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AJNR. American Journal of Neuroradiology May 2023An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging... (Review)
Review
BACKGROUND AND PURPOSE
An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging presentations have emerged in parallel with a growing recognition of clinical and outcome variability, which pose a diagnostic challenge to neurologists and radiologists and may impact an individual patient's response to therapeutic interventions. By evaluating clinical, neuroimaging, laboratory, and genetic findings, we sought to improve our understanding of the sources of potential phenotype variability in patients with MELAS.
MATERIALS AND METHODS
This retrospective single-center study included individuals who had confirmed mitochondrial DNA pathogenic variants and a diagnosis of MELAS and whose data were reviewed from January 2000 through November 2021. The approach included a review of clinical, neuroimaging, laboratory, and genetic data, followed by an unsupervised hierarchical cluster analysis looking for sources of phenotype variability in MELAS. Subsequently, experts identified "victory-variables" that best differentiated MELAS cohort clusters.
RESULTS
Thirty-five patients with a diagnosis of mitochondrial DNA-based MELAS (median age, 12 years; interquartile range, 7-24 years; 24 female) were eligible for this study. Fifty-three discrete variables were evaluated by an unsupervised cluster analysis, which revealed that two distinct phenotypes exist among patients with MELAS. After experts reviewed the variables, they selected 8 victory-variables with the greatest impact in determining the MELAS subgroups: developmental delay, sensorineural hearing loss, vision loss in the first strokelike episode, Leigh syndrome overlap, age at the first strokelike episode, cortical lesion size, regional brain distribution of lesions, and genetic groups. Ultimately, 2-step differentiating criteria were defined to classify atypical MELAS.
CONCLUSIONS
We identified 2 distinct patterns of MELAS: classic MELAS and atypical MELAS. Recognizing different patterns in MELAS presentations will enable clinical and research care teams to better understand the natural history and prognosis of MELAS and identify the best candidates for specific therapeutic interventions.
Topics: Female; Humans; Acidosis, Lactic; MELAS Syndrome; Retrospective Studies; Stroke; DNA, Mitochondrial; Phenotype
PubMed: 37024306
DOI: 10.3174/ajnr.A7837 -
Orthopaedics & Traumatology, Surgery &... Feb 2020An anterior approach to the lumbar spine is increasingly used in performing fusion. Depending on the level to be treated, several approaches have been developed to deal... (Review)
Review
An anterior approach to the lumbar spine is increasingly used in performing fusion. Depending on the level to be treated, several approaches have been developed to deal with the anatomic obstacles encountered: pure anterior, oblique anterior or lateral, and trans- or pre-psoas. Conventional techniques incur risk of muscle lesion and severe bleeding, and have been replaced by minimally invasive approaches, often with video assistance after rapid closure of laparoscopic approaches with gas insufflation. There has, in parallel, been great progress in anterior spinal instrumentation systems. Non-existent when these techniques were first developed, they have become increasingly sophisticated, and now employ a variety of stand-alone or not cages and anterior screwed plate that can be associated together or to posterior fixation. Each approach and type of fixation has its specific technical requirements that need to be fully mastered so as to minimize risk, especially regarding vessels, and to enable the patient to enjoy the benefit of their very low morbidity. We shall therefore detail here each step of the pure anterior approach, which is most often used for L5S1, the oblique and lateral approaches, mainly used for L2L5, and also the preparation of the lumbar spine for anterior interbody fusion, with the respective instrumentations. We shall then consider the pros, cons and risks, and also spinal or general contraindications that may sometimes preclude this option. From this, we shall derive the specific optimal and wrong indications for anterior lumbar surgery, to help decision-making when fusion is indicated.
Topics: Humans; Lumbar Vertebrae; Neurosurgical Procedures; Radiography; Spinal Diseases; Spinal Fusion
PubMed: 31818690
DOI: 10.1016/j.otsr.2019.05.024 -
European Thyroid Journal Jul 2020Standard therapeutic approaches for benign thyroid lesions that warrant intervention are surgery for cold and either surgery or radioiodine for autonomously functioning...
Standard therapeutic approaches for benign thyroid lesions that warrant intervention are surgery for cold and either surgery or radioiodine for autonomously functioning thyroid nodules (AFTN). Image-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for selected clinical conditions. Due to mounting scientific evidence and widening availability, ETA considered it appropriate to develop guidelines for the use of TA in adult patients. TA procedures are well tolerated, but a dedicated training of the operators is required and information on possible complications needs to be shared with the patients. The following factors should be considered when weighing between observation, surgery, and TA for benign thyroid nodules. In solid non-hyperfunctioning nodules, TA induces a decrease in thyroid nodule volume, paralleled by improvement in symptoms. Nodule re-growth is possible over time and may necessitate repeat treatment, or surgery, in a dialogue with the patient. In AFTN, radioactive iodine is the first-line treatment, but TA may be considered in young patients with small AFTN due to higher probability of restoring normal thyroid function and avoidance of irradiation. In cystic nodules, ethanol ablation (EA) is the most effective and least expensive treatment. TA may be considered for cystic lesions that relapse after EA or have a significant residual solid component following drainage and EA. TA should be restricted to benign lesions that cause symptoms or cosmetic concern. Presently, laser and radiofrequency ablation are the most thoroughly assessed techniques, with similar satisfactory clinical results. Microwaves and high-intensity focused ultrasound therapy options remain to be fully evaluated.
PubMed: 32903999
DOI: 10.1159/000508484 -
Italian Journal of Dermatology and... Jun 2021The indisputable contribution of dermatoscopy in early diagnosis of melanoma is widely recognized. In the last quinquennium, new data concerning specific melanoma...
