Challenges in the interpretation of a germline TERT variant in a patient with juvenile myelomonocytic leukemia

alexandrossfakianakis shared this article with you from Inoreader Challenges in the interpretation of a germline TERT variant in a patient with juvenile myelomonocytic leukemia via Pediatric Blood & Cancer Abstract Dyskeratosis congenita (DC) is a bone marrow failure syndrome with extrahematopoietic abnormalities. DC is a paradigmatic telomere biology disorder (TBD) caused by germline mutations in genes responsible for telomere maintenance including TERT. Cryptic TBD is a bone marrow failure syndrome due to premature telomere shortening but without additional symptoms, frequently clinically indistinguishable from severe aplastic anemia (SAA) or hypoplastic myelodysplastic syndrome. We present the complex diagnostic pathway in a boy with a rare germline p.Thr726Met TERT variant with previous reports of SAA association and compromised enzymatic function who presented with juvenile myelomonocytic leukemia, which is a rare myelodysplastic/myeloproliferative neoplasm of childhood. View on Web

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Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth

alexandrossfakianakis shared this article with you from Inoreader Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth via International Endodontic Journal Abstract This review guidance is a work in progress because the limitations of regenerative endodontics are still being discovered. The endodontic treatments for immature permanent teeth with a necrotic pulp can vary considerably among endodontic practitioners. Whereas, Regenerative endodontic treatments are growing in popularity and are creating ever more complex treatment protocols, involving revascularization and/or autologous platelet-rich plasma and scaffolds to elicit host stem cell de novo tissue formation to res-establish the vitality of immature teeth for the purpose of continuing root maturation. Despite much evolving controversy about their potential benefits, risks, prognosis, and contraindications. This review is aimed to discuss how to ensure that regenerative endodontic treatments are successful, by strictly adhering to case selection criteria, and following precise steps to accomplish and monitor the success of the treatment. A review of the endodontic literature was performed, together with practical observations of the problems and outcomes of performing regenerative endodontic treatments. Traditionally, apexification has long been the treatment of choice provided to immature teeth with a necrotic pulp. Regenerative endodontics may be provided as an alternative to apexification, if the tooth and patient meets all the case selection criteria, and if there are no contraindications. Regenerative endodontics has the unique potential advantage of being able to continue the root development in immature permanent teeth, thereby potentially saving the teeth for the lifetime of the patient. Whereas, conventional endodontic root canal treatment, Cvek partial pulpotomy, apexogenesis, and apexification, should always be provided when these treatments are more likely to benefit the patient because they can be more successful than regenerative endodontics. View on Web

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Clinical and Molecular Analysis of Recurrent Gram-Negative Bloodstream Infections

alexandrossfakianakis shared this article with you from Inoreader Clinical and Molecular Analysis of Recurrent Gram-Negative Bloodstream Infections via Clinical Infectious Diseases Advance Access Abstract Background The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. Methods We used a prospectively ascertained cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (both pulsed field gel electrophoresis [PFGE] and whole genome sequencing [WGS]) was used to define whether these episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors associated with recurrence. Results Of the 1423 patients with GNB-BSI that met criteria for inclusion in this study, 60 (4%) had recurrent GNB-BSI. Non-white race (OR: 2.35; CI95% 1.38-4.01; p = 0.002), admission to a surgical service (OR: 2.18; CI95% 1.26-3.75; p = 0.005) and presence of an indwelling cardiac device (OR: 2.73; CI95% 1.21-5.58, p =  0.009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30/48) and 38% were due to reinfection (18/48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47/48) of cases. Median time to relapse and reinfection was similar (113 days [IQR: 35-222 days] vs. 174 days [IQR: 69-599 days], p = 0.13). Presence of a cardiac device was associated with relapse (Relapse: 7/27 [26%]; Non-relapse: 65/988 [7%]; p = 0.002). Conclusions In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Presence of a cardiac device was a risk factor for relapse. View on Web

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SARS-CoV-2 hyperimmune intravenous human immunoglobulins neutralizes Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5 for treatment of COVID-19

alexandrossfakianakis shared this article with you from Inoreader SARS-CoV-2 hyperimmune intravenous human immunoglobulins neutralizes Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5 for treatment of COVID-19 via Clinical Infectious Diseases Advance Access ABSTRACT Our study demonstrates that neither 2020-convalescent plasma (CP) nor 2019/2020-immunoglobulin (IVIG) neutralize Omicron subvariants BA.1 to BA.5. In contrast, hyperimmune 2020-hCoV-2IG lots neutralized Omicron VOCs, similar to 2022-CP from BA.1 breakthrough infections. Therefore, high-titer hCoV-2IG and CP could be evaluated for treatment of high-risk individuals infected with circulating Omicron subvariants. View on Web

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Two cases of oral steroid and local tacrolimus combination therapy for oral lichen planus ineffective with local steroid therapy

alexandrossfakianakis shared this article with you from Inoreader Two cases of oral steroid and local tacrolimus combination therapy for oral lichen planus ineffective with local steroid therapy via ScienceDirect Publication: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Publication date: Available online 5 August 2022 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Yusuke Aoki, Masaki Minabe, Junichiro Inada, Yurie Akiyama, Kazuhiko Hashimoto, Michiyoshi Kouno, Shinichi Takahashi, Takeshi Nomura View on Web

