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This letter to the editor discusses the successful treatment of a 16-year-old boy with concurrent vitiligo and atopic dermatitis using the JAK inhibitor upadacitinib. The article explains that vitiligo is a depigmentation disorder caused by the destruction of melanocytes, and atopic dermatitis is characterized by a type 2 immune response. The authors suggest that there may be a potential association between vitiligo and atopic dermatitis due to overlapping genetic and immune mechanisms. The patient in the case study experienced repigmentation and relief from symptoms after treatment with upadacitinib. The authors conclude that upadacitinib can be an effective treatment option for patients with both vitiligo and atopic dermatitis. [Extracted from the article]

Disrupted redox status primarily contributes to myocardial ischemia/reperfusion injury (MIRI). NRF2, the endogenous antioxidant regulator, might provide therapeutic benefits. Dihydrotanshinone-I (DT) is an active component in Salvia miltiorrhiza with NRF2 induction potency. This study seeks to validate functional links between NRF2 and cardioprotection of DT and to investigate the molecular mechanism particularly emphasizing on NRF2 cytoplasmic/nuclear translocation. DT potently induced NRF2 nuclear accumulation, ameliorating post-reperfusion injuries via redox alterations. Abrogated cardioprotection in NRF2-deficient mice and cardiomyocytes strongly supports NRF2-dependent cardioprotection of DT. Mechanistically, DT phosphorylated NRF2 at Ser40, rendering its nuclear-import by dissociating from KEAP1 and inhibiting degradation. Importantly, we identified PKC- δ -(Thr505) phosphorylation as primary upstream event triggering NRF2-(Ser40) phosphorylation. Knockdown of PKC- δ dramatically retained NRF2 in cytoplasm, convincing its pivotal role in mediating NRF2 nuclear-import. NRF2 activity was further enhanced by activated PKB/GSK-3 β signaling via nuclear-export signal blockage independent of PKC- δ activation. By demonstrating independent modulation of PKC- δ and PKB/GSK-3 β /Fyn signaling, we highlight the ability of DT to exploit both nuclear import and export regulation of NRF2 in treating reperfusion injury harboring redox homeostasis alterations. Coactivation of PKC and PKB phenocopied cardioprotection of DT in vitro and in vivo , further supporting the potential applicability of this rationale. Dihydrotanshinone-I activates PKC- δ -regulated NRF2 nuclear import signaling and meanwhile blocks nuclear export via PKB/GSK-3 β /Fyn cascades, convergently potentiating nuclear accumulation and activation of NRF2 signaling and ameliorates myocardial ischemia/reperfusion injury. Image 1 [ABSTRACT FROM AUTHOR]

