Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+ CD163+ CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996.

OBJECTIVES: Published reports were reviewed to evaluate the characteristics of peripartal management and the late pregnancy outcome in women with pulmonary vascular disease (PVD). BACKGROUND: Pulmonary hypertension poses one of the highest risks for maternal mortality, but actual data on the maternal and neonatal prognosis in this group are lacking. METHODS: Reports published from 1978 through 1996 of Eisenmenger's syndrome (n = 73), primary pulmonary hypertension (PPH) (n = 27) and secondary vascular pulmonary hypertension (SVPH) (n = 25) complicating late pregnancy were included and analyzed using logistic regression analysis. RESULTS: Maternal mortality was 36% in Eisenmenger's syndrome, 30% in PPH and 56% (p < 0.08 vs. other two groups) in SVPH. Except for three prepartal deaths due to Eisenmenger's syndrome, all fatalities occurred within 35 days after delivery. Neonatal survival ranging from 87% to 89% was similar in the three groups. Previous pregnancies, timing of the diagnosis and hospital admission, operative delivery and diastolic pulmonary artery pressure were significant univariate (p < 0.05) maternal risk factors. Late diagnosis (p = 0.002, odds ratio 5.4) and late hospital admission (p = 0.01, odds ratio 1.1 per week of pregnancy) were independent predictive risk factors of maternal mortality. CONCLUSIONS: In the last two decades maternal mortality was comparable in patients with Eisenmenger's syndrome and PPH; however, it was relevantly higher in SVPH. Maternal prognosis depends on the early diagnosis of PVD, early hospital admission, individually tailored treatment during pregnancy and medical therapy and care focused on the postpartal period.

Improving a preventive services reminder system using feedback from focus groups.

OBJECTIVE: To improve the computer-generated preventive services patient reminder letter used by a department of family medicine at a medical university in South Carolina. DESIGN: A qualitative method chosen because of its demonstrated efficacy in generating in-depth attitude and opinion data was used for 12 focus groups (111 participants) in which participants were asked to evaluate the reminder letter and other preventive services reminder materials. Information from these groups was used to design a revised patient reminder system that was tested in six additional focus groups (50 participants). SETTING: University-based family medicine center. PARTICIPANTS: Adults 19 years of age or older of whom approximately one half were selected from a random sample of family medicine center patients and the remainder from volunteers recruited from the general community by newspaper advertisement. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Participants' perceptions and attitudes about the reminder letter and other materials as well as suggestions for improving the preventive services reminder system. RESULTS: The revised patient reminder materials resulted in a warmer, more personal letter sent to patients at the time of their birthdays in an envelope containing a prevention message. A leaflet describing the rationale for preventive services and answering common questions about prevention and a booklet describing the preventive services available at the family medicine center were also developed. CONCLUSION: This study illustrated the benefits of incorporating patients' perspectives in the design of preventive services reminders.

Barriers to adherence to preventive services reminder letters: the patient's perspective.

BACKGROUND: Despite an emerging consensus as to which preventive services are appropriate, a minority of patients receive them. Although adherence to recommendations for some interventions has increased, research studies have shown that adherence rates can be further improved through a better understanding of patient attitudes and motivations regarding preventive services. METHODS: Using components of the Patient Path Model, this study examined the response to patient reminder letters for cholesterol screening sent to 1077 adult patients between August and October 1990. The research strategy incorporated both quantitative and qualitative methods, including a telephone survey and focus group interviews of nonresponders to the reminder letter. RESULTS: Three hundred seven patients were surveyed by telephone to ascertain their reasons for nonresponse. One hundred fifty-four (50.2%) did not recall receiving the reminder letter, 84 (27.4%) recalled receiving the letter but did not recall its content, and 69 (22.5%) recalled both receiving the letter and its content. No consistent reason for nonadherence emerged among the 69 nonresponders who recalled the reminder. Twenty-seven of the nonresponders who did not recall receiving the cholesterol reminder participated in the focus groups. The participants stressed the importance of distinguishing the reminder letter from a bill, conveying a personally relevant message, and addressing logistical barriers to preventive services. CONCLUSIONS: Careful attention to the format and content of patient reminder letters is necessary to improve adherence to preventive services recommendations.

The effect of routine use of computer-generated preventive reminders in a clinical practice.

Computer-generated reminders for patients and physicians can increase provision of preventive services. On July 1, 1989, the Department of Family Medicine at the Medical University of South Carolina extended a computerized prevention reminder system to all physicians and adult patients in the department's clinical practice. The prevention program consisted of computer-generated physician reminders for any deficiencies in five preventive services at the time of patient visits, a personalized patient reminder letter sent just before a patient's birthday, and educational interventions. We defined adherence using a population-based approach, that is, the percentage of all eligible patients who had received the preventive services within the recommended period of time. The data revealed that the percentage of patients who received preventive services either increased or remained stable during the 12-month study period, which ended July 1, 1990. Adherence was greater for women, for older patients, and for those with Medicare/Medicaid and HMO insurance. We noted higher rates of adherence for all five preventive services, compared with baseline rates of adherence recorded on July 1, 1988. A population-based approach to prevention allows physicians to become more active in providing preventive care to patients. Computer-based reminder and tracking systems can integrate population-based prevention into practice.

Compliance with five health promotion recommendations in a university-based family practice.

Although numerous recommendations are available to guide the primary care physician's provision of preventive health services, a minority of Americans receive recommended care. This study assessed the extent to which patients in a large, university-based family medicine program were receiving five well-accepted health promotion services. These services included fecal occult blood testing, Papanicolaou smears, mammography, serum cholesterol measurements, and tetanus immunization. Demographic factors associated with receipt of these services were assessed. A minority of active patients received the five health promotion services in the recommended interval: fecal occult blood testing 13%, Papanicolaou smear 41%, mammography 16%, cholesterol measurements 20%, and tetanus immunization 19%. The patient's physician practice group, type of medical insurance, physician visit frequency, and increasing age were associated with compliance with the five studied health promotion services.

Evaluation of the DINAMAP blood pressure monitor in an ambulatory primary care setting.

Automatic blood pressure recorders have gained acceptance in many clinical settings. New devices have usually been validated with invasive monitoring as the "gold standard." There is a lack of sound empirical evidence, however, supporting the routine use of these monitors in ambulatory settings. This study evaluated the DINAMAP 8100, an oscillometric automated blood pressure monitor, using the Hawksley Random-Zero Sphygmomanometer as the standard. A sample of 80 normotensive and hypertensive ambulatory patients from the Department of Family Medicine at the Medical University of South Carolina were studied. A clinical trial was conducted in which readings from the DINAMAP 8100 were compared with those from the Hawksley Random-Zero Sphygmomanometer, in a 2 (instrument) X 2 (arm) X 2 (investigators) X 4 (pairs of simultaneous measurements) factorial design. The DINAMAP 8100 overestimated systolic readings (mean difference = 7.6 +/- 9.1 mmHg, P less than .0001, paired t test). More than one third of systolic measurements and one quarter of diastolic measurements were greater than 10 mmHg discrepant from the standard. The results of this study suggest that routine use of the DINAMAP 8100 would lead to serious misclassification errors in screening for hypertension and in the follow-up of known hypertensive patients. The DINAMAP 8100, therefore, is not an appropriate instrument for routine use in primary care settings.