How many is too many? A review of the significant numbers in pediatric skin lesions and their recommended evaluation.

Pediatric dermatologists are frequently consulted to evaluate children for cutaneous signs of systemic disorders. Numerical thresholds of significance have been described in the dermatologic literature for various skin findings where the likelihood of an associated extracutaneous abnormality or known genetic syndrome increases significantly. Knowledge of these numerical thresholds facilitates diagnosis and management, which improves clinical outcomes and avoids severe complications. This review highlights the clinical presentation, complications, evaluation, and numerical significance, when applicable, for the following skin findings: infantile hemangiomas, capillary malformations, café-au-lait macules, hypopigmented macules, juvenile xanthogranulomas, pilomatricomas, and angiofibromas.

Cancer and the Microbiome of the Human Body.

Cancer remains a public health concern worldwide, with its incidence increasing worldwide and expected to continue growing during the next decades. The microbiome has emerged as a central factor in human health and disease, demonstrating an intricate relationship between the microbiome and cancer. Although some microbiomes present within local tissues have been shown to restrict cancer development, mainly by interacting with cancer cells or the host immune system, some microorganisms are harmful to human health and risk factors for cancer development. This review summarizes the recent evidence concerning the microbiome and some of the most common cancer types (i.e., lung, head and neck, breast, gastric, colorectal, prostate, and cervix cancers), providing a general overview of future clinical approaches and perspectives.

PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.

A Novel Minimally Invasive Surgically Induced Skeletal Muscle Injury Model in Sheep.

Sports-related muscle injuries account for 10-55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.

BRAF-Mutated Melanoma Journey in Latin America: Expert Recommendations From Diagnosis to Treatment.

OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region. INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region. METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment. RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.

Assessing occupational pesticide exposure in Latin America and the Caribbean: Methods review for agricultural vulnerability reduction.

B A rapid review was conducted to describe pesticide exposure assessment methodologies in Agricultural Work Contexts (AWC)s in Latin America and the Caribbean (LAC), in order to provide elements to reduce vulnerabilities within the agricultural population. A final number of 79 articles were selected from Medline via Pubmed, LILACS, and SciELO. In the region, family agriculture is the predominant form of agricultural production (72%) in informal agricultural work contexts (AWCs), which are characterized by small-scale diversified agricultural production, lower educational attainment, limited income, and a lack of social and healthcare security for the families. Indirect exposure assessment methods were the most commonly reported (58%), and its use was associated with informal AWCs (p = 0.011). Understanding AWCs and employing appropriate assessment methods can contribute to addressing vulnerabilities in the agricultural sector.

Delphi Consensus on Diagnostic Criteria for LUMBAR Syndrome.

OBJECTIVE: To develop consensus on diagnostic criteria for LUMBAR syndrome, the association of segmental infantile hemangiomas that affect the Lower body with Urogenital anomalies, Ulceration, spinal cord Malformations, Bony defects, Anorectal malformations, Arterial anomalies and/or Renal anomalies. STUDY DESIGN: These diagnostic criteria were developed by an expert multidisciplinary and multi-institutional team based on analysis of peer-reviewed data, followed by electronic-Delphi consensus of a panel of 61 international pediatric specialists. RESULTS: After 2 Delphi rounds, a 92% or higher level of agreement was reached for each Delphi statement. 98% of panelists agreed with the diagnostic criteria, and 100% agreed the criteria would be useful in clinical practice. The diagnosis of LUMBAR requires the presence of a segmental, or patterned, infantile hemangioma of the lumbosacral, sacrococcygeal, or pelvic cutaneous regions plus one additional criterion of the urogenital, spinal, bony, anorectal, arterial, or renal organ systems. CONCLUSIONS: These diagnostic criteria will enhance clinical care by improving screening, detection, and overall awareness of this poorly understood neurocutaneous disorder. The criteria can be utilized by a wide variety of pediatric subspecialists. In addition, formal criteria will improve phenotypic uniformity among LUMBAR syndrome cohorts and a patient registry, allowing investigators to assess clinical features, long-term outcomes, and results of genetic sequencing in a standardized manner. Finally, these criteria will serve as a starting point for prospective studies to establish formal screening and management guidelines.

A PTER-dependent pathway of taurine metabolism linked to energy balance.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

An analysis of information about infantile hemangiomas on TikTok: A cross-sectional study.

