Search

Objective Whether cervical disc arthroplasty (CDA) is superior to anterior cervical discectomy and fusion (ACDF) remains controversial, especially in relation to long‐term results. The present study aimed to evaluate the long‐term safety and efficiency of CDA and ACDF for cervical disc disease. Methods We performed this study according to the Cochrane methodology. An extensive search was undertaken in PubMed, Embase, and Cochrane databases up to 1 June 2019 using the following key words: “anterior cervical fusion,” “arthroplasty,” “replacement” and “artificial disc”. RevMan 5.3 (Cochrane, London, UK) was used to analyze data. Safety and efficiency outcome measures included the success rate, functional outcome measures, adverse events (AE), adjacent segment degeneration (ASD), secondary surgery, and patients’ satisfaction and recommendation rates. The OR and MD with 95% confidence interval (CI) were used to evaluate discontinuous and continuous variables, respectively. The statistically significant level was set at P

Objective To assess the long‐term outcomes after percutaneous reduction (PR) and screw fixation versus plate fixation via the sinus tarsi approach (STA) for displaced intra‐articular calcaneal fractures (DIACF). Methods This retrospective study included a total of 150 patients (June 2008–August 2011), comprising 85 men and 65 women (mean age, 38.4 years), who were assigned to the PR group or the STA group. The inclusion criteria were DIACF (>2 mm) including Sanders type II and III, closed fracture, unilateral fracture, no history of smoking or no smoking during hospitalization and 3 months after surgery, and follow‐up time not less than 8 years. The exclusion criteria were clear surgical contraindications (severe cardiovascular and cerebrovascular diseases), local or systemic infection symptoms, diagnosis with diabetes or lower extremity vascular disease, and Sanders type IV or open fractures. Outcomes were assessed by means of the American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scores, radiographic images, and postoperative complications. Results The mean follow‐up period was 8.7 years (range, 8.0–10.0 years). The AOFAS scores in the PR group during the follow‐up period were 54.2 ± 5.1, 85.8 ± 4.0, 88.1 ± 3.8, 87.9 ± 3.6, 87.8 ± 3.9, 86.9 ± 3.9, respectively, and in the STA group were 55.0 ± 5.6, 84.5 ± 5.2, 87.1 ± 3.8, 86.9 ± 3.8, 87.7 ± 3.3, and 87.6 ± 2.8, respectively. There was no significant difference in AOFAS scores, Bohler's angle, Gissane's angle, calcaneal length, and height between the two groups (P > 0.05). The good to excellent rate of the PR group (80.8%) was less than that of the STA group (91.7%) (P = 0.055). For Sanders III fractures, the good to excellent rate of the PR group (33.3%) was less than that of the STA group (76.9%) (P = 0.029). For calcaneal width recovery, the STA group performed better than the PR group (P 0.05). Conclusion From the 8–10‐year follow‐up results of PR and STA as surgical procedures for the treatment of DIACF, it was found that there was no significant difference in the overall efficacy between them. STA was found to be superior to the PR in terms of the recovery of calcaneal width, providing more stable fixation for Sanders III fractures. PR was found to be more effective in reducing wound complications.

AimTo study the association of caregiver factors and stroke patient factors with rehospitalizations over the first 3 months and subsequent 3–12 months post-stroke in Singapore.MethodsPatients with stroke and their caregivers were recruited in the Singapore Stroke Study, a prospective yearlong cohort. While caregiver and patient variables were taken from this study, hospitalization data were extracted from the national claims database. We used Poisson modelling to perform bivariate and multivariable analysis with counts of hospitalization as the outcome.ResultsTwo hundred and fifty-six patient with stroke and caregiver dyads (N = 512) were analysed, with patients having spouse (60%), child (29%), sibling (4%) and other (7%) as their caregivers. Among all participants, 89% of index strokes were ischemic, 57% were mild in severity and more than half (59%) of the patients had moderate or severe disability post-stroke as measured on the Modified Rankin Scale. Having social support in the form of a foreign domestic worker for general help of caregiver reduced the hospitalization rate over 3 months post-stroke by 66% (IRR: 0.342; 95% CI: 0.180, 0.651). Compared to having a spousal caregiver, those with a child caregiver had an almost three times greater rate of hospitalizations over 3–12 months post-stroke (IRR: 2.896; 95% CI: 1.399, 5.992). Higher reported caregiving burden at the 3-month point was associated with the higher subsequent rate of hospitalization.ConclusionRecommendations include the adoption of a dyadic or holistic approach to post-stroke care provision by healthcare practitioners, giving due importance to both patients with stroke and their caregivers, integrating caregivers in the healthcare system to extend the care continuum to include informal care in the community and provision of timely support for caregivers.

