Pathological Subgroups Research Articles

Clinical Usefulness of Linked Color Imaging for Detection and Characterization of UndifferentiatedType Early Gastric Cancer.

Linked color imaging is based on the bioluminescent imaging technique, which enhances differences in mucosal color allowing for contrast-based detection of lesions. There have been reports which have investigated the usefulness of linked color imaging for assessing color values in endoscopy for early gastric cancer cases. However, these primarily focused on differentiated early gastric cancer. This study aimed to assess the efficacy of linked color imaging in analyzing the color differences between cancerous and noncancerous areas in undifferentiated-type early gastric cancer patients compared with conventional white light imaging. Forty-six patients were prospectively enrolled with undifferentiated-type early gastric cancer from 3 academic hospitals. All lesions were observed first by white light imaging followed by linked color imaging. An additional biopsy was taken from the surrounding mucosa to check for intestinal metaplasia, and test for Helicobacter pylori was performed. Color difference was measured in accordance with the International Commission on Illumination details. The color difference value with linked color imaging was significantly higher, being more than twice that of white light imaging (26.82 ± 14.18 and 12.60 ± 6.42, P < .001), and this difference appeared to be similar in cases of accompanying Helicobacter pylori infection or intestinal metaplasia. In the subgroup analysis, color difference of poorly differentiated adenocarcinoma was notable in linked color imaging compared to white light imaging. Conversely, no statistically significant finding was present in signet ring cell carcinoma or mixed-type histology. Linked color imaging provides a significantly greater color difference between cancerous lesions and background noncancerous mucosa in undifferentiated-type early gastric cancer. Moreover, linked color imaging may differentiate between pathologic subgroups of undifferentiated-type early gastric cancer possibly due to characteristic cellular growth pattern.

Correlations between contrast-enhanced ultrasound and microvessel density in non-small cell lung cancer: A prospective study.

Immunohistochemical microvessel density (MVD) is an early indicator of angiogenesis and it could be used to evaluate the therapeutic efficacy of non-small cell lung cancer (NSCLC). We sought to identify the ability of contrast-enhanced ultrasound (CEUS) in evaluating MVD of subpleural NSCLC. We prospectively collected CEUS data of NSCLC confirmed by ultrasound-guided transthoracic needle biopsy from October 2019 to February 2021, The MVD of NSCLC counted by CD34-positive vessels of immunohistochemical staining. Microflow enhancement (MFE) of CEUS was divided into "dead wood", "cotton", and "vascular" patterns. Pathology subgroup and MVD between different MFE patterns were analyzed, respectively. The arrival time, time to peak, peak intensity (PI), and area under curve (AUC) derivefrom time-intensity curve of CEUS with MVD in NSCLC and its pathological subgroups (adenocarcinoma and squamous cell carcinoma) were subjected to correlation analysis. A total of 87 patients were included in this study, consisting of 53 cases of adenocarcinoma and 34 cases of squamous cell carcinoma with a mean MVD of 27.8 ± 12.2 mm-1. There was a significant statistical difference in MFE patterns between two pathological subgroups (p < 0.05). Besides, the MVD of "cotton" and "vascular" patterns were significantly higher than that of "dead wood" pattern (both of p < 0.05), whereas there was no significant difference in MVD between "cotton" pattern and "vascular" pattern. PI and AUC of CEUS were positively correlated with the MVD of NSCLC (r = 0.497, p < 0.001, and r = 0.367, p < 0.001, respectively). Besides, PI and AUC of CEUS were positively correlated with the MVD of squamous cell carcinoma (r = 0.802, and r = 0.663, respectively; both of p < 0.001). Only the PI was positively correlated with the MVD of lung adenocarcinoma (r = 0.288, p = 0.037). MFE patterns and quantitative parameters of CEUS had good correlation with MVD of NSCLC, especially in squamous cell carcinoma.

Abstract P3-02-06: Demographic and clinical features of patients with metastatic HER2 positive breast cancer: a retrospective multicenter registry study of the Turkish Oncology Group

