bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iliac Conduits for Endovascular Treatment of Aortic Pathologies: A Systematic Review and Meta-analysis
Authors: Giannopoulos Stefanos , Malgor Rafael D. , Sobreira Marcone L. , Siada Sammy S. , Rodrigues Diego , Al-Musawi Mohammed , Malgor Emily A. , Jacobs Donald L. 
Published: April 2021

Purpose: The treatment of thoracoabdominal aortic aneurysm has largely shifted to endovascular techniques. However, severe iliofemoral arterial disease often presents a challenge during these interventions. As a result, iliac conduits have been introduced to facilitate aortic endovascular therapy. The goal of the current study was to gauge utilization and to analyze iliac artery conduit outcomes to facilitate endovascular therapy to treat aortic pathologies. Materials and Methods: A meta-analysis of 14 studies was conducted with the use of random effects modeling. The incidence of periprocedural adverse events was gauged based on iliac conduit vs nonconduit cases and planned vs unplanned iliac conduit placement. Outcomes of interest included length of hospital stay, morbidity and mortality associated to conduits, and all-cause mortality. Results: Iliac conduits, either open or endo-conduits, were utilized in 17% (95% CI: 9%–27%) of 16,855 cases, with technical successful rate of 94% (95% CI: 80%–100%). Periprocedural complications occurred in 32% (95% CI: 22%–42%) of the cases, with overall bleeding complication rate being 10% (95% CI: 5%–16%). Female patients, positive history for smoking, pulmonary disease, and peripheral artery disease at baseline were associated with more frequent utilization of iliac conduits. Conduit use was associated with longer hospitalization, higher periprocedural all-cause mortality (OR: 2.85; 95% CI: 1.75–4.64; p<0.001), and bleeding complication rate (OR: 2.38; 95% CI: 1.58–3.58; p<0.001). Sensitivity analysis among conduit cases showed that planned conduits were associated with fewer periprocedural complications compared to unplanned conduits (OR: 0.38; 95% CI: 0.20–0.73; p=0.004). Conclusion: Iliac conduit placement is a feasible strategy, associated with high technical success to facilitate complex aortic endovascular repair. However, periprocedural adverse event rate, including bleeding complications is not negligible. All-cause mortality and morbidity rates among cases that require iliac conduits should be strongly considered during clinical decision making. High-quality comparative analyses between iliac conduit vs nonconduit cases and between several types of iliac conduit grafts aiming at facilitating endovascular aortic repair are still needed to determine the best strategy to address challenging iliac artery accesses.
A Hyperosmolar Saline Solution Fortified with Anti-Inflammatory Components Mitigates Articular Cartilage Pro-Inflammatory and Degradative Responses in an In Vitro Model of Knee Arthroscopy
Authors: Oladeji Lasun O. , Stoker Aaron M. , Stannard James P. , Cook James L. 
Published: April 2021

Objective To evaluate differences in pro-inflammatory and degradative mediator production from osteoarthritic knee articular cartilage explants treated with a hyperosmolar saline solution supplemented with anti-inflammatory components (l-glutamine, ascorbic acid, sodium pyruvate, epigallocatechin gallate [EGCG], and dexamethasone) or normal saline using an in vitro model for knee arthroscopy. Design Full-thickness 6 mm articular cartilage explants ( n = 12/patient) were created from femoral condyle and tibial plateau samples collected from patients who received knee arthroplasty. One explant half was treated for 3 hours with hyperosmolar saline (600 mOsm/L) supplemented with anti-inflammatory components and the corresponding half with normal saline (308 mOsm/L). Explants were cultured for 3 days and then collected for biomarker analyses. Media biomarker concentrations were normalized to the wet weight of the tissue (mg) and were analyzed by a paired t test with significance set at P < 0.05. Results Cartilage was collected from 9 females and 2 males (mean age = 68 years). Concentrations of MCP-1 ( P < 0.001), IL-8 ( P = 0.03), GRO-α ( P = 0.02), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), and MMP-3 ( P < 0.001) were significantly lower in explant halves treated with the enhanced hyperosmolar solution. When considering only those cartilage explants in the top tercile of tissue metabolism, IL-6 ( P = 0.005), IL-8 ( P = 0.0001), MCP-1 ( P < 0.001), GRO-α ( P = 0.0003), MMP-1 ( P < 0.001), MMP-2 ( P < 0.001), MMP-3 ( P < 0.001), and GAG expression ( P = 0.0001) was significantly lower in cartilage explant halves treated with the enhanced hyperosmolar solution. Conclusions Treatment of cartilage explants with a hyperosmolar saline arthroscopic irrigation solution supplemented with anti-inflammatory components was associated with significant decreases in inflammatory and degradative mediator production and mitigation of proteoglycan loss.
Activated IL-6 signaling contributes to the pathogenesis of, and is a novel therapeutic target for, CALR-mutated MPNs
Authors: Balliu Manjola , Calabresi Laura , Bartalucci Niccolò , Romagnoli Simone , Maggi Laura , Manfredini Rossella , Lulli Matteo , Guglielmelli Paola , Vannucchi Alessandro Maria 
Published: April 2021

