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BACKGROUND: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. METHODS: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). RESULTS: 666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %. ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. CONCLUSION: This first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Cisplatino , Desoxicitidina , Gemcitabina , Humanos , Masculino , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/mortalidad , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents. METHODS: We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group. RESULTS: Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; Pâ =â .95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; Pâ =â .4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; Pâ =â .9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, Pâ =â .27). CONCLUSION: HR-/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.
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Neoplasias del Sistema Biliar , Reparación del ADN por Recombinación , Humanos , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/patología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Reparación del ADN por Recombinación/genética , Reparación del ADN por Recombinación/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Platino (Metal)/uso terapéutico , Platino (Metal)/farmacologíaRESUMEN
BACKGROUND: Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy. OBJECTIVE: This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer. METHODS: We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects. CONCLUSIONS: This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.
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BACKGROUND: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). OBJECTIVE: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting. PATIENTS AND METHODS: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone. The impact of adding durvalumab to chemotherapy in terms of overall survival (OS) and progression free survival (PFS) was investigated with univariate and multivariate analysis. RESULTS: Overall, 563 patients were included in the analysis: 213 received cisplatin/gemcitabine alone, 350 received cisplatin/gemcitabine plus durvalumab. At the univariate analysis, the addition of durvalumab was found to have an impact on survival, with a median OS of 14.8 months versus 11.2 months [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.80, p = 0.0002] in patients who received cisplatin/gemcitabine plus durvalumab compared to those who received cisplatin/gemcitabine alone. At the univariate analysis for PFS, the addition of durvalumab to cisplatin/gemcitabine demonstrated a survival impact, with a median PFS of 8.3 months and 6.0 months (HR 0.57, 95% CI 0.47-0.70, p < 0.0001) in patients who received cisplatin/gemcitabine plus durvalumab and cisplatin/gemcitabine alone, respectively. The multivariate analysis confirmed that adding durvalumab to cisplatin/gemcitabine is an independent prognostic factor for OS and PFS, with patients > 70 years old and those affected by locally advanced disease experiencing the highest survival benefit. Finally, an exploratory analysis of prognostic factors was performed in the cohort of patients who received durvalumab: neutrophil-lymphocyte ratio (NLR) and disease stage were to be independent prognostic factors in terms of OS. The interaction test highlighted NLR ≤ 3, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0, and locally advanced disease as positive predictive factors for OS on cisplatin/gemcitabine plus durvalumab. CONCLUSION: In line with the results of the TOPAZ-1 trial, adding durvalumab to cisplatin/gemcitabine has been confirmed to confer a survival benefit in terms of OS and PFS in a real-world setting of patients with advanced BTC.
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Biliar , Cisplatino , Desoxicitidina , Gemcitabina , Humanos , Cisplatino/uso terapéutico , Cisplatino/farmacología , Cisplatino/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/farmacología , Desoxicitidina/administración & dosificación , Masculino , Femenino , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/administración & dosificación , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. METHODS: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50â¯mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43â¯% in arm A and 50â¯% in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41â¯% (77â¯%) vs 14 (27â¯%) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A). CONCLUSIONS: First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.
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Administración Metronómica , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Ciclofosfamida , Doxorrubicina , Calidad de Vida , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Persona de Mediana Edad , Ciclofosfamida/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Receptor ErbB-2/metabolismo , Supervivencia sin Progresión , Esquema de Medicación , Resultado del Tratamiento , Antraciclinas/administración & dosificación , PolietilenglicolesRESUMEN
BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Anciano , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Heterogeneidad Genética , PronósticoRESUMEN
BACKGROUND: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting. MATERIAL AND METHODS: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included. RESULTS: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs. CONCLUSIONS: These results confirm the effectiveness and safety of pemigatinib in a real-world setting.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Morfolinas , Pirimidinas , Pirroles , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Estudios de Cohortes , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
Cystic fibrosis (CF) is the most common severe autosomal recessive genetic disorder among Caucasians. The improvement of genetic techniques has allowed the identification of an increasing number of genetic variants, including large rearrangements such as duplications. We report the first case of a whole CFTR gene duplication in a healthy newborn, who had normal sweat test, also carrying R74W and V855I variants on the same allele. Familial segregation analysis and the observed frequencies of all the CFTR gene variants, revealed that R74W and V855I were probably both present in a cis arrangement on the allele also containing the duplication (i.e., in a double complex allele). Since R74W is a "variant of varying clinical consequence" its arrangement in trans with one pathogenic variant may not be sufficient to cause a classic CF disease phenotype. Moreover, its duplication could even be an advantage that could compensate for the effect of the alteration.