Summary Background Taxane–platinum combinations have shown promising activity in metastatic castration-resistant prostate cancers in single-group clinical studies but not in randomised trials. Distinct biological subsets of the disease might derive the greatest benefit from the addition of platinum. We aimed to determine whether adding carboplatin to cabazitaxel would improve the outcomes of men with metastatic castration-resistant prostate cancer. Methods We did a phase 1–2, open label, randomised study at two centres in men with progressive metastatic castration-resistant prostate cancer. In phase 1, patients received intravenous cabazitaxel 20–25 mg/m2 and intravenous carboplatin area under the curve (AUC) 3–4 mg/mL per min every 21 days. The maximum tolerated dose was defined as the highest dose cohort studied in which one of six or fewer patients experienced a dose-limiting toxicity. In phase 2, patients were randomly assigned (1:1) centrally by a computerised algorithm to intravenous cabazitaxel 25 mg/m2 with or without intravenous carboplatin AUC 4 mg/mL per min. All patients received growth factor support and oral prednisone 10 mg daily. The primary endpoints were the maximum tolerated dose of the combination in phase 1 and investigator-assessed progression-free survival in phase 2. This trial is registered at ClinicalTrials.gov , number NCT01505868 . Findings Between Aug 17, 2012, and May 11, 2015, nine patients completed phase 1 as planned, and 160 were randomly assigned to cabazitaxel (n=79) or cabazitaxel plus carboplatin (n=81) in phase 2. During phase I, grade 3 adverse events were anaemia (n=2), fatigue (n=1), thrombocytopenia (n=1), hypomagnesaemia (n=1), diarrhoea (n=1), hypokalaemia (n=1), anorexia (n=1), and dehydration (n=1), and no grade 4 adverse events occurred. No dose-limiting toxicities were observed, therefore, a maximum tolerated dose of cabazitaxel of 25 mg/m2 and carboplatin of AUC 4 mg/mL per min was selected for phase 2. At a median follow-up of 31·0 months (IQR 20·5–37·1), the combination improved the median progression-free survival from 4·5 months (95% CI 3·5–5·7) to 7·3 months (95% CI 5·5–8·2; hazard ratio 0·69, 95% CI 0·50–0·95, p=0·018). In the phase 2 study, the most common grade 3–5 adverse events were fatigue (7 [9%] of 79 in the cabazitaxel group vs 16 [20%] of 81 in the combination group), anaemia (3 [4%] vs 19 [23%]), neutropenia (3 [4%] vs 13 [16%]), and thrombocytopenia (1 [1%] vs 11 [14%]). There were no treatment-related deaths. Interpretation Carboplatin added to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant prostate cancer. Although adverse events were more common with the combination, the treatment was safe and generally well tolerated. Our data suggest that taxane–platinum combinations have a clinically beneficial role in advanced prostate cancer and a randomised phase 3 study is planned. Funding Sanofi Genzyme, University of Texas MD Anderson Cancer Center Prostate Cancer Moon Shot Program, Solon Scott III Prostate Cancer Research Fund, National Institutes of Health, and National Cancer Institute.