Abstract
Calreticulin (CALR), an endoplasmic reticulum–associated chaperone, is frequently mutated in myeloproliferative neoplasms (MPNs). Mutated CALR promotes downstream JAK2/STAT5 signaling through interaction with, and activation of, the thrombopoietin receptor (MPL). Here, we provide evidence of a novel mechanism contributing to CALR-mutated MPNs, represented by abnormal activation of the interleukin 6 (IL-6)-signaling pathway. We found that UT7 and UT7/mpl cells, engineered by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) to express the CALR type 1–like (DEL) mutation, acquired cytokine independence and were primed to the megakaryocyte (Mk) lineage. Levels of IL-6 messenger RNA (mRNA), extracellular-released IL-6, membrane-associated glycoprotein 130 (gp130), and IL-6 receptor (IL-6R), phosphorylated JAK1 and STAT3 (p-JAK1 and p-STAT3), and IL-6 promoter region occupancy by STAT3 all resulted in increased CALR DEL cells in the absence of MPL stimulation. Wild-type, but not mutated, CALR physically interacted with gp130 and IL-6R, downregulating their expression on the cell membrane. Agents targeting gp130 (SC-144), IL-6R (tocilizumab [TCZ]), and cell-released IL-6 reduced proliferation of CALR DEL as well as CALR knockout cells, supporting a mutated CALR loss-of-function model. CD34+ cells from CALR-mutated patients showed increased levels of IL-6 mRNA and p-STAT3, and colony-forming unit–Mk growth was inhibited by either SC144 or TCZ, as well as an IL-6 antibody, supporting cell-autonomous activation of the IL-6 pathway. Targeting IL-6 signaling also reduced colony formation by CD34+ cells of JAK2V617F-mutated patients. The combination of TCZ and ruxolitinib was synergistic at very low nanomolar concentrations. Overall, our results suggest that target inhibition of IL-6 signaling may have therapeutic potential in CALR, and possibly JAK2V617F, mutated MPNs.
Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP
Authors: Eyre Toby A. , Wilson William , Kirkwood Amy A. , Wolf Julia , Hildyard Catherine , Plaschkes Hannah , Griffith John , Fields Paul , Gunawan Arief , Oliver Rebecca , Booth Stephen , Kothari Jaimal , Fox Christopher P. , Martinez-Calle Nicolas , McMillan Andrew , Bishton Mark , Collins Graham P. , Hatton Chris S. R. 
Published: April 2021

Abstract
Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI ≥80%, 33% were hospitalized with ≥1 infections compared with 23.3% of 355 patients receiving an IDI of &lt;80% (odds ratio, 1.61; 95% confidence interval, 1.15-2.25; P = .006). An increased risk of infection-related admission was independently associated with IDI &gt;80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score ≥6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin &gt;36 g/L, CIRS-G score &lt;6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial.
Spinal subdural hematoma and subdural anesthesia following combined spinal–epidural anesthesia: a case report
Authors: Bi Yanmei , Zhou Junying 
Published: April 2021

Abstract
Background
Subdural anesthesia and spinal subdural hematoma are rare complications of combined spinal-epidural anesthesia. We present a patient who developed both after multiple attempts to achieve combined spinal–epidural anesthesia.

Case presentation
A 21-year-old parturient, gravida 1, para 1, with twin pregnancy at gestational age 34+ 5 weeks underwent cesarean delivery. Routine combined spinal–epidural anesthesia was planned; however, no cerebrospinal fluid outflow was achieved after several attempts. Bupivacaine (2.5 mL) administered via a spinal needle only achieved asymmetric blockade of the lower extremities, reaching T12. Then, epidural administration of low-dose 2-chlorprocaine caused unexpected blockade above T2 as well as tinnitus, dyspnea, and inability to speak. The patient was intubated, and the twins were delivered. Ten minutes after the operation, the patient was awake with normal tidal volume. The endotracheal tube was removed, and she was transferred to the intensive care unit for further observation. Postoperative magnetic resonance imaging suggested a spinal subdural hematoma extending from T12 to the cauda equina. Sensory and motor function completely recovered 5 h after surgery. She denied headache, low back pain, or other neurologic deficit. The patient was discharged 6 days after surgery. One month later, repeat MRI was normal.

Conclusions
All anesthesiologists should be aware of the possibility of SSDH and subdural block when performing neuraxial anesthesia, especially in patients in whom puncture is difficult. Less traumatic methods of achieving anesthesia, such as epidural anesthesia, single-shot spinal anesthesia, or general anesthesia should be considered in these patients. Furthermore, vital signs and neurologic function should be closely monitored during and after surgery.
Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function
Authors: Campbell Duncan J. , Coller Jennifer M. , Gong Fei Fei , McGrady Michele , Boffa Umberto , Shiel Louise , Liew Danny , Stewart Simon , Owen Alice J. , Krum Henry , Reid Christopher M. , Prior David L. 
Published: April 2021

Abstract
Background
Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual’s kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors.

Methods
We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years.

