Tumor growth and overall survival modeling to support decision making in phase Ib/II trials: A comparison of the joint and two-stage approaches.

Model-based tumor growth inhibition (TGI) metrics are increasingly used to predict overall survival (OS) data in Phase III immunotherapy clinical trials. However, there is still a lack of understanding regarding the differences between two-stage or joint modeling methods to leverage Phase I/II trial data and help early decision-making. A recent study showed that TGI metrics such as the tumor growth rate constant KG may have good operating characteristics as early endpoints. This previous study used a two-stage approach that is easy to implement and intuitive but prone to bias as it does not account for the relationship between the longitudinal and time-to-event processes. A relevant alternative is to use a joint modeling approach. In the present article, we evaluated the operating characteristics of TGI metrics using joint modeling, assuming an OS model previously developed using historical data. To that end, we used TGI and OS data from IMpower150-a study investigating atezolizumab in over 750 patients suffering from non-small cell lung cancer-to mimic randomized Phase Ib/II trials varying in terms of number of patients included (40 to 15 patients per arm) and follow-up duration (24 to 6 weeks after the last patient included). In this context, joint modeling did not outperform the two-stage approach and provided similar operating characteristics in all the investigated scenarios. Our results suggest that KG geometric mean ratio could be used to support early decision-making provided that 30 or more patients per arm are included and followed for at least 12 weeks.

Transoral endoscopic vestibular approach Sistrunk procedure (TEVAS)-case report and scoping review.

Background: Thyroglossal duct cyst (TGDC) is the most common congenital neck mass among the pediatric population. Less than 10% of the cases occur in adults. The standard of care for TGDC is surgical treatment with the Sistrunk procedure via a traditional transverse cervicotomy. This technique involves the resection of the cyst with its tract and the central portion of the hyoid bone body to avoid recurrence. The transoral vestibular approach has gained popularity as an alternative approach to open neck surgery in order to eliminate the transcervical scar associated with these procedures. Methods: We describe a case of an endoscopic Sistrunk procedure performed by the transoral vestibular approach. A scoping review of the transoral endoscopic vestibular approach Sistrunk procedure (TEVAS) was performed. The PubMed, Medline, Cochrane, Lilacs, Scielo, Mary Ann Libert and Scopus databases were systematically searched by using a Medical Subject Heading (MeSH)-optimized search strategy. The selection of papers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines after setting inclusion and exclusion criteria. Results: The case was successful and without complications. Five studies were included in the final analysis for this review. Conclusions: This novel approach to the Sistrunk procedure is an effective alternative way to treat TGDC in selected patients who are motivated to avoid a visible neck scar.

Comparison of two-stage and joint TGI-OS modeling using data from six atezolizumab clinical studies in patients with metastatic non-small cell lung cancer.

Two-stage and joint modeling approaches are the two main approaches to investigate the link between longitudinal tumor size data and overall survival (OS) and anticipate clinical trial outcome. We here used a large database composed of one phase II and five phase III clinical trials evaluating atezolizumab (an immunotherapy) in monotherapy or in combination with chemotherapies in 3699 patients with non-small cell lung cancer to evaluate the differences between both approaches in terms of parameter estimates, magnitude of covariate effects, and ability to predict OS. Although the two-stage approach may underestimate the magnitude of the impact of tumor growth rate (KG ) on OS compared to joint modeling approach (hazard ratios [HRs] of 0.42-2.52 vs. 0.25-2.85, respectively, for individual KG varying from the 5th and 95th percentiles), this difference did not lead into poorer performance of the two-stage approach to describe the OS distribution in the six clinical studies. Overall, two-stage and joint modeling approaches accurately predicted OS HR with a median (range) difference with the observed OS HR of 0.02 (0.01-0.18) and 0.03 (0.00-0.19), in all cases considered, respectively (e.g., for IMpower150: 0.80 [0.66-0.95] vs. 0.82 [0.70-0.95], respectively, whereas the observed OS HR was 0.80). In our setting, the two-stage approach accurately predicted the benefit of atezolizumab on OS. Further work is needed to verify if similar results are achieved using phase Ib or phase II clinical trials where the number of patients and measurements is limited as well as in other cancer indications.

Population Pharmacokinetics and Exposure-Response Analysis for the CTLA-4 Inhibitor Tremelimumab in Metastatic NSCLC Patients in the Phase III POSEIDON Study.

