Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains 651% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD-L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD-L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD-L1 status (positive versus negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD-L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD-L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD-L1 status of primary TNBCs

The effective case management of childhood diarrhoea with oral rehydration therapy in the kingdom of Lesotho

In Lesotho prior to 1986, diarrhoea was the leading cause of hospital mortality in children \u3c 5 years of age. At the Queen Elizabeth II Hospital, diarrhoee-related admissions as a proportion of all admissions in children \u3c 5 years of age declined from 23% in the year prior to the opening of the Oral Rehydration Theraphy Unit (ORTU) to 13% in the first nine months of 1987 (p\u3c0.05). In addition, the case-fatality ratio of children treated in the ORTU declined from 1.4% in the first quarter of 1986 to zero in the second and third quarters of 1987 (p\u3c0.05). In a case-control study conducted to identify reasons for children failing ORTU treatment, factors associated with an increased risk of hospitalization included male gender (odds ratio [OR] = 4.9; 95% Confidence limits [CL] = 2.0, 11.9), fever ≫38.5°C (OR = 2.0; CL = 1.2, 3.3), undernutrition (OR = 3.2; CL = 1.1, 9,4), and moderate dehydration (OR= 2.3; CL = 1.2, 4.4) or severe dehydration (OR= 12.1; CL=3.8, 38.5). Breastfed children \u3c 2 years of age were at decreased risk of hospitalization (OR = 0.4; CL = 0.2, 0.7). At this major hospital in Lesotho, the standardization of outpatient treatment for diarrhoea with oral rehydration salts (ORS) in the context of an ORTU resulted in a marked decrease in diarrhoea-associated hospitalization and deaths in children \u3c 5 years of age. © 1990 International Epidemiological Association

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Patients with advanced triple‐negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD‐L1/SP142‐positive immune cells. Numbers of tumor‐infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter‐pathologist agreement in the assessment of PD‐L1/SP142 immunohistochemistry and TILs. Ten pathologists evaluated PD‐L1/SP142 expression in a proficiency test comprising 28 primary TNBCs, as well as PD‐L1/SP142 expression and levels of TILs in 49 distant TNBC metastases with various localizations. Interobserver agreement for PD‐ L1 status (positive versus negative) was high in the proficiency test: the corresponding scores as percentages showed good agreement with the consensus diagnosis. In TNBC metastases, there was substantial variability in PD‐L1 status at the individual patient level. For one in five patients, the chance of treatment was essentially random, with half of the pathologists designating them as positive and half negative. Assessment of PD‐L1/SP142 and TILs as percentages in TNBC metastases showed poor and moderate agreement, respectively. Additional training for metastatic TNBC is required to enhance interobserver agreement. Such training, focusing on metastatic specimens, seems worthwhile, since the same pathologists obtained high percentages of concordance (ranging from 93% to 100%) on the PD‐L1 status of primary TNBCs