Brazilian Reference Center Research Articles

Growth charts of Brazilian girls with Turner syndrome without the use of GH or oxandrolone

ObjectiveThe development of specific growth charts for Turner Syndrome (TS) promotes adequate assessment of growth and weight gain, and earlier diagnosis of comorbidities, and may help to analyze the effectiveness of treatments to promote growth and puberty. The aim of this study was to construct a growth chart with the largest possible series of patients with a cytogenetic diagnosis of TS from a Brazilian reference center. MethodsThis is a longitudinal study, with 259 cases of TS born between 1957 and 2014 and followed between 1975 and 2019, without the use of GH or oxandrolone. 3,160 height measurements and 2,918 wt measurements were used, with subsequent calculation of the Body Mass Index (BMI). For data analysis, the “GAMLSS” package of the “R” software was used. ResultsThe mean target height was 157.8 cm (standard deviation 5.2; median 160.4 cm). The mean height of patients with TS at 20 years of age was 145.6 cm (standard deviation 5.9; median 146.7 cm). Height, weight, and BMI by age graphs were developed for TS girls between 2 and 20 years. ConclusionThese growth charts may be used to monitor the growth of girls with TS and to verify the effect of adjuvant treatments on promoting growth.

Real-world evidence of survival outcomes in breast cancer subtypes after neoadjuvant chemotherapy in a Brazilian reference center.

Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.

SARS-CoV-2 infection and vaccination in patients with pituitary diseases: the experience of a Brazilian reference center.

To evaluate the prevalence and characteristics of SARS-CoV-2 infection, and the prevalence, efficacy, and safety of anti-SARS-CoV-2 vaccination in patients with pituitary diseases. Observational, cross-sectional study of adult patients with pituitary diseases followed in a reference center. Clinical data were collected and a questionnaire about SARS-CoV-2 infection, vaccination and its possible adverse effects was applied. COVID-19 disease severity was defined as mild, moderate, and severe according to the WHO classification. 145 patients were studied (79 women; age 50 ± 15.8 years; duration of pituitary disease 16.8 ± 11.5 years), the cause of pituitary disease was tumoral in 74.5%, and 45.9% were on glucocorticoid replacement due to ACTH deficiency. SARS-CoV-2 infection was confirmed in 51 patients (35.2%; 32 women; age 53.8 ± 14.8 years, 22 before vaccination), with 28 (54.9%), 17 (33.3%) and 6 (11.8%) cases of mild, moderate, and severe disease, respectively, and hospitalization was indicated in 7 (14%) cases. One mild case presented pituitary apoplexy after SARS-CoV-2 infection. Advanced age was a risk factor for COVID-19. Patients with moderate and severe forms of COVID-19 had higher prevalence of dyslipidemia and duration of pituitary disease. All but one of the participants were vaccinated against COVID-19, and 60.4% had adverse events, the most common local pain (54.0%), fever (33.3%), and headache (18.4%), with one case of alopecia and two of persistent fatigue. The prevalence of SARS-CoV-2 infection in our cohort was 35.2%, including 14% of moderate and severe cases requiring hospitalization. The vaccination was universal and safe.

Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Analyzing Neoadjuvant Chemotherapy Effects in HER2-Low Breast Cancer: Real World Data.

Neoadjuvant chemotherapy (NAC) can be used as upfront therapy in aggressive breast cancer (BC). human epidermal growth factor receptor 2 (HER2)-low BC, defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization, lacks information on real-world data (RWD) outcomes, especially in the NAC setting. This subgroup, which does not reach the HER2 positive criteria due to its lower receptor expression, represents a distinct clinical category potentially requiring tailored therapeutic approaches. The objective of this study is to characterize patients with BC with HER2-low status who received NAC in a Brazilian public reference center for female tumors and key outcomes such as pathological complete response (pCR), overall survival (OS), and metastasis-free survival (MFS). A retrospective cohort study based on a large BC database from a reference cancer center in Brazil. Patients with BC that received NAC, diagnosed between 2011 and 2020, were included if they presented HER2-low status (defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization) and had complete data on outcomes. Clinical and demographicdata were collected, such as age, menopausal status, Ki-67, hormone receptorexpression and others. Key outcomes from the study comprised pCR (defined as ypT0/TIs/ypN0), overall survival, and metastasis-free survival (MFS). Survival analyses were conducted through the semiparametric Kaplan-Meier method to assess OS and MFS by pCR status, considering BC diagnosis as the index date. Overall, 297 patients were eligible and 141 were included in the study after matching the HER2-low definition. The pCR was seen in 18 out of 141 patients (12.7%). The median overall survival was 8.2 years, and the median MFS was 2.7 years. The OS of pCR was 83.4% and non-pCR was 58.1%; the DFS of pCR was 55.5% and non-pCR 40.6%. This study gives updated insights on pCR, OS, and MFS in women with HER2-low BC exposed to NAC.

