Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

Appendicitis in children: correlation between the surgical and histological diagnosis.

PURPOSE: Study was designed in order to evaluate the discrepancies between surgical and histological diagnosis in pediatric acute appendicitis (AA) and to compare the outcomes of laparoscopic (LA) and open appendectomies (OA). METHODS: In a retrospective observational cohort, AA patients were included under 18 years of age, operated between 2011 and 2020. Surgical diagnosis was defined by the operating surgeon. The histological findings were classified as uncomplicated and complicated AA. The LOS and complications were also statistically analyzed. RESULTS: Altogether, 1444 patients were included. Significant strong correlation and a moderate to substantial agreement were found between the surgeon's and the histopathological findings in all appendectomy cases (weighted kappa value in OA: 0.633, LA: 0.639, total sample: 0.637). If the surgeon's diagnosis was less severe than the pathologist's, the LOS was 4 (3;7) days, whereas if the surgical diagnosis was correct, the LOS was 3 (3;5) days (p < 0.0001). CONCLUSIONS: In contrary to the literature, our study revealed a strong correlation and moderate agreement between the intraoperative and histopathological findings regarding the severity of AA. Complicated cases are distinctly recognizable during the surgery. In case the surgeon underestimates the severity of AA, the chance of complications is higher. LEVEL OF EVIDENCE: II.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Validation of large language models for detecting pathologic complete response in breast cancer using population-based pathology reports.

AIMS: The primary goal of this study is to evaluate the capabilities of Large Language Models (LLMs) in understanding and processing complex medical documentation. We chose to focus on the identification of pathologic complete response (pCR) in narrative pathology reports. This approach aims to contribute to the advancement of comprehensive reporting, health research, and public health surveillance, thereby enhancing patient care and breast cancer management strategies. METHODS: The study utilized two analytical pipelines, developed with open-source LLMs within the healthcare system's computing environment. First, we extracted embeddings from pathology reports using 15 different transformer-based models and then employed logistic regression on these embeddings to classify the presence or absence of pCR. Secondly, we fine-tuned the Generative Pre-trained Transformer-2 (GPT-2) model by attaching a simple feed-forward neural network (FFNN) layer to improve the detection performance of pCR from pathology reports. RESULTS: In a cohort of 351 female breast cancer patients who underwent neoadjuvant chemotherapy (NAC) and subsequent surgery between 2010 and 2017 in Calgary, the optimized method displayed a sensitivity of 95.3% (95%CI: 84.0-100.0%), a positive predictive value of 90.9% (95%CI: 76.5-100.0%), and an F1 score of 93.0% (95%CI: 83.7-100.0%). The results, achieved through diverse LLM integration, surpassed traditional machine learning models, underscoring the potential of LLMs in clinical pathology information extraction. CONCLUSIONS: The study successfully demonstrates the efficacy of LLMs in interpreting and processing digital pathology data, particularly for determining pCR in breast cancer patients post-NAC. The superior performance of LLM-based pipelines over traditional models highlights their significant potential in extracting and analyzing key clinical data from narrative reports. While promising, these findings highlight the need for future external validation to confirm the reliability and broader applicability of these methods.

A weighted and cumulative point system for accurate scoring of intestinal pathology in a piglet model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a serious condition in premature infants, in which a portion of the intestine undergoes inflammation and necrosis. The preterm pig develops NEC spontaneously, making it a suitable model for exploring novel NEC treatments. We aimed to revise the intestinal scoring system to more accurately describe the diversity of NEC lesions in the preterm piglet model. We included 333 preterm piglets from four experiments, each delivered via cesarean section. The piglets were fed either a gently processed (GP) or harshly processed (HP) milk formula for 96 h before euthanasia. At necropsy, the gastrointestinal tract was assessed with 1) an established 6-grade score and 2) a descriptive approach focusing on the distribution and severity of hyperemia, hemorrhage, pneumatosis intestinalis (intramural gas), and necrosis. Subsequently, the descriptive registrations were converted into a weighted and cumulative point (WCP) score. Compared to the 6-grade score, the WCP score enabled a greater segregation of severity levels, especially among organs with more prominent NEC lesions. IL-1ß in small intestinal lesions and both IL-8 and IL-1ß in colon lesions correlated positively with the WCP scale. A histopathological grade system (0-8) was established and revealed mucosal pathology in lesion biopsies, which were not recognized macroscopically. Finally, the WCP score showed a higher NEC-promoting effect of the HP formula compared to the GP formula. The descriptive registrations and extended score range of this revised intestinal scoring system enhance the accuracy of describing NEC lesions in preterm pigs. This approach may increase the efficiency of preclinical NEC experiments.

