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Computational pathology1,2 has witnessed considerable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders3,4. However, despite the explosive growth of generative artificial intelligence (AI), there have been few studies on building general-purpose multimodal AI assistants and copilots5 tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We built PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and fine-tuning the whole system on over 456,000 diverse visual-language instructions consisting of 999,202 question and answer turns. We compare PathChat with several multimodal vision-language AI assistants and GPT-4V, which powers the commercially available multimodal general-purpose AI assistant ChatGPT-4 (ref. 6). PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases with diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive vision-language AI copilot that can flexibly handle both visual and natural language inputs, PathChat may potentially find impactful applications in pathology education, research and human-in-the-loop clinical decision-making.PathChat, a multimodal generative AI copilot for human pathology, has been trained on a large dataset of visual-language instructions to interactively assist users with diverse pathology tasks. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation‐based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA‐HFPEF‐DZHK27 (CAtheter‐Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF. Methods: CABA‐HFPEF‐DZHK27 (NCT05508256) is an investigator‐initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two‐sided alpha = 0.05, 1‐beta = 0.8). Conclusion: CABA‐HFPEF‐DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF. [ABSTRACT FROM AUTHOR]

In the context of wire electrical discharge machining (WEDM), determining the fraction of thermal energy transferred to the workpiece (fc) is crucial for numerical modelling. This information is necessary to anticipate material removal mechanisms and understand thermal behaviour. In this study, two metaphor-less Rao algorithms are modified to solve the inverse heat conduction problem (IHCP) for the estimation of fc during the WEDM process without knowing any prior information on the transient functional form of fc. These two algorithms are compared in terms of accuracy and convergence speed. The Rao-1 algorithm stands out with high accuracy and rapid convergence. To evaluate the algorithm applicability in estimating fc, the following cases are considered: (1) a numerical investigation with artificial Gaussian error in simulated temperature readings and (2) a real-time experiment on WEDM setup with varying discharge currents. The RMS error between the actual and estimated value of fc with SS-304 material during numerical investigation is found to be 562 W/m which is just 0.008 times of heat source. Real-time experiments reveal that the discharge current is directly proportional to the total energy supplied by the wire as well as fc. The fc values estimated by the proposed inverse algorithm with various discharge currents fall within the range of 15–18%, aligning with the existing literature. This shows the proposed methodology is accurate and can be extended to incorporate other machining processes. [ABSTRACT FROM AUTHOR]

Background: During the Covid19 pandemic, the potential spread of the SARS-CoV-2 virus during surgeries, especially in laparoscopic surgeries, is a key concern. Surgical smoke released during laparoscopic surgeries may cause viral transmission. Therefore, the risk and benefits of viral transmission during laparoscopic surgery needs to be carefully evaluated. For the safety of healthcare professionals are adapted from the previous pandemics/epidemics, the preventive measures especially applicable to laparoscopic surgeries include care during CO2 insufflation/desufflation, minimal use of energy sources, personal protection measures are recommended. Objective: The aim of this article is to review the contemporary literature pertaining to the risk of conducting laparoscopic surgeries during the Covid-19 pandemic. In addition, we summarize the relevant safety protocols for the patients, surgical team, anesthetists, and the operation room staff. Materials and Methods: A systematic literature search was performed using the key words: Covid-19 laparoscopy, Surgical smoke, Covid safety in operation rooms, Laparoscopic surgeries and Covid safety, prevention, Aerosol transmission, Laparoscopic surgery, Covid-19’ Search articles were considered from the aims of the articles, nature, safety protocols, and risk mentioned in the literature. Results and Conclusions: Although the initial guidelines advocated by various organizations stated that Laparoscopy generally should not be used as it is considered to carry some risks of aerosol-type formation and infection and considerable caution is advised. Though some reports have suggested the use of Laparoscopy in selected cases where clinical benefit to the patient substantially exceeds the risk of potential viral transmission to the surgical team. Based on this review of the current scientific knowledge, no scientific evidence was found to support the use of open surgery over laparoscopy to reduce viral transmission of COVID-19 if the advocated Covid-19 guidelines are followed strictly; however, there is still much to discover about the viral transmission. [ABSTRACT FROM AUTHOR]

