Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, ...and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2-69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had "low risk of bias", and three were in the "some concerns" category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.
Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still ...represent a pitfall. This study aims to determine the role of dendritic cells upon RCM in the epidermis and dermo‐epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%) and many (>5/mm2) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma.
Background
Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID‐19 infection. The purpose of this review was to analyze the correlation between the ...prevalence of MTHFR C677 T gene polymorphism and COVID‐19 incidence and mortality worldwide.
Methods
Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web“https://gnomad.broadinstitute.org.” COVID‐19 cases, including prevalence and mortality, were obtained from“https://www.worldometers.info/coronavirus” 27 August 2020.
Results
There is a clear trend toward the worldwide prevalence of MTHFR 677 T and COVID‐19 incidence and mortality. The prevalence of MTHFR 677 T allele in the Latino population, and the incidence and mortality for COVID‐19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between C677 T and death from coronavirus.
Conclusions
Genetic polymorphism of MTHFR C677 T may modulate the incidence and severity of COVID‐19 pandemic infection.
Background
Atopic dermatitis (AD) is a chronic inflammatory disease. Recently, dupilumab was approved for moderate‐to‐severe AD. D‐OCT is a noninvasive tool for the characterization of skin diseases.
...Objective
To describe the changes observed with D‐OCT in lesional and clinically healthy skin of patients with refractory severe AD under dupilumab treatment.
Methods
We analyzed AD lesions and healthy skin by D‐OCT. Clinical scores of AD severity were assessed at baseline (T0) and after 1 and 3 months of treatment (T1, T2). Descriptive statistics, chi‐square test, and t test were used to compare the analyzed parameters over time and between AD lesions and clinically healthy skin.
Results
At baseline, average EASI was 45.7. During the follow‐up, EASI75 and EASI90 were achieved in 57% and 36% of patients at T1 and 100% and 86% of patients at T2, respectively. Lesional skin D‐OCT parameters related to epidermal remodeling and inflammation evidenced a significant improvement after 1 month of treatment. In clinically healthy skin, D‐OCT parameters improved significantly after 3 months of treatment, especially for collagen remodeling and inflammation.
Conclusion
The study demonstrates that the clinical improvement of severe AD patients under dupilumab treatment is correlated with specific D‐OCT changes of patients’ lesional and clinically healthy skin.
The association between the metabolic profile and inflammatory cytokines in psoriasis is poorly understood. We analyzed the metabolic and cytokine/chemokine profiles in serum and skin from patients ...with new-onset psoriasis and healthy subjects (n = 7/group) by HR-MAS NMR and Bio-Plex immunoassay. Immuno-metabolic correlation matrix was analyzed in skin and serum to identify a potential immune-metabolic signature. Metabolomics analysis showed a significant increase in ascorbate and a decrease in scyllo-inositol, and a trend towards an increase in eight other metabolites in psoriatic skin. In serum, there was a significant increase of dimethylglycine and isoleucine. In parallel, psoriatic skin exhibited an increase of early inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β) and correlation analysis highlighted some major clusters of immune-metabolic correlations. A cluster comprising scyllo-inositol and lysine showed correlations with T-cell cytokines; a cluster comprising serine and taurine showed a negative correlation with early inflammatory cytokines (IL-6, G-CSF, CCL3). A strong positive correlation was enlightened between glutathione and inflammatory cytokines/angiogenesis promoters of psoriasis. The integration of metabolic and immune data indicated a molecular signature constituted by IL-6, IL1-ra, DMG, CCL4, Ile, Gly and IL-8, which could discriminate patients and healthy subjects and could represent a candidate tool in the diagnosis of new-onset psoriasis.
Objective
To report the first application of ex vivo fluorescence confocal microscopy (FCM) ‐ a novel optical technology that is capable of providing fast microscopic imaging of unfixed tissue ...specimens‐ in the urological field assessing its diagnostic accuracy for non neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the 'gold standard' histopathological diagnoses.
