Paulo Medical School Research Articles

Hypertension may associate with cerebral small vessel disease and infarcts through the pathway of intracranial atherosclerosis

Hypertension, a major modifiable risk factor for cardiovascular diseases, is linked to late-life neurocognitive disorders such as vascular dementia and Alzheimer's disease (AD). This study explores the associations between hypertension, intracranial atherosclerotic disease (ICAD), cerebral small vessel disease (cSVD), and Alzheimer's disease neuropathologic change (ADNC) in a large community-based autopsy study.This cross-sectional study used data from the Biobank for Aging Studies of the University of São Paulo Medical School. Sociodemographic and clinical information was gathered from a reliable next-of-kin informant. Neurofibrillary tangles, neuritic plaques, lacunar infarcts, hyaline arteriolosclerosis, and cerebral amyloid angiopathy were evaluated. Causal mediation analyses with natural effect models were performed to examine indirect associations of hypertension with cerebrovascular pathologies and ADNC through morphometric measurements of intracranial artery lumen obstruction.Hypertensive participants (n = 354) presented a higher rate of stenosed arteries (obstruction ≥ 50%), critically stenosed arteries (obstruction ≥ 70%), and more severe ICAD, shown by higher maximum and mean obstruction indexes compared to nonhypertensive participants (n = 166). These measurements of atherosclerosis were associated with neurofibrillary tangles and cSVD lesions. Hypertension was indirectly associated with hyaline arteriolosclerosis and lacunar infarcts through the pathway of ICAD. Presenting hypertension indirectly increased the odds of displaying hyaline arteriolosclerosis by 26% (95% CI: 1.08, 1.45, p = 0.002) and lacunar infarcts by 17% (95% CI: 1.01, 1.35, p = 0.029). Cognitive and APOE ε4 carrier status did not alter the investigated associations. In this community sample, hypertension was indirectly associated with cSVD through ICAD.

Occupational therapy and chronic pain - the didactic experience at academic pain league at the University of São Paulo medical school

Occupational Therapy interventions for people with chronic pain focus on promoting independence/autonomy and rescuing meaningful activities (interrupted after the limitations brought about by illness). Various strategies can be used, such as: guidance on energy conservation and joint protection techniques, prescription and/or manufacture of positioning devices, prescription and/or manufacture of assistive technology equipment, development of creative and expressive activities, training activities of daily living, environmental assessment, guidance for family members and caregivers. This article aims to present the implementation of the Occupational Therapy Service at the FMUSP Pain League, developed since 2023. The work focused on implementing Occupational Therapy as one of the professions that make up the FMUSP Pain League, on a permanent and continuous basis; and, in addition, allow undergraduates teaching opportunities (theoretical and practical) related to the multidisciplinary care of people with chronic pain, as well as promoting research actions in the area of ​​Occupational Therapy and Chronic Pain. In OT, a student and the supervising teacher work, together with the multidisciplinary team. Activities are weekly and take place at night. Remote and in-service supervision is carried out. The implementation took place in 3 stages. In the first stage, we sought to understand the dynamics of the league, as well as characterize the patients and their specific demands, through participant observation. The second stage was structured around the specific OT intervention; evaluations of league users were carried out, with the application of evaluation and recording instruments. The third stage focused on monitoring patients and families, with new assessments carried out when necessary. Interventions follows through individual plan care, family guidance, development of educational material, prescription and/or production of assistive technology devices. The service uses a specific evolution form and the data feeds into a service database. We consider that the results obtained are satisfactory, as theoretical and practical learning was possible for the participating student. Currently, Occupational Therapy is already part of the League's routine activities, with participation in the Introductory Course, in the Board of Directors and in planning activities for 2024.

