathic growth hormone deficiency. She displayed several dysmorphic features including genu valgum, cubitus valgus, and recurrent patellar dislocations. She presented with progressive advancement of BA compared to that for chronological age and whole exome sequencing confirmed the presence of a novel heterozygous nonsense variant c.1968C>G, p.(Tyr656*) of ACAN. ACAN variants should be considered in short stature patients born SGA with joint problems, particularly those with recurrent patellar dislocation and genu valgum.

Background Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin exerts its neuronal and non-neuronal in vitro and in vivo effects through LPA receptor subtypes. However, it is unknown whether gintonin can bind to the plasma membrane of cells and can transactivate the epidermal growth factor (EGF) receptor. In the present study, we examined whether gintonin-biotin conjugates directly bound to LPA receptors and transactivated the EGF receptor. Methods We designed gintonin-biotin conjugates through gintonin biotinylation and examined whether gintonin-biotin conjugate binding sites co-localized with the LPA receptor subtype binding sites. We further examined whether gintonin-biotin transactivated the EGF receptor via LPA receptor regulation via phosphor-EGF and cell migration assays. Results Gintonin-biotin conjugates elicit [Ca2+]i transient similar to that observed with unbiotinylated gintonin in cultured PC3 cells, suggesting that biotinylation does not affect physiological activity of gintonin. We proved that gintonin-biotin conjugate binding sites co-localized with the LPA1/6 receptor binding sites. Gintonin-biotin binding to the LPA1 receptor transactivates the epidermal growth factor (EGF) receptor through phosphorylation, while the LPA1/3 receptor antagonist, Ki16425, blocked phosphorylation of the EGF receptor. Additionally, an EGF receptor inhibitor AG1478 blocked gintonin-biotin conjugate-mediated cell migration. Conclusions We observed the binding between ginseng-derived gintonin and the plasma membrane target proteins corresponding to the LPA1/6 receptor subtypes. Moreover, gintonin transactivated EGF receptors via LPA receptor regulation. Our results suggest that gintonin directly binds to the LPA receptor subtypes and transactivates the EGF receptor. It may explain the molecular basis of ginseng physiology/pharmacology in biological systems.

The study investigated the osteogenic capacity of a prefabricated periosteal flap created using only skeletonized pedicle transfer without fascia or muscle for vascular induction in rabbit calvarium. A critical-sized bone defect was made in the parietal bone centered on the sagittal suture, and the demineralized bone matrix was implanted. The periosteofascia over the defect was used as a form of prefabricated periosteofascial flap (PPF group, N=10), conventional periosteofascial flap (CPF group, N=10), and nonvascularized free periosteofascial graft (FPG group, N=6). The prefabricated flap was designed via vascular induction by transferring the central artery and vein of the right auricle onto the periosteofascia for 4 weeks prior to flap elevation. A quantitative comparison of volume restoration and radiodensity in the bone defect and a histological study were performed after 6 weeks of covering the bone defect with periosteofascia. The volume restoration of the bone defect covered with the PPF (43.4%) was not different from that of the CPF (46.2%), but significantly increased compared with that of the FPG (24.6%). The radiodensity of the bone defect covered with the PPF (-186.3 HU) was not different from that of the CPF (-153.6 HU), but significantly increased compared with that of the FPG (-329.8 HU). The results were based on adequate vascular development of the periosteum and were closely related to the osteogenic changes in the implanted demineralized bone matrix (DBM). In conclusion, even in the PPF created by transferring only skeletonized vascular pedicles, the osteogenic capacity of the periosteofascial flap is well maintained.

The thalamic connectivity system, with the thalamus as the central node, enables transmission of the brain’s neural computations via extensive connections to cortical, subcortical and cerebellar regions. Emerging reports suggest deficits in this system across multiple psychiatric disorders, making it a unique network of high translational and transdiagnostic utility in mapping neural alterations that potentially contribute to symptoms and disturbances in psychiatric patients. However, despite considerable research effort, it is still debated how this system contributes to psychiatric disorders. This review characterizes current knowledge regarding thalamic connectivity system deficits in psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder and autism spectrum disorder, across multiple levels of the system. We identify the presence of common and distinct patterns of deficits in the thalamic connectivity system in major psychiatric disorders and assess their nature and characteristics. Specifically, this review assembles evidence for the hypotheses of 1) thalamic microstructure, particularly in the mediodorsal nucleus, as a state marker of psychosis; 2) thalamo-prefrontal connectivity as a trait marker of psychosis; and 3) thalamo-somatosensory/parietal connectivity as a possible marker of general psychiatric illness. Furthermore, possible mechanisms contributing to thalamocortical dysconnectivity are explored. We discuss current views on the contributions of cerebellar-thalamic connectivity to the thalamic connectivity system and propose future studies to examine its effects at multiple levels, from the molecular (e.g., glutamatergic) to the behavioral (e.g., cognition), to gain a deeper understanding of the mechanisms that underlie the disturbances observed in psychiatric disorders.

