There are questions surrounding the real-world effectiveness of chemotherapeutic treatments for pancreatic ductal adenocarcinoma. This literature review compared the clinical characteristics and ...outcomes of available real-world evidence (RWE) for liposomal irinotecan in combination with 5-fluorouracil (5-FU) and leucovorin (LV), a treatment regimen indicated for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously progressed on gemcitabine-based therapy.
A targeted literature search was conducted in the PubMed Central® and Embase® databases to identify available RWE regarding patients with mPDAC receiving liposomal irinotecan published within the last 5 years (January 2014–September 2019). Data were extracted for prior lines of therapy, performance status, overall survival (OS), progression-free survival (PFS), duration of exposure, and adverse events.
Six studies met inclusion criteria. A comparison of baseline patient characteristics and results with the included evidence reveals a clinically fragile, real-world patient population in terms of age (range: 61–68), prior lines of therapy with 34–61% of patients receiving ⩾2 lines of lines of prior therapy and performance status 49.8–100% of patients with Eastern Cooperative Oncology Group (ECOG) 0–1. Studies observed wide OS (range: 5.3–9.4 months) and similar PFS (range: 2.3–4.1 months), with two studies measuring duration of exposure (7.3 weeks, 3.1 months). Patients analyzed by RWE studies tended to be older with significant disease progression, poor performance status, and more heavily pretreated compared with the phase III registrational trial (NAPOLI-1). Despite this, patients treated with liposomal irinotecan + 5-FU/LV therapy had similar outcomes as those in NAPOLI-1.
Objectives:
Evaluate all-cause and endometriosis-related health care resource utilization and costs among newly diagnosed endometriosis patients with high-risk versus low-risk opioid use or patients ...with chronic versus non-chronic opioid use.
Methods:
A retrospective analysis of IBM MarketScan® Commercial Claims data from 2009 to 2018 was performed for females aged 18 to 49 with newly diagnosed endometriosis (International Classification of Diseases, Ninth Edition code: 617.xx; International Classification of Diseases, Tenth Edition code: N80.xx). Two sub-cohorts were identified: high-risk (⩾1 day with ⩾90 morphine milligram equivalents per day or ⩾1-day concomitant benzodiazepine use) or chronic opioid utilization (⩾90-day supply prescribed or ⩾10 opioid prescriptions). High-risk or chronic utilization was evaluated during the 12-month assessment period after the index date. Index date was the first opioid prescription within 12 months following endometriosis diagnosis. All outcomes were assessed over 12-month post-assessment period while adjusting for demographic and clinical characteristics.
Results:
Out of 61,019 patients identified, 18,239 had high-risk opioid use and 5001 chronic opioid use. Health care resource utilization drivers were outpatient visits and pharmacy fills, which were higher among high-risk versus low-risk patients (outpatient visits: 17.49 vs 15.51; pharmacy fills: 19.58 vs 16.88, p < 0.0001). Chronic opioid users had a higher number of outpatient visits (19.53 vs 15.00, p < 0.0001) and pharmacy fills (23.18 vs 16.43, p < 0.0001) compared to non-chronic opioid users. High-risk opioid users had significantly higher all-cause health care costs compared to low-risk opioid users (US$16,377 vs US$13,153; p < 0.0001). Chronic opioid users also had significantly higher all-cause health care costs compared to non-chronic opioid users (US$20,930 vs US$12,272; p < 0.0001). Similar patterns were observed among endometriosis-related HCRU, except pharmacy fills among high-risk and chronic sub-cohorts.
Conclusion:
This analysis demonstrates significantly higher all-cause and endometriosis-related health care resource utilization and total costs for high-risk opioid users compared to low-risk opioid users among newly diagnosed endometriosis patients over 1 year. Similar trends were observed for comparing chronic opioid users with non-chronic opioid users, except for endometriosis-related pharmacy fills and associated costs.