Abstract Background: Although HER2 is an aggressive subtype of BC, the outcomes have improved over the past two decades due to advances in targeted therapies. Here, we present data of HER2-positive subset from the multicenter registry study of the Turkish Oncology Group (TOG) for metastatic breast cancer with an evolving treatment landscape for over a decade (MBC). Methods: The study of TOG for MBC was a retrospective registry study aimed to collect the data of adult metastatic BC patients diagnosed between 2010-2019, at seven tertiary oncology clinics in Turkey. Patient and disease characteristics were recorded from chart reviews. HER2 (+) was defined as IHC scores of IHC3+ or IHC2+ and ISH (+). Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates comprising of cohorts based on disease presentation (recurrent vs de-novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010-December 2014 and Cohort II: between January 2015-December 2019). Results: Of the 1381 patients analyzed over the whole period, 333 (24.1%) HER2 (+) MBC patients were identified. 55.0% of the patients were in Cohort I. The majority (56.8%) had de novo MBC. Despite a decreasing frequency over time (63.4% in Cohort I vs 48.7% in Cohort II, p=0.007), this was the largest group with among all pathological subgroups presenting with de novo disease. 17 patients (2.4% of recurrent patients) demonstrated changes in HER2 receptor status from negative to positive between the primary tumor and subsequent metastasis. Recurrent BC patients were significantly younger than de novo MBC patients [44 (22-80) years vs 49 (20-91) years, p=0.006] and 43.1% (n=62) had relapsed within two years from initial diagnosis. Recurrent BC patients showed a higher frequency of brain metastasis as compared to de novo patients (13.2% vs 1.1%), whereas non-CNS visceral organ metastases were more common in de novo MBC patients (58.7% vs 47.9%, respectively, p&amp;lt; 0.001). Following conditional approval of use in de novo visceral metastatic disease in 2016, dual-HER2 blockade including pertuzumab was more frequently used in Cohort II compared to Cohort I (p&amp;lt; 0.001). Although overall median PFS was not statistically significant between the two cohorts (Cohort II vs I; 22 vs 17 months, respectively, p=0.609), there was a significantly higher PFS in the de novo group in Cohort II (29 vs 17 months, p=0.037). Furthermore, there was a significant improvement in median OS in Cohort II compared to Cohort I [not reached vs 48.0 (40.0-71.0) months, respectively; p=0.017]; mainly driven by the de novo group in alignment with the approval indication for dual blockade (Cohort I vs II; 3-year OS; 62.0% vs 84.7%; p=0.009); especially those with visceral metastatic presentation (59.4% vs 83.4%, p=0.020); HR (+) HER2 (+) disease (61.2% vs 89.2%; p=0.013) and age&amp;lt; 40 years (40.0% vs 94.7%; p=0.009). Conclusion: There was a significant survival benefit achieved in patients with metastatic HER2 (+) disease over time, regardless of high-risk factors such as visceral involvement or young age, mirroring advances in the timeline of anti-HER2 treatment. Citation Format: Yeşim ERALP, İzzet DOĞAN, Sercan Aksoy, Burcu ÇAKAR, Gül BAŞARAN, Özlem ERCELEP, Nil MOLİNAS MANDEL, Taner KORKMAZ, Erhan GÖKMEN, Adnan AYDINER, Pınar SAİP. Demographic and clinical features of patients with metastatic HER2 positive breast cancer: a retrospective multicenter registry study of the Turkish Oncology Group [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-06.

Development of a New Self-Assessment Tool for Laryngopharyngeal Reflux Screening in Singers (SVHI-12-LPR)

Introduction: The present study aimed to develop a new tool for the evaluation of singers with self-reported symptoms suggestive of laryngopharyngeal reflux (LPR) (the SVHI-12-LPR), by correlating RSI with SVHI in a population sample of 163 subjects (both professional and amateur singers), evaluated also by videolaryngostroboscopy. This study was a cross-sectional, double-observational study. Methods: RSI and SVHI were administered to 159 singers (amateurs, singing students, and professional singers). All subjects underwent videolaryngostroboscopy to objectively identify four subgroups: normal subjects (41.5%), subjects with organic lesions occupying the glottic space (17.6%), subjects with functional dysphonia (18.2%), and subjects presenting solely signs suggestive of LPR (22.6%). Using the validated RSI threshold, 33.9% of participants presented an RSI total score >13, suggestive of LPR. Results: Subjects with a suspected diagnosis of LPR at videolaryngostroboscopy presented a mean RSI significantly higher than other subgroups (p < 0.001). Moreover, the SVHI-36 score did not statistically differ between pathological subgroups. A significant positive relationship was observed between RSI and SVHI total score (Spearman’s rank correlation coefficient [ρ] = 0.474, p < 0.001). 12 SVHI items (items 1, 2, 4, 5, 6, 7, 12, 20, 24, 25, 26, 30) showed a significant association with RSI pathology classification. Statistical analysis demonstrated for the 12 selected items (SVHI-12-LPR) acceptable specificity (0.691) and sensibility (0.833) for the suspected diagnosis of LPR with a cut-off of 15. Conclusions: From the SVHI-36, 12 items were extracted that correlated with the specific impact that LPR has on the singer’s voice (SVHI-12-LPR), as evaluated by RSI and videolaryngostroboscopy. Such questionnaire represents a new tool that could be applied to singers with symptoms suggestive of LPR to select which patients would benefit from a further phoniatric and videolaryngostroboscopic evaluation.

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT for diagnosis of metastatic lesions in patients with recurrent papillary thyroid carcinoma.