Background The insidious nature of BCG-osteomyelitis makes it challenging for clinicians to detect it early on. Methods This 12-year retrospective analysis was conducted at a single tertiary hospital in central Taiwan. Electronic medical records of pediatric patients treated for BCG-osteomyelitis were reviewed. Demographics, clinical features, and laboratory findings were compared with patients diagnosed with culture-proven pyogenic osteomyelitis. Results In total, eight patients fulfilled our inclusion criteria. Their median age was 16 months, and no obvious gender prevalence was found. Six of the eight patients had lesions involving the lower extremities. When compared with the pyogenic osteomyelitis group, age of disease onset was found to be significantly younger in the BCG osteomyelitis group (p=0.038). Absence of fever and pain in the BCG osteomyelitis group was found to be statistically significant when compared with the pyogenic group (p=0.002 and p=0.026 respectively). CRP and ESR were found to be significantly higher in the pyogenic osteomyelitis group (p=0.000 and p=0.004 respectively). Conclusion BCG-related osteomyelitis must be considered when evaluating an afebrile child presenting with an unexplainable swelling or limp, and especially when the lesion is located on a lower limb. Laboratory studies may reveal normal WBC and CRP, with a normal to modest elevation of ESR. Imaging studies, including plain radiographs, magnetic resonance imaging (MRI), or computed tomography (CT) should be employed to rule out BCG-related osteomyelitis. Early diagnosis help minimize inappropriate antibiotics use, and may lead to a better outcome.

STUDY QUESTION Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization? SUMMARY ANSWER Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization. WHAT IS KNOWN ALREADY Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias. STUDY DESIGN, SIZE, DURATION Massachusetts deliveries among women ≥18 years old during 2013–2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD). PARTICIPANTS/MATERIALS, SETTING, METHODS PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories ( MAIN RESULTS AND THE ROLE OF CHANCE Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38–1.65) and a 25% greater risk of preeclampsia (CI: 1.15–1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06–1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09–1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI LIMITATIONS, REASONS FOR CAUTION PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured. WIDER IMPLICATIONS OF THE FINDINGS In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients’ PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women’s Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

This article examines peer influences from network relationships within a social network game (i.e., embeddedness) and across such games (i.e., multiplexity). Drawing on social influence theory, we develop a bivariate Poisson model of users’ repeated visits and latent attrition that accommodates peer interaction after controlling for homophily. We estimate the model using data from two social network games with considerable overlap among network members. We find that friends who are only multiplex across games exert greater peer influence on users’ game visits than members who are embedded within a single game. We also determined that ignoring network multiplexity across games may lead firms to mistarget users due to biased peer influences of embedded friends. This result provides an unresearched explanation—strength of peer influence—for the mixed findings in previous literature on network embeddedness. We utilized our results to conduct several scenario analyses to demonstrate how firms can effectively manage users’ engagement and target users in multiple social network games.

Invasive mucinous adenocarcinoma (IMA) of the lung frequently presents with diffuse pneumonic-type features or multifocal lesions, which are regarded as a pattern of intrapulmonary metastases. However, the genomics of multifocal IMAs have not been well studied. We performed whole exome sequencing on samples taken from 2 to 5 regions in seven patients with synchronous multifocal IMAs of the lung (24 regions total). Early initiating driver events, such as KRAS, NKX2-1, TP53, or ARID1A mutations, are clonal mutations and were present in all multifocal IMAs in each patient. The tumor mutational burden of multifocal IMAs was low (mean: 1.13/mega base), but further analyses suggested intra-tumor heterogeneity. The mutational signature analysis found that IMAs were predominantly associated with endogenous mutational process (signature 1), APOBEC activity (signatures 2 and 13), and defective DNA mismatch repair (signature 6), but not related to smoking signature. IMAs synchronously located in the bilateral lower lobes of two patients with background usual interstitial pneumonia had different mutation types, suggesting that they were double primaries. In conclusion, genomic evidence found in this study indicated the clonal intrapulmonary spread of diffuse pneumonic-type or multifocal IMAs, although they can occur in multicentric origins in the background of usual interstitial pneumonia. IMAs exhibited a heterogeneous genomic landscape despite the low somatic mutation burden. Further studies are warranted to determine the clinical significance of the genomic characteristics of IMAs in expanded cohorts.

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Objective Human microRNA-185 (miR-185) has been reported to act as a regulator of fibrosis and angiogenesis in cancer. However, miR-185 has not been investigated in patients with ST-segment elevation myocardial infarction (STEMI). We hypothesized that the changes in miR-185 levels in STEMI patients are related to the processes of myocardial healing and remodeling. Methods Between January 2011 and December 2013, 145 patients with STEMI (65.9±11.6 years old; 41 women) were enrolled. Initial and discharge serum samples collected from 20 patients with STEMI and mixed sera from 8 healthy controls were analyzed by a microarray. A quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis of miR-185 was performed in all 145 patients. The correlation between the miR-185 levels and the clinical, laboratory, angiographic, and echocardiographic parameters was analyzed. Results The microarray analysis revealed a biphasic pattern in miR-185 levels, with an initial decrease followed by an increase at discharge. The miR-185 levels at discharge were significantly correlated with the troponin-I, CK-MB, and area under the curve of CK-MB levels. There was a positive correlation between the transforming growth factor-β and miR-185 levels at discharge (ρ=0.242, p=0.026). A high wall motion score index and a low ejection fraction, as measured by echocardiography, and high B-type natriuretic peptide level at one month after STEMI were related to high miR-185 levels. Conclusion Our results showed that elevated miR-185 levels at the late stage of STEMI were related to a large amount of myocardial injury and adverse remodeling.