Dynamic 18F-fluorodeoxyglucose (FDG) PET can be used to quantitatively assess the rate of myocardial glucose uptake (MRGlu). The aim of this study was to evaluate the clinical significance and prognostic value of right ventricular (RV) MRGlu in patients with coronary artery disease and heart failure with reduced ejection fraction. Patients with left ventricular ejection fraction (LVEF) ≤ 40% were consecutively enrolled for FDG PET between November 2012 and May 2017. Global LV and RV MRGlu (μmol/min/100 g) were analyzed. Outcome events were independently assessed using electronic medical records to determine hospitalization for revascularization, new-onset ischemic events, heart failure, cardiovascular, and all-cause death. Differences between LV and RV MRGlu and associations with clinical characteristics and echocardiographic data were evaluated. Associations among FDG PET findings and outcomes were analyzed using Kaplan-Meier survival analysis. Seventy-five patients (mean age 62.2 ± 12.7 years, male 85.3%, LVEF 19.3 ± 8.6%) were included for analysis. The mean glucose utilization ratio of RV-to-LV (RV/LV MRGlu) was 89.5 ± 264.9% (r = 0.77, p

We present here the earliest known Asian fossil records of the Menispermaceae based on fossil fruits from Paleocene and Eocene localities in South China. A new genus and species, Paleoorbicarpum parvum sp. nov., and two new species of Stephania Loureiro, S. ornamenta sp. nov. and S. geniculata sp. nov., are recognized from Paleocene deposits of the Sanshui Basin, Guangdong, and a new occurrence of the widespread Eocene species Stephania auriformis (Hollick) Han & Manchester is recognized from the Maoming Basin, Guangdong. The Paleocene Stephania specimens described here represent the earliest fossil endocarp record of the Menispermaceae in eastern Asia. This discovery shows that the moonseed family had arrived in tropical and humid South China by at least the middle Paleocene, which provides important evidence for the origin and phytogeographic history of the family.

Heterogeneous distribution of components in the biological membrane is critical in the process of cell polarization. However, little is known about the mechanisms that can generate and maintain the heterogeneous distribution of the membrane components. Here, we report that the propagating wave patterns of the bacterial Min proteins can impose steric pressure on the membrane, resulting in transport and directional accumulation of the component in the membrane. Therefore, the membrane component waves represent transport of the component in the membrane that is caused by the steric pressure gradient induced by the differential levels of binding and dissociation of the Min proteins in the propagating waves on the membrane surface. The diffusivity, majorly influenced by the membrane anchor of the component, and the repulsed ability, majorly influenced by the steric property of the membrane component, determine the differential spatial distribution of the membrane component. Thus, transportation of the membrane component by the Min proteins follows a simple physical principle, which resembles a linear peristaltic pumping process, to selectively segregate and maintain heterogeneous distribution of materials in the membrane. VIDEO ABSTRACT

A new fossil leaf species, Liquidambar bella (Altingiaceae), is described from the lower part of the Eocene Huangniuling Formation, Maoming Basin, South China. Suprabasal venation in the fossil lobed Liquidambar leaves is reported for the first time. The new species provides additional palaeobotanical evidence on the morphological variability of this genus supporting the idea of combining the genera Liquidambar, Semiliquidambar and Altingia into the single genus Liquidambar as proposed based on molecular markers.

Herein, a multifunctional photochromic two-dimensional metal–organic framework (PMOF), [Zn(bcbpy)0.5(pma)0.5(H2O)]·3H2O (1), was synthesized (H2bcbpy·2Cl = 1,1′-bis(3-carboxylatobenzyl)-(4,4′-bipyridinium) dichloride, H4pma = pyromellitic acid). It showed an efficient ultraviolet light detection ability with an obvious color change from colorless to blue and fast response to an ultraviolet intensity of as low as 0.001 mW cm−2 in the narrow-band UV region. Furthermore, based on the Lewis acidic site and redox ability of the bipyridinium ligand, compound 1 showed amine-selective sensing upon contact with different amine vapors (NH3, ethylamine, n-propylamine, n-butylamine, diethylamine and triethylamine) and was also deposited on paper for use as portable test strips. The finely powdered sample could also be deposited on paper by coating it with a solution of ethanol, and the paper was used as an inkless and erasable print medium, which could be reprinted at least five times.

