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In 2016 the Choosing Wisely guidelines advised against routine performance of a sentinel lymph node biopsy (SLNB) in women ≥ 70 years of age with clinically node negative (cN0), early-stage, oestrogen receptor positive/ human epidermal growth factor receptor 2 negative (ER+/HER2-), invasive breast cancer. The argument in favour of its continued performance is that it may serve as a useful guide for subsequent management. This systematic review was performed in accordance with the PRISMA guidelines. Studies reporting on rate of adjuvant chemotherapy, adjuvant radiotherapy and performance of completion axillary lymph node dissection (cALND) post SLNB in women aged ≥ 65 years with cN0, early-stage, ER+/HER2-, invasive breast cancer were included. A random effects meta-analysis was performed with summary estimates made using the Mantel-Haenszel method. Dichotomous outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Ten retrospective studies across 4 countries. Of 105,514 patients, 15,509 had a positive SLNB and 90,005 had a negative SLNB. On meta-analysis, a positive SLNB was significantly associated with receipt of adjuvant chemotherapy (OR 4.64 (95% CI 3.18, 6.77), P < .00001), adjuvant radiotherapy (1.71 (95% CI 1.18, 2.47), P = .005) and undergoing completion axillary lymph node dissection (OR 68.97 (95% CI, 7.47, 636.88), P = .0002). Adjuvant treatment decisions continue to be influenced by SLNB positivity in the era of the Choosing Wisely guidelines. The effects of a positive SLNB and subsequent treatments on outcomes remain inconclusive. However, it is likely clinicians are continuing to over-investigate and over-treat this cohort., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Infections by multidrug-resistant organisms (MDROs) pose significant public health challenges, including increased mortality rates, healthcare costs, and significant impacts on the quality of life for patients. Utilizing a systematic review methodology adhering to PRISMA guidelines, we performed a comprehensive search across three databases, identifying 20 relevant studies that investigated the psychological effects of infections due to MDROs on hospitalized adults. The primary outcomes examined included depression, anxiety, and other psychosocial impacts, while secondary outcomes included patient and caregiver understanding of the infection. Findings revealed consistent associations between contact isolation due to MDRO infections and heightened levels of depression and anxiety among patients, although evidence regarding the impact on anger was mixed. Other psychological aspects, such as feelings of stigmatization and reduced healthcare provider interactions, were also recorded. The current systematic review highlights the importance of addressing these psychological effects through holistic, patient-centered care approaches, emphasizing the need for better communication and comprehensive education for both patients and healthcare providers. Our findings suggest that mitigating the psychological burden of MDROs can enhance overall patient care and outcomes and call for further research to optimize care strategies for patients hospitalized for infections due to MDROs.

Purpose of Review: Homologous recombination repair deficiency (HRD) increases breast cancer susceptibility and influences both prophylactic and active management of breast cancer. This review evaluates HRD testing and the therapeutic implications of HRD in a global context., Recent Findings: Ongoing research efforts have highlighted the importance of HRD beyond BRCA1/2 as a potential therapeutic target in breast cancer. However, despite the improved affordability of next-generation sequencing (NGS) and the discovery of PARP inhibitors, economic and geographical barriers in access to HRD testing and breast cancer screening do not allow all patients to benefit from the personalized treatment approach they provide. Advancements in HRD testing modalities and targeted therapeutics enable tailored breast cancer management. However, inequalities in access to testing and optimized treatments are contributing to widening health disparities globally., (© 2024. The Author(s).)

