Nevin Manimala

Skin Res Technol. 2023 Jan;29(1):e13269. doi: 10.1111/srt.13269.

ABSTRACT

BACKGROUND: Acne is the eighth-most prevalent inflammatory skin disease with no optimal treatment. Photodynamic therapy (PDT) is an effective treatment for severe acne.

AIMS: The effect of PDT on the composition and diversity of skin microflora in severe acne patients was studied.

MATERIALS AND METHODS: A total of 18 patients with severe acne and 8 healthy individuals were selected for this study. Patients were treated with 5-aminolevulinic acid-mediated PDT once a week three times in total; the skin microbiome was measured by 16S ribosomal RNA gene sequencing before and after treatment (1 week after each PDT).

RESULTS: The microflora composition was different between healthy controls and patients, and between patients before and after treatment. Alpha diversity indices were lower in patients than those in control. There were 15 bacterial genera with high relative abundance that had noticeable changes during treatment. At the genus level,particularly Cutibacterium acnes (C. acnes formerly Propionibacterium acnes), there was no statistically significant difference among different group. The abundances of Staphylococcus epidermidis and Staphylococcus aureus were low.

DISCUSSION: The microbial composition is different between severe acne patients acne patients and healthy individuals. The therapeutic efficacy of severe acne treated with PDT is associated with the composition and diversity of skin microbiota.

CONCLUSION: The skin microbial composition changes after PDT treatment. PDT is an effective method for the treatment of severe acne.

PMID:36704881 | DOI:10.1111/srt.13269

Skin Res Technol. 2023 Jan;29(1):e13260. doi: 10.1111/srt.13260.

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease. Monoclonal antibody dupilumab was approved to treat moderate-to-severe AD in recent years. An objective assessment of treatment response by skin imaging modality is adjuvant for clinical evaluations. This study aimed to explore the value of dermoscopy and high-frequency ultrasound (HFUS) imaging characteristics in treatment evaluation for moderate-to-severe AD patients treated with dupilumab.

METHODS: Moderate-to-severe AD patients refractory to conventional therapy were enrolled in the study. All patients went through at least a 16-week standardized treatment of dupilumab. Clinical scores (eczema area scoring index [EASI], SCOARD, numerical rating scale of pruritus, dermatology life quality index), dermoscopy, and HFUS examinations were conducted at 0, 2, 4, 8, 12, and 16 weeks of treatment. Erythema, scales, erosion, and pigmentation under dermoscopy were scored, and subepidermal low-echogenic band (SLEB) thickness under HFUS was measured as quantitative indexes. Descriptive analysis and mixed effect linear regression models were used for statistical analysis.

RESULTS: Sixteen patients were enrolled in the study and their average age was 45.63 ± 18.18 years. All clinical scores decreased with significant difference after 16-week treatment compared with baseline. All patients achieved EASI 50 (EASI score decreased by 50% or more), and 9/16 patients reached EASI 75 after 16-week treatment. Dermoscopy evaluation of erythema, scales and erosion scores were decreased, and the sign of pigmentation score was increased after treatment. For HFUS, the mean SLEB value was 0.51 ± 0.29 mm and decreased to 0.27 ± 0.15 mm after 16-week treatment (p < 0.01). SLEB value decreased linearly with treatment time and correlated with clinical scores. However, SLEB values of two patients were 0.57 and 0.68 mm at week 16, respectively, which were higher than the average, and one of the patients showed EASI 75.

CONCLUSION: Dermoscopy and HFUS were able to reveal deeper inflammation response than clinical scores in AD and can be an effective method to evaluate and monitor clinical improvement during dupilumab treatment for AD patients. The preliminary value of imaging methods for predicting the treatment endpoint of dupilumab remains to be verified.

PMID:36704877 | DOI:10.1111/srt.13260

Int J Paediatr Dent. 2023 Jan 26. doi: 10.1111/ipd.13053. Online ahead of print.

ABSTRACT

The aim of the present cross-sectional study was to investigate whether family income modifies associations between dental caries and sex, age, mother’s education, type of preschool, sugar intake and tooth brushing. A randomly selected sample of 308 Brazilian preschool children aged one to three years underwent a clinical oral examination for the assessment of moderate/extensive dental caries using codes 3 to 6 of the International Caries Detection and Assessment System. Mothers were asked to fill out a form addressing the child’s demographic and socioeconomic characteristics as well as the frequency of sugar intake. Statistical analysis involved descriptive statistics, the chi-squared test and Poisson regression models. The prevalence of moderate/extensive dental caries was 42.5%. The adjusted model revealed that within low-income families (<2 times the monthly minimum wage), the prevalence of dental caries was higher among children with a high frequency of sugar intake (≥ twice per day) than in those with a low frequency of sugar intake (< twice a day) (RR=1.79; CI: 1.38-2.33). However, in families with higher income (≥2 times the monthly wage), no significant association between sugar intake and dental caries was found. In conclusion, monthly family income can modify the association between the high frequency of sugar intake and dental caries.