Exclusive breastfeeding and length of hospital stay in premature infants at a Brazilian reference center for kangaroo mother care

ObjectiveTo evaluate exclusive breastfeeding at discharge and hospital length-of-stay in preterm infants undergoing or not the Kangaroo-Mother Care Method (KMC). MethodsA retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. Results115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85–109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76–0.86) compared to the non-KMC group. ConclusionsThe KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals.

Oral leukoplakia and erythroplakia in young patients: a southern Brazilian multicenter study.

The objective of the present study was to investigate the frequency of oral leukoplakia and oral erythroplakia among young patients from three Brazilian reference centers in Oral and Maxillofacial Pathology. A retrospective study was carried out from 2011 to 2021 on 861 patients diagnosed with oral leukoplakia and oral erythroplakia. Demographic and clinicopathological data were evaluated. Fisher's exact test was used to evaluate the association among sex, age, anatomical location, and histopathological diagnosis. A total of 83 (9.64%) cases involved young patients (aged <40 years). Among these, biopsy records were included in 31 (37.34%) cases, all of which received a clinical diagnosis of oral leukoplakia. Seventeen (54.84%) patients were female, mostly in their fourth decade of life (n = 22/70.97%), and their mean age at diagnosis was 32.61(± 5.21) years. Among informed cases, seven (22.58%) patients were smokers. The lateral border of the tongue (n = 9/29.03%) was the most affected site. In 13 (41.94%) cases, oral leukoplakias showed a homogeneous appearance. The mean size of the lesions was 1.47 cm (0.2-3.0 cm) and the mean time of disease progression was 64.37 (± 65.90) months. The histopathological analysis showed that 11 cases (35.48%) exhibited some degree of epithelial dysplasia. Acanthosis and/or hyperkeratosis were observed in 20 cases (64.52%). No significant associations were observed between sex and anatomical location, age and anatomical location, nor between sex and histological diagnosis (p > 0.05). Oral leukoplakia and oral erythroplakia are uncommon diseases in young patients. In this population, oral leukoplakia shows a slight predilection for women aged between 30 and 39 years.

Assessment of Skin Maturity by LED Light at Birth and Its Association With Lung Maturity: Clinical Trial Secondary Outcomes