Abstract PO3-11-08: High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors

Abstract Much literature already depicts the relationship between metabolic syndrome (MS), obesity, and breast cancer. Despite that, up to one-third of non-obese individuals may exhibit undiagnosed MS or metabolic dysfunction, posing an independent cancer risk and worse outcomes even for those with a body mass index (BMI) < 30kg/m². In that manner, our study aims to evaluate the metabolic profile of non-obese women with postmenopausal breast cancer compared to non-obese women without breast cancer. In this cross-sectional clinical study at the State University of São Paulo Medical School - UNESP. The study group (n=130) included women aged ≥ 45 and < 75 years, in amenorrhea for at least 12 months, BMI ≤ 30kg/m2, histological diagnosis of breast cancer, without metastatic disease, and without established cardiovascular disease (CVD). The control group (n=130) comprised women with all the same criteria except for breast cancer diagnosis. The groups were matched by age and menopause time in a ratio of one case to one control (1:1). We aimed to analyze their clinical, biochemical, and oncological data to establish relationships between these groups. We presented the data in tables 1 - 3. The groups showed homogeneity in age, time since menopause, BMI, waist circumference (WC), and cholesterol levels. There was a higher occurrence of MS and hypertension (HTN) among women treated for breast cancer compared to the control group (30.8% vs. 20.0% and 25.4% vs.14.6%, respectively) (p< 0.05). Similarly, a higher percentage of women treated for breast cancer had abnormal values for total cholesterol and glucose (56.2% vs. 43.1% and 29.2% vs. 15.4%, respectively) (p< 0.05). In the analysis of metabolic profile risk-adjusted for age time since menopause and BMI, women treated for breast cancer showed an increased risk for MS (OR=2.76, 95% CI 1.48-5.15), elevated glucose (OR=2.69, 95% CI 1.46-4.96), and HTN (OR=3.03, 95% CI 1.51-6.10). In the evaluation of factors influencing the metabolic profile, women with breast cancer had significantly higher mean values of WC (82.6±8.5 vs. 79.9±6.4 cm, p=0.048), systolic and diastolic blood pressure (129.2±17.1 and 77.7±8.8 mmHg vs. 118.2±15.1 and 73.6±8.8 mmHg, p=0.0002 and p=0.01, respectively), and glucose (99.7±32.5 vs. 86.6±7.6 mg/dL, p=0.0002) compared to control group. We conducted a sub-analysis among women with BMI < 25kg/m² from both groups. Women with breast cancer (n=64) had a higher occurrence of MS compared to women without breast cancer (n=53) (17.2% vs. 1.9%, respectively). Even though this sub-analysis did not reach the minimum number of patients with BMI < 25 kg/m² to achieve p value < 0,05, this analysis reveals a significant difference in MS incidence between the groups (p=0.007). This reinforces the hypothesis that oncological diagnosis substantially affects metabolic health, and therefore, breast cancer patients should receive special attention regarding their metabolic profile, regardless of their BMI. Conclusion: Non-obese women with breast cancer showed a higher risk of MS, HTN, and diabetes, with a worse metabolic profile than non-obese postmenopausal women without breast cancer. These findings suggest that postmenopausal women diagnosed with breast cancer, even in the absence of obesity, exhibit significant metabolic dysfunction characterized by a higher occurrence of MS and its components. The findings highlight the importance of a comprehensive assessment of metabolic health in women with breast cancer, regardless of their body mass index, to ensure appropriate and individualized care for these patients. Table 1 - Comparison of clinical and laboratory characteristics among 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control) (average values ± standard deviation). Table 2 - Comparison of categorized clinical and laboratory characteristics that influence the metabolic profile between 130 non-obese postmenopausal women with breast cancer and 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; WC, waist circumference; MS, metabolic syndrome; HDL, high-density lipoprotein, LDL, low-density lipoprotein; TG, triglycerides. *Significant difference p<0.05 (Chi-square Test). Table 3. Association between the presence of Metabolic Syndrome, and its clinical and laboratory components, among the 130 non-obese postmenopausal women with breast cancer and the 130 non-obese postmenopausal women (control). Values expressed as number and percentage in parentheses. CA, cancer; BP, blood pressure; WC, waist circumference; TG, triglycerides. *Odds ratio (OR) adjusted for age, menopause duration and BMI. **Significant difference if p<0.05 (Logistic Regression). Citation Format: Pedro Paulo Perroni Filho, Daniel Buttros, Eliana Aguiar Petri Nahas. High Risk of Metabolic Dysfunction in Non-Obese Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-08.

ICP wave morphology as a screening test to exclude intracranial hypertension in brain-injured patients: a non-invasive perspective.