We aimed to evaluate the gallium-68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in localizing papillary thyroid carcinoma (PTC) foci in patients with biochemical relapse. Papillary thyroid carcinoma has achieved biochemical recovery after appropriate treatment and had biochemical relapse in the last follow-up were included in this retrospective study. Gallium-68-FAPI and fluorine-18-fluorodeoxyglucose (68F-FDG) PET/CT were performed to detect recurrence foci. Biochemically relapsed patients who underwent total thyroidectomy and were diagnosed with pathologically differentiated thyroid cancer were included in our study. Gallium-68-FAPI and 18F-FDG PET/CT imaging methods were used to determine the focus of metastasis or recurrence in all patients. Among 29 patients enrolled to the study, pathological subgroups were papillary (n=26) and poorly differentiated (n=3) PTC. Anti-thyroglobulin (TG) antibody positivity were noted in 5 of the patients, while all 29 of them were TG positive and had been consist of three groups as follows: 2-10ng/mL (n=4), 11-300ng/mL (n=14), 301ng/mL and above (n=11). Recurrence was detected in 72.4% (n=21) and 86% (n=25) of the patients via 18F-FDG and 68Ga-FAPI, respectively. Accuracy of detection noted as 100% (5/5), 75% (3/4), and 92.9% (13/14) in groups with the anti-TG antibody positivity, TG levels of 2-10ng/mL and 11-300ng/mL, respectively, when the two imaging modalities were utilized together. Furthermore, accuracy of 68Ga-FAPI was 100% (11/11) in the group with TG levels of 301ng/mL and above, whereas accuracy of 18F-FDG was 81.8% (9/11). Lastly, median maximum standardized uptake value (SUVmax) of recurrent lesions detected by the 68Ga-FAPI (median SUVmax: 6.0) were statistically higher than the ones detected by the 18F-FDG (median SUVmax: 3.7) (P=0.002). In recurrent PTC especially in case of higher TG levels, 68Ga-FAPI can be used in patients with inconclusive 18F-FDG findings.

Confirmatory Factor Analysis of the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Associated Sub-scales.

Hip Disability and Osteoarthritis Outcome Score (HOOS), HOOS-Joint Replacement (JR), HOOS Physical Function (PS), and HOOS-12 item scale have been suggested as reliable and valid instruments for assessing hip disability. However, factorial validity, invariance across subgroups, and repeated measures of the scale across different populations have not been well supported in the literature. The primary study objectives were to: (1) assess model fit and psychometric properties of the original 40-item HOOS scale, (2) assess model fit of the HOOS-JR, (3) assess model fit of the HOOS-PS, and (4) assess model fit of the HOOS-12. A secondary objective was to perform multigroup invariance testing across physical activity level and hip pathology subgroups for models that met recommended fit indices. Cross-Sectional Study. Individual confirmatory factor analyses (CFAs) were conducted for the HOOS, HOOS-JR, HOOS-PS, and HOOS-12. Additionally, multigroup invariance testing (i.e., activity level, injury type) was conducted on the HOOS-JR and HOOS-PS. Model fit indices did not meet contemporary recommendations for the HOOS and the HOOS-12. Model fit indices for the HOOS-JR and the HOOS-PS met some, but not all, contemporary recommendations. Invariance criteria was met for the HOOS-JR and HOOS-PS. The scale structure of the HOOS and HOOS-12 were not supported; however, preliminary evidence to support the scale structure of the HOOS-JR and HOOS-PS was found. Clinicians and researchers who utilize the scales should do so with caution due to their limitations and untested properties until further research establishes the full psychometric properties of these scales and recommendations for their continued use.

Serum and ascites tumor markers in the diagnostic and prognostic prediction for appendiceal pseudomyxoma peritonei

BackgroundTo investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and CA125 in serum and ascites of appendiceal pseudomyxoma peritonei (PMP) patients relative to their diagnostic and predictive value.MethodsThe study comprised 183 patients with pathologically confirmed appendiceal PMP, enrolled from May 2012 to June 2020, in Aerospace Center Hospital. Serum and ascites tumor markers were obtained, and their diagnostic values were compared by receiver operating characteristic (ROC) curves. The prognostic factors of appendiceal PMP with different pathologic subgroups were calculated by univariate and multivariate Cox proportional hazard regression models.ResultsThere were significant differences between the numbers of patients with positive CEA and CA199 in serum vs. ascites: p = 0.034 in CEA and p = 0.006 in CA199, respectively. The sensitivities with optimal cut-off values for ascites markers of CEA, CA199 and CA125 were 83.5%, 88.9% and 72.6%, respectively. CEA in ascites showed significant difference in the diagnosis of appendiceal PMP (p = 0.000); the areas under the ROC curves (AUROCs) and specificity were 0.725, 70.7%, respectively. Univariate analysis showed that the higher the ascites tumor markers, the poorer the survival (p = 0.014). Multivariate analysis indicated that completeness of cytoreduction (CCR), ascites CEA and pathological grade were independent risk factors for overall survival (OS).ConclusionCEA in ascites can be used to help specify the origin of PMP. Furthermore, elevation of ascites CEA, high pathological grade and incomplete cytoreduction predicted poor prognosis of appendiceal PMP.