Characterising delayed villous maturation: A narrative literature review.

The normal development of the placenta is vital for fetal growth and a healthy pregnancy outcome. Delayed villous maturation (DVM) is a placental lesion that has been implicated in stillbirth. In DVM, villi do not maturate adequately for their gestational age. DVM is characterised by larger and fewer terminal placental villi, low numbers of syncytial knots, and thicker and fewer vasculosyncytial membranes. DVM is most commonly reported in conjunction with maternal diabetes; however, the occurrence of idiopathic DVM suggests that there may be multiple mechanistic pathways that contribute to DVM. DVM can only be diagnosed through histopathological examination after birth, and there is significant interobserver variability in diagnosis. Establishing objective criteria to distinguish between DVM and healthy placentas is key to increasing the understanding of DVM. Vasculosyncytial membrane count, numbers of syncytial knots and CD15, among others, have been presented as potential diagnostic criteria in the literature. This review aims to compile information on DVM, including the pathophysiology, conditions that have reported associations with DVM and potential markers that could be used as criteria to differentiate between DVM and healthy placentas.

Special AT-rich sequence-binding protein 2 immunohistochemistry in the diagnosis of osteosarcoma in dogs.

Malignant osteoblasts can have markedly pleomorphic phenotypes and variable amounts of tumour-associated matrix, complicating the ability of pathologists to accurately differentiate osteosarcoma (OSA) from other types of neoplasms using only histopathology. Current immunohistochemical markers for animals have limited sensitivity and specificity in identifying OSA or produce inconsistent results. Immunohistochemistry (IHC) for special AT-rich sequence-binding protein 2 (SATB2) has been used in human medicine to aid in identification of normal and neoplastic osteoblasts, and the objective of this study was to determine whether this marker could also be useful for the diagnosis of canine OSA. Initially, SATB2 IHC was performed on eight samples from cases of well-differentiated canine OSA and on other tumour types for which OSA is a differential diagnosis, as well as on normal tissues, to assess sensitivity and cross-reactivity. Following confirmation that SATB2 is immunoreactive for normal and neoplastic canine osteoblasts and negative in other non-osseous mesenchymal cell types and organs, SATB2 IHC was tested on 123 cases of poorly differentiated malignant neoplasms as part of a panel with other immunohistochemical markers, as appropriate, based on histomorphology and differential diagnoses. The conclusion is that SATB2 IHC is a sensitive and specific marker for identifying canine OSA when used in a panel with other immunohistochemical markers and in conjunction with supportive clinical history.

The Use of Artificial Intelligence Technologies in Cancer Care.

Artificial intelligence (AI) is already an essential tool in the handling of large data sets in epidemiology and basic research. Significant contributions to radiological diagnosis are emerging alongside increasing use of digital pathology. The future lies in integrating this information together with clinical data relevant to each individual patient. Linkage with clinical protocols will enable personalized management options to be presented to the oncologist of the future. Radiotherapy has the distinction of being the first to have a National Institute for Health and Care Excellence (NICE)-approved AI-based recommendation. There is the opportunity to revolutionize the workflow with many tasks currently undertaken by clinicians taken over by AI-based systems for volume outlining, planning, and quality assurance. Education and training will be essential to understand the AI processes and inputs. Clinicians will however have to feel confident interrogating the AI-derived information and in communicating AI-derived treatment plans to patients.

Understanding Insulin Resistance in NAFLD: A Systematic Review and Meta-Analysis Focused on HOMA-IR in South Asians.