Background Clinicians face barriers when assessing lung maturity at birth due to global inequalities. Still, strategies for testing based solely on gestational age to predict the likelihood of respiratory distress syndrome (RDS) do not offer a comprehensive approach to addressing the challenge of uncertain outcomes. We hypothesize that a noninvasive assessment of skin maturity may indicate lung maturity. Objective This study aimed to assess the association between a newborn’s skin maturity and RDS occurrence. Methods We conducted a case-control nested in a prospective cohort study, a secondary endpoint of a multicenter clinical trial. The study was carried out in 5 Brazilian urban reference centers for highly complex perinatal care. Of 781 newborns from the cohort study, 640 were selected for the case-control analysis. Newborns with RDS formed the case group and newborns without RDS were the controls. All newborns with other diseases exhibiting respiratory manifestations were excluded. Skin maturity was assessed from the newborn's skin over the sole by an optical device that acquired a reflection signal through an LED sensor. The device, previously validated, measured and recorded skin reflectance. Clinical data related to respiratory outcomes were gathered from medical records during the 72-hour follow-up of the newborn, or until discharge or death, whichever occurred first. The main outcome measure was the association between skin reflectance and RDS using univariate and multivariate binary logistic regression. Additionally, we assessed the connection between skin reflectance and factors such as neonatal intensive care unit (NICU) admission and the need for ventilatory support. Results Out of 604 newborns, 470 (73.4%) were from the RDS group and 170 (26.6%) were from the control group. According to comparisons between the groups, newborns with RDS had a younger gestational age (31.6 vs 39.1 weeks, P&lt;.001) and birth weight (1491 vs 3121 grams, P&lt;.001) than controls. Skin reflectance was associated with RDS (odds ratio [OR] 0.982, 95% CI 0.979-0.985, R2=0.632, P&lt;.001). This relationship remained significant when adjusted by the cofactors antenatal corticosteroid and birth weight (OR 0.994, 95% CI 0.990-0.998, R2=0.843, P&lt;.001). Secondary outcomes also showed differences in skin reflectance. The mean difference was 0.219 (95% CI 0.200-0.238) between newborns that required ventilatory support versus those that did not and 0.223 (95% CI 0.205-0.241) between newborns that required NICU admission versus those that did not. Skin reflectance was associated with ventilatory support (OR 0.996, 95% CI 0.992-0.999, R2=0.814, P=.01) and with NICU admission (OR 0.994, 95% CI 0.990-0.998, R2=0.867, P=.004). Conclusions Our findings present a potential marker of lung immaturity at birth using the indirect method of skin assessment. Using the RDS clinical condition and a medical device, this study demonstrated the synchrony between lung and skin maturity. Trial Registration Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-3f5bm5; https://tinyurl.com/9fb7zrdb International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2018-027442

Evaluation of parasitemia by qPCR in patients with chronic Chagas disease treated with benznidazole

Objective: To evaluate parasitemia by qPCR in patients undergoing etiological treatment and followed in a Brazilian reference center. Methods: Parasite load was quantified by qPCR in 32 participants with chronic Chagas disease who were treated with benznidazole. Serological analyses were performed before and after the treatment and parasite loads were compared prior and 12/18 months post the treatment. Results: Thirty-two participants were recruited and treated with benznidazole, and 20 were followed-up. Adverse events (AE) were observed in 22 out of 29 participants that had safety data (76%), and dermatological alterations were the most frequently observed AE. Of the 20 participants analyzed, 13 and 7 completed 12 and 18 months follow-up after the treatment, respectively. 12 Months after the final treatment, Trypanosoma cruzi was detectable in 3 patients by qPCR; 18 months after the final treatment, Trypanosoma cruzi was detectable per qPCR in 4 of the 7 participants. Thus, between 12 and 18 months, 7 participants of the 20 initial follow-up cases showed positive qPCR, indicating treatment failures. Conclusions: qPCR can be used as an alternative method for evaluating the effectiveness of the etiological treatment of CD, and can be applied to analyze early therapeutic failures. The study showed that benznidazole therapy had limited effectiveness in treating chronic CD patients, thus emphasizing the importance of conducting continued research for developing more effective therapies and diagnosis for CD.

Clinical and epidemiological features of mpox in a Brazilian reference center for HIV and sexually transmitted infections: A cross-sectional study

BackgroundThe 2022 mpox outbreak has affected disproportionately people living with HIV (PLWH) and pre-exposure prophylaxis (PrEP) users. MethodsWe conducted a cross-sectional study to evaluate factors associated with laboratory diagnosis of mpox among suspected cases, and access differences between PrEP users and PLWH with confirmed diagnostic. Results394 mpox suspected cases were analyzed, 309 (78.4%) confirmed. Most patients with mpox were PLWH (54.4%) and 99 (32%) PrEP users. Mpox cases were likely to be between 25 and 39 years old (aOR=2.8; p=0.042), men who have sex with men/bisexual or transgender women (aOR=17.2; p< 0.001) and to have fever (aOR=4.7; p< 0.001), adenomegaly (aOR=7.2; p< 0.001) and multiple vesicular lesions (aOR=4.2; p< 0.001). Comparing PrEP users to PLWH with confirmed mpox, PrEP users had lesions predominantly with exclusive genital involvement (p=0.016); while PLWH had higher extragenital involvement (p=0.018). ConclusionsPrEP users and PLWHA were the main epidemiological groups in our cohort. Recognizing the differences between vulnerable populations can contribute to the development public policies to control mpox in settings with reduced access to vaccines

Real-world evidence of the burden of sickle cell disease: a 5-year longitudinal study at a Brazilian reference center

