The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

INTRODUCTION: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. METHODS: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. RESULTS: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). CONCLUSION: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Lesson learned from the pandemic: Isolation and hygiene measures for COVID-19 could reduce the nosocomial infection rates in oncology wards.

INTRODUCTION: It was previously demonstrated that seasonal influenza incidence was significantly decreased during the COVID-19 pandemic, possibly due to respiratory and hygiene precautions. From this point, we hypothesized that the COVID-19 precautions could lead to a decrease in nosocomial infection rates in oncology inpatient wards. METHODS: We evaluated the nosocomial infection rates in an inpatient palliative oncology ward in the first 3 months of the COVID-19 pandemic in our country and compared this rate with the same time frame of the previous year in our institution. RESULTS: The percentage of nosocomial infections complicating the hospitalization episodes were significantly reduced in the first 3 months of the pandemic compared to the previous year (43 vs. 55 nosocomial infection episodes; 18.6% vs. 32.2%, p = 0.002). The decrease in the nosocomial infections was consistent in the different types of infections, namely pneumonia (4.8% vs. 7.6%), urinary tract infection (5.2% vs. 7.6%), bacteremia (5.2% vs. 7%) and intraabdominal infections (2.6% vs. 3.5%). The median monthly disinfectant use was significantly increased to 98 liters (interquartile range: 82 - 114) in 2020 compared to 72 L (interquartile range: 36 - 72) in 2019 (p = 0.046). CONCLUSION: The continuation of the simple and feasible hygiene and distancing measures for healthcare workers and patient relatives and adaptations for earlier discharge could be beneficial for preventing nosocomial infections in oncology wards. These measures could be implemented routinely even after the COVID-19 pandemic for patient safety, especially in settings with higher nosocomial infection rates like inpatients palliative care units.

Lower prognostic nutritional index is associated with poorer survival in patients receiving immune checkpoint inhibitors.

Aim: Blood-based biomarkers like prognostic nutritional index (PNI) are readily available biomarkers for immunotherapy efficacy, although the data are limited. So, we aimed to evaluate the association between PNI and overall survival (OS) in immunotherapy-treated patients. Materials & methods: For this retrospective cohort study, data of 150 immunotherapy-treated advanced cancer patients were evaluated. The association between clinical factors and OS was evaluated with multivariate Cox-regression analyses. Results: After a median follow-up of 8.5 months, 94 patients died. The median OS was 11.07 months. The low PNI (hazard ratio [HR]: 2.065; p = 0.001), high lactate dehydrogenase (HR: 2.515; p = 0.001) and poor Eastern Cooperative Oncology Group (ECOG) status (HR: 2.164; p = 0.009) was associated with poorer OS in multivariate analyses. Conclusion: In our experience, survival with immunotherapy was impaired in patients with lower PNI and higher lactate dehydrogenase levels and poorer ECOG status.

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient.

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

Slight conductive hearing loss in children with narrowed maxilla and deep palatal vault.

UNLABELLED: PROBLEM/OBJECTIVES: Maxillary constriction and high palatal arch are associated with increased risk of chronic eustachian tube dysfunction and conductive hearing loss (CHL) due to chronic effusion. However, this relationship has not been clearly demonstrated. This study assessed CHL in school children with a narrowed maxilla and deep palatal vault. METHODOLOGY: Thirty-two children with maxillary constriction were randomly selected for the study group and 28 children with normal transverse maxillary development were selected for the control group. Pure-tone audiograms were obtained for all children, and hearing levels and air-bone gaps were measured. RESULTS: Air-bone gap measurements in the control group ranged from 5.50 to 14.50 decibels (dB), and in the study group they were between 5.00 and 24.00 dB. In the study group, 14 (43.8%) children had slight CHL, and the remaining 18 (56.2%) children had normal hearing levels. In the control group, all of the children had normal hearing levels. Hearing levels and air-bone gaps were greater in the study group than the control group. CONCLUSION: This study showed that children with a narrowed maxilla and deep palatal vault may have slight CHL. Therefore, the onset of CHL should be followed with hearing screening programs.

Lipoprotein subfraction profile and HDL-associated enzymes in sickle cell disease patients.

Although hypocholesterolemia is a reported finding in sickle cell disease (SCD), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) subfractions and HDL-associated enzymes have not been determined in SCD patients. Blood was collected from 38 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients who had not received blood transfusions in the last 3 months. Serum lipids were measured by automated analyzer while LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Serum levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were significantly decreased, while TG levels were significantly increased in SCD patients compared to controls. A significant decrease in intermediate-density lipoprotein (IDL)-C, IDL-B, IDL-A and LDL-1 fractions were seen in SCD patients, while no significant difference was observed in small dense LDL particles. A significant decrease was seen in HDL-large, HDL-intermediate and HDL-small fractions in SCD patients versus controls. Levels of LCAT and ApoA-1 protein measured in SCD patients were significantly lower while no significant difference was observed in CETP and ApoB protein levels compared to controls. The reduction observed in LDL- and HDL-C in SCD patients was reflected as significantly decreased IDL, LDL-1 and HDL-subfractions. Decreased HDL subfractions may possibly lead to the reduced ApoA-1 and LCAT protein levels observed in SCD patients.

