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BACKGROUND: In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. MATERIALS AND METHODS: A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. RESULTS: A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. DISCUSSION: This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to explore the value of patient self-report assessment in heart transplant candidacy evaluation, utilizing the Millon Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to important pretransplant patient characteristics and posttransplant measures of health behavior, medical morbidity, and mortality.Method: Ninety heart patients with end-stage cardiac disease completed the MBHI during pretransplant candidacy evaluations, and also were interviewed concerning their coping effectiveness, support resources, and compliance history. Postransplant follow-up of 61 living and 29 deceased patients included measures of survival time, postsurgical medical care, rejection and infection episodes, and nurse ratings of medication compliance and problematic interpersonal health behaviors.Results: The MBHI coping scales were found to significantly discriminate good and poor pretransplant compliance, and interview judgments of good and poor coping and support resources, with modest accuracy. The MBHI also was superior to these interview judgments in predicting posttransplant survival time and medical care used. Certain scales were also positively associated with physical parameters of pretransplant and posttransplant status.Conclusions: Patient self-report with the MBHI can contribute to identification of patients at risk for a problematic outcome with transplant, by providing information pertinent to clinical decision making and outcome management analysis with this special population of cardiac patients. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumor (GIST), now the most common mesenchymal tumor of the gastrointestinal tract (GIT), has been frequently studied, especially with regard to its successful targeted therapy using imatinib mesylate. Aim: Our aim was to describe the clinicopathological features of a large number of cases from a tertiary care hospital in India and report on the follow-up after treatment of some of the cases, comparing them with series described in the west. Design: This is a retrospective study of cases encountered over a 7-year period (1999-2005). Results: Ninety-two cases of GIST were studied, which made up the largest group (52.8%) of mesenchymal tumors of the GIT, with smooth muscle tumors comprising 38.1%, the next large group. GISTs were almost equally prevalent in the stomach and the small intestine, unlike in most studies where stomach is the most common site. GIST may be considered as a cause of bleeding when upper and lower GI endoscopy is normal. Ninety-five percent of the GISTs were positive for CD117 (KIT), as is known. A majority of them (70.4%) were of the high-risk malignant category, unlike most studies where high-risk tumors make up 30-45%. Histologically, the majority had a pure spindle cell morphology and skenoid fibers were rare. Follow-up of 11 cases, the majority with high-risk tumor, treated with adjuvant imatinib for 6 months after surgical resection showed stable disease for periods from 2 to 5 years. However, 11 cases treated with imatinib for longer than 6 months had a poorer outcome due to recurrent, metastatic, or inoperable disease. Conclusion: In our study of a large number of GISTs, which were equally prevalent in the stomach and small intestine, the majority were of the high-risk malignant category and of pure spindle cell morphology. Limited numbers had follow-up after imatinib therapy, which showed in one group treated for 6 months, after resection of high-risk GIST, stable disease for periods ranging from 2 to 5 years. Molecular studies and larger numbers are required for meaningful conclusions to be drawn.

Oral lesions of tuberculosis though uncommon, are seen in both the primary and secondary stages of the disease. In secondary tuberculosis, the oral manifestations may be accompanied by lesions in the lungs, lymph nodes, or in any other part of the body and can be detected by a systemic examination. Primary oral tuberculosis may present as a diagnostic challenge for the clinician. Here we report two patients with primary tuberculosis in the oral cavity who presented to the dental department, were diagnosed and referred for medical management.