IntroductionSickle cell disease (SCD) is an inherited and multisystem blood disorder characterized by hemolytic anemia, vaso-occlusive crises (VOCs), progressive multiorgan damage and increased mortality. In Brazil, it is one of the most common monogenic diseases afflicting 60,000 to 100,000 individuals, however, there are sparse epidemiological data, as well as information on the utilization of public healthcare resources. Method: This was a 5-year (2016 - 2020) retrospective study conducted at one Brazilian reference center on SCD - Santa Casa de Sao Paulo, in Sao Paulo, Brazil. ResultsAmong a total of 100 eligible adult patients, the median age was 31.0 years old, 84% of the patients were aged between 18 and 45 years old; 59% were women and 91% presented the genotype HbSS. The number of hematologist and non-hematologist visits at the outpatient unit were 2,198 and 1,436, respectively. The number of hospital ER visits was 758, of which 51% required 864 days of hospitalization. The main cause for seeking hospital medical care was the VOCs. The numbers and ratios of VOCs were: 1 to 10 VOCs, 64%; 11 to 20, 15%, and; 21 or more, 1%. There was a statistically significant difference between the number of VOCs and hospitalizations, as well as infection. Conclusion: Results indicate the burden of SCD on Brazilian patients’ daily lives, the impact of VOCs on public healthcare resources, the importance of having a national surveillance program to improve resource utilization and clinical outcomes of patients with SCD and the urgent need for the revitalizing of the current national comprehensive SCD care programs.

Misdiagnosis in multiple sclerosis in a Brazilian reference center: Clinical, radiological, laboratory profile and failures in the diagnostic process-Cohort study.

Multiple sclerosis misdiagnosis remains a problem despite the well-validated McDonald 2017. For proper evaluation of errors in the diagnostic process that lead to misdiagnosis, it is adequate to incorporate patients who are already under regular follow-up at reference centers of demyelinating diseases. To evaluate multiple sclerosis misdiagnosis in patients who are on follow-up at a reference center of demyelinating diseases in Brazil. We designed an observational study including patients in regular follow-up, who were diagnosed with multiple sclerosis at our specialized outpatient clinic in the Hospital of Clinics in the University of Sao Paulo, from 1996 to 2021, and were reassessed for misdiagnosis in 2022. We evaluated demographic information, clinical profile, and complementary exams and classified participants as "established multiple sclerosis," "non-multiple sclerosis, diagnosed," and "non-multiple sclerosis, undiagnosed." Failures in the diagnostic process were assessed by the modified Diagnostic Error Evaluation and Research tool. A total of 201 patients were included. After analysis, 191/201 (95.02%) participants were confirmed as "established multiple sclerosis," 5/201 (2.49%) were defined as "non-multiple sclerosis, diagnosed," and 5/201 (2.49%) were defined as "non-multiple sclerosis, undiagnosed." Multiple sclerosis misdiagnosis persists in reference centers, emphasizing the need for careful interpretation of clinical findings to prevent errors.

Liver transplant in patients with primary sclerosing cholangitis: A retrospective cohort from Northeastern Brazil.

Primary sclerosing cholangitis (PSC) manifests within a broad ethnic and racial spectrum, reflecting different levels of access to health care. To evaluate the clinical profile, complications and survival rates of patients with PSC undergoing liver transplantation (LTx) at a Brazilian reference center. All patients diagnosed with PSC before or after LTx were included. The medical records were reviewed for demographic and clinical variables, including outcomes and survival. The level of statistical significance was set at P < 0.05. Our cohort represented 1.6% (n = 34) of the 2113 patients receiving liver grafts at our service over the past two decades. Most were male (n = 19; 56%). The average age (40 ± 14 years) was similar for men and women (P = 0.347). The mean follow-up time from diagnosis to LTx was 68 mo. Most patients had the classic form of PSC. Three women had PSC/autoimmune hepatitis overlap syndrome, and one patient had small-duct PSC. Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease. scores were significantly higher in males. Inflammatory bowel research (IBD) was investigated by colonoscopy in 26/34 (76%) and was present in most cases (18/26; 69%). IBD was less common in women than in men (44.4% vs. 55.6%) (P = 0.692). Cholangiocarcinoma (CCA) was diagnosed in 2/34 (5.9%) patients by histopathology of the explant (survival: 3 years 6 mo, and 4 years 11 mo). Two patients had complications requiring a second LTx (one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction). Five patients (14.7%) developed biliary stricture. The overall median post-LTx survival was 66 mo. Most deaths occurred in the first year (infection n = 2, primary liver graft dysfunction n = 3, unknown cause n = 1). The 1-year and 5-year survival rates of this cohort were 82.3% and 70.6%, respectively, matching the mean overall survival rates of LTx patients at our center (87.1% and 69.43%, respectively) (P = 0.83). Survival after 1 and 5 years was similar to that of other LTx indications. The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.