Non‐amnestic initial cognitive symptoms have faster trajectories of clinical progression than amnestic symptoms in Alzheimer’s, Lewy body and mixed dementia neuropathologies

AbstractBackgroundDiagnostic guidelines currently exist for typical and atypical Alzheimer’s disease (AD). Significant heterogeneity exists among initial predominant clinical symptoms among Lewy body‐related pathology (LRP) in addition to primary AD pathology (ADP) and. However, the clinical relevance of initial amnestic or non‐amnestic cognitive symptoms among them are unclear. Our objective was to determine if initial cognitive symptoms had similar rates of functional decline across ADP, LRP and mixed ADP‐LRP neuropathologies.MethodA retrospective longitudinal cohort study was conducted among 2422 participants with autopsy confirmed ADP, LRP, or mixed ADP‐LRP in the National Alzheimer Coordinating Center database from June 20, 2005, to September 4, 2019. All participants had a Clinical Dementia Rating‐Global (CDR‐G) scale ≤1 at initial clinical visit. The primary outcome of interest was Clinical Dementia Rating‐sum of boxes (CDR‐SB). Linear mixed models adjusted for baseline CDR‐SB, age, sex, education and APOEε4 status were used to evaluate longitudinal outcomes. Multiple imputations using fully conditional specification was performed to account for missing data in the multivariable modelsResult2422 Participants (1187 with ADP, 904 with ADP‐LRP and 331 with LRP) had a mean (SD) interval of 5.5 (2.8) years from initial visit to autopsy. Language symptoms had a consistently faster rate of decline per year than amnestic symptoms across all three pathologies (ADP, β 0.29, [95%CI, 0.16 to 0.41], p&lt;0.001; LRP, β 0.69 [95%CI, 0.44 to 0.94], p&lt;0.001;ADP‐LRP, β 0.40, [95%CI, 0.22 to 0.57], p&lt;0.001). Executive symptoms had a faster rate of decline than amnestic symptoms in ADP, β 0.36, [95%CI, 0.21 to 0.51], p&lt;0.001 and ADP‐LRP, β 0.25 [95%CI, 0.07 to 0.42], p = 0.008. Visuospatial symptoms had a faster rate of decline than amnestic symptoms in ADP‐LRP, β 0.38 [95%CI, 0.12 to 0.65], p = 0.013.ConclusionNon‐amnestic phenotypes have faster trajectories of clinical progression than amnestic across three pathology subgroups. Language phenotypes have the fastest progression.

Myopic maculopathy and posterior staphyloma. Correlation with ATN classification and severe pathological myopia

AbstractPurpose: The aims of this study were: (1) to correlate posterior staphyloma with the ATN classification; (2) identify differences in clinical characteristics in terms of axial length (AL), age and best corrected visual acuity (BCVA) in eyes with the presence and absence of posterior staphyloma; (3) correlate the presence of posterior staphyloma with severe pathological myopia.Methods: This was a cross‐sectional and observational study developed in consecutive patients with high myopia. A complete ophthalmological examination, classification of myopic maculopathy according to the ATN grading system, staphyloma classification according to Curtin, and multimodal imaging tests (retinography, swept‐source OCT, autofluorescence and OCT‐angiography) were performed.Results: 336 eyes of 178 patients with high myopia were included. 71.4% of the sample were woman. The mean AL was 29.7 ± 2.6 mm (26–36.7). The mean age was 62.7 ± 13.1 years (27–92). The BCVA was 0.5 ± 0.3 (0–1). 238 eyes (70.8%) presented staphyloma; classifying 73.5% (n = 175/238) as simple and 26.5% as compound (n = 63/238). The most frequent types of staphylomas were type 2 and type 3, both present in 18.1% of the total (n = 43/238). Eyes with staphyloma had higher AL, worse BCVA and older age (p &lt; 0.01), with no differences between sexes (p &gt; 0.05). When differentiating between eyes with simple staphyloma and compound staphyloma, statistically significant differences were observed with respect to AL (p &lt; 0.01), being higher in compound staphylomas. The severe pathological myopia subgroup (LA &gt; 29.5 mm) presented a higher incidence of posterior staphyloma, with statistically significant differences (p &lt; 0.01). Regarding the ATN classification, when analysing the eyes with the presence and absence of staphyloma, statistically significant differences (p &lt; 0.01) were observed in the three components (atrophic [A], tractional [T] and neovascular [N]); having more advanced stages of A, T and N the eyes with staphyloma.Conclusions: Posterior staphyloma in highly myopic patients is a crucial finding in the progression of myopic maculopathy, being related to worse visual acuity, greater AL, older age and more advanced stages of the ATN classification. There is a higher prevalence of posterior staphyloma in eyes with severe pathological myopia.

