Negative Cases Research Articles

Incidence and outcomes of Merkel cell carcinoma related to Merkel cell polyomavirus status in Iceland in 1981-2023

BackgroundImpact of Merkel cell polyomavirus (MCPyV) associated Merkel cell carcinoma (MCC) has not been assessed in the Icelandic population, nor in a whole population elsewhere. ObjectivesThe primary objective was to assess trends in the incidence of MCC in Iceland and the association with MCPyV. Secondary objectives aimed to analyze MCC outcomes. MethodsIn this retrospective cohort study, patients diagnosed with MCC between 1981 and 2021 were identified from the Icelandic Cancer Registry. Patients were separated into two groups based on MCPyV immunochemistry staining. Age-standardized incidence was calculated and Joinpoint analysis was used to assess incidence trends. A Cox proportional hazards model was used to assess survival differences between the two groups. ResultsOverall incidence of MCC increased from 0.015 to 0.26 per 100,000 persons, though the incidence of MCPyV positive cases recently decreased while negative cases increased. MCPyV negative tumors were associated with sun exposure (p<0.01), a history of keratinocyte carcinoma, smaller tumor size, and lower overall survival. LimitationsEven with population level data, comprehensively investigating associations with MCC is difficult due to its rarity. ConclusionMCPyV negative MCC tumors were associated with lower survival despite smaller tumor size. Thus, MCPyV status could be an important prognostic biomarker.

Asymptomatic malaria and predictors among migrant farmworkers East Shewa zone Oromia Ethiopia

Asymptomatic malaria can impact existing malaria control and elimination efforts around the world, particularly in Africa, where the majority of malaria cases and death occurs. This is a cross-sectional study aimed to determine the prevalence and predictors of asymptomatic malaria among migrant farmworkers from June to July 2020 in the Upper Awash Agro-industry, East Shewa zone, Oromia Regional State, Ethiopia. A total of 254 migrant farmworkers without signs and symptoms of malaria were enrolled. Data on socio-demographic characteristics and malaria prevention practices were obtained through a structured questionnaire. Venous blood samples were collected and diagnosed using microscopy, rapid diagnostic tests, and polymerase chain reaction (PCR). Data were coded, entered, and analyzed using SPSS version-21 statistical software. Multivariable logistic regression was used to assess associated factors. A p < 0.05 was considered statistically significant. The overall prevalence of asymptomatic malaria among farmworkers in this study was 5.1% [95% CI 1.6, 6.7]. The proportions of Plasmodium falciparum was 90.0% (9/10) while it was 10.0% (1/10) for Plasmodium vivax. Out of the microscopy and/or RDT-confirmed malaria cases, (n = 9; 100%) were confirmed to be P. falciparum by nested PCR, while (n = 3/122; 2.46%) were found to be P. falciparum among 50% negative cases with the microscopy and/or RDT. The gametocyte stage was detected in 40% of microscopically positive cases out of which 44.4% belongs to P. falciparum. Home area/origin of migrant laborers [AOR = 6.08, (95% CI 1.08, 34.66)], family history of malaria [AOR = 8.15, (95% CI 1.43, 46.44)], and outdoor sleeping [AOR = 10.14, (95% CI 1.15, 89.14)] were significantly associated with asymptomatic malaria. In conclusion, asymptomatic malaria was detected among farmworkers in the study area and it was significantly associated with outdoor sleeping, home area, and family history of malaria. Prevention tools and control strategies, particularly focusing on migrant farmworkers, should be considered to support the ongoing malaria control and elimination effort in Ethiopia.

Streamlined two-step fragment analysis PCR and exome sequencing of RFC1 for diagnostic testing of suspected CANVAS patients.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two-step PCR consisting of a short-allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection. Exome sequencing of RFC1 was additionally foreseen to resolve potential compound heterozygosity cases. Specificity of our approach was evaluated using ataxia patients with known non-CANVAS diagnoses, and optimized using Southern blot confirmed CANVAS patients. We evaluated our approach by testing patients consecutively referred for clinically suspected CANVAS using first the two-step PCR, followed by exome sequencing. Our approach was able to accurately identify negative and confirm positive cases in prospectively collected suspected CANVAS patients presenting with at least three typical clinical signs. The proposed testing approach provides an alternative method able to clearly distinguish between CANVAS negative and positive cases and can be easily incorporated into the genetic diagnostic laboratory workflow.

