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Heart failure with supranormal ejection fraction: clinical characteristics and outcomes compared to mildly reduced and preserved ejection fraction
No full textBackground: Little is known about the recently emerging entity, heart failure with supranormal ejection fraction (HFsnEF). Objective: To describe the clinical characteristics and outcome of HFsnEF, compared to HF with mildly reduced EF (HFmrEF) and HF with preserved EF (HFpEF) patients. Design: A single center retrospective analysis. Patients: Hospitalized and ambulatory heart failure (HF) patients who underwent echocardiography with left ventricular ejection fraction (LVEF) > 40%. Main measures: Clinical and echocardiographic parameters, hospitalization rates and mortality. Key results: A total of 6,202 patients (mean age 81.4 ± 14.1 years, 52% females) were analyzed: 750 in the HFmrEF group (LVEF 41–49%), 4360 in the HFpEF group (LVEF 50–64%), and 1092 in the HFsnEF group (LVEF ≥ 65%). Patients were followed for a median of 32 (11–65) months. HFsnEF patients were older, predominantly female, exhibited higher hypertension prevalence, more severe LV hypertrophy, smaller LV dimensions, and higher filling pressures compared to the other groups (p < 0.001 for all). These features were consistent in both hospitalized and ambulatory patients. In a univariable model, HFsnEF patients had higher mortality rates compared to HFmrEF and HFpEF patients (HR 1.258, 95% CI 1.117–1.418; p < 0.001 and HR 1.112, 95% CI 1.023–1.208; p = 0.012, respectively). However, in a multivariable model, adjusted for age, sex, comorbidities, and echocardiographic parameters, there was no significant difference in the mortality rates between all groups. The total hospitalization rate was similar between the HFpEF and HFsnEF groups, and lower in the HFmrEF group (p = 0.022). However, the HFsnEF group had the lowest rate of HF-related hospitalizations (p = 0.002). Conclusion: HFsnEF represents a group of patients with a distinct clinical and echocardiographic profile accompanied by worse outcomes, likely mediated by older age and a higher comorbidity burden, compared to HFmrEF and HFpEF. Therefore, the supranormal EF may serve as a marker rather than an independent prognostic factor
Analyzing the interaction between time to surgery and tumor burden score in hepatocellular carcinoma
No full textBackground: The effect of “time to surgery (TTS)” on outcomes for curative-intent hepatectomy of hepatocellular carcinoma (HCC) remains debated. The interaction between tumor burden score (TBS) and TTS remains unclear. We sought to evaluate the effects of TBS and TTS on long-term HCC outcomes. Methods: Patients with HCC who underwent curative-intent hepatectomy (2000–2022) were analyzed from a multi-institutional database and categorized by TTS (≤60 or >60 days). Overall survival (OS) and cancer-specific survival were assessed. Results: Among 910 patients, median TTS estimates were 22 days in the short TTS group (n = 485) and 120 days in the long TTS group (n = 425). Patients with long TTS were older and were more likely to have American Society of Anesthesiologists class >2, diabetes mellitus, and cirrhosis. There was no difference in median TBS among patients who had short versus long TTS (4.61 vs 5.00, respectively). In addition, there was no difference in 5-year OS (70.0% vs 63.1%, respectively; P =.05). On multivariate analysis TBS (hazard ratio [HR], 1.07; 95% CI, 1.03–1.11; P <.001), log alpha-fetoprotein (HR, 1.08; 95% CI, 1.01–1.14; P =.02), and albumin-bilirubin score (HR, 2.52; 95% CI, 1.66–3.82; P <.001) were associated with OS. In contrast, TTS was not associated with OS (HR, 1.18; 95% CI, 0.78–1.77; P =.43). Interaction analysis demonstrated that TBS was asssociated with OS among patients with short TTS (HR, 1.12; 95% CI, 1.07–1.17; P <.001), but not among patients with long TTS (HR, 0.98; 95% CI, 0.91–1.05; P =.56). Among patients with low TBS (≤5), higher mortality was observed with long TTS versus short TTS (5-year