Artificial intelligence (AI) is rapidly being introduced into the clinical workflow of many specialties. Despite the need to train physicians who understand the utility and implications of AI and mitigate a growing skills gap, no established consensus exists on how to best introduce AI concepts to medical students during preclinical training. This study examined the effectiveness of a pilot Digital Health Scholars (DHS) non-credit enrichment elective that paralleled the Dartmouth Geisel School of Medicine's first-year preclinical curriculum with a focus on introducing AI algorithms and their applications in the concurrently occurring systems-blocks. From September 2022 to March 2023, ten self-selected first-year students enrolled in the elective curriculum run in parallel with four existing curricular blocks (Immunology, Hematology, Cardiology, and Pulmonology). Each DHS block consisted of a journal club, a live-coding demonstration, and an integration session led by a researcher in that field. Students' confidence in explaining the content objectives (high-level knowledge, implications, and limitations of AI) was measured before and after each block and compared using Mann-Whitney U tests. Students reported significant increases in confidence in describing the content objectives after all four blocks (Immunology: U  = 4.5, p  = 0.030; Hematology: U  = 1.0, p  = 0.009; Cardiology: U  = 4.0, p  = 0.019; Pulmonology: U  = 4.0, p  = 0.030) as well as an average overall satisfaction level of 4.29/5 in rating the curriculum content. Our study demonstrates that a digital health enrichment elective that runs in parallel to an institution's preclinical curriculum and embeds AI concepts into relevant clinical topics can enhance students' confidence in describing the content objectives that pertain to high-level algorithmic understanding, implications, and limitations of the studied models. Building on this elective curricular design, further studies with a larger enrollment can help determine the most effective approach in preparing future physicians for the AI-enhanced clinical workflow.

Objective: This study aims to evaluate the application and effectiveness of fractal analysis (FA) in assessing temporomandibular joint disorders (TMDs) with dental imaging., Methods: This systematic review, conducted in adherence to PRISMA-P and Cochrane Handbook guidelines, involved a comprehensive search of five electronic indexed databases up to September 15, 2024. The thorough search aimed to ensure the inclusion of all relevant studies on dental imaging with fractal dimension (FD) analysis for TMDs. The risk of bias was performed using the revised QUADAS 2 tool., Results: Out of 342 studies retrieved, 15 met the inclusion criteria and were included in the systematic review. These studies comprised 7 retrospective and 8 prospective nonrandomized clinical studies. Various imaging modalities were used including panoramic, CT, CBCT, and MRI. Most studies reported significantly lower FD values in TMD patients than in controls suggesting FD analysis' potential for detecting early TMJ degenerative changes. However, a few studies did not find significant differences or lacked control groups, highlighting the variability in findings across the research. The overall risk of bias was high regarding the applicability of all included studies., Conclusion: The fractal dimension (FD) analysis of dental images shows potential as a valuable tool for detecting early degenerative changes in temporomandibular disorders (TMDs). It could enhance diagnostic efficiency by providing additional insights from routine radiographs. However, the variability in findings and methodologies underscores the need for further research to validate and standardize these techniques., Competing Interests: Declarations. Conflict of interest: The authors declare that there is no conflict of interest. Ethics approval: No ethical approval is required. The study was registered in PROSPERO. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Background: Artificial intelligence (AI) enabled tools have been proposed as 1 solution to improve health care delivery. However, research on downstream effects of AI integration into the clinical workflow is lacking., Objective: We aim to analyze how integration of an automated basal cell carcinoma detection and tumor mapping algorithm in a Mohs micrographic surgery unit impacts the work efficiency of clinical and laboratory staff., Methods: Slide, staff, and histotechnician waiting times were analyzed over a 20-day period in a Mohs micrographic surgery unit. A simulated AI workflow was created and the time differences between the real and simulated workflows were compared., Results: Simulated nonautonomous algorithm integration led to savings of 35.6% of slide waiting time, 18.4% of staff waiting time, and 18.6% of histotechnician waiting time per day. Algorithm integration on days with increased reconstruction complexity resulted in the greatest time savings., Limitations: One Mohs micrographic surgery unit was analyzed and simulated AI integration was performed retrospectively., Conclusions: AI integration results in reduced staff waiting times, enabling increased productivity and a streamlined clinical workflow. Schedules containing surgical cases with either increased repair complexity or numerous tumor removal stages stand to benefit most. However, significant logistical challenges must be addressed before broad adoption into clinical practice is realistic., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

