Whey protein and male acne: A double-blind, randomized controlled trial.

BACKGROUND: Acne vulgaris (AV) exacerbation after whey protein (WP) consumption remains inconclusive among experts. OBJECTIVES: To investigate the association between WP consumption and acne severity in men with acne. METHODS: A noninferiority trial was conducted in men with mild to moderate facial and/or truncal acne. After randomization, participants in an intervention group took daily WP 30 g with a non-WP nutritional supplement 18 g (WP group, n = 25), while the control group took a non-WP nutritional supplement 46 g (non-WP group, n = 24). At each follow-up appointment, investigators evaluated acne count (total acne lesions, comedonal lesions, and inflammatory lesions) and severity. RESULTS: Forty-nine participants had a mean age of 19.7 years (standard deviation [SD], 0.9) and 20.3 years (SD, 1.4) in the WP and non-WP groups, respectively. The mean differences in the facial and truncal total acne lesions for the WP and non-WP group were -5.99 (95% confidence interval [CI], -13.18 to 1.19, p = 0.09) and -2.18 (95% CI, -11.83 to 7.48, p = 0.65), respectively. For severity changes, only one (4.3%) participant in the non-WP group reported an increase in the Investigator Global Assessment scale of at least two levels. CONCLUSIONS: In this 6-month trial, men with acne who undertook WP supplementation showed a noninferior difference in the changes in total acne lesions and severity of facial and truncal acne compared with the non-WP group.

IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity.

BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

Skin manifestations and biophysical changes following weight reduction induced by bariatric surgery: A 2-year prospective study.

Skin manifestations and biophysical changes are observed in patients with morbid obesity. However, reports of changes after significant weight loss, particularly through post-bariatric surgery (BaS), are limited. The aim of this 2-year prospective study was to evaluate the prevalence of skin signs and their changes in patients with morbid obesity who underwent BaS. Thirty-one patients were recruited for the study, with a mean age of 38.35 (SD 10.61) years and a male preponderance (male = 19 [61.29%], female = 12 [38.71%]). Patients were scheduled for multiple visits at months 0, 3, 6, 12, 18, and 24 post-BaS. Each subject had a thorough skin examination, biophysical measurements, and laboratory tests at each visit. Striae, acanthosis nigricans (AN), and plantar hyperkeratosis were the most common skin findings (n = 30 [96.77%], 29 [93.55%], 29 [93.55%], respectively). BaS provided improvements in many skin manifestations, namely striae, AN, acrochordons, plantar hyperkeratosis, hirsutism, lymphedema, pruritus, acne, finger pebbles, and chronic venous insufficiency with varied cumulative rates of improvements. However, acute telogen effluvium was observed in 17 (54.84%) patients. Regarding skin biophysical properties, transepidermal water loss, skin hydration, and pH did not change, while sebum production on the face significantly decreased at months 3 and 6, and elasticity decreased at months 6 and 24. In conclusion, weight reduction by BaS provided improvements in various skin signs, although telogen effluvium was a common sequelae.

Association of reproductive factors and exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States: results from 1999 to 2004 NHANES.

Postmenopausal status is a risk factor for distal sensory polyneuropathy-the most common type of peripheral neuropathy. We aimed to investigate associations between reproductive factors and history of exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States using data from the National Health and Nutrition Examination Survey 1999-2004, and to explore the modifying effects of ethnicity on these associations. We conducted a cross-sectional study among postmenopausal women aged ≥ 40 years. Women with a history of diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak or failing kidneys, or amputation were excluded. Distal sensory polyneuropathy was measured using a 10-g monofilament test, and a questionnaire was used to collect data on reproductive history. Multivariable survey logistic regression was used to test the association between reproductive history variables and distal sensory polyneuropathy. In total, 1144 postmenopausal women aged ≥ 40 years were included. The adjusted odds ratios were 8.13 [95% confidence interval (CI) 1.24-53.28] and 3.18 (95% CI 1.32-7.68) for age at menarche < 11 years and time since menopause > 20 years, respectively, which were positively associated with distal sensory polyneuropathy; adjusted odds ratios were 0.45 for the history of breastfeeding (95% CI 0.21-0.99) and 0.41 for exogenous hormone use (95% CI 0.19-0.87) were negatively associated. Subgroup analysis revealed ethnicity-based heterogeneity in these associations. Age at menarche, time since menopause, breastfeeding, and exogenous hormone use were associated with distal sensory polyneuropathy. Ethnicity significantly modified these associations.

