bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metaplastic Breast Carcinoma: Experience of a Tertiary Cancer Center in the Middle East
Authors: Erjan Ayah , Almasri Hanan , Abdel-Razeq Hikmat , Al-Masri Mahmoud , Haddad Hussam , Alnsour Anoud , Rahman Fadwa Abdel , Dayyat Abdulmajeed 
Published: April 2021

Background: Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center. Methods: Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS. Results: 81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (<2 mm). Almost all patients received chemotherapy. 75.3% received radiotherapy, 23.5% received hormonal therapy and 6.2% received Trastuzumab. With a median follow-up of 54 months, 18.5% developed loco-regional recurrence and 34.6% relapsed distally. Five-year OS was 66.0%. On multivariate analysis: adjuvant radiotherapy correlated with better OS ( P < .0001), and tumor size >5 cm, nodal involvement and LVI correlated with worse OS, ( P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype. Conclusion: We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.
The impact of the SARS-CoV-2 epidemic outbreak on the vascular access team operations after conversion to COVID-19 dedicated hospital
Authors: Deganello Elisa , Gastaldo Francesco , Masiero Sonia , Fasson Milena , Colopi Riccardo Ivan , Girotto Luciano , Monticelli Jacopo , Marcante Elena , Furlan Patrizia , Baldo Vincenzo , Pilerci Claudio , Realdon Piero , Montemurro Domenico , Rigo Alberto , Benini Patrizia , Baratto Fabio 
Published: April 2021

Background: On February 21 2020, in Schiavonia Hospital occurred the first death by COVID-19 in Italy and since this date SARS-CoV-2 caused more than 100,000 deaths in our country. Our hospital was immediately closed and re-opened after 15 days as a reference Covid Hospital. Among services involved in a process of destruction and rebirth there was also the Vascular Access Team. Methods: We analyzed our Vascular Access Team activity comparing data from the first month (March) in which basically it did not work and data from the following month (April) in which we began to re-build the Team adapting it to the new reality. Results: In all patients admitted to Intensive Care Unit a Centrally Inserted Central Catheter multilumen was placed, but in March only 5.5% of patients admitted to Medicine-Sub-intensive Unit had a catheter different from the short peripheral cannula while in April it was possible to guarantee a more suitable catheter 31.7% of patients admitted to Medicine-Sub-intensive Unit ( p < 0.000). In April, compared to March, a significant higher number of Midline were implanted in Medicine-Sub-intensive Unit (36/139 vs 12/238 p < 0.000) where also a higher number of Centrally Inserted Central Catheter and Femoral Inserted Central Catheter were implanted (8/139 vs 1/238 p = 0.003). This change allowed us to implant more vascular accesses in Medicine-Sub-intensive Unit favoring Midline with a longer average duration. Only one patient with Midline developed a catheter vein thrombosis, and in only one patient the device was removed for suspected infection. Conclusions: The experience we gained will allow us to be more prepared in the future and our experience has highlighted that a structured Vascular Access Team is necessary to respond adequately to COVID-19 patients’ needs, to ensure the effectiveness of the maneuver, to reduce complications and to avoid the waste of resources, always working in safe condition.
Erroneous placement of central venous catheters in subclavian artery: Retrieval and successful hemostasis with a femoral closure device
Authors: Verloh Niklas , Scharf Gregor , Bäumler Wolf , Pfister Karin , Oikonomou Kyriakos , Stroszczynski Christian , Uller Wibke , Dollinger Marco 
Published: April 2021

Background: Retrospective evaluation of the safety and efficacy of the retrieval of misplaced central venous catheters (CVCs) in subclavian arteries using the femoral closure device Angio-Seal™. Methods: The clinical data of five patients (female, n = 2; mean age, 55.0 years ± 11.9) in whom a misplaced CVC within a subclavian artery was removed followed by closure of the vessel entry site with 8-French (F) Angio-Seal™ was analyzed. Results: In 4/5 patients (80%; CVC diameter, 7-8F) the procedure was technically successful without complications. In 1/5 patients (20%; CVC diameter, 11.5F) the procedure failed and an additional covered stent was placed for successful closure of the vessel entry site. There were no complications associated with the Angio-Seal™ or stent implantation during follow-up. Conclusion: Retrieval of a misplaced CVC within a subclavian artery using the percutaneous closure device Angio-Seal™ is quite safe and effective; however, caution is required if there is a mismatch in the diameter of the Angio-Seal™ and CVC. In the case of procedure failure, successful closure of the vessel entry site can be achieved by covered stent placement.
Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV
Authors: André Saudade , Pinto António E , Silva Giovani L , Silva Fernanda , Serpa Jacinta , Félix Ana 
Published: April 2021