Central serous chorioretinopathy (CSC) is the fourth most common retinopathy and can reduce quality of life. CSC is assessed using optical coherence tomography (OCT), but deep learning systems have not been used to classify CSC subtypes. This study aimed to build a deep learning system model to distinguish CSC subtypes using a convolutional neural network (CNN). We enrolled 435 patients with CSC from a single tertiary center between January 2015 and January 2020. Data from spectral domain OCT (SD-OCT) images of the patients were analyzed using a deep CNN. Five-fold cross-validation was employed to evaluate the model’s ability to discriminate acute, non-resolving, inactive, and chronic atrophic CSC. We compared the performances of the proposed model, Resnet-50, Inception-V3, and eight ophthalmologists. Overall, 3209 SD-OCT images were included. The proposed model showed an average cross-validation accuracy of 70.0% (95% confidence interval [CI], 0.676–0.718) and the highest test accuracy was 73.5%. Additional evaluation in an independent set of 104 patients demonstrated the reliable performance of the proposed model (accuracy: 76.8%). Our model could classify CSC subtypes with high accuracy. Thus, automated deep learning systems could be useful in the classification and management of CSC.

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, which is transmitted through chigger mites. Delayed treatment results in various complications and, in severe cases, death. Granzymes are secreted by cytotoxic T lymphocytes or natural killer cells and are known to play an important role in controlling intracellular pathogens. To date, few studies have been done on granzymes in patients with scrub typhus. In this study, granzymes A and B showed a significant increase during the acute stage of scrub typhus compared with healthy control subjects, and decreased sharply after treatment. In addition, granzymes A and B were significantly high in the moderately elevated liver enzyme group. In conclusion, it appears that the host during the acute phase of scrub typhus increases cytotoxic T-cell activity to control infection.

We aimed to compare clinical and radiologic outcomes in patients with cam-type femoroacetabular impingement (FAI), with and without a partial ligamentum teres (LT) tear, who underwent hip arthroscopy (HA) with ≥10 years of follow-up. Among the patients who underwent HA for a cam-type FAI diagnosis with a labral tear, 28 patients (28 hips) with a partial LT tear and 87 patients (99 hips) with an intact LT were assigned to Groups A and B, respectively. All patients underwent partial labral debridement and femoroplasty. Debridement and thermal shrinkage were performed for LT tears. The grade of chondral damage was measured intraoperatively. Clinical items were assessed preoperatively and at the last follow-up. Patients’ satisfaction with the surgery and changes in postoperative sports ability in those who had previously been active in sports were assessed at the last follow-up. The Tönnis grade was assessed preoperatively and at the last follow-up for radiologic evaluation. Chondral damage to the acetabular and femoral head detected intraoperatively was significantly different between the groups (P = 0.005 and P

Background Bentonite, a montmorillonite clay, has been used as a classical remedy strategy for a long time. Recently, bentonite has been used as a raw material in cosmetic products because of its antibacterial and antioxidant properties. However, the therapeutic effect of bentonite on burn injuries has not yet been identified. Here, we explored the therapeutic effect of a novel bentonite complex, which was developed for medical use, on burn wounds and the anti-inflammatory function of bentonite clay in the complex in vitro. Methods A novel bentonite complex and bentonite clay were provided by C&L Biotech Co., Ltd. (Seoul, Korea). The elements of bentonite clay were analysed using inductively coupled plasma optical emission spectroscopy. Burn wounds were induced on the dorsal skin of two Yucatan minipigs, and tissue regeneration was determined by cell proliferation, angiogenesis, and collagen deposition using immunohistochemistry and Masson’s trichrome staining. Anti-inflammatory function was determined using quantitative real-time PCR and enzyme-linked immunosorbent assays. Results We found that by inducing collagen synthesis, cell proliferation, and angiogenesis, the bentonite complex improved skin regeneration in burn wounds. It was also identified that the expression of inflammatory cytokines associated with cyclooxygenase 2 (COX-2) signalling was significantly inhibited by treatment of the burn wounds with the bentonite complex. An in vitro study to identify the anti-inflammatory effect of bentonite clay, a major component of the bentonite complex, showed that COX-2 signalling was significantly regulated in both HacaT keratinocytes and 3D4/2 macrophage cell lines in vitro. Conclusions This study identified the therapeutic effect of a novel bentonite complex in burn wounds by inducing skin regeneration and bentonite-mediated anti-inflammatory responses with bentonite complex treatment.

In 2010, the World Health Organization classified mucin-producing bile duct tumors of the liver into two distinct entities; mucinous cystic neoplasm of the liver (MCN-L) and intraductal papillary mucinous neoplasm of the bile duct. We present the case of a patient with MCN-L having a uniquely pedunculated shape. A 32‐year‐old woman was referred to our institution with a diagnosis of biliary cystic neoplasm. She had undergone left salpingo-oophorectomy for ovarian cancer 15 years ago. Imaging studies showed an 8 cm-sized well defined, multiloculated cystic lesion suggesting a mucinous cystic neoplasm. The cystic mass was pedunculated at the liver capsule and pathologically diagnosed as MCN-L. The mass was resected with partial hepatectomy. The patient recovered uneventfully. She was discharged 7 days postoperatively. The patient has been doing well for 6 months after the operation. The patient will be followed up annually because of the favorable postresection prognosis of MCN-L.

Sedentary behavior (SB) and physical activity (PA) are important risk factors of cardiovascular disease morbidity and mortality. In addition to increasing the amount of moderate-to-vigorous PA (MVPA), the current PA guidelines recommend that adults should reduce SB, or any waking activity performed while sitting, reclining, or lying, with low energy expenditure. While mounting evidence has emphasized the benefits of increasing MVPA, little has focused on the effect of SB on health. Therefore, this review discusses the pathophysiological effects of SB and the potential physiological benefits of reducing/breaking up SB at the levels below the current guidelines for PA. Such knowledge is important, given that the majority of the United States population performs insufficient or no MVPA and is at high risk of being negatively impacted by SB. Interventions targeting sedentary time, such as breaking up SB by standing and moving, may be safe, feasible, and applicable to execute daily for a wide range of the population. This review also discusses the importance of monitoring SB in the era of the coronavirus disease 2019 (COVID-19) pandemic and the clinical implications of sitting less and moving more.