Background: Increasing evidence supports the finding that patients undergoing a total knee arthroplasty with high-volume physicians and hospitals achieve better outcomes. Unfortunately, the existing definitions for high-volume surgeons and hospitals are highly variable and entirely arbitrary. The aim of this study was to identify a set of meaningful hospital and surgeon total knee arthroplasty volume thresholds.Methods: Using 289,976 patients undergoing primary total knee arthroplasty from an administrative database, we applied stratum-specific likelihood ratio (SSLR) analysis of a receiver operating characteristic (ROC) curve to generate sets of volume thresholds most predictive of adverse outcomes. The outcomes considered for surgeon volume included 90-day complication and 2-year revision. For hospital volume, we considered 90-day complications and 90-day mortality.Results: SSLR analysis of the ROC curves for 90-day complication and 2-year revision rates by surgeon volume identified four volume categories: 0 to 12, 13 to 59, 60 to 145, and ≥146 total knee arthroplasties per year. Complication rates decreased significantly (p < 0.05) in progressively higher-volume categories. Revision rates followed a similar pattern, but did not decrease between surgeons performing 60 to 145 arthroplasties per year and those performing ≥146 arthroplasties per year. SSLR analysis of 90-day complication and 90-day mortality rates by hospital volume also identified four volume categories: 0 to 89, 90 to 235, 236 to 644, and ≥645 total knee arthroplasties per year. Complication rates decreased significantly (p < 0.05) in progressively higher-volume categories, but the rates did not decrease between hospitals performing 236 to 644 arthroplasties per year and those performing ≥645 arthroplasties per year. Mortality rates for hospitals with ≥645 total knee arthroplasties per year were significantly lower (p < 0.05) than those below the threshold.Conclusions: Our study supports the use of SSLR analysis of ROC curves for risk-based volume stratification in total knee arthroplasty volume-outcomes research. SSLR analysis established meaningful volume definitions for low, medium, high, and very high-volume total knee arthroplasty surgeons and hospitals. This should help patients, surgeons, hospitals, and policymakers to make decisions with regard to the optimal delivery of total knee arthroplasty.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on long-term revision rates following cervical spine arthrodeses. The purposes of this study were to define reoperation rates after primary cervical arthrodeses and to identify risk factors for revisions.Methods: New York State's all-payer health-care database was queried to identify all primary subaxial cervical arthrodeses occurring in the 16 years from 1997 through 2012. A total of 87,042 patients were included in the study cohort. Demographic information was extracted. Patients' preoperative medical comorbidities, surgical indications, and operative approaches were assembled using codes from the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification). The cohort was followed to revision surgical procedures, death, or the end of the study period. All subsequent contiguous spinal arthrodeses, including in the subaxial cervical spine, were considered revisions. The overall revision risk and the risk associated with various preoperative characteristics, surgical indications, and operative approaches were assessed using a Cox proportional hazard model.Results: During the study period, 6,721 patients (7.7%) underwent revision. The median time to revision was 24.5 months. The probability of undergoing at least one revision by 192 months was 12.6%. Arthrodeses performed via anterior-only approaches had a significantly higher probability of revision (p < 0.001) at 13.4% (95% confidence interval [95% CI], 12.9% to 13.9%) than those performed via posterior approaches at 7.4% (95% CI, 6.6% to 8.4%) or circumferential (anterior and posterior) approaches at 5.2% (95% CI, 4.0% to 6.8%). This relationship persisted in multivariate analysis; compared with anterior surgical procedures, there was a significantly lower risk of revision (p < 0.001) for posterior surgical approaches at a hazard ratio of 0.76 (95% CI, 0.69 to 0.84) and circumferential approaches at a hazard ratio of 0.53 (95% CI, 0.42 to 0.66). Patient age of 18 to 34 years, white race, insurance status of Workers' Compensation or Medicare, and surgical procedures for spinal stenosis, spondylosis, deformity, and neoplasm were associated with elevated revision risk. Arthrodeses spanning few levels and those performed for fractures had a lower revision risk.Conclusions: Primary subaxial cervical spine arthrodeses had a probability of revision approaching 13% over a 16-year period, with elevated reoperation rates in patients undergoing anterior-only surgical procedures. Age, race, insurance status, surgical indication, and number of spinal levels included in the arthrodesis were also associated with reoperation risk.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Previous studies of racial disparities in total joint replacement, particularly total knee arthroplasty, in the U.S. have predominantly focused on disparities between blacks and whites and were limited to Medicare patients or veterans, populations that are not representative of the entire U.S.Population: We sought to study racial disparities in the utilization of total knee arthroplasty, the use of high-volume hospitals, and total knee arthroplasty outcomes, including mortality and complications, using all-payer databases.Methods: We analyzed data from 8 years and 8 racially diverse states in the State Inpatient Databases (SID). Patient race was categorized according to the SID as white, black, Hispanic, Asian, Native American, and mixed race. Both crude and adjusted racial and/or ethnic disparities were evaluated.Results: In comparison with whites (4.65 per 1000 population per year), black (3.90), Hispanic (3.71), Asian (3.89), Native American (4.40), and mixed-race (3.69) populations had lower rates of total knee arthroplasty utilization (p < 0.0001). After risk adjustment, the rate of total knee arthroplasty utilization was significantly lower for blacks (odds ratio [OR] = 0.87 [95% confidence interval (CI), 0.85 to 0.89]; p < 0.0001), Hispanics (OR = 0.76 [95% CI, 0.68 to 0.83]; p < 0.0001), Asians (OR = 0.83 [95% CI, 0.78 to 0.89]; p < 0.0001), Native Americans (OR = 0.87 [95% CI, 0.81 to 0.93]; p < 0.0001), and mixed race (OR = 0.84 [95% CI, 0.79 to 0.90]; p < 0.0001) compared with the rate for whites. Lower rates of total knee arthroplasty utilization for blacks, Hispanics, and mixed-race groups became worse over the years. Patients from minority groups were less likely to undergo total knee arthroplasty in high-volume hospitals than were whites. Moreover, the rates of mortality were significantly higher for blacks (OR = 1.52 [95% CI, 1.17 to 1.97]; p = 0.0017), Native Americans (OR = 6.52 [95% CI, 4.63 to 9.17]; p < 0.0001), and mixed-race patients (OR = 4.35 [95% CI, 3.24 to 5.84]; p < 0.0001). Blacks (OR = 1.08 [95% CI, 1.01 to 1.15]; p = 0.01) and mixed-race patients (OR = 1.17 [95% CI, 1.001 to 1.36]; p = 0.04) had higher rates of complications than whites.Conclusions: Minorities had lower rates of total knee arthroplasty utilization but higher rates of adverse health outcomes associated with the procedure, even after adjusting for patient-related and health-care system-related characteristics. Utilization rates were based on overall population as the proportion of the population with osteoarthritis requiring arthroplasty is unknown. Future studies that consider specific patient-level information with psychosocial and behavioral factors are needed.Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The article presents a study that measures the frequency of meniscal repairs, discover the failure rate for a meniscal repair as reflected by subsequent meniscectomies. The study determines the risk factors for a subsequent meniscectomy after repair in a large population-based cohort. It supports the notion that repairing a meniscus is a safe and effective procedure in the long term.