Pixel-wise segmentation of cells in digitized Pap smear images

A simple and cheap way to recognize cervical cancer is using light microscopic analysis of Pap smear images. Training artificial intelligence-based systems becomes possible in this domain, e.g., to follow the European recommendation to screen negative smears to reduce false negative cases. The first step for such a process is segmenting the cells. A large and manually segmented dataset is required for this task, which can be used to train deep learning-based solutions. We describe a corresponding dataset with accurate manual segmentations for the enclosed cells. Altogether, the APACS23 (Annotated PAp smear images for Cell Segmentation 2023) dataset contains about 37 000 manually segmented cells and is separated into dedicated training and test parts, which could be used for an official benchmark of scientific investigations or a grand challenge.

A Systematic Review &amp; Meta-Analysis on Criteria for Transcranial Motor Evoked Potential for Intraoperative Neuromonitoring during Spine Surgeries

Abstract Background Spine Surgery is the definitive treatment and indication for many traumatic spine illnesses, as well as several pathologies and deformities. Surgery in such a vital organ, formed in its core of the neural pathway that controls the whole of the human body, must be as safe, and least risky as possible, so as to prevent injuries to the neural pathway, or the surrounding vessels, or vital organs. Such great importance of the spine and the spinal cord, has urged surgeons and researchers to create techniques through which spine surgeries are well monitored, and the efficacy and normal physiology is well assessed intraoperatively. Objective to conduct a systematic review and meta-analysis of what has been published of the studies using transcranial motor evoked potential for intraoperative neuromonitoring during spine surgeries. This is for acquiring the best criteria for transcranial motor evoked potential (TcMEP) utilization for intraoperative neuromonitoring, as well as identifying the most accurate alarm point for TcMEP during intraoperative neuromonitoring. Patients and Methods a comprehensive and detailed search of literature was conducted through the Pubmed, Google Scholar, and Research Gate databases including articles related to intraoperative neuromonitoring modalities and transcranial motor evoked potential alarm points and criteria. Searches were performed with a combination of MeSH (medical subject headings). Only Studies published in the English Language with no lower date limit were included. The following search string was used in all databases; (“Intraoperative Neuromonitoring” or “Transcranial Motor Evoked Potential”). Results In a prospective study conducted in 2018, performed on 2867 patients, using a 70 % decrease in amplitude of the TcMEP curve as an alarm point during high-risk spinal surgeries, the number of true positive to false positive cases was found to be 126/234, while the number of true negative cases to false negative cases was found to be 2362/9 cases in total. The study demonstrates the necessity of intraoperative neuromonitoring for high-risk spinal surgery. 136 cases in this study were identified as rescue cases, as intraoperative TcMEP alert occurred and intraoperative maneuverings were done to overcome those alerts, hence hindering occurrence of postoperative neural deficit. Conclusion As regards different TcMEP alarm point values, it has been concluded that an alarm point of 50-60% decrease in amplitude of TcMEP is a more sensitive alarm point, than a higher value alarm point of the same modality. An alarm point of &amp;gt; 70% decrease in amplitude has a much less sensitivity value than lower alarm points, which in turn will result in a lot of missed adverse events, and a higher percentage of false negative values.

A new antigen test device for rapid influenza A and B detection

IntroductionTests for detection of influenza must demonstrate high sensitivity and specificity, affordability, and rapidness. MethodsThis study aimed to evaluate the performance of the LabOn-Time™ Influenza A + B Rapid test device (BMT Diagnostics, Ltd), as compared to Real-time polymerase chain reaction (RT-PCR), in identifying influenza A/B among 183 nasopharyngeal samples collected between February and April 2023 from patients with Influenza-like symptoms. ResultsOut of 70 participants with a positive RT-PCR result, 53 (75.7 %) had a positive LabOn-Time result. The LabOn-Time kit had a sensitivity of 75.7 % and specificity of 100 %. The odds ratio for showing a false negative LabOn-Time result for influenza B, compared to influenza A was 5.24 (95%CI: 1.35–20.31). All false negative LabOn-Time samples had a RT-PCT cycle threshold ≥20. Mean time from symptom onset was significantly lower in the false negative LabOn-Time cases compared to the positive cases (36 ± 15.3 vs. 42.6 ± 10.1, respectively). The mean number of symptoms reported per patient was significantly higher in positive compared to negative LabOn-Time cases (2.5 ± 0.5 vs. 1.9 ± 0.4, p < 0.001). ConclusionsThe LabOn-Time device, which is very simple and intuitive to operate, could significantly contribute to early detection of influenza A/B infection.