Blockade of CTLA-4 by tremelimumab combined with anti-PD-L1 durvalumab and chemotherapy provided increased antitumor activity and long-term survival benefits in first-line metastatic non-small cell lung cancer (mNSCLC) in the phase III POSEIDON study. We performed population pharmacokinetic modeling for tremelimumab using data from 1,605 patients across 6 studies (including POSEIDON) in multiple tumors (lung cancer, bladder cancer, malignant mesothelioma, and other solid tumors), and identified a 2-compartment model with linear and time-varying clearance for tremelimumab. Cox proportional hazard regression models were applied to 326 patients with mNSCLC from POSEIDON to evaluate the association between exposure metrics and efficacy end points, adjusting for baseline prognostic covariates. Improved progression-free survival (PFS) and overall survival (OS) in the tremelimumab arm (in combination with durvalumab and chemotherapy) was associated with higher tremelimumab exposure (e.g., minimum concentration at 5th dose (Cmin,dose5 ) and area under the curve at 5th dose (AUCdose5 )). However, further case-matching analyses yielded hazard ratios for the comparison of tremelimumab-treated patients in the Cmin,dose5 quartile 1 (Q1) subgroup with matched chemotherapy-treated patients of 1.04 (95% confidence interval (CI): 0.76-1.44) for OS and 0.99 (95% CI: 0.72-1.36) for PFS, suggesting that the observed apparent exposure-response relationship might be confounded. No relationship between tremelimumab exposure and safety (grade ≥3 treatment-emergent adverse events [AEs], AEs of special interest, or discontinuation due to AEs) was identified. These results support the consistent benefit observed with tremelimumab 75 mg every 3 weeks for up to 5 doses in combination with durvalumab and chemotherapy in POSEIDON as first-line therapy for mNSCLC.

Transoral thyroid and parathyroid surgery in Brazil: where are we?

INTRODUCTION: thyroid surgery through the transoral vestibular approach is a reality in many countries. While several competing remote access techniques have been developed in the last 20 years, many were not reproducible. Transoral Endoscopic Neck Surgery (TNS) has been shown to be reproducible in different centers around the world, and approximately five years after its description it has been adopted relatively quickly for various reasons. To date, there are at least 7 Brazilian studies published, including a series of more than 400 cases. The aim of this work is to study the progression of Transoral Neck Surgery in Brazil and describe the profile of surgeons involved in this new approach. METHODS: this is a retrospective study with descriptive statistics. A REDCap based survey about transoral endoscopic thyroidectomy and parathyroidectomy vestibular approach (TOETVA/TOEPVA) was done with 66 Brazilian surgeons regarding surgeon profile, numbers of cases performed by geographic region, what kind of training was necessary prior to the first case and behavior of the surgeon proposing these new approaches. RESULTS: response rate of this survey was 53%. To date, 1275 TOETVA/TOEPVA cases had been performed in Brazil, 1229 thyroidectomies (96.4%), 42 parathyroidectomies (3.3%) and 4 combined procedures (0.3%). Most of the cases were done in the southeast region (821, 64.4%), 538 (42.2%) cases in the State of São Paulo and 283 (22.2%) cases in the State of Rio de Janeiro. CONCLUSIONS: TOETVA is becoming popular in Brazil. Younger surgeons, especially those between 30 and 50 years old were more likely to adopt this approach.

Early Decision Making in a Randomized Phase II Trial of Atezolizumab in Biliary Tract Cancer Using a Tumor Growth Inhibition-Survival Modeling Framework.

