Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single‐institution retrospective study

alexandrossfakianakis shared this article with you from Inoreader Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single‐institution retrospective study via Head & Neck Abstract Background Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC. Methods Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included. Survival was estimated using the Kaplan–Meier method, and Cox regression was used for multivariate logistic regression. Results Two-year overall survival after salvage surgery was 68.6% and after immunotherapy patients was 24.6%. Multivariate logistic regression showed that salvage surgery was associated with improved survival without statistical significance (hazard ratio [HR] 0.12, p = 0.25). Subgroup analysis of patients with oral cavity/oropharyngeal cancer noted improved survival with salvage surgery over immunotherapy (HR 0.006, p = 0.01) and decreased survival with neutrophil-to-lymphocyte ratio (NLR) > 5 (HR 6.4, p = 0.02). Conclusion Our retrospective single-institutional data suggest that resectable advanced stage recurrent HNSCC may have improved survival with salvage surgery in appropriately selected patients, but larger prospective studies are required. 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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COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study)

alexandrossfakianakis shared this article with you from Inoreader COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study) via Clinical Infectious Diseases Advance Access Abstract Background Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. Methods A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. Results The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months a fter dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. Conclusions In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level. View on Web

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Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences

alexandrossfakianakis shared this article with you from Inoreader Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: Review of the rationale and current clinical experiences via Journal of Clinical Pharmacy and Therapeutics Extracorporeal hemoadsorption with the CytoSorb device as a potential therapeutic option in severe intoxications: review of the rationale and current clinical experiences. Abstract What is known and objective Many severe intoxications occur with substances with no specific antidote, which is why methods of extracorporeal elimination represent a particularly useful and even critical component in their management. The purpose of this review is to summarize the accumulating evidence and clinical results from the application of CytoSorb hemoadsorption therapy in patients with severe intoxications. Comment The technology represents a promising technique with an increasing number of publications in a variety of severe intoxication scenarios suggesting that early intervention might provide rapid substance removal with subsequent overall clinical improvement. What is new and conclusion Given the tremendous challenges in performing prospective, randomized trials in this field, the strong safety profile of the device and the high acuity of these life-threatening situations, CytoSorb should be considered as a therapeutic option in severe intoxications, particularly when direct antidotes are not available. However, further clinical data are desirable to provide precise recommendations. View on Web

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Downregulation of miRNA‐26 in Chronic Periodontitis Interferes with Innate Immune Responses and Cell Migration by Targeting Phospholipase C Beta 1 (PLCB1)

alexandrossfakianakis shared this article with you from Inoreader Downregulation of miRNA‐26 in Chronic Periodontitis Interferes with Innate Immune Responses and Cell Migration by Targeting Phospholipase C Beta 1 (PLCB1) via Journal of Clinical Periodontology Abstract Aim To evaluate the potential role of miR-26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization. Methods Expression of miR-26a-5p and miR-26b-5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non-surgical (scaling and root planing) therapy by RT-qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR-26a-5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetocomitans (Aa) or Pg LPS. Wound closure assays were performed in cells transfected with miR-26a-5p, while the impact on cytoskeletal organization was assessed by F-actin staining. Results miR-26a-5p and miR-26b-5p are downregulated in diseased gingiva and restored 4-6 weeks post-therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase c beta 1 (PLCB1) as a bona-fide novel target exhibiting antagonistic expression pattern in disease and post-therapy cohorts. miR-26a-5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement. Conclusion Downregulated miR-26a-5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defense and wound healing. View on Web

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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis via The Laryngoscope The aim of this systematic review and meta-analysis was to determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. We demonstrated that TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. Objective To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. Methods PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. Results Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7–88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7–89.4), 53.9% (38.5–75.3), and 39.1% (25.2–60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0–95.3), 67.8% (50.9–90.3), and 58.9% (42.7–81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9–104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7–80.6), 53.2% (42.2–66.9), and 40.4% (29.6–55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5–99.1), 77.0% (64.4–92.0), and 67.1% (51.6–87.3). Conclusions TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. Level of Evidence NA Laryngoscope, 2022 View on Web

