Dynamics and features of transmission clusters of HIV-1 subtypes in the state of São Paulo, Brazil.

Background: Molecular epidemiology techniques allow us to track the HIV-1 transmission dynamics. Herein, we combined genetic, clinical and epidemiological data collected during routine clinical treatment to evaluate the dynamics and characteristics of transmission clusters of the most prevalent HIV-1 subtypes in the state of São Paulo, Brazil. Methods: This was a cross-sectional study conducted with 2,518 persons living with HIV (PLWH) from 53 cities in São Paulo state between Jan 2004 to Feb 2015. The phylogenetic tree of protease/reverse transcriptase (PR/RT) regions was reconstructed by PhyML and ClusterPicker used to infer the transmission clusters based on Shimodaira-Hasegawa (SH) greater than 90% (phylogenetic support) and genetic distance less than 6%. Results: Of a total of 2,518 sequences, 2,260 were pure subtypes at the PR/RT region, being B (88%), F1 (8.1%), and C (4%). About 21.2% were naïve with a transmitted drug resistance (TDR) rate of 11.8%. A total of 414 (18.3%) of the sequences clustered. These clusters were less evident in subtype B (17.7%) and F1 (15.1%) than in subtype C (40.2%). Clustered sequences were from PLWH at least 5 years younger than non-clustered among subtypes B (p < 0.001) and C (p = 0.037). Men who have sex with men (MSM) predominated the cluster in subtype B (51%), C (85.7%), and F1 (63.6%; p < 0.05). The TDR rate in clustered patients was 15.4, 13.6, and 3.1% for subtypes B, F1, and C, respectively. Most of the infections in subtypes B (80%), C (64%), and F1 (59%) occurred within the state of São Paulo. The metropolitan area of São Paulo presented a high level of endogenous clustering for subtypes B and C. The São Paulo city had 46% endogenous clusters of subtype C. Conclusion: Our findings showed that MSM, antiretroviral therapy in Treatment-Naive (ART-naïve) patients, and HIV1-C, played an important role in the HIV epidemic in the São Paulo state. Further studies in transmission clusters are needed to guide the prevention intervention.

The meaning in loss protocol: A clinical trial of online grief therapy.

For a minority of the bereaved, the loss of a significant other can trigger an overwhelming emotional reaction and impaired functioning across life domains, known as prolonged grief disorder (PGD). Hence, ongoing efforts have been made to refine existing treatments to increase their efficacy and to accommodate the idiosyncrasies of grief reactions. This study presents the results of an open clinical trial of the feasibility and effectiveness of the Meaning in Loss (MIL) protocol in an online format. The brief intervention of 12 to 16 sessions combines constructivist and narrative strategies to explore and work through impediments to meaning reconstruction in loss. The sample included 25 participants diagnosed with PGD who were treated by six therapists. Baseline and post-therapy comparisons showed a significant improvement in all clinical measures (grief symptomatology, depression and general distress) and an increase of meaning making regarding the loss. Meaning making was found to be a prospective mediator of symptomatic improvement in grief across the course of therapy. These findings suggest the effectiveness of the MIL protocol in decreasing grief specific and associated symptomatology and argue for the relevance of further controlled evaluations of its efficacy. Moreover, results confirm previous findings that meaning making is a relevant factor in the evolution of grief reactions, including in the context of psychotherapy.

Lenalidomide or Thalidomide for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma? An Overview of Systematic Reviews.

OBJECTIVES: To present an overview of evidence of efficacy, safety, and health-related quality of life of lenalidomide or thalidomide for transplant-ineligible multiple myeloma. METHODS: A literature search was performed in 5 databases until July 2022. We included systematic reviews with network meta-analyses of randomized controlled trials on the use of lenalidomide compared with thalidomide for transplant-ineligible multiple myeloma. The A Measurement Tool to Assess Systematic Reviews 2 was used to appraise the quality of included reviews. The results were focused on the lenalidomide + dexamethasone until disease progression (RDc) versus thalidomide + dexamethasone until disease progression (TDc) and induction with melphalan + prednisone + lenalidomide, followed by maintenance with lenalidomide (MPR-R) versus induction with melphalan + prednisone + thalidomide, followed by maintenance with thalidomide (MPT-T) regimens. RESULTS: Nine studies were included. Only 1 study did not show any weakness in critical domains of A Measurement Tool to Assess Systematic Reviews 2. For overall survival, RDc proved to be superior to TDc; however, no study showed significant difference between MPR-R and MPT-T. For progression-free survival, 2 of 3 studies showed that RDc is better than TDc; however, no difference between MPR-R and MPT-T was found. Regarding safety, these lenalidomide-based regimens had a lower risk for neurologic adverse events, with an increased risk of hematologic adverse events. No health-related quality of life meta-analyses were found. CONCLUSIONS: These findings suggest that, in terms of efficacy and safety, lenalidomide-based regimen is a good option for treatment of transplant-ineligible multiple myeloma in the public health system of Brazil, especially for those patients who develop severe neuropathy with thalidomide.