We assess the longitudinal tumor growth inhibition (TGI) metrics and overall survival (OS) predictions applied to patients with advanced biliary tract cancer (BTC) enrolled in IMbrave151 a multicenter randomized phase II, double-blind, placebo-controlled trial evaluating the efficacy and safety of atezolizumab with or without bevacizumab in combination with cisplatin plus gemcitabine. Tumor growth rate (KG) was estimated for patients in IMbrave151. A pre-existing TGI-OS model for patients with hepatocellular carcinoma in IMbrave150 was modified to include available IMbrave151 study covariates and KG estimates and used to simulate IMbrave151 study outcomes. At the interim progression-free survival (PFS) analysis (98 patients, 27 weeks follow-up), clear separation in tumor dynamic profiles with a faster shrinkage rate and slower KG (0.0103 vs. 0.0117 week-1 ; tumor doubling time 67 vs. 59 weeks; KG geometric mean ratio of 0.84) favoring the bevacizumab containing arm was observed. At the first interim analysis for PFS, the simulated OS hazard ratio (HR) 95% prediction interval (PI) of 0.74 (95% PI: 0.58-0.94) offered an early prediction of treatment benefit later confirmed at the final analysis, observed HR of 0.76 based on 159 treated patients and 34 weeks of follow-up. This is the first prospective application of a TGI-OS modeling framework supporting gating of a phase III trial. The findings demonstrate the utility for longitudinal TGI and KG geometric mean ratio as relevant end points in oncology studies to support go/no-go decision making and facilitate interpretation of the IMbrave151 results to support future development efforts for novel therapeutics for patients with advanced BTC.

Small anticancer drug release by light: Photochemical internalization of porphyrin-ß-cyclodextrin nanoparticles.

Aiming to engineer simple, neutral, strongly amphiphilic photoactive nanoparticles (NPs) to specifically target cancer cell lysosomes for drug transport and light-controlled release, new conjugates of ß-cyclodextrin with highly hydrophobic triphenylporphyrin bearing different alkyl chains, were synthesized. Although differently sized, all conjugates self-assemble into ~60 nm NPs in water and display similar photoactivity. The NPs target selectively the lysosomes of breast adenocarcinoma MCF-7 cells, embedding in vesicular membranes, as experiments with model liposomes indicate. Either empty or drug-loaded, the NPs lack dark toxicity for 48 h. They bind with differently structured anticancer drugs tamoxifen and gemcitabine as its N-adamantyl derivative. Red light irradiation of cells incubated with drug-loaded NPs results in major reduction of viability (>85 %) for 48 h displaying significant synergy of photo-chemotoxicity, as opposed to empty NPs, and to loaded non-irradiated NPs, in manifestation of photochemical internalization (PCI). Our approach expands the field of PCI into different small molecule chemotherapeutics.

Thermoelectric Properties of Nickel and Selenium Co-Doped Tetrahedrite.

As the search continues for novel, cheaper, more sustainable, and environmentally friendly thermoelectric materials in order to expand the range of applications of thermoelectric devices, the tetrahedrite mineral (Cu12Sb4S13) stands out as a potential candidate due to its high abundance, low toxicity, and good thermoelectric performance. Unfortunately, as most current thermoelectric materials achieve zTs above 1.0, ternary tetrahedrite is not a suitable alternative. Still, improvement of its thermoelectric performance has been achieved to zTs ≈ 1 via isovalent doping and composition tuning, but most studies were limited to a single doping element. This project explores the effects of simultaneous doping with nickel and selenium in the thermoelectric properties of tetrahedrite. Simulated properties for different stoichiometric contents of these dopants, as well as the measured thermoelectric properties of the correspondent materials, are reported. One of the samples, Cu11.5Ni0.5Sb4S12.5Se0.5, stands out with a high power factor = 1279.99 µW/m·K2 at 300 K. After estimating the thermal conductivity, a zT = 0.325 at 300 K was obtained for this composition, which is the highest for tetrahedrites for this temperature. However, analysis of the weighted mobility shows the presence of detrimental factors, such as grain boundaries, disorder, or ionized impurity scattering, pointing to the possibility of further improvements.

Palliative medicine in the emergency department: symptom control and aggressive care.

OBJECTIVES: Identifying the prevalence of palliative care (PC) needs among patients who die at the emergency department (ED) and to assess symptom control and aggressiveness of care. METHODS: We conducted a decedent cohort study of adults deceased at the ED of a Portuguese teaching hospital in 2016. PC needs were identified using the National Hospice Organization terminality criteria and comorbidities measurement by the Charlson's Index. RESULTS: 384 adults died at the ED (median age 82 (IQR 72-89) years) and 78.4% (95% CI 73.9% to 82.2%) presented PC needs. Only 3.0% (n=9) were referred to the hospital PC team. 64.5%, 38.9% and 57.5% experienced dyspnoea, pain and confusion, respectively. Dyspnoea was commonly medicated (92%), against 56% for pain and 8% for confusion. Only 6.3% of the patients were spared from aggressive interventions, namely blood collection (86.0%) or intravenous fluid therapy (63.5%). The burden of aggressive interventions was similar between those with or without withhold cardiopulmonary resuscitation order (median 3 (2-4) vs 3 (2-5)), p=0.082. CONCLUSIONS: Nearly four out of five adults who died at the ED had PC needs at the time of admission. Most experienced poor symptom control and care aggressiveness in their last hours of life and were mostly unknown to the PC team. The findings urge improvements in the care provided to patients with PC needs at the ED, focusing on patient well-being and increased PC referral.