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International variations in hepatic tumours incidence in children and adolescents

alexandrossfakianakis shared this article with you from Inoreader International variations in hepatic tumours incidence in children and adolescents via Japanese Journal of Clinical Oncology - current issue In order to compare the subtype distribution of hepatic tumours in children and adolescents between Japan and other countries, we extracted information on cancer incidence in children and adolescents from the third volume of the International Incidence of Childhood Cancer series (IICC-3) (1). The IICC-3 reports the number or incidence rates of cancers diagnosed in childhood and adolescence from cancer registries (regional or national) worldwide. We analyzed hepatic tumour incidence in four countries in Asia (Japan, China, the Republic of Korea and Thailand), two countries in Africa (Egypt and Uganda), four countries in the Americas (North: The USA and Canada, Latin and Caribbean: Brazil and Colombia), three countries in Europe (the UK, France and Germany) and two countries in Oceania (Australia and New Zealand). Information from the Republic of Korea, USA, UK, Australia and New Zealand were obtained at the national level and those from the other countries were extracted from one or multiple regional cancer registries. The years of incidence included in the analyses varied from country to country, ranging from 1990 to 2014, with the shortest being 12 years (Egypt: 1999–2010, UK: 2000–11) and the longest being 24 years (Japan and China, both: 1990–2013). In this study, we compared the incidence and proportional distribution of hepatic tumour subtype in children (0–14 years old) and adolescents (15–19 years old) between these countries. View on Web

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Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration

alexandrossfakianakis shared this article with you from Inoreader Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 5 August 2022 Source: Experimental Cell Research Author(s): Bing Zhou, Nan Wu, Yuan Yan, Lu-Lu Wu, Guo-Qing Zhu, Xiao-Qing Xiong View on Web

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Characterizing the epithelial–mesenchymal transition status of circulating tumor cells in head and neck squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader Characterizing the epithelial–mesenchymal transition status of circulating tumor cells in head and neck squamous cell carcinoma via Head & Neck Abstract Background Circulating tumor cells (CTCs), in particular those undergoing an epithelial–mesenchymal transition (EMT), are a promising source of biomarkers in head and neck squamous cell carcinoma (HNSCC). Our aim was to validate a protocol using microfluidic enrichment (Parsortix platform) with flow-cytometry CTC characterization. Method Blood samples from 20 treatment naïve HNSCC patients underwent Parsortix enrichment and flow cytometry analysis to quantify CTCs and identify epithelial or EMT subgroups—correlated to clinical outcomes and EMT gene-expression in tumor tissue. Results CTCs were detected in 65% of patients (mean count 4 CTCs/ml). CTCs correlated with advanced disease (p = 0.0121), but not T or N classification. Epithelial or EMT CTCs did not correlate with progression-free or overall survival. Tumor mesenchymal gene-expression did not correlate with CTC EMT expression (p = 0.347). Discussion Microfluidic enrichment and flow cytometry successfully characterizes EMT CTCs in HNSCC. The lack of association between tumor and CTC EMT profile suggests CTCs may undergo an adaptive EMT in response to stimuli within the circulation. View on Web

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Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts‐mediated osteogenic differentiation of BMSCs

alexandrossfakianakis shared this article with you from Inoreader Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts‐mediated osteogenic differentiation of BMSCs via Journal of Oral Rehabilitation Abstract Background Bone homeostasis is a dynamic process maintained by osteoblasts and osteoclasts, which may be regulated by excessive mechanical stress (EMS). Objectives Our study aims to explore the relationship between osteogenic differentiation of BMSCs and EMS-activated osteoclast differentiation of RAW 264.7 cells in order to optimize orthodontic treatment. Methods We established the model of EMS in vivo and in vitro. In vivo, HE, Safranin-O staining, micro-CT, and immunofluorescence double-labeling were utilized to assess the changes in condylar, the distributions of osteoblasts, osteoclasts and MAPKs. In vitro, the effects of EMS-activated osteoclast differentiation exerting on osteogenic differentiation of BMSCs were observed by Western Blot, qRT-PCR and Alizarin Red staining. Furthermore, the role of MAPKs in this progress was explored by using inhibitors of MAPKs and co-culture supernatants. Results In vivo, EMS led to the degradation of condylar cartilage and destruction of subchondral bone, diagnosed as temporomandibular joint osteoarthritis (TMJ OA). Osteoclasts and osteoblasts were both enriched in subchondral bone, but osteoclast predominated. The expressions of p-JNK, p-ERK1/2, and p-p38 were all activated in vitro and in vivo, which were localized mainly in the Trap+ area in subchondral bone. Interestingly, only the inactivation of p-ERK1/2 in osteoclasts significantly inhibited the osteogenic differentiation of BMSCs in vitro. This revealed that p-ERK1/2 played a key role in the osteoclasts-induced osteogenic differentiation of BMSCs. Conclusion Our results proved that EMS led to TMJ OA, in which up-regulated p-ERK1/2 in osteoclasts was mechanosensitive and facilitated the osteogenic differentiation of BMSCs. View on Web

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