Peer reviewed: True, OBJECTIVE: The aim of this systematic review is to evaluate the various modalities available for extended ECG monitoring in the detection of atrial fibrillation (AF) following a cryptogenic stroke. METHODS: MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 2011 to November 2021. All randomised controlled trials and prospective cohort studies including the use of extended ECG monitoring >24 hours with a minimum duration of AF of 30 s in patients with either cryptogenic strokes or transient ischaemic attacks were included. A random-effects model was used to pool effect estimates of AF detection rates from different ECG modalities. RESULTS: 3924 studies were identified, of which 47 were included reporting on a pooled population of 6448 patients with cryptogenic stroke. The pooled AF rate for implantable loop recorders (ILRs) increased from 4.9% (3.0%-7.9%) at 1 month to 38.4% (20.4%-60.2%) at 36 months. Mobile cardiac outpatient telemetry (MCOT) had a significantly higher pooled AF detection rate of 12.8% (8.9%-17.9%) versus 4.9% (3.0%-7.9%) for ILR at 1 month (p

Background Glycolysis is an important metabolic manner in glioblastoma multiforme (GBM)'s rapid growth. It has been reported that glutamate-oxaloacetate transaminase 1 (GOT1) is low-expressed in GBM and patients with high-expressed GOT1 have better prognosis. However, the effect and mechanism of GOT1 on glycolysis and malignant phenotypes of GBM cells are still unclear. Methods The expression differences of GOT1 between GBM parenchyma and adjacent tissues were detected. The prognosis and clinical data with different levels of GOT1 were also analyzed. The glucose consumption, production of lactate and pyruvate were measured after GOT1 was knocked down or overexpressed. The effects of GOT1 on GBM cell's malignant phenotypes were analyzed by Western blot, CCK-8 assay, and flow cytometry. The relationship between GOT1 and pyruvate carboxylase (PC) was examined by immunoprecipitation and immunofluorescence. Results GOT1 was expressed little in GBM, and patients with highly expressed GOT1 had longer survival periods. Overexpressed GOT1 inhibited the glycolysis and malignant phenotypes of GBM cells. 2-DG treatment could partially reverse the enhancement of malignant phenotypes caused by knockdown of GOT1. The expression of GOT1 was positively correlated with PC. The inhibitory effect of GOT1 on glycolysis could be partially reversed by PC's knockdown. Conclusions GOT1 could impair glycolysis by interacting with PC and further inhibit the malignant phenotypes of GBM cells.

Elevated serum uric acid (SUA) levels, body shape index (BSI) and body roundness index (BRI) were associated with incident metabolic syndrome (MetS). We aimed to investigate the relationship among the SUA level, BSI, and BRI on the incidence of MetS.We retrospectively included 6221 healthy individuals from annual health exams at our hospital between 2016/1/1 and 2016/12/31. We defined hyperuricemia as SUA levels greater than 7 mg/dl in men and 6 mg/dl in women and MetS according to the contemporary definition. The study cohort included 6221 healthy individuals with an overall incidence rate of MetS of 9.8%. Compared with the normouricemic group, the hyperuricemic group had a greater incidence of MetS (17.2% vs. 9.6%, P 0.001). After full adjustment for confounders, the SUA level was significantly associated with incident MetS in addition to body mass index (BMI) (adjusted OR [aOR]: 1.161, 95% CI: 1.071-1.259, P 0.001), BRI (aOR: 1.196, 95% CI: 1.104-1.296, P 0.001), and BSI (aOR: 1.297, 95% CI: 1.200-1.403, P 0.001). Regarding the anthropometric indices, BMI and BRI were independent predictors of incident MetS, but the BSI lost its significant association in multivariate logistic regression analyses. In sensitivity analyses, various thresholds of elevated SUA levels remained associated with incident MetS.We showed a dose-response effect of SUA on incident MetS independent of BMI, BRI and BSI in healthy individuals. Future studies can use SUA levels to stratify cardiometabolic risk in healthy individuals.ClinicalTrials.gov with the identification number NCT03473951.

Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.

Simple Summary We postulate that a virus is more likely to cause cancer when it infects a progenitor stem-like cell rather than a progeny differentiated cell. We propose that the virus may turn out to be a surreptitious agent and a serendipitous model in our quest to investigate the origin of cancer. When it pertains, oncology recapitulates ontogeny, although genetic makeup is king. Cellular context may be the key to elucidating a stem cell origin of cancer. Abstract In 1911, Peyton Rous (Nobel Prize winner in 1966) demonstrated that a virus (i.e., RSV) caused cancer in chickens. In 1976, Bishop and Varmus (Nobel Prize winners in 1989) showed that the cellular origin of retroviral oncogenes was actually normal cellular genes (i.e., proto-oncogenes). In this article, we revisit the role viruses play in the genetic origin of cancer. We review a link between viruses or cancer and autoimmunity in an alternative stem cell origin of cancer. We propose that a virus is more likely to cause cancer when it infects a progenitor stem-like cell rather than a progeny differentiated cell. We postulate that both known (e.g., HBV and HPV) and novel viruses (e.g., SARS-CoV-2) pose an imminent threat in the emergence of chronic viral diseases as well as virally induced malignancies. Knowing the origin of cancer has profound implications on our current conception and perception of cancer. It affects our conduct in cancer research and our delivery of cancer care. It would be ironic if viruses turn out to be a useful tool and an ideal means in our quest to verify a genetic versus stem cell origin of cancer. When it pertains, oncology recapitulates ontogeny; although genetic makeup is pivotal, cellular context may be paramount to elucidating a stem cell origin of cancer.

Background: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. Objectives: We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. Methods: A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. Results: A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). Conclusion: We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Introduction: Endovascular thrombectomy(EVT) is considered standard of care for anterior circulation acute ischemic stroke(AIS) with large vessel occlusion(LVO). Young AIS-LVO patients have distinctly different underlying stroke mechanisms and etiologies. Methods: In this multicenter cohort study conducted from August 2014 to January 2020, we investigated the safety and effectiveness of EVT in young AIS-LVO patients aged≤50 years and evaluated associations between demographics, stroke etiology, neuroimaging factors and clinical outcomes, including functional outcomes, in-hospital mortality and symptomatic intracranial haemorrhage(sICH) in univariable and multivariable regression models. Results: 275 AIS-LVO patients from 10 tertiary centers in Germany, Sweden, Singapore and Taiwan were included. The more common TOAST subtypes included cardioembolism (82/275, 29.8%) and stroke of undetermined etiology (85/275, 30.9%). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%) and had the highest rate of good functional outcomes (29/42, 69.0%). Successful reperfusion was achieved in 85.1% (234/275). Excellent and good functional outcomes were achieved in 48.0% (132/275) and 66.0% (182/275) respectively. sICH occurred in 6.5% (18/275). National Institute of Health Stroke Scale (NIHSS) at presentation was inversely related with good functional outcomes (aOR0.92, 95% CI 0.88- 0.96 per point increase, p Conclusion: While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT.

Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.

