bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRI and CT imaging biomarkers of cerebral amyloid angiopathy in lobar intracerebral hemorrhage
Authors: Schwarz Ghil , Banerjee Gargi , Hostettler Isabel C , Ambler Gareth , Seiffge David J , Ozkan Hatice , Browning Simone , Simister Robert , Wilson Duncan , Cohen Hannah , Yousry Tarek , Al-Shahi Salman Rustam , Lip Gregory Y H , Brown Martin M , Muir Keith W , Houlden Henry , Jäger Rolf , Werring David J 
Published: January 2022

Background: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. Methods: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. Results: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3–93.4) specificity, 29.6% (95% CI: 18.0–43.6) sensitivity, 59.3% (95% CI: 38.8–77.6) positive predictive value, and 66.4% (95%: CI 56.9–75.0) negative predictive value, 2.3 (95% CI: 1.2–4.6) positive likelihood ratio and 0.8 (95% CI 0.7–1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54–0.71). Conclusion: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.
Cerebral hemodynamic effects of early blood pressure lowering after TIA and stroke in patients with carotid stenosis
Authors: Mazzucco Sara , Li Linxin , McGurgan Iain J , Tuna Maria Assuncao , Brunelli Nicoletta , Binney Lucy E , Rothwell Peter M 
Published: January 2022

Background: Effects of early blood pressure (BP) lowering on cerebral perfusion in patients with moderate/severe occlusive carotid disease after transient ischemic attack (TIA) and non-disabling stroke are uncertain. Aims: We aimed to evaluate the changes in transcranial Doppler (TCD) indices in patients undergoing blood pressure lowering soon after TIA/non-disabling stroke. Methods: Consecutive eligible patients (1 November 2011 to 30 October 2018) attending a rapid-access clinic with TIA/non-disabling stroke underwent telemetric home blood pressure monitoring (HBPM) for 1 month and middle cerebral artery velocities measurements ipsilateral to carotid stenosis on TCD ultrasound in the acute setting and at 1 month. Hypertensive patients (HBPM ⩾ 135/85) underwent intensive BP-lowering guided by HBPM unless they had bilateral severe occlusive disease (⩾ 70%). Changes in BP and TCD parameters were compared in patients with extracranial moderate/severe carotid stenosis (between 50% and occlusion) versus those with no or mild (< 50%) stenosis. Results: Of 764 patients with repeated TCD measures, 42 had moderate/severe extracranial carotid stenosis without bilateral severe occlusive disease. HBPM was reduced from baseline to 1 month in hypertensive patients both with versus without moderate/severe carotid stenosis (−12.44/15.99 vs −13.2/12.2 mmHg, respectively, p-difference = 0.82), and changes in TCD velocities (4.69/14.94 vs 2.69/13.86 cm/s, respectively, p-difference = 0.52 for peak systolic velocity and 0.33/7.06 vs 1.75/6.84 cm/s, p-difference = 0.34 for end-diastolic velocity) were also similar, with no evidence of greater hemodynamic compromise in patients with stenosis/occlusion. Conclusion: There was no evidence of worsening of TCD hemodynamic indices in patients with moderate/severe occlusive carotid disease treated with BP-lowering soon after TIA/non-disabling stroke, suggesting that antihypertensive treatment in this group of patients is safe in the acute setting of TIA clinics.
Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress
Authors: Anderson Craig S , Rodgers Anthony , de Silva H Asita , Martins Sheila Ouriques , Klijn Catharina JM , Senanayake Bimsara , Freed Ruth , Billot Laurent , Arima Hisatomi , Thang Nguyen Huy , Zaidi Wan Asyraf Wan , Kherkheulidze Tinatin , Wahab Kolawole , Fisher Urs , Lee Tsong-Hai , Chen Christopher , Pontes-Neto Octavio , Robinson Thompson , Wang Jiguang , Naismith Sharon , Song Lili , Schreuder Floris H , Lindley Richard I , Woodward Mark , MacMahon Stephen , Al-Shahi Salman Rustam , Chow Clara K , Chalmers John 
Published: January 2022