Background: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients’ advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. Objective: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. Material and methods: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. Results: Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. Conclusions: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.
Epistaxis After Orthognathic Surgery: Literature Review and Three Case Studies
Authors: Girard Alisa , Lopez Christopher D. , Chen Jonlin , Perrault David , Desai Nikhil , Bruckman Karl C. , Bartlett Scott P. , Yang Robin 
Published: April 2021

Study Design: This is a literature review with 3 case studies. Objective: Intraoperative and postoperative bleeding are the most common complications of orthognathic surgery and have the potential to become life-threatening. The rarity of severe postoperative epistaxis has resulted in limited characterization of these cases in the literature. The purpose of this study is to 1) differentiate various presentations of epistaxis following orthognathic surgery in the literature, 2) identify management approaches, and 3) to synthesize a treatment algorithm to guide future management of postoperative epistaxis. Methods: A literature search of PubMed was conducted and 28 cases from 17 studies were assessed. Results: Bleeding within the first week may indicate isolated epistaxis, often resolved with local tamponade. Half of cases were attributed to pseudoaneurysm rupture (n = 14), with epistaxis onset ranging from postoperative day 6 to week 9. Angiography was used in most cases (n = 17), often as the primary imaging modality (n = 11). Nasal endoscopy is a less invasive and effective alternative to angiography with embolization. Proximal vessel ligation was used in 3 cases but is not preferred because collaterals may reconstitute flow through the defect and cause rebleeding. Repeat maxillary down-fracture with surgical exploration was described in 4 cases. Conclusions: As outlined in our management algorithm, nasal packing and tamponade should be followed by either local electrocautery or vascular imaging. Angiography with embolization is the preferred approach to diagnosis and management, whereas surgical intervention is reserved for cases of embolization failure or unavailability.
High Histamine Control Concentration Leads to False Negative Allergy Skin Testing
Authors: Amirneni Amulya , Tversky Jody 
Published: April 2021

Background Allergy skin test reliability depends on the reagents and controls selected. Histamine is used at 1 mg/ml and 6 mg/ml concentration but few studies address the rationale for selecting one versus the other and how this may impact diagnostic accuracy. Objective To determine the rate of false negative allergen skin tests responses between UniTest PC (using the 1 mg/mL histamine) and Quintip devices (using 6 mg/mL) for 4 common aeroallergens. Methods Subjects aged 18-65 with symptoms of allergy to cat and/or ragweed received skin testing with 4 aeroallergens (dust mite mix, timothy grass, ragweed, cat), histamine and control diluent. Those individuals who tested positive to cat or ragweed with one skin prick test (SPT) device but not the other then proceeded to nasal allergen challenge (NAC). The primary outcomes were the aeroallergen false negative rates and sensitivities of the skin test devices followed by nasal allergen (NAC). Results Twenty-five individuals were recruited and underwent a total of 300 SPTs. SPT to allergens (ragweed, dust mite, cat, and timothy grass) resulted in a statistically significant difference in wheal size among the two skin testing devices ( p value <0.0001, 0.0001, 0.0006, and 0.0053 respectively). Six NAC procedures were performed to cat/ragweed and 5 of 6 (83% were positive). The overall allergen sensitivity rate for UniTest and Quintip were 97% and 78% respectively with most false negatives due to the use of 6 mg/ml histamine control reagent. Conclusion Our study shows that 6 mg/ml concentration of histamine control reagent may contribute to a false interpretation of aeroallergen skin prick test results.
Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services
Authors: Paton Carol , Craig Tom K. J. , McConnell Brittany , Barnes Thomas R. E. 
Published: April 2021