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Survival and complications of implant‐supported cantilever fixed dental prostheses with zirconia and metal frameworks: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Survival and complications of implant‐supported cantilever fixed dental prostheses with zirconia and metal frameworks: A retrospective cohort study via Clinical Implant Dentistry and Related Research Abstract Background Current evidence about long-term survival of all-ceramic implant-supported cantilever fixed dental prostheses (cFDP) is limited. Purpose To evaluate the survival and complication rates of all-ceramic and metal–ceramic implant-supported cFDPs located in anterior and posterior sites, under consideration of risk factors. Methods of study The retrospective analysis compared an experimental group (75 implant-supported cFDPs among 48 patients [mean age 60.47 ± 9.25 years; 21 men]; mean observation period 3.56 years) with a control group (300 implant-supported non-cantilever FDPs [ncFDP] among 241 patients [mean age 62.85 ± 10.72 years; 109 men]; mean observation period 7.25 years). Kaplan–Meier estimates were used to describe the long-term survival and success of both groups. Log-rank tests were used for group comparisons. Mixed-effects Cox proportional hazards regression models were used to examine the effects of restoration- and site-specific risk factors. A random intercept was included in the models to take multiple FDPs per patient into account. Results Five-year cumulative survival until loss of restoration was 97.1% (95% confidence interval [CI] 0.93–1.00) for cFDPs and 97.0% (95% CI 0.95–0.99) for ncFDPs. Ten-year survival was 93.7% (95% CI 0.86–1.00) for cFDPs and 92.8% (95% CI 0.87–0.98) for ncFDPs, no difference between the survival curves of these groups was observed. Success differed between cFDPs and ncFDPs (p Log  = 0.002), zirconia and metal frameworks (p Log  < 0.001), and provisional and definitive cements (p Log  = 0.025). The effects of the variables "framework material" and "attachment method" were confirmed in a mixed-effects Cox regression model. Loss of retention was the predominant complication for both cFDPs and ncFDPs and usually affected provisionally cemented FDPs. Conclusions cFDPs do not differ from ncFDPs with regard to long-term failure, whereas additional complications were higher for cFDPs. Fewer complications were observed for zirconia frameworks without occlusal veneers and definitive cemented FDPs. Clinical trial registration: the trial has no registration number because it commenced before January 31, 2017. View on Web

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Susceptibility to mice and potential evolutionary characteristics of porcine deltacoronavirus

alexandrossfakianakis shared this article with you from Inoreader Susceptibility to mice and potential evolutionary characteristics of porcine deltacoronavirus via Journal of Medical Virology ABSTRACT Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes diarrhoea in suckling piglets and has the potential for cross-species transmission, posing a threat to animal and human health. However, the susceptibility profile of different species of mice to PDCoV infection and its evolutionary characteristics are still unclear. In current study, we identified that BALB/c and Kunming mice are susceptible to PDCoV. Our results showed that there were obvious lesions in intestinal and lung tissues from the infected mice. PDCoV RNAs were detected in the lung, kidney and intestinal tissues from the infected mice of both strains, and there existed wider tissue tropism in the PDCoV-infected BALB/c mice. The RNA and protein levels of aminopeptidase N from mice (mAPN) were relatively high in the kidney and intestinal tissues and obviously increased after PDCoV infection. The viral specific IgG and neutralizing antibodies against PDCoV were detected in serum from the infected mice. An interesting finding was that, two key amino acid mutations D138H and Q641K in the S protein were identified from the PDCoV-infected mice. The essential roles of these two mutations for PDCoV-adaptive evolution were confirmed by cryo-EM structure model analysis. The evolutionary characteristics of PDCoV among Deltacoronaviruses (δ-CoVs) were further analyzed. δ-CoVs from multiple mammals are closely related based on the phylogenetic analysis. The codon usage analysis demonstrated similar codon usage patterns were used by most of the mammalian δ-CoVs at the global codon usage, synonymous codon usage and amino acid usage levels. These results may provide more insights into the evolution, host ranges and the cross species potential of PDCoV. This article is protected by copyright. All rights reserved. View on Web

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BK polyomavirus in Iranian Patients with Papillary Thyroid Cancer: Is It a Major Future Challenge?

alexandrossfakianakis shared this article with you from Inoreader BK polyomavirus in Iranian Patients with Papillary Thyroid Cancer: Is It a Major Future Challenge? via Journal of Medical Virology Abstract BK polyomavirus (BKPyV) is a well-known cause of nephropathy in renal transplant recipients. It has recently received much attention from researchers as a major predisposing factor for various cancers. This study aimed to investigate how BKPyV affected the advancement of papillary thyroid carcinoma (PTC). A total of 1057 samples were tested for BKPyV DNA and RNA, comprising 645 paraffin-embedded PTC biopsy samples (PEBS), 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples. The BKPyV DNA was found in 511 (48.3%) of the specimens, including 347 (84.2%) FBS and 164 (25.4%) PEBS. The mean BKPyV copy number was significantly lower in patients with PEBS (0.5 × 10-4 ± 0.1 × 10-4 copies/cell) than in FBS (1.3 × 10-1 ± 0.2 × 10-1 copies/cell) and non-PTC normal samples (0.3 × 10-5 ± 0.04 × 10-5 copies/cell). The PEBS had lower LT-Ag RNA expression than FBS, and no V P1 gene transcript expression was detected. In conclusion, although our findings indicated the presence of BKPyV in some Iranian PTC patients, more research is needed to corroborate these findings. This article is protected by copyright. All rights reserved. View on Web

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