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PURPOSE: The aim of this study was to investigate choroidal parameters in patients with systemic sclerosis (SSc) using enhanced depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT) and to determine their relationships with clinical variables and ocular features. METHODS: Thirty-three patients with SSc and 40 controls were enrolled. The groups did not differ with regard to age, sex, and axial length. The mean choroidal thickness and volume were obtained in each conventional Early Treatment of Diabetic Retinopathy Study grid subfield. The choroidal vascularity index (CVI), which provides a quantitative analysis of vasculature by calculating the proportion of the luminal area (LA) to the total choroidal area (TCA), was determined. RESULTS: Lower choroidal thickness and volume were observed in the SSc group. The CVI was significantly higher in SSc patients, whereas the TCA, LA, and stromal area were significantly lower in the SSc group; however, the significant difference of the stromal component was more pronounced than that of the luminal component. Regression analyses did not identify any clinical factors associated with the CVI (except Ca-blocker use), central macular thickness, or volume. No significant differences in choroidal parameters were found within the SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) vs. limited cutaneous systemic sclerosis (lcSSc)), or between eyes stratified according to SSc pattern (early, active, or late) using nailfold capillaroscopy (p > 0.05 for all). CONCLUSION: Our results, with notably higher CVI values, may shed new light on choroidal impairment in patients with SSc. Stromal involvement appeared to dominate the vascular component.
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Retinopatía Diabética , Esclerodermia Sistémica , Humanos , Coroides/irrigación sanguínea , Esclerodermia Sistémica/diagnóstico , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
Introduction: Patients with systemic sclerosis (SSc) present an increased risk of developing glaucomatous optic neuropathy (GON). We investigated peripapillary choroidal parameters and peripapillary retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) to determine the relationships of these factors with clinical variables. Methods: A total of 33 patients with SSc were enrolled and compared to 40 controls. After obtaining circular scans around the optic disc, the global and quadrant peripapillary choroidal thickness (pCT) and RNFL thickness were measured. Additionally, the peripapillary choroidal vascularity index (pCVI), which allows for a quantitative analysis of the choroidal vasculature, was determined. Results: No significant differences were found in pCT and RNFL thickness between patients with SSc and controls, or within SSc subtypes (diffuse cutaneous systemic sclerosis (dcSSc) compared to limited cutaneous systemic sclerosis (lcSSc)) (p > 0.05). The pCVI was significantly lower in patients with SSc than in control subjects (64.25 ± 1.94 vs.65.73 ± 2.12, p < 0.001). Conclusion: Our results suggest that the statistically significant decrease in pCVI in patients with SSc compared to the control group is probably due to a decrease in the vascular layer, which would partially explain an increased risk of GON in patients with SSc.
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The aim of this study was to compare the aqueous humor (AH) and serum concentrations of metabolites in diabetic (n = 36) and nondiabetic (n = 36) senior adults undergoing cataract surgery. Blood samples were collected before surgery and AH during surgery. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted metabolomic and lipidomic analyses of samples were performed using the AbsoluteIDQ® p180 kit. Out of 188 metabolites targeted by the kit, 41 and 133 were detected in >80% of AH and serum samples, respectively. Statistical analysis performed to indicate metabolites differentiating diabetic and nondiabetic patients showed 8 and 20 significant metabolites in AH and serum, respectively. Pathway analysis performed for significant metabolites revealed that galactose metabolism is mostly affected in the AH, while arginine biosynthesis is mostly affected in the serum. Among metabolites that differentiate diabetic and nondiabetic patients, arginine was the only metabolite common to both serum and AH samples, as well as the only one with a decreased concentration in both body fluids of diabetic patients. Concentrations of the rest were elevated in AH and lowered in serum. This may suggest different mechanisms of diabetes-related dysregulation of the local metabolism in the eye in comparison to systemic changes observed in the blood.