Background: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. Objectives: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC “Triple Pill,” three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. Design: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130–160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. Results: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024. Conclusion: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.
Outcomes of day case shoulder replacement surgery in a stand-alone day care unit in the United Kingdom
Authors: Elgalli Mosab , Hind Jamie , Lahart Ian , Sidhu Gur Aziz Singh , Athar Sajjad , Ashwood Neil 
Published: January 2022

Background: This review aims to compare the outcomes for day case shoulder replacement with in-patient shoulder replacement surgery in a district general hospital. Methods: Seventy-three patients had 82 shoulder arthroplasty procedures. Forty-six procedures were undertaken in a dedicated stand-alone day-case unit and 36 were undertaken as in-patient cases. Patient were followed up at 6 weeks, 6 months and annually. Results: There was no significant difference between the outcomes of shoulder arthroplasty procedures performed in the day case or in-patient settings making this a safe option for surgical care in a unit with an appropriate care pathway. Six complications in total were observed, three in each group. Operation time was statistically shorter for day cases by 25.1 min (95% CI - 36.5 to −13.7; d = −0.95, 95% CI −1.42 to 0.48). Estimated marginal means (EMM) revealed lower post-surgery oxford pain scores in day cases (EMM = 3.25, 95% CI 2.35, 4.16) compared with inpatients (EMM = 4.65, 95% CI 3.64 to 5.67). Constant shoulder scores were higher in day cases versus inpatients. Conclusion: Day case shoulder replacement is safe with comparable outcomes to routine inpatient care for patients up to ASA 3 classification with high satisfaction and excellent functional outcomes.
Treatment of Chronic Ankle Instability in the Military Population: A Systematic Review
Authors: Goodrich Ezra , Vopat Bryan , Herda Ashley 
Published: January 2022

Background The high incidence of ankle sprain within the military sets the stage for prevalent chronic ankle instability. The purpose of this review was to compare and evaluate chronic ankle instability treatment strategies in the military population. Methods Electronic databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews guidelines for English-language, human studies with a military patient population that had been diagnosed with and treated for chronic ankle instability. Exclusion criteria were animal, cadaver, and review studies and case reports. Results Eight studies met the inclusion criteria, representing 695 military service members—625 males (89.9%) and 70 females (10.1%)—and 4 treatment strategies: Broström-related procedures, modified Watson-Jones procedure, Colville’s technique, and anatomic lateral ligament reconstruction using semitendinosus tendon allograft. The percentage of satisfactory outcomes was 100% for Colville’s technique, and ranged from 73.2% to 94.7% for Broström-related procedures and 72% to 80% for the modified Watson-Jones procedure. Mean American Orthopaedic Foot and Ankle Society scores, anterior drawer displacement, talar tilt, and visual analogue scale scores were also reported. Conclusion This review demonstrates that the Bröstrom procedure has consistently satisfactory outcomes within the military population, and Colville’s technique is another promising option for this patient population but would require additional studies to support this claim. Levels of Evidence: Level IV
Accuracy of CT-Derived Patient-Specific Instrumentation for Total Ankle Arthroplasty: The Impact of the Severity of Preoperative Varus Ankle Deformity
Authors: Umbel Benjamin D. , Hockman Taylor , Myers Devon , Sharpe B. Dale , Berlet Gregory C. 
Published: January 2022

