bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early neurological deterioration as a predictor of outcomes after endovascular thrombectomy for stroke: A systematic review and meta-analysis
Authors: Kobeissi Hassan , Ghozy Sherief , Seymour Trey , Bilgin Cem , Kadirvel Ramanathan , Kallmes David F. 
Published: October 2022

Background Early neurological deterioration (END) is a potential predictor for 90-day outcomes following mechanical thrombectomy for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis to better understand whether END can be used as a surrogate for long-term outcomes. Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase. END definition was cataloged for each included study. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, symptomatic intracranial hemorrhage (sICH), mortality, and thrombolysis in cerebral infarction (TICI) 2b-3. We calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI) for all definitions of END. Results We included seven studies with 2992 patients in our analysis. There was a significant, inverse association with END and mRS 0–2 rates (OR = 0.15; 95% CI = 0.08–0.29; P-value< 0.001). Moreover, END was a significant predictor of increased odds for reported sICH rates (OR = 16.37; 95% CI = 7.66–34.99; P-value< 0.001). Furthermore, there was a significant association between END and increase in mortality rates (OR = 6.79; 95% CI = 2.62–17.62; P-value< 0.001). There was no significant association between END and rates of TICI 2b-3 (OR = 0.53; 95% CI = 0.27–1.05; p = 0.069). Conclusions Broadly defined, END holds value as a potential predictor of rates of mRS 0–2 at 90 days and is associated with higher rates of mortality and sICH, but had no correlation with TICI 2b-3.
A qualitative study evaluating the discharge process for vascular surgery patients to identify significant themes for organizational improvement
Authors: Vogel Todd R , Kruse Robin L , Schlesselman Chase , Doss Elizabeth , Camazine Maraya , Popejoy Lori L 
Published: October 2022

Objective Transition from the hospital to an outpatient setting is a multifaceted process requiring coordination among a variety of services and providers to ensure a high-quality discharge. Vascular surgery patients comprise a complex population that experiences high unplanned readmission rates. We performed a qualitative study to identify themes for process improvement for vascular surgery patients. A validated discharge process, RED (Re-Engineered Discharge), was used to identify additional actionable themes to create a more efficient discharge process tailored specifically to the vascular surgery population. Methods A prospective, qualitative analysis at a tertiary center using a semi-structured focus group interview guide was performed to evaluate the current discharge process and identify opportunities for improvement. Focus groups were Zoom recorded, transcribed into electronic text files, and were loaded into Dedoose qualitative software for analysis using a directed content analysis approach. Two researchers independently thematically coded each transcript, starting with accepted discharge components to identify new thematic categories. Prior to analysis, all redundancy of codes was resolved, and all team members agreed on text categorization and coding. Results Eight focus groups with a total of 38 participants were conducted. Participants included physicians ( n = 13), nursing/ancillary staff ( n = 14), advanced nurse practitioners ( n = 2), social worker/dietitian/pharmacist ( n = 3), and patients ( n = 6). Transcript analyses revealed facilitators and barriers to the discharge process. In addition to traditional RED components, unique concepts pertinent to vascular surgery patients included patient complexity, social determinants of health, technology literacy, complexity of ancillary services, discharge appropriateness, and use of advanced nurse practitioners for continuity. Conclusions Specific themes were identified to target and enhance the future vRED (vascular Re-Engineered Discharge) bundle. Thematic targets for improvement include increased planning, organization, and communication prior to discharge to address vascular surgery patients’ multiple comorbidities, extensive medication lists, and need for complex ancillary services at the time of discharge. Other thematic barriers discovered to improve include provider awareness of patient health literacy, patient understanding of complex discharge instructions, patient technology barriers, and intrinsic social determinants of health in this population. To address these discovered barriers, organizational targets to improve include enhanced social support, the use of advanced nurse practitioners for education reinforcement, and increased coordination. These results provide a framework for future quality improvement targeting the vascular surgery discharge process.
Inflammatory Optic Neuropathy as a Presenting Feature of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Moura João , Mendes Pinto Catarina , Pinto Pedro , Santos Ernestina 
Published: October 2022

