Ki-67 index as a predictive marker of meningioma recurrence following surgical resection.

BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. Although benign in a majority of cases, they have a variable clinical course and may recur even after a thorough surgical resection. Ki-67, a nuclear protein involved in cell cycle regulation, has been widely studied as a marker of cellular proliferation in various cancers. However, the prognostic significance of Ki-67 in meningiomas remains controversial. Here, we investigate the Ki-67 index, as a predictive marker of meningioma recurrence following surgical resection and compare it to established prognostic markers such as WHO grade and degree of resection. METHODS: The medical records of 451 patients with previously untreated cranial meningiomas who underwent resections from January 2011 to January 2021 at North Shore University Hospital (NSUH) were reviewed. Collected data included WHO grade, Ki-67 proliferative index, degree of resection - gross (GTR) vs subtotal (STR) - as judged by the surgeon, tumor location, and meningioma recurrence. This study was approved by the NSUH Institutional Review Board IRB 21-1107. RESULTS: There were 290 patients with grade I, 154 with grade II, and 7 with grade III meningiomas. The average post-resection follow-up period was 4 years, and 82 tumors (18 %) recurred. Higher WHO grades were associated with higher rates of recurrence, with rates of 11.4 %, 27.9 %, and 71.4 % for grades 1, 2, and 3, respectively, and subtotal resection corresponded to a higher rate of recurrence than total resection (34.3 % and 13.4 %, respectively). Higher WHO grades also correlated with higher Ki-67 scores (2.59, 10.01, and 20.71) for grades 1, 2, and 3, respectively. A multivariate logistic regression model identified Ki-67 and degree of resection as independent predictive variables for meningioma recurrence, with Ki-67 specifically predicting recurrence in the WHO grade II subset when analyzed separately for WHO grades I and II. CONCLUSION: Our 10-year retrospective study suggests that the Ki-67 index is an important predictive marker for recurrence of intracranial meningiomas following surgical resection, particularly among patients with WHO grade II tumors. Our findings add to a growing body of data that support inclusion of Ki-67 index in the WHO grading criteria for patients with meningiomas.

Rates of Occult Invasive Disease in Patients With Biopsy-Proven Oral Cavity Squamous Cell Carcinoma in Situ.

Importance: The likelihood that an oral cavity lesion harbors occult invasive disease after biopsy demonstrating carcinoma in situ (CIS) is unknown. While de-escalated treatment strategies may be appealing in the setting of CIS, knowing whether occult invasive disease may be present and its association with survival outcomes would lead to more informed management decisions. Objective: To evaluate rate of occult invasive disease and clinical outcomes in patients with oral cavity CIS. Design, Setting, and Participants: This was a retrospective population-based cohort study using the National Cancer Database and included adults with biopsy-proven oral cavity CIS as the first diagnosis of cancer between 2004 and 2020. Data were analyzed from October 10, 2022, to June 25, 2023. Exposures: Surgical resection vs no surgery. Main Outcomes and Measures: Analyses calculated the rate of occult invasive disease identified on resection of a biopsy-proven CIS lesion. Univariate and multivariate logistic regression with odds ratios and 95% CIs were used to identify significant demographic and clinical characteristics associated with risk of occult invasion (age, year of diagnosis, sex, race and ethnicity, oral cavity subsite, and comorbidity status). Kaplan-Meier curves for overall survival (OS) were calculated for both unresected and resected cohorts (stratified by presence of occult invasive disease). Results: A total of 1856 patients with oral cavity CIS were identified, with 122 who did not undergo surgery (median [range] age, 65 [26-90] years; 48 female individuals [39.3%] and 74 male individuals [60.7%]) and 1458 who underwent surgical resection and had documented pathology (median [range] age, 62 [21-90] years; 490 female individuals [33.6%] and 968 male individuals [66.4%]). Of the 1580 patients overall, 52 (3.3%) were Black; 39 (2.5%), Hispanic; 1365 (86.4%), White; and 124 (7.8%), other, not specified. Among those who proceeded with surgery with documented pathology, 408 patients (28.0%) were found to have occult invasive disease. Higher-risk features were present in 45 patients (11.0%) for final margin positivity, 16 patients (3.9%) for lymphovascular invasion, 13 patients (3.2%) for high-grade invasive disease, and 14 patients (3.4%) for nodal involvement. For those patients with occult disease, staging according to the American Joint Committee on Cancer's AJCC Cancer Staging Manual, eighth edition, was pT1 in 341 patients (83.6%), pT2 in 41 (10.0%), and pT3 or pT4 disease in 26 (6.4%). Factors associated with greater odds of occult invasive disease at resection were female sex, Black race, and alveolar ridge, vestibule, and retromolar subsite. With median 66-month follow-up, 5-year OS was 85.9% in patients who proceeded with surgical resection vs 59.7% in patients who did not undergo surgery (difference, 26.2%; 95% CI, 19.0%-33.4%). Conclusions and Relevance: This cohort study assessed the risk of concurrent occult invasion with biopsy-proven CIS of the oral cavity, demonstrating that 28.0% had invasive disease at resection. Reassuringly, even in the setting of occult invasion, high-risk disease features were rare, and 5-year OS was nearly 80% with resection. The findings support the practice of definitive resection if feasible following biopsy demonstrating oral cavity CIS.