Survival and Response Outcomes for Gastrointestinal Neuroendocrine Tumor (GEP-NETs) Patients Treated with Lutetium-177-DOTATATE in a Brazilian Reference Center: A Six-Year Follow-Up Experience.

PRRT can be an option for all-grade GEP-NETs, but selecting patients is challenging. In this scenario, clinical-pathological and radiological characteristics, such as pre-treatment Ga-68 DOTA PET/CT, might have the potential to help. A retrospective chart review was conducted on advanced GEP-NETs treated with at least one PRRT dose. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Krenning Score (KS), and the maximum standardized uptake value (SUVmax) were derived from the pre-treatment scans. A maximally selected rank statistics test was used for SUVmax simple cut point estimate. Among 36 patients, 19 had primary pancreatic tumors. The numbers of G1, G2, and G3 tumors were 10, 18, and 7, respectively. During a median follow-up of 90.5 months, 4 patients died. Median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 (p = 0.001). Median PFS was 23 months, with G3 showing lower PFS compared to G1 [7 versus 30 months; HR 8.41 (95%CI 2.2-31.0; p = 0.001)]. PRRT provides long-term PFS in patients with G1/G2 GEP-NETs independent of clinical characteristics and primary site. G3 has worse survival, but selected patients may experience long OS after PRRT treatment.

Prevalence and incidence of health problems and their characteristics in Brazilian para athletes: A one-season single-center prospective pilot study

BackgroundPara athletes experience high prevalence and incidence of health problems related to sport. Despite this, there are few longitudinal studies. ObjectiveTo describe the characteristics, prevalence, incidence, and severity of health problems in para athletes from one of the Brazilian Paralympic Reference Centers during a sports season and to compare the prevalence of health problems between para athletics, para powerlifting, and para swimming. MethodsThis prospective pilot study was conducted from October 2019 to March 2020. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used to record injuries and illnesses every week for 24 weeks. The characteristics, prevalence, incidence, and severity of health problems were described for each modality. The prevalence of health problems was compared among the three sport modalities. ResultsThirty-five para athletes participated. Most of the injuries occurred in the shoulder, and most illnesses caused respiratory and gastrointestinal symptoms. The average weekly prevalence and the incidence rate of health problems were 40.6% (95% CI 17.0–64.4) and 12.7 (95% CI 9.6–15.9) per 1000 athlete hours, respectively. Para powerlifting had the highest prevalence of all and substantial health problems; para swimming had the lowest prevalence of injuries; and para athletics had the lowest prevalence of illnesses. ConclusionsThis group of Brazilian para athletes showed a high prevalence and incidence of health problems throughout the season. Para athletics, para powerlifting, and para swimming each had a different prevalence of injuries and illnesses.

Development and validation of a new quantitative reverse transcription PCR assay for the diagnosis of human sporotrichosis.

Sporotrichosis is an emergent public health problem. The mycological diagnosis of this infection is based on culture, which is fastidious and may represent a biohazard for technicians. Although not widely implemented in routine diagnosis, molecular methodologies are fast, have good accuracy, and can be easily standardized, aiding in the early diagnosis of neglected mycoses. This study aimed at implementing a new pan-Sporothrix quantitative reverse transcription PCR (RT-qPCR) assay, and then validating it on clinical samples from confirmed human sporotrichosis cases. Sixty-eight human samples with culture-confirmed diagnostic of sporotrichosis were collected from 64 patients followed at a Brazilian reference center for endemic mycoses. These samples were submitted to whole nucleic acids extraction, followed by a RT-qPCR protocol. The limit of detection was 244 fg, the efficiency was 2.0 (100%), and the assay could amplify the genetic material of the three major clinically relevant species of the genus Sporothrix. Among the 68 samples analyzed, 62 were positive in RT-qPCR, showing an overall sensitivity of 91.18%, which variated according to the type of biological sample: 96.72% in skin samples (n=61), 100% in respiratory (n=3), whereas all cerebrospinal fluid specimens (n=4) were negative. The specificity was 100% when tested in 25 samples from patients with other mycoses and tuberculosis. In addition, DNA from 93 fungal species did not yield positive results, confirming the high specificity of this test. Our RT-qPCR presented high sensitivity and specificity, representing an excellent tool for a fast and reliable diagnosis of human sporotrichosis.

