Melanocyte transplantation to skin prepared by controlled PUVA-induced sunburn-like blistering for vitiligo treatment - A pilot clinical trial.

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells.

Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke.

A Case of Retroperitoneal Paraganglioma Presenting As Dizziness and Chest Pain With a Coexisting Contralateral Primary Renal Tumor.

Paraganglioma is a rare type of neuroendocrine tumor with variable clinical presentations, making diagnosis relatively challenging. In this report, we present a case of retroperitoneal paraganglioma in a patient who experienced intermittent episodes of dizziness and chest pain. Imaging studies conducted during the patient's hospitalization revealed the presence of a lesion in the upper region of the right kidney, as well as a mass in the left retroperitoneal area that was suspected to be a paraganglioma. Biochemical studies were collected, including 24-hour urine metanephrines, urine catecholamines, urine cortisol, plasma metanephrines, renin, and aldosterone. However, it took an extended period of time for these results to come back. Given high clinical suspicion, alpha-blockade was initiated without a definite diagnosis of paraganglioma. Ultimately, the patient underwent tumor resection and the final pathology confirmed paraganglioma. The pathology of the contralateral renal mass showed oncocytoma. This case serves as an illustration of the difficulties that can arise when diagnosing and treating undiagnosed paragangliomas within a community healthcare setting.

Solitary Extramedullary Plasmacytoma With Development of T-cell Anaplastic Large-Cell Lymphoma: A Rare Case Report and Literature Review.

Solitary extramedullary plasmacytomas are an exceedingly rare form of malignant neoplasms characterized by a single localized mass located in any soft tissue that consists of abnormal plasma cells. This type of tumor is characterized by the absence of plasmacytosis on bone marrow biopsy, the absence of other lesions on imaging, and no clinical signs of multiple myeloma. They usually present with mass effect, so the clinical picture varies based on the location of the tumor. In cases where the tumor is located in the gastrointestinal tract, patients may experience abdominal pain, small bowel obstruction, or gastrointestinal bleeding. The diagnostic process typically involves imaging to identify the tumor and its location, followed by a biopsy of the lesion with subsequent immunohistochemical analysis, as well as fluorescence in situ hybridization, and finally, bone marrow biopsy. Treatment options vary depending on the tumor's location and may include radiation therapy, surgical resection, and chemotherapy. Currently, radiation therapy is the preferred first-line treatment, with the best outcomes reported in the literature. Surgery is also frequently used and is often followed by radiation therapy. While chemotherapy has not been shown to have significant benefits, the available data is insufficient, and further studies are required to make better conclusions. Disease progression is often associated with transformation to multiple myeloma, but due to the rarity of the disease, data is limited, and it remains unclear if other forms of progression exist.   We report a case of a 63-year-old male who presented to the hospital with symptoms of abdominal pain, nausea, and vomiting. A computed tomography scan revealed a mass causing bowel obstruction, which was subsequently resected and evaluated by pathology. The final diagnosis was determined to be a solitary extramedullary plasmacytoma. Since the margins of the resected mass were clear, the patient was managed with solely clinical observation. Approximately eight months later, the patient was diagnosed with T-cell anaplastic large-cell lymphoma, ultimately leading to his passing 15 months after the initial diagnosis of solitary extramedullary plasmacytoma. We present this case to increase awareness of the rare condition of solitary extramedullary plasmacytoma and to highlight the potential association with T-cell anaplastic large-cell lymphomas, as demonstrated in this patient's case. Given the possibility of malignant transformation, close monitoring is warranted in similar cases.

Online Searching and Social Media to Detect Alcohol Use Risk at Population Scale.

INTRODUCTION: Harnessing engagement in online searching and social media may provide complementary information for monitoring alcohol use, informing prevention and policy evaluation, and extending knowledge available from national surveys. METHODS: Relative search volumes for 7 alcohol-related keywords were estimated from Google Trends (data, 2014-2017), and the proportion of alcohol use-related Twitter posts (data, 2014-2015) was estimated using natural language processing. Searching/posting measures were created for all 50 U.S. states plus Washington, D.C. Survey reports of alcohol use and summaries of state alcohol policies were obtained from the Behavioral Risk Factor Surveillance System (data, 2014-2016) and the Alcohol Policy Scale. In 2018-2019, associations among searching/posting measures and same state/year Behavioral Risk Factor Surveillance System reports of recent (past-30-day) alcohol use and maximum number of drinks consumed on an occasion were estimated using logistic and linear regression, adjusting for sociodemographics and Internet use, with moderation tested in regressions that included interactions of select searching/posting measures and the Alcohol Policy Scale. RESULTS: Recent alcohol use was reported by 52.93% of 1,297,168 Behavioral Risk Factor Surveillance System respondents, which was associated with all state-level searching/posting measures in unadjusted and adjusted models (p<0.0001). Among drinkers, most searching/posting measures were associated with maximum number of drinks consumed (p<0.0001). Associations varied with exposure to high versus low levels of state policy controls on alcohol. CONCLUSIONS: Strong associations were found among individual alcohol use and state-level alcohol-related searching/posting measures, which were moderated by the strength of state alcohol policies. Findings support using novel personally generated data to monitor alcohol use and possibly evaluate effects of alcohol control policies.

Sleep Apnea Screening for Commercial Drivers: A Retrospective Comparison of the 2016 FMCSA MRB Recommendations and the 2006 Joint Task Force Consensus Guidelines.