Transoral thyroid and parathyroid surgery in Brazil: where are we? / Cirurgia transoral de tireóide e paratireóide no Brasil: onde estamos?

ABSTRACT Introduction: thyroid surgery through the transoral vestibular approach is a reality in many countries. While several competing remote access techniques have been developed in the last 20 years, many were not reproducible. Transoral Endoscopic Neck Surgery (TNS) has been shown to be reproducible in different centers around the world, and approximately five years after its description it has been adopted relatively quickly for various reasons. To date, there are at least 7 Brazilian studies published, including a series of more than 400 cases. The aim of this work is to study the progression of Transoral Neck Surgery in Brazil and describe the profile of surgeons involved in this new approach. Methods: this is a retrospective study with descriptive statistics. A REDCap based survey about transoral endoscopic thyroidectomy and parathyroidectomy vestibular approach (TOETVA/TOEPVA) was done with 66 Brazilian surgeons regarding surgeon profile, numbers of cases performed by geographic region, what kind of training was necessary prior to the first case and behavior of the surgeon proposing these new approaches. Results: response rate of this survey was 53%. To date, 1275 TOETVA/TOEPVA cases had been performed in Brazil, 1229 thyroidectomies (96.4%), 42 parathyroidectomies (3.3%) and 4 combined procedures (0.3%). Most of the cases were done in the southeast region (821, 64.4%), 538 (42.2%) cases in the State of São Paulo and 283 (22.2%) cases in the State of Rio de Janeiro. Conclusions: TOETVA is becoming popular in Brazil. Younger surgeons, especially those between 30 and 50 years old were more likely to adopt this approach.

RESUMO Introdução: a cirurgia de tireoide por via transoral vestibular é uma realidade em muitos países. Embora várias outras técnicas de acesso remoto tenham sido desenvolvidas nos últimos 20 anos, muitas não eram reprodutíveis. A cirurgia endoscópica cervical transoral (TNS - Transoral Neck Surgery) tem se mostrado reprodutível em diferentes centros ao redor do mundo sendo que, aproximadamente cinco anos após sua descrição, foi adotada de forma relativamente rápida por vários motivos. Até o momento, existem pelo menos 7 estudos brasileiros publicados, incluindo uma série de mais de 400 casos. O objetivo deste trabalho é estudar a evolução da Cirurgia Transoral do Pescoço (TNS) no Brasil e descrever o perfil dos cirurgiões envolvidos nesta nova abordagem. Métodos: trata-se de um estudo descritivo. Uma pesquisa online hospedada no REDCap sobre tireoidectomia e paratireoidectomia endoscópica transoral por abordagem vestibular (TOETVA/TOEPVA) foi realizada com 66 cirurgiões brasileiros. Foram levantados dados sobre o perfil do cirurgião, número de casos realizados por região geográfica, que tipo de treinamento foi necessário antes do primeiro caso e comportamento do cirurgião durante o relacionamento com o paciente ao abordar essas novas técnicas. Resultados: a taxa de resposta desta pesquisa foi de 53%. Até o momento, 1.275 casos de TOETVA/TOEPVA foram realizados no Brasil, sendo 1.229 tireoidectomias (96,4%), 42 paratireoidectomias (3,3%) e 4 procedimentos combinados (0,3%). A maioria dos casos foi realizada na região sudeste (821, 64,4%), 538 (42,2%) casos no estado de São Paulo e 283 (22,2%) casos no estado do Rio de Janeiro. Conclusões: a TOETVA está se popularizando no Brasil. Cirurgiões mais jovens, especialmente aqueles entre 30 e 50 anos, são mais propensos a adotar essa abordagem.