Usefulness of monocyte chemoattractant protein-1 to predict no-reflow and three-year mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Although monocyte chemoattractant protein-1 (MCP-1) levels are increased in patients with ST-segment elevation myocardial infarction, the prognostic value of MCP-1 in primary percutaneous coronary intervention (pPCI) is not clear. The goal of the present study was to investigate the association of MCP-1 levels with myocardial perfusion and prognosis in patients with ST-segment elevation myocardial infarction undergoing pPCI. Consecutive pPCI patients (n = 192) were assigned to tertiles according to their admission serum MCP-1 levels. Angiographic no-reflow, Thrombolysis In Myocardial Infarction flow grade, myocardial blush grade, and ST-segment resolution were assessed. Mortality and major adverse cardiac events were evaluated during hospitalization and at the 3-year clinical follow-up visit. Failure of ST resolution was associated with greater admission MCP-1 levels. The risk of no-reflow (Thrombolysis In Myocardial Infarction flow ≤2 or Thrombolysis In Myocardial Infarction flow 3 with final myocardial blush grade ≤2 after pPCI and ST resolution <30%) increased as the admission MCP-1 increased. The 3-year mortality increased as the MCP-1 level increased (8% vs 22% vs 28% for the 3 tertiles, p <0.01). Multivariate logistic regression analysis demonstrated that MCP-1 levels at admission are a significant independent correlate of 3-year mortality in patients with no-reflow as detected by myocardial blush grade. A receiver operating characteristics analysis identified an optimum cut point of ≥254 pg/ml, which was associated with a negative predictive value of 95% in association with 1-year mortality. In conclusion, the plasma MCP-1 levels at admission are independently associated with the development of no-reflow and 3-year mortality in patients with ST-segment elevation myocardial infarction undergoing pPCI.

Mycoflora and natural occurrence of aflatoxin, cyclopiazonic acid, fumonisin and ochratoxin A in dried figs.

Mycoflora, the mycotoxigenic properties of moulds, and natural contamination with mycotoxins such as aflatoxins (AFs), cyclopiazonic acid (CPA), fumonisin B(1) (FB(1)) and ochratoxin A (OTA) were investigated in dried figs. Dry fig samples were collected from orchards during the drying stage in the Aegean Region of Turkey. Fungal isolates were identified using morphological, chemical as well as molecular methods. Mycotoxigenic characteristics of moulds were assessed by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Mycotoxins except CPA (by TLC) were determined by HPLC. All the fig samples were contaminated with moulds and 94.7% contained one or more mycotoxigenic species. The most prevalent moulds present in dried figs belong to the Aspergillus section Nigri members, being 93.9% positive for the samples, followed by Fusarium spp., Aspergillus section Flavi and Penicillium spp. On the other hand, Fusarium spp. had the highest count and the number of fumonisin producing Fusarium was also high. A total of 48% of 115 dried fig samples contained OTA (range = 0.1-15.3 ng g(-1)), 74.7% of the samples had FB(1) (range = 0.05-3.65 mg kg(-1)), 10.0% of the samples had aflatoxin (range = 0.1-763.2 ng g(-1)) and 24.3% of the samples were tentatively identified as being contaminated with CPA (range = 25-187 ng g(-1)). Dried fig samples were contaminated with one (33.0%), two (47.0%), three (5.2%) and four mycotoxins (3.5%). A total of 11.3% of dried fig samples were not contaminated with any of the four mycotoxins. To the best of our knowledge, CPA and fumonisin have been found for the first time in dried figs.

Gas6-axl receptor signaling is regulated by glucose in vascular smooth muscle cells.

OBJECTIVE: The receptor tyrosine kinase Axl and its ligand Gas6 are involved in the development of renal diabetic disease. In vascular smooth muscle cells (VSMCs) Axl is activated by reactive oxygen species and stimulates migration and cell survival, suggesting a role for Axl in the vascular complications of diabetes. METHODS AND RESULTS: We investigated the effect of varying glucose concentration on Axl signaling in VSMCs. Glucose exerted powerful effects on Gas6-Axl signaling with greater activation of Akt and mTOR in low glucose, and greater activation of ERK1/2 in high glucose. Plasma membrane distribution and tyrosine phosphorylation of Axl were not affected by glucose. However, coimmunoprecipitation studies demonstrated that glucose changed the interaction of Axl with its binding partners. Specifically, binding of Axl to the p85 subunit of PI3-kinase was increased in low glucose, whereas binding to SHP-2 was increased in high glucose. Furthermore, Gas6-Axl induced migration was increased in high glucose, whereas Gas6-Axl mediated inhibition of apoptosis was greater in low glucose. CONCLUSIONS: This study demonstrates a role for glucose in altering Axl signaling through coupling to binding partners and suggests a mechanism by which Axl contributes to VSMC dysfunction in diabetes.