Type I or Type II Endometrial Carcinoma? Role of BRCA1 Immunohistochemistry.

Investigation of diagnostic and prognostic relevance of BRCA1 immunohistochemistry (IHC) in endometrial carcinoma. Ninty four specimens of endometrial carcinomas were evaluated. Full sections stained with hematoxylin & eosin were revaluated for assessment of tumor type, grade, myometrial, & lympho-vascular invasion (LVI). Tissue microarray blocks were constructed using the pencil tip method and immunostained with Anti-BRCA1 antibody. BRCA1 was correlated with clinicopathological parameters as well as disease free survival and overall survival. There was a statistically significant difference (P=0.001) between serous and endometroid carcinomas regarding BRCA1 expression where most cases of serous carcinoma showed negative expression. No statistically significant difference was found between BRCA1 positive and negative cases regarding disease free survival (DFS) or overall survival. Serous histotype, high grade, advanced stage, and omental deposits were the parameters significantly associated with decreased DFS. Results of this study can support inclusion of BRCA1 IHC in a panel to differentiate both endometroid and serous carcinomas. The current study found no prognostic relevance for BRCA1 in terms of overall survival and disease-free survival.

Diagnosis of oral cancer using deep learning algorithms

The aim of this study was to use deep learning for the automatic diagnosis of oral cancer, employing images of the lips, mucosa, and oral cavity. A deep convolutional neural network (CNN) model, augmented with data, was proposed to enhance oral cancer diagnosis. We developed a Mobile Net deep CNN designed to detect and classify oral cancer in the lip, mucosa, and oral cavity areas. The dataset comprised 131 images, including 87 positive and 44 negative cases. Additionally, we expanded the dataset by varying cropping, focus, rotation, brightness, and flipping. The diagnostic performance of the proposed CNN was evaluated by calculating accuracy, precision, recall, F1 score, and area under the curve (AUC) for oral cancer. The CNN achieved an overall diagnostic accuracy of 90.9% and an AUC of 0.91 with the dataset for oral cancer. Despite the limited number of images of lips, mucosa, and oral cavity, the CNN method developed for the automatic diagnosis of oral cancer demonstrated high accuracy, precision, recall, F1 score, and AUC when augmented with data.

Invasive methods for detection of Helicobacter pylori infection in gastric disorders patients undergoing endoscopy from Mosul city, Iraq

Objectives. The identification of H. pylori in Iraq lacks a standardized technique and there is limited information on the efficacy of different diagnostic methods. This research aims to determine the prevalence of H. pylori and evaluate the effectiveness of invasive techniques, namely the Rapid Urease Test (RUT), histopathological examination, and ure A gene by PCR, for detecting H. pylori. Method. Gastric biopsies specimens were collected from 50 patients with gastric disorders who underwent endoscopy after meeting the inclusion criteria. Patients were classified into H. pylori-positive cases and negative cases by testing positive with at least two of the three testing methods, according to the case definition used in the study. Outcomes. Of the 50 gastric biopsies, 58% were H. pylori-positive cases, 26% were H. pylori -negative cases, and the last 16% were indeterminate case according to cases definition. The ure A gene PCR was the most sensitive method, followed by histopathological examination and RUT testing, with sensitivities of 96.6%, 86.2% and 79.3% respectively. Histopathology examination was the most specific with a specificity of 95.2%, followed by ure A gene PCR with 85.7%, while RUT was the least specific with a specificity of 81%. Conclusion. The current study revealed a moderate prevalence of H. pylori infection compared with previous studies. The sensitivity and specificity of the three invasive methods varied, and a combination of two methods may be necessary for a definitive diagnosis of H. pylori infection.