Background: Long-acting injectable (LAI) antipsychotic medications are used to optimise treatment outcomes in schizophrenia. Guaranteed medication delivery increases the responsibility of prescribers to monitor and manage adverse effects. Methods: In the context of a quality improvement programme conducted by the Prescribing Observatory for Mental Health, a clinical audit addressed documented side-effect monitoring in patients prescribed continuing LAI antipsychotic medication under the care of United Kingdom adult mental health services. Results: A total of 62 mental health services submitted data on 5169 patients prescribed LAI antipsychotic medication for more than a year. An assessment of side effects had been documented in the past year in 2304 (45%) cases. Post hoc analysis showed that extrapyramidal side effects were more likely to have been assessed and found to be present in those patients prescribed LAI haloperidol, flupentixol or zuclopenthixol. There was little other targeting of assessments to the known side effects profiles of individual LAI antipsychotic medications, but when dysphoria had been assessed it was most commonly found with LAI haloperidol treatment and when weight gain, sexual and prolactin-related side effects had been assessed, they were more often identified with LAI paliperidone. Conclusion: The data suggest a relatively low frequency of side-effect assessments, largely untargeted. This is likely to result in many adverse effects going unrecognised and unmanaged, thus failing to tackle their potential to confound mental state assessment and adversely affect physical health and adherence. Patients receiving LAI antipsychotic medication have regular contact with a healthcare professional who administers the medication, which provides an opportunity to potentially remedy this situation.
The Impact of Immunization and Use of Oseltamivir on Influenza-Related Hospitalizations: A Population-Based Study
Authors: Athanassoglou Vassilis , Wilson Lauren A. , Liu Jiabin , Poeran Jashvant , Zhong Haoyan , Memtsoudis Stavros G. 
Published: April 2021

Background As the COVID-19 pandemic continues into flu season, it is critical to minimize hospitalizations to maximize capacity and preserve critical care resources. We sought to identify risk factors for influenza-related hospitalization, specifically the role of immunization and oseltamivir prescriptions. Methods Patients with influenza diagnoses were identified from the MarketScan database (2014-2018). Primary risk factors of interest were an influenza vaccination within 6 months prior to infection and oseltamivir prescriptions (filled on the day diagnosis, the following day, or 2-5 days). A multivariable logistic regression model was run to identify risk factors for influenza-related hospitalizations within 30 days of diagnosis. Results Among 2 395 498 influenza infections, 0.27% were hospitalized. Of those prescribed oseltamivir the day of diagnosis, 0.13% were later hospitalized, compared to 0.67% among those who filled prescriptions the following day and 11.8% when filled within 2 to 5 days. Upon adjustment, oseltamivir prescriptions filled on the day of diagnosis were associated with significantly decreased odds of hospitalization (OR 0.51 CI 0.48-0.55). Prescriptions filled within 1 to 5 days of diagnosis were associated with significantly increased odds of hospitalization (1 day OR 2.01 CI 1.81-2.24; 2-5 days OR 34.1 CI 31.7-36.6). Flu vaccination was associated with a lower odds for hospitalization (OR 0.84 CI 0.74-0.95). Conclusions We recommend oseltamivir be prescribed to patients when they first present with influenza-like symptoms to reduce the burden on the healthcare system. We also identified reduced odds of hospitalization associated with influenza vaccination, which is already well established, but particularly important this coming flu season.
Preservation of the Tibial Stump During Anterior Cruciate Ligament Reconstruction Surgery Did Not Increase the Rate of Surgery for Symptomatic Cyclops Lesions
Authors: Webster Kate E. , Murgier Jerome , Feller Julian A. , Klemm Haydn J. , Devitt Brian M. , Whitehead Timothy S. 
Published: April 2021

Background: Preservation of the tibial stump during anterior cruciate ligament reconstruction (ACLR) is controversial. While proposed benefits include enhanced graft revascularization, improved proprioception, and decreased graft rupture rates, a potential complication is the development of a symptomatic cyclops lesion. It is therefore important to determine whether any benefits outweigh potential complications. Purpose: To determine whether greater preservation of the tibial stump remnant would be associated with a decreased graft rupture rate without a concomitant increase in the rate of surgery for symptomatic cyclops lesions at 2 years after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A cohort of 658 patients in whom the amount of tibial stump preserved was classified as no stump (n = 228), <50% (n = 342), or >50% (n = 88) was followed up for 2 years, with graft ruptures and surgical treatment for cyclops lesions recorded. Contingency and Kaplan-Meier survival analyses were used to determine trends among the 3 remnant preservation groups in terms of graft rupture rates and surgery for cyclops lesions. Subgroup analysis was also conducted to examine sex-based differences. Results: There was no significant association between graft rupture rates and remnant preservation. There was a significant trend for fewer operations for symptomatic cyclops lesions with greater remnant preservation when the entire cohort was analyzed ( P = .04) and also when only female patients were analyzed ( P = .04). Conclusion: Although preservation of the tibial stump remnant was not associated with a reduced graft rupture rate, it was also not associated with increased rates of surgery for symptomatic cyclops lesions.
Plasmin-mediated cleavage of high-molecular-weight kininogen contributes to acetaminophen-induced acute liver failure
Authors: Henderson Michael W. , Sparkenbaugh Erica M. , Wang Shaobin , Ilich Anton , Noubouossie Denis F. , Mailer Reiner , Renné Thomas , Flick Matthew J. , Luyendyk James P. , Chen Zu-Lin , Strickland Sidney , Stravitz R. Todd , McCrae Keith R. , Key Nigel S. , Pawlinski Rafal 
Published: April 2021