Non-alcoholic fatty liver disease (NAFLD), a metabolic condition, is becoming increasingly common in South Asia. While its clinical diagnosis primarily relies on sonography and altered hepatic biomarkers, the significance of non-hepatic indicators, such as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), in relation to NAFLD requires further examination in the South Asian population due to ethnic differences in these markers. This study examined the relationship between insulin resistance, quantified using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and NAFLD, along with other non-hepatic biomarkers. A thorough literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, and Google Scholar databases, yielding 287 articles. After applying the selection criteria and screening, 22 studies were selected for inclusion in the analysis. We extracted and meta-analyzed the data on HOMA-IR in patients with NAFLD, along with other relevant parameters. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of observational studies, whereas the RoB 2.0 tool was employed for randomized controlled trials (RCTs). The systematic review uncovered that individuals with NAFLD demonstrated statistically significant elevations in HOMA-IR levels, with a weighted mean difference (WMD) of 1.28 (95% confidence interval (CI): 1.00-1.58, I² = 98%, p < 0.0001) when compared to healthy subjects. Additionally, NAFLD patients showed markedly higher fasting blood glucose (FBG) levels, with a combined mean difference of 15.64 mg/dL (95% CI: 11.03-20.25, I² = 92%, p < 0.0001). The analysis also revealed increased triglyceride levels in NAFLD patients, with a pooled mean difference of 42.49 mg/dL (95% CI: 29.07-55.91, I² = 97%, p < 0.0001), and elevated C-reactive protein (CRP) levels, with a pooled mean difference of 2.17 mg/L (95% CI: 2.01-2.33, I² = 23%, p < 0.0001). Interestingly, subgroup analysis indicated that obese NAFLD patients exhibited significantly higher HOMA-IR levels than their non-obese counterparts, with a weighted mean difference of 5.85 (95% CI: 4.88-6.81, I² = 0%, p < 0.0001). Variations in study methodology, diagnostic techniques, and subject demographics were identified as sources of heterogeneity. The analysis found little evidence of publication bias, which lends credibility to the results. In South Asian populations, higher HOMA-IR, triglyceride-glucose (TyG) index, and CRP levels are associated with an increased risk of NAFLD. To improve the understanding and treatment of NAFLD in this specific demographic group, it is necessary to establish uniform diagnostic criteria and conduct additional studies, particularly RCTs.

Spotlight on the Uncommon: A Rare Case of a Malignant Glomus Tumor of the Skin.

Glomus tumors arise from a neuromyoarterial plexus origin, typically demonstrating branching vascular channels and aggregates of specialized glomus cells. They are characteristically identified in the subungual region of the hand, with the presentation of firm, red or blue nodules that are painful and sensitive to temperature. However, very few cases of malignant glomus tumors of the skin have been reported in the medical literature, making this case quite unique. This case report aims to identify an additional case of this rare condition, discuss the treatment plan pursued, and bring awareness to this distinct oncological entity. A 41-year-old female patient initially presented to her primary care physician with an enlarging and painful nodule on her left temple that had been present for the last two months. The patient was then referred to plastic surgery for excision and pathological workup of the mass. The pathology report of the excised specimen revealed a malignant glomus tumor of the skin. The patient was subsequently scheduled for an oncologic workup with medical oncology and radiation oncology, and a wide excision was performed after the pathologic diagnosis. With negative margins from the wide excision and no evidence of disease spread, it was determined that there was no role for systemic therapy or radiation therapy at that time. Biannual dermatologic examination and monitoring are indicated for follow-up. With very few reports of similar cases and little information in the medical literature on the treatment of this type of neoplasm, this is a unique and rare case that warrants discussion and exposure. Making the correct diagnosis, performing a complete workup, and removing the malignant glomus tumor are all essential parts of medical management in this case, and this type of neoplasm should not be excluded when evaluating the presentation of unusual cutaneous lesions.

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy.

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted.

Large language model answers medical questions about standard pathology reports.