This clinical trial investigated the efficacy of platelet-rich fibrin (PRF) as an adjunct to conventional scaling and root planing (SRP) in non-surgical periodontal therapy. In a split-mouth randomized controlled trial with 13 patients and 26 periodontal pocket sites, PRF was inserted in test group pockets alongside SRP, while control group pockets received SRP alone. Measurements at baseline and six weeks included probing pocket depths (PPDs), clinical attachment loss (CAL), gingival recession (GR), the plaque index, and the gingivitis index. The wound healing index was assessed at six weeks. The results show statistically significant improvements in the SRP+PRF group compared to SRP alone, demonstrating a better CAL gain (SRP+PRF group: 2.69 ± 0.63; SRP alone group: 4.15 ± 0.69—p-value: 0.001), PPD reduction (SRP+PRF group: 2.62 ± 0.65; SRP alone group: 3.85 ± 0.80—p-value: 0.001), and GR minimization (SRP+PRF group: 0.46 ± 0.62; SRP alone group: 0.81 ± 0.72—p-value: 0.21). The adjunctive use of PRF enhanced healing, reduced pocket depths, decreased tissue morbidity, and minimized gingival recession. This study concludes that PRF placement is effective in 5–6 mm pockets, potentially reducing the number of periodontal treatment sessions needed for pocket closure. [ABSTRACT FROM AUTHOR]

This research explores the development of new composite material by integrating Azadirachta Indica (AI) with LLDPE to create wood‐plastic composites using the rotational molding process. By examining various proportions of AI wood flour blended with LLDPE, we investigated their impact on mechanical and physical properties. Our tests elucidate a clear correlation between mechanical properties and composite morphologies. Despite identical molding conditions, higher wood particle concentrations reduced mechanical properties compared to lower concentrations. Remarkably, a 12% wood content emerges as optimal, yielding a tensile modulus of 3.69 MPa and a flexural modulus of 468.5 MPa, with an acceptable reduction of 11% density and 13% porosity versus pure LLDPE. Additionally, we observed declines in tensile strength, impact strength, and hardness by up to 23%, 62%, and 11%, respectively, compared to neat LLDPE. Natural fillers enhance aesthetics, making these materials ideal for consumer products like garden equipment and furniture accessories. [ABSTRACT FROM AUTHOR]

Objective: The Visiopharm artificial intelligence (AI) algorithm for oestrogen receptor (ER) immunohistochemistry (IHC) in whole slide images (WSIs) has been successfully validated in surgical pathology. This study aimed to assess its efficacy in cytology specimens. Methods: The study cohort comprised 105 consecutive cytology specimens with metastatic breast carcinoma. ER IHC WSIs were seamlessly integrated into the Visiopharm platform from the Image Management System (IMS) during our routine digital workflow, and an AI algorithm was employed for analysis. ER AI scores were compared with pathologists' manual consensus scores. Optimization steps were implemented and evaluated to reduce discordance. Results: The overall concordance between pathologists' scores and AI scores was excellent (99/105, 94.3%). Six cases exhibited discordant results, including two false‐negative (FN) cases due to abundant histiocytes incorrectly counted as negatively stained tumour cells by AI, two FN cases owing to weak staining, and two false‐positive (FP) cases where pigmented macrophages were erroneously counted as positively stained tumour cells by AI. The Pearson correlation coefficient of ER‐positive percentages between pathologists' and AI scores was 0.8483. Optimization steps, such as lowering the cut‐off threshold and additional training using higher input magnification, significantly improved accuracy. Conclusions: The automated ER AI algorithm demonstrated excellent concordance with pathologists' assessments and accurately differentiated ER‐positive from ER‐negative metastatic breast carcinoma cytology cases. However, precision in identifying tumour cells in cytology specimens requires further enhancement. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients who present to the emergency department (ED) for suspected pulmonary embolism (PE) are often on active oral anticoagulation (AC). However, the diagnostic yield of computed tomography pulmonary angiography (CTPA) in screening for PE in patients who present on AC has not been well characterized. We aim to investigate the diagnostic yield of CTPA in diagnosing PE depending on AC status. METHODS: We reviewed and analyzed the electronic medical records of patients who underwent CTPA for PE at a university hospital ED from June 1, 2019, to March 25, 2022. Primary outcome was the incidence of PE on CTPA depending on baseline AC status and indication for AC. RESULTS: Of 2,846 patients, 242 were on AC for a history of venous thromboembolism (VTE), 210 were on AC for other indications, and 2,394 were not on AC. The incidence of PE on CTPA was significantly lower in patients on AC for other indications (5.7%) when compared to patients on AC for prior VTE (24.3%) and patients not on AC at presentation (9.8%) (P<0.001). In multivariable analysis among the whole cohort, AC was associated with a positive CTPA (odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.15–0.45, P<0.001). CONCLUSION: The incidence of PE among patients undergoing CTPA in the ED is lower in patients previously on AC for indications other than VTE when compared to those not on AC or those on AC for history of VTE. AC status and indication for AC may affect pre-test probability of a positive CTPA, and AC status therefore warrants consideration as part of future diagnostic algorithms among patients with suspected PE. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives). [ABSTRACT FROM AUTHOR]

