Candida keratitis and endopthalmitis after corneal transplantation; two case reports, a novel regimen and literature overview of therapeutic options

Purpose: To evaluate treatment options for candida keratitis and endopthalmitis after corneal transplantation. Methods: Case reports and literature review. Results: Two patients with keratitis due to Candida glabrata/parapsilosis after corneal transplantation were successfully treated with a combination of topical voriconazole, intracameral voriconazole and amphotericin B, and systemic treatment with flucytosine. Conclusions: Natamycine and voriconazole topically are preferred therapeutic options for the treatment of fungal keratitis. Systemic flucytosine is a useful alternative additive, particularly for countries where natamycine is not registered as a pharmaceutical agent

Erratum to: Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors.

The following error appeared in Section 3.5 in Ref. [1]. Instead of ‘Progressive disease-L1 expression data were available for 87 patients’, the text should read ‘PD-L1 expression data were available for 87 patients’. We apologize for this error.</p

Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients

Circulating cell-free DNA (ccfDNA) may contain DNA originating from the tumor in plasma of cancer patients (ctDNA) and enables noninvasive cancer diagnosis, treatment predictive testing, and response monitoring. A recent multicenter evaluation of workflows by the CANCER-ID consortium using artificial spiked-in plasma showed significant differences and consequently the importance of carefully selecting ccfDNA extraction methods. Here, the quantity and integrity of extracted ccfDNA from the plasma of cancer patients were assessed. Twenty-one cancer patient-derived cell-free plasma samples were selected to compare the Qiagen CNA, Maxwell RSC ccfDNA plasma, and Zymo manual quick ccfDNA kit. High-volume citrate plasma samples collected by diagnostic leukapheresis from six cancer patients were used to compare the Qiagen CNA (2 mL) and QIAamp MinElute ccfDNA kit (8 mL). This study revealed similar integrity and similar levels of amplified short-sized fragments and tumor-specific mutants comparing the CNA and RSC kits. However, the CNA kit consistently showed the highest yield of ccfDNA and short-sized fragments, while the RSC and ME kits showed higher variant allelic frequencies (VAFs). Our study pinpoints the importance of standardizing preanalytical conditions as well as consensus on defining the input of ccfDNA to accurately detect ctDNA and be able to compare results in a clinical routine practice, within and between clinical studies

Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.1 criteria, progression-free survival (PFS), DCB, and overall survival (OS). To this aim, blood tubes were collected from advanced-stage lung adenocarcinoma patients (n = 100) receiving immune checkpoint inhibitors (ICI) at baseline (t(0)) and prior to first treatment evaluation (4-6 weeks; t(1)). Nontargetable (driver) mutations detected in the pretreatment tumor biopsy were used to quantify tumor-specific ctDNA levels using droplet digital PCR. We found that changes in ctDNA levels were strongly associated with tumor response. A > 30% decrease in ctDNA at t(1) correlated with a longer PFS and OS. In total, 80% of patients with a DCB of >= 26 weeks displayed a > 30% decrease in ctDNA levels. For patients with a PD-L1 tumor proportion score of >= 1%, decreasing ctDNA levels were associated with a higher frequency a DCB (80%) and a prolonged median PFS (85 weeks) and OS (101 weeks) compared with patients with no decrease in ctDNA (34%; 11 and 39 weeks, respectively). This study shows that monitoring of ctDNA dynamics is an easy-to-use and promising tool for assessing PFS, DCB, and OS for ICI-treated NSCLC patients

Invasive Candidiasis in the Elderly:Considerations for Drug Therapy

Candida infections in the elderly are an important and expanding clinical problem, with significantly higher mortality in this group than in younger patients. The increasing problem of invasive Candida infections may be related to higher prevalence of immunocompromised older people and the emergence of treatment resistance. Older people, especially the frail and critically ill, are at higher risk of medication-related harmful effects due to changes in pharmacokinetics and pharmacodynamics, which may be further complicated by organ dysfunction, diminished homeostatic control, co-morbidities and polypharmacy. Here, we review the available options for the treatment of Candida infections and provide insights into the challenges surrounding the optimal use of antifungal drugs in the elderly

The mast cell: A Janus in kidney transplants

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting

A shortened version of Raven's standard progressive matrices for children and adolescents

Numerous developmental studies assess general cognitive ability, not as the primary variable of interest, but rather as a background variable. Raven's Progressive Matrices is an easy to administer non-verbal test that is widely used to measure general cognitive ability. However, the relatively long administration time (up to 45 min) is still a drawback for developmental studies as it often leaves little time to assess the primary variable of interest. Therefore, we used a machine learning approach - regularized regression in combination with cross-validation - to develop a short 15-item version. We did so for two age groups, namely 9 to 12 years and 13 to 16 years. The short versions predicted the scores on the standard full 60-item versions to a very high degree r = 0.89 (9-12 years) and r = 0.93 (13-16 years). We, therefore, recommend using the short version to measure general cognitive ability as a background variable in developmental studies

Practice effects on the modified Concept Shifting Task (mCST): A convenient assessment for treatment effects on prefrontal cognitive function

<p>Abstract</p> <p>Background</p> <p>Trail-making tests, such as the Concept Shifting Task (CST), can be used to test the effects of treatment on cognitive performance over time in various neuropsychological disorders. However, cognitive performance in such experimental designs might improve as a result of the practice obtained during repeated testing rather than the treatment itself. The current study investigated if practice affects the accuracy and duration of performance on the repeatedly administered Concept Shifting Task modified to make it resistant to practice (mCST). The mCST was administered to 54 healthy participants twice a day, before and after a short break, for eight days. Results. The ANOVA and meta-analysis showed that there was no improvement in the mCST accuracy on the last vs. the first trial (Hedges' <it>g </it>= .14, <it>p </it>= .221) or within the session (after vs. before the break on all days; <it>g </it>= .01, <it>p </it>= .922). However, the participants performed the task faster on the last vs. the first trial (<it>g </it>= -.75, <it>p </it>< .001) and after vs. before the break on all days (<it>g </it>= -.12, <it>p </it>= .002). Conclusions. Repeated administration of the mCST does not affect the accuracy of performance on the test. However, practice might contribute to faster performance on the mCST over time and within each session.</p

Treatment decision-making and the added value of the general practitioner: A qualitative exploration of cancer patients' perspectives

OBJECTIVE: Cancer patients are increasingly involved in decision-making for cancer treatment. General practitioners' (GPs) support in this process is advocated. Therefore, GPs need to be aware of patients' treatment decision-making process and their potential role. We aim to understand the treatment decision-making process and to explore the added value of GP involvement, from the perspective of cancer patients treated with curative intent. METHODS: An explorative qualitative study was performed. Semi-structured interviews were conducted with 20 purposively sampled Dutch cancer patients treated with curative intent. RESULTS: Patients' treatment decision-making process was dominated by a focus on 'safeguarding survival'. Patients generally followed the treatment plan as proposed by their physician and did not always experience having a treatment choice. The majority of patients expressed added value for GP involvement, mainly to provide psychological support, but also for providing shared decision-making (SDM) support. CONCLUSION: The treatment decision-making process of cancer patients treated with curative intent is dominated by the urge to 'safeguard survival'. GPs should be aware of their added value in providing psychological support and their potential role to support SDM following a cancer diagnosis