Correlation between the vascular resistance index and arteriography for assessment of the distal arterial bed in chronic limb threatening ischemia.

Background: Patients with chronic limb threatening ischemia (CLTI) of the lower limbs (LL) undergo arteriography for revascularization surgery planning. Doppler ultrasound (DU) is non-invasive and can provide information about the distal arteries through measurement of the resistance index (RI). Objectives: To correlate the Rutherford Angiographic Classification with the RI for assessment of the distal arterial bed of the LL. Methods: A cross-sectional study, conducted at a public tertiary hospital with 120 patients with LL CLTI, from September 2019 to April 2022. The RI of arteries that were candidates for revascularization was compared with the images of the same arteries obtained using arteriography, using the Rutherford Angiographic Classification of the distal bed. Results: A total of 120 LL were assessed in 120 patients with a mean age of 68.6 years. The sample was 50.0% male and 90.0% of the patients in the sample were classified as Rutherford category five. The RI values found for the arteries of the leg exhibited a statistically significant positive correlation with the Rutherford Classification (anterior tibial, p< 0.01; posterior tibial, p = 0.012 fibular, p = 0.034; and dorsalis pedis, p < 0.001). Conclusions: In this study, RIs for the arteries of the leg measured using Doppler ultrasound exhibited a positive correlation with the Rutherford Classification. This index could be useful for assessment of the distal arterial bed of the lower limbs of patients with chronic limb threatening ischemia.

Vascular resistance index and the immediate hemodynamic success of lower limb distal artery revascularization.

Background: Revascularization surgery is used to attempt to restore blood flow to the foot in patients with critical ischemia (CI) caused by peripheral arterial occlusive disease of the lower limbs (LL). Ultrasonography with Doppler (USD) SAH emerged in recent years as a highly valuable method for planning this surgical intervention. Objectives: To evaluate the relationship between the resistance index (RI), measured with USD, and immediate hemodynamic success of LL revascularization surgery in patients with CI. Methods: The study design was a prospective cohort assessing 46 patients with LL CLI who underwent operations to perform infrainguinal revascularization by angioplasty or bypass from August 2019 to February 2022. All patients underwent preoperative clinical vascular assessment with USD including measurement of the RI of distal LL arteries, LL arteriography, and measurement of the ankle-brachial index (ABI). All patients had their ABI measured again in the immediate postoperative period. Results: Forty-six patients were assessed, 25 (54.3%) of whom were male. Age varied from 32 to 89 years (mean: 67.83). Hemodynamic success was assessed by comparison of preoperative and postoperative ABI, showing that hemodynamic success was achieved in 31 (67.4%) patients after revascularization surgery (ABI increased by 0.15 or more). A positive correlation (p ≤ 0.05) was observed between the RI of the distal revascularized LL artery and immediate hemodynamic success assessed by ABI (lower RI and hemodynamic success). Conclusions: This study observed a positive correlation between the resistance index of the distal artery and immediate hemodynamic success of lower limb revascularizations, as assessed by the ankle-brachial index, so that the lower the RI the greater the hemodynamic success achieved.

Single and combination immunotherapy with chemotherapy and the risk of AKI in patients with solid cancer.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) has emerged as an important toxicity among patients with advanced cancer treated with immune checkpoint inhibitors. The aim of this study was to describe the incidence, risk factors and mortality of AKI in patients receiving immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy. DESIGN, SETTING AND PARTICIPANTS: We included all patients who received immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy at AC Camargo Cancer Center from January 2015 to December 2019. AKI was defined as a ≥ 1.5 fold increase in creatinine from baseline within 12 months of immune checkpoint inhibitor initiation. We assessed the association between baseline demographics, comorbidities, medications and risk of AKI using a competing risk model, considering death as a competing event. RESULTS: We included 614 patients in the analysis. The mean age was 58.4 ± 13.5 years, and the mean baseline creatinine was 0.8 ± 0.18 mg/dL. AKI occurred in 144 (23.5%) of the patients. The most frequent AKI etiologies were multifactorial (10.1%), hemodynamic (8.8%) and possibly immunotherapy-related (3.6%). The likelihood of AKI was greater in patients with genitourinary cancer (sHR 2.47 95% CI 1.34-4.55 p < 0.01), with a prior AKI history (sHR 2.1 95% CI 1.30-3.39 p < 0.01) and taking antibiotics (sHR 2.85 95% CI 1.54-5.27 p < 0.01). CONCLUSIONS: In this study, genitourinary cancer, previous AKI and antibiotics use were associated with a higher likelihood of developing AKI.