Purpose: There are a wide variety of intraoperative techniques available in breast surgery to achieve low rates for positive margins of excision. The objective of this systematic review was to determine the pooled diagnostic accuracy of intraoperative breast margin assessment techniques that have been evaluated in clinical practice., Methods: This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the diagnostic accuracy of intraoperative margin assessment techniques. Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included in the meta-analysis. A bivariate model for diagnostic meta-analysis was used to determine overall pooled sensitivity and specificity., Results: Sixty-one studies were eligible for inclusion in this systematic review and meta-analysis. Cytology demonstrated the best diagnostic accuracy, with pooled sensitivity of 0.92 (95 % CI 0.77-0.98) and a pooled specificity of 0.95 (95 % CI 0.90-0.97). The findings also indicate good diagnostic accuracy for optical spectroscopy, with a pooled sensitivity of 0.86 (95 % CI 0.76-0.93) and a pooled specificity of 0.92 (95 % CI 0.82-0.97)., Conclusion: Pooled data indicate that optical spectroscopy, cytology and frozen section have the greatest diagnostic accuracy of currently available intraoperative margin assessment techniques. However, long turnaround time for results and their resource intensive nature has prevented widespread adoption of these methods. The aim of emerging technologies is to compete with the diagnostic accuracy of these established techniques, while improving speed and usability., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The overamplification of human epidermal growth factor (HER2) in breast cancer (BC) has been the subject of numerous research publications since its discovery in 1987. This is the first bibliometric analysis (BA) conducted on HER2-positive (HER2+) BC. The purpose of this BA is to analyze the published research on HER2+ BC from 1987 to 2024, highlighting the most significant scientific literature, as well as the main contributing authors and journals, and evaluating the impact of clinical and lab-based publications on HER2+ BC research., Methods: The Web of Science Core Collection (WoSCC) was searched using the terms "Breast cancer" OR "Breast carcinoma" OR "Breast tumor" AND "HER2 positive" OR "HER2+". The search was limited by publication year (1987-2024) and only full English articles were included. WoS returned 7,469 relevant results, and from this dataset, a bibliometric analysis was conducted using the "analyze results" and "journal citation report" functions in WoS and the VOSviewer 1.6.16 software to generate bibliographic coupling and co-citation analysis of authors., Results: The analysis encompassed a total of 7,469 publications, revealing a notable increase in the annual number of publications, particularly in recent years. The United States, China, Italy, Germany, and Spain were the top five most prolific countries. The top five significant institutions that published HER2+ research were the University of Texas System, Unicancer, UTMD Anderson Cancer Center, Harvard University, and University of California System. Breast Cancer Research and Treatment , Clinical Cancer Research , and Clinical Breast Cancer were the top three notable journals with the highest number of HER2+ BC publications. Dennis Slamon (Nc = 45,411, H-index = 51) and Jose Baselga (Nc = 32,592, H-index = 55) were the most prolific authors. Evolving research topics include anti-HER2 therapy in the neoadjuvant setting, treatment of metastatic HER2+ BC, and overcoming therapy resistance., Conclusion: This study provides an overview of HER2+ BC research published over the past three decades. It provides insight into the most cited papers and authors, and the core journals, and identifies new trends. These manuscripts have had the highest impact in the field and reflect the continued evolution of HER2 as a therapeutic target in BC., Competing Interests: The 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 © 2024 Ali-Thompson, Daly, Dowling, Kilkenny, Cox, McGrath, AlRawashdeh, Naidoo, Power and Hill.)

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background  Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis  We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods  In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results  Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions  Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Purpose of Review: In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in the treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss the current uses, limitations, and future directions for PARP inhibitors (PARPis) in the treatment of breast cancer., Recent Findings: Following the results of the OlympiAD and EMBRACA trials, PARPis were approved in HER2-negative breast cancer with a germline BRCA mutation. We reviewed this class of drugs' mechanism of action, efficacy, and limitations, as well as further studies that discussed resistance, impaired homologous recombination repair (HRR), and the combination of PARPis with other drugs. Improving understanding of HRR, increasing the ability to target resistance, and combining PARPis with other novel agents are continuing to increase the clinical utility of PARPis., (© 2024. The Author(s).)

Objectives: To perform the first meta-analysis regarding the pooled risk of malignancy (ROM) of each category of the Yokohama system for reporting breast fine-needle aspiration, as well as assess the latter's diagnostic accuracy using this new system., Methods: Two databases were searched, followed by data extraction, study quality assessment, and statistical analysis., Results: The "Insufficient," "Benign," "Atypical," "Suspicious," and "Malignant" Yokohama system categories were associated with a pooled ROM of 17% (95% CI, 10%-28%), 1% (95% CI, 1%-3%), 20% (95% CI, 17%-23%), 86% (95% CI, 79%-92%), and 100% (95% CI, 99%-100%), respectively. When both "Suspicious" and "Malignant" interpretations were regarded as cytologically positive, sensitivity (SN) was 91% (95% CI, 87.6%-93.5%) and false-positive rate (FPR) was 2.33% (95% CI, 1.30-4.14%). A summary receiver operating characteristic curve was constructed and the pooled area under the curve was 97.3%, while the pooled diagnostic odds ratio was 564 (95% CI, 264-1,206), indicating a high level of diagnostic accuracy. When only "Malignant" interpretations were regarded as cytologically positive, the pooled FPR was lower (0.75%; 95% CI, .39%-1.42%) but at the expense of SN (76.61%; 95% CI, 70.05%-82.10%)., Conclusions: Despite Yokohama's system early success, more data would be needed to unravel the system's value in clinical practice., (© American Society for Clinical Pathology, 2022.)

The study of the effects of SARS-CoV-2 infection and/or vaccination on semen fluid analysis (SFA) parameters is still incomplete. The aim of this study is to assess the effect of COVID-19 infection and vaccination on sperm parameters for a sample of individuals visiting multi-infertility clinics in Jordan. SFA records were collected retrospectively between September and November 2021 and analyzed using Jamovi software (version 2.2.5 for Windows); p-values < 0.05 were considered statistically significant. Sperm concentration, progressive motility, normal morphology, and semen liquefaction time, volume, and viscosity were compared among two data categories. In the first category of data, SFA records from 354 participants were separated into four groups: only vaccinated, infected and vaccinated, neither infected nor vaccinated, and only infected. In the other category, SFA from 49 subjects before their infection and/or vaccination and after were classified into the same mentioned groups and analyzed. There were no statistically significant differences between the studied parameters in the SFA records in the first data category and the second. Nevertheless, the sperm concentration was higher among vaccinated subjects compared to unvaccinated ones (p = 0.04). It is concluded that SARS-CoV-2 infection and vaccines have no negative effects on SFA parameters.