A common application for intraoral scanners is the digitization of the morphology of teeth and palatal rugae. Palatal scans are most commonly required to fabricate complete dentures and immediate transitional dentures and serve as a reference point for assessing orthodontic results. However, they are also frequently included by accident, even though the main purpose of intraoral scanning is to reconstruct dentition using computer-aided manufacturing (CAM). The literature shows that the identification of disaster victims has frequently involved palatal rugae impressions. As the skull provides sound insulation, the rugae are resistant to heat, chemicals, and stress. Antemortem data might be difficult to find during a forensic inquiry, particularly in disaster victim identification cases. In contrast with DNA and fingerprints, there is a greater likelihood of having a dental record that contains palatal scans. With specialized software, the scans can be exported as open stereolithography (STL) files. Considering that a full case consumes up to about 100 MB of hard drive space, long-term storage should not be an issue compared to a plaster model. Additionally, dentists widely use online databases to exchange data for smile design, implant registration, and orthodontic purposes. This will produce a digital database that grows quickly and is readily usable for forensic investigations. The uniqueness of forensic features is frequently challenged; however, palatal morphology's unique trait could make it possible as it is characteristic of individuals as well as the most distinguishing factor. This review will highlight how rugae, palatal morphology, mirroring, superimposition, and geometrics can serve in forensic identification.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408)., (© 2024. The Author(s).)

Background: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma., Material and Methods: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively., Results: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34)., Conclusions: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

The formation of large interstellar molecules starting from small reactants constitutes the bottom-up approach in astrochemistry. An experimental setup wherein the ionic reactant is prepared and allowed to react with neutral reactants within a confined interaction space is most desirable for this approach. Here, we present our efforts in constructing a 22-pole radio-frequency ion trap experimental setup that could act as a reaction chamber for the neutral reactant and trapped ions. A compact piezo-based pulsed supersonic expansion discharge source was developed to achieve efficient production of anions, particularly metal-bearing ions. In addition, two other ion sources, namely, the electron impact ion source and the plasma supersonic discharge ion source, were developed to cater to the production of specific ions. The geometry of this experimental setup facilitates photo excitation of trapped ions. The trapping efficiency was studied by trapping SF5+ and SF6- for a few seconds. The control exhibited by various parameters on the efficiency of the trapping is discussed in detail. Potential studies that could be performed with this new experimental setup are also discussed., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p<0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p=0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p<0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p=0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p=0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor ® dataset, n=408)., Competing Interests: Additional Declarations: There is a conflict of interest Dan Zhao is an advisory board member for Affini-T and she has clinical trial contract with CARsgen and Mirati. Disclosures and Competing interests: This data has not been previously presented. COI disclosures pending from authors.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A boy in his middle childhood with severe haemophilia reported with facial swelling following dental treatment for a carious upper primary molar done at a private dental clinic elsewhere. On presentation, he had a large, tense and tender swelling of the left cheek and a haematoma on the buccal mucosa adjacent to the treated tooth. The child was found to have a low haemoglobin level. He was taken for an emergency procedure under general anaesthesia for dental extraction with incision and drainage, and simultaneously underwent packed cells and factor replacement. He recovered in the ward postoperatively with no complications and with a gradual reduction of the swelling. This report highlights the importance of caries prevention in children, especially those with haemophilia. They need to be educated about restricting cariogenic foods in their diet and maintaining good oral hygiene. Management of such patients should be carefully coordinated to minimise undesirable outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC), with the most frequent amplified region being 3q26 to 3q28., Methods: In this analysis, we aim to describe the prognostic relevance of 3q amplification by focusing on a minimal common region (MCR) of amplification constituted of 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas and included 476 in the final analysis., Results: We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease-specific survival (not reported [NR] versus 9.25 y, 95% confidence interval [CI]: 5.24-NR, log-rank p  = 0.011) and a progression-free interval of 8 years (95% CI: 5.1-NR) versus 4.9 years (95% CI: 3.5-NR, log-rank p  = 0.020). Multivariable analysis revealed that MCR amplification was associated with improved disease-specific survival and progression-free interval., Conclusions: Amplification of the 25-gene MCR within 3q was present in 44% of this cohort, consisting mainly of Caucasian patients with early stage LUSC. This analysis strongly indicates the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic and predictive relevance in a racially diverse patient population with advanced LUSC., (© 2023 The Authors.)