A Microcost Analysis of the Use of Personal Protective Equipment During and Before the COVID-19 Pandemic From a Hospital Perspective.

OBJECTIVES: To calculate the direct cost of personal protective equipment (PPE) used during the COVID-19 pandemic from the perspective of a Brazilian tertiary public hospital. METHODS: We evaluated the cost of PPE during the pandemic to the cost before (2021 vs 2019, respectively) using the microcosting method. Cost estimates were converted into US dollars in 2023, taking inflation into account and using purchasing power parity conversion rates. Our expenses included gloves, disposable gowns, head coverings, masks, N95 respirators, and eye protection. The number of PPE used was determined by the hospital's usual protocol, the total number of hospitalized patients, and the number of days of hospitalization. We used the following variables for uncertainty analysis: PPE adherence, an interquartile range of median length of hospitalization, and variance in the cost of each PPE. RESULTS: In 2021, 26 618 individuals were hospitalized compared with 31 948 in 2019. The median length of stay was 6 and 4 days, respectively. The total and per-patient direct cost of PPE were projected to be 2 939 935.47 US dollar (USD) and 110.45 USD, respectively, during the pandemic, and 1 570 124.08 USD and 49.15 USD, respectively, before the pandemic. The individual cost of PPE was the most influential cost variable. CONCLUSIONS: According to the hospital's perspective, the total estimated direct cost of PPE during the COVID-19 pandemic was nearly twice as high as the previous year. This difference might be explained by the 3-fold increase in PPE in the treatment of patients with COVID-19 compared with patients without isolation precautions.

Insights Into Pediatric Asthma: A Population Study From Alto Minho Health Center.

Background Asthma represents one of the most common diseases in childhood, with a prevalence ranging between 9% and 13% in Portugal. Therefore, it holds significant importance in pediatric health. While existing studies have shed light on asthma in the Portuguese population, they have predominantly concentrated on urban centers, with the population of Alto Minho remaining underrepresented in the literature. This study aims to understand the main factors of exposure, exacerbation, and the most prevalent allergens in a pediatric sample from the Alto Minho Local Health Unit, Portugal. Methodology A retrospective cohort study was conducted among 239 pediatric asthma patients aged between five and 18 years at the Alto Minho Health Center. Data on demographics, clinical information, family history, environmental exposures, exacerbating factors, and prick test results were analyzed. Results Of the 239 patients, 64.44% were male and 35.56% were female. The majority of the sample exhibited a normal body mass index (82.17%) and a family history of atopy (66.67%). Noteworthy patterns emerged in comorbidities, notably an increased association with allergic rhinitis, the most frequent concomitant atopic pathology (79.50%), followed by atopic dermatitis (27.61%) and food allergy (10.88%). Sensitization to dust mites, particularly Dermatophagoides pteronyssinus, was widespread among the participants. Environmental exposures were marked by significant factors such as proximity to plants and trees, soft toys, and living in rural areas. Exacerbating factors included common triggers such as exercise, seasonal variations, and even laughter. Statistically significant associations were found between atopic comorbidities, exacerbation factors, exposure factors, and prick test results. Conclusions Our findings align with global trends, emphasizing the prevalence of atopic pathologies in pediatric asthma. Sensitization patterns and environmental exposures are indicative of regional influences. Study limitations include sample size and data standardization issues. Despite these limitations, the study significantly contributes to understanding pediatric asthma in Alto Minho, offering valuable insights for prompt diagnosis and targeted treatments.

Potential of the Blue Calm® food supplement in the treatment of alcohol withdrawal-induced anxiety in adult zebrafish (Danio rerio).

Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents. In this context, this study aimed to evaluate the potential of the BC in the treatment alcohol withdrawal-induced anxiety in adult zebrafish (aZF). Initially, BC was submitted to antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl radical. Subsequently, the aZF (n = 6/group) were treated with BC (0.1 or 1 or 10 mg/mL; 20 µL; p.o.), and the sedative effect and acute toxicity (96 h) were evaluated. Then, the anxiolytic-like effect and the possible GABAergic mechanism were analyzed through the Light & Dark Test. Finally, BC action was evaluated for treating alcohol withdrawal-induced anxiety in aZF. Molecular docking was performed to evaluate the interaction of the major chemical constituents of BC with the GABAA receptor. BC showed antioxidant potential, a sedative effect, was not toxic, and all doses of BC had an anxiolytic-like effect and showed potential for the treatment of alcohol withdrawal-induced anxiety in aZF. In addition to the anxiolytic action, the main chemical constituents of BC were confirmed in the molecular docking, thus suggesting that BC is an anxiolytic that modulates the GABAergic system and has pharmacological potential for the treatment of alcohol withdrawal-induced anxiety.

Serological screening in a large-scale municipal survey in Cascais, Portugal, during the first waves of the COVID-19 pandemic: lessons for future pandemic preparedness efforts.

Background: Serological surveys for SARS-CoV-2 were used early in the COVID-19 pandemic to assess epidemiological scenarios. In the municipality of Cascais (Portugal), serological testing combined with a comprehensive socio-demographic, clinical and behavioral questionnaire was offered to residents between May 2020 and beginning of 2021. In this study, we analyze the factors associated with adherence to this municipal initiative, as well as the sociodemographic profile and chronic diseases clinical correlates associated to seropositivity. We aim to contribute with relevant information for future pandemic preparedness efforts. Methods: This was a cross-sectional study with non-probabilistic sampling. Citizens residing in Cascais Municipality went voluntarily to blood collection centers to participate in the serological survey. The proportion of participants, stratified by socio-demographic variables, was compared to the census proportions to identify the groups with lower levels of adherence to the survey. Univariate and multivariate logistic regression were used to identify socio-demographic, clinical and behavioral factors associated with seropositivity. Results: From May 2020 to February 2021, 19,608 participants (9.2% of the residents of Cascais) were included in the study. Based on the comparison to census data, groups with lower adherence to this survey were men, the youngest and the oldest age groups, individuals with lower levels of education and unemployed/inactive. Significant predictors of a reactive (positive) serological test were younger age, being employed or a student, and living in larger households. Individuals with chronic diseases generally showed lower seroprevalence. Conclusion: The groups with low adherence to this voluntary study, as well as the socio-economic contexts identified as more at risk of viral transmission, may be targeted in future pandemic situations. We also found that the individuals with chronic diseases, perceiving higher risk of serious illness, adopted protective behaviors that limited infection rates, revealing that health education on preventive measures was effective for these patients.

Chest Computed Tomography for Lymphoma Staging: A Wasted Opportunity for Cardiovascular Risk Stratification?

AIM: Patients with a lymphoma diagnosis undergo non-gated chest computed tomography (CT) scans as part of cancer diagnosis or staging. Although coronary artery calcification (CAC) is traditionally evaluated on dedicated cardiac CT, CAC can also be detected on standard chest CT. This exploratory study aimed to determine the prognostic value of CAC detected on non-gated chest CT and to report its use on clinical practice. METHOD: Consecutive patients with a lymphoma diagnosis who performed non-contrasted non-gated chest CT for cancer diagnosis or staging were included and retrospectively evaluated. Coronary artery calcification was evaluated by quantitative (Agatston score) and qualitative (visual) assessment. RESULTS: Fifty-seven patients were included in this study (mean age 61±15 years; 58% male). Coronary artery calcification was identified in 22 patients (39%), most of them with multi-vessel involvement. Coronary artery calcification was qualitatively classified as mild, moderate and severe in 11%, 19% and 9% patients, respectively. This study suggested that moderate or severe CAC was an independent predictor of all-cause mortality (odds ratio 3, 95% confidence interval 2-11; p=0.04) after adjusting for cardiovascular risk factors and lymphoma staging. Regarding quantitative evaluation, a higher CAC score was also associated with higher mortality. While significant CAC was identified in 22 patients, it was only reported in four patients. CONCLUSIONS: The preliminary findings of this hypothesis-generating study support the investigation of CAC identified by chest CT for diagnosis/staging of cancer as a risk modifier in the global risk assessment of patients with lymphoma. The unrecognition and underreporting of this finding may represent a wasted opportunity to detect subclinical coronary atherosclerosis in these patients and may help in guiding preventive cardiology care.