Postoperative stereotactic radiosurgery for intracranial solitary fibrous tumors: systematic review and pooled quantitative analysis.

BACKGROUND: Intracranial solitary fibrous tumors (SFTs), formerly hemangiopericytomas (HPCs), are rare, aggressive dural-based mesenchymal tumors. While adjuvant radiation therapy has been suggested to improve local tumor control (LTC), especially after subtotal resection, the role of postoperative stereotactic radiosurgery (SRS) and the optimal SRS dosing strategy remain poorly defined. METHODS: PubMed, EMBASE, and Web of Science were systematically searched according to PRISMA guidelines for studies describing postoperative SRS for intracranial SFTs. The search strategy was defined in the authors' PROSPERO protocol (CRD42023454258). RESULTS: 15 studies were included describing 293 patients harboring 476 intracranial residual or recurrent SFTs treated with postoperative SRS. At a mean follow-up of 21-77 months, LTC rate after SRS was 46.4-93% with a mean margin SRS dose of 13.5-21.7 Gy, mean maximum dose of 27-39.6 Gy, and mean isodose at the 42.5-77% line. In pooled analysis of individual tumor outcomes, 18.7% of SFTs demonstrated a complete SRS response, 31.7% had a partial response, 18.9% remained stable (overall LTC rate of 69.3%), and 30.7% progressed. When studies were stratified by margin dose, a mean margin dose > 15 Gy showed an improvement in LTC rate (74.7% versus 65.7%). CONCLUSIONS: SRS is a safe and effective treatment for intracranial SFTs. In the setting of measurable disease, our pooled data suggests a potential dose response of improving LTC with increasing SRS margin dose. Our improved understanding of the aggressive biology of SFTs and the tolerated adjuvant SRS parameters supports potentially earlier use of SRS in the postoperative treatment paradigm for intracranial SFTs.

Diagnostic Testing for von Willebrand Disease: Trends and Insights from North American Laboratories over the Last Decade.

Accurate diagnosis of von Willebrand disease (VWD) depends on the quality, precision, and variability of the laboratory assays. The North American Specialized Coagulation Laboratory Association (NASCOLA) is a provider of external quality assessment (EQA) for approximately 60 specialized coagulation laboratories in North America. In this report, NASCOLA EQA data from 2010 to 2021 are reviewed for trends in methodology and precision among various assays. In particular, recent ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Hemophilia Federation) guidelines for diagnosis of VWD are reviewed in light of EQA data. In contrast to other geographic regions, laboratories in North America predominantly use three-assay screening panels (antigen, platelet-binding activity, and factor VIII [FVIII] activity) rather than four-assay panels (antigen, platelet-binding activity, FVIII activity, and collagen-binding activity). They also use latex immunoassays rather than chemiluminescence immunoassays, and the classic ristocetin cofactor (VWF:RCo) assay and monoclonal antibody (VWF:Ab) assay to assess VWF platelet-binding activity over newer recommended assays (VWF:GPIbM and VWF:GPIbR). Factors that may be influencing these North American practice patterns include lack of Food and Drug Administration approval of the VWF:GPIbM, VWF:GPIbR, collagen binding assays, and chemiluminescence methodologies, and the influence of the 2008 National Heart, Lung, and Blood Institute guidelines on laboratory practice. Lastly, systems-based solutions are urgently needed to improve the overall accuracy of laboratory testing for VWD by minimizing preanalytical variables and adopting assay standardization.