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Catarata , Diabetes Mellitus , Adulto , Humanos , Humor Acuoso , Cromatografía Liquida , Espectrometría de Masas en Tándem , Metabolómica , Arginina , MetabolomaRESUMEN
BACKGROUND: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting. METHODS: The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression-free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model. RESULTS: From February 2022 to November 2022, 145 patients were enrolled. After a median follow-up of 8.5 months (95% CI: 7.9-13.6), the median PFS was 8.9 months (95% CI: 7.4-11.7). Median OS was 12.9 months (95% CI: 10.9-12.9). The investigator-assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3-4 AEs occurred in 51 patients (35.2%). The rate of immune-mediated AEs (imAEs) was 22.7%. Grades 3-4 imAEs occurred in 2.1% of the patients. In univariate analysis, non-viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS. CONCLUSION: The results reported in this first real-world analysis mostly confirmed the results achieved in the TOPAZ-1 trial in terms of PFS, ORR and safety.
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Neoplasias de los Conductos Biliares , Gemcitabina , Humanos , Cisplatino/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Aims: Interocular comparison of the metabolomic signature of aqueous humor (AH) was performed. The aim of the study was to quantitatively evaluate the symmetry in concentrations of various metabolites belonging to different categories. Methods: The study included AH samples from 23 patients, 74.17 ± 11.52 years old, undergoing simultaneous bilateral cataract surgery at the Ophthalmology Department of the Medical University of Bialystok, Poland. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted metabolomics and lipidomics analyses of AH samples were performed using the AbsoluteIDQ® p180 kit. Out of 188 metabolites available in the kit, 67 were measured in the majority (>70%) of the samples: 21/21 amino acids, 10/22 biogenic amines, 9/40 acylcarnitines, 0/14 lysophosphatidylcholines, 21/76 phosphatidylcholines, 5/15 sphingolipids, and 1/1sum of hexoses. Results: The comparison of both eyes revealed that the concentrations of metabolites did not differ significantly (p < 0.05) except for taurine (p = 0.037). There was moderate-to-strong positive interocular correlation (r > 0.5) between most metabolites regarding concentration. This was confirmed by the high intraclass correlation coefficient (ICC) values of different levels, which varied for the different metabolites. However, there were exceptions. Correlations were not significant for 2 acylcarnitines (tiglylcarnitine and decadienylcarnitine) and 3 glycerophospholipids (PC aa C32:3, PC aa C40:2, and PC aa C40:5). Conclusion: With a few exceptions, a single eye was found to be representative of the fellow eye in terms of the concentration of most of the analyzed metabolites. The degree of intraindividual variability in the AH of fellow eyes differs for particular metabolites/metabolite categories.
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Purtscher-like retinopathy (PLR) is an uncommon occlusive microangiopathy associated with various systemic conditions. We report a case of PLR related to severe progressive systemic sclerosis (SSc), an autoimmune disease characterized by widespread angiopathy and fibrosis, in a 44-year-old Caucasian male diagnosed with early diffuse cutaneous systemic sclerosis (dSSc). Upon ophthalmological examination, pathognomonic fundoscopy abnormalities were found. Spectral domain optical coherence tomography (SD-OCT), angio-OCT, and visual field results are documented at initial diagnosis and follow-up visits. The detailed ophthalmological assessment is juxtaposed with rheumatological evaluation and treatment. Current literature on probable pathophysiological mechanisms is reviewed in accordance with the described case. The PLR seems to be connected to severe SSc-related angiopathy initiated by capillary endothelial damage, with ultimate arteriolar precapillary occlusion in the inner retinal layer. Although this is not routinely recommended, we suggest that ophthalmological examinations may be advantageous in patients with SSc, as serious eye pathology may be present despite the lack of symptoms reported by the patient. Patients with PLR require a differential diagnosis and regular follow-up. Proper treatment of the underlying disease may have beneficial effects on the natural course of PLR.