Chemical Characterization, Phenolic Compounds Quantification, and Assessment of Antioxidant and Anti-Acetylcholinesterase Activities of Byrsonima sericea DC fruits.

Byrsonima sericea is a species native to Brazil that is widely used in traditional medicine. The seed ethanol extract (SEE) had the highest content of total phenols (179.35 mg GAE g-1 extract) and flavonoids (10.42 mg QE g-1 extract) and was the most active in relation to antioxidant activity (DPPH: IC50 =4.25 µg mL-1 and ABTS: IC50 =4.82 µg mL-1 ). The peel/pulp ethanol extract (PEE) had the best anticholinesterase activity (IC50 =6.02 µg mL-1 ). Chromatographic investigation identified gallic acid, isoquercitrin, quercetin and amentoflavone in SEE, and gallic acid, isoquercitrin, quercetin and rutin in PEE. Six fatty acid methyl esters and seven triterpenes were identified, highlighting oleic acid in the seed hexane extract (61.85 %) and in the peel/pulp hexane extract (52.61 %), and betulin in the peel/pulp hexane extract (5.25 %). The substances and biological activities identified in B. sericea characterize this fruit as a functional food for future studies.

SARS-CoV-2 trends in Italy, Germany and Portugal and school opening during the period of Omicron variant dominance: A quasi experimental study in the EuCARE project.

OBJECTIVES: We investigated the impact of school reopening on SARS-CoV-2 transmission in Italy, Germany, and Portugal in autumn 2022 when the Omicron variant was prevalent. METHODS: A prospective international study was conducted using the case reproduction number (Rc) calculated with the time parametrization of Omicron. For Germany and Italy, staggered difference-in-differences analysis was employed to explore the causal relationship between school reopening and Rc changes, accounting for varying reopening dates. In Portugal, interrupted time series analysis was used due to simultaneous school reopenings. Multivariable models were adopted to adjust for confounders. RESULTS: In Italy and Germany, post-reopening Rc estimates were significantly lower compared to those from regions/states that had not yet reopened at the same time points, both in the student population (overall average treatment effect for the treated subpopulation [O-ATT]: -0.80 [95% CI: -0.94;-0.66] for Italy; O-ATT-0.30 [95% CI: -0.36;-0.23] for Germany) and the adult population (O-ATT: -0.04 [95% CI: -0.07;-0.01] for Italy; O-ATT: -0.07 [95% CI: -0.11;-0.03] for Germany). In Portugal, there was a significant decreasing trend in Rc following school reopenings compared to the pre-reopening period (sustained effect: -0.03 [95% CI: -0.04; -0.03] in students; -0.02 [95% CI: -0.03; -0.02] in adults). CONCLUSIONS: We found no evidence of a causal relationship between school reopenings in autumn 2022 and Omicron SARS-CoV-2 transmission.

Manejo familiar da criança que espera por um transplante de órgãos / Family management of child waiting for a organ transplant / Manejo familiar del niño en espera de un trasplante de órganos

Objetivo: conhecer a experiência de manejo familiar da criança à espera de um transplante de órgãos sólidos de acordo com o Modelo de estilos de manejo familiar. Método: foi realizado um estudo qualitativo que utilizou o modelo supracitado como referencial teórico. Foram aplicadas entrevistas, de forma remota, a nove familiares de crianças que aguardavam por um transplante de órgãos. Os dados foram analisados através do modelo híbrido de análise temática. Resultados: as famílias definem que essa fase oscila entre o medo do transplante, da rejeição do órgão e possibilidade de morte em fila de espera, e a esperança na melhora do quadro clínico. Considerações finais: identificar as necessidades da família que aguarda por um transplante possibilita ao profissional de saúde implementar intervenções