Key factors predicting the in-hospital mortality of patients with severe cutaneous adverse reactions in Thailand.

BACKGROUND: At present, no predictive models are available to determine the probability of in-hospital mortality rates (HMRs) in all phenotypes of severe cutaneous adverse reactions (SCARs). OBJECTIVES: Our study explored whether simple clinical and laboratory assessments could help predict the HMRs in any phenotypes of SCAR patients. METHODS: Factors influencing HMRs in 195 adults diagnosed with different SCAR phenotypes were identified, and their optimal cut-offs were determined by Youden's index. Predictive equations for HMRs for all SCAR patients and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) patients were determined using the exact logistic regression models. RESULTS: Acute generalized exanthematous pustulosis (AGEP) patients were significantly older, with a short time from drug exposure to reaction, and higher neutrophil count compared to SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS, p < 0.001). Peripheral blood eosinophilia, atypical lymphocytosis and elevated liver transaminase enzymes were significantly higher in DRESS. SJS/TEN phenotype, age ≥ 71.5 years, neutrophil-to-lymphocyte ratio ≥ 4.08 (high NLR) and systemic infection were factors predicting in-hospital mortality in all SCAR subjects. The ALLSCAR model developed from these factors demonstrated high-diagnostic accuracy for predicting HMRs in all SCAR phenotypes (area under the receiver-operator curve (AUC) = 0.95). The risk of in-hospital death was significantly increased in SCAR patients with high NLR after adjusting for systemic infection. The model derived from high NLR, systemic infection and age yielded higher accuracy than SCORTEN (AUC = 0.77) for predicting the HMRs in SJS/TEN patients (AUC = 0.97). CONCLUSIONS: Being older, having systemic infection, having a high NLR and SJS/TEN phenotype increases ALLSCAR scores, which in turn increases the risk of in-hospital mortality. These basic clinical and laboratory parameters can easily be obtained in any hospital setting. Despite its simple approach, further validation of the model is warranted.

Health-related quality of life of daily-life-affected benign essential blepharospasm: Multi-center observational study.

PURPOSE: To compare Thais' health-related quality of life (HRQOL) and severity grading, efficacy and safety in daily-life-affected benign essential blepharospasm (BEB) patients at baseline and after Botulinum toxin type A (BTX-A) treatment. DESIGN: Prospective-observational study. PARTICIPANTS: BEB patients with Jankovic rating scale (JRS) at least 3 in both severity and frequency graded from 14 institutes nationwide were included from August 2020 to June 2021. METHODS: Demographic data, HRQOL evaluated by the Thai version of EQ-5D-5L and NEI-VFQ-25 questionnaires, and severity grading score evaluated by Jankovic rating scale (JRS) at baseline, 1, and 3 months after the treatment were collected. The impact of the BTX-A injections and their complications were recorded. RESULTS: 184 daily-life-affected BEB patients were enrolled; 159 patients (86.4%) had complete data with a mean age of 61.40±10.09 years. About 88.05% were female, and 10.1% were newly diagnosed. Most of the patients had bilateral involvement (96.9%) and 12.6% had history of BEB-related accident. After BTX-A treatment, HRQOL improved significantly in 4 dimensions of EQ-5D-5L, except self-care. The EQ_VAS (mean±SD) was 64.54±19.27, 75.13±15.37, 73.8±15.85 (p<0.001) and EQ-5D-5L utility score was 0.748±0.23, 0.824±0.19 and 0.807±0.19 at baseline, 1, 3 months after treatment, respectively. From NEI-VFQ-25, HRQOL also improved in all dimensions, except eye pain. The JRS improved in all patients. Self-reported minor adverse events were 22.6%, which mostly resolved within the first month. CONCLUSION: Daily-life-affected BEB impacted HRQOL in most dimensions from both generic and visual-specific questionnaires. BTX-A treatment not only decreased disease severity, but also improved quality of life.