This study analyzed RNA expression of genes for three serum tumor markers, alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH), in patients with testicular germ cell tumors (TGCT) type 2. The gene AFP encodes AFP, the gene for chorionic gonadotropin beta polypeptide 5 (CGB5) encodes a major part of the specific beta subunit of hCG, and the genes for LDH subunit A (LDHA), LDH subunit B (LDHB), and LDH subunit C (LDHC) encode three different subunits of LDH. LDHB encodes the LDHB subunit present as a tetramer in LDH isoenzyme 1 (LDH-1). We examined three datasets with 203 samples of normal testis tissue (NT) and TGCT type 2. Yolk sac tumor (YST) expressed RNA of AFP fourteen thousand times higher than seminoma (SE), embryonal carcinoma (EC), and teratoma (TER) combined (P = 0.00015). In the second microarray, choriocarcinoma (CC) expressed RNA of CGB5 ten times higher than other histologic types of TGCT combined. EC expressed RNA of LDHB twice higher than SE, YST and TER combined (P = 0.000041). EC expressed RNA of LDHB higher than that YST expressed RNA of AFP and that CC expressed RNA of CGB5. In conclusion, TGCT type 2 expressed RNA of LDHB markedly higher than the RNA of 23 other candidate genes for TGCT type 2.

Treatment options for unresectable, locally advanced or metastatic penile squamous cell carcinoma (SCC) are limited. Previous studies have shown that 40-62% of patients with penile SCC express PD-L1. We report three cases of locally advanced or metastatic penile SCC treated with pembrolizumab.Herein, we present three patients with recurrent, locally advanced or metastatic penile SCC who progressed on a platinum-based chemotherapy triplet and were treated with pembrolizumab, administered as part of a phase II clinical trial for rare tumors (NCT02721732). One patient with a microsatellite instability high (MSI-H) tumor experienced a durable partial response to pembrolizumab, underwent surgical consolidation, and remains disease-free 38.7 months later. Two patients experienced progressive disease within 3 months of beginning pembrolizumab. No one experienced a grade 3 or worse treatment-related adverse event.In sum, single-agent pembrolizumab was well tolerated as salvage therapy in a small cohort of patients with unresectable, locally advanced or metastatic penile SCC. Pembrolizumab produced an objective response in an MSI-H tumor, yet it did not control disease in two patients with MSS penile SCC. Rationale combination therapies, including pembrolizumab, warrant further investigation.ClinicalTrials.gov identifier: NCT02721732 . Registered March 23, 2016.

Simple Summary The observation that genetic mutations often do not cause cancer or disease in the phenomena of mosaicism, clonal hematopoiesis of indeterminate potential (CHIP), and heteroplasmy provides us with important clues about the origin and nature of cancer. We should be wary that the cancer genome may lead us astray to the wrong destination on a bad expedition unless we adopt the right cancer theory to elucidate it, and adhere to the proper scientific method to investigate it. Abstract Nowadays, many professionals are sequencing the DNA and studying the cancer genome. However, if the genetic theory of cancer is flawed, our faith in the cancer genome will falter. If gene sequencing is only a tool, we should question what we are making or creating with this tool. When we do not have the right cancer theory at our disposal, we cannot be sure that what we create from the cancer genome is meaningful or useful. In this article, we illustrate that mosaicism, CHIP, and heteroplasmy dispute our traditional perspectives about a genetic origin of cancer and challenge our current narratives about the cancer genome. We caution that when we have the wrong cancer theory, big data can provide poor evidence. Precision medicine may become rather imprecise. Targeted therapy either does not work or work for the wrong reasons. The cancer genome thus becomes a paradox rather than a paradigm.