Objective: to understand the family management experience of children waiting for a solid organ transplant in accordance with the Family Management Styles Model. Method: a qualitative study was carried out using the aforementioned model as a theoretical framework. Interviews were conducted remotely with nine family members of children waiting for an organ transplant. Data were analyzed using the hybrid thematic analysis model. Results: families define that this phase oscillates between fear of transplantation, organ rejection and the possibility of death on the waiting list, and hope for an improvement in the clinical condition. Final considerations: identifying the needs of the family waiting for a transplant allows the health professional to implement interventions

Objetivos:comprender la experiencia de gestión familiar de niños en espera de trasplante de órgano sólido de acuerdo con el Modelo de Estilos de Gestión Familiar. Método: se realizó un estudio cualitativo utilizando como marco teórico el modelo antes mencionado. Las entrevistas se realizaron de forma remota con nueve familiares de niños que esperaban un trasplante de órgano. Los datos se analizaron utilizando el modelo de análisis temático híbrido. Resultados: las familias definen que esta fase oscila entre el miedo al trasplante, el rechazo del órgano y la posibilidad de muerte en lista de espera, y la esperanza de mejora del cuadro clínico. Consideraciones finales: identificar las necesidades de la familia en espera de un trasplante permite al profesional de la salud implementar intervenciones

Manejo familiar da criança que espera por um transplante de órgãos / Family management of child waiting for a organ transplant / Manejo familiar del niño en espera de un trasplante de órganos

Objetivo: conhecer a experiência de manejo familiar da criança à espera de um transplante de órgãos sólidos de acordo com o Modelo de estilos de manejo familiar. Método: foi realizado um estudo qualitativo que utilizou o modelo supracitado como referencial teórico. Foram aplicadas entrevistas, de forma remota, a nove familiares de crianças que aguardavam por um transplante de órgãos. Os dados foram analisados através do modelo híbrido de análise temática. Resultados: as famílias definem que essa fase oscila entre o medo do transplante, da rejeição do órgão e possibilidade de morte em fila de espera, e a esperança na melhora do quadro clínico. Considerações finais: identificar as necessidades da família que aguarda por um transplante possibilita ao profissional de saúde implementar intervenções

Objective: to understand the family management experience of children waiting for a solid organ transplant in accordance with the Family Management Styles Model. Method: a qualitative study was carried out using the aforementioned model as a theoretical framework. Interviews were conducted remotely with nine family members of children waiting for an organ transplant. Data were analyzed using the hybrid thematic analysis model. Results: families define that this phase oscillates between fear of transplantation, organ rejection and the possibility of death on the waiting list, and hope for an improvement in the clinical condition. Final considerations: identifying the needs of the family waiting for a transplant allows the health professional to implement interventions

Objetivos:comprender la experiencia de gestión familiar de niños en espera de trasplante de órgano sólido de acuerdo con el Modelo de Estilos de Gestión Familiar. Método: se realizó un estudio cualitativo utilizando como marco teórico el modelo antes mencionado. Las entrevistas se realizaron de forma remota con nueve familiares de niños que esperaban un trasplante de órgano. Los datos se analizaron utilizando el modelo de análisis temático híbrido. Resultados: las familias definen que esta fase oscila entre el miedo al trasplante, el rechazo del órgano y la posibilidad de muerte en lista de espera, y la esperanza de mejora del cuadro clínico. Consideraciones finales: identificar las necesidades de la familia en espera de un trasplante permite al profesional de la salud implementar intervenciones

Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.

Effectiveness of the peripherally inserted central catheter for hematopoietic stem cell transplantation: a systematic review protocol

OBJECTIVE: to assess the effectiveness and safety of the peripherally inserted central catheter for hematopoietic stem cell transplantation. METHOD: this review will follow the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the search steps will be presented through the flow diagram. The search strategy aims to locate both published and unpublished studies. No time or language restrictions will be applied. The review will consider experimental and observational studies that include adult and pediatric patients undergoing hematopoietic stem cell transplantation. Patients using peripherally inserted central catheters will be compared with those using other central catheters.

Antioxidant and anticholinesterase activities of amentoflavone isolated from Ouratea fieldingiana (Gardner) Engl. through in vitro and chemical-quantum studies.