Intracranial hypertension (IH) is a life-threating condition especially for the brain injured patient. In such cases, an external ventricular drain (EVD) or an intraparenchymal bolt are the conventional gold standard for intracranial pressure (ICPi) monitoring. However, these techniques have several limitations. Therefore, identifying an ideal screening method for IH is important to avoid the unnecessary placement of ICPi and expedite its introduction in patients who require it. A potential screening tool is the ICP wave morphology (ICPW) which changes according to the intracranial volume-pressure curve. Specifically, the P2/P1 ratio of the ICPW has shown promise as a triage test to indicate normal ICP. In this study, we propose evaluating the noninvasive ICPW (nICPW-B4C sensor) as a screening method for ICPi monitoring in patients with moderate to high probability of IH. This is a retrospective analysis of a prospective, multicenter study that recruited adult patients requiring ICPi monitoring from both Federal University of São Paulo and University of São Paulo Medical School Hospitals. ICPi values and the nICPW parameters were obtained from both the invasive and the noninvasive methods simultaneously 5 min after the closure of the EVD drainage. ICP assessment was performed using a catheter inserted into the ventricle and connected to a pressure transducer and a drainage system. The B4C sensor was positioned on the patient's scalp without the need for trichotomy, surgical incision or trepanation, and the morphology of the ICP waves acquired through a strain sensor that can detect and monitor skull bone deformations caused by changes in ICP. All patients were monitored using this noninvasive system for at least 10min per session. The area under the curve (AUC) was used to describe discriminatory power of the P2/P1 ratio for IH, with emphasis in the Negative Predictive value (NPV), based on the Youden index, and the negative likelihood ratio [LR-]. Recruitment occurred from August 2017 to March 2020. A total of 69 patients fulfilled inclusion and exclusion criteria in the two centers and a total of 111 monitorizations were performed. The mean P2/P1 ratio value in the sample was 1.12. The mean P2/P1 value in the no IH population was 1.01 meanwhile in the IH population was 1.32 (p < 0.01). The best Youden index for the mean P2/P1 ratio was with a cut-off value of 1.13 showing a sensitivity of 93%, specificity of 60%, and a NPV of 97%, as well as an AUC of 0.83 to predict IH. With the 1.13 cut-off value for P2/P1 ratio, the LR- for IH was 0.11, corresponding to a strong performance in ruling out the condition (IH), with an approximate 45% reduction in condition probability after a negative test (ICPW). To conclude, the P2/P1 ratio of the noninvasive ICP waveform showed in this study a high Negative Predictive Value and Likelihood Ratio in different acute neurological conditions to rule out IH. As a result, this parameter may be beneficial in situations where invasive methods are not feasible or unavailable and to screen high-risk patients for potential invasive ICP monitoring.Trial registration: At clinicaltrials.gov under numbers NCT05121155 (Registered 16 November 2021-retrospectively registered) and NCT03144219 (Registered 30 September 2022-retrospectively registered).

A pediatria além dos muros de um hospital

Xingu + Catu is a non-governmental organization (NGO) that promotes expeditions to the Xingu National Park region with the aim of providing health care for the indigenous population. The NGOs third expedition took place between June and July 2023, in partnership with the Department of Pediatrics of the University of São Paulo Medical School and with the participation of two resident doctors in the third year of the general pediatrics course during their elective rotation. This expedition provided 225 consultations, 75 of which were in the pediatric age group (ages between 0 and 14 years of age). The focus of the pediatric care was on weight-height development, neuropsychomotor development, assessment of global health, in addition to evaluating specific demands and complaints. The experience of providing care in a remote region, with little access to the healthcare system, which is generally not included in the traditional training of a pediatrician, is enriching. It allows the resident to be exposed to different healthcare realities and different cultures, expanding your worldview and your positioning as a doctor and human being.

Which detergent is most suitable for the generation of an acellular pancreas bioscaffold?

Pancreatic bioengineering is a potential therapeutic alternative for type 1 diabetes (T1D) in which the pancreas is decellularized, generating an acellular extracellular matrix (ECM) scaffold, which may be reconstituted by recellularization with several cell types to generate a bioartificial pancreas. No consensus for an ideal pancreatic decellularization protocol exists. Therefore, we aimed to determine the best-suited detergent by comparing sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC), and Triton X-100 at different concentrations. Murine (n=12) and human pancreatic tissue from adult brain-dead donors (n=06) was harvested in accordance with Institutional Ethical Committee of the University of São Paulo Medical School (CEP-FMUSP) and decellularized under different detergent conditions. DNA content, histological analysis, and transmission and scanning electron microscopy were assessed. The most adequate condition for pancreatic decellularization was found to be 4% SDC, displaying: a) effective cell removal; b) maintenance of extracellular matrix architecture; c) proteoglycans, glycosaminoglycans (GAGs), and collagen fibers preservation. This protocol was extrapolated and successfully applied to human pancreas decellularization. The acellular ECM scaffold generated was recelullarized using human pancreatic islets primary clusters. 3D clusters were generated using 0.5×104 cells and then placed on top of acellular pancreatic slices (25 and 50 μm thickness). These clusters tended to connect to the acellular matrix, with visible cells located in the periphery of the clusters interacting with the ECM network of the bioscaffold slices and continued to produce insulin. This study provided evidence on how to improve and accelerate the pancreas decellularization process, while maintaining its architecture and extracellular structure, aiming at pancreatic bioengineering.

Drug use among medical students in São Paulo, Brazil: a cross-sectional study during the coronavirus disease 2019 pandemic.

