The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors.

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR's predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100-2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020-1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562-0.747, p= 0.001) and 0.671 (95% CI: 0.598-0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

Extremely high erythrocyte sedimentation rate revisited in rheumatic diseases: a singlecenter experience.

BACKGROUND: The objectives were to define the distribution of rheumatic diseases in patients with erythrocyte sedimentation rate (ESR) ≥ 100 mm/h and to find variables that can differentiate main study groups from others. METHODS: Charts of patients admitted with ESR ≥ 100 mm/h between 2015 and 2020 were reviewed. Patients were divided into four diagnostic groups based on etiology: infection (without a rheumatic diagnosis), oncologic (without a rheumatic diagnosis), rheumatic, and no definitive diagnosis. Patients with the rheumatic diagnosis were divided into three main study groups: those who had been recently diagnosed with a rheumatic disease, those who had a flare-up of the rheumatic disease, and those who had an infection in the course of the rheumatic disease. Appropriate statistical tests and decision-tree analysis by R and ROC curve were applied. p < 0.05 was considered statistically significant. RESULTS: A total of 2442 patients (311 (12.7%) with rheumatic disorders) were identified. Eightysix (27.7%) patients had newly diagnosed rheumatic disease (41; 47.7% with vasculitis); 111 (35.7%) had rheumatic disease flare-up (92; 82.9% with inflammatory arthritis); and 114 (36.6%) had coexisting infection (61; 53.5% inflammatory arthritis). Irrespective of the study group, the most commonly encountered diseases were rheumatoid arthritis and spondyloarthritis. Serum albumin levels (2.78 mg/dL) and platelet count (290/mm6 ) were valuable to discriminate disease flare-up and coexisting infection; moreover, high ferritin levels were accounted for adult-onset Still disease among patients with newly diagnosed rheumatic diseases. DISCUSSION: Extremely high ESR is still a valuable clinical parameter, and rheumatic causes are significant besides malignancy and infections. Albumin, thrombocyte count, and ferritin are other tests that clinicians should consider when caring for a patient with ESR ≥ 100 mm/h who has rheumatic disease.

Knowledge and Attitudes of Turkish Physicians towards Human Monkeypox Disease and Related Vaccination: A Cross-Sectional Study.

Background: In May 2022, the monkeypox virus outbreak in multiple countries on various continents marked a potential resurgence of the disease as a global health issue. Considering the crucial role of physicians in mitigating the monkeypox outbreak, we sought to evaluate physicians' knowledge, attitude, concerns, and vaccine acceptance for monkeypox, in the shadow of the COVID-19 pandemic. Methods: A large-scale, cross-sectional survey was conducted among 283 physicians between 20 August−2 September 2022, in Turkey. The participants' sociodemographic characteristics, knowledge, attitudes, concerns, and vaccine acceptance toward monkeypox infection were collected via a questionnaire. Results: Our study revealed that 32.5% of physicians achieved a good level of knowledge; similarly, 31.4% of the physicians planned to have the monkeypox vaccine. Multivariate binary logistic regression analysis showed that female physicians (p = 0.031) and older people (≥30 vs. <30) were more likely to be knowledgeable about monkeypox (p = 0.007). We found that participants from divisions of internal medicine (p = 0.033) who knew about the monkeypox disease during medical school or residency (p = 0.005) and were previously exposed to COVID-19 disease (p = 0.005) were more likely to have a good knowledge score of monkeypox. We also found that physicians with a good knowledge score were more worried about monkeypox compared to COVID-19 (AOR: 2.22; 95% CI:1.13−4.33; p = 0.019). Additionally, those who had information on monkeypox during medical education (AOR = 2.16, 95% CI = 1.10−4.21; p = 0.024) were more likely to receive the smallpox vaccine to prevent monkeypox viral infection when available. Conclusions: The present study pointed out that physicians in Turkey have unsatisfactory levels of knowledge about the emerging monkeypox. This study results can impede attempts to detect and manage cases of monkeypox and should be addressed through appropriate and timely awareness and educational programs, alerts, and seminars. These might serve as the basis for policymakers' decisions about promoting national monkeypox vaccination strategies and addressing potential vaccine hesitancy and misinformation when needed.

Newly diagnosed cancer and the COVID-19 pandemic: tumour stage migration and higher early mortality.

BACKGROUND: We compared the new outpatient clinic referrals during the first 10 months of the COVID-19 pandemic with the year before. METHODS: We compared baseline characteristics of the 2208 new referrals in 2020 (n=922) and 2019 (n=1286) with Χ2 and Mann-Whitney U tests and calculated ORs with binary logistic regression. To evaluate the expected changes in the cancer survival secondary to stage migration, we used the 5-year survival data of Survival, Epidemiology and End Results (SEER) Program 2010-2016. RESULTS: The percentage of patients with inoperable or metastatic disease was significantly increased during the pandemic (49.8% vs 39%, OR: 1.553, 95% CI: 1.309 to 1.843, p<0.001). We observed a significant decrease in the percentage of patients diagnosed via the screening methods (18.8% vs 28.7%, OR: 1.698, 95% CI: 1.240 to 2.325, p=0.001). The 90-day mortality after the cancer diagnosis was significantly higher during the pandemic (10.5% vs 6.6%, OR: 1.661, 95% CI: 1.225 to 2.252, p=0.001). Due to the increased advanced-stage disease rate at first referral, significant decreases in 5-year survival rates were expected for breast cancer (-8.9%), colorectal cancer (-11.1%), cervix cancer (-10.3%) and melanoma (-7%). CONCLUSION: We think that collaborative efforts are paramount to prevent the pandemic of late cancer diagnoses and ensure patient safety during the pandemic.

