Differential diagnosis of bone marrow failure syndromes guided by machine learning.

The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter. For model development, patients were labeled as having acquired or inherited BMF depending on their genomic data. Data sets were unbiasedly clustered, and an ensemble model was trained with cases from the largest cluster of a training cohort (n = 359) and validated with an independent cohort (n = 127). Cluster A, the largest group, was mostly immune or inherited aplastic anemia, whereas cluster B comprised underrepresented BMF phenotypes and was not included in the next step of data modeling because of a small sample size. The ensemble cluster A-specific model was accurate (89%) to predict BMF etiology, correctly predicting inherited and likely immune BMF in 79% and 92% of cases, respectively. Our model represents a practical guide for BMF diagnosis and highlights the importance of clinical and laboratory variables in the initial evaluation, particularly telomere length. Our tool can be potentially used by general hematologists and health care providers not specialized in BMF, and in under-resourced centers, to prioritize patients for genetic testing or for expeditious treatment.

Uterine Smooth Muscle Tumors: An Overview.

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa. Recent advances in molecular diagnostics have refined the classification of smooth muscle tumors, but most cases are diagnosed purely on histologic grounds.

The "Other" Uterine Mesenchymal Neoplasms: Recent Developments and Emerging Entities.

Uterine mesenchymal neoplasms are a challenging group of tumors that often show overlapping morphologic features and immunohistochemical profiles. The increasing use of molecular testing in these tumors has enabled a better appreciation of their pathobiology, resulting in a wave of emerging neoplasms and improved characterization of ones previously considered exceptionally rare. Identification of specific molecular alterations has permitted targeted therapy options in tumors that were typically unresponsive to conventional therapies, as well as recognition that a subset can have a hereditary basis. This review will discuss the more "common" of the uncommon uterine mesenchymal neoplasms, including inflammatory myofibroblastic tumor, perivascular epithelioid cell tumor, uterine tumor resembling ovarian sex cord tumor, and embryonal rhabdomyosarcoma. This will be followed by an overview of emerging entities, including NTRK-rearranged uterine sarcoma, SMARCA4-deficient uterine sarcoma, KAT6B/A::KANSL1 fusion uterine sarcoma, and MEIS1::NCOA2/1 fusion sarcoma.

Mediation effects of lean mass and fat mass on the relationship between body mass index and handgrip strength.

OBJECTIVE: This study aimed to assess the mediation effects of lean mass and fat mass on the relationship between body mass index (BMI) and handgrip strength (HGS) in adolescents. METHOD: The sample included 118 adolescents (60 girls) aged 10-14 years. Body composition, determined from lean mass (LM) and fat mass (FM), was measured by dual-energy x-ray absorptiometry. HGS was measured using a digital dynamometer. Moderate-to-vigorous physical activity and sexual maturation, treated as covariates, were evaluated by accelerometry and pubic hair development, respectively. Spearman correlation and simple mediation analysis were used for statistical analysis. RESULTS: A positive relationship was observed between BMI and HGS (rho = .364, p < .001), BMI and LM (rho = .466, p < .001), LM and HGS (rho = .784, p < .001), BMI and FM (rho = .907, p < .001), and FM and HGS (rho = .291, p = .001). LM was the only significant mediator of the relationship between BMI and HGS. CONCLUSION: Only LM mediated the association between BMI and HGS, almost entirely explaining the relationship. The findings reinforce the need to include LM measurements in routine strength testing. Furthermore, strategies focused on LM development may be promising in preventing low muscle strength in adolescents.

Secular trends and sociodemographic, biological, and behavioural factors associated with handgrip strength in adolescents in southern Brazil: An allometric approach.