Changes in Ocular Biomarkers from Normal Cognitive Aging to Alzheimer's Disease: A Pilot Study.

Purpose: To identify ophthalmic findings in Alzheimer's type dementia (ATD) compared to normal subjects. Patients and Methods: This comparative descriptive study included participants from the institution's cognitive fitness center. Complete ophthalmic examinations were performed. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to analyze retinal thickness and vascular density. The Ocular Surface Disease Index (OSDI) score and tear breakup time (TBUT) were used to assess dry eye. The blink rate was counted by a well-trained observer. Cognitive function was evaluated using the Thai Mental State Examination (TMSE) score. Correlation analysis was performed to compare OCT, OCTA parameters, and TMSE. Results: We included 24 ATD patients and 39 normal participants as a control group by age and sex-matched. The prevalence of dry eye using the Asia Dry Eye Society criteria was 15% and 13% in normal and ATD patients, respectively. The differences in OSDI scores, TBUT, and blink rate between the two groups were not statistically significant. The parafoveal and perifoveal macular thickness of the ATD group were significantly lower than that of the control group (p<0.01). All parameters of the vessel density of the ATD group were significantly lower than in the control group, including the whole macular vessel density (p<0.01), optic disc vessel density at the nerve head level (p<0.01), and optic disc vessel density at the radial peripapillary capillary level (p<0.05). After age adjustment, there were no statistically significant differences in all the OCT and OCTA parameters. There was a positive correlation between retinal thickness and vessel density in the macular and optic disc region and TMSE scores. Conclusion: Perifoveal and parafoveal retinal thickness might be more sensitive than peripapillary RNFL thickness to detect neurodegenerative changes in patients with ATD. Macular thickness and vessel density reduction were also positively correlated with cognitive decline.

The role of the topical nasal decongestant oxymetazoline as a novel therapeutic option for post-acne erythema: A split-face, double-blind, randomized, placebo-controlled trial.

Post-acne erythema (PAE) is one of the most common sequelae of acne inflammation. Unfortunately, the treatment of PAE remains challenging due to limited effective topical treatments. The objectives of this study were to evaluate the efficacy and safety of topical oxymetazoline hydrochloride (OxH) 0.05% solution for PAE. This study was a split-face, participants-and investigators-blinded, randomized, placebo-controlled trial conducted between December 2021 and March 2022 in Bangkok, Thailand. Healthy adults aged from 18 to 45 years with mild to severe PAE, according to the Clinician's Erythema Assessment (CEA), on both sides of the face were eligible. After randomization, each participant applied the OxH to one side of their face and a placebo to the contralateral face twice daily for 12 weeks. The primary outcome was PAE lesion counts. The secondary outcomes were erythema index, clinical response rate at week 12 ("clear," "almost clear," or "at least two-grade improvement" by CEA), and patient satisfaction scores. A total of 30 participants were enrolled. The OxH-treated skin showed a significantly greater mean difference (MD) reduction in PAE lesion counts than the placebo after 8 weeks of treatment (4.30, 95% confidence interval [CI] 1.42-7.18). Similarly, the MD reduction of the erythema index was higher in the OxH-treated skin from the second week (11.82, 95% CI 8.48-15.15). Additionally, the OxH-treated side also achieved a higher clinical response rate after 8 weeks of treatment (40.00% vs. 6.67%; p = 0.002) and rated higher satisfaction than those using the placebo at the end of the study (mean [standard deviation] satisfaction score 8.30 [0.18] vs 7.40 [0.18], P < 0.001). There were no serious adverse events or flares of erythema during the study. In conclusion, our study demonstrated that the topical OxH 0.05% solution was effective, well-tolerated, and safe for reducing PAE without a rebound effect. It could be a choice of PAE management. Trial Registration: Thai Clinical Trials Registry No. TCTR20211207004.

Beta-lactam hypersensitivity diagnosis in ambulatory and hospitalized settings require different approaches.