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted. [ABSTRACT FROM AUTHOR]

Background: One of the key symptoms of Internet gaming disorder is the impulsive pursuit of Internet games, which causes individuals with this disorder to have a tendency to approach gaming cues. Dual processing theory states that this approach bias is caused by the suppression of reflective processing and the hyperactivity of impulsive processing. Therefore, reverse modification training for approach bias can suppress impulsive processing, thereby reducing or treating the disorder.Method: In this study, 48 individuals with Internet gaming disorder were selected and randomly assigned to the following two groups: the experimental group and the control group. The 24 participants in the experimental group received a 4-day stimulus-response compatibility (SRC) approach bias modification treatment, whereas the 24 participants in the control group received a corresponding SRC pseudomodification training.Results: The approach response time of both groups to the gaming cues was significantly shorter than that to the neutral cues at baseline. After the modification, the response time of the experimental group to the gaming cues significantly increased, whereas the scores for Internet gaming disorder severity, anxiety level and craving significantly decreased. However, the control group subjects did not show these effects.Conclusion: The current results imply that individuals with Internet gaming disorder show approach bias toward Internet gaming cues, and SRC reverse modification training can significantly correct this bias and therefore have therapeutic effects to some extent. [ABSTRACT FROM AUTHOR]

Background: To investigate whether unilateral pedicle screw fixation is superior than bilateral pedicle screw fixation for lumbar degenerative diseases. Methods: Electronic databases including PubMed, Embase, and the Cochrane Library up to August 2018 were searched. All the high-quality randomized controlled trials (RCTs) and prospective clinical controlled studies comparing the unilateral pedicle screw fixation and bilateral pedicle screw fixation for lumbar degenerative diseases were enrolled in this study. Fusion rate was the main outcome. Stata 12.0 was used for the meta-analysis. Results: Twelve RCTs including 808 patients (unilateral pedicle screw fixation = 393, bilateral pedicle screw fixation = 415) were included in our meta-analysis. There was a significant difference between unilateral pedicle screw fixation and bilateral pedicle screw fixation in terms of the fusion rate (risk ratio (RR) = 0.96, 95%CI [0.92, 1.00], P = 0.073), visual analog scale (VAS) at final follow-up, Oswestry Disability Index (ODI), Japanese Orthopedic Association scores (JOA), short-form health survey (SF-36), and length of hospital stay. Compared with bilateral pedicle screw fixation, unilateral pedicle screw fixation was associated with a reduction of the total blood loss and operation time (P < 0.05). Unilateral pedicle screw fixation was associated with an increase of the cage migration than bilateral pedicle screw fixation (17.1% vs 7.1%, RR = 2.40, 95% CI = 1.17 to 4.93; P = 0.017). Conclusions: Unilateral pedicle screw fixation and bilateral pedicle screw fixation has similar fusion rate when treating for lumbar degenerative diseases. Our meta-analysis suggested that compared with bilateral pedicle screw fixation, unilateral pedicle screw fixation significantly reduced total blood loss and operation time for lumbar degenerative diseases. The use of unilateral pedicle screw for lumbar degenerative diseases increases the cage migration. [ABSTRACT FROM AUTHOR]

• Indirubin alleviated BLM-induced pulmonary fibrosis. • Indirubin inhibited fibroblast to myofibroblast differentiation by repression TGF-β/Smad signaling. • Indirubin had no significant toxicity to mice and cells. Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis. Indirubin, a compound obtained from indigo-bearing plants or mollusks of the family Muricidae, has various bioactivities, including anti-tumor activity and anti-inflammation effect. However, whether indirubin could mediate its therapeutic effects on bleomycin (BLM)-induced pulmonary fibrosis has not been addressed. The impacts of indirubin on bleomycin (BLM)-induced pulmonary fibrosis were evaluated by pathological staining, western blot, RT-PCR and immunofluorescent staining. The effects of indirubin on fibroblast differentiation and related signaling were next investigated to demonstrate the underlying mechanisms. The results indicated that indirubin-treated mice exhibited a definitively improved survival rate than that of the BLM-induced mice in a dose-depend manner. Additionally, administration of indirubin significantly alleviated inflammatory cells infiltration in BLM mice. Importantly, indirubin provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuating expression of fibrotic hallmarks, including fibronectin, collagen I and α-smooth muscle actin (α-SMA). Subsequently, we provided in vitro evidence revealing that indirubin suppressed fibroblast to myofibroblast differentiation by repressed TGF-β/Smad signaling in a dose-dependent manner. Notably, our data showed that indirubin seemed to be safe in mice and fibroblasts. Overall, indirubin could protect the mice against BLM-induced pulmonary fibrosis by alleviated fibroblast differentiation and may be therapeutically beneficial for IPF patients. [ABSTRACT FROM AUTHOR]