Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (&lt;3 months) aged ≥85 versus &lt;85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all‐cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient‐years follow‐up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%‐CI [0.52, 0.81]) and &lt; 85 years (HR&lt;85y = 0.79, 95%‐CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and &lt; 85 years (+1.90 to +3.36 events/100 patient‐years for ICH‐weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 202

The Raman Spectrum of the CH₃NH₃PbI₃ Hybrid Perovskite: Interplay of Theory and Experiment

We report the low-frequency resonant Raman spectrum of methylammonium lead-iodide, a prototypical perovskite for solar cells applications, on mesoporous Al₂O₃. The measured spectrum assignment is assisted by DFT simulations of the Raman spectra of suitable periodic and model systems. The bands at 62 and 94 cm^–1 are assigned respectively to the bending and to the stretching of the Pb–I bonds, and are thus diagnostic modes of the inorganic cage. We also assign the librations of the organic cations at 119 and 154 cm^–1. The broad, unstructured 200–400 cm^–1 features are assigned to the torsional mode of the methylammonium cations, which we propose as a marker of the orientational disorder of the material. Our study provides the basis to interpret the Raman spectra of organohalide perovskites, which may allow one to further understand the properties of this important class of materials in relation to their full exploitation in solar cells

The Raman Spectrum of the CH₃NH₃PbI₃ Hybrid Perovskite: Interplay of Theory and Experiment

We report the low-frequency resonant Raman spectrum of methylammonium lead-iodide, a prototypical perovskite for solar cells applications, on mesoporous Al₂O₃. The measured spectrum assignment is assisted by DFT simulations of the Raman spectra of suitable periodic and model systems. The bands at 62 and 94 cm^–1 are assigned respectively to the bending and to the stretching of the Pb–I bonds, and are thus diagnostic modes of the inorganic cage. We also assign the librations of the organic cations at 119 and 154 cm^–1. The broad, unstructured 200–400 cm^–1 features are assigned to the torsional mode of the methylammonium cations, which we propose as a marker of the orientational disorder of the material. Our study provides the basis to interpret the Raman spectra of organohalide perovskites, which may allow one to further understand the properties of this important class of materials in relation to their full exploitation in solar cells

Time trends, frequency, characteristics and prognosis of short-duration transient global amnesia

Background Transient global amnesia (TGA) is characterised by a sudden onset of anterograde amnesia lasting up to 24 hours. One major differential for TGA is transient epileptic amnesia (TEA), which typically lasts Methods We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK (Oxford cohort 1977‐1987 vs. Oxford Vascular Study‐ OXVASC 2002‐2018) to determine the time‐trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy (Northern Umbria registry‐NU 2002‐2018). We compared the risk factors, clinical features and long‐term prognosis (major cardiovascular events–MaCE, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting Results Overall 639 TGA patients were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared to the original Oxford cohort, there were more cases with TGA lasting Conclusions Short‐duration TGA episodes (<1h) are not uncommon and are more frequent now than in earlier studies. The clinical features and long‐term prognosis of short‐duration TGA did not differ from more typical episodes lasting≥1h.</p

Time trends, frequency, characteristics and prognosis of short‐duration transient global amnesia

Background Transient global amnesia (TGA) is characterised by a sudden onset of anterograde amnesia lasting up to 24 hours. One major differential for TGA is transient epileptic amnesia (TEA), which typically lasts Methods We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK (Oxford cohort 1977‐1987 vs. Oxford Vascular Study‐ OXVASC 2002‐2018) to determine the time‐trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy (Northern Umbria registry‐NU 2002‐2018). We compared the risk factors, clinical features and long‐term prognosis (major cardiovascular events–MaCE, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting Results Overall 639 TGA patients were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared to the original Oxford cohort, there were more cases with TGA lasting Conclusions Short‐duration TGA episodes (<1h) are not uncommon and are more frequent now than in earlier studies. The clinical features and long‐term prognosis of short‐duration TGA did not differ from more typical episodes lasting≥1h.</p

Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial

BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype ( 652 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum