ELANE neutropenia and solid tumors: Four cases from the French severe chronic neutropenia registry

alexandrossfakianakis shared this article with you from Inoreader ELANE neutropenia and solid tumors: Four cases from the French severe chronic neutropenia registry via Pediatric Blood & Cancer Abstract Neutropenia related to ELANE gene mutations predisposes patients to infection and leukemia/myelodysplasia, but little is known about the predisposition to cancer. Among a cohort of 147 patients, we identified four with malignant solid tumors (papillary thyroid cancer, anal squamous cell cancer, papillary renal cell carcinoma, and adrenocortical carcinoma), all aged 25–50 years. Three occurred with cyclic neutropenia, and one occurred with severe chronic neutropenia. Previous radiotherapy was identified as a risk factor in one patient. No genetic predisposition was identified in the three other patients. View on Web

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Investigations Into Obesity and the Risk of Malignant Disease in Pediatric Thyroid Nodules—Reply

alexandrossfakianakis shared this article with you from Inoreader Investigations Into Obesity and the Risk of Malignant Disease in Pediatric Thyroid Nodules—Reply via JAMA Otolaryngology–Head & Neck Surgery Current Issue In Reply We thank Gallant et al for their interest in our recent publication regarding the association of body mass index (BMI) with thyroid cancer in children with thyroid nodules. We agree that differences in design may account for some discrepancies between our study and theirs. Different methods of calculating BMI z-scores might play a role, although our selection of the Centers for Disease Control and Prevention nomograms reflects their wide use in clinical practice. Similarly, our use of nodule diameter rather than nodule volume reflects current recommendations for thyroid nodule evaluation, and is unlikely to be relevant given the excellent correlation of these measures in our cohort (r = 0.97; 95% CI, 0.96-0.97). View on Web

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Sodium‐glucose cotransporter‐2 inhibitor‐induced euglycemic diabetic ketoacidosis: A case report

alexandrossfakianakis shared this article with you from Inoreader Sodium‐glucose cotransporter‐2 inhibitor‐induced euglycemic diabetic ketoacidosis: A case report via Journal of Clinical Pharmacy and Therapeutics SGLT-2i-induced euDKA. View on Web

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The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus

alexandrossfakianakis shared this article with you from Inoreader The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus via Journal of Medical Virology ABSTRACT Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,00 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long non-coding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes (PHHs), with subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases. This article is protected by copyright. All rights reserved. View on Web

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A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics

alexandrossfakianakis shared this article with you from Inoreader A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics via Neuro-Oncology Advance Access Abstract Background Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD. Methods This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the Phase I; the Phase II was limited to HER2-positive breast cancer. Results Intrathecal trastuzumab was well tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended Phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80mg w ere included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for Phase 2 dose treated patients was 8.3 months (95% CI 5.2 to 19.6). The Phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2 to 20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable CSF concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. Conclusion This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients. View on Web

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Could red cell distribution width be used for predicting cardiac injury in neonates with COVID‐19?

alexandrossfakianakis shared this article with you from Inoreader Could red cell distribution width be used for predicting cardiac injury in neonates with COVID‐19? via Journal of Medical Virology ABSTRACT Background Coronavirus disease 2019 (COVID-19) can affect people of all age groups and it can occasionally cause life-threatening clinical illness in immunologically immature population, especially in newborns. High red cell distribution width (RDW) values were used as early prognostic biomarker of some neonatal diseases. We aimed to determine the prognostic value of red cell distribution width in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infected neonates. Methods Newborns with positive SARS-CoV-2 polymerase chain reaction (PCR) test from a nasopharyngeal swab sample, who had refractory fever (>38°C and lasting more than 24 hours during hospitalization) screened for multisystem inflammatory syndrome in newborns (MIS-N), systemic inflammatory indexes calculated and cardiologic evaluation performed to these patients. Due to troponin levels (high: >45 ng/L and low: ≤45 ng/L) patients were grouped. Results Of the 68 SARS-CoV-2 PCR-positive newborns, 26 patients had refractory fever. Comparison of laboratory findings between the high and low troponin groups showed that RDW and neutrophil/lymphocyte ratio values were significantly higher in patients with high troponin levels (p = 0.022 and p = 0.030, respectively). The cut-off values with optimal sensitivity and specificity were determined as 1.00 for neutrophil/lymphocyte ratio (p = 0.205) and 16.6 for red cell distribution width (p = 0.014). None of the patients died. Conclusions Neonatal coronavirus disease 2019 generally has a benign prognosis, but can progress to severe disease and cases of MIS-N are rare. RDW could be prognostic in diagnosis and management of neonates with SARS-CoV-2 infection with high troponin levels. This article is protected by copyright. All rights reserved. View on Web

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Rapid quantitative monitoring of SARS‐CoV‐2 spike protein mediated syncytia formation using split NanoLuc

alexandrossfakianakis shared this article with you from Inoreader Rapid quantitative monitoring of SARS‐CoV‐2 spike protein mediated syncytia formation using split NanoLuc via Journal of Medical Virology Abstract SARS-CoV-2 infection causes syncytial pneumocyte in patients and this has been considered as a defining feature of severe COVID-19 cases. Traditional methods of syncytia quantification require the morphology characterization of fused cells either with light microscope or fluorescent microscope, which is time-consuming and not accurate. Here we developed a rapid and sensitive coculture system measuring spike-induced syncytia by using NanoLuc complementation system. We found the formation of syncytia occurred rapidly after ACE2-expressing cells exposure to spike protein. In addition, we found furin cleavage as well as the cell surface protease TMPRSS2 enhanced syncytia formation. Finally, we showed that this coculture system can be used to test the ability of different compound to inhibit syncytia formation, thus providing a useful tool to screen anti-syncytial drugs. This article is protected by copyright. All rights reserved. View on Web

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