BACKGROUND: Data on beta-lactam hypersensitivity (BLH) are mainly focused on immediate or mild nonimmediate reactions in the ambulatory setting, but limited in patients with concurrent illness and moderate-to-severe nonimmediate reactions in the hospitalized setting. OBJECTIVE: To investigate the entire spectrum of BLH in Thai tertiary hospital. METHODS: Clinical characteristics of 357 patients with suspected BLH were evaluated in a 7-year period. Culprit drug identification was performed in 335 patients by combined skin testing, in vitro testing, or drug provocation tests. RESULTS: The predominant BLH presentations were non-immunoglobulin (Ig)E-mediated reactions with severe cutaneous adverse reactions of 18.9%, and BLH status was definitively confirmed in 18.1%. The most common verified culprits were cephalosporins (34.8%), particularly in hypersensitivity type IV reactions. Natural penicillins were the main implicated drugs in 48.5% of ambulatory patients. In contrast, cephalosporins and carbapenems were the main implicated drugs in hospitalized patients. Non-IgE-mediated anaphylaxis and serum sickness-like reaction remained diagnostically challenged. New generations of beta-lactams, hospitalized patients, recent allergic history, and underlying malignancies or autoimmune diseases were associated with increased BLH risk. CONCLUSION: At present, cephalosporins are the leading causes of BLH, particularly in non-IgE-mediated reactions. More research on the verification of non-IgE hypersensitivity reactions from new generations of beta-lactams should be better emphasized. CLINICAL TRIAL REGISTRATION: The registry was approved by the Ethics and Research Committee of the Faculty of Medicine, Chulalongkorn University, and listed on ClinicalTrials.gov (Identifier: NCT01667055; https://www. CLINICALTRIALS: gov/ct2/show/NCT01667055).

Association Between Breastfeeding and Reduced Distal Sensory Polyneuropathy in Postmenopausal Women Aged 40-70 Years: Analysis of Data from the 1999-2004 National Health and Nutrition Examination Survey.

Background: Distal sensory polyneuropathy (DSP) is a common peripheral neuropathy subtype. We aimed to determine the association between breastfeeding and DSP among postmenopausal women aged 40-70 years, and the effect modification of obesity on this association. Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey 1999-2004. Postmenopausal women aged 40-70 years were included. Women with diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak/failing kidneys, or amputation were excluded. Binary logistic regression was used to analyze the association between breastfeeding and DSP. Results: Among 798 participants, 386 (44.30%) reported breastfeeding history and 51 (5.29%) were defined as having DSP using the monofilament test. A significant inverse association was observed between breastfeeding and DSP (odds ratio [OR] = 0.29; 95% confidence interval [CI]: 0.11-0.79; p = 0.017) after adjusting for other confounding variables. In subgroup analysis, this adjusted association was observed only in the obese group (OR = 0.21; 95% CI: 0.06-0.73, p = 0.013). Conclusions: Breastfeeding was found to have potential benefits in the presence of DSP in postmenopausal women aged 40-70 years, and obesity modified the association between breastfeeding and DSP. Promoting breastfeeding may reduce the burden of peripheral neuropathy in middle-aged postmenopausal women.

The Impact of Dietary Fiber as a Prebiotic on Inflammation in Children with Obesity.

Background: Obesity is associated with dysbiosis, contributing to inflammation and insulin resistance. Inulin might reduce inflammation by manipulating intestinal microbiota. Objective: We aimed to determine the effects of inulin supplementation on inflammation and assess the relationships of inflammatory cytokines with adiposity and insulin resistance in obese Thai children. Design: Obese Thai children ages 7−15 years were randomly assigned to inulin (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received monthly follow-up and identical advice on lifestyle modification for six visits. Body composition was evaluated using bioelectrical impedance analysis. IL-1ß, IL-6, TNF-α, and fecal calprotectin were analyzed by ELISA technique at baseline and the final visit. Spearman correlation was used to assess the associations between inflammation and other clinical outcome variables. Results: A total of 155 obese children completed the study (mean age: 10.4 ± 2.2 years, 59% male). All groups showed a significant decrease in BMI z-score, fat mass index (FMI), percent body fat, and trunk FMI. A generalized estimating equation (GEE) model showed significantly decreased IL-1ß and TNF-α of 34.8% and 25.8%, (p < 0.0001) but increased IL-6 (21.5%, p = 0.006) in all groups. There were no significant differences in inflammatory cytokines and fecal calprotectin between groups. Mean IL-6 was higher in obese children with acanthosis nigricans (p = 0.048). Only IL-6 was positively correlated with body fat percentage and FMI (r = 0.29, p = 0.008 and r = 0.25, p = 0.049, respectively). Conclusions: Intensive behavioral modification and frequent follow-up visits were effective methods to reduce BMI and adiposity leading to decreased inflammatory cytokines. The additional benefits of inulin on inflammation could not be demonstrated due to the Hawthorne effect. Among the three cytokines, IL-6 was the most likely mediator relating FM and insulin resistance at baseline; therefore, it could be used as a surrogate marker of inflammation in obese children who are at risk for insulin resistance and metabolic syndrome.

Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity.

Inulin might improve body composition in obese children. We aimed to determine the effects of inulin supplementation on body composition and metabolic outcomes in obese children. A randomized, double-blinded placebo-controlled study was conducted in obese Thai children aged 7-15 years. Participants were assigned to 3 treatment groups for 6 months: 13 g of extracted inulin powder from Thai Jerusalem artichoke, isocaloric maltodextrin, and dietary fiber advice groups. Body composition was assessed by bioelectrical impedance analysis. One-hundred and fifty-five children completed the study (mean age 10.4 ± 2.2 years, BMI z-score 3.2 ± 1.0, 59% male). The drop-out rate was 6%. The inulin extract yielded more than 90% compliance without significant gastrointestinal side effects. All three groups demonstrated a significant decrease in BMI z-score, fat mass index (FMI), and trunk FMI, but the differences between groups were not observed. Fat-free mass index significantly increased only in the inulin group (16.18 ± 1.90 vs. 16.38 ± 1.98 kg/m2, P = 0.009). There were no significant differences in the metabolic profiles between groups. Despite showing no substantial effect on adiposity, inulin may increase fat-free mass in obese children. Further research in the change of gut microbiota composition is needed to determine inulin's impact on host-microbe interaction in pediatric obesity.

On and off-label uses of interleukin-17 inhibitors for patients with plaque-type psoriasis in Thailand: a real-world study.

BACKGROUND: Off-label uses of biologics in the treatment of psoriasis are usually implemented in limited-resource settings and studies regarding their response profiles are limited. METHOD: This was a retrospective study performed in moderate-to-severe plaque-type psoriasis patients who had been treated with either secukinumab, ixekizumab or brodalumab at a university hospital in Thailand between 1 January 2017 and 1 April 2021. RESULTS: A total of 142 patients were included in the data analysis consisting of three groups of 48 patients, 86 patients, and 8 patients treated by secukinumab, ixekizumab, and brodalumab, respectively. Patients were then classified into five groups according to the dosing pattern they received; on-label, off-label with induction, off-label with specific pattern, off-label with irregular dosing interval <8 weeks and >8 weeks. Considering both secukinumab and ixekizumab, the adjusted hazard ratios (95%CI) for complete skin clearance of the four off-label regimens were 2.2(0.9-5.2), 1.9 (0.9-3.9), 1.0 (0.4-2.2), and 1.6 (0.7-3.6), compared to on-label regimen, respectively. In each biologic drug, almost all off-label dosing regimens demonstrated higher adjusted hazard ratios compared to on-label regimen. CONCLUSION: Off-label, patient-oriented regimens could be a promising choice of IL-17 inhibitors for administration in special settings. Off-label regimens are not inferior in terms of skin clearance to an on-label regimen in the efficacy of psoriasis treatment of secukinumab and ixekizumab but do cause more flares. The decision to use off-label regimens must account for the benefits and associated risks.

Pediatric Prediction Model for Low Immunoglobulin G Level Based on Serum Globulin and Illness Status.