The purpose of this study was to analyse secular trend in handgrip strength (HGS) in adolescents using an allometric approach and identify the factors associated. The sample comprised 657 and 1004 adolescents (14 to 19 years) in 2007 and 2017/2018, respectively, of public schools in Florianópolis, Brazil. The dependent variable was HGS normalised to body mass and height. Covariance analysis was used to examine secular trends in HGS, and multiple linear regression was used to identify associated factors. The independent variables were sociodemographic, biological, and behavioural factors. Comparison of HGS between surveys indicated a negative secular trend in both sexes (p < 0.001). In boys, there was a positive association of HGS with age and FFM in both surveys. In 2017/18, there was a positive association with sexual maturation and a negative association with sitting time and fat percentage. In girls, FFM was positively associated with HGS in both surveys. In 2007, there were positive associations of HGS with age and vigorous physical activity, whereas, in 2017/18, negative associations were observed with economic level and sitting time. The findings of the present study show a decline in adolescent HGS. And behavioural changes appear to be contributing to declines in HGS.

Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial.

Androgens have been reported to elongate telomeres in retrospective and prospective trials with patients with telomeropathies, mainly with bone marrow failure. In our single-arm prospective clinical trial (clinicaltrials gov. Identifier: NCT02055456), 17 patients with short telomeres and/or germline pathogenic variants in telomere biology genes associated with at least one cytopenia and/or radiologic diagnosis of interstitial lung disease were treated with 5 mg/kg of intramuscular nandrolone decanoate every 15 days for 2 years. Ten of 13 evaluable patients (77%) showed telomere elongation at 12 months by flow-fluorescence in situ hybridization (average increase, 0.87 kb; 95% confidence interval: 0.20-1.55 kb; P=0.01). At 24 months, all ten evaluable patients showed telomere elongation (average increase, 0.49 kb; 95% confidence interval: 0.24-1.23 kb; P=0.18). Hematologic response was achieved in eight of 16 patients (50%) with marrow failure at 12 months, and in ten of 16 patients (63%) at 24 months. Seven patients had interstitial lung disease at baseline, and two and three had pulmonary response at 12 and 24 months, respectively. Two patients died due to pulmonary failure during treatment. In the remaining evaluable patients, the pulmonary function remained stable or improved, but showed consistent decline after cessation of treatment. Somatic mutations in myeloid neoplasm-related genes were present in a minority of patients and were mostly stable during drug treatment. The most common adverse events were elevations in liver function test levels in 88%, acne in 59%, and virilization in 59%. No adverse events grade ≥4 was observed. Our findings indicate that nandrolone decanoate elongates telomeres in patients with telomeropathies, which correlated with clinical improvement in some cases and tolerable adverse events.

Intra-racial disaggregation reveals associations between nativity and overall survival in women with endometrial cancer.

OBJECTIVE: Prior studies have demonstrated survival differences between Black women with endometrial cancer (EC) born in the US and Caribbean. Our objective was to determine if country of birth influences EC overall survival (OS) in disaggregated subpopulations of Black women. METHODS: Using the Florida Cancer Data System, women with EC diagnosed from 1981 to 2017 were identified. Demographic and clinical information were abstracted. Women who self-identified as Black and born in the US (USB), Jamaica (JBB), or Haiti (HBB) were included. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods with significance set at p < 0.05. RESULTS: 3817 women met the inclusion criteria. Compared to USB, JBB and HBB had more high-grade histologies, more advanced stage disease, had a greater proportion of uninsured or Medicaid insured, and had a higher proportion of women who received chemotherapy (all p < 0.05). In multivariate analyses, age (HR 1.03 [1.02-1.05]), regional stage (HR 1.52 [1.22-1.89]), distant stage (HR 3.73 [2.84-4.89]), lymphovascular space invasion (HR 1.96 [1.61-2.39]), receipt of surgery (HR 0.47 [0.29-0.75]), and receipt of chemotherapy (HR 0.77 [0.62-0.95]) were independently associated with OS. Compared to USB, Haitian nativity was an independent negative predictor of OS when evaluating all histologies together (HR 1.54 [1.18-2.00]) and for endometrioid EC specifically (HR 1.77 [1.10-2.83]). Among women with serous EC, HBB had markedly worse median OS (18.5 months [13.4-46.5]) relative to USB (29.9 months [26.3-35.9]) and JBB (41.0 months, [34.1-82.6], p = 0.013). CONCLUSION: Country of birth is associated with endometrial cancer survival in Black women, with HBB demonstrating worse outcomes.