Patients and methods
In all, 89 specimens from 13 patients with clinically localised prostate cancer were enrolled into the study. All patients underwent robot‐assisted laparoscopic radical prostatectomy with fresh prostatic tissue biopsies taken at the end of each intervention using an 18‐G biopsy punch. Specimens were randomly assigned to the three collaborating pathologists for evaluation. Intra‐ and inter‐observer agreement was tested by the means of Cohen's κ. The diagnostic performance was evaluated on receiver operating characteristic curve analysis.
Results
The overall diagnostic agreement between FCM and histopathological diagnoses was substantial with a 91% correct diagnosis (κ = 0.75) and an area under the curve of 0.884 (95% confidence interval 0.840–0.920), 83.33% sensitivity, and 93.53% specificity.
Conclusion
FCM seems to be a promising tool for enhanced specimens' reporting performance, given its simple application and very rapid microscopic image generation (<5 min/specimen). This technique may potentially be used for intraoperative pathological specimens' analysis.
Purpose
To evaluate the role of magnetic resonance imaging (MRI) performed before and after neoadjuvant chemoradiotherapy (nCRT) in predicting risk of recurrence in rectal cancer and to investigate ...the prognostic significance of MR-detected extramural venous invasion (mr-EMVI) and of its regression after nCRT.
Methods
During 2005–2016, 87 patients with rectal cancer underwent pre- and post-nCRT MRI before surgery. Two radiologists independently reviewed MR examinations retrospectively, assessing T stage, nodal involvement, circumferential resection margin (CRM) status, and mr-EMVI. All four parameters assessed in pre- and post-nCRT MRI were correlated with the risk of recurrence. Correlation with disease-free survival (DFS) was investigated for significant predictive factors in pre-nCRT MRI and for mr-EMVI and its possible regression in post-nCRT MRI.
Results
15 of 87 patients developed recurrence, with a relapse-rate of 17.2%. Statistical analysis showed a significant correlation between CRM involvement and mr-EMVI assessed in pre-nCRT MRI and the risk of recurrence; 3 years-DFS in patients positive for these two parameters was significantly shorter compared with negatives. In post-nCRT MRI, all four parameters correlated significantly with recurrence: mr-EMVI affected significantly 3 years-DFS and its regression after nCRT correlated with a trend toward improvement of survival outcomes, although not statistically significant.
Conclusions
CRM involvement and mr-EMVI assessed in pre-nCRT MRI should be considered early predictive factors of recurrence in rectal cancer. MRI performed after nCRT has a significant value in predicting risk of recurrence: mr-EMVI confirmed to be a poor prognosis predictor and its regression or persistence after nCRT could have influences on treatment and follow-up strategies.
Few studies have combined high‐resolution, non‐invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age‐related ...skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high‐resolution, non‐invasive imaging according to age‐related skin pattern distribution. A set of 140 non‐pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high‐resolution, non‐invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.
Melanoma is the deadliest type of skin cancer characterized by high cellular heterogeneity, which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating ...reflectance confocal microscopy morphology with histopathological type, we identified four distinct melanoma subtypes: dendritic cell, round cell, dermal nest, and combined-type melanomas. In this study, each reflectance confocal microscopy melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. Markers of tumor aggressiveness, including Ki-67, MERTK, nestin, and stemness markers were highest in the most invasive combined-type and dermal nest melanomas than in dendritic cell and round cell melanomas. This was also confirmed in multicellular tumor spheroids. Transcriptomic analysis showed modulation of cancer progression-associated genes from dendritic cell to combined-type melanomas. The switch from E- to N-cadherin expression proved the epithelial-to-mesenchymal transition from dendritic cell to combined-type subtypes. The dermal nest melanoma was predominantly located in the dermis, as also shown in skin reconstructs. It displayed a unique behavior and a molecular profile associated with a high degree of aggressiveness. Altogether, our results show that each reflectance confocal microscopy melanoma subtype has a distinct biological and gene expression profile related to tumor aggressiveness, confirming that reflectance confocal microscopy can be a dependable tool for in vivo detection of different types of melanoma and for early diagnostic screening.
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