Therapeutic Adherence According to the Morisky Scale in Patients with Hypertension

Abstract Background In view of the high prevalence of hypertension and the importance of adequate drug therapy in the prevention of complications, it is necessary to know the adherence to drug treatment in this population. Objective To verify adherence to antihypertensive drug treatment in Brazilian patients with hypertension using the Morisky-Green Test (MGT), relating it with demographic data. Methods Prospective, observational, multicenter, national registry study, with 2,578 hypertensive patients participating in study I, the Brazilian Cardiovascular Registry of Arterial Hypertension (I-RBH), recruited in the five regions of Brazil. The analyses carried out on the data were descriptive statistics, qui-square tests, ANOVA, and logistic regression, adopting 5% as the significance level for the tests. Results The research shows that 56.13% of patients in the sample were female; 56.71% were elderly (≥ 65 years); 55.86% were White; 52.37% were from the Southeast Region; and 59.74% were non-adherent. Logistic regression showed an independent relationship between patients' age, ethnicity, and region with medication adherence. Conclusion Adherence to treatment is the key to reducing high rates of cardiovascular complications. The study brings a successful outcome in the relationship between the factors ethnicity, age, and region of patients with hypertension and medication adherence. To this end, it is necessary to understand these factors, considering systematic evaluation in the care of patients with hypertension and other chronic non-communicable diseases. This study is a significant contribution to multidisciplinary teams, as it highlights which risk factors interfere with medication adherence, incorporating better strategies in health education.

Relação entre o índice de resistência vascular e o sucesso hemodinâmico de revascularizações distais dos membros inferiores / Vascular resistance index and the immediate hemodynamic success of lower limb distal artery revascularization

Resumo Contexto A cirurgia de revascularização é proposta para restaurar o fluxo sanguíneo para o pé nos casos de isquemia crítica (IC) devido a doença arterial obstrutiva periférica dos membros inferiores (MMII). O uso de ultrassonografia com Doppler (USD) vem despontando nos últimos anos como um método de grande valor para o planejamento cirúrgico dessa intervenção. Objetivos Avaliar a relação entre o índice de resistência (IR), mensurado por meio de USD, e o sucesso hemodinâmico imediato da cirurgia de revascularização dos MMII em pacientes com IC. Métodos O tipo de estudo empregado foi a coorte prospectiva, na qual foram avaliados 46 pacientes portadores de IC dos MMII submetidos à operação de revascularização infrainguinal por angioplastia ou em ponte de agosto de 2019 a fevereiro de 2022. Todos os pacientes foram submetidos à avaliação clínica vascular, à USD com medida do IR das artérias distais dos MMII, à arteriografia dos MMII e à aferição do índice tornozelo-braquial (ITB) no período pré-operatório. No pós-operatório imediato, todos os pacientes foram submetidos à nova aferição do ITB. Resultados Entre os 46 pacientes avaliados, 25 (54,3%) eram do sexo masculino. A idade variou de 32 a 89 anos (média de 67,83). Quanto ao sucesso hemodinâmico, avaliado pela comparação do ITB pré e pós-operatório, constatou-se que 31 (67,4%) pacientes apresentaram sucesso hemodinâmico após cirurgia de revascularização (aumento do ITB em 0,15 ou mais). Foi observada correlação positiva (p ≤ 0,05) entre o IR da artéria distal revascularizada do MMII e o sucesso hemodinâmico imediato avaliado pela aferição do ITB (IR menor e sucesso hemodinâmico). Conclusões Na presente pesquisa foi observada uma correlação positiva entre o índice de resistência arterial distal e o sucesso hemodinâmico nas revascularizações dos membros inferiores, avaliada através do índice tornozelobraquial, de forma que, quanto menor foi o IR, maior o sucesso hemodinâmico obtido.