This study aims to evaluate the feasibility of large language model (LLM) in answering pathology questions based on pathology reports (PRs) of colorectal cancer (CRC). Four common questions (CQs) and corresponding answers about pathology were retrieved from public webpages. These questions were input as prompts for Chat Generative Pretrained Transformer (ChatGPT) (gpt-3.5-turbo). The quality indicators (understanding, scientificity, satisfaction) of all answers were evaluated by gastroenterologists. Standard PRs from 5 CRC patients who received radical surgeries in Shanghai Changzheng Hospital were selected. Six report questions (RQs) and corresponding answers were generated by a gastroenterologist and a pathologist. We developed an interactive PRs interpretation system which allows users to upload standard PRs as JPG images. Then the ChatGPT's responses to the RQs were generated. The quality indicators of all answers were evaluated by gastroenterologists and out-patients. As for CQs, gastroenterologists rated AI answers similarly to non-AI answers in understanding, scientificity, and satisfaction. As for RQ1-3, gastroenterologists and patients rated the AI mean scores higher than non-AI scores among the quality indicators. However, as for RQ4-6, gastroenterologists rated the AI mean scores lower than non-AI scores in understanding and satisfaction. In RQ4, gastroenterologists rated the AI scores lower than non-AI scores in scientificity (P = 0.011); patients rated the AI scores lower than non-AI scores in understanding (P = 0.004) and satisfaction (P = 0.011). In conclusion, LLM could generate credible answers to common pathology questions and conceptual questions on the PRs. It holds great potential in improving doctor-patient communication.

A deep learning approach to case prioritisation of colorectal biopsies.

AIMS: To create and validate a weakly supervised artificial intelligence (AI) model for detection of abnormal colorectal histology, including dysplasia and cancer, and prioritise biopsies according to clinical significance (severity of diagnosis). MATERIALS AND METHODS: Triagnexia Colorectal, a weakly supervised deep learning model, was developed for the classification of colorectal samples from haematoxylin and eosin (H&E)-stained whole slide images. The model was trained on 24 983 digitised images and assessed by multiple pathologists in a simulated digital pathology environment. The AI application was implemented as part of a point and click graphical user interface to streamline decision-making. Pathologists assessed the accuracy of the AI tool, its value, ease of use and integration into the digital pathology workflow. RESULTS: Validation of the model was conducted on two cohorts: the first, on 100 single-slide cases, achieved micro-average model specificity of 0.984, micro-average model sensitivity of 0.949 and micro-average model F1 score of 0.949 across all classes. A secondary multi-institutional validation cohort, of 101 single-slide cases, achieved micro-average model specificity of 0.978, micro-average model sensitivity of 0.931 and micro-average model F1 score of 0.931 across all classes. Pathologists reflected their positive impressions on the overall accuracy of the AI in detecting colorectal pathology abnormalities. CONCLUSIONS: We have developed a high-performing colorectal biopsy AI triage model that can be integrated into a routine digital pathology workflow to assist pathologists in prioritising cases and identifying cases with dysplasia/cancer versus non-neoplastic biopsies.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: A case series.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases have been reported since its initial description in 1986 by Vuitch et al. when it presented in one patient as a palpable breast mass. We retrospectively reviewed data from 2020 to 2023 of patients diagnosed with PASH by surgical excision. Our 13 cases represent one of the most numerous reported from a single institution. All histologic specimens were examined by a single pathologist. All patients had breast masses on imaging or were clinically evident. Eleven of the patients (84.6%) were diagnosed by surgical excision, whilst only two (15.4%) were diagnosed by core needle biopsy. Imaging revealed no strongly distinctive features for PASH. The age of the patients ranged from 25 to 68 years. All but one of the women were premenopausal at the time of diagnosis. This study suggests that PASH is a lesion whose diagnosis is often incidental and the recommended treatment is more commonly surgical.

Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy.

BACKGROUND: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. METHODS: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. RESULTS: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. CONCLUSION: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.

Socioeconomic and medical determinants of state-level subjective cognitive decline in the United States.