Medical students demonstrate higher rates of substance use than other university students and the general population. The challenges imposed by the coronavirus disease 2019 (COVID-19) pandemic raised significant concerns about mental health and substance use. Assess the current prevalence of substance use among medical students at the University of São Paulo and evaluate the impact of the COVID-19 pandemic on drug consumption. A cross-sectional study was conducted on 275 medical students from the University of São Paulo Medical School (São Paulo, Brazil) in August 2020. Substance use (lifetime, previous 12 months, and frequency of use before and during the COVID-19 pandemic) and socioeconomic data were assessed using an online self-administered questionnaire. Symptoms of depression were assessed using the Patient Health Questionnaire-9. Alcohol was the most consumed substance in their lifetime (95.6%), followed by illicit drugs (61.1%), marijuana (60%), and tobacco (57.5%). The most commonly consumed substances in the previous year were alcohol (82.9%), illicit drugs (44.7%), marijuana (42.5%), and tobacco (36%). Students in the first two academic years consumed fewer substances than those from higher years. There was a decreasing trend in the prevalence of most substances used after the COVID-19 pandemic among sporadic users. However, frequent users maintained their drug use patterns. The prevalence of substance use was high in this population and increased from the basic to the clinical cycle. The COVID-19 pandemic may have affected the frequency of drug use and prevalence estimates.

#5978 SUBCAPSULAR INJECTION OF EXTRACELLULAR VESICLES FROM MESENCHYMAL STEM CELLS, PROMOTED ADDITIONAL RENOPROTECTION IN AN EXPERIMENTAL MODEL OF CKD

Abstract Background and Aims Chronic kidney disease (CKD) is considered a public health concern worldwide, both due to its insidious and highly debilitating feature and to its high global prevalence. Clinical management of CKD is often achieved by the blockade of the renin-angiotensin-aldosterone system (RAAS). However, this treatment alone is not efficient to prevent CKD progression completely, motivating the scientific community to search for alternative treatments to control CKD progression and to detain its evolution to the end-stage renal failure. In this context, we have recently shown that the association of a single renal subcapsular injection of 2 × 106 adipose-derived mesenchymal stem cells (ASC) to RAAS blockade with the AT1RB Losartan (LOS) promoted greater renoprotection when compared to LOS monotherapy, leading to the normalization of urinary protein excretion (UPE) and to the regression of established glomerulosclerosis (GS), in experimental CKD. Since there are methodological limits for the number of ASC that can be injected under the renal capsule, and based on the current literature, which suggests the main beneficial effects of ASC are not due to direct in situ cell differentiation, but to paracrine factors produced and released by the ASC; in the present study we aimed to investigate if the association of a renal subcapsular injection of extracellular vesicles (EV) derived from ASC, to the oral treatment with LOS would promote additional renoprotective effects in a model of experimental CKD. Method The present experimental protocol was approved by the Ethics Committee for the Use of Experimental Animals of the University of São Paulo Medical School (CEUA-FMUSP No 1761/2022). EV were obtained from ASC isolated from gonadal adipose tissue of 5 male Wistar rats. Cells were cultured until P4, characterized by flow cytometry and in vitro differentiation, and kept under serum deprivation for 24 h. The conditioned culture media, containing the EV released by these cells, was ultracentrifuged and the resulting EV pellets were diluted in 100 μL of sterile PBS and used for the renal subcapsular injections. Experimental CKD was induced in 25 male Wistar rats through the surgical ligation of 2 from the 3 branches of the left renal artery, followed by the total nephrectomy of the right kidney, resulting in a 5/6 renal ablation. Additional 10 Sham-operated rats were used as control. After 15 days from surgery, the animals submitted to renal ablation were stratified into 3 groups, with closely similar mean values of body weight (BW), systolic blood pressure (SBP), UPE and urinary albumin excretion (UAE), before the start of the different treatments. Animals from CKD group were kept untreated, LOS and LOS+EV animals received diary 50 mg/Kg/d of Losartan, diluted in drinking water and LOS+EV rats underwent a second surgery for the renal subcapsular application of EV. All animals were followed until 30 days after CKD induction, when BW, SBP, UPE and UAE were analyzed again. Animals where then euthanized for the assessment of serum creatinine (SCr) and blood urea nitrogen (BUN) concentration, as well as for histological studies to determine the percentage of GS and the renal interstitial infiltration by macrophages (CD68). Results The association of a single subcapsular injection of EV derived from ASC, to the oral treatment with the AT1RB LOS, significantly improved the effects of this antihypertensive drug. CKD+LOS+EV animals exhibited normal SBP, in spite of having only 1/6 of functioning renal mass. Moreover, the combined treatment significantly reduced UAE and numerically diminished de percentage of glomerulosclerosis, compared to LOS alone. Detailed obtained results are presented in Table 1. Data are presented as Mean ± SE. Differences among groups were analyzed by one-way ANOVA: p&amp;lt;0.05 vs.*CONT, #CKD, †LOS. as Mean ± SE. Conclusion Despite the small number of animals in the association group, our preliminary results suggest EV from ASC to exert additional renoprotective effects when associated to LOS, especially regarding the control of SBP and the protection of the glomerular filtration barrier integrity.