EE335 A Multicenter Microcosting Study for COVID-19 in Brazil

This study aims to evaluate COVID-19 in-hospital costs and identify predictors at a patient-level in Brazil. This is multicenter, prospective cohort study that applied time-driven activity-based costing (TDABC) method in five Brazilian reference centers for COVID-19 treatment. Patients hospitalized between March and August 2020 (first wave of the disease) and had their COVID-19 status confirmed by reverse transcription-polymerase chain reaction (RT–PCR) at arrival were included in our sample. The cost information was calculated at the patient level and multivariable analyses were applied to identify clinical predictors of cost variability, considering ICU admissions and patient’s comorbidities. 830 patients were included into the analysis. The median cost per patient was I$4,428 (IQR 2,019; 11,464), and patients hospitalized in ICU demonstrated significative higher costs (p<0.001). Patients hospitalized in ICU the median was I$11,596 (IQR 6,016; 23,374), while for those who were hospitalized in ward was 1,895 (IQR 1,050; 3,317). Median cost per day was I$ 455 (IQR 308; 711) for the total sample, I$690 (IQR I,528; 1,046) for ICU patients and I$350 (IQR 255; 449) for non-ICU. Gender (p<0.001), Obesity (p = 0.005) and Chronic pulmonary diseases (p = 0.044) were identified as clinical predictors for hospital costs. By developing a multicenter microcosting study for COVID-19 this study allowed to measure the variability in resource consumption per patients’ according their clinical characteristics. These findings can sustain the development of financially sustainable health policies in middle-income countries such as Brazil.

Telehealth for amyotrophic lateral sclerosis in a multidisciplinary service in a Brazilian reference center.

Telehealth has been used in the treatment of different diseases, and it has been shown to provide benefits for patients with amyotrophic lateral sclerosis (ALS). Due to the social distancing measures put into effect during the coronavirus disease 2019 (COVID-19) pandemic, there was an urgent need for telehealth to ensure the provision of healthcare. To evaluate the feasibility of telehealth for the provision of multidisciplinary ALS care, and to assess its acceptability among patients and caregivers. We conducted a retrospective cohort study in which multidisciplinary evaluations were performed using the Teleconsulta platform. The patients included had ALS and at least one in-person clinical evaluation. The patients and the caregivers answered satisfaction questionnaires. The sample was composed of 46 patients, 32 male and 14 female subjects. The average distance from their residences to the reference services was of 115 km. Respiratory adjustment was the most addressed topic. The strategy is viable and well accepted in terms of satisfaction. It was even more positive for patients in advanced stages of the disease or for those living far from the referral center.

Comparison of COVID-19 hospitalization costs across care pathways: a patient-level time-driven activity-based costing analysis in a Brazilian hospital