Hypogammaglobulinemia is a condition that requires prompt diagnosis and treatment. Unfortunately, serum immunoglobulin (Ig) measurements are not widely accessible in numerous developing countries. Serum globulin is potentially the best candidate for screening of low IgG level (IgGLo) due to its high availability, low cost, and rapid turnover time. However, multiple factors may influence the probability of prediction. Our study aimed to establish a simple prediction model using serum globulin to predict the likelihood of IgGLo in children. For retrospective data of patients who were suspected of having IgGLo, both serum IgG and globulin were simultaneously collected and measured. Potential factors interfering with serum globulin and IgG levels were investigated for their impact using bivariate binary logistic regression. A multivariate binary logistic regression was used to generate a formula and score to predict IgGLo. We obtained 953 samples from 143 pediatric patients. A strong positive correlation between serum globulin and IgG levels was observed (r=0.83, p < 0.001). A screening test model using serum globulin and illness status was constructed to predict IgGLo. The formula for predicting IgGLo was generated as follows; Predicted score = (2 x globulin (g/dl)) - illness condition score (well=0, sick=1). When the score was <4, the patient has the probability of having IgGLo with a sensitivity of 0.78 (0.71, 0.84), a specificity of 0.71 (0.68, 0.74), PPV of 0.34 (0.29, 0.40) and NPV of 0.94 (0.92, 0.96). This formula will be useful as rapid and inexpensive screening tool for early IgGLo detection, particularly in countries/locations where serum IgG measurement is inaccessible.

Tumor Prognostic Prediction of Nasopharyngeal Carcinoma Using CT-Based Radiomics in Non-Chinese Patients.

PURPOSE: We aimed to construct predictive models for the overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) for nasopharyngeal carcinoma (NPC) patients by using CT-based radiomics. MATERIALS AND METHODS: We collected data from 197 NPC patients. For each patient, radiomic features were extracted from the CT image acquired at pretreatment via PyRadiomics. Feature selection was performed in two steps. First, features with high inter-observer variability based on multiple tumor delineations were excluded. Then, stratified bootstrappings were performed to identify feature combinations that most frequently achieved the highest (i) area under the receiver operating characteristic curve (AUC) for predicting 3-year OS, PFS, and DMFS or (ii) Harrell's C-index for predicting time to event. Finally, regularized logistic regression and Cox proportional hazard models with the most frequently selected feature combinations as input were tuned using cross-validation. Additionally, we examined the robustness of the constructed model to variation in tumor delineation by simulating 100 realizations of radiomic feature values to mimic features extracted from different tumor boundaries. RESULTS: The combined model that used both radiomics and clinical features yielded significantly higher AUC and Harrell's C-index than models using either feature set alone for all outcomes (p < 0.05). The AUCs and Harrell's C-indices of the clinical-only and radiomics-only models ranged from 0.758 ± 0.091 to 0.789 ± 0.082 and from 0.747 ± 0.062 to 0.767 ± 0.074, respectively. In comparison, the combined models achieved AUC of 0.801 ± 0.075 to 0.813 ± 0.078 and Harrell's C-indices of 0.779 ± 0.066 to 0.796 ± 0.069. The results showed that our models were robust to variation in tumor delineation with the coefficient of variation ranging from 4.8% to 6.4% and from 6.7% to 9.3% for AUC and Harrell's C-index, respectively. CONCLUSION: Our results demonstrated that using CT-based radiomic features together with clinical features provided superior NPC prognostic prediction than using either clinical or radiomic features alone.

The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions.

PROPOSE: The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS: Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. RESULTS: Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells. CONCLUSION: The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02574988.

Clinical parameters and biological markers associated with acute severe ocular complications in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions with high mortality rates. Its sequelae, such as blindness, persist even after recovery. Patients with SJS/TEN should be accurately diagnosed and receive appropriate treatment as soon as possible. Therefore, identifying the factors for severity prediction is necessary. We aimed to clarify the clinical parameters and biological markers that can predict acute severe ocular complications (SOCs) in SJS/TEN. This retrospective cross-sectional study enrolled 47 patients with SJS/TEN who were divided into two groups according to ocular severity at acute onset: non-severe ocular complications group (n = 27) and severe ocular complications group (n = 20). Multivariate logistic regression analysis revealed that disease severity (body surface area detachment ≥ 10%) was a predictive factor for acute SOCs, and older age (≥ 60 years) was marginally significantly predictive of SOCs. Serum biomarker levels of S100A8/A9 and granulysin were marginally significant and tended to increase in the SOC group. Therefore, during the early acute stage, focusing on disease severity, patient age, and serum inflammatory biomarkers (S100A8/A9 and granulysin) might help predict SOC progression in patients with SJS/TEN who need prompt and aggressive ocular management to prevent severe ocular sequelae.