Background: Since the World Health Organization declared coronavirus disease (COVID-19) as a pandemic, most countries started treating their patients with various therapies. However, the data regarding their safety and effectiveness is still lacking., Objectives: We aimed to evaluate the adverse drug reactions (ADRs) incidence and their predisposing factors among COVID-19 patients., Methods: A retrospective observational study that was conducted at a tertiary academic hospital from March - June 2020. Patients were included if they were ≥ 18 years old, inpatient, had a reverse transcriptase-polymerase chain reaction (PCR) positive for COVID-19, and were treated with; (lopinavir-ritonavir, hydroxychloroquine, chloroquine, favipiravir, ribavirin, or interferon-ß) either as monotherapy or combination therapy for three days or longer. The data of eligible patients were retrieved from the electronic medical records. A standardized data collection form was designed to collect patient demographics, COVID-19 severity based on the Saudi Ministry of Health management protocols, antiviral therapies, duration of therapy, and length of stay (LOS). The ADRs were identified via conducting a comprehensive review using predefined triggers and were evaluated using Naranjo Score., Results: A total of 155 patients were included of which 123 (79.4%) were males. In our sample, the incidence proportion of ADRs per patient was 72.3%. A total of 287 ADRs were identified most of them were hepatic (n =  101 , 35.2%), gastrointestinal (n =  59 , 20.6%), hematological (n =  47 , 16%), and endocrine (n =  45 , 15%). Hydroxychloroquine was the most common drug associated with ADRs (n =  155 ). The length of stay (10 - 20 days) was the only statistically significant with the ADR incidence (p-value = 0.008; 95 %CI 1.216:3.568)., Conclusions: The ADRs are prevalent among COVID-19 patients, which assure the importance of implementing active hospital-based pharmacovigilance systems., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification. Three sizes were developed from nickel-cobalt-chromium MP35N alloy tubes: Small/23 mm, Medium/26 mm and Large/29 mm. Crimp-diameters of valves with both bioprosthetic (sandwich-crosslinked decellularized pericardium) and polymer leaflets (triblock polyurethane combining siloxane and carbonate segments) match those of modern clinically used BE TAVR. Balloon expansion favors the wing-structures of the stent thereby creating supra-annular anchors whose diameter exceeds the outer diameter at the waist level by a quarter. In the pulse duplicator, polymer and bioprosthetic TAVR showed equivalent fluid dynamics with excellent EOA, pressure gradients and regurgitation volumes. Post-deployment fatigue resistance surpassed ISO requirements. The radial force of the helical deployment balloon at different filling pressures resulted in a fully developed anchorage profile of the valves from two thirds of their maximum deployment diameter onwards. By combining a unique balloon-expandable TAVR system that also caters for non-calcific AR with polymer leaflets, a powerful, potentially disruptive technology for heart valve disease has been incorporated into a TAVR that addresses global needs. While fulfilling key prerequisites for expanding the scope of TAVR to the vast number of patients of low- to middle income countries living with rheumatic heart disease the system may eventually also bring hope to patients of high-income countries presently excluded from TAVR for being too young., Competing Interests: “Strait Access Technologies” (SAT) is a start-up company of the University of Cape Town. HA, DB, JSc, HC, DW, and PZ own shares in SAT. JV, RC, and RS are employed by SAT. KP, BB, and MC are former employees and shareholders of SAT. BJ is a former employee of SAT. CS is employed by Auto Tissue Berlin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Appa, Park, Bezuidenhout, van Breda, de Jongh, de Villiers, Chacko, Scherman, Ofoegbu, Swanevelder, Cousins, Human, Smith, Vogt, Podesser, Schmitz, Conradi, Treede, Schröfel, Fischlein, Grabenwöger, Luo, Coombes, Matskeplishvili, Williams and Zilla.)