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly associated with early-onset stroke, migraine and vascular dementia. However, optic nerve involvement has been previously recognised. Results: We report a case of a 21-year-old female presenting with right inferior temporal scotoma, dyschromatopsia, relative pupillary afferent defect and bilateral disk oedema in the fundoscopic examination. Visual evoked potential latencies were bilaterally increased, suggesting optic neuropathy. Cerebrospinal fluid (CSF) evaluation showed 11 leukocytes, .45 mg/dL proteins, elevated IgG (4.55 mg/dL) and 2 oligoclonal bands (OCB) restricted to the CSF. ESR was 17 mm/h and CRP 5 mg/dL. Anti-Aquaporin4 anti-MOG antibodies were negative. The MRI showed right optic nerve hyperintensity, enhancing after the administration of contrast product, and multiple FLAIR focal lesions present throughout the white matter, with a noticeable confluence in the anterior temporal horns. She improved after IV high-dose methylprednisolone. Because the lesions of the white matter were highly atypical for an inflammatory disease and highly suggestive of CADASIL genetic testing was requested. A heterozygous pathogenic variant c994C>T p (Arg332Cys) in the exon 6 of the NOTCH3 gene, compatible with the diagnosis of CADASIL was found. Conclusions: This case highlights isolated optic nerve involvement as a presenting feature of CADASIL, possibly reflecting an inflammatory process associated with this hereditary vasculopathy.
Predicting non-initiation of care and dropout in a blended care CBT intervention: Impact of early digital engagement, sociodemographic, and clinical factors
Authors: Wu Monica S. , Chen Shih-Yin , Wickham Robert E. , Leykin Yan , Varra Alethea , Chen Connie , Lungu Anita 
Published: October 2022

Objective This study examines predictors of non-initiation of care and dropout in a blended care CBT intervention, with a focus on early digital engagement and sociodemographic and clinical factors. Methods This retrospective cohort analysis included 3566 US-based individuals who presented with clinical levels of anxiety and depression and enrolled in a blended-care CBT (BC-CBT) program. The treatment program consisted of face-to-face therapy sessions via videoconference and provider-assigned digital activities that were personalized to the client's presentation. Multinomial logistic regression and Cox proportional hazard survival analysis were used to identify predictors of an increased likelihood of non-initiation of therapy and dropout. Results Individuals were more likely to cancel and/or no-show to their first therapy session if they were female, did not disclose their ethnicity, reported poor financial status, did not have a college degree, endorsed more presenting issues during the onboarding triage assessment, reported taking antidepressants, and had a longer wait time to their first appointment. Of those who started care, clients were significantly more likely to drop out if they did not complete the digital activities assigned by their provider early in treatment, were female, reported more severe depressive symptoms at baseline, reported taking antidepressants, and did not disclose their ethnicity. Conclusions Various sociodemographic and clinical predictors emerged for both non-initiation of care and for dropout, suggesting that clients with these characteristics may benefit from additional attention and support (especially those with poor early digital engagement). Future research areas include targeted mitigation efforts to improve initiation rates and curb dropout.
Inverted Papilloma of the Middle Ear: Two New Cases and Systematic Review
Authors: Miller Peter L. , Walsh Erika , Cho Do-Yeon , Woodworth Bradford A. , Grayson Jessica W. 
Published: October 2022

Introduction Inverted papillomas of the middle ear are extremely rare tumors that carry an increased risk of recurrence and malignant transformation. There are currently 59 cases of middle ear inverted papillomas reported in the literature. The objective in this study was to systematically evaluate outcomes regarding middle ear inverted papillomas with respect to demographics, anatomical tumor sites, malignant transformation status, recurrence rate and HPV status. Study Design Retrospective case series and systematic review. Methods A systematic review was completed on June 25, 2020 with a search strategy including PubMed, Embase, Scopus and Google Scholar. This revealed 181 articles. Full-text review was completed, and 66 articles were included. 115 articles were eliminated due to duplication of articles from databases, article titles not applicable to the aims of the systematic review and articles describing inverted papilloma of body sites other than middle ear. Discussion Thirty-one cases of primary inverted papillomas of the middle ear were found in the literature with an additional 26 cases of secondary tumors. Four case reports did not specify primary versus secondary. The malignant transformation rate was 34.4% with a 53.6% recurrence rate. Treatment of middle ear inverted papillomas is primarily surgical with adjuvant radiation therapy considered for patients with recurrence or malignant transformation. Frequent clinical follow up of these patients is critical due to the increased rate of recurrence and malignant transformation. Conclusion Inverted papillomas of the middle ear are rare tumors that carry a high risk of recurrence and malignant transformation necessitating complete resection and frequent clinical follow up.
HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia
Authors: Lai Tzung-Huei , Ozer Hatice Gulcin , Gasparini Pierluigi , Nigita Giovanni , Distefano Rosario , Yu Lianbo , Ravikrishnan Janani , Yilmaz Selen , Gallegos Juan , Shukla Sachet , Puduvalli Vinay , Woyach Jennifer , Lapalombella Rosa , Blachly James , Byrd John C. , Sampath Deepa 
Published: October 2022