Ouratea fieldingiana, popularly known as batiputá, is a tree species easily found in the coastal part of northeastern Brazil. Its leaves are rich in biflavonoids, its major compound being amentoflavone. Biflavonoids are well studied due to their high antioxidant capacity. Alzheimer's disease (AD) is a disease characterized by the progressive loss of neurons. Currently, the pharmacological treatment of AD has four drugs: donepezil, galantamine, rivastigmine and memantine. Where these drugs, with the exception of memantine, are inhibitors of acetylcholinesterase, thus inhibiting the enzyme that destroys acetylcholine, thus increasing the availability of this neurotransmitter. This article aims to determine in vitro and in silico the antioxidant and anticholinesterase action of amentoflavone isolated from the leaves of Ouratea fieldingiana. The antioxidant capacity of amentoflavone was evaluated using the DPPH* free radical scavenging method, with an IC50 of 5.73 ± 0.08 µg/mL. The antiradical properties of the molecule were also studied in silico through several HAT, SET-PT and SPLET mechanisms via DFT M06-2X/6-311++G(d,p). It was found that in the hydrogen atom transfer mechanism (HAT) the best trend was obtained as an anti-radical mechanism. Amentoflavone has the ability to inhibit acetylcholinesterase when tested in vitro, having an IC50 of 8.68 ± 0.73 µg/mL, corroborating its effect in the in silico test, presenting four strong covalent hydrogen bonds for having a bond length up to 2.5 Å. Thus, amentoflavone is an important target for further testing against Alzheimer's disease. Communicated by Ramaswamy H. Sarma.

Prevalence of vitamin A deficiency in women of childbearing age in Brazil: a systematic review and meta-analysis.

Vitamin A is an essential micronutrient, especially during pregnancy. We aimed to assess the prevalence of vitamin A deficiency in Brazilian women of childbearing age. We conducted a systematic review with meta-analysis of studies that assessed vitamin A deficiency in women of childbearing age following the registered protocol (CRD42020171856). Independent peer researchers selected the studies retrieved from MEDLINE, Embase, Scopus and other sources. Data from the eligible studies were extracted in pairs and assessed for methodological quality. The prevalence of vitamin A deficiency (< 0·70 µmol/l or <0·20 µg/dl) and 95 % CI was combined by meta-analysis, and heterogeneity was estimated by I2. Out of 3610 screened records, thirty-two studies were included, which assessed 12 577 women from 1965 to 2017, mostly in maternity hospitals. Main limitations of the studies were in sample frame (30/32) and sampling method (29/32). Deficiency occurred in 13 % (95 % CI 9·4, 17·2 %; I² = 97 %) of all women and was higher in pregnant women (16·1 %; 95 % CI 5·6, 30·6 %; I² = 98 %) than non-pregnant women (12·3 %; 95 % CI 8·4, 16·8 %; I² = 96 %). The prevalence increased according to the decade, from 9·5 % (95 % CI 1·9­21·6 %; I² = 98 %) up to 1990, 10·8 % (95 % CI 7·9, 14·2 %; I² = 86 %) in the 2000s and 17·8 % (95 % CI 8·7, 29·0 %; I² = 98 %) in the 2010s. Over 10 % of Brazilian women in childbearing age were deficient in vitamin A. Higher prevalence was observed in pregnant women, and deficiency seemed to be increasing over the decades. Low representativeness of the studies, mainly based on convenience sampling that included pregnant, postpartum, lactating and non-pregnant women, as well as high heterogeneity, limits the findings.

A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma.

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.

A New Cytology Staining Method: A Fast Approach for Rapid On-Site Evaluation on Thyroid Fine-Needle Aspiration Cytology.

