Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019

AlexandrosSfakianakis shared this article with you from Inoreader Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019 via Cancer Medicine The curative approach for gallbladder cancer (GBC) is radical cholecystectomy with adjuvant chemotherapy. GBC has non-specific symptoms, so screening/early detection is not possible. We report that 90% of GBC patients presented with late-stage inoperable disease. Patients with late-stage disease who received chemotherapy had significantly better survival over those who did not (p < 0.0001). Our real-world data suggests that GBC is a chemosensitive disease. Clinical trials in low-middle income countries to reposition available therapies are urgently required. Abstract Background The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. Methods Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. Results There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50–65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100–100); 61% (95% CI: 45–83); 30% (95% CI: 21–43); and 9% (95% CI: 6–13) for stages I–IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39–64), compared to 29% (95% CI: 22–38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6–14) in patients who were palliated (N = 107) (p = <0.0001). Conclusion The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III–IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required. View on Web

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An fNIRS-Based Dynamic Functional Connectivity Analysis Method to Signify Functional Neurodegeneration of Parkinson’s Disease

AlexandrosSfakianakis shared this article with you from Inoreader An fNIRS-Based Dynamic Functional Connectivity Analysis Method to Signify Functional Neurodegeneration of Parkinson’s Disease via Neural Systems and Rehabilitation Engineering, IEEE Transactions on - new TOC Parkinson's disease (PD) is a prevalent brain disorder, and PD diagnosis is crucial for treatment. Existing methods for PD diagnosis are mainly focused on behavior analysis, while the functional neurodegeneration of PD has not been well investigated. This paper proposes a method to signify functional neurodegeneration of PD with dynam ic functional connectivity analysis. A functional near-infrared spectroscopy (fNIRS)-based experimental paradigm was designed to capture brain activation from 50 PD patients and 41 age-matched healthy controls in clinical walking tests. Dynamic functional connectivity was constructed with sliding-window correlation analysis, and k-means clustering was applied to generate the key brain connectivity states. Dynamic state features including state occurrence probability, state transition percentage and state statistical features were extracted to quantify the variations of brain functional networks. A support vector machine was trained to classify PD patients and healthy controls. Statistical analysis was conducted to investigate the difference between PD patients and healthy controls as well as the relationship between dynamic state features and the MDS-UPDRS sub-score of gait. The results showed that PD patients had a higher probability of transiting to brain connectivity states with high levels of information transmission compared with healthy controls. The MDS-UPDRS sub-score of gait and the dynamics state features showed a significant correlation. Moreover, the proposed method had better classification performances than the available fNIRS-based methods in terms of accuracy and F1 score. Thus, the proposed method well signified functional neurodegeneration of PD, and the dynamic state features may serve as promising functional biomarkers for PD diagnosis. View on Web

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Intelligent Headband System for Evaluating Rehabilitation Effectiveness

AlexandrosSfakianakis shared this article with you from Inoreader Intelligent Headband System for Evaluating Rehabilitation Effectiveness via Neural Systems and Rehabilitation Engineering, IEEE Transactions on - new TOC Stroke is an acute cerebrovascular condition causing damage to cranial nerves and requires subsequent rehabilitation treatment. In clinical practice, the effectiveness of rehabilitation is usually subjectively assessed by experienced physicians or using global prognostic scales. Several brain imaging techniques, such as positron emissio n tomography, functional magnetic resonance imaging, and computed tomography angiography, can be applied in rehabilitation effectiveness evaluation, but their complexity and long measurement times limit the activity of patients during measurement. This paper proposes an intelligent headband system based on near-infrared spectroscopy. An optical headband continuously and noninvasively monitors changes in hemoglobin parameters in the brain. The system's wearable headband and wireless transmission provide convenience of use. According to the change of hemoglobin parameters during rehabilitation exercise, several indexes were also defined to evaluate the state of cardiopulmonary function and further build the neural network model of the cardiopulmonary function evaluation. Finally, the relationship between the defined indexes and the cardiopulmonary function state were investigated and the neural network model for the cardiopulmonary function evaluation was also applied in the rehabil itation effect evaluation. The experimental results show the cardiopulmonary function state could reflect on most of the defined indexes and the output of neural network model, and the rehabilitation therapy could also improve the cardiopulmonary function. View on Web

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Current Management of Generalized Pustular Psoriasis

