Descemet's membrane transplantation for the treatment of recurrent high myopic macular hole associated with retinal detachment : Descemet's membrane for myopic macular hole.

PURPOSE: To report the efficacy of Descemet's Membrane (DM) transplantation over the macular hole in patients with recurrent high myopic macular hole (HMMH) associated with retinal detachment (RD). METHODS: Six eyes of six patients with wide posterior staphyloma including MH and recurrent HMMH associated with RD were included to this retrospective study. All patients underwent pars plana vitrectomy and DM obtained from eye bank was placed over the macular hole during the surgery. Silicone oil endotamponade was used as endotamponade and removed within 6 months following surgery. Pre-operative and post-operative ophthalmologic examination and optical coherence tomography findings were recorded. RESULTS: The mean follow-up time was 18.53 ± 7.36 months. Macular hole closure was achieved in all patients (100%). Best-corrected visual acuity was improved from 1.51 ± 0.55 logMAR to 1.08 ± 0.50 logMAR (p = 0.043). No complications due to surgery or DM during follow-up. No DM dislocation or hole re-opening occurred after surgery. CONCLUSION: DM transplantation during vitrectomy may be an effective treatment for the recurrent HMMH associated with RD. KEY MESSAGES: What is known Various surgical techniques have been tried for recurrent high myopic macular hole associated with retinal detachment, but satisfactory anatomical and functional success rates have still not been achieved. WHAT IS NEW: The study demonstrates that Descemet's membrane transplantation is a safe and effective option for treating recurrent high myopic macular hole associated with retinal detachment. This is a novel technique that may overcome the limitations of existing approaches. The findings suggest that Descemet's membrane transplantation could become a promising addition to the surgical options for recurrent high myopic macular hole associated with retinal detachment.

Vascular mimicry and mosaic vessels in parathyroid tumours: a new diagnostic approach?

AIMS: Evaluation of 'alternative' vascularisation in human cancer is considered an important prognostic parameter; the 2022 WHO classification of parathyroid tumours despite progresses in clinical triaging of patients strongly emphasises new histopathological parameters to properly stratify these lesions. 'Alternative' and 'classic' vessels were here investigated for the first time in parathyroid tumours for their possible histopathological and clinical relevance during progression. METHODS: Using a double CD31/PAS staining, microvessel density (MVD, 'classic' CD31+ vessels), mosaic vessel density (MoVD, 'alternative' CD31+/-vessels) and vessel mimicry density (VMD, 'alternative' CD31-/PAS+ vessels) were evaluated in 4 normal parathyroid glands (N), 50 Adenomas (A), 35 Atypical Tumours (AT) and 10 Carcinomas (K). RESULTS: Compared with N, MVD significantly increased in A (p=0.012) and decreased in K (p=0.013) with vessel counts lower than in AT and A (p<0.001). MoVs and VMs, absent in normal tissue, were documented in non-benign parathyroid lesions (AT, K) (p<0.001), with MoVs and VMs most represented in AT and K, respectively (p<0.001), in peripheral growing areas. Vessel distribution was correlated to neoplastic progression (r=-0.541 MVD; r=+0.760 MoVD, r=+0.733 VMD), with MVD decrease in AT and K inversely related to MoVD and VMD increase (r=-0.503 and r=-0.456). CONCLUSIONS: 'Alternative' vessel identification in parathyroid tumours is crucial because it: (1) explains the paradox of non-angiogenic tumours, consisting in a new bloody non-endothelial vessel network and (2) helps pathologists to unmask worrisome lesions. Furthermore, detection of alternative vascular systems in human tumours might explain the limited success of antiangiogenic therapies and encourage new oncological studies.

Major pathologic response and long-term clinical benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: The majority of HR+/HER2-breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2-breast cancer after neoadjuvant chemotherapy. METHODS: We analyzed HR+/HER2-breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3-5 and positive lymph node ratio of ≤10 %, was used as a pathological evaluation indicator. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. RESULTS: From January 2010 to December 2020, 386 patients were included in the final analysis. 28 patients (7.3 %) achieved pCR and 118 patients (30.6 %) achieved MPR. The median duration of follow-up was 54.4 months,5-year EFS was 87 % in the MPR group vs. 68 % in the non-MPR group. Multivariate analysis showed that low PR expression, high clinical stage, lower Miller-Payne grades and Positive lymph node ratio were independent poor prognostic factors for EFS (all P values < 0.05). The prognostic effect of MPR remained in multivariable models (hazard ratio (HR), 0.45; 95 % confidence interval (CI), 0.26-0.76; P = 0.008), In non-pCR patients, those who achieved MPR exhibited a similar EFS compared with pCR patients (HR, 2.25; 95 % CI, 0.51-9.84; P = 0.28). CONCLUSION: MPR may be a novel pathologic end point in HR+/HER2-breast cancer after neoadjuvant chemotherapy, holding greater applicability in the prognosis evaluation than pCR.

