The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma.

A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective study of ipi/nivo-treated mRCC at two US academic cancer centers was conducted. A landmark analysis at week 6 was performed to assess the association between the change in NER and clinical responses (progression-free survival (PFS)/overall survival (OS)). Week 6 NER was modeled as a continuous variable, after log transformation (Ln NER), and a categorical variable by percent change. There were 150 mRCC patients included: 78% had clear cell histology, and 78% were IMDC intermediate/poor risk. In multivariable regression analysis, every decrease of 1 unit of Ln NER at week 6 was associated with improved PFS (adjusted hazard ratio (AHR): 0.78, p-value:0.005) and OS (AHR: 0.67, p-value: 0.002). When NER was modeled by percent change, decreased NER > 50% was associated with improved PFS (AHR: 0.55, p-value: 0.03) and OS (AHR: 0.37, p-value: 0.02). The decrease in week 6 NER was associated with improved PFS/OS in ipi/nivo-treated mRCC. Prospective studies are warranted to validate NER change as a biomarker to predict ICI responses.

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis.

Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.

Electrocardiographic and vectorcardiographic findings of patients undergoing reductive ventriculectomy (Batista operation).

BACKGROUND: The Batista operation, or partial ventriculectomy, has been designed by the Brazilian surgeon Dr. Randas Batista as an alternative method for treating patients with idiopathic dilated cardiomyopathy. HYPOTHESIS: This study aimed to analyze electro- and vectorcardiographic data obtained from patients who underwent such surgery, and to evaluate its electrical repercussions on the heart. METHODS: Pre- and postoperative electrocardiography (ECG) and vectorcardiography (VCG) were performed 45 days apart in 15 patients undergoing reductive ventriculectomy. RESULTS: All ECGs showed sinus rhythm, with unchanged QRS duration. Left atrial enlargement (86.6%) and left ventricular hypertrophy (100%) were the most common findings. Bundle-branch blocks (BBBs) were often demonstrated on preoperative studies, predominantly (46.7%) left BBBs. Left anterior fascicular blocks were seen in four patients (26.6%), one associated with right BBB. Electrocardiographic changes suggestive of myocardial infarction (MI) were seen in four patients preoperatively; postoperatively, all had extended to or within the lateral wall. Five additional patients developed lateral MIs postoperatively, for a total of 9 patients (60%) with postoperative signs of infarction (p < 0.05). Electro- and vectorcardiography also showed significant postoperative lowering of QRS voltages (mean 40.74%) in all patients and a consequent difficulty to diagnose left ventricular hypertrophy, although the morphologic features did not change. CONCLUSIONS: These important ECG and VCG alterations are reflections of both the surgical technique and its clinical consequences.

Update of ocular manifestations in sarcoidosis.

Although the lung is the primary target of involvement, sarcoidosis can involve any organ in the body, including the eye. Ocular involvement may also be the initial manifestation of sarcoidosis in many patients. Since no characteristic clinical feature heralds the onset of ocular involvement in sarcoidosis, a systematic eye examination is advised. This review discusses ocular manifestations and changes based upon the anatomic site of the eye, ocular tissue biopsy, and treatment. Early recognition and intervention are essential for the reduction of ocular morbidity and the improvement of the patient's quality of life.

Análise do bloqueio do ramo esquerdo pelo mapeamento eletrocardiográfico de superfície. Comparação com os achados eletro-vetorcardiográficos / Left bundle branch block analysis by body surface mapping. Comparison with electrocardiographic and vectocardiographic findings

PURPOSE: To compare the correlation between the departure areas (DA), negative or positive, in patients whose electrocardiogram showed left bundle branch block (LBBB) and association with left ventricular hipertrophy (LVH) and myocardial infarction (MI), to the electrocardiographic (ECG) and vectocardiographic (VCG) classic criteria. METHODS: The study was carried out with 46 patients (27 males) with LBBB. These patients had hypertension (19.5), coronary heart disease (34.7) and 21 patients with no heart disease (45.8). RESULTS: The statistic analysis using the Cluster method divided the patients in two groups. Group I (22 patients) showed an average rate for the DA (-2 SD) of 1091 for QRS and of 640 for ST-T. For the DA (+2 SD), the average rate was 618 for QRS and 881 for ST-T; group II (24 patients) showed an averaged for the DA (-2 SD) of 1063 for QRS and of 225 for ST-T. For the DA (+2 SD), the averaged rate was 428 for QRS and 600 for ST-T. CONCLUSION: In general the current ECG/VCG findings, can not differentiate the presence of the association of LBBB to LVH and MI. The DA of ST-T, mainly negative was the most efficient to separate the two groups and help in the differential diagnosis.