Abstract
Chronic lymphocytic leukemia (CLL) is a quiescent B-cell malignancy that depends on transcriptional dysregulation for survival. The histone deacetylases are transcriptional regulators whose role within the regulatory chromatin and consequence on the CLL transcriptome is poorly characterized. Here, we profiled and integrated the genome-wide occupancy of HDAC1, BRD4, H3K27Ac, and H3K9Ac signals with chromatin accessibility, Pol2 occupancy, and target expression signatures in CLL cells. We identified that when HDAC1 was recruited within super-enhancers (SEs) marked by acetylated H3K27 and BRD4, it functioned as a transcriptional activator that drove the de novo expression of select genes to facilitate survival and progression in CLL. Targeting HDACs reduced BRD4 and Pol2 engagement to downregulate the transcript and proteins levels of specific oncogenic driver genes in CLL such as BLK, a key mediator of the B-cell receptor pathway, core transcription factors such as PAX5 and IKZF3, and the antiapoptotic gene, BCL2. Concurrently, HDAC1, when recruited in the absence of SEs, repressed target gene expression. HDAC inhibition reversed silencing of a defined set of protein-coding and noncoding RNA genes. We focused on a specific set of microRNA genes and showed that their upregulation was inversely correlated with the expression of CLL-specific survival, transcription factor, and signaling genes. Our findings identify that the transcriptional activator and repressor functions of HDACs cooperate within the same tumor to establish the transcriptional dependencies essential for survival in CLL.
Health following recovery from immune thrombotic thrombocytopenic purpura: the patient’s perspective
Authors: Kelley Rachel A. , Cheney Marshall K. , Martin Clare M. , Cataland Spero , Quick Lauren B. , Keller San , Vesely Sara K. , Llaneza Amanda J. , Khawandanah Mohamad O. , Journeycake Janna M. , Panepinto Julie A. , Terrell Deirdra R. 
Published: October 2022

Abstract
The impact of residual symptoms following recovery from immune-mediated thrombotic thrombocytopenic purpura (iTTP) on activities of daily living during remission is not routinely discussed or evaluated by hematologists. This study used qualitative methodology to understand 3 issues from the patient’s perspective: the most important symptoms during remission, the impact of these symptoms on their daily activities, and the effectiveness of communication with hematologists. Oklahoma and Ohio patients participated in either focus groups or individual interviews. Eligibility included age ≥18 years, ADAMTS13 deficiency (&lt;10% activity) at diagnosis or relapse, and in clinical remission (≥1 year from episode). A nonprobabilistic purposive sampling approach was used. The most important symptoms were defined as symptoms mentioned across all 7 focus groups. The interviews supplemented focus group data. The analysis focused on describing the impact of symptoms and barriers to communicating with hematologists. A total of 44 patients participated (focus groups, N = 25; interviews, N = 19). The most important symptoms affecting the patients’ daily activities were cognitive issues, anxiety, depression, and fatigue. These symptoms affected patients’ ability to return to their previous level of functioning and created difficulties in relationships. A key communication barrier with their hematologists was forgetting to mention these symptoms. Although hematologists pronounce patients as recovered, iTTP remains a life-changing event. Patients often did not return to their previous functioning; relationships and careers were affected. However, patients may forget to discuss these concerns with their hematologist. To improve remission care, hematologists should incorporate patient-reported outcome measures evaluating these symptoms in remission visits.
Pirtobrutinib targets BTK C481S in ibrutinib-resistant CLL but second-site BTK mutations lead to resistance
Authors: Naeem Aishath , Utro Filippo , Wang Qing , Cha Justin , Vihinen Mauno , Martindale Stephen , Zhou Yinglu , Ren Yue , Tyekucheva Svitlana , Kim Annette S. , Fernandes Stacey M. , Saksena Gordon , Rhrissorrakrai Kahn , Levovitz Chaya , Danysh Brian P. , Slowik Kara , Jacobs Raquel A. , Davids Matthew S. , Lederer James A. , Zain Rula , Smith C. I. Edvard , Leshchiner Ignaty , Parida Laxmi , Getz Gad , Brown Jennifer R. 
Published: October 2022