Objectives The high incidence of prostate cancer causes prostatic samples to significantly affect pathology laboratories workflow and turnaround times (TATs). Whole-slide imaging (WSI) and artificial intelligence (AI) have both gained approval for primary diagnosis in prostate pathology, providing physicians with novel tools for their daily routine. Methods A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was carried out in electronic databases to gather the available evidence on the application of AI-based algorithms to prostate cancer. Results Of 6290 articles, 80 were included, mostly (59%) dealing with biopsy specimens. Glass slides were digitized to WSI in most studies (89%), roughly two-thirds of which (66%) exploited convolutional neural networks for computational analysis. The algorithms achieved good to excellent results about cancer detection and grading, along with significantly reduced TATs. Furthermore, several studies showed a relevant correlation between AI-identified histologic features and prognostic predictive variables such as biochemical recurrence, extraprostatic extension, perineural invasion, and disease-free survival. Conclusions The published evidence suggests that AI can be reliably used for prostate cancer detection and grading, assisting pathologists in the time-consuming screening of slides. Further technologic improvement would help widening AI's adoption in prostate pathology, as well as expanding its prognostic predictive potential. [ABSTRACT FROM AUTHOR]

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor. [ABSTRACT FROM AUTHOR]

Background. Whole slide imaging (WSI) represents a paradigm shift in pathology, serving as a necessary first step for a wide array of digital tools to enter the field. It utilizes virtual microscopy wherein glass slides are converted into digital slides and are viewed by pathologists by automated image analysis. Its impact on pathology workflow, reproducibility, dissemination of educational material, expansion of service to underprivileged areas, and institutional collaboration exemplifies a significant innovative movement. The recent US Food and Drug Administration approval to WSI for its use in primary surgical pathology diagnosis has opened opportunities for wider application of this technology in routine practice. Main Text. The ongoing technological advances in digital scanners, image visualization methods, and the integration of artificial intelligence-derived algorithms with these systems provide avenues to exploit its applications. Its benefits are innumerable such as ease of access through the internet, avoidance of physical storage space, and no risk of deterioration of staining quality or breakage of slides to name a few. Although the benefits of WSI to pathology practices are many, the complexities of implementation remain an obstacle to widespread adoption. Some barriers including the high cost, technical glitches, and most importantly professional hesitation to adopt a new technology have hindered its use in routine pathology. Conclusions. In this review, we summarize the technical aspects of WSI, its applications in diagnostic pathology, training, and research along with future perspectives. It also highlights improved understanding of the current challenges to implementation, as well as the benefits and successes of the technology. WSI provides a golden opportunity for pathologists to guide its evolution, standardization, and implementation to better acquaint them with the key aspects of this technology and its judicial use. Also, implementation of routine digital pathology is an extra step requiring resources which (currently) does not usually result increased efficiency or payment. [ABSTRACT FROM AUTHOR]

The molecular mechanism by which Swertiamarin (SM) prevents advanced glycation end products (AGEs) induced diabetic nephropathy (DN) has never been explored. To evaluate the effect of SM in preventing the progression of DN in high fat diet-streptozotocin-induced diabetic rats. After 1 week of acclimatisation, the rats were divided randomly into five groups as follows: (1) Control group, which received normal chow diet; (2) High-fat diet (HFD) group which was fed diet comprising of 58.7% fat, 27.5% carbohydrate and 14.4% protein); (3) Aminoguanidine (AG) group which received HFD + 100 mg/k.b.w.AG (intraperitoneal); (4) Metformin (Met) group which received HFD + 70 mg/k.b.w. the oral dose of Met and (5) SM group which was supplemented orally with 50 mg/k.b.w.SM along with HFD. After 12 weeks all HFD fed animals were given a single 35 mg/k.b.w. dose of streptozotocin with continuous HFD feeding for additional 18 weeks. Later, various biochemical assays, urine analyses, histopathological analysis of kidneys, levels of AGEs, expression of various makers, and in-silico analysis were performed. The diabetic group demonstrated oxidative stress, increased levels of AGEs, decreased renal function, fibrosis in the renal tissue, higher expression of the receptor for advanced glycation end products (RAGE), which were ameliorated in the SM treated group. In-silico analysis suggests that SM can prevent the binding of AGEs with RAGE. SM ameliorated DN by inhibiting the oxidative stress induced by AGEs. SM reduces the levels of hyperglycaemia-induced advanced glycation end products in serum and renal tissue. SM prevents renal fibrosis by inhibiting the EMT in the kidney tissue. The in-silico analysis proves that SM can inhibit the binding of various AGEs with RAGE, thereby inhibiting the AGE-RAGE axis. [ABSTRACT FROM AUTHOR]