Retrospective Analysis Study of False-Positive Amphetamine Immunoassay Cases and Negative Cases after Withdrawal while Taking Herbal Medicine-Containing Ephedra Sinica Confirmed in a Korean Medicine Obesity Clinic

Retrospective Analysis Study of False-Positive Amphetamine Immunoassay Cases and Negative Cases after Withdrawal while Taking Herbal Medicine-Containing Ephedra Sinica Confirmed in a Korean Medicine Obesity Clinic

Morphology, immunophenotype, and suggested diagnostic criteria of TCL1 family–negative T-prolymphocytic leukemia

Abstract Objectives We sought to investigate the morphologic and immunophenotypic characteristics of TCL1 family–negative T-cell prolymphocytic leukemia (T-PLL) Methods Twenty cases of TCL1 family–negative T-PLL were studied. Results The doubling time of leukemic cells ranged from less than 2 days to more than 5 years, with a median of 5.5 months. Leukemic cells were small to medium-sized, with round to irregular nuclei, variably condensed chromatin, and small amounts of agranular cytoplasm. A visible nucleolus was identified in 11 (55%) cases. Cytoplasmic blebs/protrusions were identified in all cases, but their occurrence was highly variable from case to case. Bone marrow biopsy showed an interstitial pattern in 90% of cases and a diffuse pattern in the remaining 10% of cases. Flow cytometric immunophenotypic analysis showed that the leukemic cells in all cases were CD4 positive; 3 (15%) also showed concurrent CD8 expression. All cases were positive for CD2 and CD5. Surface CD3 and CD7 were positive in 19 of 20 (95%) cases, and all CD3-positive cases expressed the T-cell receptor αβ. Compared with prototypic T-PLL cases, these 2 groups shared many immunophenotypic findings, except CD8 and CD26, both of which were more commonly expressed in prototypic T-PLL cases. Conclusions TCL1 family–negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αβ phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL.

Evaluation of Efficacy of Serum Adenosine Deaminase Values for Detection of Pulmonary and Extra Pulmonary Tuberculosis

Background Tuberculosis is one of the leading cause of morbidity and mortality worldwide and in Nepal. Despite advances in its diagnosis, majority of the cases still go undetected. These account for sputum smear negative and extra pulmonary cases where demonstration of the microorganism is challenging. ADA an enzyme found in all mammalian species is found raised in various effusion body fluids of organs affected by the disease. Time tested studies have also shown that serum values of ADA are elevated in patients affected with the disease thus can aid as supportive evidence in doubtful cases.MethodsAn Analytical cross sectional Hospital Based study involving 110 with 75 cases and 35 healthy participants was conducted in College of Medical Sciences for 5 months from January to June 2024. Serum ADA levels were measured in all participants, diseased and healthy and collected data was analyzed for significance.ResultsThe mean Serum ADA level in TB patients was found to be 47.01 and that of healthy participants was 14.68. Significant difference in the mean serum ADA level between TB and non TB patients (p-value &lt; 0.001) was found concluding that TB patients have high serum ADA level. Comparisons between mean serum ADA levels in Different types of TB found no significant difference among them with all p- values in each pair being more than 0.5 suggesting that serum ADA levels rise in all forms of TB.Conclusions Serum ADA values are raised in all forms of tuberculosis and can serve as a supportive evidence in patients with Smear negative and Extrpulonary TB where microorganisms is difficult to demonstrate. However further validation need to be done by more studies in the future.

INTRA-FAMILIAL TRANSMISSION OF HEPATITIS B VIRUS IN ADEN -YEMEN

Hepatitis B virus (HBV) is a major challenge to public health worldwide. Close contacts between susceptible family members and the index cases who live with HBV infection increase the rate intra-familial transmission of HBV. So our study aimed to determine the prevalence of HBV infection among family members of confirmed positive HBV patients and to identify the intra and extra-familial risk factors contributing for transmission of HBV infection among those members. Analytical cross-sectional study was conducted on 100 family members who belong to the 14 index cases were included in this study, the average was 7.1(100/14) members. HBsAg in both index cases and family members was determined by using ELISA kit. Analysis of the data was performed by using SPSS (Version 21), the quantitative data were expressed as mean values, (SD) because the data was normal distributed. The qualitative data was expressed as percentages and χ2 test was used for comparison of two variables to determine the p- value where &lt;0.05 was considered statistically significant. They were 50 (50 %) males with a total mean± SD of age were 25±15.9 years. The overall prevalence of HBV infection was 19 (19. 0%). The highest rates were 41.2% in age group 30—39 years, 22% males, 26.7% married, 19.4% among those family members who were in close contact with female index cases and 40% father relatives. A statistically significance association between HBV infection and age group 30—39 years (p=0.011). There were no positive cases was found among those members who were vaccinated against HBV and no significant association between HBV infection and either intra or extra risk factors among family members. It can be concluded that Intra-familial transmission of HBV infection was high among family member in Yemen. The highest prevalence was found in age group 30-39 years, males, married and among those family members who were in close contact with female index cases. The most frequent relatives with HBV infection were fathers, while a negative HBV cases was observed among mothers and wives and vaccinated members. There were no significant association between HBV infection and either intra or extra risk factors among family members.