Evaluation of the inclination in posterior dentoalveolar structures after rapid maxillary expansion: a new method.

OBJECTIVES: In order to compare the skeletal and dental effects of rapid maxillary expansion, orthodontists need an assessment of buccal dentoalveolar inclination. The aim of the present paper is to introduce a new technique for the evaluation of buccal inclinations in dentoalveolar structures. METHODS: Using barium sulphate solution with a paintbrush, a thin line was drawn on and between the first molars of the maxillary stone casts. Then, radiographic images of the stone casts were obtained. Buccal tipping of molar crowns and alveolar processes were evaluated on these images by means of a computerized imaging software program. CONCLUSIONS: This new evaluation technique is inexpensive, simple and reliable for the assessment of dentoalveolar inclination. In addition, the changes in dentoalveolar structures may also be visualized by superimposing the pre- and post-treatment images.

The effect of rapid maxillary expansion on conductive hearing loss.

The effects of rapid maxillary expansion (RME) on conductive hearing loss were investigated in 14 subjects (11 females and 3 males). The subjects ranged in age from 10 years 4 months to 16 years 9 months (mean age 12 years 11 months +/- 1 year 9 months) and had narrow maxillary arches and conductive hearing loss. Hearing levels were determined by means of pure-tone audiometric records. Three records were taken for each subject. The first was taken before RME, the second after sufficient midpalatal suture opening was achieved (mean = 15 days), and the third after the retention period (mean = 4.5 months). All the audiometric records were assessed by an otolaryngologist. Changes in both hearing level and air-bone gap were investigated by means of analysis of variance. It has been determined that hearing improved at a statistically significant level (P < 0.05) after the active treatment period, but that the improvement reversed at the end of the retention period. Five patients experienced significant and stable hearing improvement over the duration of this study.

A study on the pharyngeal size in different skeletal patterns.

In the present study, pharyngeal size was investigated on the lateral cephalometric head films of 90 subjects, 45 males and 45 females, having different ANB angles. All of the subjects were aged 13 to 15 years. The films were taken at natural head position, and all were divided into three groups according to the ANB angle: ANB angles smaller than 1 degree, between 1 degree and 5 degrees, and larger than 5 degrees. In addition, each group was also divided into two subgroups according to sex. The effects of the ANB angle and sex on the pharyngeal size were investigated by means of variance analysis. It has been observed that two measurements, hy-apw4 and oropharynx area measurements, were affected by the change of ANB angle, and two other measurements, t-ppw and hy-apw2 measurements, by the sex; and that hy-apw4 measurement and oropharynx area became smaller with the increase of ANB angle.

The study of the maxillary sinus areas in different orthodontic malocclusions.

In the present study, the maxillary sinus areas have been investigated on orthopantomographs of 103 male and 86 female subjects either with ideal occlusions or with malocclusions. It has been found that malocclusions and sex factors have no effect on the size of the maxillary sinuses, and that sex is a significant factor only in Angle Class II malocclusions. The female subjects with Angle Class II malocclusions have larger maxillary sinuses than the male subjects and the other groups of female subjects.

Twenty-year follow-up of 160 patients with ataxia-telangiectasia.

The clinical and immunological findings of 160 patients diagnosed over a period of twenty years as having ataxia-telangiectasia (AT) are presented. The study group composed of 68 females and 92 males were members of 117 families. The rate of parental consanguinity was 65 percent. The incidence of AT in 117 families was 36.6 percent. All patients had the characteristic facial and postural features of AT. The mean duration of follow-up of 160 patients was 6.35 years. Fifty patients had died during the follow-up (36 of pulmonary infections, 14 of malignancies). Somatic growth retardation was a prominent feature. Recurrent sinopulmonary infections were detected in 66 percent of patients. Two patients had hypothyroidism, one had diabetes mellitus, and one had both conditions. The incidence of malignancies was found to be 2.3 percent in the immediate relatives of the patients. The total lymphocyte count was low in 57 percent, and skin tests to PHA, candida, PPD and SK-SD were negative in 17.7%, 72.6%, 43.6%, and 78.2% of patients, respectively. In vitro blastogenic response to PHA was low in 61 percent of patients. The mean value of E-rosette formation was significantly lower than control values. Six patients had low serum IgG levels. The serum IgM level was high in 26.6 percent of patients and the IgA level was low or absent in 51.3 percent. There was no correlation between immune disturbance and duration of illness.

A comparison of ANB, WITS, AF-BF, and APDI measurements.

In the present study, the relationships among ANB, Wits, AF-BF, and APDI measurements used in the assessment of the anteroposterior jaw disorders were examined on the cephalometric radiographs of 63 male and 82 female subjects, and high correlations were found among them. Furthermore, relationships were explored between these parameters and some measurements that were thought to have influenced them. The results of the geometric studies could not be proved on the basis of statistical evaluation.