Background: Response to neoadjuvant chemotherapy is associated with improved outcomes for patients with triple negative breast cancer (TNBC). Patients with residual disease are at increased risk of relapse and death from breast cancer. In this retrospective study, we aimed to evaluate the efficacy and safety of cisplatin added to standard neoadjuvant chemotherapy for locally advanced TNBC., Materials and Methods: All TNBC treated with neoadjuvant cisplatin 60mg/m2 once in 3 weeks with weekly paclitaxel for 12 weeks, following 8 weeks of dose-dense epirubicin 90mg/m2 or doxorubicin 60mg/m2 with cyclophosphamide 600mg/m2 were analyzed retrospectively. The data related to pathological complete response, adherence to planned therapy, disease-free survival and overall survival were collected., Results: Eighty-three patients were included, of whom 80% had stage III disease. Pathological complete response in both breast (T0/Tis) and axilla (N0) was observed in 48.1% of patients. Miller Payne grade 5 pathological response in the breast was seen in 61% of patients. Good partial responses (Miller Payne grades 3,4) were observed in 32.5% of patients. The remaining 6.5% were poor responders. Seventy-seven patients underwent surgery. The disease-free survival at 1 and 3 years for those who had a pathological complete response was 96.7% and 77.6%, respectively, and 92.3% and 62.7% for those who did not, respectively. The predominant adverse events were hematological, with anemia being the most common one., Conclusion: The addition of cisplatin to neoadjuvant chemotherapy with anthracycline and taxane in TNBC was tolerable and produced a high rate of pathological complete response. Cisplatin added to standard chemotherapy in patients with locally advanced TNBC could improve clinical outcomes.

We report a neural network model for predicting the electromagnetic response of mesoscale metamaterials as well as generate design parameters for a desired spectral behavior. Our approach entails treating spectral data as time-varying sequences and the inverse problem as a single-input multiple output model, thereby compelling the network architecture to learn the geometry of the metamaterial designs from the spectral data in lieu of abstract features., (© 2021. The Author(s).)

Mandibular osteomyelitis in paediatric population presents as painful swelling with progressive trismus. Often the aetiology for this form of progressive osteomyelitis is inconclusive. The infective aetiology in this condition is difficult to assign as bone tissue culture is found to be seldom positive. We present a case of an 11-year-old girl, with hearing and speech impairment, who presented with report of painful right-sided mandibular swelling with progressive trismus. Clinical, radiographic and histopathological findings were suggestive of sclerotic osteomyelitis. Bone tissue culture grew Methicillin-resistant Staphylococcus aureus , indicating a rare infective variant. Unlike the common belief, where osteomyelitic mandible needs a combination of medical and surgical management, our case was managed conservatively with only antibiotic therapy. Our patient responded well to the treatment with reduction in pain and gradual improvement in the mouth opening. Radiographically the mandibular involvement also showed complete regression., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patients with coronavirus disease 2019 (COVID-19) can develop rapidly progressive respiratory failure. Ventilation strategies during the COVID-19 pandemic seek to minimize patient mortality. In this study we examine associations between the availability of emergency department (ED)-initiated high-flow nasal cannula (HFNC) for patients presenting with COVID-19 respiratory distress and outcomes, including rates of endotracheal intubation (ETT), mortality, and hospital length of stay., Methods: We performed a retrospective, non-concurrent cohort study of patients with COVID-19 respiratory distress presenting to the ED who required HFNC or ETT in the ED or within 24 hours following ED departure. Comparisons were made between patients presenting before and after the introduction of an ED-HFNC protocol., Results: Use of HFNC was associated with a reduced rate of ETT in the ED (46.4% vs 26.3%, P <0.001) and decreased the cumulative proportion of patients who required ETT within 24 hours of ED departure (85.7% vs 32.6%, P <0.001) or during their entire hospitalization (89.3% vs 48.4%, P <0.001). Using HFNC was also associated with a trend toward increased survival to hospital discharge; however, this was not statistically significant (50.0% vs 68.4%, P = 0.115). There was no impact on intensive care unit or hospital length of stay. Demographics, comorbidities, and illness severity were similar in both cohorts., Conclusions: The institution of an ED-HFNC protocol for patients with COVID-19 respiratory distress was associated with reductions in the rate of ETT. Early initiation of HFNC is a promising strategy for avoiding ETT and improving outcomes in patients with COVID-19.