A Multicenter, Phase III Study of Chidamide, Azacitidine Combined with CHOP Versus CHOP in Patients with Untreated Peripheral T-Cell Lymphoma

Introduction The biology of peripheral T-cell lymphoma (PTCL) is characterized by recurrent mutations affecting epigenetic regulators such as TET2, DNMT3A, IDH2, and RHOA, particularly in patients with angioimmunoblastic T-cell lymphoma (AITL) or PTCL-not otherwise specified. Azacitidine, a DNA methyl transferase (DNMT) inhibitor, has shown clinical activity as a single agent and in combination in R/R PTCL. Single-agent of the histone deacetylase (HDAC) inhibitors, including romidepsin, belinostat, and chidamide are associated with overall response rates of 25-30% in R/R PTCL. These evidence suggests that PTCL may have a unique vulnerability to epigenetic modulators which also provide the rationale for combining an HDAC inhibitor with a DNMT inhibitor in the backbone of the CHOP regimen forming a novel double-epigenetic regulating chemotherapy as an initial treatment for PTCL. Herein, we report the finding of the phase III trial of chidamide and azacitidine combined with CHOP (AC-CHOP) versus CHOP in patients with untreated PTCL (ClinicalTrials.gov - NCT05075460). Methods This study is a multicenter, non-randomized, phase III trial conducted at 4 centers in China. Eligible patients were aged between 18-75 years with newly diagnosed PTCL. Patients were non-randomly assigned to the AC-CHOP or the CHOP group according to the investigator's and patient's choice. Patients in the AC-CHOP group received azacitidine 200 mg subcutaneously on days 1-2 and 100 mg on day 3, chidamide 20mg orally twice weekly, combined with the CHOP regimen in a 3-week cycle for six cycles. Patients in the CHOP group received the CHOP regimen alone. The primary endpoint was the overall response rate (ORR) after the protocol treatment. Results Between August 2021 and March 2022, 35 patients were enrolled in the study and finished protocol treatment (20 in the AC-CHOP arm and 15 in the CHOP arm). Main pathological subgroups were PTCL not specified (n = 14) and AITL (n = 21). The baseline characteristics and pathological subtypes were mostly similar between the two treatment arms. At the end of treatment, the ORR and complete response (CR) rates were 60.0% and 55.0% in the AC-CHOP arm versus 53.3% and 26.7% in the CHOP arm (P = 0.693 for ORR and P = 0.184 for CR rate) , respectively. With a median follow-up time of 9 months, the median progression-free survival was 8 months in the AC-CHOP arm and 7 months in the CHOP arm (P = 0.602). The most frequent grade 3 to 4 adverse events included neutropenia (55.0% in the AC-CHOP arm versus 40.0% in the CHOP arm), thrombocytopenia (20.0% in the AC-CHOP arm versus 13.3% in the CHOP arm), and Anemia (5.0% in the AC-CHOP arm versus 6.7% in the CHOP arm) which showed no significant difference between the two arms. Conclusions According to the preliminary result of the study, the addition of azacytidine and chidamide to the CHOP regimen did not show a significant improvement of ORR or PFS for patients with untreated PTCL. A trend of higher CR rate was observed which did not reach statistical significance. The safety profile of AC-CHOP regimen was manageable.

Comprehensive genomic profiling of colorectal cancer patients reveals differences in mutational landscapes among clinical and pathological subgroups.

With the widespread of colonoscopy, colorectal cancer remains to be one of the most detrimental types of cancer. Though there were multiple studies investigating the genomic landscape of colorectal cancer, a comprehensive analysis uncovering the differences between various types of colorectal cancer is still lacking. In our study, we performed genomic analysis on 133 patients with colorectal cancer. Mutated FAT1 and PKHD1 and altered Hippo pathway genes were found to be enriched in early-onset colorectal cancer. APOBEC signature was prevalent in microsatellite stable (MSS) patients and was related to lymph node metastasis. ZNF217 mutations were significantly associated with early-stage colorectal cancer. In all, this study represents a comprehensive genomic analysis uncovering potential molecular mechanisms underneath different subgroups of colorectal cancer thus providing new targets for precision treatment development.

Distinct implications of body mass index in different subgroups of nonobese patients with heart failure with preserved ejection fraction: a latent class analysis of data from the TOPCAT trial

BackgroundObesity is a well-defined risk factor for heart failure with preserved ejection fraction (HFpEF), but it is associated with a better prognosis in patients with diagnosed HFpEF. The paradoxically poor prognosis in nonobese patients with HFpEF may be driven by a subset of high-risk patients, which suggests that the nonobese HFpEF subpopulation is heterogeneous.MethodsLatent class analysis (LCA) was adopted to identify the potential subgroups of 623 nonobese patients enrolled in the TOPCAT trial. The baseline characteristics of the identified nonobese subgroups were compared with each other and with the obese patients. The risks of all-cause, cardiovascular, and noncardiovascular mortality, and an HF composite outcome were also compared.ResultsTwo subgroups of nonobese patients with HFpEF (the physiological non-obesity and the pathological non-obesity) were identified. The obese patients were younger than both nonobese subgroups. The clinical profile of patients with pathological non-obesity was poorer than that of patients with physiological non-obesity. They had more comorbidities, more severe HF, poorer quality of life, and lower levels of physical activity. Patients with pathological non-obesity showed low serum hemoglobin and albumin levels. After 2 years of follow-up, more patients in the pathological group lost ≥ 10% of body weight compared with those in the physiological group (11.34% vs. 4.19%, P = 0.009). The prognostic implications of the two subgroups were opposite. Compared to patients with obesity, patients with physiological non-obesity had a 47% decrease in the risk of HF composite outcome (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40–0.70, P<0.001) and a trend of decreased all-cause mortality risk (HR 0.75, 95% CI 0.55–1.01, P=0.06), while patients with pathological non-obesity had a 59% increase (HR 1.59, 95% CI 1.24–2.02, P<0.001) in all-cause mortality risk.ConclusionsTwo subgroups of nonobese patients with HFpEF with distinct clinical profiles and prognostic implications were identified. The low BMI was likely physiological in one group but pathological in the other group. Using a data-driven approach, our study provided an alternative explanation for the “obesity paradox” that the poor prognosis of nonobese patients with HFpEF was driven by a pathological subgroup.