Retrieval of the Clipped Axillary Lymph Node and Its Impact on Treatment Decisions.

We examined clinically node-positive (cN+) breast cancer patients undergoing neoadjuvant chemotherapy and clipped lymph node (CLN) localization to determine the rate of CLN = non-sentinel lymph node (SLN), the factors associated with cN+ to pN0 conversion, and the treatment impact. We conducted a single institution review of cN+ patients receiving NAC from 2016 to 2022 with preoperative CLN localization (N = 81). Demographics, hormone receptor (HR) and HER2 status, time to surgery, staging, chemotherapy regimen, localization method, pathology, and adjuvant therapy were analyzed. Pathologic complete response (pCR) of the CLN was observed in 41 patients (50.6%): 18.8% HR+/HER2-, 75% HR+/HER2+, 75% HR-/HER2+, and 62.5% triple-negative breast cancer (p-value = 0.006). CLN = SLN in 68 (84%) patients, while CLN = non-SLN in 13 (16%). In 14 (17.3%) patients, the final treatment was altered based on +CLN status: 11 patients underwent axillary lymph node dissection (ALND), and 3 had systemic treatment changes. pCR rates varied, with the highest conversion rates observed in HER2+ disease and the lowest in HR+/HER2- disease. In 2 (2.5%) patients, adjuvant therapy changes were made based on a non-sentinel CLN, while in 97.5% of patients, a SLN biopsy alone represented the status of the axilla. This demonstrates that a +CLN often alters final plans and that, despite also being a SLN in most cases, a subset of patients will be undertreated by SLN biopsy alone.

Histological Assessment and Interobserver Agreement in Major Pathologic Response for Non-Small Cell Lung Cancer with Neoadjuvant Therapy.

Purpose: Major pathologic response (MPR), defined as ≤10% of residual viable tumor (VT), is a prognostic factor in non-small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction. Materials and Methods: This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images. Results: Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; IoU score, 0.92). Excellent agreement was achieved for VT (%) (ICC=0.959) and MPR using 10% cutoff (Fleiss' kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p<0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012). Conclusion: While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.

Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy.

BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND AND OBJECTIVE: To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). METHODS: Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. RESULTS: A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). CONCLUSIONS: Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

Non-invasive multimodal CT deep learning biomarker to predict pathological complete response of non-small cell lung cancer following neoadjuvant immunochemotherapy: a multicenter study.

OBJECTIVES: Although neoadjuvant immunochemotherapy has been widely applied in non-small cell lung cancer (NSCLC), predicting treatment response remains a challenge. We used pretreatment multimodal CT to explore deep learning-based immunochemotherapy response image biomarkers. METHODS: This study retrospectively obtained non-contrast enhanced and contrast enhancedbubu CT scans of patients with NSCLC who underwent surgery after receiving neoadjuvant immunochemotherapy at multiple centers between August 2019 and February 2023. Deep learning features were extracted from both non-contrast enhanced and contrast enhanced CT scans to construct the predictive models (LUNAI-uCT model and LUNAI-eCT model), respectively. After the feature fusion of these two types of features, a fused model (LUNAI-fCT model) was constructed. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. SHapley Additive exPlanations analysis was used to quantify the impact of CT imaging features on model prediction. To gain insights into how our model makes predictions, we employed Gradient-weighted Class Activation Mapping to generate saliency heatmaps. RESULTS: The training and validation datasets included 113 patients from Center A at the 8:2 ratio, and the test dataset included 112 patients (Center B n=73, Center C n=20, Center D n=19). In the test dataset, the LUNAI-uCT, LUNAI-eCT, and LUNAI-fCT models achieved AUCs of 0.762 (95% CI 0.654 to 0.791), 0.797 (95% CI 0.724 to 0.844), and 0.866 (95% CI 0.821 to 0.883), respectively. CONCLUSIONS: By extracting deep learning features from contrast enhanced and non-contrast enhanced CT, we constructed the LUNAI-fCT model as an imaging biomarker, which can non-invasively predict pathological complete response in neoadjuvant immunochemotherapy for NSCLC.