Abstract
We prove that the projection from graph complex with at least one source to oriented graph complex is a quasi-isomorphism, showing that homology of the “sourced” graph complex is also equal ...to the homology of standard Kontsevich’s graph complex. This result may have applications in theory of multi-vector fields $T_{\textrm{poly}}^{\geq 1}$ of degree at least one, and to the hairy graph complex that computes the rational homotopy of the space of long knots. The result is generalized to multi-directed graph complexes, showing that all such graph complexes are quasi-isomorphic. These complexes play a key role in the deformation theory of multi-oriented props recently invented by Sergei Merkulov. We also develop a theory of graph complexes with arbitrary edge types.
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We prove that the trace of categorified quantum
sl
3
introduced by Khovanov and Lauda can also be identified with quantum
sl
3
, thus providing an alternative way of decategorification. This is the ...second step of trace decategorification of quantum
sl
n
groups over the integers, the first being the
sl
2
case. The main technique used is decoupling of categorified quantum group into its positive and negative part. This technique can be used for more general categorified quantum groups to reduce the problem to the trace decategorification of its positive part. In the case of quantum
sl
3
, there is an explicit form of the canonical basis of the positive (and isomorphically negative) part of it based on indecomposables found by Stošić, leading to the full result in this case.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin ...(bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with testicular cancer (TC), the application of these tumor markers may be accompanied with certain limitations, implying the need for additional biomarkers. Contrary to TC, there is a lack of established serological biomarkers for penile cancer (PC) and the management of this urological malignancy is based on multiple clinicopathological parameters. Therefore, the identification and rigorous analytical and clinical validation of reliable biomarkers are considered pivotal for improving PC management. Inflammation may be associated with all stages of oncogenesis, from initial neoplastic transformation to angiogenesis, tissue invasion, and metastasis. Accordingly, an array of inflammation-related indices have gained increasing attention as emerging predictors of oncological outcomes. The clinical usefulness of systemic inflammation markers was reported in many urological and non-urological malignancies. The aim of this narrative review is to summarize current scientific data regarding the prognostic and predictive significance of systemic inflammation markers in TC and PC patients.
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We continue studying the cohomology of the hairy graph complexes which compute the rational homotopy of embedding spaces, generalizing the Vassiliev invariants of knot theory, after the second part ...in this series. In that part we have proven that the hairy graph complex
HGC
m
,
n
with the extra differential is almost acyclic for even
m
. In this paper, we give the expected same result for odd
m
. As in the previous part, our results yield a way to construct many hairy graph cohomology classes by the waterfall mechanism also for odd
m
. However, the techniques are quite different. The main tool used in this paper is a new differential, deleting a vertex in non-hairy Kontsevich’s graphs, and a similar map for hairy vertices. We hope that the new differential can have further applications in the study of Kontsevich’s graph cohomology. Namely it is conjectured that the Kontsevich’s graph complex with deleting a vertex as an extra differential is acyclic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular skin condition that is associated with significant psychosocial and economic burden and a diminished quality of life and work ...productivity. Accurate diagnosis of HS is challenging due to its unknown etiology, which can lead to underdiagnosis or misdiagnosis that results in increased patient and healthcare system burden. We applied machine learning (ML) to a medical and pharmacy claims database using data from 2000 through 2018 to develop a novel model to better understand HS underdiagnosis on a healthcare system level. The primary results demonstrated that high-performing models for predicting HS diagnosis can be constructed using claims data, with an area under the curve (AUC) of 81%-82% observed among the top-performing models. The results of the models developed in this study could be input into the development of an impact of inaction model that determines the cost implications of HS diagnosis and treatment delay to the healthcare system.
The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development ...of testicular germ cell tumor (GCT), as well as the progression of the disease.
(rs6721961),
(rs1332018),
(rs4880) and
(rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant
*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant
*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined
*TT/
*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant
*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease.
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There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features ...determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm,
= 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%,
= 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%,
= 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38,
= 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (
= 0.381) or non-seminoma (
= 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm.
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Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding ...antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of
rs4925,
rs156697, and
rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the
*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of
rs2297235*A/G*G/G genotype, and in carriers of combined
rs156697*A/G*G/G and
rs2297235*A/G*G/G genotypes. Haplotype H7 (
rs4925*C/
rs2297235*G/
rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (
> 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that
polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development.
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