INTRODUCTION: It is important to understand the socioeconomic and medical determinants of subjective cognitive decline (SCD) at a population level in the United States. METHODS: The primary outcomes are state-level rates of SCD and SCD-related functional impairment in adults aged ≥ 45, both measured in the Behavioral Risk Factor Surveillance System from 2016 to 2022. The exposures are state-level rates of poverty, unemployment, homelessness, college education, racial and ethnic minorities, uninsurance, smoking, hypertension, diabetes, and obesity as well as household income and physician density. RESULTS: The strongest state-level associations with rates of SCD were the prevalence of diabetes (rho = 0.64), hypertension (rho = 0.59), and poverty (rho = 0.58; all p < 0.001), and with SCD-related functional impairment were prevalence of poverty (rho = 0.71), diabetes (rho = 0.68), and hypertension (rho = 0.53; all p < 0.001). DISCUSSION: This study highlights critical links between SCD and socioeconomic and medical determinants in adults aged ≥ 45 in the United States, including the prevalence of poverty, diabetes, and hypertension. HIGHLIGHTS: State-level analysis reveals socioeconomic and medical risk factors for subjective cognitive decline (SCD) at a population level. The prevalence of poverty is a critical contributor to the state-level prevalence of SCD. The prevalence of diabetes and hypertension are also strong state-level determinants of SCD. Addressing the burden of cognitive decline at the population level necessitates targeting socioeconomic and medical factors.

Standardization through education of molecular pathology: a spotlight on the European Masters in Molecular Pathology.

Despite advancements in precision medicine, many cancer patients globally, particularly those in resource-constrained environments, face significant challenges in accessing high-quality molecular testing and targeted therapies. The considerable heterogeneity in molecular testing highlights the urgent need to harmonize practices across Europe and beyond, establishing a more standardized and consistent approach in MP laboratories. Professionals, especially molecular pathologists, must move beyond traditional education to cope with this heterogeneity. This perspective addresses critical issues in molecular pathology (MP), such as limited access to high-quality molecular testing, leading to disparities in cancer treatment, and the consequences of inconsistent practices. Recognizing the necessity for a standardized framework for education to address these issues, educational programs play a pivotal role in updating professionals' skills to achieve standardization in MP. European experts from the Steering Committee, the Pathology Section of the European Union of Medical Specialists, and the European Society of Pathology have proposed creating a comprehensive Master's degree program called the "European Masters in Molecular Pathology" (EMMP). This program emerges as a strategic response to the demand for a specialized and standardized framework for education in MP, catering to professionals who concurrently work and study. The program's design aligns with evidence-based education methods, ensuring effective learning and engagement while integrating computational pathology to analyze complex molecular data, enhance diagnostic accuracy, and improve treatment outcomes. EMMP's structured curriculum, strategic partnerships, and regular updates underscore its significance in standardizing MP practices. Exploring future developments, this perspective delves into technology integration and interdisciplinary collaboration, anticipating ongoing advances and harmonization. Challenges and future directions in MP education are discussed, emphasizing the necessity for dynamic curriculum updates, seamless technology integration, and interdisciplinary cooperation. This perspective underscores EMMP's pivotal role in preparing pathologists for this dynamic field, advocating continuous advancements in education and training to uphold excellence in MP practices and maintain the highest patient care standards.

Galileo-an Artificial Intelligence tool for evaluating pre-implantation kidney biopsies.

BACKGROUND: Pre-transplant procurement biopsy interpretation is challenging, also because of the low number of renal pathology experts. Artificial intelligence (AI) can assist by aiding pathologists with kidney donor biopsy assessment. Herein we present the "Galileo" AI tool, designed specifically to assist the on-call pathologist with interpreting pre-implantation kidney biopsies. METHODS: A multicenter cohort of whole slide images acquired from core-needle and wedge biopsies of the kidney was collected. A deep learning algorithm was trained to detect the main findings evaluated in the pre-implantation setting (normal glomeruli, globally sclerosed glomeruli, ischemic glomeruli, arterioles and arteries). The model obtained on the Aiforia Create platform was validated on an external dataset by three independent pathologists to evaluate the performance of the algorithm. RESULTS: Galileo demonstrated a precision, sensitivity, F1 score and total area error of 81.96%, 94.39%, 87.74%, 2.81% and 74.05%, 71.03%, 72.5%, 2% in the training and validation sets, respectively. Galileo was significantly faster than pathologists, requiring 2 min overall in the validation phase (vs 25, 22 and 31 min by 3 separate human readers, p < 0.001). Galileo-assisted detection of renal structures and quantitative information was directly integrated in the final report. CONCLUSIONS: The Galileo AI-assisted tool shows promise in speeding up pre-implantation kidney biopsy interpretation, as well as in reducing inter-observer variability. This tool may represent a starting point for further improvements based on hard endpoints such as graft survival.