Endometrioid Squamous Proliferations of the Endometrium Express Alpha-Methylacyl-CoA Racemase (P504s).

Squamous morular metaplasia is closely associated with endometrioid proliferative lesions such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinoma may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and in a subset of gynecologic carcinomas, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferations can be challenging, given their anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas. Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity for AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens.

Novel photoelectrochemical 3D-system for water disinfection by deposition of modified carbon nitride on vitreous carbon foam.

Graphitic carbon nitride (GCN) is an optical semiconductor with excellent photoactivity under visible light irradiation. It has been widely applied for organic micropollutant removal from contaminated water, and less investigated for microorganisms' inactivation. The photocatalytic degradation mechanism using GCN is attributed to a series of reactions with reactive oxygen species and photogenerated holes that can be boosted by modifying its physical-chemical structure. This work reports a successful improvement of the overall photocatalytic and electrocatalytic activities of the pristine material by thermal and chemical modification by a copolymerisation synthesis method. The copolymerisation of dicyandiamide as a precursor with barbituric acid strongly reduced photoluminescence due to the enhanced charge separation thus improving the catalyst efficiency under visible light irradiation. The material with 1.6 wt% of barbituric acid showed the best photocatalytic performance and electrochemical properties. This photocatalyst was selected for immobilisation on a conductive carbon foam, which promotes a higher electrochemical active surface area and enhanced mass transfer. This three-dimensional metal-free electrode was employed for the photoelectrochemical inactivation of two different microorganisms, Escherichia coli, and Enterococcus faecalis, obtaining removals below the detection limit after 30 min in simulated faecal-contaminated waters. This photoelectrochemical reactor was also applied to treat polluted river and urban waste waters, and the faecal contamination indicators were vastly reduced to values below the detection limit in 60 min in both cases, showing the wide applicability of this innovative photoelectrode for different types of polluted aqueous matrices.

Uterine PEComas: correlation between melanocytic marker expression and TSC alterations/TFE3 fusions.

Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32-77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm. All patients with malignant PEComas were alive with disease or dead  of disease at last follow-up, while all those of uncertain malignant potential were alive and well (median follow-up, 47 months).Seventeen of 19 (89%) PEComas harbored either a TSC1 or TSC2 alteration. One of the two remaining tumors showed a TFE3 rearrangement, but the other lacked alterations in all genes evaluated. All showed at least focal (usually strong) positivity for HMB-45, with 15/19 (79%) having >50% expression, while the tumor lacking TSC or TFE3 alterations was strongly positive in 10% of cells. Melan-A and MiTF were each positive in 15/19 (79%) tumors, but staining extent and intensity were much more variable than HMB-45. Five of six (83%) malignant PEComas also harbored alterations in TP53, ATRX, or RB1, findings not identified in any tumors of uncertain malignant potential. One malignant PEComa was microsatellite-unstable/mismatch repair protein-deficient.In summary, TSC alterations/TFE3 fusions and diffuse (>50%) HMB-45 expression are characteristic of uterine PEComas. In morphologically ambiguous mesenchymal neoplasms with myomelanocytic differentiation, especially those with metastatic or recurrent disease, next-generation sequencing is recommended to evaluate for TSC alterations; as such, patients can be eligible for targeted therapy.

Unusual Variants of Teratoma Involving the Gynecologic Tract.

Teratomas are tumors of germ cell origin, and in the female genital tract are subclassified as immature or mature based on the presence or absence, respectively, of immature elements. Somatic tumors may also develop in association with teratomas, and most commonly include thyroid tumors, carcinoids and carcinomas. We report herein 2 rare forms of gynecologic teratomas: 1 case of immature teratoma of the uterus and 1 case of a benign follicular hamartoma arising in association with mature cystic teratoma of the ovary.

Relationship Between Muscle Strength, Body Composition and Bone Mineral Density in Adolescents.