Abstract Background Revascularization surgery is used to attempt to restore blood flow to the foot in patients with critical ischemia (CI) caused by peripheral arterial occlusive disease of the lower limbs (LL). Ultrasonography with Doppler (USD) SAH emerged in recent years as a highly valuable method for planning this surgical intervention. Objectives To evaluate the relationship between the resistance index (RI), measured with USD, and immediate hemodynamic success of LL revascularization surgery in patients with CI. Methods The study design was a prospective cohort assessing 46 patients with LL CLI who underwent operations to perform infrainguinal revascularization by angioplasty or bypass from August 2019 to February 2022. All patients underwent preoperative clinical vascular assessment with USD including measurement of the RI of distal LL arteries, LL arteriography, and measurement of the ankle-brachial index (ABI). All patients had their ABI measured again in the immediate postoperative period. Results Forty-six patients were assessed, 25 (54.3%) of whom were male. Age varied from 32 to 89 years (mean: 67.83). Hemodynamic success was assessed by comparison of preoperative and postoperative ABI, showing that hemodynamic success was achieved in 31 (67.4%) patients after revascularization surgery (ABI increased by 0.15 or more). A positive correlation (p ≤ 0.05) was observed between the RI of the distal revascularized LL artery and immediate hemodynamic success assessed by ABI (lower RI and hemodynamic success). Conclusions This study observed a positive correlation between the resistance index of the distal artery and immediate hemodynamic success of lower limb revascularizations, as assessed by the ankle-brachial index, so that the lower the RI the greater the hemodynamic success achieved.

Correlação entre o índice de resistência vascular e a arteriografia na avaliação do leito arterial distal na isquemia crítica dos membros inferiores / Correlation between the vascular resistance index and arteriography for assessment of the distal arterial bed in chronic limb threatening ischemia

Resumo Contexto Pacientes com isquemia crítica (IC) dos membros inferiores (MMII) precisam de arteriografia para o planejamento da cirurgia de revascularização. A ultrassonografia Doppler (UD) não é invasiva e, através da aferição do índice de resistência (IR), pode fornecer informações sobre as artérias distais. Objetivos Correlacionar a Classificação Angiográfica de Rutherford com o IR na avaliação do leito arterial distal dos MMII. Métodos Estudo transversal, realizado em hospital público terciário, com 120 pacientes portadores de IC dos MMII, entre setembro de 2019 a abril de 2022. Foi comparado o IR das artérias da perna passíveis de serem receptoras de revascularização com a imagem obtida através da arteriografia dessas artérias em acordo com a Classificação Angiográfica de leito distal de Rutherford. Resultados Foram avaliados 120 MMII em 120 pacientes com idade média de 68,6 anos. A amostra foi composta de 50,0% de pacientes do sexo masculino. Na amostra, 90,0% pacientes encontravam-se na classe cinco de Rutherford. Os valores do IR encontrados para as artérias de perna apresentaram uma correlação positiva, estatisticamente significativa, quando comparados com a Classificação de Rutherford (tibial anterior, p< 0,01; tibial posterior, p = 0,012 e fibular, p = 0,034 e artéria dorsal do pé, p < 0,001). Conclusões Neste estudo, os IRs das artérias da perna obtidos através da ultrassonografia Doppler apresentaram uma correlação positiva quando comparados à classificação de Rutherford. Em pacientes com isquemia crítica, esse índice pode ser útil na avaliação do leito arterial distal dos membros inferiores.

Abstract Background Patients with chronic limb threatening ischemia (CLTI) of the lower limbs (LL) undergo arteriography for revascularization surgery planning. Doppler ultrasound (DU) is non-invasive and can provide information about the distal arteries through measurement of the resistance index (RI). Objectives To correlate the Rutherford Angiographic Classification with the RI for assessment of the distal arterial bed of the LL. Methods A cross-sectional study, conducted at a public tertiary hospital with 120 patients with LL CLTI, from September 2019 to April 2022. The RI of arteries that were candidates for revascularization was compared with the images of the same arteries obtained using arteriography, using the Rutherford Angiographic Classification of the distal bed. Results A total of 120 LL were assessed in 120 patients with a mean age of 68.6 years. The sample was 50.0% male and 90.0% of the patients in the sample were classified as Rutherford category five. The RI values found for the arteries of the leg exhibited a statistically significant positive correlation with the Rutherford Classification (anterior tibial, p< 0.01; posterior tibial, p = 0.012 fibular, p = 0.034; and dorsalis pedis, p < 0.001). Conclusions In this study, RIs for the arteries of the leg measured using Doppler ultrasound exhibited a positive correlation with the Rutherford Classification. This index could be useful for assessment of the distal arterial bed of the lower limbs of patients with chronic limb threatening ischemia.