The utility of 18F-FDG PET/CT for predicting the pathological response and prognosis to neoadjuvant immunochemotherapy in resectable non-small-cell lung cancer.

OBJECTIVE: To evaluate the potential utility of 18F-FDG PET/CT to assess response to neoadjuvant immunochemotherapy in patients with resectable NSCLC, and the ability to screen patients who may benefit from neoadjuvant immunochemotherapy. METHODS: Fifty one resectable NSCLC (stage IA-IIIB) patients were analyzed, who received two-three cycles neoadjuvant immunochemotherapy.18F-FDG PET/CT was carried out at baseline(scan-1) and prior to radical resection(scan-2). SULmax, SULpeak, MTV, TLG, T/N ratio, ΔSULmax%,ΔSULpeak%, ΔMTV%, ΔTLG%,ΔT/N ratio% were calculated. 18F-FDG PET/CT responses were classified using PERCIST. We then compared the RECIST 1.1 and PERCIST criteria for response assessment.With surgical pathology of primary lesions as the gold standard, the correlation between metabolic parameters of 18F-FDG PET/CT and major pathologic response (MPR) was analyzed. All metabolic parameters were compared to treatment response and correlated to PFS and OS. RESULTS: In total of fifty one patients, MPR was achieved in 25(49%, 25/51) patients after neoadjuvant therapy. The metabolic parameters of Scan-1 were not correlated with MPR.The degree of pathological regression was negatively correlated with SULmax, SULpeak, MTV, TLG, T/N ratio of scan-2, and the percentage changes of the ΔSULmax%, ΔSULpeak%, ΔMTV%,ΔTLG%,ΔT/N ratio% after neoadjuvant therapy (p < 0.05). According to PERCIST, 36 patients (70.6%, 36/51) showed PMR, 12 patients(23.5%, 12/51) had stable metabolic disease(SMD), and 3 patients(5.9%, 3/51) had progressive metabolic disease (PMD). ROC indicated that all of scan-2 metabolic parameters and the percentage changes of metabolic parameters had ability to predict MPR and non-MPR, SULmax and T/N ratio of scan-2 had the best differentiation ability.The accuracy of RECIST 1.1 and PERCIST criteria were no statistical significance(p = 0.91). On univariate analysis, ΔMTV% has the highest correlation with PFS. CONCLUSIONS: Metabolic response by 18F-FDG PET/CT can predict MPR to neoadjuvant immunochemotherapy in resectable NSCLC. ΔMTV% was significantly correlated with PFS.

Clinical and Prognostic Characteristics of Acute BAD-Related Stroke: A Multicenter MRI-Based Prospective Study.

BACKGROUND: Branch atheromatous disease (BAD)-related stroke has emerged as a meaningful subtype of ischemic stroke yet remained understudied. We aimed to investigate the demographic, clinical, therapeutic, and prognostic characteristics of BAD-related stroke. METHODS: The BAD-study was a nationwide, multicenter, prospective, observational cohort study in 20 Chinese hospitals from June 2021 to June 2023, enrolling patients aged 18 to 80 years with BAD-related stroke within 72 hours of onset. Eligible single subcortical infarct in the territory of lenticulostriate artery and paramedian pontine artery was included. Clinical, laboratory, and treatment data were collected at baseline. The primary outcome was a proportion of good outcomes (modified Rankin Scale score, 0-2) at 90 days. Main secondary outcomes included early neurological deterioration (END), cerebrovascular event, major bleeding, and excellent outcome (modified Rankin Scale score, 0-1) during 90-day follow-up. RESULTS: We finally enrolled 476 patients, with a median age of 60 (interquartile range, 53-68) years, and 70.2% were male. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 2-6) at enrollment. Involvement of the lenticulostriate artery was more common than the paramedian pontine artery (60.7% versus 39.3%). END occurred in 14.7% of patients, with a median time from onset of 38 (interquartile range, 22-62) hours. The rates of good and excellent outcomes were 86.5% and 72%, respectively. Its 90-day stroke recurrence rate was 1.9%. Acute-phase therapy (from onset to 7 days of enrollment) showed heterogeneity and was not associated with prognosis. Multivariable logistic regression analysis identified the National Institutes of Health Stroke Scale score ≥4 at admission and END as negative predictors and extracranial artery stenosis as a positive predictor of good outcomes. Age ≥60 years, National Institutes of Health Stroke Scale score ≥4 at admission, and END were negative predictors of excellent outcomes. CONCLUSIONS: With distinct demographic, clinical, and prognostic characteristics, along with a high incidence of END and a low risk of stroke recurrence, BAD-related stroke could be categorized as a separate disease entity. Moreover, its acute-phase treatment strategies were undetermined, awaiting further high-quality studies.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Pathologic Complete Response After Neoadjuvant Chemotherapy in Breast Cancer Patients Treated With Mastectomy: Indications for Treatment and Oncological Outcomes.