Dynamics of Peripheral Blood T-lymphocytes Have Predictive Values for the Clinical Outcome of COVID-19 Patients in Intensive Care Unit.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients with severe disease had a high mortality rate. It's imperative to identify risk factors associated with disease progression and prognosis. Immune responses played an important role in the host's defense against the virus. We studied the dynamics of peripheral blood lymphocytes (PBLs) in relation to the clinical outcome in COVID-19 patients in intensive care unit (ICU). DESIGN: This cohort included 342 COVID-19 patients who were admitted to ICU between February 1 and May 30, 2020, with 178 having follow-up PBL analysis. The patients were divided into a group that survived and an expired group. PBL analysis was performed by flow cytometry. RESULTS: At time of initial flow analysis, there were no statistically significant differences in lymphocyte, T-cell and subsets, B-cell or natural killer (NK) cell counts between the 2 groups. However, during the ICU course, the surviving group demonstrated a full recovery of CD3+ T-cells, CD4+ T-cells, and CD8+ T-cells, with no significant change in B-cells, and a slight upward trend in NK-cells. In contrast, the expired group showed no recovery in T-cells (and subsets) and no significant changes in B-cells and NK-cells. We identified the earliest time points and cut-off values for T-cell subsets that predict clinical outcomes. CONCLUSION: The results of this study suggest that evaluation of PBL in COVID-19 patients could be valuable in the study of the immune responses to the disease and the prognostication of outcome.

Prognostic factors associated with COVID-19 related severity in sickle cell disease.

BACKGROUND: Equipoise exists regarding sickle cell disease (SCD) as a risk factor for COVID-19 disease severity and variables that increase risk of COVID-19 severity in SCD. Given our health system's large SCD patient catchment, we analyzed our own experience in this regard. STUDY METHODS: Retrospective analysis of the clinical course and factors associated with need for hospitalization and ICU admission of SCD patients diagnosed with COVID-19 through the Northwell Health system from March 1 to Dec 31, 2020. RESULTS: Of 1098 patients with SCD, 3.3% were diagnosed with COVID-19. Overall rates of hospitalization, ICU admission, cohort mortality, and in-hospital mortality were 80%, 19%, 2.5%,and 3.1%, respectively. By multivariable analysis, hospitalization risk was decreased by 60% for every 1 g/dL increase in admission Hb. ICU admission risk was increased by 84% as a health care worker; increased by 45% for every 1000/uL increase in admission immature granulocyte count; and decreased by 17% with hydroxyurea use. DISCUSSION: High hospitalization rates are compatible with worsened severity upon COVID-19 infection in SCD compared to the general population. Patients should be placed on hydroxyurea to increase their Hb and perhaps lower their neutrophil counts. Health care workers with SCD may warrant special safety precautions.

Diagnosis of von Willebrand disease: An assessment of the quality of testing in North American laboratories.

BACKGROUND: Laboratory diagnosis of von Willebrand Disease (VWD) is complex. Reliance on laboratory testing can be problematic as different VWD screening panels, assays and methodologies can produce analytic variability in test results. OBJECTIVES: To compare the degree of imprecision among the VWD assays and within the platelet binding activity (PBA) assays, to determine the consensus among the VWD assays for correct classification of sample results, and to determine consensus among laboratories' von Willebrand factor (VWF) multimer interpretations and final interpretations of the VWD panels. PATIENTS/METHODS: Proficiency testing results from the North American Specialized Coagulation Laboratory Association (NASCOLA) submitted by laboratories from 2010 to 2019 for all normal, type (T) 1 VWD and T2 VWD samples were analysed. RESULTS AND CONCLUSIONS: Imprecision was lowest for VWF antigen and highest for collagen binding activity (CBA) with median coefficient of variation (CV) of 12% (interquartile range (IQR) 7%) and 23% (IQR 21%) respectively. Within the VWF PBA assays, the gain-of-function mutant GP1b binding (VWF: GP1bM) methods had the least imprecision (CV 9%, IQR 10%). All assays, including the various PBA methods had excellent consensus. The majority of laboratories agreed that normal (median consensus-82%, IQR 16%) and T1 VWD (median consensus-100%, IQR 9%) samples had normal multimer distribution. Consensus among laboratories for final interpretations was excellent for normal samples (median 81%, IQR 8%), good for T1 VWD samples (median 59%, IQR 9%), and fair for T2 VWD samples (median 44%, IQR 21%). Consensus on final interpretation decreased as sample complexity increased.