Purpose To examine risk factors for strabismus surgery reoperation in patients with thyroid eye disease (TED). Design Retrospective cohort study METHODS: An insurance claims database was used to identify patients with TED who underwent at least one strabismus operation between 2003 and 2019. We recorded specific muscles operated on, as well as the timing and frequency of reoperations. Cox regressions were used to estimate associations between time to reoperation and patient and primary surgery characteristics. Results Of the 448 patients who met inclusion criteria, 111 (24.8%) underwent a reoperation. Patients were followed for an average of 5.4 ± 3.0 years after their initial strabismus surgery. The rates of reoperation among patients whose initial surgery involved horizontal muscles only, vertical muscles only, and horizontal and vertical muscles were 29/120 (24.2%), 33/169 (19.5%), and 49/159 (30.8%) respectively (p = .05). The number of muscles operated on initially was the only independent predictor for undergoing a strabismus surgery reoperation (Odds Ratio [OR] 1.27; 95% CI 1.03-1.57; p = 0.03). The number of muscles operated on initially was also associated with shorter time to first reoperation (Hazard Ratio [HR] 1.22; 95% CI 1.02-1.46; p = 0.03). Age at first surgery, time between diagnosis of TED and first strabismus surgery, gender, race, and use of adjustable sutures were not associated with time to reoperation. Conclusions Approximately 1 in 4 patients with TED require reoperation after strabismus surgery. The number of muscles operated on was the only independent predictor for both undergoing a reoperation and time to first reoperation.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan–Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour–node–metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019–1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Background Follow-up of subjects with putative pre-psychotic states is essential to clarify the transition process to psychosis, while "non-converters" also deserve clinical attention as many may evolve into other psychiatric disorders with diverse outcomes. This study aimed to examine help-seeking individuals who have been labelled at clinical high-risk state but not converting to full-blown psychosis during first two years of follow-up. Methods A retrospective observational cohort study of help-seeking subjects was conducted by reviewing medical records of participants in a previous early psychosis study at the study hospital between 2006 and 2020. We portrayed those who developed first episode psychosis after first 2-year follow-up in detail, and provided sketches of clinical macrophenotypes other than psychosis emerging from subjects among different risk groups. Results Among 132 eligible subjects, data of 98 (74.2%) were available for detailed evaluation. Of these, 15 transitioned to first-episode psychosis (11.4%) with time to psychosis from 2 to 11 years, 11 had anxiety spectrum (8.3%), 11 had depressive spectrum (8.3%), 10 had obsessive compulsive (7.6%), 5 had bipolar spectrum disorders (3.8%), 13 had predominantly schizotypal (9.8%) and 4 had other personality traits (3%), and 13 had problems attributable to adjustment or developmental issues (9.8%). Conclusions Various diagnoses, either full- or sub-threshold, appropriately describe the diverse clinical phenomenology of a cohort presenting with non-specific and/or subthreshold psychotic symptoms. The clinical high-at-risk mental state (CHARMS) paradigm provides a reasonable transdiagnostic approach for orienting clinicians' attention toward young subjects seeking mental health help at an early stage of illness to potentially pluripotent trajectories.

Background Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10–24 years by age group (10–14 years, 15–19 years, and 20–24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10–24 years with that in children aged 0–9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10–24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39–1·59) worldwide in people aged 10–24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10–14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15–19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1–4 years (2·4%), and around a third less than in females aged 1–4 years (2·5%). The proportion of global deaths in people aged 0–24 years that occurred in people aged 10–24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10–24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group. Funding Bill & Melinda Gates Foundation.

Visual Abstract, Highlights • Our study supports the feasibility of measuring thrombogenicity in patients with acute myocardial infarction, with intent to predict periprocedural and long-term clinical events, in real-world clinical practice. • Preprocedural assessment of ex vivo thrombogenicity (eg, platelet-fibrin clot strength by thromboelastography) was significantly associated with the risk of coronary microvascular dysfunction. • A combined risk stratification with coronary microvascular dysfunction and platelet-fibrin clot strength increased the prognostic implication to predict the rates of long-term clinical outcomes., Summary The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N = 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet-fibrin clot strength (P-FCS) (≥68 mm) significantly increased the risk of postprocedural CMD (odds ratio: 4.35; 95% CI: 1.74-10.89). Patients with both CMD and high P-FCS had a higher rate of ischemic events compared to non-CMD subjects with low P-FCS (odds ratio: 5.58; 95% CI: 1.31-23.68). This study showed a close association between heightened thrombogenicity and CMD and their prognostic implications after reperfusion in acute myocardial infarction patients.

To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.