Objective: The aim of this study was to evaluate the clinical outcomes of breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC) followed by mastectomy, focusing on cases achieving pathologic complete response (pCR). The implications of residual ductal carcinoma in situ (DCIS) on prognosis and survival were examined. Materials and Methods: A retrospective cohort study included BC patients treated with NAC followed by mastectomy at the breast unit of IRCCS Humanitas Research Hospital between March 2010 and October 2021. Patients were sub-grouped into two: Those with residual DCIS (ypTis) and those with complete response without residual tumor (ypT0). Key variables such as demographics, tumor characteristics, treatment regimens, and survival outcomes were analyzed. Results: Of 681 patients treated with NAC, 175 achieved pCR, with 60 undergoing mastectomy. Among these 60 patients, 24 had residual DCIS (ypTis) while 36 had no residual invasive or in situ disease (ypT0). Patients with ypTis had higher rates of multifocal disease (62.5% vs. 27.8%, p = 0.006) and stage III disease (37.5% vs. 11.1%, p = 0.046). Triple-negative breast cancer was more prevalent in the ypT0 group (55.6% vs. 20.8%, p = 0.005). During a mean follow-up of 47 months, 11 patients experienced recurrence, with no significant differences in disease-free survival (DFS) and overall survival (OS) between the groups (p = 0.781, p = 0.963, respectively). Conclusion: Residual DCIS after NAC did not significantly impact DFS or OS compared to complete pathologic response without residual DCIS. This study underscores the need for further research to refine pCR definitions and improve NAC's prognostic and therapeutic roles in BC management.

Feasibility of breast conserving surgery alone in HER2-positive exceptional responders to neoadjuvant systemic therapy.

It is unknown if radiation therapy provides additional benefit among patients who achieve pathologic complete response (pCR) following neoadjuvant systemic therapy (NST). We sought to assess feasibility of radiation omission after breast conserving surgery in early-stage, node-negative, HER2+ breast cancer patients with pCR after NST. This was a single-arm study of women 30 years and older with cT2N0 disease based on imaging. Six patients were followed with mammography or MRI every 6 months following surgery. The median age of patients was 58 years (IQR: 46-66). At a median follow-up of 31.6 months (range: 21-40 months), no Ipsilateral Breast Tumor Recurrences (IBTR) were identified. This approach was found to be feasible, warranting further study in larger prospective trials.

Influence of diabetes on microbiome in prostate tissues of patients with prostate cancer.

Background: Although microbiota in prostatic tissues of patients with prostate cancer have been studied, results of different studies have been inconsistent. Different ethnicity of study subjects, different study designs, and potential contaminations during sample collection and experiments might have influenced microbiome results of prostatic tissues. In this study, we analyzed microbiota and their potential functions in benign and malignant tissues of prostate cancer considering possible contaminants and host variables. Materials and methods: A total of 118 tissue samples (59 benign tissues and 59 malignant tissues) obtained by robot-assisted laparoscopic radical prostatectomy were analyzed and 64 negative controls (from sampling to sequencing processes) were included to reduce potential contaminants. Results: Alteration of the microbiome in prostate tissues was detected only in patients with diabetes. Furthermore, the influence of diabetes on microbiome was significant in malignant tissues. The microbiome in malignant tissues of patients with diabetes was influenced by pathologic stages. The relative abundance of Cutibacterium was reduced in the high pathologic group compared to that in the intermediate group. This reduction was related to microbial pathways increased in the high pathologic group. Conclusion: Results of this study indicate that diabetes can influence the progression of prostate cancer with microbiome alteration in prostate tissues. Although further studies are necessary to confirm findings of this study, this study can help us understand tissue microbiome in prostate cancer and improve clinical therapy strategies.