This retrospective study is to assess the performance of (18)F-Fluciclovine PET/CT in prostate cancer (PC) patients with multiple treatment failures and prostate-specific antigen (PSA) ≤ 0.5 ng/mL. PC patients with multiple treatment failures who had PSA level within 2-week interval of (18)F-Fluciclovine PET/CT (PSA(PET)) ≤ 0.5 ng/mL were identified in retrospective review of our institution’s database (n=28). Patient, tumor, treatment, PSA and castration characteristics as well as findings on (18)F-Fluciclovine PET/CT were collected and compared between positive and negative (18)F-Fluciclovine PET/CT subgroups by using Fisher’s exact test. The overall detection rate of (18)F-Fluciclovine PET/CT was 7 of 28 studies (25%). PSA(PET) > 0.2 ng/mL was associated with higher detection rates in all (33.3 vs 10%, P=0.172), castration-resistant (CR) (50 vs 20%, P=0.343) and castration-sensitive (CS) (28.6 vs 0%, P=0.179) patients. Sites of recurrence were local 42.9% (3/7), nodal 42.9% (3/7) and bone metastases 14.3% (1/7). Higher Gleason score (GS 8-10) (33.3 vs 14.5%, P=0.396), advanced tumor stage (T3-T4) (35.7 vs 20%, P=0.653), second-line androgen deprivation therapy (ADT) uses (66.7 vs 20%, P=0.145), chemotherapy uses (50 vs 23.1%, P=0.444) and CRPC (33.3 vs 21.1%, P=0.483) related to positivity of (18)F-Fluciclovine PET/CT but none reached statistical significance. Performance of (18)F-Fluciclovine PET/CT in prostate cancer patients with multiple treatment failures and PSA(PET) ≤ 0.5 ng/mL was acceptable particularly in patients with PSA(PET) ≥ 0.3 ng/mL, CRPC, initial GS ≥ 8 or T3-T4.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p

CA extern - Weitere Nicht-UDE-Autoren sind nicht genannt. Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiology

5059 Background: Response to androgen signaling inhibitors is highly variable and dictates prognosis in castration resistant prostate cancer (CRPC). The development of effective combinations for CRPC has been hampered by the absence of biomarkers to identify its distinct biological subsets, obligating the homogeneous application of therapies to a heterogeneous disease in clinical trials. We previously defined the aggressive variant prostate cancers as a framework for the study of those with poor responses to androgen signaling inhibitors (dubbed ‘androgen indifferent’) and observed improved outcomes in this subset when carboplatin was added to cabazitaxel (CABCARB). In contrast, results of prospective trials suggested that anti-CTLA-4 therapy may benefit patients with androgen responsive disease. We hypothesized that said combinations applied to subsets defined by early marker declines to androgen ablation would improve overall survival (OS) over historical data in unselected CRPC. Methods: In an open-label, phase II trial (NCT02703623), men with mCRPC received abiraterone and apalutamide (ABIpAPA; Mod 1). At week 8, patients had either a ‘satisfactory’ (S) decline in PSA (≥ 50% from baseline) and CTC (≤5/7.5mL) or ‘unsatisfactory’ (US). S patients ( Mod 2) were randomized to continue ABIpAPA alone ( 2A) or with up to 4 cycles of ipilimumab (IPI, 2B). US patients ( Mod 3) continued ABIpAPA with up to 10 cycles of CABCARB. Thereafter patients continued ABIpAPA until progression. OS was calculated from entry into Mod 2 or 3. Based on historical data, the estimated median OS for men in Mod 2 and Mod 3 were 36 and 16 months respectively. Results: 195 men with CRPC were enrolled between May 2016 and August 2019. 128 (67%) were allocated to S of which 64 each were randomized to receive IPI vs. not. 3 went off study during Mod 1 without clinical decline. Of 64 patients allocated to US, 59 were treated with CABCARB on study . Men in US were more likely to have had de novo metastasis (33% vs 59%, p < 0.001), RECIST measurable disease (23% vs 42%, p = 0.01), and liver metastases (3% vs 13%, p = 0.01). Differences in baseline circulating markers between the groups are shown in Table 1. Serious adverse events were reported for 3 (4.7%), 21 (33%), and 6 (10.2%) patients for M od 2A, 2B, and 3 respectively. One death due to neutropenic sepsis occurred in Mod 3. At a median follow-up of 48 months, the median (95% CI) OS in Mod2A was 44.3 (38.1, 47.7) months, 41.4 (33.3 months, not reached) in Mod 2B, and 18.7 (14.3, 36.3) months in Mod 3. Conclusions: These data substantiate the impact of underlying biology on CRPC patient outcomes and the urgent need for biomarkers that can enable the development of therapies specific to each subset. Correlative studies to identify said biomarkers will be presented. Clinical trial information: NCT02703623.