A higher SYNTAX score (SS) is strongly associated with poor prognosis in patients with cardiogenic shock complicating ST-segment elevation myocardial infarction (CS-STEMI). However, the predictive value of culprit-lesion SYNTAX score (cul-SS) and SS has not been compared although the culprit-lesion-only primary percutaneous coronary intervention (PCI) strategy showed improved long-term survival recently. This study compared the predictive utility of cul-SS and SS for in-hospital mortality among the patients with CS-STEMI from during 2010-2019. Of the 215 patients, 79 (37%) died. SS ≥22, cul-SS ≥11, final thrombolysis in myocardial infarction (TIMI) flow ≤2, and no-reflow phenomenon were associated with in-hospital mortality. In patients with multi-vessel disease, the nonsurvivors with cul-SS ≥11 had a higher mortality rate than the survivors (75.0% vs. 44.9%, p = 0.001), whereas the SS ≥22 showed no significant difference. The cul-SS ≥11 revealed only an independent factor in the multivariate analysis (OR 2.6, p = 0.010). the AUC of cul-SS ≥11 for in-hospital mortality was modest (0.617 p < 0.05), which might be augmented up to 0.745 (p < 0.001) by the combination with TIMI flow ≤2, no-reflow phenomenon, and blood total CO2 content

Slow-cycling/dormant cancer cells (SCCs) have pivotal roles in driving cancer relapse and drug resistance. A mechanistic explanation for cancer cell dormancy and therapeutic strategies targeting SCCs are necessary to improve patient prognosis, but are limited because of technical challenges to obtaining SCCs. Here, by applying proliferation-sensitive dyes and chemotherapeutics to non-small cell lung cancer (NSCLC) cell lines and patient-derived xenografts, we identified a distinct SCC subpopulation that resembled SCCs in patient tumors. These SCCs displayed major dormancy-like phenotypes and high survival capacity under hostile microenvironments through transcriptional upregulation of regulator of G protein signaling 2 (RGS2). Database analysis revealed RGS2 as a biomarker of retarded proliferation and poor prognosis in NSCLC. We showed that RGS2 caused prolonged translational arrest in SCCs through persistent eukaryotic initiation factor 2 (eIF2α) phosphorylation via proteasome-mediated degradation of activating transcription factor 4 (ATF4). Translational activation through RGS2 antagonism or the use of phosphodiesterase 5 inhibitors, including sildenafil (Viagra), promoted ER stress-induced apoptosis in SCCs in vitro and in vivo under stressed conditions, such as those induced by chemotherapy. Our results suggest that a low-dose chemotherapy and translation-instigating pharmacological intervention in combination is an effective strategy to prevent tumor progression in NSCLC patients after rigorous chemotherapy.

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg(-1) IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg(-1) IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...

BackgroundThe most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

OBJECTIVE The objective of this study was to evaluate the feasibility and complications of the over-the-arch (OTA) technique for screw insertion into the C1 lateral mass in patients in whom conventional techniques (i.e., posterior arch [PA] and inferior lateral mass [ILM]) are not feasible due to 1) PA with a very small height (< 3.5 mm), 2) a caudally tilted PA blocking the inferior part of the C1 lateral mass, or 3) loss of height at the ILM (< 3.5 mm). METHODS The authors reviewed the medical records of 60 patients who underwent C1 screw fixation with the OTA technique (13 screws) and the PA/ILM technique (107 screws) between 2011 and 2019. Vertebral artery (VA) injuries, screw malposition, and bony union were radiologically assessed. Clinical outcome measures, including Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) scale score, and occipital neuralgia, were recorded. RESULTS Thirteen OTA screws were successfully inserted without any major complications. NDI and JOA scale scores did not show significant differences between the two groups at final follow-up. No VA injuries were recognized during screw insertion. There was no evidence of ischemic damage to the VA or bony erosion in the occiput or atlas. Medial wall violation was observed in 1 screw (7.7%); however, no C0–1, C1–2, or lateral wall violations were observed. No patients developed new-onset neuralgia postoperatively after C1 fixation with the OTA technique. CONCLUSIONS The OTA technique was safe and useful for C1 screw fixation in patients in whom conventional techniques could not be employed.

In mammography, calcifications are one of the most common signs of breast cancer. Detection of such lesions is an active area of research for computer-aided diagnosis and machine learning algorithms. Due to limited numbers of positive cases, many supervised detection models suffer from overfitting and fail to generalize. We present a one-class, semi-supervised framework using a deep convolutional autoencoder trained with over 50,000 images from 11,000 negative-only cases. Since the model learned from only normal breast parenchymal features, calcifications produced large signals when comparing the residuals between input and reconstruction output images. As a key advancement, a structural dissimilarity index was used to suppress non-structural noises. Our selected model achieved pixel-based AUROC of 0.959 and AUPRC of 0.676 during validation, where calcification masks were defined in a semi-automated process. Although not trained directly on any cancers, detection performance of calcification lesions on 1,883 testing images (645 malignant and 1238 negative) achieved 75% sensitivity at 2.5 false positives per image. Performance plateaued early when trained with only a fraction of the cases, and greater model complexity or a larger dataset did not improve performance. This study demonstrates the potential of this anomaly detection approach to detect mammographic calcifications in a semi-supervised manner with efficient use of a small number of labeled images, and may facilitate new clinical applications such as computer-aided triage and quality improvement.

Background Early diagnosis of vocal cord iatrogenic injury is crucial, as is perioperative vocal cord evaluation. Methods Vocal cord mobility detected via transcutaneous laryngeal ultrasonography was compared with that detected via laryngoscopy (the reference). The vocal cord visualization rate of ultrasonography for evaluation of mobility was explored. Results The diagnostic odds ratio of transcutaneous laryngeal ultrasonography was 303.2212 (95% CI, [86.7944; 1059.3198]). The area under the summary receiver operating characteristic curve was 0.944. The sensitivity, specificity, and negative predictive value were 0.9154 [0.8471; 0.9548], 0.9771 [0.9541; 0.9887], and 0.9915 [0.9868; 0.9946], respectively. The vocal cord visualization of ultrasonography used to evaluate vocal cord mobility was high (0.9572 [0.9091; 0.9804]). Conclusions Since transcutaneous laryngeal ultrasonography has the advantage in vocal cord visualization, it can be considered when laryngoscopy is unavailable or patients refuse laryngoscopy. Also, it is diagnostically accurate regardless of the used landmarks, VCP definition, and timing for application.