OS: 82.4% vs 63.0%, respectively; P =.001); however, TTS was not associated with OS among patients with high TBS (5-year OS: 57.9% vs 63.3%, respectively; P =.92). Multivariate analysis demonstrated that long TTS was a risk factor for OS among patients with low TBS (HR, 3.12; 95% CI, 1.60–6.01; P <.001), but not among individuals with high TBS (HR, 0.57; 95% CI, 0.30–1.07; P =.08). Similar trends were observed relative to cancer-specific survival. Conclusion: TTS needs to be considered in light of patient and tumor-specific factors. Expediting TTS may be particularly important among patients with HCC and a low TBS.Background: The effect of “time to surgery (TTS)” on outcomes for curative-intent hepatectomy of hepatocellular carcinoma (HCC) remains debated. The interaction between tumor burden score (TBS) and TTS remains unclear. We sought to evaluate the effects of TBS and TTS on long-term HCC outcomes. Methods: Patients with HCC who underwent curative-intent hepatectomy (2000–2022) were analyzed from a multi-institutional database and categorized by TTS (≤60 or >60 days). Overall survival (OS) and cancer-specific survival were assessed. Results: Among 910 patients, median TTS estimates were 22 days in the short TTS group (n = 485) and 120 days in the long TTS group (n = 425). Patients with long TTS were older and were more likely to have American Society of Anesthesiologists class >2, diabetes mellitus, and cirrhosis. There was no difference in median TBS among patients who had short versus long TTS (4.61 vs 5.00, respectively). In addition, there was no difference in 5-year OS (70.0% vs 63.1%, respectively; P =.05). On multivariate analysis TBS (hazard ratio [HR], 1.07; 95% CI, 1.03–1.11; P <.001), log alpha-fetoprotein (HR, 1.08; 95% CI, 1.01–1.14; P =.02), and albumin-bilirubin score (HR, 2.52; 95% CI, 1.66–3.82; P <.001) were associated with OS. In contrast, TTS was not associated with OS (HR, 1.18; 95% CI, 0.78–1.77; P =.43). Interaction analysis demonstrated that TBS was asssociated with OS among patients with short TTS (HR, 1.12; 95% CI, 1.07–1.17; P <.001), but not among patients with long TTS (HR, 0.98; 95% CI, 0.91–1.05; P =.56). Among patients with low TBS (≤5), higher mortality was observed with long TTS versus short TTS (5-year OS: 82.4% vs 63.0%, respectively; P =.001); however, TTS was not associated with OS among patients with high TBS (5-year OS: 57.9% vs 63.3%, respectively; P =.92). Multivariate analysis demonstrated that long TTS was a risk factor for OS among patients with low TBS (HR, 3.12; 95% CI, 1.60–6.01; P <.001), but not among individuals with high TBS (HR, 0.57; 95% CI, 0.30–1.07; P =.08). Similar trends were observed relative to cancer-specific survival. Conclusion: TTS needs to be considered in light of patient and tumor-specific factors. Expediting TTS may be particularly important among patients with HCC and a low TBS
Post-Vaccination Anaphylaxis in Adults: A Systematic Review and Meta-Analysis
No full textBackground/Objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults. Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates. Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines (n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases). Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of −10.45 (95% CI: −12.09 to −8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations. Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs
Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy
No full textBackground: In SERENA-6, switching from aromatase inhibitor (AI) to camizestrant with continuation of CDK4/6 inhibitor (CDK4/6i) guided by emergence of ESR1 mutations (ESR1-mut) during first-line AI-CDK4/6i in patients with hormone receptor (HR)-positive advanced breast cancer (ABC) resulted in statistically significant and clinically meaningful improvement in progression-free survival compared with AI-CDK4/6i and reduction in the risk of deterioration in global health status (GHS)/quality of life (QoL) (hazard ratio 0.54). Here we report additional data from patient-reported outcomes (PROs). Patients and methods: Patients completed PRO questionnaires at pre-specified timepoints, including the European Organisation for Research and Treatment of Cancer (EORTC) oncology-specific EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and breast cancer-specific (QLQ-BR23) and Patient Global Impression of Treatment Tolerability (PGI-TT). All PRO endpoints and analyses were pre-defined, including secondary endpoints of time to deterioration (TTD) in pain, physical functioning, breast symptoms and arm symptoms. Results: EORTC QLQ-C30 and EORTC QLQ-BR23 baseline scores were similar between treatment arms. Switching to camizestrant-CDK4/6i delayed TTD and reduced the risk of deterioration in patient-reported cancer symptoms [pain (hazard ratio 0.57, 95% confidence interval 0.37-0.86), fatigue (0.75, 0.46-1.24), shortness of breath/dyspnoea (0.52, 0.28-0.93), breast symptoms (0.59, 0.28-1.24) and arm symptoms (0.69, 0.34-1.39)] and functioning [physical (0.74, 0.44-1.24), role (0.73, 0.48-1.10) and emotional (0.51, 0.29-0.87)] compared with AI-CDK4/6i. Most patients reported they were ‘not at all’ or ‘a little bit’ bothered by the side effects of cancer therapy across timepoints (e.g. week 2: 86% camizestrant-CDK4/6i versus 82% AI-CDK4/6i). Conclusions: Together with the clinical efficacy and manageable safety profile of camizestrant-CDK4/6i, and reduced risk of GHS/QoL deterioration, the PROs from the SERENA-6 trial support switching to this combination as a potential new treatment strategy to optimise and improve outcomes in patients with HR-positive/HER2-negative ABC and ESR1-mut emergence, ahead of disease progression, during first-line AI-CDK4/6i
Independent histological validation of MR-derived radio-pathomic maps of tumor cell density using image-guided biopsies in human brain tumors
No full textPurpose: In brain gliomas, non-invasive biomarkers reflecting tumor cellularity would be useful to guide supramarginal resections and to plan stereotactic biopsies. We aim to validate a previously-trained machine learning algorithm that generates cellularity prediction maps (CPM) from multiparametric MRI data to an independent, retrospective external cohort of gliomas undergoing image-guided biopsies, and to compare the performance of CPM and diffusion MRI apparent diffusion coefficient (ADC) in predicting cellularity. Methods: A cohort of patients with treatment-naïve or recurrent gliomas were prospectively studied. All patients underwent pre-surgical MRI according to the standardized brain tumor imaging protocol. The surgical sampling site was planned based on image-guided biopsy targets and tissue was stained with hematoxylin–eosin for cell density count. The correlation between MRI-derived CPM values and histological cellularity, and between ADC and histological cellularity, was evaluated both assuming independent observations and accounting for non-independent observations. Results: Sixty-six samples from twenty-seven patients were collected. Thirteen patients had treatment-naïve tumors and fourteen had recurrent lesions. CPM value accurately predicted histological cellularity in treatment-naïve patients (b = 1.4, R2 = 0.2, p = 0.009, rho = 0.41, p = 0.016, RMSE = 1503 cell/mm2), but not in the recurrent sub-cohort. Similarly, ADC values showed a significant association with histological cellularity only in treatment-naive patients (b = 1.3, R2 = 0.22, p = 0.007; rho = -0.37, p = 0.03), not statistically different from the CPM correlation. These findings were confirmed with statistical tests accounting for non-independent observations. Conclusion: MRI-derived machine learning generated cellularity prediction maps (CPM) enabled a non-invasive evaluation of tumor cellularity in treatment-naïve glioma patients, although CPM did not clearly outperform ADC alone in this cohort
Prospettiva sull'autonomia del politico. De Feo su Mario Tronti