The video app TikTok, a controversial platform, has increasingly been utilized for the dissemination of health-related topics. In this study, the quality of information on the top 50 most viewed TikTok videos on infantile hemangiomas (IHs) labeled #hemangioma was analyzed. The results showed that the videos were skewed toward more severe subtypes of IH, and most were directed at raising awareness about IH or combating stigmatizing attitudes toward birthmarks. Providers should be aware that social media applications such as TikTok are a commonly used venue for parents to cope and connect but may relay inaccurate or misleading information.

Efficacy of photobiomodulation therapy combined with mobile health education in patients with head and neck cancer suffering from chronic xerostomia after radiotherapy: protocol for a three-arm, randomised, placebo-controlled, double-blinded study.

INTRODUCTION: The role of photobiomodulation (PBM) therapy for oral tissue damage induced by cancer treatment is currently unclear, and there is low-quality to moderate-quality evidence supporting the use of this approach for treating xerostomia and/or hyposalivation. Consequently, patients with head and neck cancer increasingly turn to basic oral hygiene to alleviate salivary gland dysfunction, and their adherence can be improved by mobile health (mHealth) education. The primary objective of this study will be to analyse the effects of different doses of PBM therapy (7.5 J/cm2 vs 3 J/cm2) plus mHealth education on quality of life (QoL), oral health, salivary secretion and salivary gland ultrasound assessment at postintervention and at the 6-month follow-up in patients with head and neck cancer after radiotherapy compared with those in control group. METHODS AND ANALYSIS: A prospective, three-arm, randomised, placebo-controlled, double-blinded study will be conducted among patients with head and neck cancer suffering from chronic xerostomia. A total of 20 patients per arm will be included and randomly assigned to receive 7.5 J/cm2 of PBM, 3 J/cm2 of PBM or placebo therapy. PBM therapy will be applied during 24 sessions at 22 points extra and intraorally two times per week for 3 months, combined with a mobile application (https://www.laxer.es). The assessments will be recorded at the beginning of the study, at postintervention and at the 6-month follow-up. The primary outcomes will be QoL, oral health, salivary secretion and salivary gland ultrasound. The pain pressure threshold, functional performance, mood and sleep quality will be secondary indicators. ETHICS AND DISSEMINATION: This study received ethics approval from the Andalusian Biomedical Research Ethics Portal (2402-N-21 CEIM/CEI Provincial de Granada) according to the Declaration of Helsinki for Biomedical Research. The results of this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05106608.

Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Utilization of Healthcare Resources by Vascular Anomaly Patients: An Assessment of Healthcare Burden by Lesion Complexity.

Background: Vascular anomalies (VAs) are heterogeneous lesions. Symptoms vary widely by lesion type and complexity. VA patients often require life-long interdisciplinary care; however, there is a paucity of data on the healthcare utilization of VA patients, and their burden on the healthcare system remains largely unquantified. We hypothesize that healthcare utilization by complex lymphatic malformation (LM) and venous malformation (VM) patients will be significantly higher compared with simple LM and VM patients. Methods: A retrospective, longitudinal study was performed of LM/VM patients seen through multidisciplinary VA clinics between January 1, 2019 and December 31, 2020. Data were collected from each patient's first presentation through December 31, 2021 and included number of office visits, imaging studies, specialists involved, procedures, hospitalization data, and approximate costs, normalized to per year utilization. Patients were divided into "simple" and "complex" LMs/VMs. Involvement of the airway, more than one anatomic area, and/or complex lymphatic anomalies were defined as "complex." Results: In total, 28 simple and 29 complex LM patients and 51 simple and 18 complex VM patients were identified. Complex LM and VM patients had significantly higher numbers of imaging studies, specialists involved, procedures and hospitalizations, and costs incurred. Complex LM patients also had significantly higher per year office visits. Conclusions: VA care is chronic and costly, especially for complex LM/VM patients. LM/VM complexity was a predictor for increased inpatient and outpatient healthcare utilization and higher costs. Better awareness of the healthcare utilization trends of LM/VM patients will allow for improved counseling for these patients regarding prognosis and expectations.

Gait analysis in chemotherapy-induced peripheral neurotoxicity rodent models.

Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis in in vivo studies has evolved from simple observations carried out by a trained operator to computerised systems with machine learning that allow the quantification of any variable of interest and the establishment of algorithms for behavioural classification. However, there is not a consensus on gait analysis use in CIPN animal models; therefore, we carried out a systematic review. Of 987 potentially relevant studies, 14 were included, in which different methods were analysed (observation, footprint and CatWalk™). We presented the state-of-the-art of possible approaches to analyse sensory ataxia in rodent models, addressing advantages and disadvantages of different methods available. Semi-automated methods may be of interest when preventive or therapeutic strategies are evaluated, also considering their methodological simplicity and automaticity; up to now, only CatWalk™ analysis has been tested. Future studies should expect that CIPN-affected animals tend to reduce hind paw support due to pain, allodynia or loss of sensation, and an increase in swing phase could or should be observed. Few available studies documented these impairments at the last time point, and only appeared later on respect to other earlier signs of CIPN (such as altered neurophysiological findings). For that reason, gait impairment could be interpreted as late repercussions of loss of sensory.

Persistent pain management in an oncology population through pain neuroscience education, a multimodal program: PaiNEd randomized clinical trial protocol.

INTRODUCTION: Pain is one of the most persistent symptoms after cancer treatment. The central nervous system can erroneously stay in its alarm phase, altering the pain experience of patients who have cancer. Pain neuroscience education (PNE) with multimodal approaches may benefit these patients. OBJECTIVE: This protocol aims to determine the effectiveness of a PNE tool on pain, physical function and quality of life, as a supplement to a multimodal rehabilitation (MR) program in patients who had breast cancer (BC). METHODS: An 8-week double-blinded randomized controlled trial will be conducted, including 72 participants who had BC and who have persistent pain, randomized into three groups: PNE program + MR program, traditional biomedical information + MR program and control group. The PNE program will include educational content that participants will learn through a mobile app and the MR program will include a concurrent exercise program and manual therapy. The primary outcome will be the perceived pain assessed using the Visual Analogue Scale and secondary outcomes are others related to pain, physical function and quality of life. All outcomes will be evaluated at baseline, at the end of the intervention and 6 months after the end of intervention. DISCUSSION: The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. This treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04877860. (February18, 2022).

Characteristics and complications of anogenital infantile hemangiomas: A multicenter retrospective analysis.

BACKGROUND: Infantile hemangiomas (IHs) of the anogenital region remain poorly characterized. OBJECTIVE: To examine the distribution, ulceration rate, and associated congenital anomalies of anogenital IHs. METHODS: Retrospective study at 8 tertiary referral centers. RESULTS: A total of 435 infants with an IH of the anogenital region were enrolled (of which, 319 [73%] were girls). Congenital anomalies were present in 6.4% (n = 28) of infants with an anogenital IH. Segmental or partial segmental anogenital IHs ulcerated in 72% (n = 99 of 138) of infants, whereas 45% (n = 133 of 297) of focal anogenital IHs experienced ulceration (P < .001). In a multivariable logistic regression analysis, segmental or partial segmental morphology (adjusted odds ratio [aOR], 2.70; 95% CI, 1.60-4.64), mixed type (aOR, 3.44; 95% CI, 2.01-6.07), and perianal (aOR, 3.01; 95% CI, 1.53-6.12) and buttocks location (aOR, 2.08; 95% CI, 1.17-3.76) had increased odds of ulceration. Segmental or partial segmental IHs of the genitalia were confined to distinct anatomic territories and were predominantly distributed unilaterally, with a linear demarcation at the perineal raphe. LIMITATIONS: Possible selection bias, given recruitment at tertiary referral centers. CONCLUSION: This study improves our understanding of high-risk features of anogenital IHs and demonstrates that genital segmental or partial segmental IHs develop within distinct anatomic territories.

Nonlinear, Multicomponent Physical Exercise With Heart Rate Variability-Guided Prescription in Women With Breast Cancer During Treatment: Feasibility and Preliminary Results (ATOPE Study).