Vγ9Vδ2 T cells represent a promising cancer therapy platform because the implementation of allogenic, off-the-shelf product candidates is possible. However, intravenous administration of human Vγ9Vδ2 T cells manufactured under good manufacturing practice (GMP)-compliant, serum-free conditions are not tested easily inmostmousemodels,mainly because they lack the ability to migrate from the blood to tissues or tumors. We demonstrate that these T cells do not migrate from the circulation to the mouse bone marrow (BM), the site of many malignancies. Thus, there is a need to better characterize human γδ T-cell migration in vivo and develop strategies to direct these cells to in vivo sites of therapeutic interest. To better understand the migration of these cells and possibly influence their migration, NSG mice were conditioned with agents to clear BM cellular compartments, i.e., busulfan or total body irradiation (TBI), or promote T-cell migration to inflamed BM, i.e., incomplete Freund's adjuvant (IFA), prior to administering γδ T cells. Conditioning with TBI, unlike busulfan or IFA, increases the percentage and number of γδ T cells accumulating in the mouse BM, and cells in the peripheral blood (PB) and BM display identical surface protein profiles. To better understand the mechanism by which cells migrate to the BM, mice were conditioned with TBI and administered γδ T cells or tracker-stained red blood cells. The mechanism by which γδ T cells enter the BM after radiation is passive migration from the circulation, not homing. We tested if these ex vivo-expanded cells can migrate based on chemokine expression patterns and showed that it is possible to initiate homing by utilizing highly expressed chemokine receptors on the expanded γδ T cells. γδ T cells highly express CCR2, which provides chemokine attraction to C-C motif chemokine ligand 2 (CCL2)-expressing cells. IFNγ-primed mesenchymal stromal cells (MSCs) (γMSCs) express CCL2, and we developed in vitro and in vivo models to test γδ T-cell homing to CCL2-expressing cells. Using an established neuroblastoma NSG mouse model, we show that intratumorally-injected γMSCs increase the homing of γδ T cells to this tumor. These studies provide insight into the migration of serum-free, ex vivo-expanded Vγ9Vδ2 T cells in NSG mice, which is critical to understanding the fundamental properties of these cells. [ABSTRACT FROM AUTHOR]

Effective drug delivery at a targeted site had given the possibility to perform the precise function to control the release rates and have a better compliance on the health care system but the chemistry possessing complex form had made conditions complicated. But the invention of nanosponges has given a significant approach toward solving this problem. Nanosponges are tiny sponges having size of about a virus and can be filled with variety of drugs. This sponges can circulate around the body until interact with specific target site and stick on surface and start releasing drug in a controlled manner. Some cyclodextrins based nanosponges proposed nanodelivery system and form porous insoluble nanoparticle having crystalline and amorphous nature. Important characteristic of these sponges is their solubility in aqueous form and give a effect to the drugs with poor solubility. This review is focusing on the preparation methods, applications of nanosponges in the field of drug delivery. [ABSTRACT FROM AUTHOR]

Background: The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation. Methods: A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature. Results: The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals' autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation. Conclusion: The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine. [ABSTRACT FROM AUTHOR]

This review discusses the profound impact of artificial intelligence (AI) on breast cancer (BC) diagnosis and management within the field of pathology. It examines the various applications of AI across diverse aspects of BC pathology, highlighting key findings from multiple studies. Integrating AI into routine pathology practice stands to improve diagnostic accuracy, thereby contributing to reducing avoidable errors. Additionally, AI has excelled in identifying invasive breast tumors and lymph node metastasis through its capacity to process large whole-slide images adeptly. Adaptive sampling techniques and powerful convolutional neural networks mark these achievements. The evaluation of hormonal status, which is imperative for BC treatment choices, has also been enhanced by AI quantitative analysis, aiding interobserver concordance and reliability. Breast cancer grading and mitotic count evaluation also benefit from AI intervention. AI-based frameworks effectively classify breast carcinomas, even for moderately graded cases that traditional methods struggle with. Moreover, AI-assisted mitotic figures quantification surpasses manual counting in precision and sensitivity, fostering improved prognosis. The assessment of tumor-infiltrating lymphocytes in triple-negative breast cancer using AI yields insights into patient survival prognosis. Furthermore, AI-powered predictions of neoadjuvant chemotherapy response demonstrate potential for streamlining treatment strategies. Addressing limitations, such as preanalytical variables, annotation demands, and differentiation challenges, is pivotal for realizing AI's full potential in BC pathology. Despite the existing hurdles, AI's multifaceted contributions to BC pathology hold great promise, providing enhanced accuracy, efficiency, and standardization. Continued research and innovation are crucial for overcoming obstacles and fully harnessing AI's transformative capabilities in breast cancer diagnosis and assessment. [ABSTRACT FROM AUTHOR]