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The present study investigated the interaction effects (additive, synergistic, and antagonistic) of different groups of spices, their constituent phenolic compounds, and synthetic antioxidants on the total phenol (TP) content and antioxidant activity, as measured by the ferric-reducing antioxidant power (FRAP) of the mixtures. The results showed that there was an additive effect in all the groups studied, except for the group containing turmeric or curcumin. The groups containing turmeric or curcumin showed a moderate synergistic effect. Among the groups of spices, the highest summated TP (50.6 mg GAE/mL) and FRAP (106.2 mg Trolox/mL) values were observed in the group containing clove, cinnamon, pimento, rosemary, oregano, and cardamom. In the case of the groups of pure phenolics, the highest summated TP (364.96 mg GAE/mL) and FRAP (1124.25 mg Trolox/mL) values were observed in the group containing eugenol, acetyl eugenol, caffeic acid, and protocatechuic acid. The summated and combined TP and FRAP values of the samples correlated highly with the correlation coefficients (r2) of 0.976 and 0.988, respectively, inferring an additive nature of the interaction effect in most of the groups studied. The interactions of phenolics in mixtures are very complex, being affected by a number of factors, and requires more investigations. The current study will add considerable knowledge to the existing literature to understand the diversity and mechanisms of interactions.
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Recently, the quest for novel glaucoma surgical techniques and devices has been underway. Trabeculectomy remains the gold standard, but it requires the implantation of glaucoma drainage devices and frequent follow-ups, and it also carries a high risk of serious complications. The need for less invasive and safer procedures has led to the development of minimally invasive glaucoma surgery (MIGS), particularly for patients with mild-to-moderate disease. Among them, minimally invasive bleb surgery seems to be effective in classical glaucoma surgery, while maintaining MIGS benefits. The relatively new PreserFlo® MicroShunt (Santen, Osaka, Japan) is registered in Europe. It was released in 2019 for the treatment of patients with early-to-advanced open-angle glaucoma, where intraocular pressure (IOP) remains uncontrolled while on maximum tolerated medication and/or where glaucoma progression warrants surgery. This review focuses on the place of the PreserFlo MicroShunt, characterized by ab externo implantation, among MIGS procedures, discussing its advantages and disadvantages. The mechanisms of action, technical aspects, efficacy, and safety issues are summarized. The surgical technique, its efficacy, and safety profile are described, and directions for future studies are indicated. The PreserFlo MicroShunt ensures a high safety profile, minimal anatomical disruption, meaningful IOP-lowering effect, and ease of use for patients and physicians.
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Implantes de Drenaje de Glaucoma , Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Glaucoma de Ángulo Abierto/etiología , Glaucoma de Ángulo Abierto/cirugía , Presión Intraocular , Implantes de Drenaje de Glaucoma/efectos adversos , Tonometría OcularRESUMEN
The aim of the study was to analyze patients' experiences with immediate sequential bilateral cataract surgery (ISBCS). An anonymous survey was sent by post to patients who underwent ISBCS between 1 May 2020 and 30 April 2022. A total of 195 participants completed the survey. Specifically, 94.6% of the respondents were satisfied with the possibility of having both eyes treated during one surgical procedure, 89.7% would choose ISBCS again if offered a choice, and 89.2% would recommend this procedure to their family members. ISBCS provided a subjective benefit for 84.6% of the respondents. The most commonly reported ISBCS-related problems were the necessity to sleep in a supine position (32.8%), inability to read shortly after the surgery (27.7%), having both eyes protected with a dressing (24.6%), and application of eyedrops to both eyes at the same time (17.4%). All patients were able to identify some pros of ISBCS, with the most common being single stay in the operating room (82.6%), lower number of visits to the clinic (62.6%), quick normalization of eyesight (61%), time savings for family members (54.9%), quick adjustment of reading glasses (32.3%), and economical aspects (23.6%). The perception of difficulties associated with ISBCS and the benefits offered by this procedure differed depending on patients' gender, age, marital status, education, place of residence, occupational activity, level of care dependence, and everyday activities. Understanding patients' opinions about ISBCS provides insight into the advantages and disadvantages of this procedure from a broader perspective.
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Extracción de Catarata , Catarata , Humanos , Implantación de Lentes Intraoculares/métodos , Extracción de Catarata/métodos , Catarata/complicaciones , Encuestas y Cuestionarios , OjoRESUMEN
Aqueous humor (AH) is a transparent fluid that fills the anterior segment of the eye. The composition and level of metabolites in AH are important for understanding its physiology and changes caused by the occurrence of eye disease. A simple method for the preparation and analysis of AH samples was developed using the liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) technique. The analyses were performed using two types of chromatography: reversed-phase liquid chromatography-mass spectrometry (LC-RP-MS) and hydrophilic interaction liquid chromatography-mass spectrometry (LC-HILIC-MS), in the sample prepared by one protocol.