Can CAPRIN-1 Be Responsible for the Recurrence Potential of Odontogenic Keratocysts?

The purpose of this retrospective study is to compare dentigerous cysts and odontogenic keratocysts for cytoplasmic activation/proliferation - associated protein-1 antibodies via immunohistochemical staining to obtain a new perspective about the specific behavioural characteristics of odontogenic keratocysts at the molecular level. Forty dentigerous cysts (DC) and forty odontogenic keratocysts (OKC) tissue samples were examined using immunohistochemical staining to detect cytoplasmic activation/proliferation - associated protein-1 (CAPRIN-1) antibodies. Nuclear and/or cytoplasmic staining was evaluated as "positive". Cell staining rate (%) and cell staining intensity were determined, and a staining intensity distribution (SID) score was calculated for each sample. Cases were considered "negative" if they showed no staining for CAPRIN-1 antibodies, thus were given a SID score of zero. According to the SID scores, the expression levels were rated as negative, mild, moderate, or high. Of 80 samples, 16 that could adversely affect immunohistochemical evaluation were excluded. Ten negative, 21 positive and three negative, 30 positive CAPRIN-1 expressions were observed in DC and OKC groups, respectively. The difference between the negative and positive cases within groups was significant only in the OKC group (P = 0.000). The SID score range and mean were 0 to 160 and 31.1 (SD 35.7) for DC and 0 to 160 and 57.3 (SD 42.3) for OKC groups. CAPRIN-1 expression was significantly higher in the OKC group (P = 0.043). The molecular basis for increased mitotic activity, high recurrence rates or presence of satellite cysts in odontogenic keratocysts may be attributed to the expression of cytoplasmic activation/proliferation - associated protein-1.

A NOVEL COVID-19 CLASSIFICATION METHOD BASED ON CURE CLUSTERING

COVID-19 is a serious disease that spreads rapidly and affects the world. Alternative methods based on machine learning are recommended to diagnose COVID-19 positive and negative cases cheaper and faster. However, as the data size increases, problems such as space requirement or classification time may arise. KNN (K-nearest neighbor), a simple but effective machine learning method, is widely used in various fields. However, the effectiveness of the KNN algorithm decreases considerably when the sample size is large and the number of features is too large. To solve these problems, it is important to use datasets more effectively and to select meaningful parts of the data. The current study proposes an improved neighborhood-based classification method called CURE-NN and compares its performance with standard NN and KNN algorithms. The proposed CURE-NN method obtains reduced structural information from the data by applying clustering before classification to use the dataset more effectively. The resulting reduced structural information was used as a training set in the classification process. The proposed method was applied to the COVID-19 dataset. With this method, while the classification success is preserved as much as possible compared to the NN and KNN methods, the data used in the test phase is reduced by up to 96%. Experimental results show that the reduced data obtained based on structural information can be used instead of the entire data set. In addition, the method works by using only one neighbor, thus eliminating the need for the K parameter compared to the KNN algorithm.

Stress and Coping of Self-Quarantined People Focusing on Negative Cases of the Coronavirus Disease: A Qualitative Study

Background: In South Korea, many people have experienced self-quarantine due to coronavirus disease (COVID-19). This study explored stress, coping, and post-quarantine changes among people who were self-quarantined because of close contact but tested negative for COVID-19 in the early days of the pandemic.Methods: Qualitative interviews were conducted with four focus groups, each comprising five people. Data were analyzed using inductive content analysis.Results: Three categories of stress and coping during self-quarantine and post-quarantine changes emerged. First, the category of content related to stress comprised “problems that are difficult to handle alone.” The subcategories were “painful body and mind,” “the experience of being in a jail without bars,” and “repeated internal and external conflicts.” Second, the category for various stress-coping methods was labeled “struggling my way,” and the subcategories were “coping methods that helped me overcome” and “coping methods that added difficulty.” Finally, the category for changes after self-quarantine was labeled “more mature me.” The subcategories involved “thorough observation of infection prevention measures in daily life,” “living together,” and “a new realization of life.”Conclusions: Our findings contribute toward developing online or offline health programs to help individuals who self-quarantined but tested negative for infectious diseases, allowing them to feel confident to self-quarantine in good health.