Analysis of the status of treatment of benign thyroid diseases - a public health problem aggravated in the COVID-19 pandemic era / Análise da situação do tratamento das doenças benignas da tireoide - Um problema de saúde pública agravado pela pandemia de Covid-19

Abstract Objective: Goiters and benign nodules detected in the thyroid are growing lesions and the COVID-19 pandemic have negatively impacted on their surgical treatment. The appropriate selection of patients to treatment will improve the overall health status. This article review will focus on the impact of the COVID-19 pandemic on treatment of benign conditions of the thyroid gland and their implications. Methods: This review pointed out the status of the health system in developing country and the problems to treat benign surgical diseases of thyroid. Aspects of epidemiology, incidence, clinical presentation and surgical treatment of goiters, economic and health status impact were cited. Results: All surgical treatment of goiter and other benign conditions were postponed, forced to redirect, and reschedule all benign surgeries, situation aggravated by poor public management and closure of hospital beds. These conditions have caused deterioration in patients' physical (decompensated thyroid disease) and mental health status, increasing work disabilities and burdening society by increasing the social and health cost. The overall situation could be catastrophic in emergent countries where this increased disease-related social expenditure on surgical treatment may increase the risk of national impoverishment as increase the treatment cost. Brazilian Society Head and Neck Surgery related some recommendations and new suggestions were made to safely treat these high potential hazard surgical conditions. Conclusions: Surgeries for goiter and benign thyroid conditions can be performed during the COVID-19 pandemic, following strict safety protocols for the patient and the medical team, reducing the negative economic and on patient health impact.

Resumo Objetivo: Bócios e nódulos benignos detectados na tireoide são lesões em crescimento e a pandemia de Covid-19 impactou negativamente seu tratamento cirúrgico. A seleção adequada de pacientes para o tratamento vai melhorar o estado geral de saúde. Esta revisão de artigos se concentrará no impacto da pandemia de Covid-19 no tratamento de condições benignas da glândula tireoide e suas implicações. Método: Esta revisão evidenciou a situação do sistema de saúde em países em desenvolvimento e os problemas para tratar doenças cirúrgicas benignas da tireoide. Aspectos da epidemiologia, incidência, apresentação clínica e tratamento cirúrgico do bócio, impacto econômico e no estado de saúde foram relatados. Resultados: Todos os tratamentos cirúrgicos de bócio e outras condições benignas foram adiados, forçados a se redirecionar e a remarcar todas as cirurgias benignas, situação agravada pela má gestão pública e fechamento de leitos hospitalares. Essas condições têm causado deterioração do estado de saúde física (doença da tireoide descompensada) e mental dos pacientes, aumentam as incapacidades para o trabalho e sobrecarregando a sociedade e o custo social e de saúde. A situação geral pode ser catastrófica em países emergentes, onde esse aumento dos gastos sociais relacionados à doença sob tratamento cirúrgico pode aumentar o risco de empobrecimento nacional à medida que aumenta o custo do tratamento. A Sociedade Brasileira de Cirurgia de Cabeça e Pescoço forneceu algumas recomendações e novas sugestões foram feitas para tratar com segurança essas condições cirúrgicas de alto risco potencial. Conclusão: As cirurgias para bócio e condições benignas da tireoide podem ser feitas durante a pandemia de Covid-19, se forem seguidos rigorosos protocolos de segurança para o paciente e equipe médica, o que reduz o impacto negativo na economia e na saúde do paciente.

Capacidade Preditiva dos Parâmetros do Teste de Esforço Cardiopulmonar em Pacientes com Insuficiência Cardíaca em Terapia de Ressincronização Cardíaca / Predictive Ability of Cardiopulmonary Exercise Test Parameters in Heart Failure Patients with Cardiac Resynchronization Therapy