AlexandrosSfakianakis shared this article with you from Inoreader Current Management of Generalized Pustular Psoriasis via Wiley: Experimental Dermatology: Table of Contents Abstract Generalized pustular psoriasis (GPP) is a rare subset of psoriasis involving episodes of sterile pustules accompanied by inflammation and, often, systemic involvement. The inflammatory nature of GPP has potential for severe multisystem complications including high-output cardiac failure, infections, digestive system issues, and disfiguring or lethal acute flare episodes. The disease tends to have higher prevalence in females and Asians. The IL-1/IL-36 inflammatory pathway is a critical facet of GPP's pathology. Genetic mutations that are associated with GPP include modifications of Interleukin 36 Receptor Antagonist (IL36RN), Caspase Recruitment Domain Family Member 14 (CARD14), Adaptor Related Protein Complex 1 Subunit Sigma 3 (AP1S3), Myeloperoxidase (MPO), and Serpin Peptidase Inhibitor Clade A Member 3 (SERPINA3) genes. Treatment guidelines for GPP are not well-entrenched. Currently, only one GPP-specific treatment, the interleukin-36 recepto r antagonist (IL-36Ra) spesolimab, has been approved for use in the United States. Additional anti-IL-36 pathway therapies are currently being developed. Other treatment options include other biologic therapies such as IL-17 inhibitors, IL-23 inhibitors, and TNFα inhibitors. Non-biologic therapeutic options include retinoids, cyclosporine, and methotrexate. Treatment options differ throughout the world; most countries utilize retinoids, cyclosporine, and methotrexate as first-line non-biologic options. China and United Kingdom have no GPP-specific biologic therapies approved for use, while several biologic therapies are approved for use in Japan. This review aims to serve as an update on the current global management of GPP while also including relevant aspects of disease pathogenesis, diagnosis, clinical presentation, histopathology, etiology, and epidemiology. View on Web

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A systematic comparison of pan‐Trk immunohistochemistry assays across multiple cancer types

AlexandrosSfakianakis shared this article with you from Inoreader A systematic comparison of pan‐Trk immunohistochemistry assays across multiple cancer types via Histopathology Aims NTRK-rearranged tumours are rare but can be successfully treated using anti-TRK–targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-Trk immunohistochemistry (IHC) has become a valuable and affordable screening tool in many laboratories. Unfortunately, the choice of antibodies and IHC protocols to investigate biomarkers is not standardized. In this study, we compared the performance of four pan-Trk IHC methods, using three different clones, primarily in NTRK- fusion positive tumours. Method We studied the performance of four pan-Trk IHC methods, using three different clones: EPR17341 (Abcam and Ventana), EP1058Y (Abcam), A7H6R (Cell Signaling) in 22 molecularly confirmed NTRK-rearranged tumours. Additionally, selected NTRK-fusion negative tumours were further included: NTRK mutated (n=8) and amplified (N=15) tumours as well as NTRK-fusion negative tumours driven by other gene fusions such as ALK, ROS1 and BCOR (n=20) as well as salivary gland tumours (n=16). Interrater agreement of three pathologist was additionally calculated, including H-score. Result With clone EPR17341 (Abcam in house and ready to use Ventana protocol) all molecularly confirmed NTRK 1-3 rearranged tumours were positively detected by immunohistochemistry, while the other clones missed NTRK2-3-rearranged tumours. For the fusion negative cohort we found the best performance (least false positive cases) using the clone A7H6R (Cell Signalling). Conclusion Given the therapeutic importance, testing for NTRK rearrangements in daily practice has become necessary and despite IHC being a fast and affordable tool, using it in routine diagnostics is complicated and requires a high level of expertise. View on Web

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Combined proliferation and apoptosis index provides better risk stratification in breast cancer

AlexandrosSfakianakis shared this article with you from Inoreader Combined proliferation and apoptosis index provides better risk stratification in breast cancer via Histopathology Introduction Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in vivo growth rate measure and a precise prognostic predictor. Methods and Results Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour including high grade, high pleomorphism score, and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BC patients with a high combined AI and MI had the shortest survival. Replacing the mitosis score with the mitosis-apoptosis index, in the Nottingham grading system, revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio. Conclusion Apoptotic figures count provides additional prognostic value in BC when combined with MI, such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC. View on Web

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Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon [Report]

AlexandrosSfakianakis shared this article with you from Inoreader Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon [Report] via RNA In Advance Transfer RNA fragments are proposed to regulate numerous processes in eukaryotes, including translation inhibition, epigenetic inheritance and cancer. In the bacterium Salmonella enterica serovar Typhimurium, 5' tRNA halves ending in 2', 3' cyclic phosphate are proposed to bind the RtcR transcriptional activator, resulting in transcription of an RNA repair operon. However, since 5' and 3' tRNA halves can remain base paired after cleavage, the 5' tRNA halves could potentially bind RtcR as nicked tRNAs. Here we report that nicked tRNAs are ligands for RtcR. By isolating RNA from bacteria under conditions that preserve base pairing, we show that many tRNA halves are in the form of nicked tRNAs. Using a circularly permuted tRNA that mimics a nicked tRNA, we show that nicked tRNA ending in 2', 3' cyclic phosphate is a better ligand for RtcR than the corresponding 5' tRNA half. In human cells, we show that some tRNA halves similarly remain base paired as nicked tR NAs following cleavage by anticodon nucleases. Our work supports a role for the RNA repair operon in repairing nicked tRNAs and has implications for the functions proposed for tRNA fragments in eukaryotes. View on Web

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