Resource utilization and costs related to the management of obstructive hypertrophic cardiomyopathy under the Brazilian supplementary healthcare system´s perspective: results from a modified Delphi panel / Utilização de recursos e custos relacionados ao manejo da cardiomiopatia hipertrófica obstrutiva sob a perspectiva do sistema de saúde suplementar brasileiro: resultados de um painel Delphi modificado

Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive ypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods: A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient's NYHA functional class while promoting a decrease in the need for invasive therapies.

Objetivo: Gerar dados acerca dos custos associados ao diagnóstico e tratamento da cardiomiopatia hipertrófica (CMH) obstrutiva, sob a perspectiva do sistema de saúde privado no Brasil. Métodos: Um painel Delphi modificado incluindo sete especialistas (três cardiologistas clínicos com experiência em CMH obstrutiva, dois hemodinamicistas com experiência em ablação de septo e dois cirurgiões cardíacos com experiência em miectomia) de dois estados brasileiros (São Paulo e Pernambuco) foi conduzido entre agosto e novembro de 2022. Foram realizadas duas rodadas de perguntas acerca da utilização de recursos de acordo com a classe funcional (NYHA I-IV) e uma reunião virtual para obtenção do consenso final. Os custos foram definidos por meio de microcusteio, e os valores unitários foram definidos com base em listas de preço oficiais. Resultados: O custo total do diagnóstico por paciente foi estimado em R$ 11.486,81. A análise de custos de manejo da CMH obstrutiva mostrou custos médios anuais por paciente de R$ 17.026,74, R$ 19.401,46, R$ 73.310,07 e R$ 94.885,75 para as classes funcionais NYHA I, NYHA II, NYHA III e NYHA IV, respectivamente. Os custos médios por paciente relacionados a procedimentos em um ano foram de R$ 12.698,53, R$ 13.462,30, R$ 58.841,67 e R$ 75.595,90 para as classes NYHA I, II, III e IV, respectivamente. Conclusões: Os custos anuais com o manejo da CMH aumentam de acordo com a classe funcional, destacando a necessidade de estratégias seguras e eficazes capazes de melhorar a classe funcional NYHA do paciente, ao mesmo tempo que promove diminuição da necessidade de terapias invasivas.

Local therapy in advanced melanoma after immune checkpoint inhibitors aiming to achieve complete response.

Background and Objectives: New scenarios for local therapy have arisen after starting immune checkpoint inhibitors (ICIs) to treat advanced melanoma (AM). The aim of this study is to examine the role of local therapies with curative intention for patients with AM that have been on ICI. Methods: This was a single institution, retrospective analysis of unresectable stage III or IV melanoma patients on treatment with anti-PD1 ± anti-CTLA-4 who underwent local therapy with curative intention with no other remaining sites of disease (NRD). Results: Of the 170 patients treated with ICI, 19 (11.2%) met the criteria of curative intention. The median time on ICI before local therapy was 16.6 months (range: 0.92-43.2). At the time of the local treatment, the disease was controlled in 16 (84.25%) and progressing in 3 patients (15.75%); 14 patients (73.7%) treated a single lesion and 5 (26.3%) treated 2 to 3 lesions. In a median follow-up of 17 months (range: 1.51-38.2) after the local therapy and 9.8 months after the last ICI cycle (range: 0.56-31), only 2 (10.5%) out of 19 patients relapsed. Conclusions: Patients with AM on treatment with ICI were able to achieve NRD after local treatment and may benefit from long-term disease control without systemic treatment.

Imaging-calculated splenic volume is associated with response in melanoma patients treated with immunotherapy.

Background: Predicting the roughly 50% of melanoma patients that will respond to immunotherapy is challenging. We tested if splenic volume could be a predictive biomarker. Methods: Splenic volume was measured by a semiautomated commercial software tool in pre- and post-treatment PET/CT, CT or MRI in 50 melanoma patients treated with immune checkpoint inhibitors. Results: Subjects with smaller spleens had better progression-free survival (median not achieved after 30.6 months of follow-up vs median 11.2 months; p = 0.0213) than their counterparts. A cut-off of <244 cm3 yielded a sensitivity of 83% and specificity of 54% to identify responders. Conclusion: Measuring splenic volume on imaging scans is feasible. Smaller pretreatment spleen volume is associated with better responses to immune checkpoint inhibitors.