Rates of PTSD remain elevated among U.S. Veterans, highlighting a need for innovative management tools. Previous studies have shown mobile apps to have positive effects on PTSD symptoms, but few apps have been examined systematically. This pilot study evaluated the perceived effectiveness and usability of Mindset, a novel mobile app that monitors user stress level via heart rate to encourage e-therapy use. The study sample included 30 community-residing Veterans who completed baseline assessments. They used the Mindset app and associated smartwatch until their approximate 1-month follow-up. Self-reported assessments included pre- and post-deployment experiences; experience with Mindset; and standard screeners for PTSD (PCL-M), anxiety (GAD-7), depression (PHQ-9), and alcohol use problems (AUDIT). Among the 24 participants who completed follow-up interviews, a significant decrease ( p  < 0.05) was found in PCL-M, PHQ-9, and modified AUDIT scores. Respondents reported moderate to high acceptance and satisfaction with Mindset features, though considerable frustration with the associated smartwatch. These findings highlight mHealth apps such as Mindset as potentially useful tools for PTSD and depression symptom management. These findings are also encouraging in the context of the current COVID-19 pandemic, which may accelerate further innovation and implementation of mHealth technologies to improve mental health self-care.

Machine learning and data analytics are being increasingly used for quantitative structure property relation (QSPR) applications in the chemical domain where the traditional Edisonian approach towards knowledge-discovery have not been fruitful. The perception of odorant stimuli is one such application as olfaction is the least understood among all the other senses. In this study, we employ machine learning based algorithms and data analytics to address the efficacy of using a data-driven approach to predict the perceptual attributes of an odorant namely the odorant characters (OC) of "sweet" and "musky". We first analyze a psychophysical dataset containing perceptual ratings of 55 subjects to reveal patterns in the ratings given by subjects. We then use the data to train several machine learning algorithms such as random forest, gradient boosting and support vector machine for prediction of the odor characters and report the structural features correlating well with the odor characters based on the optimal model. Furthermore, we analyze the impact of the data quality on the performance of the models by comparing the semantic descriptors generally associated with a given odorant to its perception by majority of the subjects. The study presents a methodology for developing models for odor perception and provides insights on the perception of odorants by untrained human subjects and the effect of the inherent bias in the perception data on the model performance. The models and methodology developed here could be used for predicting odor characters of new odorants.

Introduction: It is generally expected that the time required for a clot to form in an extraction socket must be similar to that of the average physiological bleeding time (2-9 minutes). However, in dental practice does hemostasis require the full clot to form or does it occur earlier? Conventionally there is no accepted average time range for socket hemostasis with estimates ranging from 20 minutes to 40 minutes. This study is an attempt to quantify the average time period required for hemostasis to occur in an extraction socket., Methodology: 1205 consecutive patients attending the dental clinic and requiring dental extractions were evaluated for the average duration of hemostasis after extraction. Exclusion criteria were children (<15 years), pregnant mothers and patients who had a systemic bleeding disorder or were on anticoagulants. The socket was inspected first after five minutes after an extraction and later at 10 minutes and 15 minutes if bleeding continued., Results: Bleeding from an extraction socket settled in less than five minutes in about 83% of individuals and in 10 minutes in 96.5% of cases. Hence it is expected that in an otherwise normal healthy individual socket compression by biting over gauze for around 10 minutes will produce adequate haemostasis. Prolonged bleeding beyond 10 minutes was rare and was controlled with suturing and pressure applied with a gauze pack in healthy individuals., Conclusion: Checking for hemostasis after placing a pressure pack for 5-10 minutes over an extraction socket is a useful act of risk management before discharge of the patient from the clinic to rule out any hemorrhagic tendency., Competing Interests: None