Aims In patients with atrial flutter (AFL), ablation of the cavotricuspid isthmus (CTI) is a highly effective procedure to prevent AFL recurrence, but atrial fibrillation (AF) may occur during follow-up. The presented FLUTFIB study was designed to identify the exact incidence, duration, timely occurrence, and associated symptoms of AF after CTI ablation using continuous cardiac monitoring via implantable loop recorders. Methods and results One hundred patients with AFL without prior AF diagnosis were included after CTI ablation (mean age 69.7 ± 9.7 years, 18% female) and received an implantable loop recorder for AF detection. After a median follow-up of 24 months 77 patients (77%) were diagnosed with AF episodes. Median time to first AF occurrence was 180 (43–298) days. Episodes lasted longer than 1 h in most patients (45/77, 58%). Forty patients (52%) had AF-associated symptoms. Patients with and without AF development showed similar baseline characteristics and neither HATCH- nor CHA2DS2-VASc scores were predictive of future AF episodes. Oral anticoagulation (OAC) was stopped during FU in 32 patients (32%) and was re-initiated after AF detection in 15 patients (15%). No strokes or transient ischaemic attack episodes were observed during follow-up. Conclusion This study represents the largest investigation using implantable loop recorders (ILRs) to detect AF after AFL ablation and shows a high incidence of AF episodes, most of them being asymptomatic and lasting longer than 1 h. In anticipation of trials determining the duration of AF episodes that should trigger OAC initiation, these results will help to guide anticoagulation management after CTI ablation. [ABSTRACT FROM AUTHOR]

The aim of this qualitative study was to explore desired ways to deliver comprehensive sexuality education (CSE) and topics, among secondary school students in a low-resource setting in Western Kenya. One school (n = 440) has received 8–9-h CSE intervention, while the other school (n = 496) served as a control. After one-year follow-up the students were asked (one open-ended question) to suggest desired topics of CSE, with a response rate of 93% (n = 867). The following topics were suggested by the students: abortion, contraception, sexual rights, abstinence and STI/HIV, and preferred CSE delivery means were school-based teaching, online resources and social media, community-based elements or trusted individuals. The students who had not received the intervention were more in favor of an abstinence-only approach and demonstrated more negative attitudes toward abortion. [ABSTRACT FROM AUTHOR]

Nutritional status of patients, specially prolonged starvations is an important sub-component of the environmental factors, speculated to have indirect impact on the initiation, propagation, resolution, and exacerbation stages of autoimmunity. The study was based on the hypothesis of conscious, selective, and self-destruction, that is, deregulated autophagy of skin and hair in low dietary protein scenario triggered with prolonged starvations. It was aimed to reverse the self-destruction/deregulated autophagy by providing early morning, low carb-high protein nutrition, and correcting underlying micronutrient deficiency and studying its effect on reducing auto-immunity and eventually reducing disease burden and recurrence. Methods: In this retrospective study, patients were divided into two categories based on disease activity and nutrition. Group A: "novice group" of vitiligo patients who presented at an early stage of their disease were managed with basic standard of therapeutics. Group B: "stabilized group" of vitiligo who were given surgical treatment and followed up for 3 years for any recurrences. Personalized diet plan aimed at reversing high carb-low protein diet and avoiding prolonged overnight starvation adhering to early morning breakfast respecting the circadian rhythm and balanced with additional plant based protein was advised. All detectable underlying micronutrient deficiencies were corrected. Results: Thirty patients were enrolled in the study, 20 in group A and 10 in group B. We observed visible signs of improvement in group A, with early vitiligo (90%) with topical therapy and nutritional intervention as early as 3 weeks. Following surgical procedure in group B, 50% patients had near complete pigmentation at the end of 3 months and 30% within next 3 months. At the end of 6 months, all patients had significant improvement in VASI and VIDA score, however two patients in each group had recurrence at end of 1 year who deviated from nutritional protocol and were found to be deficient in protein intake and micronutrients deficiency was detected on blood investigation. The improvement in VASI scores with conventional treatment and nutritional intervention was found to be statistically significant at 6 months and 1-year interval in group A with paired t test (P=0.013). Similarly, improvement in VASI was statistically very significant at 6 months and 1- year duration in surgically treated vitiligo group B (P=0.001). These patients were put on immunosuppressive therapies in first group after correction of deficiencies and managed with supportive and conventional therapy in second group in subsequent 3 years follow up. Conclusion: Nutritious diet aimed at correction of underlying protein and micronutrient deficiency with special emphasis on circadian rhythm may arrest the natural progression of disease at an early stages of the disease and prime the body for oral immunosuppressive drugs. This approach may prevent the recurrence in patients already stabilized with standard care of therapeutics and surgery in future. [ABSTRACT FROM AUTHOR]

The article focuses on the Court of Justice of the European Union's decision on the concept of "same global marketing authorisation" in the Tecfidera case. Topics include the regulatory framework for medicinal products, the balance between generic and innovative products, and the court's interpretation of the concept, leading to the rejection of Polpharma's application for marketing authorisation for its generic version of Tecfidera.