Blood Vessel Invasion Is an Independent Prognostic Factor in Endometrial Endometrioid Carcinoma Compared to Lymph Vessel Invasion and Myometrial Invasion Pattern.

We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures.

Implications of unconventional histological subtypes on magnetic resonance imaging and oncological outcomes in patients who have undergone radical prostatectomy

The prognostic significance of unconventional histology (UH) subtypes including intraductal carcinoma of the prostate (IDC-P), ductal adenocarcinoma, and cribriform pattern has been investigated for prostate cancer (PCa). However, little is known about magnetic resonance imaging (MRI) features and the oncological impact of tumor localization in localized PCa with UH. Clinical data of 211 patients with acinar adenocarcinoma (conventional histology [CH]) and 82 patients with UH who underwent robotic-assisted radical prostatectomy (RARP) were reviewed. Patients with UH are more likely to be older and have higher Gleason grade group, higher Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score, and larger tumor volume (TV) than those with CH. Multivariate analysis identified the presence of UH as an independent prognostic factor for progression-free survival (PFS) (hazard ration (HR) 2.41, 95% confidence interval (CI) 0.22–0.79, P = 0.0073). No significant difference in PFS was seen regarding tumor localization (transition zone [TZ] or peripheral zone [PZ]) in patients with UH (P = 0.8949), whereas PZ cancer showed shorter PFS in patients with CH (P = 0.0174). PCa with UH was associated with higher progression than PCa with CH among resection margin (RM)-negative cases (P < 0.0001). Further, increased PI-RADS v2.1 score did not correlate with larger TV in UH (P = 0.991), whereas a significant difference in TV was observed in CH (P < 0.0001). The prognostic significance of UH tumor was independent of tumor localization, and shorter PFS was observed even in RM-negative cases, indicating an aggressive subtype with micro-metastatic potential. Furthermore, UH tumors are more likely to harbor a large TV despite PI-RADS v2.1 score ≤ 3. These findings will help optimal perioperative management for PCa with UH.

Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial

Pathologists’ assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin–eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the ‘Metastasis Detection’ app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347–0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance.

ROS1 fusions in resected stage I-III adenocarcinoma: Results from the European Thoracic Oncology Platform Lungscape project

BackgroundROS1 fusion is a relatively low prevalence (0.6–2.0%) but targetable driver in lung adenocarcinoma (LUAD). Robust and low-cost tests, such as immunohistochemistry (IHC), are desirable to screen for patients potentially harboring this fusion. The aim was to investigate the prevalence of ROS1 fusions in a clinically annotated European stage I-III LUAD cohort using IHC screening with the in vitro diagnostics (IVD)-marked clone SP384, followed by confirmatory molecular analysis in pre-defined subsets. MethodsResected LUADs constructed in tissue microarrays, were immunostained for ROS1 expression using SP384 clone in a ready-to-use kit and Ventana immunostainers. After external quality control, analysis was performed by trained pathologists. Staining intensity of at least 2+ (any percentage of tumor cells) was considered IHC positive (ROS1 IHC + ). Subsequently, ROS1 IHC + cases were 1:1:1 matched with IHC0 and IHC1 + cases and subjected to orthogonal ROS1 FISH and RNA-based testing. ResultsThe prevalence of positive ROS1 expression (ROS1 IHC + ), defined as IHC 2+/3+, was 4 % (35 of 866 LUADs). Twenty-eight ROS1 IHC + cases were analyzed by FISH/RNA-based testing, with only two harboring a confirmed ROS1 gene fusion, corresponding to a lower limit for the prevalence of ROS1 gene fusion of 0.23 %. They represent a 7 % probability of identifying a fusion among ROS1 IHC + cases. Both confirmed cases were among the only four with sufficient material and H-score ≥ 200, leading to a 50 % probability of identifying a ROS1 gene fusion in cases with an H-score considered strongly positive. All matched ROS1 IHC- (IHC0 and IHC1 + ) cases were also found negative by FISH/RNA-based testing, leading to a 100 % probability of lack of ROS1 fusion for ROS1 IHC- cases. ConclusionsThe prevalence of ROS1 fusion in an LUAD stage I-III European cohort was relatively low. ROS1 IHC using SP384 clone is useful for exclusion of ROS1 gene fusion negative cases.