Pseudotumours of haemophilia (PTH) are locally expansile destructive haematomas which result in varying morbidity among haemophilic patients. Adequate haematological treatment and prophylaxis helps in preventing these haematomas. Currently, there is no uniform standard management protocol for this entity due to rarity of these lesions. PTH are seen in 1%-2% of the severe haemophilic patients. They may also be seen in moderate cases when adequate factor coverage is not provided or in cases with factor VIII inhibitors. We report a rare case of mandibular pseudotumour in a patient with moderate haemophilia and Glanzmann's thrombasthenia, treated successfully with decompression of the haematoma. Postdecompression, sequential radiography revealed spontaneous bone regeneration at the site of the lesion. With 2 years follow-up, the mandible had no residual lesion. This reveals the role and potential of conservative decompression even in cases with severe osteodestruction secondary to developing haematoma of the mandible in haemophilic patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims and Objectives: Osteoradionecrosis (ORN) of the jaw is a significant yet rare complication of radiotherapy (RT) associated with the management of head-and-neck malignancies. Recent decrease in the incidence of ORN following RT to the head and neck is being mainly attributed to refinement in RT techniques and improvement in our understanding of this morbid disease. The aim of this study is to assess the patients with ORN following head-and-neck RT to determine the various contributing risk factors involved in the development of ORN., Subjects and Methods: A retrospective data review from 2003 onward was conducted on the cases of ORN which presented to the Department of Dental and Oral Surgery, Christian Medical College, Vellore. Details of the patients with regard to the site of primary malignancy, type of treatment provided - RT alone or in combination of surgery and chemotherapy, dose of RT, presenting complaint, duration between the RT and presentation of ORN, and method of management considered were evaluated., Results: A total of 25 patients were evaluated. The average age of the 25 patients in our study was 58 years. Oropharynx (about 50%) was the leading site of primary malignancy. More than half of the patients in the study (52%) had undergone radical RT for the primary malignancy and all the patients were given >60 Gy dose of RT. About 48% of the patients in the study reported with pus discharge as their chief complaint. The average intervening time period from completion of RT to the presentation of ORN was 48 months. The mandibular alveolus was the most common site for ORN. Twelve of the 25 cases in the study were managed conservatively with only 3 patients requiring major resection., Conclusion: Due to its rare presentation, ORN still remains a challenge for the clinician in its management. Our study revealed that radical RT and concurrent chemo-RT for the oropharyngeal and base of the tongue malignancies have a higher risk of developing ORN. Patients subjected to the dose of RT above 60 Gy for head-and-neck malignancies have an increased risk of future ORN; henceforth, newer modality treatment like intensity-modulated RT regimen is recommended for such sites. Most of the patients in the study were satisfactorily managed of the symptoms with conservative modality treatment; hence, it is recommended to consider for surgical methods only in severe end-stage form of ORN., Competing Interests: There are no conflicts of interest.

Ventilator-associated pneumonia (VAP) is one of the major nosocomial infections in the intensive care unit (ICU), contributing to increased mortality and morbidity. Studies have shown that oral decontamination through the use of mechanical and pharmacological agents significantly reduces the incidence of VAP, but oral care practices in ICUs are not consistent. A double-blind randomised controlled trial was undertaken in the medical ICU of a tertiary care centre in India, to assess the efficacy of a toothbrush-based oral care technique in reducing incidence of VAP. Tooth-brushing with concurrent suctioning technique was not proved to be superior to mouth-swabbing. The greatest risk factor for developing VAP was the number of ventilator days (length of time on a ventilator). There was a statistical association between gender and presence of antibiotics with VAP.