The application of immunotherapies such as chimeric antigen receptor (CAR) T therapy or bi-specific T cell engager (BiTE) therapy to manage myeloid malignancies has proven more challenging than for B-cell malignancies. This is attributed to a shortage of leukemia-specific cell-surface antigens that distinguish healthy from malignant myeloid populations, and the inability to manage myeloid depletion unlike B-cell aplasia. Therefore, the development of targeted therapeutics for myeloid malignancies, such as acute myeloid leukemia (AML), requires new approaches. Herein, we developed a ligand-based CAR and secreted bi-specific T cell engager (sBite) to target c-kit using its cognate ligand, stem cell factor (SCF). c-kit is highly expressed on AML blasts and correlates with resistance to chemotherapy and poor prognosis, making it an ideal candidate for which to develop targeted therapeutics. We utilize γδ T cells as a cytotoxic alternative to αβ T cells and a transient transfection system as both a safety precaution and switch to remove alloreactive modified cells that may hinder successful transplant. Additionally, the use of γδ T cells permits its use as an allogeneic, off-the-shelf therapeutic. To this end, we show mSCF CAR- and hSCF sBite-modified γδ T cells are proficient in killing c-kit+ AML cell lines and sca-1+ murine bone marrow cells in vitro. In vivo, hSCF sBite-modified γδ T cells moderately extend survival of NSG mice engrafted with disseminated AML, but therapeutic efficacy is limited by lack of γδ T-cell homing to murine bone marrow. Together, these data demonstrate preclinical efficacy and support further investigation of SCF-based γδ T-cell therapeutics for the treatment of myeloid malignancies. [ABSTRACT FROM AUTHOR]

Papillary renal neoplasm with reverse nuclear polarity (PRNRP) is an emerging oncocytic renal tumor. Cytomorphologic features of this tumor have not been described in the literature before. Thee objective of this study was to review the cytomorphology of a case PRNRP and compare with cytomorphologic features of papillary renal cell carcinomas (pRCCs) reported in the literature. 1 case of core needle biopsy (CNB) with touch preparation (TP) of a renal mass diagnosed as PRNRP was reviewed retrospectively. Clinical presentation, cytomorphologic features, ancillary tests and histopathology results were analyzed. The touch preparation was cellular and showed tight 3-D clusters of cuboidal epithelial cells with variable presence of fibrovascular cores (FC), granular eosinophilic cytoplasm, round apically located grade 1 nuclei compared to cases of pRCC that consistently showed presence of FCs lined by cuboidal to columnar epithelial cells with variable degree of cytologic atypia. Features characteristic of pRCC like foamy macrophages, hemosiderin laden macrophages, nuclear grooves or psammoma bodies were not present. No necrosis or mitosis were identified. By immunohistochemistry (IHC) the tumor cells were positive for cytokeratin 7, GATA-3 and AMACR (focal) and negative for CA-IX, CD117 and vimentin. Cytomorphologic features of PRNRP are unique and characterized by tight 3-D clusters (with or without FCs) of cuboidal cells with small round apically located nuclei and finely granular oncocytic cytoplasm. Specific diagnosis of PRNRP on cytology or CNB is feasible along with use of ancillary tests IHC and /or molecular tests. [ABSTRACT FROM AUTHOR]

The early career professionals in the field of Cardiovascular Magnetic Resonance (CMR) face unique challenges and hurdles while establishing their careers in the field. The Society for Cardiovascular Magnetic Resonance (SCMR) has expanded the role of the early career section within the society to foster the careers of future CMR leaders. This paper aims to describe the obstacles and available opportunities for the early career CMR professionals worldwide. Societal opportunities and actions targeted at the professional advancement of the early career CMR imagers are needed to ensure continuous growth of CMR as an imaging modality globally. [ABSTRACT FROM AUTHOR]