Resumo Fundamento Há evidências sugerindo que um corte do pico de consumo de oxigênio (pVO2) de 10ml/kg/min fornece uma estratificação de risco mais precisa em pacientes com Terapia de Ressincronização Cardíaca (TRC). Objetivo Comparar o poder prognóstico de vários parâmetros do teste cardiopulmonar de exercício (TCPE) nesta população e avaliar a capacidade discriminativa dos valores de corte de pVO2 recomendados pelas diretrizes. Métodos Avaliação prospectiva de uma série consecutiva de pacientes com insuficiência cardíaca (IC) com fração de ejeção do ventrículo esquerdo ≤40%. O desfecho primário foi um composto de morte cardíaca e transplante cardíaco urgente (TC) nos primeiros 24 meses de acompanhamento, e foi analisado por vários parâmetros do TCPE para a maior área sob a curva (AUC) no grupo TRC. Uma análise de sobrevida foi realizada para avaliar a estratificação de risco fornecida por vários pontos de corte diferentes. Valores de p < 0,05 foram considerados significativos. Resultados Um total de 450 pacientes com IC, dos quais 114 possuíam aparelho de TRC. Esses pacientes apresentaram um perfil de risco basal mais alto, mas não houve diferença em relação ao desfecho primário (13,2% vs 11,6%, p = 0,660). A pressão expiratória de dióxido de carbono no limiar anaeróbico (PETCO2AT) teve o maior valor de AUC, que foi significativamente maior do que o de pVO2 no grupo TRC (0,951 vs 0,778, p = 0,046). O valor de corte de pVO2 atualmente recomendado forneceu uma estratificação de risco precisa nesse cenário (p <0,001), e o valor de corte sugerido de 10 ml/min/kg não melhorou a discriminação de risco em pacientes com dispositivos (p = 0,772). Conclusão A PETCO2AT pode superar o poder prognóstico do pVO2 para eventos adversos em pacientes com TRC. O ponto de corte de pVO2 recomendado pelas diretrizes atuais pode estratificar precisamente o risco dessa população.

Abstract Background There is evidence suggesting that a peak oxygen uptake (pVO2) cut-off of 10ml/kg/min provides a more precise risk stratification in cardiac resynchronization therapy (CRT) patients. Objective To compare the prognostic power of several cardiopulmonary exercise testing (CPET) parameters in this population and assess the discriminative ability of the guideline-recommended pVO2cut-off values. Methods Prospective evaluation of consecutive heart failure (HF) patients with left ventricular ejection fraction ≤40%. The primary endpoint was a composite of cardiac death and urgent heart transplantation (HT) in the first 24 follow-up months, and was analysed by several CPET parameters for the highest area under the curve (AUC) in the CRT group. A survival analysis was performed to evaluate the risk stratification provided by several different cut-offs. p values <0.05 were considered significant. Results A total of 450 HF patients, of which 114 had a CRT device. These patients had a higher baseline risk profile, but there was no difference regarding the primary outcome (13.2% vs 11.6%, p =0.660). End-tidal carbon dioxide pressure at anaerobic threshold (PETCO2AT)had the highest AUC value, which was significantly higher than that of pVO2in the CRT group (0.951 vs 0.778, p =0.046). The currently recommended pVO2cut-off provided accurate risk stratification in this setting (p <0.001), and the suggested cut-off value of 10 ml/min/kg did not improve risk discrimination in device patients (p =0.772). Conclusion PETCO2ATmay outperform pVO2's prognostic power for adverse events in CRT patients. The current guideline-recommended pVO2 cut-off can precisely risk-stratify this population.

Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology Patients.

Serial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.

Comparative analysis of anal colposcopy with histology in the follow-up of patients under treatment for anal condyloma

Objectives: To compare morphological abnormalities on anal colposcopy against histology to determine anal high-grade squamous intraepithelial lesions (HSILs). Methods: This is a retrospective data assessment of HIV-negative and HIV-positive patients undergoing outpatient follow-up. The sample comprised 54 patients presenting acetowhite lesions on anal colposcopy. Acetowhite lesions were classified according to their morphology into punctation, verrucous, mosaic, ulcerated, or hypervascularized, and biopsies of these specimens were classified as anal HSIL, low-grade squamous intraepithelial lesion (LSIL), or normal. The data were analyzed using SPSS forWindows version 13.0 (SPSS Inc., Chicago, IL, USA). The results were analyzed using the nonparametric Mann-Whitney test, the Fisher exact test and the chi-squared parametric test. A 95% confidence interval (CI) was used and a level of significance <5% was adopted for all statistical tests. Results Fifty-four patients (50 males, 80% HIV+) with biopsied acetowhite lesions were assessed. There were 31 punctation lesions, 1 classified as HSIL (3.2%; 95%CI: 0- 40.0), 17 verrucous lesions, 3 HSIL (17.7%; 95%CI: 0-10.7), and 1 ulcerated, classified as HSIL (100%), and 4 mosaic and 1 atypical vessel lesion, all classified as LSIL. The results showed no association of presence of anal HSIL with positivity for HIV infection or with counts above or below 500/µl in HIV+patients. Statistical analysis was performed using the Mann-Whitney nonparametric test, the Fisher exact test, and the chi-squared parametric test. Conclusion: The comparison of morphological findings on anal colposcopy against histology revealed no morphological pattern suggesting anal HSIL. (AU)

Radiotherapy Information System in Cancer Treatment Improvement: A Case Study at the Brazilian National Cancer Institute.

