Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this

Successful Isolation of Burkholderia pseudomallei from Soil by Extended Incubation of Ashdown’s Agar: A Cross-sectional Study

Introduction: Melioidosis is an infectious disease of humans and animals caused by an environmental saprophyte Burkholderia pseudomallei. Although the organism is associated with soil and water, environmental isolation is rarely successful which could be due to the existence of viable but non culturable forms. Aim: To isolate B. pseudomallei from the soil to detect the environmental presence of this organism in and around Puducherry, India. Materials and Methods: A descriptive cross-sectional study was carried out from July 2018 to January 2021 at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. A total of 473 soil samples were collected from areas surrounding the residence and workplaces of seven cultureproven melioidosis cases, from Puducherry and three districts of Tamil Nadu (Cuddalore, Nagapattinam and Villupuram) during the dry and wet seasons. Soil samples were enriched in Ashdown’s broth and cultured on Ashdown’s agar. The plates were incubated at 37°C and examined daily for seven days with a further extended period of incubation till the tenth day for samples that did not show growth. Suspected isolates were subjected to Vitek 2 system for biochemical identification. Confirmation of the isolates was carried out by antigen detection and Polymerase Chain Reaction (PCR). Results: From 473 soil samples processed, bacteria with colony morphology similar to B. pseudomallei were isolated in 56 (11.83%) samples. Only one isolate, which was detected on the tenth day of incubation was confirmed as B. pseudomallei using antigen detection and PCR. This sample was collected during the wet season (December 2020) from Endur, in the Villupuram district of Tamil Nadu, India. Conclusion: The study findings highlight the importance of extended incubation of culture plates at 37°C for up to ten days to improve the chances of isolation from the soi

Variable Virulence Genes in Clinical Isolates of Burkholderia pseudomallei: Impact on Disease Severity and Outcome in Melioidosis

Objectives To isolate Burkholderia pseudomallei from clinical specimens and study the association of virulence genes with clinical manifestations and outcome in patients with melioidosis. Materials and Methods Burkholderia pseudomallei isolates obtained from melioidosis cases diagnosed during 2018 to 2021 were identified using VITEK 2 system and confirmed by polymerase chain reaction (PCR) targeting a Type III secretion system gene cluster. Multiplex PCR was performed to detect the genotypes of lipopolysaccharide (LPS) namely A, B, and B2, and singleplex PCR was performed to detect the presence of the Burkholderia intracellular motility gene (BimA) and filamentous hemagglutinin gene (fhaB3). Statistical Analysis Chi-square/Fisher's exact tests were performed to study the association between various clinical manifestations and outcome and different virulence genes. The results were expressed as unadjusted odds ratios with 95% confidence intervals. Results Sixty-seven isolates were available for characterization. BimABm and BimABp were observed among 82 and 18% of the isolates, respectively. Both sepsis and mortality were significantly associated with BimABm . Majority of the isolates had fhaB3 (97%). Most of the isolates showed the presence of LPS A gene (65.7%) followed by LPS B gene (6%), while LPS B2 was not detected. Nineteen isolates could not be assigned to any LPS genotypes. Conclusion Among the virulence genes studied, only BimABm was significantly associated with sepsis and mortality. More than a quarter (28.3%) of the isolates could not be assigned to any LPS genotypes, hinting at a greater genetic diversity in our isolates

DataSheet_1_Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.pdf

ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.</p

DataSheet_2_Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.pdf

ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.</p

Image_1_Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival.tif

ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.</p