Adolescence is an important period for the acquisition of bone mass, which can be enhanced by several factors. This study aimed examine the relationships of handgrip strength, free-fat mass, and fat mass with bone mineral density in adolescents. 118 adolescents (60 girls), aged 10 to 14 years, participated in the study. Information on sex, age, handgrip strength, free-fat mass, fat mass and bone mineral density were collected. Multiple linear regression analyses were conducted to examine possible relationships between bone mineral density and handgrip strength, free-fat mass and fat mass. There was a relation between handgrip strength and free-fat mass with bone mineral density in both sexes. Fat mass was correlated with bone mineral density only in girls (r= 0.314, p< 0.014). The final models, adjusted for sexual maturation, included free-fat mass (girls - ß= 0.419, p< 0.001; boys - ß= 0.455; p< 0.001) and handgrip strength (girls - ß= 0.358, p< 0.05; boys - ß= 0.325; p< 0.05) and these variables together explained 51.8% and 62.9% of the variation of bone mineral density, in girls and boys, respectively. Handgrip strength and free-fat mass were positively associated with bone mineral density. A sex-specific difference indicated that higher levels of free-fat mass are of paramount importance for both sexes.

Prediction models of low-power holmium laser effectiveness in renal stone lithotripsy during retrograde intrarenal surgery.

The objectives of this study are to develop prediction models for total laser energy (TLE) in order to infer surgical time and assist operative planning of intrarenal low-power Ho:YAG laser lithotripsy, and to predict the fragmented volume as well as the stone-free status (SFS). A retrospective review was performed, comprising all single surgeon standardized retrograde intrarenal surgery and low-power Ho:YAG laser lithotripsy at a tertiary care centre between October 2014 and September 2019. Automated measurement of stone volume and stone density (MSD), measured in Hounsfield units (HU), was employed in both pre- and post-operative non-contrast-enhanced computed tomography (NCCT), using a standardized technique on Osirix Lite® software. SFS was defined as complete absence of stone fragments, or fragments < 0.1 cm on meticulous inspection at the end of the procedure, and residual stone burden < 0.0005 cm3 on postoperative NCCT at 3 months. Statistical analysis was performed using the STATA® version 13.1 software for regression models. A p value < .05 was considered statistically significant. A total of 100 patients met the inclusion criteria, requiring a median of 22.3 kJ/cm3 (13.4-36.0) and resulting in a SFS of 41% at 3 months. In a multivariate analysis, according to stone composition, predicted TLE is equal: for uric acid (UA), 11.17 × volume(cm3) + 0.17 × MSD(HU) + 7.48 kJ; for mixed stones, 11.17 × volume(cm3) + 0.17 × MSD(HU) + 6.26 kJ; for calcium oxalate monohydrate (CaOM) stones, 11.17 × volume(cm3) + 0.17 × MSD(HU) + 1.14 kJ; and for calcium phosphate (CaPh) stones 11.17 × volume(cm3) + 0.17 × MSD(HU) - 1.94 kJ. Predicted fragmented volume is equal to 0.93 × volume(cm3) cm3. The significant predictors for SFS were UA stones, the presence of multiple stones, and lower TLE. In clinical practice, our models for intrarenal low-power Ho:YAG laser lithotripsy indicate that larger, denser, and UA stones are associated to higher TLE, and that single and UA stones are more commonly associated to SFS. Since higher TLE means longer operative time, when adjusting for laser parameters, our prediction models may help urologists plan surgeries more precisely based on stone characteristics, ultimately optimizing patients' treatment.

Identifying and validating emotion regulation latent profiles and their relationship with affective variables.

OBJECTIVE: We investigated and validated the presence of emotion regulation profiles in an adult sample. METHOD: In a cross-sectional study, 1165 individuals completed the Emotion Regulation Questionnaire (ERQ), Difficulties in Emotion Regulation Scale (DERS), Positive and Negative Affect Scale (PANAS), and Following Affective States Test (FAST). Sample was divided into three to establish and validate emotion regulation profiles using a latent profile analysis. RESULTS: Sample 1 (n = 375) showed three different profiles: dysregulated, adapted, and unaware regulator. Sample 2 (n = 390) shows a consistent pattern with the same number of profiles that remained stable over time. In Sample 3 (n = 400), we validate and find that cognitive reappraisal and lack of awareness were essential to differentiating profiles. CONCLUSIONS: Three emotional regulation profiles differ due to the levels of positive/negative affect and the propensity to avoid/follow emotions, increasing the understanding of how different regulatory strategies interact and explain different outcomes with mental health.

Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations.

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (≤20%) of classic morphology, with anaplasia noted in four and tumor cell necrosis in three. The most frequent mutations detected were in DICER1 (14/21), TP53 (7/20), PI3K/AKT/mTOR pathway (7/20), and KRAS/NRAS (5/20). Copy-number alterations were present in 10/19 tumors. Overall, 8/14 DICER1-associated ucERMS showed concurrent loss of function and hotspot mutations in DICER1, which is a feature more likely to be seen in tumors associated with DICER1 syndrome. Germline data were available for two patients, both DICER1 wild type (one with concurrent loss of function and hotspot alterations). DICER1-associated ucERMS were more likely to show a classic histological appearance including heterologous elements than DICER1-independent tumors. No differences in survival were noted between the two groups, but both patients with extrauterine disease at diagnosis and two with recurrences died from disease. As no patients had a known personal or family history of DICER1 syndrome, we favor most DICER1-associated ucERMS to be sporadic.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Papillary Squamous Cell Carcinoma of the Uterine Cervix: Biopsy Samples Frequently Underrepresent the Presence of Stromal Invasion.

Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma, histologically characterized by thin or broad papillae lined by epithelium showing the features of high-grade squamous intraepithelial lesion. Given the exophytic nature of these neoplasms, the diagnosis, assessment and quantification of invasion may be difficult in small biopsies. The goal of this study was to determine the presence and extent of cervical stromal invasion by comparing biopsy samples with excisional specimens in a cohort of patients diagnosed with papillary squamous cell carcinoma. Cases were identified from the surgical pathology files between the years 2003 and 2018 and only cases in which the patients underwent an excisional procedure following the diagnostic biopsy were included. Eighteen cases were identified. Patients age ranged 21 to 72 yr (mean: 46.2 yr). Review of the initial, presurgical biopsies showed that 17/18 (94%) patients had no evidence of stromal invasion. In the surgical excision specimens (2 cone biopsies, 1 loop electrosurgical excision procedure, and 15 hysterectomies), 13 cases (76.5%) showed invasive squamous cell carcinoma. Tumor sizes ranged 1.0 to 6.1 cm; stromal invasion ranged in depth 0.2 to 2.2 cm (median: 1.2), and in horizontal length 0.3 to 4.0 cm (median: 2.01). Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of the cervix that may impose some diagnostic difficulties in small biopsies. Our findings demonstrated that the significant majority of cases might only show the presence of invasive cancer in excisional samples. Awareness of this data is important to guide proper management and avoid under-treatment.

Consumption of Ultra-Processed Foods in Brazilian Children: An Analysis of Regional Trends.

PURPOSE: Childhood obesity has become a concern for the Brazilian Unified Health System, which has recently started to investigate children's eating habits in basic health units. This study examined the trends and ultra-processed foods (UPF) consumption in Brazilian children. DESIGN AND METHODS: This repeated cross-sectional study included 492,630 children (2-9 years old), from different Brazilian regions, in the years 2015 and 2019. The children's food consumption was assessed by nurses using a nationally standardized instrument. Information was provided by the Food and Nutrition Surveillance System Brazilian. RESULTS: The UPF consumption in Brazilian children is generally high and was higher among children in the South and Midwest regions. The consumption of sweetened beverages was more prevalent among all the UPF assessed and continues to increase among children in the Northeast region. Declining trends in UPF consumption were observed in children from all regions, except for the Northeast region, whose trends increased in almost all evaluated foods. PRACTICE IMPLICATIONS: Nurses, especially, have a primary role in guiding the reduction of UPF consumption, as they are the first health professionals to have access to this information. Increasing trends in UPF consumption can be mitigated by the inclusion of nutritionists in basic health units. Brazilian children need to be assisted by public policies that promote food education.

Differentiated exophytic vulvar intraepithelial lesion: Clinicopathologic and molecular analysis documenting its relationship with verrucous carcinoma of the vulva.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words "verruciform" and "verrucous" were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.