Abstract
Acetaminophen (APAP)-induced liver injury is associated with activation of coagulation and fibrinolysis. In mice, both tissue factor–dependent thrombin generation and plasmin activity have been shown to promote liver injury after APAP overdose. However, the contribution of the contact and intrinsic coagulation pathways has not been investigated in this model. Mice deficient in individual factors of the contact (factor XII [FXII] and prekallikrein) or intrinsic coagulation (FXI) pathway were administered a hepatotoxic dose of 400 mg/kg of APAP. Neither FXII, FXI, nor prekallikrein deficiency mitigated coagulation activation or hepatocellular injury. Interestingly, despite the lack of significant changes to APAP-induced coagulation activation, markers of liver injury and inflammation were significantly reduced in APAP-challenged high-molecular-weight kininogen-deficient (HK−/−) mice. Protective effects of HK deficiency were not reproduced by inhibition of bradykinin-mediated signaling, whereas reconstitution of circulating levels of HK in HK−/− mice restored hepatotoxicity. Fibrinolysis activation was observed in mice after APAP administration. Western blotting, enzyme-linked immunosorbent assay, and mass spectrometry analysis showed that plasmin efficiently cleaves HK into multiple fragments in buffer or plasma. Importantly, plasminogen deficiency attenuated APAP-induced liver injury and prevented HK cleavage in the injured liver. Finally, enhanced plasmin generation and HK cleavage, in the absence of contact pathway activation, were observed in plasma of patients with acute liver failure due to APAP overdose. In summary, extrinsic but not intrinsic pathway activation drives the thromboinflammatory pathology associated with APAP-induced liver injury in mice. Furthermore, plasmin-mediated cleavage of HK contributes to hepatotoxicity in APAP-challenged mice independently of thrombin generation or bradykinin signaling.
Requirement for antiapoptotic MCL-1 during early erythropoiesis
Authors: Turnis Meghan E. , Kaminska Ewa , Smith Kaitlyn H. , Kartchner Brittany J. , Vogel Peter , Laxton Jonathan D. , Ashmun Richard A. , Ney Paul A. , Opferman Joseph T. 
Published: April 2021

AbstractAlthough BCL-xL is critical to the survival of mature erythrocytes, it is still unclear whether other antiapoptotic molecules mediate survival during earlier stages of erythropoiesis. Here, we demonstrate that erythroid-specific Mcl1 deletion results in embryonic lethality beyond embryonic day 13.5 as a result of severe anemia caused by a lack of mature red blood cells (RBCs). Mcl1-deleted embryos exhibit stunted growth, ischemic necrosis, and decreased RBCs in the blood. Furthermore, we demonstrate that MCL-1 is only required during early definitive erythropoiesis; during later stages, developing erythrocytes become MCL-1 independent and upregulate the expression of BCL-xL. Functionally, MCL-1 relies upon its ability to prevent apoptosis to promote erythroid development because codeletion of the proapoptotic effectors Bax and Bak can overcome the requirement for MCL-1 expression. Furthermore, ectopic expression of human BCL2 in erythroid progenitors can compensate for Mcl1 deletion, indicating redundancy between these 2 antiapoptotic family members. These data clearly demonstrate a requirement for MCL-1 in promoting survival of early erythroid progenitors.
Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results
Authors: Advani Ranjana H. , Moskowitz Alison J. , Bartlett Nancy L. , Vose Julie M. , Ramchandren Radhakrishnan , Feldman Tatyana A. , LaCasce Ann S. , Christian Beth A. , Ansell Stephen M. , Moskowitz Craig H. , Brown Lisa , Zhang Chiyu , Taft David , Ansari Sahar , Sacchi Mariana , Ho Linda , Herrera Alex F. 
Published: April 2021

AbstractThis phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.