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Long-term dual antiplatelet therapy (DAPT) has substantially reduced the risk of post-percutaneous coronary intervention (PCI) myocardial infarction and stent thrombosis at the expense of major bleeding. We hypothesized that a short-term DAPT followed by extended P2Y

inhibitor monotherapy might be appropriate for patients with both high ischemic and bleeding risks.

We searched the databases Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to identify randomized trials assessing the antiplatelet strategies after PCI. The primary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The efficacy outcome was a composite of all-cause mortality/cardiovascular disease (CVD) death, myocardial infarction, or stroke. A random-effect model was used to calculate the pooled hazard ratios (HRs) with 95% confidence intervals (CIs).

We identified 5 randomized trials comparing P2Y

inhibitor monotherapy with standard DAPT (12months) (16,057 versus 16,088). P2Y

inhibitor monotherapy following short-term DAPT (1 to 3months) significantly reduced the risk of BARC type 3 or 5 bleeding compared to standard DAPT (pooled HR 0.63, 95%CI 0.46-0.86). The difference between P2Y

inhibitor monotherapy and standard DAPT in reducing the composite CVD outcomes was not statistically significant (HR 0.88, 95%CI 0.77-1.01).

P2Y

inhibitor monotherapy might be an effective strategy for lowering severe bleeding complications and simultaneously preserving the ischemic benefit in patients receiving PCI.

P2Y12 inhibitor monotherapy might be an effective strategy for lowering severe bleeding complications and simultaneously preserving the ischemic benefit in patients receiving PCI.

Persons with dementia (PwD) are at greater risk for various adverse health outcomes, and the best care model remains to be determined. This study aimed to compare the physical and neurocognitive performance of PwD in the Program of All-inclusive Care for the Elderly (PACE) and residential dementia care units.

This was a case-control study comparing outcomes between care recipients of PACE services (PC group) and residential dementia care (RC group). Demographic characteristics, underlying diseases, physical function, cognitive function, mood status, and behavioral and psychotic symptoms of dementia (BPSDs) were assessed every 3-6 months in both groups, while frailty status and Timed Up-and-Go Test (TUGT) performance were assessed every 6 months in the PC group only.

Overall, 96 participants (PC group 25, RC group 71; mean age 86.4 ± 6.8 years) were enrolled with the median follow-up period of 43.6 weeks. Lower incidence of hospital admissions was noted in the PC group (0.52 ± 1.12 vs 1.38 ± 2.49 admissie needed to determine the most appropriate care model for PwD.Resistance of extramedullary leukemia growth post-transplant prevents cure. Review of its behavior detailed in 585 published cases should lead to better treatment. Leukemic tumors were found up to 13 years after transplant, most in sites inaccessible to physical exam. In 83%, marrow was not in morphologic relapse; next relapse was most often extramedullary. GABA Receptor antagonist Induction protocols alone produced few durable responses in acute leukemias and fatal marrow aplasia in 17 %. Overall, 120 patients survived over 2 years, 43 relapse-free up to 18 years, the majority after combined tumor-directed and systemic therapy. Overall median survival was 9 months. This review highlights how results can improve by defining extent of leukemia involvement with scans before transplant, and emergently when leukemic tumor is found after, ablating tumor directly to abort metastasis, and determining dosing of systemic chemotherapy that protects, without ablating, donor marrow. Monitoring total body remission with body scans should increase transplant cures.Number words allow us to describe exact quantities like sixty-three and (exactly) one. How do we derive exact interpretations? By some views, these words are lexically exact, and are therefore unlike other grammatical forms in language. Other theories, however, argue that numbers are not special and that their exact interpretation arises from pragmatic enrichment, rather than lexically. For example, the word one may gain its exact interpretation because the presence of the immediate successor two licenses the pragmatic inference that one implies "one, and not two". To investigate the possible role of pragmatic enrichment in the development of exact representations, we looked outside the test case of number to grammatical morphological markers of quantity. In particular, we asked whether children can derive an exact interpretation of singular noun phrases (e.g., "a button") when their language features an immediate "successor" that encodes sets of two. To do this, we used a series of tasks to compare English-speaking children who have only singular and plural morphology to Slovenian-speaking children who have singular and plural forms, but also dual morphology, that is used when describing sets of two. Replicating previous work, we found that English-speaking preschoolers failed to enrich their interpretation of the singular and did not treat it as exact. New to the present study, we found that 4- and 5-year-old Slovenian-speakers who comprehended the dual treated the singular form as exact, while younger Slovenian children who were still learning the dual did not, providing evidence that young children may derive exact meanings pragmatically.