Melanoma is an aggressive skin cancer with increasing incidence and mortality worldwide. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Recent advances in immunology and cancer biology have led to the discovery and development of novel therapeutics, such as immune checkpoint inhibitors (ICIs) and targeted therapies, which have revolutionized the clinical care of patients with metastatic melanoma. Despite recent successes with ICIs, many melanoma patients do not experience long-term benefits from ICI therapies, highlighting the need for alternative treatments with novel targets such as lymphocyte-activated gene 3 (LAG-3). In this review, we explore new therapeutic agents and novel combinations that are being tested in early-phase clinical trials. We discuss newer promising tools such as nanotechnology to develop nanosystems that act as drug carriers and/or light absorbents to potentially improve therapy outcomes. Finally, we also highlight challenges such as management after resistance and intervention with novel immunotherapies and the lack of predictive biomarkers to stratify patients to targeted treatments after primary treatment failure. [ABSTRACT FROM AUTHOR]

Digital pathology (DP) is being increasingly employed in cancer diagnostics, providing additional tools for faster, higher-quality, accurate diagnosis. The practice of diagnostic pathology has gone through a staggering transformation wherein new tools such as digital imaging, advanced artificial intelligence (AI) algorithms, and computer-aided diagnostic techniques are being used for assisting, augmenting and empowering the computational histopathology and AI-enabled diagnostics. This is paving the way for advancement in precision medicine in cancer. Automated whole slide imaging (WSI) scanners are now rendering diagnostic quality, high-resolution images of entire glass slides and combining these images with innovative digital pathology tools is making it possible to integrate imaging into all aspects of pathology reporting including anatomical, clinical, and molecular pathology. The recent approvals of WSI scanners for primary diagnosis by the FDA as well as the approval of prostate AI algorithm has paved the way for starting to incorporate this exciting technology for use in primary diagnosis. AI tools can provide a unique platform for innovations and advances in anatomical and clinical pathology workflows. In this review, we describe the milestones and landmark trials in the use of AI in clinical pathology with emphasis on future directions. [ABSTRACT FROM AUTHOR]

Primary renal synovial sarcoma is a rare aggressive mesenchymal neoplasm of the kidney that accounts for less than 1% of renal sarcomas. Herein, we describe the clinicopathologic and molecular findings of 14 renal synovial sarcoma patients in one of the largest case series to date and to our knowledge, the only renal synovial sarcoma series to use novel SS18-SSX IHC. Clinicopathologic, IHC, molecular, management, and follow-up data were reviewed and analyzed. Macroscopically, the tumors had either homogeneous, tan-white, and solid (n = 10), variegated and solid (n = 3), or variegated and solid-cystic (n = 1) cut surfaces. Spindle cell (n = 10), round cell (n = 3), and round to epithelioid morphologies (n = 1) were observed. SS18-SSX IHC was positive in all 14 tumors (diffuse, n = 10; multifocal, n = 2; focal, n = 2). All the tumors harbored SS18::SSX1/2 gene rearrangement. Metastases to the liver, brain, and lung (n = 1); liver and bone (n = 1); liver and diaphragm (n = 1) were identified. Adjuvant chemotherapy was administered in 11/12 patients. Follow-up was available for 10 patients (time period range: 5 to 24 months). Four patients died of disease, and six patients are alive with no recurrence or metastasis. As SS18-SSX IHC showed an excellent concordance with the FISH results, this may reliably be used in the IHC panel of spindle/round cell sarcomas of the kidney and as a molecular surrogate for renal synovial sarcoma, particularly in a resource-limited setting. Also, the tumors with focal SS18-SSX expression had lower break apart signals in the FISH assay (19% and 23% in two tumors with focal SS18-SSX IHC positivity). [ABSTRACT FROM AUTHOR]