Background Significant preoperative varus tibiotalar deformity was once believed to be a contraindication for total ankle arthroplasty (TAA). Our primary goal was to evaluate the influence of increasing preoperative varus tibiotalar deformity on the accuracy of final implant positioning using computed tomography (CT)-derived patient-specific guides for TAA. Methods Thirty-two patients with varus ankle arthritis underwent TAA using CT-derived patient-specific guides. Patients were subcategorized into varying degrees of deformity based on preoperative tibiotalar angles (0°-5° neutral, 6°-10° mild, 11°-15° moderate, and >15° severe). Postoperative weightbearing radiographs were used to measure coronal plane alignment of the tibial implant relative to the target axis determined by the preoperative CT template. Average follow-up at the time of data collection was 36.8 months. Results Average preoperative varus deformity was 6.06° (range: 0.66°-16.3°). Postoperatively, 96.9% (30/31) of patients demonstrated neutral implant alignment. Average postoperative tibial implant deviation was 1.54° (range: 0.17°-5.7°). Average coronal deviation relative to the target axis was 1.61° for the neutral group, 1.78° for the mild group, 0.94° for the moderate group, and 1.41° for the severe group (P = .256). Preoperative plans predicted 100% of tibial and talar implant sizes correctly within 1 size of actual implant size. Conclusion. Our study supports the claim that neutral postoperative TAA alignment can be obtained using CT-derived patient-specific instrumentation (PSI). Furthermore, final implant alignment accuracy with PSI does not appear to be impacted by worsening preoperative varus deformity. All but one patient (96.9%) achieved neutral postoperative alignment relative to the predicted target axis. Level of Evidence: Level IV, Clinical Case Series
A case report on penile duplication: A rare congenital anomaly
Authors: Nouman Ali Rao , Irfan Sohaib , Irfan Wajiha , khan Attiq-ur-rehman , Irfan Muhammad , Khalid Butt Muhammad 
Published: January 2022

Introduction: Penile duplication or penile diphallia is a rare congenital anomaly that is mainly associated with renal, anorectal or vertebral anomalies, that is, spina bifida. This condition was first described by Johannes Jacob Wecker in 1609 in Italy. Problem: Its incidence is extremely rare, about one in millions. The aetiology of this condition is unknown up till now; however, it is considered that defect of genital tubercle leads to the formation of diphallia. Methods: The condition is diagnosed clinically, and management depends on the appearance of genitalia and the associated anomalies as well as after taking into account the social and ethical considerations. Most of the time, management involves surgical incision of the non-functioning penis. Results: In this case report, a child of age 10 years presented with double penis since childhood. The child was evaluated clinically and radiologically for any other associated abnormalities, and his non-functional urethra was surgically removed. Level of evidence: Level IV
Do Clinical Outcomes and Failure Rates Differ in Patients With Combined ACL and Grade 2 MCL Tears Versus Isolated ACL Tears?: A Prospective Study With 14-Year Follow-up
Authors: Lucidi Gian Andrea , Agostinone Piero , Grassi Alberto , Di Paolo Stefano , Dal Fabbro Giacomo , Bonanzinga Tommaso , Zaffagnini Stefano 
Published: January 2022