No full textL'articolo affronta la ricezione del pensiero di Carl Schmitt in Italia da parte del pensiero operaista, con particolare riferimento a Massimo Nicola De Feo e Mario Tronti. La riflessione sull'autonomia del politico e la critica di De Feo a Carl Schmitt e Mario Tronti offrono una lente per afferrare il significato del politico in De Feo
Investigating the evolutionary dynamics and mutational pattern of SARS-CoV-2 spike gene on selected SARS-CoV-2 variants
No full textThe continuous evolution of SARS-CoV-2 has led to the emergence of several variants representing significant challenges for public health. Many studies highlight the relevance of phylogenetic inference or mutational pattern analysis to understand the evolutionary relatedness of viral variants and to estimate the potential effect of new mutations on viral transmission, virulence and antigenicity. Here we describe an evolutionary investigation approach combined with mutational analyses of SARS-CoV-2 Spike gene to annotate and potentially track important amino acid site variation of specific functional domain relevant for viral survival. This approach was applied on XBB*, EG* and BA* and their sub-lineages (see materials and methods) available from GISAID. In addition, we considered the major variants of concern (Alpha, Delta, Omicron) and Wuhan-Hu-1 strain as references. Maximum likelihood phylogenetic tree was constructed from the complete dataset while selection pressure and mutational analyses were conducted on single variants separately. The obtained phylogenetic tree of Spike amino acid gene sequence showed a clear separation of viral variants as well as their expected appearance order. This result supported the significance of selection pressure analyses outcomes combined with amino acid mutational frequencies where in many cases they showed a linear and parallel trend. This allowed also to hypothesize the potential importance of low-frequency mutations in new potential virus variants. This study constitutes an asset of important insights to be considered in regular monitoring programs. In addition, the analysis framework described here introduces a starting point for further standardization, optimization and application on different data types and in large-scale studies
Correction to: Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study (Journal of Neurology, (2024), 271, 11, (7250-7263), 10.1007/s00415-024-12608-6)
No full textIn the original version of this article, author’s name Filippo Martinelli Boneschi was incorrectly written as Filippo Giovanni Martinelli Boneschi. In Table 2, first two columns were missing. The Table 2 which previously appeared as (Table presented.) List of top-associated variants after meta-analysis. The list is obtained upon a clumping procedure (see Methods for details), filtered at p < 5 × 10–5. The effect allele is the minor allele Position Minor allele Major allele MAF P OR SE I2 Gene Genomic context Distance to gene 187,410,850 T C 0.268 1.328E−06 0.582 0.112 0 ncRNA_intronic 68,071,570 T C 0.421 1.678E−06 1.538 0.090 0 Intergenic Dist = 4552; Dist = 15,067 111,037,829 T A 0.251 2.793E−06 0.596 0.111 13 Intergenic Dist = 785,779; Dist = 579,040 20,863,249 G A 0.057 4.804E−06 2.122 0.165 0 Intergenic Dist = 56,715; Dist = 114,557 98,275,102 C G 0.429 6.938E−06 0.650 0.096 34 Intergenic Dist = 171,174; Dist = 10,744 47,775,385 A G 0.230 1.187E−05 1.561 0.102 0 Intronic 21,728,917 A G 0.142 1.191E−05 0.510 0.154 0 Intronic 187,402,360 A G 0.480 1.233E−05 1.496 0.092 0 ncRNA_intronic 115,392,100 A G 0.347 1.259E−05 1.476 0.089 0 Intronic 12,783,519 T C 0.075 1.325E−05 1.934 0.151 0 Intergenic Dist = 107,719; Dist = 19,663 43,181,587 T C 0.080 1.362E−05 1.918 0.150 0 Intergenic Dist = 64,280; Dist = 10,922 79,303,163 G A 0.430 1.475E−05 1.469 0.089 0 Intergenic Dist = 56,599; Dist = 324,572 98,347,870 C G 0.429 1.494E−05 0.676 0.091 57 ncRNA_intronic 27,204,531 C T 0.095 2.087E−05 1.775 0.135 42 Intergenic Dist = 54,515; Dist = 15,604 47,746,678 C G 0.075 2.692E−05 1.839 0.145 29 Exonic 113,293,608 G A 0.411 2.744E−05 1.461 0.090 0 Intergenic Dist = 51,109; Dist = 7750 606,173 C A 0.143 2.862E−05 1.646 0.119 0 Intronic 83,766,280 A C 0.114 2.909E−05 1.739 0.132 48 Intronic 236,647,736 T C 0.233 2.939E−05 1.495 0.096 0 UTR3 NM_145861:c.