Abstract
Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. We demonstrate that primary CLL cells from responding patients on the pirtobrutinib trial show reduced BCR signaling, cell survival, and CCL3/CCL4 chemokine secretion. At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis.
A phase 2 study of nivolumab combined with ibrutinib in patients with diffuse large B-cell Richter transformation of CLL
Authors: Jain Nitin , Senapati Jayastu , Thakral Beenu , Ferrajoli Alessandra , Thompson Philip , Burger Jan , Basu Sreyashi , Kadia Tapan , Daver Naval , Borthakur Gautam , Konopleva Marina , Pemmaraju Naveen , Parry Erin , Wu Catherine J. , Khoury Joseph , Bueso-Ramos Carlos , Garg Naveen , Wang Xuemei , Lopez Wanda , Ayala Ana , O’Brien Susan , Kantarjian Hagop , Keating Michael , Allison James , Sharma Padmanee , Wierda William 
Published: October 2022

Abstract
Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose ibrutinib was initiated from cycle 2 onward and continued daily until progression. For patients who were already on ibrutinib at the time of study entry, the same was continued while nivolumab was initiated. A total of 24 patients with RT with a median age of 64.5 years (range, 47-88) were enrolled. Ten patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTKi. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Four of 24 (17%) patients had checkpoint inhibition–related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; 1 patient had a grade 2 immunological toxicity. Combined nivolumab and ibrutinib is an active regimen for patients with DLBCL RT with an overall response rate of 42%. Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at www.clinicaltrials.gov as #NCT02420912.
Restoration of dendritic cell homeostasis and Type I/Type III interferon levels in convalescent COVID-19 individuals
Authors: Rajamanickam Anuradha , Kumar Nathella Pavan , Pandiaraj Arul Nancy , Selvaraj Nandhini , Munisankar Saravanan , Renji Rachel Mariam , Venkatramani Vijayalakshmi , Murhekar Manoj , Thangaraj Jeromie Wesley Vivian , Kumar Muthusamy Santhosh , Kumar Chethrapilly Purushothaman Girish , Bhatnagar Tarun , Ponnaiah Manickam , Sabarinathan Ramasamy , Saravanakumar Velusamy , Babu Subash 
Published: October 2022

Abstract
Background
Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity.

Results
In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNβ) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15–30 to Days 61–90 and plateau thereafter. Similarly, the levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15–30 to Days 61–90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs.

Conclusion
Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.
Can passive leg raise predict the response to fluid resuscitation in ED?
Authors: Elwan MH , Roshdy A , Elsharkawy EM , Eltahan SM , Coats TJ 
Published: October 2022

Abstract
Objective
Passive leg raise (PLR) can be used as a reversible preload challenge to stratify patients according to preload response. We aim to evaluate the accuracy of PLR, monitored by a non-invasive cardiac output monitor in predicting to response to fluid resuscitation in emergency department (ED).

Methods
We recruited adult patients planned to receive a resuscitation fluid bolus. Patients were monitored using a thoracic electrical bioimpedance (TEB) cardiac output monitor (Niccomo, Medis, Germany). A 3-min PLR was carried out before and after fluid infusion. Stroke volume changes (ΔSV) were calculated and a positive response was defined as ≥ 15% increase.

Results
We recruited 39 patients, of which 37 were included into the analysis. The median age was 63 (50–77) years and 19 patients were females. 17 patients (46%) were fluid responders compared to 11 (30%) with positive response to PLR1. ΔSV with PLR1 and fluid bolus showed moderate correlation (r = 0.47, 95% confidence interval, CI 0.17–0.69) and 62% concordance rate. For the prediction of the response to a fluid bolus the PLR test had a sensitivity of 41% (95% CI 22–64) and specificity of 80% (95% CI 58–92) with an area under the curve of 0.59 (95% CI 0.41–0.78). None of the standard parameters showed a better predictive ability compared to PLR.

Conclusion
Using TEB, ΔSV with PLR showed a moderate correlation with fluid bolus, with a limited accuracy to predict fluid responsiveness. The PLR test was a better predictor of fluid responsiveness than the parameters commonly used in emergency care (such as heart rate and blood pressure). These data suggest the potential for a clinical trial in sepsis comparing TEB monitored, PLR directed fluid management with standard care.