INTRODUCTION: Thyroid fine-needle aspiration (FNA) is a well-established technique in the cytology literature. Through the introduction of rapid stains in cytology practice, the ever-increasing utility of rapid on-site evaluation (ROSE) has strengthened the place of FNA as a primary diagnostic method in patient management. There are few stain variants available in the market for ROSE, namely Diff-Quik (DQ), Toluidine blue, and ultrafast Papanicolaou stains. Recently, our group developed a new staining variant labeled as original "BlueStain®" technique that was not previously tested in this context. METHODS: 40 FNA thyroid cases were studied. At least two slides were prepared from each patient: one stained by DQ and the other by BlueStain®. Simultaneously, a ROSE diagnosis was performed as the two staining methods were compared, evaluating the parameters of background, cellularity, details of colloid presence, cell morphology, nuclear details, cytoplasmic details, and overall staining, scored on a scale from 1 to 3, representing poor, average, and good, respectively. RESULTS: The quality index was slightly better for BlueStain® (53% vs. 47%) but not significantly different between the two stains. BlueStain® provides better details in both the presence and type of colloid as well as nuclear details, which are regarded as very important for diagnosis in thyroid cytology. There were eight cases with discordant diagnosis when compared between two stains from the same patient. In five cases of indeterminate cases, BlueStain® allows to bring them to the benign category, probably because this staining method allows a clear observation of the colloid in the background of the smears. However, since we are observing two different slides, we cannot rule out that these differences are a question of sample collecting and/or smearing. CONCLUSIONS: Our data demonstrates that BlueStain® is suitable to provide good-quality slides for primary assessments of thyroid aspirates studied by ROSE. In fact, in some aspects, this new staining method shows better preservation of colloid and cell details, revealing itself as an alternative to the DQ stain variant, upholding performance level while being 10 times cheaper and simpler because it requires just one step of staining.

Acute kidney injury in critically ill children: predictive value of renal arterial Doppler assessment.

BACKGROUND: Renal resistive index (RRI) and renal pulsatility index (RPI) are Doppler-based variables proposed to assess renal perfusion at the bedside in critically ill patients. This study aimed to assess the accuracy of such variables to predict acute kidney injury (AKI) in mechanically ventilated children. METHODS: Consecutive children aged <14 years underwent kidney Doppler ultrasound examination within 24 h of invasive mechanical ventilation. Renal resistive index (RRI) and renal pulsatility index (RPI) were measured. The primary outcome was severe AKI (KDIGO stage 2 or 3) on day 3. RESULTS: On day 3, 22 patients were classified as having AKI, of which 12 were severe. RRI could effectively predict severe AKI (area under the ROC curve [AUC] = 0.94) as well as RPI (AUC = 0.86). The optimal cut-off for RRI was 0.85 (sensitivity, 91.7%; specificity, 84.7%; PPV, 50.0%; and NPV, 98.4%). Similar results were obtained when the accuracy to predict AKI on day 5 was assessed. Significant correlations were observed between RRI and estimated glomerular filtration rate at enrollment (ρ = -0.495) and on day 3 (ρ = -0.467). CONCLUSIONS: Renal Doppler ultrasound may be a promising tool to predict AKI in critically ill children under invasive mechanical ventilation. IMPACT: Early recognition of acute kidney injury (AKI) is essential to promptly initiate supportive care aimed at restoring renal perfusion, which may prevent or attenuate acute tubular necrosis. Renal arterial Doppler-based parameters are rapid, noninvasive, and repeatable variables that may be promising for the prediction of AKI in children. To the best of our knowledge, this is the first study to evaluate the use of renal Doppler-based variables to predict AKI in critically ill children. The present study found that Doppler-based variables could accurately predict the occurrence of severe AKI and were correlated with urinary output and diuretic use.

Escala Humpty Dumpty: adaptação transcultural e validação para cultura brasileira / Escala Humpty Dumpty: adaptación transcultural y validación para la cultura brasileña / The Humpty Dumpty Scale: cross-cultural adaptation and validation for Brazilian culture

Resumo Objetivo Adaptar e validar a The Humpty Dumpty Falls Scale para a cultura brasileira. Métodos Estudo metodológico, que seguiu, para a adaptação transcultural, os estágios de tradução, síntese, retrotradução, avaliação por especialistas, pré-teste e avaliação pela autora do instrumento original. Foram selecionadas 103 crianças/adolescentes internados em um hospital público do interior do estado de São Paulo. Foram utilizados ficha de caracterização, The Humpty Dumpty Falls Scale e o Instrumento de Classificação de Pacientes Pediátricos, o qual foi utilizado para avaliar a validade de construto, com o coeficiente de correlação de Spearman. A confiabilidade interobservador foi avaliada pelo Coeficiente de Correlação Intraclasse e pelo coeficiente Kappa. Resultados O comitê de 12 especialistas avaliou as equivalências, a clareza e a relevância dos itens e, após três rodadas, foi alcançado o percentual de 100% de concordância. As reformulações tornaram os itens mais compreensíveis e, após avaliação da autora, foi obtida a versão final do instrumento. Correlações positivas e significantes foram encontradas entre a Escala Humpty Dumpty e os domínios Paciente (r=0,5184; p<0,0001) e Procedimentos terapêuticos (r=0,2143; p<0,0332) do instrumento de classificação de pacientes. Com o domínio Família (r=0,0676; p=0,5060), não foram alcançadas relações significantes. Evidências satisfatórias de confiabilidade (Coeficiente de Correlação Intraclasse de 0,93 e coeficiente Kappa de 0,80) foram observadas. Conclusão The Humpty Dumpty Falls Scale foi adaptada transculturalmente, sendo denominada Ferramenta de Avaliação de Risco de Queda - Escala Humpty Dumpty. Demonstrou evidências satisfatórias de validade e confiabilidade para avaliar o risco de queda em crianças e adolescentes, no cenário brasileiro.