For patients with relapsed or advanced melanoma, immunotherapy is the main treatment option. Not all patients respond to it and there are few ways of knowing the odds beforehand. Treatment can be costly and dangerous. We investigated if measuring the spleen using imaging scans already routinely done to monitor the disease could give doctors an idea of whether the patient had higher chances of responding to immunotherapy. Our main finding was that patients with smaller spleens before treatment initiation were more likely to respond to immunotherapy and live longer without the disease. This finding can potentially be used in day-to-day care to inform patients and their physicians of the patient's odds and help them make an informed joint decision.

Role of Annexin A1 Secreted by Neutrophils in Melanoma Metastasis.

Annexin A1 (AnxA1) is highly secreted by neutrophils and binds to formyl peptide receptors (FPRs) to trigger anti-inflammatory effects and efferocytosis. AnxA1 is also expressed in the tumor microenvironment, being mainly attributed to cancer cells. As recruited neutrophils are player cells at the tumor sites, the role of neutrophil-derived AnxA1 in lung melanoma metastasis was investigated here. Melanoma cells and neutrophils expressing AnxA1 were detected in biopsies from primary melanoma patients, which also presented higher levels of serum AnxA1 and augmented neutrophil-lymphocyte ratio (NLR) in the blood. Lung melanoma metastatic mice (C57BL/6; i.v. injected B16F10 cells) showed neutrophilia, elevated AnxA1 serum levels, and higher labeling for AnxA1 in neutrophils than in tumor cells at the lungs with metastasis. Peritoneal neutrophils collected from naïve mice were co-cultured with B16F10 cells or employed to obtain neutrophil-conditioned medium (NCM; 18 h incubation). B16F10 cells co-cultured with neutrophils or with NCM presented higher invasion, which was abolished if B16F10 cells were previously incubated with FPR antagonists or co-cultured with AnxA1 knockout (AnxA1-/-) neutrophils. The depletion of peripheral neutrophils during lung melanoma metastasis development (anti-Gr1; i.p. every 48 h for 21 days) reduced the number of metastases and AnxA1 serum levels in mice. Our findings show that AnxA1 secreted by neutrophils favors melanoma metastasis evolution via FPR pathways, addressing AnxA1 as a potential biomarker for the detection or progression of melanoma.

Effect of Obesity and Bariatric Surgery on Saphenous Veins.

PURPOSE: Obesity is a risk factor for chronic venous disease (CVD) of the lower limbs (LL), affecting venous anatomy and physiology. Weight loss after bariatric surgery (BS) can reduce intra-abdominal pressure, improve mobility, and ultimately improve venous hemodynamics and CVD-related symptoms. There are no studies in the literature that adequately assess the effect of the obesity and BS on the LL veins, especially the saphenous veins (SV). The aim of this study was to evaluate the effects of obesity and BS on the saphenous veins. METHODS: This is a longitudinal prospective study carried out from 2019 to 2021 with 19 patients, totaling 38 LL, underwent clinical evaluation (CEAP Classification) and by Doppler ultrasonography, to analyze their SV diameter and reflux measurements, in the preoperative period and again 6 months to 2 years after BS being performed. RESULTS: There was no statistical difference between the groups regarding the characteristics of reflux in the SV among the evaluated LL. There was no significant increase in the diameter of the great SV in the majority of its segments. The groups were similar in terms of the small SV diameters. Moreover, a significant reduction in the clinical class of CEAP was observed after BS. CONCLUSION: Obesity and bariatric surgery had no influence on diameter or reflux in saphenous veins, but a reduction in the CEAP Clinical Classification was observed in the postoperative period.

Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial : Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial).

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

Performance of a novel risk model for deep sternal wound infection after coronary artery bypass grafting.