Safety and benefits of automated red cell depletion-exchange compared to standard exchange in patients with sickle cell disease undergoing chronic transfusion.

BACKGROUND: The Spectra Optia allows automated performance of red blood cell reduction and isovolemic hemodilution (IHD) prior to standard red cell exchange (RCE), and is primarily intended for patients with sickle cell disease (SCD) undergoing chronic RCE. Data on the safety of inducing transient further anemia and the benefits of IHD-RCE is limited and occasionally contradictory. STUDY DESIGN AND METHODS: In this retrospective crossover analysis of six patients with SCD who underwent chronic exchange with standard RCE (Cobe Spectra) followed by IHD-RCE (Spectra Optia), we compared safety and benefit outcomes with IHD-RCE vs standard RCE. RESULTS: There were statistically but not clinically significant drops in blood pressure in the post-IHD phase. With IHD-RCE, there were significant reductions in red blood cell (RBC) usage and/or lower fraction of cells and significant increases in postprocedure hematocrit (Hct) associated with increased preprocedure Hct. There were no differences achieved in the time interval between procedures or in the net RBC gain with IHD-RCE. Overall, there were also no significant differences in pre- and postprocedure percentage of hemoglobin S, reticulocyte count, interval daily hemoglobin A decrement, or postprocedure white blood cell, neutrophil, or platelet counts. CONCLUSIONS: Our study supports that IHD-RCE can be safely used in patients with stroke risk and compared to standard RCE, results in benefits of lower RBC usage and/or fraction of cells remaining and higher postprocedure Hct associated with higher preprocedure Hct. These findings support wider use of IHD-RCE, especially in the current environment with reduced availability of minority units.

Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Social Media Engagement at Academic Conferences: Report of the Association of Pathology Chairs 2018 and 2019 Annual Meeting Social Media Committee.

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the social media committee reviews the strategies that were employed and the resultant outcome data. In addition, we categorize tweets by topic to identify the topics of greatest interest to meeting participants, and we discuss the differences between Twitter and other social media platforms. Lastly, we review the existing literature on this topic from 23 medical specialties and health care fields.

Rapid Emergence of SARS-CoV-2 in the Greater New York Metropolitan Area: Geolocation, Demographics, Positivity Rates, and Hospitalization for 46 793 Persons Tested by Northwell Health.

BACKGROUND: In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized. METHODS: Northwell Health Laboratories tested 46 793 persons for SARS-CoV-2 from 4 March through 10 April. The primary outcome measure was a positive reverse transcription-polymerase chain reaction test for SARS-CoV-2. The secondary outcomes included patient age, sex, and race, if stated; dates the specimen was obtained and the test result; clinical practice site sources; geolocation of patient residence; and hospitalization. RESULTS: From 8 March through 10 April, a total of 26 735 of 46 793 persons (57.1%) tested positive for SARS-CoV-2. Males of each race were disproportionally more affected than females above age 25, with a progressive male predominance as age increased. Of the positive persons, 7292 were hospitalized directly upon presentation; an additional 882 persons tested positive in an ambulatory setting before subsequent hospitalization, a median of 4.8 days later. Total hospitalization rate was thus 8174 persons (30.6% of positive persons). There was a broad range (>10-fold) in the cumulative number of positive cases across individual zip codes following documented first caseincidence. Test positivity was greater for persons living in zip codes with lower annual household income. CONCLUSIONS: Our data reveal that SARS-CoV-2 incidence emerged rapidly and almost simultaneously across a broad demographic population in the region. These findings support the premise that SARS-CoV-2 infection was widely distributed prior to virus testing availability.

Utilizing Social Media to Spread Knowledge: The Association of Pathology Chairs Experience at the 2018 Annual Meeting.

Participants at academic conferences frequently use social media to disseminate educational content learned while at the meeting. Although most agree that this activity is harmless, some have expressed concern regarding the accuracy of the shared content and whether it truly reflects the intent and message of the speaker. As part of the goals of the APC 2018 social media committee to promote excellence through social media, a study was conducted to measure the perceived accuracy of tweets that represented an opinion or statement from a speaker and was shared during the annual meeting. Tweets shared on Twitter using the meeting hashtag (#APCPRODS2018) were collected and a survey unique to each speaker was created, to which 54% responded. The majority of speakers regarded the use of Twitter at the conference as beneficial in spreading their intended message in an accurate way. This study exemplifies the positive impact that social media use can have at academic meetings.