Results
In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60–69 years, with similar sensitivities for men and women.

Conclusions
In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women.

Trial registration
ClinicalTrials.gov NCT00400257, NCT00604006, and NCT01581827.
Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model
Authors: Mimouni Myriam , Richard Christophe , Adenot Pierre , Letheule Martine , Tarrade Anne , Sandra Olivier , Dahirel Michèle , Lilin Thomas , Lecuelle Benoit , Gélin Valérie , Cohen Julien , Fauconnier Arnaud , Vialard François , Huchon Cyrille , Chavatte-Palmer Pascale 
Published: April 2021

Abstract
Background
Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model.

Methods
Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure (“group 12”) and N = 3 with 20 mmHg (“group 20”). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (μm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei.

Results
DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20.

Conclusions
This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.
Combined effect of hypertension and hyperuricemia on ischemic stroke in a rural Chinese population
Authors: Sun Peng , Chen Mengqi , Guo Xiaofan , Li Zhao , Zhou Ying , Yu Shasha , Yang Hongmei , Sun Guozhe , Zheng Liqiang , Sun Yingxian 
Published: April 2021

Abstract
Background
To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population.

Methods
The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis.

Results
After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment.

Conclusions
This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.
Adverse body composition and lipid parameters in patients with prolactinoma: a case-control study
Authors: Posawetz Anna Sophia , Trummer Christian , Pandis Marlene , Aberer Felix , Pieber Thomas R. , Obermayer-Pietsch Barbara , Pilz Stefan , Theiler-Schwetz Verena 
Published: April 2021

Abstract
Background
Hyperprolactinaemia might cause adverse metabolic effects. The aim of our study was to compare parameters of body composition, glucose and lipid metabolism between untreated patients with prolactinoma and controls and to assess changes after initiation of cabergoline.

Methods
Case-control study with a retrospectively analyzed follow-up in patients with prolactinoma after initiation of cabergoline therapy.

Results
21 patients with prolactinoma (9 micro- and 12 macroprolactinomas; 7 females) and 30 controls were analyzed. Patients with prolactinoma had significantly higher BMI than controls; fat mass did not differ between groups. Only men - but not women - with prolactinoma had significantly higher fat mass at all six sites measured compared to controls. Levels of LDL (130 (107–147.5) vs. 94.5 (80–127.5) mg/dl, p < 0.001) were significantly higher, levels of HDL (56 ± 16.7 vs. 69.2 ± 14.6 mg/dl, p = 0.004) significantly lower than in controls. Fasting glucose, HOMA-IR, HbA1c, adiponectin, CRP, and homocysteine did not differ between groups.
After a median of 10 weeks (IQR 7–18 weeks) after initiation of cabergoline, total (from 212.5 ± 36.2 to 196.9 ± 40.6 mg/dl, p = 0.018) and LDL cholesterol (130 (107–147.5) to 106.5 (94.3–148) mg/dl, p = 0.018) had significantly decreased. Analyzing men and women separately, this change occurred in men only.

Conclusions
Reasons for the association between prolactin and metabolic parameters include direct effects of prolactin on adipose tissue, hyperprolactinaemia-triggered hypogonadism and dopamine-agonist therapy per se. Altered lipid metabolism in patients with prolactinoma might imply an increased cardiovascular risk, highlighting the necessity to monitor metabolic parameters in these patients.
Lists of potential diagnoses that final-year medical students need to consider: a modified Delphi study
Authors: Urushibara-Miyachi Yuka , Kikukawa Makoto , Ikusaka Masatomi , Otaki Junji , Nishigori Hiroshi 
Published: April 2021

AbstractBackgroundContrastive learning is known to be effective in teaching medical students how to generate diagnostic hypotheses in clinical reasoning. However, there is no international consensus on lists of diagnostic considerations across different medical disciplines regarding the common signs and symptoms that should be learned as part of the undergraduate medical curriculum. In Japan, the national model core curriculum for undergraduate medical education was revised in 2016, and lists of potential diagnoses for 37 common signs, symptoms, and pathophysiology were introduced into the curriculum. This study aimed to validate the list of items based on expert consensus.MethodsThe authors used a modified Delphi method to develop consensus among a panel of 23 expert physician-teachers in clinical reasoning from across Japan. The panel evaluated the items on a 5-point Likert scale, based on whether a disease should be hypothesized by final-year medical students considering given signs, symptoms, or pathophysiology. They also added other diseases that should be hypothesized. A positive consensus was defined as both a 75% rate of panel agreement and a mean of 4 or higher with a standard deviation of less than 1 on the 5-point scale. The study was conducted between September 2017 and March 2018.ResultsThis modified Delphi study identified 275 basic and 67 essential other than basic items corresponding to the potential diagnoses for 37 common signs, symptoms, and pathophysiology that Japanese medical students should master before graduation.ConclusionsThe lists developed in the study can be useful for teaching and learning how to generate initial hypotheses by encouraging students’ contrastive learning. Although they were focused on the Japanese educational context, the lists and process of validation are generalizable to other countries for building national consensus on the content of medical education curricula.