Background: COVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics. The authors aim to evaluate the correlation between variability in the host genetics and the severity and susceptibility towards COVID-19 in this study., Methods: Following the PRISMA guidelines, we retrieved all the relevant articles published until September 15, 2021, from two online databases: PubMed and Scopus., Findings: High-risk HLA haplotypes, higher expression of ACE polymorphisms, and several genes of cellular proteases such as TMPRSS2, FURIN, TLL-1 increase the risk of susceptibility and severity of COVID-19. In addition, upregulation of several genes encoding for both innate and acquired immune systems proteins, mainly CCR5, IFNs, TLR, DPPs, and TNF, positively correlate with COVID-19 severity. However, reduced expression or polymorphisms in genes affecting TLR and IFNλ increase COVID-19 severity., Conclusion: Higher expression, polymorphisms, mutations, and deletions of several genes are linked with the susceptibility, severity, and clinical outcomes of COVID-19. Early treatment and vaccination of individuals with genetic predisposition could help minimize the severity and mortality associated with COVID-19., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Paragangliomas are rare, non-epithelial neuroendocrine neoplasms originating in paraganglia, for instance the adrenal medulla, or at extra-adrenal locations. The aim of this study was to review the literature regarding abdominal extra-adrenal paragangliomas diagnosed pre-operatively with fine-needle biopsy (FNA and/or FNB). The PubMed database was searched to identify such cases, using a specific algorithm and inclusion/exclusion criteria. An unpublished case from our practice was also added to the rest of the data, resulting in a total of 36 cases for analysis. Overall, 24 (67%) lesions were found in females, whereas 12 (33%) in males. Most (21/36; 58.33%) were identified around and/or within the pancreatic parenchyma. FNA and/or FNB reached or suggested a paraganglioma diagnosis in 17/36 cases (47.22%). Of the preoperative misdiagnoses, the most common was an epithelial neuroendocrine tumor (NET). Regarding follow-up, most patients were alive with no reported recurrence; however, 5/36 patients exhibited a recurrence or a widespread disease, whereas one patient died 48 months following her diagnosis. In two patients, transient hypertension was reported during the EUS-FNA procedure. In conclusion, this study showed that the preoperative diagnosis of these lesions is feasible and, while diagnostic pitfalls exist, they could significantly be avoided with the application of immunochemistry.

The COVID-19 pandemic shifted pathology education in medical schools worldwide towards online delivery. To achieve this goal, various innovative platforms were used by pathology educators and medical students, facilitating both synchronous and asynchronous learning. The aim of this study was to review the published evidence regarding remote pathology teaching at the medical school level during this period, present our own experience, and provide some perspectives regarding the best mode of pathology teaching post-pandemic. Among its advantages, virtual pathology education was considered among students and educators as convenient, flexible, and engaging, while learning outcomes were met and students' academic performance was in general satisfactory. However, several challenges were faced. For instance, suboptimal internet connection compromised the flow of classes and was even associated with a lower academic performance. The lack of hands-on laboratory activities, such as operating the light microscope and tissue grossing, and the reduced student interactions among themselves and their instructors, were also pointed out as significant drawbacks of remote pathology education. Whereas online education has multiple advantages, experiencing the physical university environment, in-person interactions and teamwork, exposure to the "hidden curriculum", and hands-on activities are vital for medical school education and future student development. In conclusion, the implementation of a blended approach in pathology education-where online and face-to-face sessions are jointly used to promote students' engagement, interaction with their instructors and peers, and learning-could be the most optimal approach to pathology teaching in medical schools post-pandemic.

Accurate detection of SARS-CoV-2, the pathogen causing the global pandemic of COVID-19, is essential for disease surveillance and control. Quantitative reverse transcription PCR (RT-qPCR) is considered the reference standard test for the diagnosis of SARS-CoV-2 by the World Health Organization and Centers for Disease Control and Prevention. However, its limitations are a prompt for a more accurate assay to detect SARS-CoV-2, quantify its levels, and assess the prognosis. This article aimed to systematically review the literature and assess the diagnostic performance of droplet digital PCR (ddPCR), also to evaluate its potential role in prognosis and management of COVID-19 patients. PubMed and Scopus databases were searched to identify relevant articles published until 13 July 2021. An additional PubMed search was performed on 21 October 2021. Data from the 39 eligible studies were extracted and an overall 3651 samples from 2825 patients and 145 controls were used for our qualitative analysis. Most studies reported ddPCR was more accurate than RT-qPCR in detecting and quantifying SARS-CoV-2 levels, especially in patients with low viral loads. ddPCR was also found highly effective in quantifying SARS-CoV-2 RNAemia levels in hospitalized patients, monitoring their disease course, and predicting their response to therapy. These findings suggest ddPCR could serve as a complement or alternative SARS-CoV-2 tool with emerging diagnostic, prognostic, and therapeutic value, especially in hospital settings. Additional research is still needed to standardize its laboratory protocols, also to accurately assess its role in monitoring COVID-19 therapy response and in identifying SARS-CoV-2 emerging variants.