Non-COVID activity in French emergency department during COVID-19 pandemic (March 2020 to March 2022)

Abstract Background The COVID-19 epidemic and mitigation actions had major impacts on health and healthcare use by the French population. Since 2004, the French public health agency daily collects individual data of visits in the emergency departments (ED) OSCOUR® network (94% of national visits in 2022). We aimed to analyse the evolution of non-Covid ED visits from 2020 to March 2022, in order to identify potential indirect impact of the epidemic. Methods The main medical diagnosis (MD) coded in ICD-10 from each ED visit from 2017 to March 2022 was classified into 17 ICD-10 chapters and in 95 disjoint subgroups of pathologies. The observed numbers of ED visits by age group and by chapters/subgroups were compared to expected numbers, estimated using an overdispersed Poisson regression model based on 2017-2019 data. Results The observed numbers of ED visits for all chapters and for a large part of subgroups were significantly lower than the expected numbers during the three lockdowns in all age groups and progressively returned to the expected level in 2021. A change in the pattern of a limited list of subgroups was observed: ED visits for purpura, chronic blood diseases and neurologic disorders in children decreased during the first lockdown and remained under the expected level until March 2022. Inversely the number of ED visits for mental health and wheezing in children, for pulmonary embolism in adults and for neoplams in the elderly increased and remained over the expected values until 2022. Conclusions Syndromic ED system was a pillar of the French reactive surveillance of direct and indirect impacts of COVID-19 epidemic. The changes observed for different subgroups of pathologies may reflect a negative impact of the epidemic, a positive effect of protective measures on the spread of other infectious diseases, a modification in the organization or in the use of health care in specific domains. Further studies using hospitalization data could explore these hypotheses. Key messages • Existing syndromic surveillance system implemented before the emergence of SARS-COV2 enabled to monitor non-Covid-19 visits to emergency departments and assess changes in patterns of pathologies. • An increase in the number of emergency department visits during the COVID-19 epidemic was observed for mental health in children, for pulmonary embolism in adults and for neoplams in the elderly.

Zone 0 thoracic endovascular aortic repair in high risk patients: A retrospective case series.

To report our experience applying endovascular stent graft repair to treat ascending aortic diseases in high-risk patients and to evaluate the safety and feasibility of this approach. Patients with comorbid conditions or older age are not suitable for open procedures but may be considered suitable for ascending endovascular repair. Eleven high-risk patients received zone 0 thoracic endovascular aortic repair from September 2014 to May 2020. All patients were followed up until death or December 2021. Primary outcomes were in-hospital and long-term all-cause mortality as well as in-hospital and long-term aorta-related mortality. The mean follow-up duration of all patients was 35.78 months. The cohort comprised of three pathology subgroups: penetrating atherosclerotic ulcer (PAU) (n =6), acute dissection (AD) (n = 3), and chronic dissecting aneurysm (CDA) (n = 2). The in-hospital all-cause mortality rates were 0%, 33.33% and 0% for PAU, AD, and CDA groups, respectively. Long-term all-cause mortality were 33.33%, 33.33%, and 50% for PAU, AD, and CDA groups, respectively. There was only one in-hospital death related to acute aortic dissection, and no long-term aorta-related deaths occurred during the study period. During the follow-up time, the majority of patients had good remodeling of ascending aorta, slow progression in cases with endoleak, and no aorta-related mortality. Ascending endovascular aortic repair appears to be a safe and feasible procedure for emergent aortic repair in carefully selected patients with prohibitive surgical risk who are not candidates for open procedures.

Digital Mammography, Ultrasound and Magnetic Resonance Imaging Characteristics in Differential Diagnosis of Papillary Carcinoma Subtypes of the Breast and Diagnostic Challenges.