Potential Pitfalls in Diagnostic Digital Image Analysis: Experience with Ki-67 and PHH3 in Gastrointestinal Neuroendocrine Tumors.

Gastrointestinal neuroendocrine tumors, or GI-NETs are a highly diverse group of tumors derived from neuroendocrine cells of the GI tract. In GI-NET, a spectrum of histological and molecular parameters exists to predict prognosis and survival. Immunohistochemistry for Ki67, a nuclear antigen that is present in all but the G0 phase of the cell cycle with specificity for proliferating cells, can be used to determine a tumors proliferation index. With this in mind, grading of gastrointestinal neuroendocrine tumors is critical for prognosis and can impact clinical decision making. Recently, digital image analysis (DIA) has been shown in studies to be a superior and less time-consuming alternative to the manual scoring of Ki-67 in breast cancer, secondary to its theoretical diagnostic reproducibility. In DIA, the correct identification of tumor cells and non-tumor is paramount to avoid over or under calculation of biomarker expression. Additionally, DIA requires a pathologist to manually outline a tumor in large tissue areas of hematoxylin and eosin (H&E) sections, which is impractical. The findings in our study showed that ventana virtuoso software computer analyzed Ki-67 only correlated well with Neuroendocrine carcinomas while manual analysis of mitotic index and Ki67 were found to be gold standard. The performance of DIA in our study was plagued by software issues. In future, the advent of new digital imaging technologies such as virtual dual staining will hopefully improve diagnostic accuracy and reproducibility across different DIA platforms. Ultimately, determination of therapeutic strategies should be guided by an amalgamation of clinicopathologic characteristics not limited to mitotic index and Ki-67. As well, A visual check of the results should always be performed and correlated with other findings.

Using Heatmaps to Identify Opportunities for Optimization of Test Utilization and Care Delivery.

BACKGROUND: When a provider orders a test in a pattern that is substantially different than their peers, it may indicate confusion in the test name or inappropriate use of the test, which can be elucidated by initiating dialog between clinicians and the laboratory. However, the analysis of ordering patterns can be challenging. We propose a utilization index (UI) as a means to quantify utilization patterns for individual providers and demonstrate the use of heatmaps to identify opportunities for improvement. MATERIALS AND METHODS: Laboratory test orders by all providers were extracted from the laboratory information system. Providers were grouped into cohorts based on the specialty and patient population. A UI was calculated for each provider's use of each test using the following formula: (UI = [provider volume of specific test/provider volume of all tests]/[cohort volume of specific test/cohort volume of all tests]). A heatmap was generated to compare each provider to their cohort. RESULTS: This method identified several hot spots and was helpful in reducing confusion and overutilization. CONCLUSION: The UI is a useful measure of test ordering behavior, and heatmaps provide a clear visual illustration of the utilization indices. This information can be used to identify areas for improvement and initiate meaningful dialog with providers, which will ultimately bring improvement and reduction in costs. Our method is simple and uses resources that are widely available, making this method effective convenient for many other laboratories.

CDC Group EO-4 and Candida tropicalis Peritonitis in a Patient on Peritoneal Dialysis after Upper Endoscopy, Colonoscopy and Coil Embolization of the Gastroduodenal Artery.

Peritoneal dialysis (PD) is an excellent form of renal replacement therapy for many patients with end-stage renal disease (ESRD). Over 10,000 patients receive PD in the United States [United States Renal Data System: 2015 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States, 2015]. PD has superior outcomes compared to hemodialysis in the first 2 years of ESRD [Sinnakirouchenan and Holley: Adv Chronic Kidney Dis 2011;18: 428-432]. However, peritonitis is a known complication and may result in significant morbidity and necessitate transition to hemodialysis, which increases medical costs [Holley and Piraino: Semin Dial 1990;3: 245-248]. We report the first case of a PD patient who underwent endoscopy, colonoscopy and CT angiogram with coil embolization for gastrointestinal bleeding without antibiotic prophylaxis and subsequently developed CDC group EO-4 organism and fungal peritonitis.