Background: A combined injury to the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) is a common injury pattern encountered during clinical practice. Recent systematic reviews have found no consensus on the optimal method of managing this combined ligament injury pattern, and no long-term studies with modern techniques are available in the literature. Purpose: To compare 2 groups of patients who underwent isolated ACL reconstruction in terms of failures and clinical scores at long-term follow-up. In the first group were patients with isolated ACL tears (ACL group), while the second was composed of patients with combined ACL and MCL grade 2 tears (ACL + MCL group). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 57 patients (37 in the ACL group and 20 in the ACL + MCL group) underwent isolated ACL reconstruction with a double-bundle technique between January and December 2005. Patients were contacted for scores on the International Knee Documentation Committee subjective form, Western Ontario and McMaster Universities Osteoarthritis Index, and Tegner activity scale as well as data regarding ipsilateral or contralateral revision ACL surgery. A 2-way analysis of variance for repeated measures was used to statistically assess the differences between the groups. Results: Overall, 49 patients (86%) completed the survey and were therefore included in the study. The minimum follow-up was 14.6 years (range, 14.1-15.2 years). There was a significant reduction in both groups of all the outcome scores between the intermediate and final-follow-up. The number of failures was 3 of 31 (9.7%) in the ACL group and 1 of 18 (5.5%) in the ACL + MCL group; this difference was not significant. Moreover, there were no clinical differences between the groups in terms of graft failures, contralateral lesions, and clinical scores. Conclusion: At 14-year follow-up, no clinical difference or increased failure rate was observed between the study groups, suggesting that isolated ACL reconstruction could represent an appropriate treatment for a combined ACL and MCL grade 2 lesion.
Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients
Authors: Wilson Matthew R. , Eyre Toby A. , Kirkwood Amy A. , Wong Doo Nicole , Soussain Carole , Choquet Sylvain , Martinez-Calle Nicolás , Preston Gavin , Ahearne Matthew , Schorb Elisabeth , Moles-Moreau Marie-Pierre , Ku Matthew , Rusconi Chiara , Khwaja Jahanzaib , Narkhede Mayur , Lewis Katharine L. , Calimeri Teresa , Durot Eric , Renaud Loïc , Øvlisen Andreas Kiesbye , McIlroy Graham , Ebsworth Timothy J. , Elliot Johnathan , Santarsieri Anna , Ricard Laure , Shah Nimish , Liu Qin , Zayac Adam S. , Vassallo Francesco , Lebras Laure , Roulin Louise , Lombion Naelle , Manos Kate , Fernandez Ruben , Hamad Nada , Lopez-Garcia Alberto , O'Mahony Deirdre , Gounder Praveen , Forgeard Nathalie , Lees Charlotte , Agbetiafa Kossi , Strüßmann Tim , Htut Thura Win , Clavert Aline , Scott Hamish , Guidetti Anna , Barlow Brett R. , Tchernonog Emmanuelle , Smith Jeffery , Miall Fiona , Fox Christopher P. , Cheah Chan Y. , El Galaly Tarec Christoffer , Ferreri Andrés J. M. , Cwynarski Kate , McKay Pamela 
Published: January 2022

Abstract
Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P = .98; 3-year difference: 0.04% (−2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.
Cumulative incidence of subsequent malignancy after allo-HCT conditioned with or without low-dose total body irradiation
Authors: Nunez Lina , Abedin Tasnima , Naqvi Syed , Shen Hua , Chaudhry Ahsan , Bellerby Scott , Savoie Lynn , Daly Andrew , Shafey Mona , Duggan Peter , Storek Jan , Jamani Kareem 
Published: January 2022

Abstract
Subsequent malignancies (SMs) present a significant burden of morbidity and are a common cause of late mortality in survivors of allogeneic hematopoietic cell transplant (allo-HCT). Previous studies have described total body irradiation (TBI) as a risk factor for the development of SMs in allo-HCT survivors. However, most studies of the association between TBI and SM have examined high-dose TBI regimens (typically ≥600 cGy), and thus little is known about the association between low-dose TBI regimens and risk of SMs. Our goal, therefore, was to compare the cumulative incidence of SMs in patients of Alberta, Canada, who received busulfan/fludarabine alone vs busulfan/fludarabine plus 400 cGy TBI. Of the 674 included patients, 49 developed a total of 56 malignancies at a median of 5.9 years’ posttransplant. The cumulative incidence of SMs at 15 years’ post-HCT in the entire cohort was 11.5% (95% confidence interval [CI], 8.5-15.6): 13.4% (95% CI, 9.1-19.3) in the no-TBI group and 10.8% (95% CI, 6.6-17.4) in the TBI group. In the multivariable model, TBI was not associated with SMs, whereas there was an association with number of pre-HCT cycles of chemotherapy. The standardized incidence ratio for the entire cohort, compared with the age-, sex-, and calendar year–matched general population, was 1.75. allo-HCT conditioning that includes low-dose TBI does not seem to increase risk of SMs compared with chemotherapy-alone conditioning.
Circulating microvesicles and exosomes in small cell lung cancer by quantitative proteomics
Authors: Pedersen Shona , Jensen Katrine Papendick , Honoré Bent , Kristensen Søren Risom , Pedersen Camilla Holm , Szejniuk Weronika Maria , Maltesen Raluca Georgiana , Falkmer Ursula 
Published: January 2022

Abstract
Background
Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection.

Methods
Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis.

Results
Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC =  − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67–0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis.

Conclusions
In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.