Clinical prediction models for deep sternal wound infections (DSWI) after coronary artery bypass graft (CABG) surgery exist, although they have a poor impact in external validation studies. We developed and validated a new predictive model for 30-day DSWI after CABG (REPINF) and compared it with the Society of Thoracic Surgeons model (STS). The REPINF model was created through a multicenter cohort of adults undergoing CABG surgery (REPLICCAR II Study) database, using least absolute shrinkage and selection operator (LASSO) logistic regression, internally and externally validated comparing discrimination, calibration in-the-large (CL), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), trained between the new model and the STS PredDeep, a validated model for DSWI after cardiac surgery. In the validation data, c-index = 0.83 (95% CI 0.72-0.95). Compared to the STS PredDeep, predictions improved by 6.5% (IDI). However, both STS and REPINF had limited calibration. Different populations require independent scoring systems to achieve the best predictive effect. The external validation of REPINF across multiple centers is an important quality improvement tool to generalize the model and to guide healthcare professionals in the prevention of DSWI after CABG surgery.

Balancing the good and the bad: controlling immune-related adverse events versus anti-tumor responses in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) have provided new hope for cancer patients, and in particular for patients with tumors that are immunologically active and classified as hot tumors. These tumors express antigenic and tumor microenvironment (TME) characteristics that make them potential candidates for therapy with checkpoint inhibitors that aim to reactivate the immune response such as anti-PD-1 and anti-CTLA-4. Examples of potentially responsive cancers are, melanoma, non-small cell lung cancer and several other metastatic or unresectable tumors with genetic instability: DNA mismatch repair deficiency (dMMR), microsatellite instability-high (MSI-H), or with a high tumor mutational burden (TMB). Immunotherapy using checkpoint inhibitors is typically associated with adverse events (AEs) that are milder than those with chemotherapy. However, a significant percentage of patients develop short-term immune-related AEs (irAEs) which range from mild (~70%) to severe cases (~13%) that can lead to modifications of the checkpoint inhibitor therapy and in some cases, death. While some studies have investigated immune mechanisms behind the development of irAEs, much more research is needed to understand the mechanisms and to develop interventions that could attenuate severe irAEs, while maintaining the anti-tumor response intact. Moreover, studies to identify biomarkers that can predict the likelihood of a patient developing severe irAEs would be of great clinical importance. Here we discuss some of the clinical ramifications of irAEs, potential immune mechanisms behind their development and studies that have investigated potentially useful biomarkers of irAEs development.

Effect of psychotherapy on recurrence of events and quality of life in patients with vasovagal syncope.

Emotional distress is related to recurrence of syncope compromising patient's quality of life (QoL). The aim of this study was to determine if weekly sessions of psychotherapy reduce recurrence of events and improve QoL by SF-36 among patients with refractory vasovagal syncope. A randomised controlled pilot trial including 10 patients with recurrent vasovagal syncope and positive tilt table test was conducted. Known cardiac disease and ongoing psychotherapeutic interventions were the main exclusion criteria. All patients received standard of care treatment. Additionally, after randomisation, half of the patients underwent weekly sessions of psychotherapy for 12 months. Analysis of recurrence of events and QoL showed no significant change in the control group but, in the intervention group, there was a significant reduction in the rate of near-syncope episodes per month (5.7 ± 1.4 × 1.7 ± 1.0; P < 0.01), syncope in 1 year (4.6 ± 0.9 × 1.0 ± 0.7; P < 0.01) and a significant improvement in the overall assessment of QoL (44.1 ± 10.0 vs. 70.3 ± 10.3, P < 0.01). In conclusion, patients with refractory vasovagal syncope undergoing regular psychotherapeutic intervention had less recurrence of events and improved their quality of life in 1 year.Trial Registration: ClinicalTrials.gov number, NCT04252729.

Validation of standard operating procedure for oral hygienization of intubated and tracheostomized patients / Validação de um procedimento operacional padrão para higienização oral de pacientes intubados e traqueostomizados

INTRODUÇÃO: In Intensive Care Units, oral hygiene is a care action directly related to the safety and well-being of the patient, being one of the main ways of preventing Pneumonia Associated with Mechanical Ventilation. Although relevant, the recommendations and standardization on oral hygiene among critically ill patients are diffuse. OBJECTIVE: To construct and validate a standard operating procedure (SOP) for oral hygiene performed by the nursing team for intubated and tracheostomized patients in an Intensive Care Unit (ICU). METHODS: Methodological study developed in five stages: technical-scientific support; construction of SOP; recruitment and selection of experts; validation and presentation of the final version. The SOP was subjected to validation by judges with academic and/or clinical expertise (n=13) from all regions of Brazil, who assessed the validity criteria for each SOP item: Scope, Clarity, Coherence, Criticism, Objectivity, Scientific writing; Relevance, Sequence, and Uniqueness. The Content Validity Indices (CVI) of each validity criterion, SOP item, and the general CVI were calculated. RESULTS: The experts were nurses (38.5%), dentists (38.5%), doctors (15.4%) and physiotherapists (7.7%). None of the SOP items had a CVI lower than 0.80. The general CVI was 0.95 and the experts' suggestions were mostly accepted (78.6%). The final version is available as an infographic, which illustrates the stages of the oral hygiene process of the intubated and tracheostomized patient. CONCLUSION: The constructed SOP has a satisfactory face and content validity, making a final total of 43 items to be used for oral hygiene of intubated and tracheostomy patients.