BackgroundThe COVID-19 pandemic raised awareness of the need to better understand where and how patient-level costs are incurred in health care organizations, as health managers and other decision-makers need to plan and quickly adapt to the increasing demand for health care services to meet patients’ care needs. Time-driven activity-based costing offers a better understanding of the drivers of cost throughout the care pathway, providing information that can guide decisions on process improvement and resource optimization. This study aims to estimate COVID-19 patient-level hospital costs and to evaluate cost variability considering the in-hospital care pathways of COVID-19 management and the patient clinical classification.MethodsThis is a prospective cohort study that applied time-driven activity-based costing (TDABC) in a Brazilian reference center for COVID-19. Patients hospitalized during the first wave of the disease were selected for their data to be analyzed to estimate in-hospital costs. The cost information was calculated at the patient level and stratified by hospital care pathway and Ordinal Scale for Clinical Improvement (OSCI) category. Multivariable analyses were applied to identify predictors of cost variability in the care pathways that were evaluated.ResultsA total of 208 patients were included in the study. Patients followed five different care pathways, of which Emergency + Ward was the most followed (n = 118, 57%). Pathways which included the intensive care unit presented a statistically significant influence on costs per patient (p < 0.001) when compared to Emergency + Ward. The median cost per patient was I$2879 (IQR 1215; 8140) and mean cost per patient was I$6818 (SD 9043). The most expensive care pathway was the ICU only, registering a median cost per patient of I$13,519 (IQR 5637; 23,373) and mean cost per patient of I$17,709 (SD 16,020). All care pathways that included the ICU unit registered a higher cost per patient.ConclusionsThis is one of the first microcosting study for COVID-19 that applied the TDABC methodology and demonstrated how patient-level costs vary as a function of the care pathways followed by patients. These findings can be used to develop value reimbursement strategies that will inform sustainable health policies in middle-income countries such as Brazil.

Survival outcomes for patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with lutetium-177-dotatate (Lu-177) in a Brazilian reference center: A six-year follow-up experience.

642 Background: GEP-NETs are the most common NETs primary site. Lu-177 is the standard treatment for patients with grade 1 (G1) or grade 2 (G2) midgut NETs who had disease progression during first-line somatostatin analog therapy. Methods: We performed a retrospective chart review including advanced GEP-NETs treated with at least one Lu-177 dose from our institution. Overall survival (OS) and progression-free survival (PFS) were calculated from the first Lu-177 dose using the Kaplan–Meier method. Cox regression analysis was performed for PFS adjusted by grade, primary tumor site, metastasis sites (1 vs.≥ 2), presence of liver metastasis, and previous local or other systemic treatments. Krenning Score (KS) and the maximum standardized uptake value (SUVmax) were calculated from the pre-treatment Ga-68 PET/CT. Maximally Selected Rank Statistics (MSRS) test was used for SUVmax simple cutpoint estimate and PFS was calculated using the Kaplan–Meier method. Results: 36 pts were included; the median age was 51 (range: 33-80). 19 (52.8%) pts had primary pancreatic NET and 17 (47.2%) had non-pancreatic primary NETs. Tumor grading was classified based on Ki67%. 10 pts were G1 (28.6%), 18 pts were G2 (51.4%), 7 pts were G3 (20%). 7 pts (19.4%) and 28 pts (77.7%) had KS 3 and 4, respectively. 125 cycles of Lu-177 were applied with 3.5 cycles per pts (mean; range: 1-6). 12 (33.3%) pts experienced grade 1 and 2 toxicity, mainly fatigue (n=4). No grade 3 or 4 toxicities were reported. 4 (11.1%) patients died (n=3 G3; n=1 G2) with median follow-up of 90.5 months (range: 16-122). 11 pts (30.6%) lost follow-up after Lu-177 treatment. 29 pts (80.5%) were eligible for OS. 24-month and 36-month survival rates were 92,7% (95% CI 73.7 - 98.1) and 86,9% (95% CI 63.5 - 95.7) respectively. The median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 tumors (p=0.001). 34 (94%) pts were eligible for PFS. The median PFS was 23 months (95% CI 30.5-64.9) for the entire cohort. The median PFS was 30 months for G1, 27 months for G2 pts, and 7 months for G3 pts. G1/G2 vs. G3 median PFS was statistically different in the uni- and multivariate analysis [HR 8.41 (95%CI 2.2-31.0; p=0.001)]. The primary site, metastasis sites, number of previous systemic treatments, previous local treatment, and presence of liver metastasis did not correlate with PFS in the multivariate analyses. Pts with SUVmax &gt; 34.53 exhibited a statistical trend toward a longer PFS (median 52.0 vs 18.7 months; p=0.06). Conclusions: This real-life study supports that Lu-177 provides long-term PFS in pts KS 3/4 with G1/G2 GEP-NETs independent of clinical characteristics and primary site. Although G3 pts have worse survival, selected G3 GEP-NETs may experience long OS after Lu-177 treatment. SUVmax values from the pre-treatment Ga-68 PET/CT study may select ideal pts for Lu-177.