OBJECTIVE: Compare the 2016 Federal Motor Carrier Safety Administration (FMCSA) and 2006 Joint Task Force (JTF) Guidelines for commercial drivers' obstructive sleep apnea (OSA) screening. METHODS: Retrospective review of all commercial driver medical examinations performed in 2017 at an academic occupational medicine clinic. Screening criteria from both the JTF and FMCSA were applied, separately, and jointly. Statistical tests were applied as appropriate. RESULTS: Applying the FMCSA or JTF criteria separately to 706 commercial drivers, the positive OSA screening yields were 15.7% and 16.9%, respectively. Using both criteria produced an overall positive OSA screen yield of 20.1%. Positive predictive values for applying both guidelines ranged from 72.7% to 95.5%. CONCLUSIONS: The combined use of the 2016 FMCSA and 2006 JTF OSA screening criteria in series has a higher screening yield than using either guideline individually.

Clarithromycin use and the risk of mortality and cardiovascular events: A systematic review and meta-analysis.

BACKGROUND: Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605). RESULTS: This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32). CONCLUSIONS: Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations.

Preclinical evaluation of melanocyte transplantation by chitosan-based melanocyte spheroid patch to skin prepared by controlled sunburn blistering.

Transplantation of autologous cultured melanocytes as cell suspension has been used for the treatment of vitiligo. The recipient site is often prepared by laser-mediated dermabrasion. Such procedures encounter disadvantages including prolonged transplantation duration, unsecured cell adherence to lesional skin and potential scarring. To improve this, here we propose a method by preparing recipient sites before transplantation by psoralen and ultraviolet A (PUVA)-induced sunburn followed by transplanting cells with a chitosan-based melanocyte spheroid patch. We evaluated the method in nude mice. Application of methoxsalen-soaked filter paper on skin for 30 min followed by ultraviolet A exposure induced controlled sunburn blisters in 2 days. Upon transplantation, the blister roof could be quickly peeled off by a waxing patch. The chitosan membrane on which melanocytes were precultured into multicellular spheroids was transplanted with cells facing the skin. The chitosan patch adhered well to skin and secured the contact of melanocytes with the recipient site. One day later, melanocyte spheroids already detached from the chitosan membrane and adhered to the recipient skin. Our results suggest that the combination of chitosan-based melanocyte spheroid patch with epidermal ablation by PUVA-induced sunburn reaction can be a feasible method to facilitate melanocyte transplantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2535-2543, 2018.

Spectrophotometric determination of a thiobarbituric acid-reactive substance in human hair.

A simple and sensitive spectrophotometric method for the determination of a thiobarbituric acid-reactive substance (TBARS) in human hair has been developed. The proposed method is based on the formation of a red-colored product by the reaction of products of lipid peroxidation with thiobarbituric acid in an acidic medium. The absorbance of the resulting red product was measured at 534 nm. The linear dynamic range was between 1.0 and 20 micromol/L. The recoveries were 98.3-105.0%, and the relative standard deviations (RSD) were 0.32-1.24, respectively. TBARS in digested hair sample was stable for 3 days at room temperature. It was found that, using this method, the hair TBARS concentration in smokers (0.116 +/- 0.030 micromol/g, n = 30) was significantly higher than that in non-smokers (0.096 +/- 0.015 micromol/g, n = 30) (p < 0.05).

Continuous multi-element (Cu, Mn, Ni, Se) monitoring in saline and cell suspension using on-line microdialysis coupled with simultaneous electrothermal atomic absorption spectrometry.

We have developed a microdialysis sampling technique coupled on-line with simultaneous electrothermal atomic absorption spectrometry (SIMAAS) for the continuous monitoring of copper (Cu), manganese (Mn), nickel (Ni), and selenium (Se) in saline solutions and in cell suspensions. These trace elements are considered to be those associated most significantly with oxidative stress in biological systems. We employed ultrapure saline (0.9% NaCl) as the perfusate and, thus, the dialysate samples contained a high concentration of salt in the matrix. The use of modifiers [Pd coupled with Mg(NO3)2] prevented the target elements from undergoing evaporation at a pyrolysis temperature of 1200 degrees C, a process that effectively eliminated interference from NaCl. The excellent linearity, detection limits, and precision of the SIMAAS technique allowed the Cu, Mn, Ni, and Se concentrations to be determined in saline. For the on-line microdialysis-SIMAAS system, the ultrapure saline was perfused at a flow rate of 1 microL/min. The probe recoveries of Cu, Mn, Ni, and Se in saline were 57.9, 65.0, 65.5, and 67.9%, respectively. A standard saline solution was measured continuously by the on-line system to ensure long-term stability; each measurement fell within a range of two standard deviations. We determined the on-line spiked recoveries of Cu, Mn, Ni, and Se (101.3, 88.8, 91.3, and 98.5%, respectively) by adding a spiking standard into the stirred saline. The spiked recoveries (Cu, 37.5%; Mn, 3.8%; Ni, 71.1%; Se, 33.8%) were also determined through on-line spiking of a standard into the stirred cell suspension; these values demonstrate that Cu, Mn, and Se were depleted in the cell suspension, but Ni was not. The use of this on-line microdialysis-SIMAAS system permitted the in situ, dynamic, and continuous monitoring of Cu, Mn, Ni, and Se in cell suspensions at a temporal resolution of 20 min.