Congenital web formations are extremely rare anomalies of the extrahepatic biliary tree. We herein report a case of common bile duct septum combined with multiple intrahepatic bile duct strictures in a 74‐year‐old female patient who was successfully treated with radiological intervention. The patient initially visited the hospital because of upper abdominal pain. Imaging studies revealed multifocal strictures with dilatation in both intra- and extrahepatic ducts; the final clinical diagnosis was congenital common bile duct web combined with multiple intrahepatic duct strictures. Surgical treatment was not indicated because multiple biliary strictures were untreatable, and the disease was clinically diagnosed as benign. The multiple strictures were extensively dilated twice through bilateral percutaneous transhepatic biliary drainage (PTBD) for 2 months. After 1 month of observation, PTBD catheters were successfully removed. The patient is doing well at 6 months after completion of the radiological intervention, with the maintenance of normal liver function. Congenital web of the bile duct is very rare, and its treatment may vary depending on the patterns of biliary stenosis. In cases where surgical intervention is not indicated for congenital web and its associated disease, radiological intervention with balloon dilatation can be a viable therapeutic option.

PurposeThe KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).Materials and MethodsIn this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B).ResultsOf the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).ConclusionThe addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as deoxyribonucleic acid (DNA) methylation, histone posttranslational modifications, and noncoding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Background: Metabolic syndrome is closely related to cardiovascular disease, and the prevalence of metabolic syndrome in postmenopausal women is increasing rapidly. Objective: The purpose of this study is to investigate the association between the number of breastfed children and the risk factors for metabolic syndrome in postmenopausal women and to evaluate the association between metabolic syndrome and bone mineral density and body composition variables in postmenopausal women depending on the number of breastfed children. Methods: Data from KNHANES V-1 and 2 (2010-2011) were used, and a total of 939 PM women with 1 to 6 breastfed children aged 65-80 years participated in this study. We divided these women into three groups (group1 with 1-2, group2 with 3-4, group3 with 5-6) depending on the number of breastfed children. Result: In analysis of the associations between metabolic syndrome and its risk factors, high-density lipoprotein cholesterol was the most negatively strongly associated with group1 (OR=0.103 [0.047-0.225]), triglyceride showed the highest association with group2 (OR=7.760 [3.770-15.97]) and group3 (OR=7.668 [4.102-14.33]). The risk factors of metabolic syndrome except for high-density lipoprotein cholesterol and triglyceride was not associated with group1, while all risk factors of metabolic syndrome displayed a high association with group2 and group3. Conclusion: The findings of the present study suggest that the number of breastfed children is significantly associated with a greater number of risk factors of metabolic syndrome in postmenopausal women, and the association between metabolic syndrome and body composition variables may differ depending on the number of breastfed children.

Motor-sparing regional anesthesia modalities, such as periarticular infiltration (PAI) and pericapsular nerve group (PENG) block, have become the mainstay of multimodal approaches used during total hip arthroplasty (THA). We hypothesized that the postoperative analgesia of the PENG block was non-inferior to that of the PAI.Sixty patients were randomly allocated into two groups. The PAI group were injected with 100 mL of cocktail solution (ropivacaine 20 mL, ketorolac 2 mL, and epinephrine 1 mL mixed with normal saline) in periarticular tissues directly by the surgeon. The PENG group were injected with 30 mL of 0.5% ropivacaine in the iliopubic eminence plane by ultrasound. The primary outcome was the resting pain score 12 h after surgery, and the prespecified non-inferiority was 1. Additionally, the cumulative opioid consumption and quality of recovery were evaluated.The mean difference in pain score 12 h postoperatively between the PENG and PAI groups was 0.6 [95% confidence interval (CI): -0.8 to 2.0]. The upper 95% CI exceeded the non-inferiority margin of 1 at all postoperative time points. There was no difference in opioid consumptions and quality of recovery scores.PENG block provided comparable analgesia with PAI following THA. It is not conclusive that PENG is inferior or non-inferior to PAI based on our study.Clinical Research information Service (CRIS, https://cris.nih.go.kr, KCT0006049).

Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.

Background: Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea.Methods: A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals.Results: A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low.Conclusion: The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required.

Purpose: The increasing use of electric personal mobility devices (ePMDs) has been accompanied by an increasing incidence of associated accidents. This study aimed to investigate the characteristics of ePMD-related injuries and their associated factors. Methods: This cross-sectional study was conducted using data from the Emergency Department-based Injury In-depth Surveillance database from 2014 to 2018. All patients who were injured while operating an ePMD were eligible. The primary outcome was the rate of severe injury, defined as an excess mortality ratio-adjusted Injury Severity Score of ≥25. We calculated the adjusted odds ratios (AORs) of outcomes associated with ePMD-related injuries. Results: Of 1,391,980 injured patients, 684 (0.05%) were eligible for inclusion in this study. Their median age was 28 years old, and most injuries were sustained by men (68.0%). The rate of ePMD-related injuries increased from 3.1 injuries per 100,000 population in 2014 to 100.3 per 100,000 population in 2018. A majority of the injuries occurred on the street (32.7%). The most commonly injured area was the head and face (49.6%), and the most common diagnosis was superficial injuries or contusions (32.9%). Being aged 55 years or older (AOR=3.88; 95% confidence interval [CI] 1.33–11.36) and operating an ePMD while intoxicated (AOR=2.78; 95% CI 1.52–5.08) were associated with severe injuries. Conclusions: The number of emergency room visits due to ePMD-related injuries is increasing. Old age and drunk driving are both associated with serious injuries. Active traffic enforcement and safety regulations regarding ePMDs should be implemented to prevent severe injuries caused by ePMD-related accidents.