Objectives: Hemispheric disconnection has been used as a treatment of medically refractory epilepsy and evolved from anatomic hemispherectomy to functional hemispherectomies to hemispherotomies. The hemispherotomy procedure involves disconnection of an entire hemisphere with limited tissue resection and is reserved for medically-refractory epilepsy due to diffuse hemispheric disease. Although it is thought to be effective by preventing seizures from spreading to the contralateral hemisphere, the electrophysiological effects of a hemispherotomy on the ipsilateral hemisphere remain poorly defined. The objective of this study was to evaluate the effects of hemispherotomy on the electrophysiologic dynamics in peri-stroke and dysplastic cortex. Methods: Intraoperative electrocorticography (ECoG) was recorded from ipsilateral cortex in 5 human subjects with refractory epilepsy before and after hemispherotomy. Power spectral density, mutual information, and phase-amplitude coupling were measured from the ECoG signals. Results: Epilepsy was a result of remote perinatal stroke in three of the subjects. In two of the subjects, seizures were a consequence of dysplastic tissue: one with hemimegalencephaly and the second with Rasmussen's encephalitis. Hemispherotomy reduced broad-band power spectral density in peri-stroke cortex. Meanwhile, hemispherotomy increased power in the low and high frequency bands for dysplastic cortex. Functional connectivity was increased in lower frequency bands in peri-stroke tissue but not affected in dysplastic tissue after hemispherotomy. Finally, hemispherotomy reduced band-specific phase-amplitude coupling in peristroke cortex but not dysplastic cortex. Significance: Disconnecting deep subcortical connections to peri-stroke cortex via a hemispherotomy attenuates power of oscillations and impairs the transfer of information from large-scale distributed brain networks to the local cortex. Hence, hemispherotomy reduces heterogeneity between neighboring cortex while impairing phase-amplitude coupling. In contrast, dysfunctional networks in dysplastic cortex lack the normal connectivity with distant networks. Therefore hemispherotomy does not produce the same effects.

Background: The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk., Methods: Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease., Results: The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29))., Conclusions: Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

Purpose: This study evaluated the healing in cystic defect of the jaw to substantiate our understanding of spontaneous bone healing after enucleation of jaw cysts subjectively and with analysis of digital postoperative panoramic radiographs., Materials and Methods: Fourty four consecutive patients reporting to the Department of Dental and Oral Surgery, during the period between 2008-2012 having maxillary and mandibular cysts treated by either surgical enucleation or by marsupialization followed by enucleation were evaluated for subsequent bone formation at the site of cystectomy defect by subjective clinical examination along with digital radiographic examination. Postoperative clinical and radiographic examinations were performed at 6,9,12, and 24 months. Bone regeneration was evaluated by reduction of the size of residual cavities at the cystectomy defect using digital orthopantomogram., Results: Out of 44 patients 15 patients completed two years of follow-up with all the patients having 6 months follow-up. The maximum size of the cystic pathology was 150.40mm and minimum of 14.73mm at the time of presentation (average size of 58.16mm). Twenty patients were diagnosed with odontogenic keratocyst, with one patient having multiple OKC associated with Gorlin Goltz Syndrome, 17 patients had dentigerous cyst, 5 had Radicular cyst; solitary bone cyst and globulomaxillary cyst formed one each. Uneventful healing and spontaneous filling of the residual cavities were obtained in all cases. The digital analysis of the postoperative radiographs showed mean values of reduction in size of the residual cavity of 25.85% after 6 months, 57.13% after 9 months, 81.03% after one year and 100% after two year., Conclusion: Spontaneous bone regeneration can occur after surgical removal of jaw cysts without the aid of any graft materials even in large cystic cavity sufficiently surrounded by enough bony walls. This simplifies the surgical procedure, decreases the overall cost of surgery, and reduces the risk of postoperative complications associated with grafting.