Robust local quantile regression for reference curves

We propose two non-parametric methods to construct locally fitted quantile reference curves that are robust with respect to outliers in the predictor variable. The first includes a weighting procedure and the second, the detection and subsequent elimination of outlying predictor variable values before the local fitting process. The reference curves fitted by the proposed methods generate quantile limits that are less affected in regions with a low frequency of the predictor variable values. The proposed procedures are used to fit reference curves to data extracted from a study conducted at the Heart Institute of the University of São Paulo Medical School.

Arquivos de Neuro-Psiquiatria: 80 years.

In June 2023, the Arquivos de Neuro-Psiquiatria (ANP) will complete 80 years of uninterrupted publication. The ANP was envisioned by the students of Professor Enjolras Vampré, founder of the São Paulo neurological school, who died prematurely.[1] The first edition of the ANP was in June 1943 and was presented by Professors Aderbal Tolosa (professor of Neurology at the University of São Paulo Medical School –USP), and Paulino Longo, (professor of Neurology at the Paulista School of Medicine – currently UNIFESP).[2] Dr. Oswaldo Lange (professor of Neurological Clinics at the University of São Paulo Medical School) was appointed editor-in-chief of the journal. Lange continued this noble work with mastery and dedication until 1986.[1] [3] [4] From 1987 to 2010, the editor-in-chief of ANP was Professor Antonio Spina-França, who was dedicated to making the ANP the leading journal of neurology in Latin America.[1] [3] [4] He was succeeded by his colleagues Professors Luís dos Ramos Machado and José Antonio Livramento, both from the Hospital das Clínicas at the University of São Paulo. They served as the editors-in-chief of the ANP between 2010 and 2017 with great harmony and dedication.[1] [3] [4] The editors chosen in 2018 were Professor Paulo Caramelli (full professor of Neurology at the University of Minas Gerais) and Hélio A. Ghizoni Teive (currently full professor of Neurology at the Federal University of Paraná).[1] [3] [4] This year, Professor Ayrton Massaro (Neurologist at the Hospital Israelita Albert Einstein, in São Paulo) replaced Professor Paulo Caramelli as editor-in-chief of the ANP. Demonstrating the great scientific evolution of Brazilian neurology in recent years, the ANP, the official journal of the Brazilian Academy of Neurology (BAN), has achieved an exponential increase in its impact factor, reaching 2.035.[5] This unprecedented achievement encourages even more its editors-in-chief, as well as all of its associated editors and the Brazilian neurological community, with the support of the BAN, to improve the scientific level of the journal, with the primary objective of reaching levels of excellence in the Latin American and world context of neurosciences.[5] This year, 2023, as current and past editors-in-chief of ANP, we are organizing a major scientific event to celebrate the 80th anniversary of the Journal, as well as the publication of a special issue of the ANP, with a series of scientific articles, covering topics of great interest in different subspecialties of neurology.

Efficacy and safety of methylphenidate and behavioural parent training for children aged 3–5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial

There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

RETALHO SURAL REVERSO NA RECONSTRUÇÃO DE MEMBROS INFERIORES

ABSTRACTIntroduction: Reconstruction of distal wounds in lower extremities can be challenging due to the lack of tissue to perform local flaps. Fasciocutaneous and muscular flaps are some options for coverage, such as the reverse-flow fasciocutaneous sural flap.Objective: To present an 18-month experience on ankle, calcaneus, and foot reconstruction using the reverse-flow sural flap, performed by the Complex Wounds Group of the Plastic Surgery Department of the University of São Paulo Medical School.Methods: An observational, retrospective and descriptive study was performed through data survey on medical records of all patients treated between November 2018 and June 2020.Results: Nine reverse-flow fasciocutaneous sural flaps were performed. All patients were men. The mean age was 38 years old. Five patients had acute wounds for traffic collision, one electrical trauma and three chronic post-traumatic injuries. The ankle was the most common injury site (6), followed by foot (2) and calcaneus (1). Four patients had complications, three of which were partial necrosis and one distal epitheliosis. No case of total necrosis was recorded. The average hospital stay was 30.1 days.Conclusion: The reverse-flow fasciocutaneous sural flap proved to be a viable, reproducible, and reliable option for distal lower limb reconstruction. Level of Evidence IV, Case Series.

