Oral cancer screening outcomes in the Latin American region with special relevance to Brazil and Cuba: a systematic review.

BACKGROUND:  The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS:  An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS:  Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS:  Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.

A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis.

No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas.

Stereotactic radiosurgery for the treatment of a distant recurrence of ependymoma on the optic nerve: illustrative case.

BACKGROUND: Ependymomas rarely disseminate to other central nervous system areas distant from the original site. Stereotactic radiosurgery (SRS) provides high control rates for recurring ependymomas. The treatment of optic nerve tumors carries high morbidity, but SRS is an acceptable option to manage these cases to reduce risks. OBSERVATIONS: The authors report the case of a 31-year-old male with a cervical spinal ependymoma who had a disseminated pattern of recurrence including the optic nerve after initial resection of the cervical lesion. The optic nerve tumor was treated with SRS, and the authors discuss the technical aspects of the treatment and its outcomes. At the last follow-up, the optic nerve tumor was controlled with SRS, and visual function was preserved. LESSONS: High-grade ependymomas such as the one in the presented case can have unpredictable patterns of recurrence. SRS provides excellent control of the distant recurring ependymoma with a low complication profile given the location of the tumor in this case.

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.

Lower adiponectin is associated with higher anthropometry and insulin resistance but not with low cardiorespiratory fitness in adolescents.

PURPOSE: The aim of this study was to analyze the relationship between adiposity, cardiometabolic risk and cardiorespiratory fitness (CRF) according to different groups of adiponectin concentration. METHODS: 255 adolescents of both sexes, aged 11-17 years old, participated. Anthropometric and biochemical parameters such as body mass, height, abdominal circumference (AC), waist circumference (WC), fat mass, fat-free mass, total cholesterol (TC), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), triglycerides (TG), glucose, insulin, adiponectin, blood pressure, peak oxygen consumption (VO2peak) were measured. Body mass index (BMI), z-score BMI (BMI-z), triponderal mass index (TMI), waist-to-height ratio (WHtR), homeostasis model to assessment insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were calculated. Adiponectin was categorized: low adiponectin concentration (LAC ≤ 5.18 µg/mL-1), intermediate (IAC = 5.18 and 7.63 µg/mL-1) and high (HAC ≥ 7.63 µg/ml-1). RESULTS: LAC showed higher BMI, BMI-z and TMI than the other groups (p < 0.05) and higher AC, WC and WHtR that the HAC (p < 0.05). IAC showed lower values of TC, LDL-c and TG, and the LAC presented the highest values of insulin, HOMA-IR and QUICKI (p < 0.05) to the IAC and HAC. HAC presented the lower VO2peak than the other groups (p < 0.01). BMI, TMI, glucose, insulin, HOMA-IR showed inverse, and QUICKI a direct and weak correlation with adiponectin (p < 0.05). No significant association was found between adiponectin and VO2peak (p > 0.05). CONCLUSION: The LAC group had higher means in the anthropometric variables and the worst results related to insulin resistance and sensitivity. Thus, adiponectin may play an important role in obesity and reduced concentration may be a factor in the development of obesity-associated morbidities.

Systemic therapies for salivary gland carcinomas: an overview of published clinical trials.

BACKGROUND: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. MATERIAL AND METHODS: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. RESULTS: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. CONCLUSIONS: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.

Sustainable trehalose lipid production by Rhodotorula sp.: a promising bio-based alternative.

Global environmental concerns drive research toward the development of new eco-friendly compounds to replace pollutant chemicals. This study focuses on optimizing the production of trehalose lipids (TLs), which are glycolipid biosurfactants (BS) with various applications like antimicrobial or surface tension reduction. New microorganism sources, growth conditions, medium composition, purification conditions, and physicochemical properties of TLs are studied. Addressing a microscale approach, TLs production was successfully achieved using Rhodotorula sp. and Rhodococcus erythropolis to compare, with different media compositions including glucose-based and salt media supplemented with glycerol, glucose, n-hexadecane, n-dodecane. Liquid-liquid extraction using ethyl acetate and methanol was employed for compound extraction, followed by characterization using analytical methods such as Thin layer chromatography (TLC), High performance liquid chromatography (HPLC), and UHPLC. The produced TLs exhibited a minimum surface tension of 47 mN/m and a critical micellar concentration of 4.4 mg/mL. This study also identified Rhodotorula sp. as a new sustainable producer of TLs with improved productivity.