The indisputable contribution of dermatoscopy in early diagnosis of melanoma is widely recognized. In the last quinquennium, new data concerning specific melanoma subtypes have come to light. The dermatoscopic morphology of superficial spreading melanoma (SSM) has been extensively investigated in the literature. Atypical network, irregular dots, irregular globules, irregular streaks and irregular blotch correspond to histopathologic alterations at the level of the junction, blue-white veil and atypical vessels suggest intradermal growth, whereas regression structures, negative network and white shiny streaks might reflect junctional or dermal alterations. The list of melanoma specific criteria has been recently updated to include features that typify early melanoma, such as irregular hyperpigmented areas and prominent skin markings and features seen in melanoma on sun damaged skin such as angulated lines. Nodular melanoma lacks most of the aforementioned criteria and is typified by the coexistence of blue and black color, atypical vessels and pink color. Lentigo maligna dermatoscopic criteria mainly develop at the outline of the follicular openings. However, at an early stage these features might be very subtle and the diagnosis should be based on the exclusion of benign tumors (inverse approach). Acral lentiginous melanoma is typified by a parallel ridge pattern, but also SSM criteria should be taken into consideration. The diagnosis of subungual melanoma is based on the assessment of the color and characteristics of the pigmented nail band. For the diagnosis of mucosal melanoma, the assessment of colors is more informative than the assessment of structures and the detection of blue, white or gray should raise the suspicion of melanoma. White shiny streaks and regression structures are the most common features of desmoplastic melanoma. The diagnosis of nevoid melanoma might be highly challenging and require information on the lesion's history. Melanoma on small- and medium-sized congenital nevi is typified by an eccentric location of the suspicious area, negative network and gray angulated lines. Recent advances in knowledge on the dermatoscopic characteristics of peculiar subtypes of the tumor significantly enrich the diagnostic armamentarium of clinicians. The challenge of the forthcoming years is to better characterize biologically aggressive melanomas and to optimize the screening strategies so as to identify them.
Topics: Dermoscopy; Diagnosis, Differential; Humans; Hyperpigmentation; Melanoma; Skin Neoplasms
PubMed: 33314891
DOI: 10.23736/S2784-8671.20.06784-X -
Journal of the American Academy of... Oct 2023Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies.
BACKGROUND
Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical instability, and both medications are potentially irritating. Microencapsulation helps overcome these challenges.
OBJECTIVE
Examine efficacy, safety, and tolerability of encapsulated BPO/encapsulated tretinoin (E-BPO/T) cream, 3%/0.1%.
METHODS
Subjects ≥9 years old with moderate to severe acne were enrolled in 2 multicenter, double-blind, vehicle-controlled, parallel trials and randomized (2:1) to 12 weeks of once-daily E-BPO/T (n = 571) or vehicle cream (n = 287).
RESULTS
E-BPO/T was significantly superior to vehicle in both studies, with more subjects achieving IGA success with E-BPO/T (38.5%/25.4%) versus vehicle (11.5%/14.7%; P < .001/P = .017). The change from baseline in inflammatory lesion count for E-BPO/T was -21.6 versus -14.8 for vehicle (P < .001) in study 1 and -16.2 versus -14.1 (P = .018) in study 2. The changes from baseline in noninflammatory lesions for E-BPO/T were -29.7 versus -19.8 for vehicle (P < .001) and -24.2 and -17.4 (P < .001) in studies 1 and 2, respectively. E-BPO/T was well tolerated in both studies.
LIMITATIONS
Long-term data are not available.
CONCLUSION
E-BPO/T provided statistically significant and clinically relevant improvements in IGA and inflammatory and noninflammatory lesion counts and was well tolerated in subjects with moderate to severe acne.
Topics: Child; Humans; Acne Vulgaris; Administration, Cutaneous; Benzoyl Peroxide; Dermatologic Agents; Double-Blind Method; Drug Combinations; Emollients; Immunoglobulin A; Treatment Outcome; Tretinoin
PubMed: 37356627
DOI: 10.1016/j.jaad.2023.05.093 -
Rambam Maimonides Medical Journal Apr 2020Coronary artery stenting is the treatment of choice for patients requiring coronary angioplasty. We describe the major advancements with this technology. There have been... (Review)
Review
Coronary artery stenting is the treatment of choice for patients requiring coronary angioplasty. We describe the major advancements with this technology. There have been significant developments in the design of stents and adjunctive medical therapies. Newer-generation drug-eluting stents (DES) have almost negligible restenosis rates and, when combined with proper anti-platelet treatment and optimal deployment, a low risk of stent thrombosis. The introduction of newer-generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new antiproliferative agents has further improved the safety profile of early-generation DES. In parallel the effectiveness has been kept, with a significant reduction in the risk of target lesion revascularization compared with the early-generation DES. However, to date, the development of completely bioresorbable vascular scaffolds has failed to achieve further clinical benefits and has been associated with increased thrombosis. Newer-generation DES-including both durable polymer as well as biodegradable polymer-have become the standard of care in all patient and lesion subsets, with excellent long-term results.
PubMed: 32374258
DOI: 10.5041/RMMJ.10403 -
JAMA Dermatology Dec 2019Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always...
IMPORTANCE
Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking.
OBJECTIVE
To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018.
MAIN OUTCOMES AND MEASURES
Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry.
RESULTS
A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).
CONCLUSIONS AND RELEVANCE
In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.
Topics: Age of Onset; Biomarkers; Biopsy; Child, Preschool; Cross-Sectional Studies; Dermatitis, Atopic; Feasibility Studies; Female; Filaggrin Proteins; Humans; Immunohistochemistry; Infant; Infant, Newborn; Male; Real-Time Polymerase Chain Reaction; Severity of Illness Index; Skin; Water Loss, Insensible
PubMed: 31596431
DOI: 10.1001/jamadermatol.2019.2983