Physical exercise for bipolar disorder: Time for action

Bipolar disorder (BD) is associated with higher rates of sedentarism, metabolic syndrome, obesity and early onset cardiovascular disease leading to premature mortality. Moreover, BD is often associated with disability and deficits in general functioning associated with residual subsyndromal depressive symptoms and persistent neurocognitive impairments.

Safety of an inactivated SARS-CoV-2 vaccine in elderly persons

Introduction. Brazil has the 2nd highest number of COVID-19 deaths (more than 530,000) and the 3rd highest number of confirmed cases (more than 19 million) worldwide. COVID-19 vaccination is the most effective strategy to prevent new cases and illness, reducing hospitalizations and deaths. The 1st vaccine used in Brazil was the Sinovac/Instituto Butantan CoronaVac, an inactivated SARS-CoV-2 vaccine. Elderly persons (EP) were among the first groups eligible for immunization, after healthcare workers, indigenous people and quilombolas. Objective. To evaluate adverse events following immunization (AEFI) with CoronaVac in EP. Methods. This observational retrospective study was conducted at the Reference Center for Special Immunobiologicals (CRIE) of the Hospital das Clínicas (HC-FMUSP), a tertiary/quaternary hospital attached to the University of São Paulo Medical School (FMUSP), in São Paulo city, from February to April 2021. EP, who searched or were referred to CRIE to receive the COVID-19 vaccine were asked for authorization for follow-up calls to evaluate AEFI. The on phone follow up was made by healthcare workers who conducted AEFI forms on day 4 and day 8 after the first and second vaccine doses; a sociodemographic questionnaire; and a modified functionality scale for EP based on the Independence in Activities of Daily Living index (ADLi), Instrumental Activities of Daily Living scale (IADLs) and Study of Osteoporotic Fractures index (SOFi). Results. During the study period, CoronaVac was used; 159 EP received the first dose and 155 EP were fully vaccinated at CRIE; 152 participants were contacted after the first dose and 142 participants were contacted after the second dose. The participants’ age ranged from 53 to 101 years (mean, 84 years), 65.4% were females, and 73.7% were white. 148 (93.1%) participants have at least one comorbidity, the most common was hypertension (59.8%) followed by heart disease (30.2%) and dyslipidemia (25.2%). 70/152 (46.1%) participants were classified as independent in IADLs, 117/152 (77.0%) in ADLi and 66/152 (43.4%) according to SOFi. 47 participants (30.2%) reported at least one AEFI at first dose. The most common local AEFI was pain at the injection site (13, 8.6%) and the most common systemic AEFI was fatigue (8, 6.0%), followed by headache (6, 4.0%). Thirty participants (21.1%) reported at least one AEFI at the second dose. The most common local AEFI was pain at the injection site (6, 4.3%) and the most common systemic AEFI was myalgia (11, 7.9%), followed by fatigue (9, 6.5%). Most AEFI were mild and had no or little interference in daily activities. There were five severe AEFI: two deaths after the first dose (a sudden death and another following a hemorrhagic stroke) and three hospitalizations (one after the first dose and two after the second dose). None of them were considered related to the vaccine. Discussion and conclusion. This unique studied population was composed of EP with comorbidities and some level of dependency. The participants reported few and mild AEFI, suggesting CoronaVac is safe in EP.

Relation between CANDIDA species isolated from vaginal mucosa and lesions caused by high-risk human papillomavirus hpv for cervical cancer

This study characterized and related yeasts of the genus Candida isolated from vaginal mucous membranes of women with lesions caused by high-risk HPV for cervical cancer. Forty-two women treated at the Lower Genital Tract Pathology Clinic of the University of São Paulo Medical School Hospital of Clinics were examined, with 30 high-grade (G1) uterine lesions with a mean age of 36.5 years ± 11. 1 and 12 with low grade (G2) uterine lesions with a mean age of 34.7 years ± 15.5. Clinical conditions and laboratory data on HPV were collected from patients’ medical records; the socio-demographic data obtained from an appropriate questionnaire. For the study of association between the variables, Odds Ratio analysis was used from the STATA 13.1 program. Patients G1 had a higher prevalence for diabetes and the results indicated 27% prevalence of Candida spp. in vaginal mucosa, in G2 this was 33% in vaginal mucosa. Among the species found in vaginal mucosa of patients, Candida albicans was the most isolated with 88%, followed by C. tropicalis (8%) and C. glabrata (4%). The strains of C. albicans isolated from mucosa presented sensitivity to all antifungal agents tested, unlike the C. tropicalis strain isolated in G2 in vaginal mucosa, which presented a resistance profile to fluconazole. Thus, monitoring and supervision through clinical and laboratory testing of HPV patients is important, reinforcing the need for care, treatment and prevention of HPV-related infections and Candida spp. KEY WORDS: vaginal mucosa; uterine cervical neoplasms; human Papillomavirus; Candida spp. Antifungal sensitivity.