Sensitivity, Specificity, Positive and Negative Predictive Values of a Postal Mail Self-Screening Tool for Frailty in French Older Adults.

BACKGROUND: Frailty has emerged as one of the major risk factors of loss of autonomy and it can be reverted through early and appropriate interventions. A wide range of available frailty screening tools are administered, mainly in clinical settings. However, few frailty instruments are self-administered. OBJECTIVES: The aim of this study was to determine the diagnostic test accuracy of a modified self-administered questionnaire derived from the Study of Osteoporotic Fractures (SOF) index against the Fried frailty phenotype in identifying frailty. DESIGN: Observational, multicenter, diagnostic test accuracy study. PARTICIPANTS: Participants aged 70 and over, living at home or in community-dwelling (n=5134) in two centers in France were contacted. MEASUREMENTS: Participants were mailed self-administered questionnaires derived from the SOF index. Responders who accepted the home evaluation were assessed by trained nurses, blinded to results of the questionnaire, using the Fried frailty phenotype as the reference method. RESULTS: The questionnaire was sent to 5134 participants, of which 1878 (36.6%) met inclusion criteria and returned the questionnaire. Fried frailty assessments were obtained in 691 (35.4%) participants. A total of 639 subjects had a complete evaluation on both the self-administered questionnaire and the Fried phenotype. Mean age was 78.9 (standard deviation [SD]: 5.95) years and 359 (56.2%) participants were women. According to the questionnaire, 159 (24.9%) subjects were considered frail, 172 (26.9%) pre-frail, and 308 (48.2) robust. With the home evaluation, Fried frailty phenotype results were respectively, 114 (17.8%), 295 (46.2%) and 230 (36%). The self-administered questionnaire presented a sensitivity of 66.6% (95% CI: 57.2-75.2) and a specificity of 84.2% (95% CI: 80.8-87.2). CONCLUSIONS: A self-administered questionnaire can be used in elders and represents an opportunity for empowering them in the management of their health in the context of frailty.

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. MATERIAL AND METHODS: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. RESULTS: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. CONCLUSIONS: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC.

Oral amyloidosis: an update.

BACKGROUND: Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors. MATERIAL AND METHODS: Electronic searches were undertaken in five databases supplemented by manual scrutiny. RESULTS: A total of 111 studies were included with 158 individuals. CONCLUSIONS: The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.

Attention deficit hyperactivity disorder and restless leg syndrome across the lifespan: A systematic review and meta-analysis.

This systematic review aims to assess the association between attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for original articles that reported prevalence data on ADHD and RLS until January 24th, 2023. Two independent reviewers evaluated the quality of the articles using the National Institutes of Health assessment tool. Among the 208 articles identified between 1996 and 2022, 29 were included. In large general population studies, 2.6-15.3% of participants met the RLS criteria, of which 3.2-17.4% presented with ADHD. In the ADHD group, RLS symptoms ranged from 11 to 42.9% in children and 20-33.0% in adults. This suggests a strong co-occurrence between RLS and ADHD. A common characteristic of these conditions is sleep fragmentation, as discussed in the reviewed papers. Although large-scale studies with comparable diagnostic criteria across the lifespan are required, our findings may advocate a possible common physiological pathway, including sleep fragmentation and dopaminergic system impairment.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Facing the challenges of air quality and health in a future climate: The Aveiro Region case study.

Air pollution and climate change are the most important environmental issues for European citizens. Despite the air quality improvements achieved in recent years, with most pollutants' concentrations below the European Union legislated values, it is necessary to understand whether this will continue in the future due to expected climate changes impacts. In this context, this work tries to answer two main questions: (i) What is the relative contribution of emission source regions/activities to air quality, now and in the future, considering a climate change scenario?; and (ii) What additional policies are needed to support win-win strategies for air quality and climate mitigation and/or adaptation, at urban scale? For that, a climate and air quality modelling system, with source apportionment tools, was applied to the Aveiro Region, in Portugal. Main results show that in the future, due to the implementation of carbon neutrality measures, air quality in the Aveiro Region may improve, with reduction up to 4 µg.m-3 for particulate matter (PM) concentrations and 22 µg.m-3 for nitrogen dioxide (NO2), and consequently, the premature deaths due to air pollution exposure will also decrease. The expected air quality improvement will ensure that, in the future, the limit values of the European Union (EU) Air Quality Directive will not be exceeded, but the same will not happen if the proposed revision of the EU Air Quality Directive is approved. Results also shown that, in the future, industrial sector will be the one with higher relative contribution for PM concentrations and the second one for NO2. For that sector, additional emission abatement measures were tested, showing that, in the future, it is possible to comply with all the new limit values proposed by the EU.