Resting-state EEG predicts cognitive decline in a neuropathologically diagnosed longitudinal community autopsied cohort.

OBJECTIVE: To assess correlative strengths of quantitative electroencephalography (qEEG) and visual rating scale EEG features on cognitive outcomes in only autopsied cases from the Arizona Study of Neurodegenerative Disorders (AZSAND). We hypothesized that autopsy proven Parkinson Disease will show distinct EEG features from Alzheimer's Disease prior to dementia (mild cognitive impairment). BACKGROUND: Cognitive decline is debilitating across neurodegenerative diseases. Resting-state EEG analysis, including spectral power across frequency bins (qEEG), has shown significant associations with neurodegenerative disease classification and cognitive status, with autopsy confirmed diagnosis relatively lacking. METHODS: Biannual EEG was analyzed from autopsied cases in AZSAND who had at least one rsEEG (>1 min eyes closed±eyes open). Analysis included global relative spectral power and a previously described visual rating scale (VRS). Linear mixed regression was performed for neuropsychological assessment and testing within 2 years of death (n = 236, 594 EEG exams) in a mixed linear regression model. RESULTS: The cohort included cases with final clinicopathologic diagnoses of Parkinson's disease (n = 73), Alzheimer disease (n = 65), and tauopathy not otherwise specified (n = 56). A VRS score of 3 diffuse or frequent generalized slowing) over the study duration was associated with an increase in consensus diagnosis cognitive worsening at 4.9 (3.1) years (HR 2.02, CI 1.05-3.87). Increases in global theta power% and VRS were the most consistently associated with large regression coefficients inversely with cognitive performance measures. CONCLUSION: Resting-state EEG analysis was meaningfully related to cognitive performance measures in a community-based autopsy cohort. EEG deserves further study and use as a cognitive biomarker.

Delta Radiomics Based on MRI for Predicting Axillary Lymph Node Pathologic Complete Response After Neoadjuvant Chemotherapy in Breast Cancer Patients.

PURPOSE: To develop and test a radiomics nomogram based on magnetic resonance imaging (MRI) and clinicopathological factors for predicting the axillary pathologic complete response (apCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients with axillary lymph node (ALN) metastases. MATERIALS AND METHODS: A total of 319 patients who underwent MRI examination and received NAC treatment were enrolled from two centers, and the presence of ALN metastasis was confirmed by biopsy pathology before NAC. The radiomics features were extracted from regions of interest of ALNs before (pre-radiomics) and after (post-radiomics) NAC. The difference of features before and after NAC, named delta radiomics, was calculated. The variance threshold, selectKbest and least absolute shrinkage and selection operator algorithm were used to select radiomics features. Radscore was calculated by a linear combination of selected features, weighted by their respective coefficients. The univariate and multivariate logistic regression was used to select the clinicopathological factors and radscores, and a radiomics nomogram was built by multivariable logistic regression analysis. The performance of the nomogram was evaluated by the area under the receiver operator characteristic curve (AUC), decision curve analysis (DCA) and calibration curves. Furthermore, to explore the biological basis of radiomics nomogram, 16 patients with RNA-sequence data were included for genetic analysis. RESULTS: The radiomics nomogram was constructed by two radscores (post- and delta- radscores) and one clinicopathological factor (progesterone hormone, PR), and showed powerful predictive performance in both internal and external test sets, with AUCs of 0.894 (95% confidence interval [CI], 0.877-0.959) and 0.903 (95% CI, 0.801-0.986), respectively. The calibration curves and DCA showed favorable consistency and clinical utility. With the assistance of nomogram, the rate of unnecessary ALND would be reduced from 60.42% to 21.88%, and the rate of final benefit rate would be increased from 39.58% to 70.83%. Moreover, genetic analysis revealed that high apCR prediction scores were associated with the upregulation of immune-mediated genes and pathways. CONCLUSION: The radiomics nomogram showed great performance in predicting apCR after NAC for breast cancer patients, which could help clinicians to identify patients with apCR and avoid unnecessary axillary lymph node dissection.

Internal validation of modified Mirels' scoring system for pathologic femur fractures.

BACKGROUND: The proximal femur is a common site of bone metastasis. The Mirels' score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels' scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels' location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series. METHODS: Retrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels' (OM) Score and Modified Mirels' (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems. RESULTS: The use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original. CONCLUSIONS: Use of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. METHODS: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. RESULTS: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. CONCLUSION: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.