We aimed to investigate mammography (MG), ultrasound (US), and magnetic resonance imaging (MRI) findings of papillary breast carcinoma subtypes and to compare the diagnostic features and performance of the imaging method in distinguishing subtypes. Forty-two patients presenting with pathological diagnosis of 45 papillary carcinoma lesions, between 2014 and 2019, were included. Cases were assigned to five subgroups according to the latest World Health Organization (WHO) classification. The clinical characteristics (n = 45) and imaging features of each pathological subgroup were retrospectively related to imaging findings from US (n = 45), MG (n = 37), and breast MRI (n = 23), and further compared. The finding of a palpable mass in all subgroups was more common than nipple discharge on clinical breast evaluation, and no significant difference was found between the subgroups. Irregular shape on MG (10/12, 83.3%, p = 0.039) and US (11/12, 91.7%, p = 0.039) was found more frequently in invasive micropapillary carcinoma (IMPC) compared to other subgroups. Circumscribed margins (4/5, 80%, p = 0.002) occurred more frequently in papillary ductal carcinoma in situ (pDCIS) and encapsulated papillary carcinoma (EPC) than in other subgroups (6/8, 75%, p = 0.002). Lower apparent diffusion coefficient (ADC) values were found in solid papillary cancer (SPC) than in other subgroups (ADC = 0.35 x 10-3, p = 0.017). Radiological findings of papillary carcinomas overlap with each other. US and MRI are complementary when revealing specific morphological characteristics.

Development and Validation of the Optimal Circumferential Resection Margin in Pathological T3 Esophageal Cancer: A Multicenter, Retrospective Study.

The clinical significance of circumferential resection margin (CRM) in esophageal squamous cell carcinoma (ESCC) remains unclear. Optimal CRM for predicting the recurrence of pathological T3 ESCC was investigated. Seventy-three patients were retrospectively investigated in the development cohort. Patients were divided into CRM-negative and CRM-positive groups, and clinicopathological factors and survival outcomes were compared between the groups. The cutoff value was validated in another validation cohort (n = 99). Receiver operating characteristic analysis in the development cohort showed the cutoff value of CRM was 600 μm. In the validation cohort, patients in the CRM-positive group showed a significantly higher rate of locoregional recurrence (p = 0.006) and worse recurrence-free survival (RFS) (p < 0.001) than those in the CRM-negative group. Multivariate analysis identified positive CRM as an independent predictive factor for poor RFS (hazard ratio, 2.695; 95% confidence interval, 1.492-4.867; p = 0.001). The predictive value of our criteria of positive CRM for RFS was higher than that of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP) criteria. Stratified analysis in the neoadjuvant chemotherapy groups also revealed that the rate of locoregional recurrence was higher in the CRM-positive group than in the CRM-negative group both in the pathological N0 and N1-3 subgroups. CRM of 600 μm can be the optimal cutoff value rather than the RCP and CAP criteria for predicting locoregional recurrence after esophagectomy. These results may support the impact of perioperative locoregional control of locally advanced ESCC.

The Need for Pancreatic Enzyme Replacement Therapy (PERT) after Pancreatic Surgery is Determined by Tumor Location: A Prospective Cohort Study

Introduction: Patients undergoing oncologic pancreatic surgery are at risk for pancreatic exocrine insufficiency (PEI) and for needing PERT. There are few well-designed studies on the magnitude of this risk. Methods: In 198 patient undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) for oncologic indications, we performed an 13C-labeled mixed-triglyceride breath test, immediately preoperative and approximately 6 weeks postoperative. This test gives an idea of the pancreatic remnant lipase-activity analyzing the 13CO2 in breath after a test meal with 1.3-distearyl-(13C-Carboxyl)octanol-glycerol. Cumulative 13CO2 recovery after 6 hours is expressed as ‘MTG%’ and a level <23% confirms PEI and the need for PERT. Results: In 159 patients undergoing PD for a pancreatic head tumor, MTG% decreased significantly from 33.69% to 15.61% postoperative (p=0.002) (table 1). The percentage patients diagnosed with PEI and need for PERT increased from 23.0% to 68.3% postoperative (p<0.001). This decrease in exocrine function was significant in all pathology subgroups (figure 1), but most important in pancreatic adenocarcinoma. The postoperative percentage PEI in this subgroup increased to 78.1%. The decrease in function was less pronounced, but still significant, in pancreatic neuroendocrine tumor and ampullary tumor patients (p=0.002). In contrast, 39 patients undergoing a DP for a body-tail tumor did not experience any significant change in exocrine function. Conclusion: Patients with a pancreatic head tumor treated with PD experience a significant drop in exocrine function, are at high risk for developing PEI and consequently need for PERT. Therefore, systematic screening for PEI is mandatory after PD. Patients undergoing DP rarely need PERT.Tabled 1EP02D-185 Table 1: Evolution MTG% in pancreaticoduodenectomy and distal pancreatectomy patients measured by 13C-labeled mixed-triglyceride breath testPD n=159MTG% median preopMTG% median postopp=Median Δ MTG%MTG% range preopMTG% range postop% PEI preop% PEI postopp=pancreatic adenoca30.6111.48<0.001-16.25.44-53.340.02-34.7326.678.1<0.001ampullary tumor35.5525.73<0.001-13.016.87 -67.22.1 -34.3710.045.00.034PNET38.8927.080.022-7.0618.67 - 127.3117.4 -36.6710.030.0nsIPMN32.615.610.009-5.343.5-52.324.23 -44.1226.760.0nsdist cholangioca34.0222.50.021-7.482.96-43.916.37 - 34.889.154.50.046total group PD33.4915.61<0.0001-14.972.96-127.310.02-64.7323,068.3<0.001DP n=39MTG% median preopMTG% median postopp=Median Δ MTG%MTG% range preopMTG% range postop% PEI preop% PEI postopp=total group DP38.2838.09ns-1.9119.31-56.665.76-48.7310.257.7ns Open table in a new tab

Sustained postoperative plasma elevations of plasminogen activator inhibitor-1 following minimally invasive colorectal cancer resection.