OBJECTIVE: The purpose of this study was to examine the feasibility, safety, adherence, and preliminary efficacy of the ATOPE program during radiotherapy (RT) or chemotherapy (CT) for women with breast cancer. METHODS: This single-blind, pretest-posttest feasibility study included 38 women with breast cancer at the beginning of their treatment. The ATOPE program consisted of 12 to 18 sessions of a multimodal physical exercise program, prescribed based on daily heart rate variability and clinimetric assessments using the ATOPE+ mHealth system. Overall health was assessed with quality of life, autonomous balance, and body composition, whereas health-related fitness was measured through functional capacity, physical activity levels, and upper and lower limb strength. RESULTS: The rates of recruitment, retention, and adherence were 52.35, 73.68, and 84.37%, respectively, and the satisfaction rating was 9.2 out of a possible 10 points. The perceived health status change score was 3.83 points, scored on a -5 to 5 point scale. No adverse effects were found. Compliance results showed that the ATOPE+ mHealth system was used on 73.38% of the days, and the Fitbit bracelet (Google, Mountain View, CA, USA) was used on 84.91% of the days. Women stayed physically active 55% of days. Regarding preliminary results, for overall health, the percentage of body fat in the RT group decreased by 1.93%, whereas it increased by 5.03% in the CT group. Lower limb strength increased in the RT group, specifically knee extensor isometric strength (6.07%), isokinetic knee flexors 180 degree/second (1.53%), and isokinetic knee extensors 300 degree/second (4.53%), in contrast with the reductions found in the CT group (11.07, 18.67, and 14.89%, respectively). CONCLUSION: The ATOPE program, through nonlinear prescription based on daily monitoring with the ATOPE+ mHealth system, is feasible and safe for application during breast cancer treatment. The results suggest that the overall health can be maintained or even improved regarding most variables. IMPACT: This study focused on the feasibility, safety, and completion of a physical therapist-led program at early diagnosis for adults with breast cancer. The multimodal, supervised, tailored, nonlinear physical exercise program is feasible and safe, showed a good completion rate, and was able to prevent the quality-of-life deficits that are often triggered by systemic breast cancer treatment. This study highlights the importance of daily morning assessments using the ATOPE+ mHealth system in patients with breast cancer to prescribe nonlinear physical exercise.

Feasibility and efficacy of telerehabilitation in the management of patients with head and neck cancer during and after oncological treatment: A systematic review.

PURPOSE: The aim in this review was to evaluate recent advances in telerehabilitation for the management of patients with head and neck cancer (HNC) during and after their oncological treatment. METHODS: A systematic review was carried out in three databases (Medline, Web of Science and Scopus) in July 2022. The methodological quality of randomised clinical trials and quasi-experimental ones was assessed using the Cochrane tool (RoB 2.0) and the Critical Appraisal Checklists of the Joanna Briggs Institute, respectively. RESULTS: 14 out of 819 studies met the inclusion criteria: 6 studies were randomised clinical trials, 1 was a single-arm study with historical controls and 7 were feasibility studies. Most studies reported high participant satisfaction and efficacy of telerehabilitation used, in addition, no adverse effects were reported. None of the randomised clinical trials achieved a low overall risk of bias, whereas the methodological risk of bias of the quasi-experimental studies was low. CONCLUSIONS: This systematic review demonstrates that telerehabilitation offers feasible and effective interventions for the patients with HNC follow-up, during and after their oncological treatment. It was observed that telerehabilitation interventions should be personalised according to the patient's characteristics and the stage of the disease. Further research on telerehabilitation to support caregivers as well as to carry out studies with a long-term follow-up of these patients are imperative.

Correction: Burgos-Mansilla et al. Effect of Physical Therapy Modalities on Quality of Life of Head and Neck Cancer Survivors: A Systematic Review with Meta-Analysis. J. Clin. Med. 2021, 10, 4696.

In the original publication [...].

An overview of interventional radiology techniques for the diagnosis and management of vascular anomalies: Part 2.

Minimally invasive percutaneous and endovascular strategies performed by interventional radiologists have become the mainstays of treatment for vascular anomalies with improved outcomes, decreased complication rates, and less morbidity. The aim of this article is to introduce physicians who care for patients with vascular anomalies to state-of-the-art advancements in interventional radiology for diagnosis and treatment. Part 2 of this review discusses embolization, endovenous laser ablation, and image-guided percutaneous biopsy. Please see Part 1 for a discussion of sclerotherapy and cryoablation. Select vascular anomalies will be discussed as examples to highlight IR diagnostic and/or treatment techniques.

An overview of interventional radiology techniques for the diagnosis and management of vascular anomalies: Part 1.

Minimally invasive percutaneous and endovascular strategies performed by interventional radiologists have become the mainstays of treatment for vascular anomalies, with improved outcomes, decreased complication rates, and reduced morbidity. The aim of this article is to introduce physicians who care for patients with vascular anomalies to state-of-the-art advancements in interventional radiology (IR) for diagnosis and treatment. Part 1 of this review will focus on sclerotherapy and cryoablation. Part 2 will discuss embolization, endovenous laser ablation, and image-guided percutaneous biopsy. Select vascular anomalies will be discussed as examples to highlight IR diagnostic and/or treatment techniques.