Radiotherapy is one of the main means of treating cancer patients. Its application has grown worldwide. Around 50% of all cancer patients should receive radiation. Brazil faces a shortage of radiotherapy treatment because of a lack of enough treatment units, equipment availability, well-trained staff, and fair reimbursement. The Radiotherapy Information System (RIS) implementation to manage information about patient scheduling is vital to improve the efficiency of care and reduce the waiting time to start cancer treatment. The information system deployed can be indicated as a disruptive innovation in the Brazilian public health system, considering the radical improvement in the cancer treatment process at the Brazilian National Cancer Institute.

The Implementation of a Mobile APP for Cancer Care Management at the Brazilian National Cancer Institute.

There is increasing recognition of the potential to use mobile health (mHealth) technologies such as smartphone apps to support clinical care. Mobile apps are progressively being implemented to manage chronic diseases like cancer to improve patient care. The app deployed at the Brazilian National Cancer Institute enables patients to access the appointments/exam booking, medication prescription, and cancer-prevent educational resources, improving self-management, autonomy, and cancer treatment outcomes in resource-limited environments. Despite acknowledging the importance of mHealth, research is still scarce regarding patients' views on using these innovations in cancer care management.

Analysis of the status of treatment of benign thyroid diseases - a public health problem aggravated in the COVID-19 pandemic era.

OBJECTIVE: Goiters and benign nodules detected in the thyroid are growing lesions and the COVID-19 pandemic have negatively impacted on their surgical treatment. The appropriate selection of patients to treatment will improve the overall health status. This article review will focus on the impact of the COVID-19 pandemic on treatment of benign conditions of the thyroid gland and their implications. METHODS: This review pointed out the status of the health system in developing country and the problems to treat benign surgical diseases of thyroid. Aspects of epidemiology, incidence, clinical presentation and surgical treatment of goiters, economic and health status impact were cited. RESULTS: All surgical treatment of goiter and other benign conditions were postponed, forced to redirect, and reschedule all benign surgeries, situation aggravated by poor public management and closure of hospital beds. These conditions have caused deterioration in patients' physical (decompensated thyroid disease) and mental health status, increasing work disabilities and burdening society by increasing the social and health cost. The overall situation could be catastrophic in emergent countries where this increased disease-related social expenditure on surgical treatment may increase the risk of national impoverishment as increase the treatment cost. Brazilian Society Head and Neck Surgery related some recommendations and new suggestions were made to safely treat these high potential hazard surgical conditions. CONCLUSIONS: Surgeries for goiter and benign thyroid conditions can be performed during the COVID-19 pandemic, following strict safety protocols for the patient and the medical team, reducing the negative economic and on patient health impact.

Healthcare-Associated Ventriculitis and Meningitis: A Retrospective Analysis.

Background and objective Healthcare-associated ventriculitis and meningitis (HAVM) is frequent in neurocritical patients and associated with significant mortality. Surgery and intracranial devices are usually necessary and may lead to infection. Classical clinical signs and cerebral spinal fluid (CSF) analysis may be unreliable. The purpose of this study was to characterize the prevalence of HAVM, risk factors, and interventions in the neurocritical population admitted in the ICU. Methods This was a retrospective single-center analysis of all adult neurocritical patients admitted to an ICU during a three-year period. Results A total of 218 neurocritical patients were included. The prevalence of HAVM was 13% and it was found to be associated with mortality. When suspected, it was not possible to exclude HAVM in 30% of the patients. HAVM was significantly associated with surgery, surgical reintervention, and brain devices. Sustained fever was the most frequent clinical sign, and it was significantly associated with unexcluded HAVM. CSF cell count was significantly higher in HAVM, though without microbiological isolation in most of the cases. Conclusion Brain damage, interventions, and devices may significantly alter cerebral homeostasis. Sustained fever is very frequent and may be attributed to several conditions. CSF cell count is useful for the diagnosis of HAVM. HAVM is a clinical challenge in the management of neurocritical patients with important therapeutic and prognostic implications.