INTRODUÇÃO: Em Unidades de Terapia Intensiva, a higienização bucal é ação de cuidado diretamente relacionada à segurança do paciente e qualidade do cuidado, sendo uma das principais formas de prevenção da Pneumonia Associada à Ventilação Mecânica. Apesar disso, as recomendações e a padronização sobre a higienização bucal entre pacientes críticos são difusas. OBJETIVO: Construir e validar um procedimento operacional padrão (POP) para higiene bucal realizada pela enfermagem a pacientes intubados e traqueostomizados em Unidade de Terapia Intensiva (UTI). MÉTODOS: Estudo metodológico desenvolvido em cinco etapas: subsídio técnico-científico; construção do POP; recrutamento e seleção de experts; validação de face e conteúdo do POP e apresentação da versão final. O POP foi submetido à validação por juízes com expertise acadêmica e/ou clínica (n=13) de todas as regiões do Brasil, os quais apreciaram os critérios de validade: Abrangência, Clareza, Coerência, Criticidade, Objetividade, Redação científica; Relevância, Sequência e Unicidade. Foram calculados os Índices de Validade de Conteúdo (IVC) de cada critério, item do POP e o IVC geral. RESULTADOS: Os experts eram enfermeiros(as) (38,5%), cirurgiãs-dentistas (38,5%), médicos(as) (15,4%) e fisioterapeuta (7,7%). Nenhum item do POP obteve IVC inferior a 0,80. O IVC geral foi de 0,95 e sugestões dos experts foram majoritariamente acatadas (78,6%). A versão final, disponível como infográfico, contempla ilustrativamente as etapas do processo de higienização bucal do paciente intubado e traqueostomizado. CONCLUSÃO: O POP alcançou validade de face e conteúdo satisfatória. A versão validada possui 43 itens processuais para higiene bucal de pacientes intubados e traqueoestomizados.

Ophthalmological manifestations of the Schuurs-Hoeijmakers syndrome: a case report / Manifestações oftalmológicas da Síndrome de Schuurs-Hoeijmakers: relato de caso

ABSTRACT This is a case report of a 2-year-old male patient with cognitive delay, facial abnormalities, and microcornea in the right eye, who was referred for ophthalmological investigation. The initial ophthalmological examination revealed hypertelorism, epicanthus, nystagmus, esotropia, and microcornea in the right eye. The examination under anesthesia revealed microphthalmia in the right eye, and iris, retina, and optic nerve coloboma in both eyes. Whole exome sequencing revealed evidence of a heterozygotic pathogenic variant in PACS1. The PACS1 pathogenic variant in association with the clinical findings confirmed the diagnosis of Schuurs-Hoeijmakers syndrome. To our knowledge, this is the first report to describe microcornea and microphthalmia as additional ocular manifestations of Schuurs-Hoeijmakers syndrome.

RESUMO Trata-se de um relato de caso de um paciente do sexo masculino de 2 anos de idade com atraso cognitivo, anormalidades faciais e microcórnea no olho direito encaminhado para investigação oftalmológica. O exame oftalmológico inicial evidenciou hipertelorismo, epicanto, nistagmo, esotropia e microcórnea no olho direito. O exame sob anestesia revelou microftalmia no olho direito e coloboma de íris, retina e nervo óptico em ambos os olhos. Foi realizado sequenciamento completo do exoma que mostrou uma variante patogênica heterozigótica no PACS1. A variante patogênica no PACS1 em associação com os achados clínicos apresentados confirmou o diagnóstico da síndrome de Schuurs-Hoeijmakers). Acredita-se este seja o estudo a descrever microcórnea e microftalmia como manifestações oculares adicionais da síndrome de Schuurs-Hoeijmakers.