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Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in de-novo acute myeloid leukemia patients receiving induction chemotherapy. Despite using posaconazole, a broad-spectrum antifungal, for IFI prophylaxis, the breakthrough IFI rate is high in the real-world setting. One of the reasons could be frequent suboptimal plasma posaconazole levels. In the present study, we evaluated if therapeutic drug monitoring (TDM) guided posaconazole prophylaxis can reduce the IFI rates in comparison to a historical cohort. We enrolled 90 patients, > / = 16 years of age, without baseline IFIs, planned for remission induction therapy. All patients were started on posaconazole suspension 200 mg TDS and the dose was increased in a stepwise manner if trough levels were found to be suboptimal (< 350 ng/ml for day 2 or < 700 ng/ml subsequently). The TDM based approach resulted in a significant decline in breakthrough IFI rates (18% versus 52%, P  < 0.0001) A total of 69 patients (78%) required dose escalation. Thirty-one patients required change in antifungals due to either suboptimal levels, persistent fever, diarrhoea or vomiting. We could not demonstrate an exposure-response relationship but the difference in IFI rates in patients with a median posaconazole level > / = 700 ng/ml (0%) and < 700 ng/ml (21.6%) was clinically meaningful. Posaconazole levels were found to be significantly lower in patients on antacids and prokinetics. The incidence of posaconazole-related grade 3 toxicity was low (2.3%). Thus TDM-based dosing of posaconazole helps reduce breakthrough IFI rate and should be a part of posaconazole prophylaxis., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01709-3., Competing Interests: Conflict of interestThe authors have declared no conflicts of interest.Ethical ApprovalAll authors declare that they approve the final version of the manuscript. In addition, the authors have declared no conflicts of interest. The study was approved by the institutional ethics committee and was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. The study was registered in the Clinical Trials Registry – India (CTRI) (CTRI/2017/06/008810)., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Multiple low-cost biosimilars of bevacizumab are now available but their clinical efficacy has never been compared against the original (innovator) molecule in glioblastoma. The aim of the current analysis is to compare the overall survival (OS) in recurrent/progressive glioblastoma patients between the biosimilar and innovator molecules., Materials and Methods: Adult recurrent/progressive glioblastoma patients treated with bevacizumab from 1 July 2015 to 30 July 2019 were identified. These patients were either offered Bevacizumab innovator (Avastin, Roche) or biosimilar (BevaciRel: Reliance Life sciences or Bryxta: Zydus Oncosciences) depending upon the financial status and affordability of the patients. The primary endpoint of the study was OS, while progression-free survival (PFS) and adverse events were the secondary endpoints., Results: There were 82 patients, out of which 57 received innovator and 25 received biosimilar bevacizumab. At median follow-up of 26 months, the median PFS was 3.66 (95% confidence interval (CI) 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and biosimilar group, respectively (Log-rank test p -value = 0.072). The hazard ratio (HR) for progression was 0.61 (95% CI 0.35 to 1.05; p -value = 0.075). At the time of data cut-off, the median OS was 5.53 (95% CI, 5.07 to 5.99) versus 7.33 months (95% CI, 5.63 to 9.03) in innovator and biosimilar group, respectively (Log-rank test p -value = 0.51). The HR for death was 1.21 (95% CI, 0.67 to 2.17; p -value = 0.51). The adverse events and safety profiles were comparable between the two groups., Conclusion: In the recurrent/progressive glioblastoma patients, both innovator and biosimilar bevacizumab seem to have similar safety and clinical efficacy., Competing Interests: The authors declare that they have no competing interests., (© the authors; licensee ecancermedicalscience.)

Competing Interests: There are no conflicts of interest.

Objective: This longitudinal study used FDG-PET imaging to predict and monitor cognitive decline from normal aging., Methods: Seventy-seven 50-80-year-old normal (NL) elderly received longitudinal clinical examinations over 6-14 years (561 person-years, mean per person 7.2 years). All subjects had a baseline FDG-PET scan and 55 subjects received follow-up PET exams. Glucose metabolic rates (MRglc) in the hippocampus and cortical regions were examined as predictors and correlates of clinical decline., Results: Eleven NL subjects developed dementia, including six with Alzheimer's disease (AD), and 19 declined to mild cognitive impairment (MCI), on average 8 years after the baseline exam. The baseline hippocampal MRglc predicted decline from NL to AD (81% accuracy), including two post-mortem confirmed cases, from NL to other dementias (77% accuracy), and from NL to MCI (71% accuracy). Greater rates of hippocampal and cortical MRglc reductions were found in the declining as compared to the non-declining NL., Conclusions: Hippocampal MRglc reductions using FDG-PET during normal aging predict cognitive decline years in advance of the clinical diagnosis. Future studies are needed to increase preclinical specificity in differentiating dementing disorders.

Purpose: This study was designed to examine the utility of visual inspection of medial temporal lobe (MTL) metabolism in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD) using FDG-PET scans., Methods: Seventy-five subjects [27 normal controls (NL), 26 MCI, and 22 AD] with FDG-PET and MRI scans were included in this study. We developed a four-point visual rating scale to evaluate the presence and severity of MTL hypometabolism on FDG-PET scans. The visual MTL ratings were compared with quantitative glucose metabolic rate (MR(glc)) data extracted using regions of interest (ROIs) from the MRI-coregistered PET scans of all subjects. A standard rating evaluation of neocortical hypometabolism was also completed. Logistic regressions were used to determine and compare the diagnostic accuracy of the MTL and cortical ratings., Results: For both MTL and cortical ratings, high intra- and inter-rater reliabilities were found (p values <0.001). The MTL rating was highly correlated with and yielded a diagnostic accuracy equivalent to the ROI MR(glc) measures (p values <0.001). The combination of MTL and cortical ratings significantly improved the diagnostic accuracy over the cortical rating alone, with 100% of AD, 77% of MCI, and 85% of NL cases being correctly identified., Conclusion: This study shows that the visual rating of MTL hypometabolism on PET is reliable, yields a diagnostic accuracy equal to the quantitative ROI measures, and is clinically useful and more sensitive than cortical ratings for patients with MCI. We suggest this method be further evaluated for its potential in the early diagnosis of AD.

We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three groups of age, education, and gender matched NL, MCI, and AD subjects were studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging modalities identified the temporal neocortex as best separating MCI and AD, whereas widespread changes accurately classified NL and AD; 3) In most between group comparisons regional MRglu measures were diagnostically superior to volume measures. These cross-sectional data show that in MCI hippocampal formation changes exist without significant neocortical changes. Neocortical changes best characterize AD. In both MCI and AD, metabolism reductions exceed volume losses.