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that inhibits urokinase-type plasminogen activator and tissue-type plasminogen activator. PAI-1 participates in angiogenesis, wound healing and tumor invasion, and additionally regulates endothelial cell proliferation, angiogenesis and tumor growth. The purpose of the present study was to measure plasma PAI-1 levels perioperatively in patients with colorectal cancer (CRC) undergoing minimally invasive colorectal resection (MICR). Patients with CRC who underwent elective MICR were eligible for the study. All patients were enrolled in an approved data/plasma bank. Patients with preoperative, postoperative day (POD) 1, POD 3, and at least one POD 7-34 plasma sample collection were studied. Plasma PAI-1 levels were determined in duplicate using ELISA, and the medians and 95% confidence intervals (CIs) were determined. The correlations between postoperative plasma PAI-1 levels and length of surgery were evaluated. PAI-1 levels were compared between patients who underwent laparoscopic-assisted vs. hand-assisted surgery. The preoperative PAI-1 levels of stage I, II, III and IV pathological stage subgroups were also compared. A total of 91 patients undergoing MICR for CRC were studied. The mean incision length was 8.0±3.9 cm, and the length of stay was 6.8±4.3 days. Compared with the median preoperative levels (17.30; 95% CI: 15.63-19.78 ng/ml), significantly elevated median levels were observed on POD 1 (28.86; 95% CI: 25.46-31.22 ng/ml; P<0.001), POD 3 (18.87; 95% CI: 17.05-21.78 ng/ml; P=0.0037), POD 7-13 (26.97; 95% CI: 22.81-28.74 ng/ml; P<0.001), POD 14-20 (25.92; 95% CI: 17.85-35.89 ng/ml; P=0.001) and POD 21-27 (22.63; 95% CI: 20.03-30.09 ng/ml; P<0.001). The PAI-1 levels in the hand-assisted group were higher compared with those in the laparoscopic-assisted group for 4 weeks after surgery; however, a significant difference was found only on POD 1. Therefore, plasma PIA-1 levels were found to be significantly elevated for 4 weeks after MICR, and the surgery-related acute inflammatory response may account for the early postoperative PIA-1 increase. Furthermore, PAI-1-associated VEGF-induced angiogenesis in the healing wounds may account for the late postoperative elevations, and increased PAI-1 levels may promote angiogenesis in residual tumor deposits.

Comprehensive transcriptomic characterization reveals core genes and module associated with immunological changes via 1619 samples of brain glioma

Glioma is the most common primary malignant brain tumor with limited treatment options and poor prognosis. To investigate the potential relationships between transcriptional characteristics and clinical phenotypes, we applied weighted gene co-expression network analysis (WGCNA) to construct a free-scale gene co-expression network yielding four modules in gliomas. Turquoise and yellow modules were positively correlated with the most malignant glioma subtype (IDH-wildtype glioblastomas). Of them, genes in turquoise module were mainly involved in immune-related terms and were regulated by NFKB1, RELA, SP1, STAT1 and STAT3. Meanwhile, genes in yellow module mainly participated in cell-cycle and division processes and were regulated by E2F1, TP53, E2F4, YBX1 and E2F3. Furthermore, 14 genes in turquoise module were screened as hub genes. Among them, five prognostic hub genes (TNFRSF1B, LAIR1, TYROBP, VAMP8, and FCGR2A) were selected to construct a prognostic risk score model via LASSO method. The risk score of this immune-related gene signature is associated with clinical features, malignant phenotype, and somatic alterations. Moreover, this signature showed an accurate prediction of prognosis across different clinical and pathological subgroups in three independent datasets including 1619 samples. Our results showed that the high-risk group was characterized by active immune-related activities while the low-risk group enriched in neurophysiological-related pathway. Importantly, the high-risk score of our immune signature predicts an enrichment of glioma-associated microglia/macrophages and less response to immune checkpoint blockade (ICB) therapy in gliomas. This study not only provides new insights into the molecular pathogenesis of glioma, but may also help optimize the immunotherapies for glioma patients.

The temporal onset of the core features in dementia with Lewy bodies.

IntroductionWe examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB).MethodsIn 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209).ResultsREM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely to have RBD and were diagnosed with probable DLB earlier than women. Visual hallucinations developed after the other core features in men, but in women, they appeared earlier and concurrently with fluctuations and parkinsonism. Women were older and more cognitively impaired at first visit, were less likely to have RBD, more likely to be diagnosed with probable DLB later than men, and more likely to have neocortical tangles.DiscussionAn earlier latency to probable DLB was associated with men, RBD, and Lewy body disease without neocortical tangles.