Characteristics and outcomes of 727 patients with mycosis fungoides and Sézary syndrome from a Brazilian cohort.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent cutaneous lymphomas. They were not described in a large Brazilian cohort yet. We aimed, with this single-center, retrospective cohort analysis, to describe the characteristics and outcomes of MF/SS in a tertiary public health service in Brazil. MF/SS patients evaluated at the University of São Paulo Medical School between 1989 and 2018 were included. Data were collected at diagnosis. Demographic, clinical, histopathological, immunopathological, molecular, laboratory, and follow-up data were analyzed. Among 727 patients, 92.6% (673) were diagnosed with MF, 7.4% (54) with SS. There were 51.2% (372) of males, 48.8% (355) of females. The median age was 51.8 years; it was higher in erythrodermic MF (60.2) and SS (60.9). Among MF, 41.8% (281) had classic MF, 4.9% (33) folliculotropic MF, 1.8% (12) granulomatous slack skin, and 0.3% (2) pagetoid reticulosis. Common subtypes included erythrodermic (14.1%, 95), hypopigmented (10.8%, 73), and poikilodermatous MF (10.8%, 73). Extracutaneous involvement was rare. Five, 10, 20, and 30-year overall survival rates were 97.3%, 92.4%, 82.6%, and 82.6% for early-stage, and 58.6%, 42.7%, 20.8%, and 15.4% for advanced-stage disease, respectively. After multivariate analysis, SS diagnosis, folliculotropic MF, erythrodermic MF, clinical stage, age (≥60 years), increased lactate dehydrogenase, and large cell transformation conferred poorer prognosis. We observed a higher percentage of hypopigmented MF compared to the literature, and demographic (older age) and prognostic (poorer prognosis) similarities between erythrodermic MF and SS, suggesting a possible relationship between these erythrodermic lymphomas. Factors associated with a poorer prognosis were compatible with the literature.

Impact of COVID-19 on coronary artery surgery: Hard lessons learned.

Journal of Cardiac SurgeryVolume 36, Issue 9 p. 3294-3295 COMMENTARY Impact of COVID-19 on coronary artery surgery: Hard lessons learned Luis Alberto O. Dallan, Luis Alberto O. Dallan orcid.org/0000-0002-8655-8966 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this authorLuiz Augusto F. Lisboa, Luiz Augusto F. Lisboa orcid.org/0000-0002-2137-0604 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this authorLuis Roberto P. Dallan, Corresponding Author Luis Roberto P. Dallan dcidallan@incor.usp.br orcid.org/0000-0001-8137-5434 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, Brazil Correspondence Luis Alberto O. Dallan, Dr. Enéas de Carvalho Aguiar, 44, Pinheiros, São Paulo, SP 05403-900, Brazil. Email: dcidallan@incor.usp.brSearch for more papers by this authorFabio B. Jatene, Fabio B. Jatene orcid.org/0000-0001-6175-5595 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this author Luis Alberto O. Dallan, Luis Alberto O. Dallan orcid.org/0000-0002-8655-8966 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this authorLuiz Augusto F. Lisboa, Luiz Augusto F. Lisboa orcid.org/0000-0002-2137-0604 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this authorLuis Roberto P. Dallan, Corresponding Author Luis Roberto P. Dallan dcidallan@incor.usp.br orcid.org/0000-0001-8137-5434 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, Brazil Correspondence Luis Alberto O. Dallan, Dr. Enéas de Carvalho Aguiar, 44, Pinheiros, São Paulo, SP 05403-900, Brazil. Email: dcidallan@incor.usp.brSearch for more papers by this authorFabio B. Jatene, Fabio B. Jatene orcid.org/0000-0001-6175-5595 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, BrazilSearch for more papers by this author First published: 02 July 2021 https://doi.org/10.1111/jocs.15769Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume36, Issue9September 2021Pages 3294-3295 RelatedInformation

COVID-19-related hospital cost-outcome analysis: The impact of clinical and demographic factors