The association of BMI and sarcopenia with survival in patients with glioblastoma multiforme.

Background: The association between obesity and sarcopenia (via temporal muscle thickness) with overall survival (OS) has been evaluated in several glioblastoma multiforme studies, however, the data are inconclusive. Methods: The authors conducted meta-analyses via the generic inverse-variance method with a random-effects model. Results: In the pooled analysis of five studies, including 973 patients, patients with lower temporal muscle thickness had significantly decreased OS (HR: 1.62, 95% CI: 1.16-2.28, p = 0.005). The pooled analysis of five studies, including 2131 patients, demonstrated decreased OS in patients with lower BMI compared with patients with obesity (HR: 1.45, 95% CI: 1.12-1.88, p = 0.005). Conclusion: Readily available body composition parameters could be used for prognosis prediction and to aid in treatment decisions in patients with glioblastoma multiforme.

Petroselinum crispum, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report.

Sirolimus is an immunosuppressive drug used to prevent graft rejection. Therapeutic drug monitoring is required as with other immunosuppressive drugs. Previous studies have shown the interactions between sirolimus and drugs that affect the activity of cytochrome P450 3A4 and P-glycoprotein. There is an increasing tendency for the use of herbal remedies in many countries. Medicinal herbs are rich sources of natural bioactive compounds that could interact with drugs. Parsley, Petroselinum crispum, is a food, spice, and also a medicinal herb. We report a case of a renal transplant recipient who had a supratherapeutic blood level of sirolimus due to consuming excessive parsley to highlight a possible herb-drug interaction. This is the first case report describing sirolimus-parsley interaction. Herb-drug interactions are especially important for drugs with a narrow therapeutic window. For this reason, healthcare professionals should question all patients, especially transplant patients, about the use of herbs or herbal products and report interactions. PLAIN LANGUAGE SUMMARY: Parsley, a commonly consumed food, affects the level of an important drug in a renal transplant recipient: A case report Sirolimus is a drug that suppresses the immune response used to prevent organ rejection in people who have had kidney transplants. In order to reach the optimum balance between therapeutic efficacy and adverse effects, sirolimus blood levels should be closely monitored. Previous studies have shown the interactions between sirolimus and drugs that affect the activities of metabolizing enzymes and transporter proteins. Parsley is a food, spice, and also a medicinal herb. Medicinal herbs are rich sources of natural bioactive compounds that could interact with a prescription drug. We report a case of a renal transplant recipient who had a rise in the blood level of sirolimus due to the ingestion of an excessive amount of parsley to highlight possible herb-drug interaction.

Poorer baseline performance status is associated with increased thromboembolism risk in metastatic cancer patients treated with immunotherapy.

PURPOSE: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors. METHODS: A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses. RESULTS: The median age was 60 (interquartile range (IQR) 48-66) years, and the median follow-up was 10.1 (IQR 5.8-18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011-9.039, p=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk. CONCLUSIONS: In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.

Evaluation of emergency departments visits in patients treated with immune checkpoint inhibitors.

BACKGROUND: The emergency department (ED) is a crucial encounter point in cancer care. Yet, data on the causes of ED visits are limited in patients treated with immune checkpoint inhibitors (ICI). Therefore, we evaluated ED visits in patients treated with ICIs in attempt to determine the predisposing factors. METHODS: We performed a retrospective chart review on adult cancer patients treated with ICIs for any type of cancer in the Hacettepe University Cancer Center. The data on ED visits after the first dose of ICIs to 6 months after the last cycle of ICIs were collected. RESULTS: A total of 221 patients were included in the study. The mean age was 58.46 ± 13.87 years, and 65.6% of patients were males. Melanoma was the most common diagnosis (27.6%), followed by kidney and lung cancers. Eighty-three of these patients (37.6%) had at least one emergency department (ED) visit. Most of the ED visits were related to symptoms attributable to the disease burden itself, while immune-related adverse events comprised less than 10% of these visits. While baseline Eastern Cooperative Oncology Group performance status, age, polypharmacy, concomitant chemotherapy, eosinophilia, and lactate dehydrogenase levels did not significantly increase the risk, patients with regular opioid use and baseline neutrophilia (> 8000/mm3) had a statistically significant increased risk of visiting the ED (p = 0.001 and 0.19, respectively). These two factors remained significant in the multivariate analyses. CONCLUSION: In this study, almost 40% of ICI-treated patients had ED visits. Collaboration with other specialties like emergency medicine is vital for improving the care of patients receiving immunotherapy.

COVID-19 pandemic: changes in cancer admissions.

BACKGROUND: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute. METHODS: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years. RESULTS: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced. CONCLUSION: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.