A hyperosmolar hyperglycemic state (HHS) is a life-threatening complication rarely seen in children and adolescents with type 1 diabetes mellitus (T1DM). However, early diagnosis and proper treatment are vital to reduce the high morbidity and mortality rates associated with HHS. We describe a male patient who presented with polydipsia, polyuria, and a drowsy mental status. His initial biochemistry results demonstrated severe hyperglycemia (1,456 mg/dL), hyperosmolarity of 359 mOsm/kg (effective osmolarity, 323 mOsm/kg), and mild acidosis (venous pH, 7.327). The patient was diagnosed with HHS and T1DM based on the presence of hyperosmolarity, hyperglycemia, and positivity for antiglutamic acid antibodies. Intensive intravenous fluid and regular insulin (0.025 units/kg/hr) were administered. After hydration and insulin treatment, the patient's mental status and serum glucose and sodium levels improved, and no neurological complications were observed. In summary, most cases of HHS are observed in adult patients with type 2 diabetes. However, occurrences in children and adolescents with T1DM have also been reported. Therefore, HHS should be considered in the differential diagnosis of hyperglycemic emergencies.

Problem definition: Among the most vexing issues in the U.S. healthcare ecosystem is inappropriate use of percutaneous coronary intervention (PCI) procedures, also known as overstenting. A key driver of overstenting is physician subjectivity in eyeballing a coronary angiogram. Advanced tests such as fractional flow reserve (FFR) provide more precise and objective measures of PCI appropriateness, yet the decision to perform these tests is endogenous and not immune to clinical ambiguity associated with eyeballing. Additionally, conflicts of interest, arising from revenue-generating incentives, play a role in overstenting. Academic/practical relevance: Conventional wisdom suggests more precise diagnostic testing will help reduce overtreatment. However, the literature rarely recognizes that the testing decision is itself endogenous. Our research highlights the role of endogeneity surrounding interventional cardiology decision making. Methodology: This study uses stochastic modeling and simulation. Results: Under a low conflict-of-interest level, the physician performs the advanced test for intermediate lesions. Under a high conflict-of-interest level, however, the physician would perform the advanced test only for high-grade lesions, because of a financial disincentive: Performing the advanced test may lower PCI revenue if the test results argue against the procedure. Surprisingly, despite this disincentive, a more revenue-driven physician can be more inclined to perform the advanced test. Managerial implications: Our model leads to implications for various efforts aimed at tackling overstenting: (1) Attention should be paid not only to the sheer quantity of FFR procedures but to which patients receive FFR procedures; (2) reducing the risk of the advanced test has a behavior-inducing effect, yet a modest risk reduction may lower patient welfare; and (3) offering a bonus to the physician for performing FFR procedures equal to a third of its reimbursement rate will cause only a 5% increase in average physician payment while inducing a 26% decline in overstenting. In addition, we show implementing a bundled payment scheme may discourage the use of FFR procedures and lead to more salient overstenting.

Background and Purpose: The outcome of endovascular treatment in stroke patients with a large ischemic core is not always satisfactory. We evaluated whether the severity of baseline diffusion-weighted imaging abnormalities, as assessed by different apparent diffusion coefficient (ADC) thresholds, correlates with the clinical outcome in these patients after successful endovascular treatment. Methods: In 82 consecutive patients with a large vessel occlusion in the anterior circulation admitted ≤24 hours after onset, a baseline diffusion lesion volume (ADC ≤620×10 −6 mm 2 /s [ADC 620 ]) ≥50 mL and successful recanalization by endovascular treatment were retrospectively investigated. Lesion volumes of 3 ADC thresholds (ADC 620 , ADC ≤520×10 −6 mm 2 /s [ADC 520 ], and ADC ≤540×10 −6 mm 2 /s [ADC 540 ]) were measured using an automated Olea software program. The performance of the ADC 520 /ADC 620 and ADC 540 /ADC 620 ratios in predicting the functional outcome was assessed by receiver operating characteristic curve analysis. The ADC ratio with optimal threshold showing better receiver operating characteristic performance was dichotomized at its median value into low versus high subgroup and its association with the outcome subsequently evaluated in a multivariable logistic regression model. Results: The median baseline diffusion lesion volume was 80.8 mL (interquartile range, 64.4–105.4). A good functional outcome (modified Rankin Scale score, ≤2) was achieved in 35 patients (42.7%). The optimal threshold for predicting the functional outcome was identified as ADC 540 /ADC 620 (area under the curve, 0.833) and dichotomized at 0.674. After adjusting for age, baseline National Institutes of Health Stroke Scale score, intravenous tissue-type plasminogen activator, baseline diffusion lesion volume, and onset-to-recanalization time, a low ADC 540 /ADC 620 was independently associated with a good functional outcome (adjusted odds ratio, 10.72 [95% CI, 3.06–37.50]; P Conclusions: A low ADC 540 /ADC 620 , which may reflect less severe ischemic stress inside a diffusion lesion, may help to identify patients who would benefit from endovascular treatment despite having a large ischemic core.