PMID:36704857 | DOI:10.1111/ipd.13053

Scand J Med Sci Sports. 2023 Jan 26. doi: 10.1111/sms.14322. Online ahead of print.

ABSTRACT

PURPOSE: To (1) identify neuromuscular and biomechanical injury risk factors in elite youth soccer players and (2) assess the predictive ability of a machine learning approach.

MATERIAL AND METHODS: Fifty-six elite male youth soccer players (age: 17.2 ± 1.1 years; height: 179 ± 8 cm; mass: 70.4 ± 9.2 kg) performed a 3D motion analysis, postural control testing, and strength testing. Non-contact lower extremities injuries were documented throughout 10 months. A least absolute shrinkage and selection operator (LASSO) regression model was used to identify the most important injury predictors. Predictive performance of the LASSO model was determined in a leave-one-out (LOO) prediction competition.

RESULTS: Twenty-three non-contact injuries were registered. The LASSO model identified concentric knee extensor peak torque, hip transversal plane moment in the single-leg drop landing task and COP sway in the single-leg stance test as the three most important predictors for injury in that order. The LASSO model was able to predict injury outcomes with a likelihood of 58% and an AUC of 0.63 (sensitivity = 35%; specificity = 79%).

CONCLUSION: The three most important variables for predicting the injury outcome suggest the importance of neuromuscular and biomechanical performance measures in elite youth soccer. These preliminary results may have practical implications for future directions in injury risk screening and planning, as well as for the development of customized training programs to counteract intrinsic injury risk factors. However, the poor predictive performance of the final model confirms the challenge of predicting sports injuries, and the model must therefore be evaluated in larger samples.

PMID:36703247 | DOI:10.1111/sms.14322

Immunology. 2023 Jan 26. doi: 10.1111/imm.13627. Online ahead of print.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumor-infiltrating lymphocytes (TILs) in pre-treated tumor tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders vs. non-pCR, with AUC values of 0.64 – 0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72 – 0.82). Lastly, performing a progression free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long and short survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival. This article is protected by copyright. All rights reserved.

PMID:36703241 | DOI:10.1111/imm.13627

Anim Microbiome. 2023 Jan 26;5(1):6. doi: 10.1186/s42523-023-00225-z.

ABSTRACT

BACKGROUND: Nondrug supplement strategies to improve gut health have largely focused on the effects of individual compounds to improve one aspect of gut homeostasis. However, there is no comprehensive assessment of the reproducible effects of oral, short-term, low-level colostrum supplementation on gut inflammation status that are specific to the ileum. Herein, a chicken animal model highly responsive to even mild gut inflammatory stimuli was employed to compare the outcomes of feeding a standard diet (CON) to those of CON supplemented with a centrifuge-defatted bovine colostrum (BC) or a nonfat dried milk (NFDM) control on the efficiency of nutrient use, ileal morphology, gut nitro-oxidative inflammation status, metabolites, and the composition of the microbiota.

RESULTS: A repeated design, iterative multiple regression model was developed to analyze how BC affected ileal digesta-associated anti-inflammatory metabolite abundance coincident with observed changes in the ileal microbiome, mitigation of epithelial inflammation, and ileal surface morphology. An improved whole body nutrient use efficiency in the BC group (v CON and NFDM) coincided with the observed increased ileum absorptive surface and reduced epithelial cell content of tyrosine-nitrated protein (NT, biomarker of nitro-oxidative inflammatory stress). Metabolome analysis revealed that anti-inflammatory metabolites were significantly greater in abundance in BC-fed animals. BC also had a beneficial BC impact on microbiota, particularly in promoting the presence of the bacterial types associated with eubiosis and the segmented filamentous bacteria, Candidatus Arthromitus.

CONCLUSION: The data suggest that an anti-inflammatory environment in the ileum was more evident in BC than in the other feeding groups and associated with an increased content of statistically definable groups of anti-inflammatory metabolites that appear to functionally link the observed interactions between the host’s improved gut health with an observed increase in whole body nutrient use efficiency, beneficial changes in the microbiome and immunometabolism.