Objective: Fragmented QRS (fQRS), as defined by additional spikes in the QRS complex of a 12-lead electrocardiogram (ECG), is a marker of scarred myocardium. In patients with coronary artery disease (CAD), fQRS is a predictor of heart failure (HF) and other major adverse cardiac events (MACE). The study was aimed to evaluate the role of fQRS in prediction of HF in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: In a prospective, non-randomized, small observational study, we enrolled 188 consecutive patients with STEMI undergoing primary PCI. Patients were grouped according to the presence or absence of fQRS and their inhospital, 1 and 6-month MACE outcomes were assessed. Results: Of the 188 patients, fQRS were noted in 92 (48.94%) patients. Patients with fQRS were more likely to have Killip class II/III/IV. Patients with fQRS had a significantly higher corrected QT interval, lower left ventricular ejection fraction (LVEF), and higher N-terminal pro brain natriuretic peptide (NT-pro BNP) at 24 hours and 48 hours compared to patients without fQRS. The in-hospital (P=0.001), 30-day (P=0.03) and 6-month (p=0.01) MACE were higher in patients with fQRS. On logistic multiple analysis, fQRS in anterior leads (OR=3.70, CI=1.68-10.02, p=0.001), fQRS in more than 2 leads (OR=5.20, CI=1.51-12.83, p=0.01), NT-proBNP (OR=1.05, CI=1.03-1.08, p=0.02) and Killip class II/III/IV were found to be significant predictors for HF hospitalization. Conclusion: Our findings suggest that fQRS can be a predictor for HF in patients with STEMI and provide a simple and readily available technique for predicting prognosis. Larger studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Ischemia with no obstructive coronary arteries (INOCA) is a relatively newly discovered ischemic phenotype that affects patients similarly to obstructive coronary artery disease (CAD) but has a unique pathophysiology and epidemiology. Patients with INOCA present with ischemic signs and symptoms but no obstructive CAD seen on coronary CTA or invasive coronary angiography, which can assess epicardial vessels. The mechanisms of INOCA can be grouped into three endotypes: coronary microvascular dysfunction, epicardial coronary vasospasm, or a combination of both. Accurate and comprehensive assessment of both epicardial and microvascular disease in suspected cases of INOCA is crucial for providing targeted therapy and improving outcomes in this underrepresented population. This review aims to clarify the complex pathophysiology of INOCA, present an overview of invasive and non-invasive diagnostic methods, and examine contemporary approaches for coronary perfusion assessment using cardiac magnetic resonance (CMR). We also explore how recent advancements in quantitative CMR can potentially revolutionize the evaluation of suspected INOCA by offering a rapid, accurate, and non-invasive diagnostic approach, thereby reducing the alarming number of cases that go undetected. [ABSTRACT FROM AUTHOR]

Harmony between facial complexion and gingival health goes hand in hand. Gingival depigmentation is an aesthetic correction of hyperactive melanocytes in gingival tissues that lead to hyperpigmentation. Current study compares depigmentation, pain scores, and itching with scalpel technique and nonsurgical intramucosal Vitamin C injection. 30 individuals in the age range of 18–40 years conscious of dark gums were randomly allocated to test and control group by lottery method. Thorough Phase I therapy was performed one week before the procedure. Area and intensity of depigmentation were evaluated preoperatively and postoperatively; pain score, itching, and repigmentation percentage were the postoperative parameters. After 24 hrs, test group showed significantly lesser VAS score for pain as compared to control group. There was no statistically significant difference in preoperative area of pigmentation between the test and control group (p = 0.936). Postoperatively also, there was no statistically significant difference in area of pigmentation between the test and control group (p = 0.932). For comparing area of pigmentation, an independent t-test was applied and Mann–Whitney test was used for differentiating the intensity of pigmentation, repigmentation, and VAS score between the groups. The study concluded that Vitamin C mesotherapy and scalpel technique showed comparable results in reduction of areas and intensity of gingival hyperpigmentation. [ABSTRACT FROM AUTHOR]

The biggest challenges with CS studies included in the present article, is variable diagnostic criteria used to identify patients with CS. FDG uptake remains highly dependent on patient preparation and myocardial metabolism, isolated use of FDG-PET in CS diagnostic algorithm remains clinically limited.[14] Diagnosis of isolated CS remains challenging. Ultimately diagnostic and prognostic evaluation of patient with CS depends on the individual patient, clinical presentation and local expertise at the center doing the testing. [Extracted from the article]

Background: SOX17 (SRY‐box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens. In this study, validation of the utility of SOX17 immunohistochemistry (IHC) in diagnosing metastatic gynecologic carcinomas in cytology specimens was sought. Methods: The study cohort included 84 cases of metastatic carcinomas that included 29 metastatic gynecologic carcinomas (24 ovarian high‐grade serous carcinomas, two endometrial serous carcinomas, one low‐grade serous carcinoma, one ovarian clear cell carcinoma, and one endometrial endometrioid carcinoma) and 55 cases of metastatic nongynecologic carcinomas (10 clear cell renal cell carcinomas, 10 papillary thyroid carcinomas, 11 gastrointestinal adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, and four urothelial carcinomas). Cytology specimen types included peritoneal fluid (n = 44), pleural fluid (n = 25), and fine‐needle aspiration (n = 15). SOX17 IHC was performed on the cell block sections. The intensity of staining and percent positivity of the tumor cells were evaluated. Results: SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse and strong nuclear expression (29 of 29; 100%). SOX17 was negative in other metastatic nongynecologic carcinomas (54 of 55; 98.18%) except for one papillary thyroid carcinoma that showed low positivity (<10%). Conclusions: SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. Therefore, SOX17 IHC should be included in the workup of differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. The results of this study showed that SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse (100%) and strong nuclear expression (29 of 29) and was negative in 54 of 55 metastatic nongynecologic carcinomas. SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the diagnosis of metastatic gynecologic carcinomas in cytology specimens. [ABSTRACT FROM AUTHOR]