IntroductionAlthough patients’ clinical conditions have been shown to be associated with coronavirus disease (COVID-19) severity and outcome, their impact on hospital costs are not known. This economic evaluation of COVID-19 admissions aimed to assess direct and fixed hospital costs and describe their particularities in different clinical and demographic conditions and outcomes in the largest public hospital in Latin America, located in São Paulo, Brazil, where a whole institute was exclusively dedicated to COVID-19 patients in response to the pandemic. MethodsThis is a partial economic evaluation performed from the hospital´s perspective and is a prospective, observational cohort study to assess hospitalization costs of suspected and confirmed COVID-19 patients admitted between March 30 and June 30, 2020, to Hospital das Clínicas of the University of São Paulo Medical School (HCFMUSP) and followed until discharge, death, or external transfer. Micro- and macro-costing methodologies were used to describe and analyze the total cost associated with each patient's underlying medical conditions, itinerary and outcomes as well as the cost components of different hospital sectors. ResultsThe average cost of the 3254 admissions (51.7% of which involved intensive care unit stays) was US$12,637.42. The overhead cost was its main component. Sex, age and underlying hypertension (US$14,746.77), diabetes (US$15,002.12), obesity (US$18,941.55), chronic renal failure (US$15,377.84), and rheumatic (US$17,764.61), hematologic (US$15,908.25) and neurologic (US$15,257.95) diseases were associated with higher costs. Age strata >69 years, reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19, comorbidities, use of mechanical ventilation or dialysis, surgery and outcomes remained associated with higher costs. ConclusionKnowledge of COVID-19 hospital costs can aid in the development of a comprehensive approach for decision-making and planning for future risk management.

Personalized medicine in Brazil: a new paradigm, old problems

PurposePersonalized medicine (PM) encompasses a set of procedures, technologies and medications; the term became more prominent from the 2000s onwards and stems from the mapping of the human genome. The purposes of this study were to analyse the development stage of the process of technological innovation for PM and the obstacles that prevent PM from being adopted in the public health system in Brazil.Design/methodology/approachAs a research method, this paper opts for a case study carried out at the Hospital das Clínicas, which belongs to São Paulo Medical School. In total, 22 in-depth interviews were carried out at the hospital to identify current practices in PM, future prospects and barriers imposed to the adoption of PM technologies in public health.FindingsPersonalized or precision medicine is already a reality for a small portion of the Brazilian population and is gradually gaining ground in public health care. One finding is that such changes are occurring in a disjointed manner in an incomplete and under development health innovation system. The analysis pointed out that the obstacles identified in Brazil are the same as those faced by high-income countries such as regulation, lack of clinical studies and need to adapt clinical studies to PM. They appear in all stages of the innovation cycle, from research to widespread use.Research limitations/implicationsThe research method was a case study, so the findings cannot be extrapolated to other contexts. A limited number of professionals were interviewed, their opinions may not reflect those of their organizations.Originality/valueThere are several studies that discuss how health-care systems in high-income countries could incorporate these new technologies, but only a few focuses on low or middle-income countries such as Brazil.

Sergio Eduardo Alonso Araujo, MD, PhD, FASCRS.

Dr. Sergio Eduardo Alonso Araujo is a Staff Colon and Rectal Surgeon and Medical Director of the Oncology Division at the Hospital Israelita Albert Einstein in São Paulo, Brasil. Sergio was born in Santos, São Paulo, Brazil, and received his MD, MSc, PhD, and Professorship in Colorectal Surgery all at the University of São Paulo Medical School in São Paulo, Brasil. He is an active teacher, having been very involved in medical student and resident education, as well as carrying a very busy clinical workload. In addition, he is the President-elect of the Brazilian Society of Colon and Rectal Surgery, one of the largest colorectal surgery societies in the world. Sergio remains a productive researcher, with over 140 articles and book chapters to his credit, and has been all over the world as an invited lecturer and panelist. He also served as the Editor-in-Chief for Revista Brasileira de Video-Cirurgia from 2004 to 2006 and currently serves on the editorial board for Surgical Laparoscopy, Endoscopy & Percutaneous Techniques. Sergio and his wife, Juliana, have two children—Caio and Clara. They enjoy doing everything together as a family, including spending time outdoors, running (including marathons), and karaoke. On a personal note, it has been an absolute pleasure getting to know him and his colleagues from Brasil. He is an excellent technical surgeon, especially within the realm of robotics, minimally invasive, and transanal surgery. On behalf of the readers and staff of Clinics in Colon and Rectal Surgery, I sincerely thank Sergio for serving as a Guest Editor and for providing us with a superb issue on minimally invasive and robotic approaches to colorectal disease.