Pharmacokinetic Modeling of 18F-FDOPA PET in the Human Brain for Early Parkinson's Disease

Objectives: Early detection is essential for the treatment approaches of Parkinson's disease (PD). Clinical criteria alone may be insufficient to distinguish early PD from other conditions. This study aimed to investigate the transfer rate constants of 6-18F-fluoro-L-dopa (18F-FDOPA) in positron emission tomography (PET) brain images as a sensitive parameter to detect early PD. Methods: Retrospective 18F-FDOPA PET data of five patients with early PD were collected. PET data were acquired for 90 min after intravenous injection of 306-379 MBq 18F-FDOPA, and reconstructed into a series of 18 five-minute frames. Reoriented PET images were coregistered and normalized with the PET brain template on the statistical parametric mapping. The 18F-FDOPA activity concentrations were measured in the striatum, caudate, and putamen on both sides: Contralateral (as PD) and ipsilateral (as control) to the main motor symptoms. The pharmacokinetic model was generated using the SAAM II simulation software. The transfer rate constants across the blood-brain barrier (forward, K1 and reverse, k2) and decarboxylation rate constants (k3) were estimated in these regions. Results: The activity uptakes in the contralateral striatum (0.0323%±0.0091%) and putamen (0.0169%±0.0054%) were significantly lower than the control (0.0353%±0.0086%, 0.0199%±0.0054%, respectively). The K1 and k3 were significantly lower in the contralateral striatum and putamen (p<0.05). There were no significant differences in any transfer rate constants in the caudate. Conclusion: The transfer rate constants (K1 and k3) of 18F-FDOPA on the contralateral striatum and putamen were significantly lower than the control. These biokinetic data could be potential indicators for quantitative detection of early PD diagnosis.

Dry Eye Disease in Hemifacial Spasm Patients Treated with Botulinum Toxin Type A.

PURPOSE: To assess the impact of botulinum toxin type A (BTX-A) on signs and symptoms of dry eye (DE) in affected eye of hemifacial spasm (HFS) patients and to compare the prevalence of DE between affected and non-affected eye in HFS patients. PATIENTS AND METHODS: This prospective study included participants with unilateral HFS, who received BTX-A injection as a treatment. The eyes ipsilateral to the spasm side were used as studied eyes and the contralateral eyes were used as controls. The Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer I test were measured at baseline, 1 and 3 months after BTX-A injection. Fluorescein clearance test (FCT) was evaluated at baseline and at 1 month after BTX-A injection. RESULTS: Thirty-one participants (6 males and 25 females; mean age 61±10 years) were included. The prevalence of DE according to the Asia Dry Eye Society was not significantly different between affected (37.93%) and non-affected eyes (27.6%); P=0.083. At baseline, there was no significant difference in TBUT, Schirmer test, basal tear secretion, presence of delayed tear clearance, and presence of reflex tear secretion between affected and non-affected eyes, while significant difference in Oxford scheme grade was observed (P=0.031). OSDI score, TBUT, Oxford scheme grade, and Schirmer test at 1 month (P=0.817, 0.796, 0.534, 0.556), and 3 months (P=0.803, 0.904, 0.936, 0.684) after BTX-A injection did not significantly change from baseline in affected eyes. FCT results were not significantly different between baseline and at 1-month follow-up in both groups. All findings were corresponding in both naïve and long-term botulinum toxin injection groups. CONCLUSION: We found no significant effect of BTX-A on signs and symptoms of DE in patients with HFS. Moreover, there was no significant association between HFS and DE. However, we found significant corneal surface damage in the affected eyes, which emphasized importance of ocular surface evaluation and prompt treatment in HFS patients.