*1787C>T; NM_080738:c.*1787C>T 93,450,212 A G 0.295 3.023E−05 1.471 0.093 0 Intergenic Dist = 334,599; Dist = 127,459 4,314,917 A G 0.220 3.087E−05 1.523 0.101 0 Intronic 81,279,746 A G 0.271 3.116E−05 1.479 0.094 6.4 Intergenic Dist = 364,485; Dist = 312,780 111,023,899 T C 0.404 3.369E−05 1.441 0.088 0 Intergenic Dist = 771,849; Dist = 592,970 189,243,943 T C 0.413 3.424E−05 1.433 0.087 0 Intergenic Dist = 200,850; Dist = 70,592 114,813,313 C T 0.267 3.459E−05 1.483 0.095 0 Intronic 110,446,839 G A 0.413 3.508E−05 1.433 0.087 0 Intergenic Dist = 7909; Dist = 258,793 177,987,660 G A 0.137 3.639E−05 1.617 0.116 0 ncRNA_intronic 31,271,788 A G 0.072 3.733E−05 1.845 0.148 60 ncRNA_intronic 206,468,850 T G 0.419 4.007E−05 1.433 0.088 0 Intronic 54,692,961 G A 0.116 4.025E−05 1.652 0.122 6.9 Intergenic Dist = 438,021; Dist = 18,608 141,938,633 C T 0.069 4.217E−05 1.890 0.155 74 Intergenic Dist = 16,509; Dist = 1923 81,959,114 T C 0.499 4.222E−05 0.697 0.088 5.8 Intergenic Dist = 343,363; Dist = 176,860 158,058,545 T C 0.436 4.257E−05 1.455 0.092 0 Intronic 180,648,923 C T 0.480 4.571E−05 0.699 0.088 0 Intergenic Dist = 1,737,019; Dist = 1,336,320 83,182,354 A G 0.299 4.605E−05 1.458 0.093 0 Intronic 10,732,844 G A 0.050 4.841E−05 2.053 0.177 53 Intronic 130,499,623 G A 0.096 4.929E−05 1.749 0.138 42 Intergenic Dist = 383,633; Dist = 211,474 156,675,608 A C 0.135 4.934E−05 1.642 0.122 0 Intergenic Dist = 17,399; Dist = 4565 50,679,081 T G 0.372 4.966E−05 1.448 0.091 0 Intergenic Dist = 661,439; Dist = 2158 For each variant, the gene harboring it or nearest gene(s) are reported, together with its genomic context and distance in base-pairs from the nearest genes, as of ANNOVAR annotation Abbreviations: MAF (Minor Allele Frequency), P (p value from fixed-effect meta-analysis), OR (odds ratio from fixed-effects meta-analysis), SE (standard error), I2 (heterogeneity index) but Table 2 should have appeared as shown below. (Table presented.) List of top associated variants after meta-analysis SNP Chromosome Position Minor allele Major allele MAF P OR SE I2 Gene Genomic context Distance to gene rs11132400 4 187410850 T C 0.268 1.328E−06 0.582 0.112 0 ncRNA_intronic rs12885261 14 68071570 T C 0.421 1.678E−06 1.538 0.090 0 Intergenic dist = 4552; dist = 15,067 rs1323374 9 111037829 T A 0.251 2.793E−06 0.596 0.111 13 Intergenic dist = 785,779; dist = 579,040 rs61166479 13 20863249 G A 0.057 4.804E−06 2.122 0.165 0 Intergenic dist = 56,715; dist = 114,557 rs1032954 15 98275102 C G 0.429 6.938E−06 0.650 0.096 34 Intergenic dist = 171,174; dist = 10,744 rs75772884 15 47775385 A G 0.230 1.187E−05 1.561 0.102 0 Intronic rs34736466 3 21728917 A G 0.142 1.191E−05 0.510 0.154 0 Intronic rs12649886 4 187402360 A G 0.480 1.233E−05 1.496 0.092 0 ncRNA_intronic rs13073759 3 115392100 A G 0.347 1.259E−05 1.476 0.089 0 Intronic rs2977141 8 12783519 T C 0.075 1.325E−05 1.934 0.151 0 Intergenic dist = 107,719; dist = 19,663 rs7286822 22 43181587 T C 0.080 1.362E−05 1.918 0.150 0 Intergenic dist = 64,280; dist = 10,922 rs9922330 16 79303163 G A 0.430 1.475E−05 1.469 0.089 0 Intergenic dist = 56,599; dist = 324,572 rs72752604 15 98347870 C G 0.429 1.494E−05 0.676 0.091 57 ncRNA_intronic rs1815323 10 27204531 C T 0.095 2.087E−05 1.775 0.135 42 Intergenic dist = 54,515; dist = 15,604 rs10789505 1 47746678 C G 0.075 2.692E−05 1.839 0.145 29 Exonic rs9577824 13 113293608 G A 0.411 2.744E−05 1.461 0.090 0 Intergenic dist = 51,109; dist = 7750 rs2159600 12 606173 C A 0.143 2.862E−05 1.646 0.119 0 Intronic rs12806160 11 83766280 A C 0.114 2.909E−05 1.739 0.132 48 Intronic rs6428955 1 236647736 T C 0.233 2.939E−05 1.495 0.096 0 UTR3 NM_145861:c.*1787C > T; NM_080738:c.