Resumen Objetivo Adaptar y validar The Humpty Dumpty Falls Scale para la cultura brasileña. Métodos Estudio metodológico, en el que se realizaron las siguientes etapas para la adaptación transcultural: traducción, síntesis, retrotraducción, evaluación por especialistas, prueba piloto y evaluación por la autora del instrumento original. Se seleccionaron 103 infantes/adolescentes internados en un hospital público del interior del estado de São Paulo. Se utilizó la ficha de caracterización, The Humpty Dumpty Falls Scale y el Instrumento de Clasificación de Pacientes Pediátricos, que se usó para evaluar la validad del constructo, con el coeficiente de correlación de Spearman. La fiabilidad interobservador fue evaluada por el coeficiente de correlación intraclase y por el coeficiente Kappa. Resultados El comité de 12 especialistas evaluó las equivalencias, la claridad y la relevancia de los ítems y, después de tres rondas, se llegó al 100 % de concordancia. Con las reformulaciones los ítems quedaron más comprensibles y, luego de la evaluación de la autora, se obtuvo la versión final de instrumento. Se observaron correlaciones positivas y significativas entre la Escala Humpty Dumpty y los dominios Paciente (r=0,5184; p<0,0001) y Procedimientos terapéuticos (r=0,2143; p<0,0332) del instrumento de clasificación de pacientes. En el dominio Familia (r=0,0676; p=0,5060) no se encontraron relaciones significativas. Se observaron evidencias satisfactorias de fiabilidad (coeficiente de correlación intraclase de 0,93 y coeficiente Kappa de 0,80). Conclusión The Humpty Dumpty Falls Scale fue adaptada transculturalmente y se la denominó Herramienta de Evaluación de Riesgo de Caída - Escala Humpty Dumpty. Demostró evidencias satisfactorias de validez y de fiabilidad para evaluar el riesgo de caída en infantes y adolescentes, en el contexto brasileño.

Abstract Objective To adapt and validate The Humpty Dumpty Scale for Brazilian culture. Methods Methodological study that followed the steps of translation, synthesis, back-translation, evaluation by specialists, pre-test and evaluation by the author of the original instrument for the cross-cultural adaptation. A total of 103 children/adolescents admitted to a public hospital in the countryside of the state of Sao Paulo were selected. We used a characterization form, The Humpty Dumpty Scale and the Pediatric Patient Classification Instrument, which was used to assess construct validity, with Spearman's correlation coefficient. Interobserver reliability was assessed using the Intraclass Correlation Coefficient and the Kappa coefficient. Results The committee of 12 experts evaluated the equivalence, clarity and relevance of the items and after three rounds, the percentage of 100% agreement was reached. The reformulations made the items more understandable and, after the author's evaluation, the final version of the instrument was obtained. Positive and significant correlations were found between The Humpty Dumpty Scale and the Patient (r=0.5184; p<0.0001) and Therapeutic Procedures (r=0.2143; p<0.0332) domains of the patient classification instrument. With the Family domain (r=0.0676; p=0.5060), no significant relationships were achieved. Satisfactory evidence of reliability (Intraclass Correlation Coefficient of 0.93 and Kappa coefficient of 0.80) was observed. Conclusion The Humpty Dumpty Scale was cross-culturally adapted and is now called (in Portuguese) the Ferramenta de Avaliação de Risco de Quedas - Escala Humpty Dumpty. It demonstrated satisfactory evidence of validity and reliability to assess the risk of falling in children and adolescents in the Brazilian context.