BACKGROUND Right ventricular outflow tract (RVOT) obstruction relief is one of the major procedures during the total correction of tetralogy of Fallot (TOF). Pulmonary insufficiency (PI) is usually inevitable after a transannular incision with a patch repair is performed. Therefore, some surgeons advocate to place a monocusp valve within the transannular patch (TAP) in order to decrease the severity of the PI. However, the monocusp valve seemed not be very effective in some patients who underwent the complete TOF repair. METHODS Patients who had the classic form of TOF between January 2009 and January 2017 and underwent the corrective surgery with a TAP by the same cardiovascular surgeon were identified for further analysis. Clinical information including demographics at operation, perioperative data, and postoperative outcome were collected retrospectively and compared between the group with and without a monocusp valve. RESULTS A total of 24 TOF cases were included in the final analysis, and 16 (66.7%) patients received a monocusp valve placement. The patients' characteristics before and during the surgery were similar between the two groups. The median duration of chest tube drainage after the total correction in the monocusp group was longer than those without the valve (p = 0.04). There was no difference in the immediate postoperative data, including the inflammation/infection status, the duration of mechanical ventilation, and the length of ICU and hospital stay. CONCLUSION Implantation of a monocusp valve during the total TOF correction using a TAP did not bring benefit to improve the immediate postoperative outcomes, especially the duration of the pleural drainage. Further study with a prospective design and a larger number of cases is needed.

Preservation of the more mobile lumbar segments is important during thoracolumbar/lumbar scoliosis surgery; however, the remaining disc wedge angle (DWA) below lowermost instrumented vertebra (LIV) and vertebral body tilt below LIV (LIV+1 tilt) can cause curve progression.This study aimed to evaluate the efficacy of intraoperative radiograph to predict the postoperative DWA below LIV and LIV+1 tilt on standing radiographs in patients with LIV of L3 or L4.Retrospective cohort study PATIENT SAMPLE: A total of 235 patients with idiopathic scoliosis who underwent posterior correction and fusion for the structural thoracolumbar curve and were followed up for5 years were reviewed.DWA below LIV, LIV+1 tilt, Cobb angle, trunk shift, apical vertebra translation, and pelvic parameters were measured.Correlation between intraoperative and postoperative measurements of DWA below LIV and LIV+1 tilt were assessed. Additional analysis was performed to identify risk factors and prognosis of LIV+1 tilt ≥10° and DWA below LIV of ≥4° RESULTS: LIV+1 tilt measured on intraoperative radiograph was significantly correlated with the postoperative 5-day and postoperative 5-year evaluation in both groups. However, the intraoperative DWA below LIV was only correlated with the postoperative 5-year value in the L3 group (p=.018). At the 5-year follow-up, patients with LIV+1 tilt ≥10° on intraoperative radiography showed significantly greater LIV+1 tilt (p.001), apical vertebral translation (p.001), thoracic curve (p=.008), and thoracolumbar curve (p.001) than patients with LIV+1 tilt10°. Intraoperative DWA below LIV of ≥4° was only associated with higher DWA below LIV at the 5-year follow-up.Intraoperative measurement of LIV+1 tilt was correlated with long-term postoperative outcomes, and intraoperative LIV+1 tilt ≥10° was associated with a less favorable radiographic outcome. Intraoperative DWA below LIV demonstrated less correlation with postoperative values and was not a prognostic factor for other radiographic parameters.

Background Active video games are a new method for increasing physical activity (PA). Fully immersive virtual reality (VR) is a hardware device on which an active video game can run. Active (video games in) VR (AVR), might increase immersion, game engagement, and MVPA, thereby yielding greater exercise-related benefits, e.g., cognitive performance. Methods We examined the induction of moderate-to-vigorous PA (MVPA) via an AVR and a sedentary VR (SVR) as well as the effects of VR play on cognitive performance, which was monitored using 2 different methods. Each of 29 sedentary college students attended three 20-min laboratory sessions (AVR, SVR, or control) in a randomized order; during the control session, they sat quietly doing nothing. A fully immersive headset was used for the 2 video game sessions. We monitored and computed participants’ PA using hip-worn accelerometers (wGT3x-bt; ActiGraph, Pensacola, FL, USA) and a heart rate band (Polar H7; Polar, Kempele, Finland). After each session, the participants completed a mnemonic similarity test (MST) to measure recognition memory. They also filled out a motion sickness questionnaire and an abbreviated game experience questionnaire. Results The AVR session induced a significantly greater heart rate and more time spent in MVPA than did either of the other 2 sessions regardless of the PA monitoring method. AVR elicited greater game experience questionnaire-assessed sensory and imaginative immersion, challenge, and positive affect than did SVR. The mnemonic similarity test recognition score was marginally higher post-AVR session than it was post-SVR session. Conclusion AVR elicited MVPA without a significant increase in motion sickness and induced a better game experience and better borderline cognitive performance than did SVR.

Purpose To compare the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair. Design Retrospective, interventional case series. Methods Eyes with an FTMH ≤ 400 µm that underwent vitrectomy with either a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Results Primary hole closure was achieved in 54 (98%) and 60 (97%) eyes in the flap and peel groups, respectively. The preoperative and postoperative 12-month BCVA were comparable between the groups but were significantly better in the flap than in the peel groups at 1 month (logMAR, mean ± SD, 0.83 ± 0.43 vs. 1.14 ± 0.50, P = 0.001), 3 months (0.58 ± 0.33 vs. 0.82 ± 0.43; P = 0.002), and 6 months (0.56 ± 0.32 vs. 0.72 ± 0.48; P = 0.028). In the flap group, foveal gliosis was less common than the peel group at 1 month (P = 0.030) and restored external limiting membrane and interdigitation zone was more common at 3 months (P = 0.046 and Conclusions Both the single-layer ILM flap and conventional ILM peel techniques closed FTMHs and improved vision. ILM flaps were associated with better visual outcomes up to 6 months postoperatively and should be considered in FTMHs ≤ 400 µm.