*1787C > T rs1072934 8 93450212 A G 0.295 3.023E−05 1.471 0.093 0 Intergenic dist = 334,599; dist = 127,459 rs1217680 8 4314917 A G 0.220 3.087E−05 1.523 0.101 0 Intronic rs12428095 13 81279746 A G 0.271 3.116E−05 1.479 0.094 6.4 Intergenic dist = 364,485; dist = 312,780 rs10739255 9 111023899 T C 0.404 3.369E−05 1.441 0.088 0 Intergenic dist = 771,849; dist = 592,970 rs6803844 3 189243943 T C 0.413 3.424E−05 1.433 0.087 0 Intergenic dist = 200,850; dist = 70,592 rs7960396 12 114813313 C T 0.267 3.459E−05 1.483 0.095 0 Intronic rs1414319 13 110446839 G A 0.413 3.508E−05 1.433 0.087 0 Intergenic dist = 7909; dist = 258,793 rs7537568 1 177987660 G A 0.137 3.639E−05 1.617 0.116 0 ncRNA_intronic rs112417083 12 31271788 A G 0.072 3.733E−05 1.845 0.148 60 ncRNA_intronic rs13031793 2 206468850 T G 0.419 4.007E−05 1.433 0.088 0 Intronic rs9475026 6 54692961 G A 0.116 4.025E−05 1.652 0.122 6.9 Intergenic dist = 438,021; dist = 18,608 rs59801030 7 141938633 C T 0.069 4.217E−05 1.890 0.155 74 Intergenic dist = 16,509; dist = 1923 rs10040233 5 81959114 T C 0.499 4.222E−05 0.697 0.088 5.8 Intergenic dist = 343,363; dist = 176,860 rs618823 6 158058545 T C 0.436 4.257E−05 1.455 0.092 0 Intronic rs4444875 4 180648923 C T 0.480 4.571E−05 0.699 0.088 0 Intergenic dist = 1,737,019; dist = 1,336,320 rs2068076 11 83182354 A G 0.299 4.605E−05 1.458 0.093 0 Intronic rs76674464 16 10732844 G A 0.050 4.841E−05 2.053 0.177 53 Intronic rs12265034 10 130499623 G A 0.096 4.929E−05 1.749 0.138 42 Intergenic dist = 383,633; dist = 211,474 rs6838876 4 156675608 A C 0.135 4.934E−05 1.642 0.122 0 Intergenic dist = 17,399; dist = 4565 rs1923523 6 50679081 T G 0.372 4.966E−05 1.448 0.091 0 Intergenic dist = 661,439; dist = 2158 The list is obtained upon a clumping procedure (see Methods for details), filtered at p < 5 × 10−5. The effect allele is the minor allele For each variant, the gene harboring it or nearest gene(s) are reported, together with its genomic context and distance in base-pairs from the nearest genes, as of ANNOVAR annotation MAF (Minor Allele Frequency), P (p-value from fixed-effect meta-analysis), OR (odds ratio from fixed-effects meta-analysis), SE (standard error), I2 (heterogeneity index
A nationwide approach to reduction in anaesthetic gas use: the Dutch Approach to decarbonising anaesthesia. Comment on Br J Anaesth 2025; 134: 1146-52
No full textSurgery versus endoscopy with digital single-operator cholangioscopy-guided therapy for Mirizzi syndrome: The SEIZE study
No full textBackground: The management of Mirizzi syndrome has been primarily surgical, but there are no comparisons between surgical and digital single-operator cholangioscopy (dSOC)-guided treatment. The objective of this study was to compare the safety and other outcomes of the two approaches. Methods: A large multicenter international retrospective analysis was conducted comparing dSOC and surgery in patients with type II-IV Mirizzi syndrome between January 2005 and June 2023. Patients with postsurgical anatomy, Mirizzi type I or V, or previous cholecystectomy were excluded. Results: 290 patients were included (dSOC, n = 176; surgery, n = 114). At baseline, patients undergoing dSOC were older P = 0.006) and exhibited more co-morbidities. While technical success was lower with dSOC (89.8 % vs. 96.5 %; P = 0.04), the need for reintervention was comparable after a median follow-up duration of 741.5 days (interquartile range [IQR] 320-1781) vs. 346 days (IQR 67-1220; P = 0.009). Overall adverse events (10.2 % vs. 41.2 %; P < 0.001) and severe adverse events (1.7 % vs. 15.8 %; P < 0.001) occurred less frequently with dSOC, findings that were confirmed with propensity score-matching. A lower need for hepaticojejunostomy (8.2 % vs. 25.4 %; P = 0.006) and lower rate of conversion to open surgery (6.0 % vs. 22.8 %; P = 0.009) were observed in patients undergoing elective cholecystectomy following dSOC compared with the primary surgery group. Conclusions: Our study demonstrates that the use of dSOC for Mirizzi syndrome is effective, showing superior safety despite being used to treat patients with more underlying co-morbidities. dSOC seems valuable in downgrading the extent of subsequent surgery, by potentially reducing the need for hepaticojejunostomy and conversion to open surgery