The impact of FSH stimulation and age on the ovarian and uterine traits and histomorphometry of prepubertal gilts.

This study investigated the effect of age and follicle stimulating hormone (FSH) treatment on the estradiol (E2) plasma concentration, ovarian follicle development, endometrial histomorphometry, and ultrasonographic parameters of the ovaries and uterus in prepubertal gilts. Thirty-five prepubertal gilts were grouped according to age (140 or 160 d), and within each age, gilts were allotted to receive 100 mg of FSH (treated; G140 + FSH [n = 10] and G160 + FSH [n = 7]) or saline solution (control; G140 + control [n = 10] and G160 + control [n = 8]). The total dose of FSH was divided into 6 similar doses administered every 8 h (days 0-2). Before and after FSH treatment, blood sample was collected, and transabdominal scanning of the ovaries and uterus was performed. Twenty-four hours after the last FSH injection, the gilts were slaughtered and their ovaries and uterus were processed for histological and histomorphometric analysis. The histomorphometric parameters of the uterus differed (P < 0.05) between prepubertal gilts at 160 d and 140 d of age. Moreover, changes (P < 0.05) in uterine and ovarian ultrasound images occurred between 140 and 160 d of age. Age and FSH treatment did not affect (P > 0.05) E2 plasma concentrations. Follicle stimulating hormone treatment did not affect (P > 0.05) the early stage of folliculogenesis in the prepubertal gilts; however, the number of early atretic follicles decreased (P < 0.05) after the FSH treatment. Follicle stimulating hormone administration increased (P < 0.05) the number of medium follicles and decreased (P < 0.05) the number of small follicles in 140 and 160 d old gilts. In the endometrium, luminal/glandular epithelium height and glandular diameter increased (P < 0.05) after FSH treatment. Thus, injections of 100 mg of FSH stimulate the endometrium epithelium and induce follicular growth to a medium follicle size without affecting the preantral stages in prepubertal gilts; also, the uterine macroscopic morphometry does not change from 140 to 160 d of age.

Co-occurrence of Functional Gonadotroph Adenoma and Lactotroph Adenoma: A Case Report and Literature Review.

Background/Objective: Functional gonadotroph adenomas (FGAs) are adenomas producing active gonadotropins, follicle-stimulating hormone or luteinizing hormone. Double pituitary adenomas are 2 distinct adenomas occurring in an individual. This report aimed to present an extremely rare case of an FGA, itself an uncommon disorder, co-occurring with a lactotroph adenoma. Case Report: A 33-year-old woman presented with menorrhagia and was found to have ovarian enlargement, large uterine leiomyomas, and bitemporal hemianopsia. Initially, the levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin were 73.3 mIU/mL (midcycle peak, 2.3-20.9 mIU/L), 3.74 mIU/L (midcycle peak, 8.7-76.3 mIU/L), 1071 pg/mL (midcycle peak 38-649 pg/mL), and 402 ng/mL (2-30 ng/mL), respectively. Pituitary magnetic resonance imaging demonstrated a single sellar mass (2.0 × 2.2 cm). Two months of cabergoline did not reverse visual field deficits; therefore, transsphenoidal resection was performed. Diagnosis of 2 separate adenomas, a gonadotroph and lactotroph adenoma, was confirmed on pathology. Discussion: In this case, gonadotropins did not suppress in response to hyperprolactinemia. Although marked hyperprolactinemia has been associated with functional and clinically silent gonadotroph adenomas in prior cases, this is the first case to confirm an FGA co-occurring with a lactotroph adenoma. Conclusion: In patients who present with elevated gonadotropin levels despite hyperprolactinemia, we suggest considering FGA. Further research is needed to clarify whether there is underdiagnosis of lactotroph adenomas co-occurring with gonadotroph adenomas.