PMID:36703224 | DOI:10.1186/s42523-023-00225-z

Genome Med. 2023 Jan 27;15(1):5. doi: 10.1186/s13073-023-01157-8.

ABSTRACT

BACKGROUND: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans.

METHODS: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant.

RESULTS: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders.

CONCLUSIONS: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

PMID:36703223 | DOI:10.1186/s13073-023-01157-8

BMC Med Educ. 2023 Jan 26;23(1):66. doi: 10.1186/s12909-023-04047-0.

ABSTRACT

BACKGROUND: Quality improvement (QI) is a systematic approach to improving healthcare delivery with applications across all fields of medicine. However, exposure to QI is minimal in early medical education. We evaluated the effectiveness of an elective QI curriculum in teaching preclinical health professional students foundational QI concepts.

METHODS: This prospective controlled cohort study was conducted at a single academic institution. The elective QI curriculum consisted of web-based video didactics and exercises, supplemented with in-person classroom discussions. An optional hospital-based QI project was offered. Assessments included pre- and post-intervention surveys evaluating QI skills and beliefs and attitudes, quizzes, and Quality Improvement Knowledge Application Tool-Revised (QIKAT-R) cases. Within-group pre-post and between-group comparisons were performed using descriptive statistics.

RESULTS: Overall, 57 preclinical medical or physician assistant students participated under the QI curriculum group (N = 27) or control group (N = 30). Twenty-three (85%) curriculum students completed a QI project. Mean quiz scores were significantly improved in the curriculum group from pre- to post-assessment (Quiz 1: 2.0, P < 0.001; Quiz 2: 1.7, P = 0.002), and the mean differences significantly differed from those in the control group (Quiz 1: P < 0.001; Quiz 2: P = 0.010). QIKAT-R scores also significantly differed among the curriculum group versus controls (P = 0.012). In the curriculum group, students had improvements in their confidence with all 10 QI skills assessed, including 8 that were significantly improved from pre- to post-assessment, and 4 with significant between-group differences compared with controls. Students in both groups agreed that their medical education would be incomplete without a QI component and that they are likely to be involved in QI projects throughout their medical training and practice.

CONCLUSIONS: The elective QI curriculum was effective in guiding preclinical students to develop their QI knowledge base and skillset. Preclinical students value QI as an integral component of their medical training. Future directions involve evaluating the impact of this curriculum on clinical clerkship performance and across other academic institutions.

PMID:36703204 | DOI:10.1186/s12909-023-04047-0

Cost Eff Resour Alloc. 2023 Jan 26;21(1):10. doi: 10.1186/s12962-023-00420-4.

ABSTRACT

OBJECTIVE: Renal cell carcinoma (RCC) is the most common type of kidney cancer. VEGF inhibitors and mTORs are the most common therapeutic options among the different classes of available treatments. In this study, the effectiveness of Everolimus was compared to Temsirolimus, and Everolimus plusLenvatinib in renal cell carcinoma patients by review of the international clinical evidence.

MATERIALS AND METHODS: A systematic review was conducted and all relevant published clinical studies on the efficacy and cost-effectiveness of Everolimus, Temsirolimus, and Lenvatinib plus Everolimus were searched comprehensively in electronic databases including Pubmed, Scopus, Medline, Cochrane Library, and ISI web of science. The Q score and I2 test checked the Heterogeneity and publication bias test, respectively. Egger’s test and Begg’s test were used to checking publication bias. The hazard ratio (HR) of included studies and subclass analysis were estimated by fixed and random effect models.

RESULTS: Out of 1816 found studies, ultimately, were included considering inclusion and exclusion criteria. None of these studies evaluated all three treatment strategies together and each study was about one strategy. Only one study was found for Everolimus plus Lenvatinib, so it was excluded from meta-analysis. Overall, data from 526 patients on Temsirolimus and 648 patients on Everolimus were included in Meta-Analysis. Accordingly, the efficacy of Everolimus and Temsirolimus was not statistically significant in assessed outcomes (PFS, TTSF, and death). However, Everlimus is superior to Temsirolimus in OS (Q = 3.61, p-value: 0.462, I2 = 0%). No heterogeneity or bias was detected.

CONCLUSION: According to the results of this study, Everolimus could be related to an increase of OS versus Temsirolimus as a second line treatment of ORCC patients.

PMID:36703202 | DOI:10.1186/s12962-023-00420-4

Fluids Barriers CNS. 2023 Jan 26;20(1):7. doi: 10.1186/s12987-023-00407-6.

ABSTRACT

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant.

METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded.

RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038).

CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.

PMID:36703181 | DOI:10.1186/s12987-023-00407-6