The efficacy of immune checkpoint inhibitors (ICIs) in microsatellite instability-high/DNA mismatch repair (MSI/dMMR) metastatic colorectal cancer (mCRC) is well established. ICIs are responsible for pseudoprogression (PSPD) that complicates clinical decisions. We evaluated the PSPD frequency in patients with MSI/dMMR mCRC treated with ICIs.

Consecutive patients with MSI/dMMR mCRC treated with ICIs from February 2015 to December 2019at Saint-Antoine Hospital were included. Imaging was retrospectively and centrally reviewed according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) and immune RECIST (iRECIST). PSPD was defined as an unconfirmed disease progression by iRECIST.

One hundred twenty-three patients with MSI/dMMR mCRC were included. Thirty-six patients (29%) had radiological PD according to RECIST 1.1 during the median follow-up of 22.3 months (95% confidence interval [CI], 1.5-62.2), including 22 in the first 3 months (the primary radiological PD). Twenty-nine patientter 3 months.

High fidelity between non-small cell lung cancer (NSCLC) primary tumours and patient-derived tumour xenografts (PDTXs) is of paramount relevance to spur their application. Extensive proteomic and kinomic analysis of these preclinical models are missing and may inform about their functional status, in terms of phosphopeptides and hyperactive signalling pathways.

We investigated tumour xenografts derived from patients with NSCLC to identify hyperactive signalling pathways. Fresh tumour fragments from 81 NSCLC surgical samples were implanted in Nod/Scid/Gamma mice, and engrafted tumours were compared with primary specimens by morphology, immunohistochemistry, gene mutationanalyses, and kinase activity profiling. Four different tyrosine and serine/threonine kinase inhibitors were tested against primary tumour and PDTX lysates using the PamGene peptide microarray platform.

The engraftment rate was 33%, with successful engraftment being more associated with poor clinical outcomes. Genomic profiles led to the recognition of hotspot mutations, some of which were initially undetected in donor samples. Kinomic analyses showed that characteristics of primary tumours were retained in PDTXs, and tyrosine kinase inhibitors (TKIs) responses of individual PDTX lines were either expected, based on the genetic status, or alternatively defined suitable targets unpredictable by single-genome fingerprints.

Collectively, PDTXs mostly resembled their parental NSCLC. Combining genomic and kinomic analyses of tumour xenografts derived from patients with NSCLC, we identified patients' specific targetable pathways, confirming PDTXs as a preclinical tool for biomarkeridentification and therapeutic algorithm improvement.

Collectively, PDTXs mostly resembled their parental NSCLC. Combining genomic and kinomic analyses of tumour xenografts derived from patients with NSCLC, we identified patients' specific targetable pathways, confirming PDTXs as a preclinical tool for biomarker identification and therapeutic algorithm
improvement.

There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL.

Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. link2 Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed.

The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25±6% and 8±4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR]=2.0 [95% confidence interval CI 1.1-3.5]; P=0.016), MYCN-amplification (HR=2.4 [95% CI 1.2-4.4]; P=0.008), liver (HR=2.5 [95% CI 1.2-5.1]; P=0.01) or >1 metastatic compartment involvement (HR=7.1 [95% CI 1.0-48.4]; P=0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time.

The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.

The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.The prevalence and antimicrobial susceptibility of Clostridium perfringens (C. perfringens) in chickens and pigs were investigated in Beijing and Shanxi, China. In total, 322 C. perfringens (chicken n = 60 and pig n = 262) were obtained from 620 feces of chickens (n = 256) and pigs (n = 364). Multiplex PCR for toxin typing of C. perfringens revealed that all the isolates belong to type A, with 45.7 % (147/322) isolates carrying beta-2 toxin-encoding gene cpb2. Minimum inhibitory concentrations of 27 antimicrobial agents showed that 91.0 % of the tested C. perfringens isolates were resistant to gentamicin and sulfonamides (sulfisoxazole and trimethoprim-sulfamethoxazole), and little resistance was showed to amoxicillin-clavulanate, ceftiofur, doxycycline, vancomycin and linezolid. link3 Additionally, nosiheptide, avilamycin, virginiamycin and bacitracin exhibited good activity against the tested C. perfringens with low MIC50 (0.06 to ≤4 μg/mL) and MIC90 values (0.25-8 μg/mL). Whole genome sequencing (WGS) of 48 representative isolates from each farm indicated that the C.

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