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Three years follow-up of Venetoclax in advanced-stage, relapsed or refractory AL amyloidosis with cardiac involvement and t(11;14) with BCL2 expression.
Get PDFFurther line treatment of patients with advanced stage AL amyloidosis with cardiac involvement is challenging. Venetoclax is a promising option, especially in t(11;14) and BCL2 expression.In our multicentre observational study, we report the 3-year follow-up of Venetoclax treatment in 9 patients with advanced, relapsed or refractory AL amyloidosis with t(11;14) and BCL-2 expression in > 50% of plasma cells. At baseline, all patients had been previously treated with daratumumab, all had cardiac involvement with revised Mayo stage III or IV/ European modification of Mayo 2004 IIIA or IIIB (1/9 unclassified due to missing troponin T), 5/9 patients had renal involvement.After a median of 35 months (range 25-49) since the start of Venetoclax, 8/9 patients were still alive (OS 89%). First and best hematological responses were observed after a median of 26 days (11-125) and 106 days (35-659), overall response rate was 100% (7/9 CR, 2/9 VGPR). Where observed, organ response was documented within the first 6 months of therapy, including cardiac (6/9) and renal (3/5) improvements. Venetoclax was discontinued in 6/9 patients after a median of 15 months (11-48) due to toxicity (2/9), disease progression (2/9), fixed treatment duration (1/9), or safety concerns (1/9).In conclusion, Venetoclax induces a rapid and deep hematologic response with consistent improvement in organ function with an acceptable safety profile in patients with pretreated, advanced stage AL amyloidosis with cardiac involvement and BCL2 expression with and potentially without detected t(11:14), which warrants further investigation
Comparative osseointegration of hydrophobic tissue-level tapered implants-A preclinical in vivo study.
Get PDFPURPOSE
To histometrically compare the osseointegration and crestal bone healing of a novel tapered, self-cutting tissue-level test implant with a standard tissue-level control implant in a submerged healing regimen.
MATERIALS AND METHODS
In a mandibular minipig model, implants were inserted and evaluated histometrically after a healing period of 3, 6, and 12 weeks. The primary outcome was the evaluation of bone-to-implant contact (BIC) and secondary outcomes were primary stability as per insertion torque and first BIC (fBIC). Outcomes for the test and control implants were compared using Wilcoxon signed-rank tests and mixed linear regression models.
RESULTS
Insertion torque values were significantly higher for the test (50.0 ± 26.4 Ncm) compared to the control implants (35.2 ± 19.7 Ncm, p = .0071). BIC values of test implants were non-inferior to those of control implants over the investigated study period. After 12 weeks, the corresponding values measured were 81.62 ± 11.12% and 90.41 ± 4.81% (p = .1763) for test and control implants, respectively. Similarly, no statistical difference was found for fBIC values, except for the 12 weeks outcome that showed statistically lower values for the test (-675.58 ± 590.88 μm) compared to control implants (-182.75 ± 197.40 μm, p = .0068).
CONCLUSIONS
Novel self-cutting tissue-level implants demonstrated noninferior osseointegration and crestal bone height maintenance to the tissue-level implants. Histometric outcomes between both implants demonstrated test implants were statistically noninferior to control implants, despite substantial differences in the bone engagement mechanism and resulting differences in insertion torque and qualitative bone healing patterns
Antimicrobial Potential of Strontium-Functionalized Titanium Against Bacteria Associated With Peri-Implantitis.
Get PDFOBJECTIVES
To explore the antimicrobial potential of strontium (Sr)-functionalized wafers against multiple bacteria associated with per-implant infections, in both mono- and multispecies biofilms.
MATERIALS AND METHODS
The bactericidal and bacteriostatic effect of silicon wafers functionalized with a strontium titanium oxygen coating (Sr-Ti-O) or covered only with Ti (controls) against several bacteria, either grown as a mono-species or multispecies biofilms, was assessed using a bacterial viability assay and a plate counting method. Mono-species biofilms were assessed after 2 and 24 h, while the antimicrobial effect on multispecies biofilms was assessed at Days 1, 3, and 6. The impact of Sr functionalization on the total percentage of Porphyromonas gingivalis in the multispecies biofilm, using qPCR, and gingipain activity was also assessed.
RESULTS
Sr-functionalized wafers, compared to controls, were associated with statistically significant less viable cells in both mono- and multispecies tests. The number of colony forming units (CFUs) within the biofilm was significantly less in Sr-functionalized wafers, compared to control wafers, for Staphylococcus aureus at all time points of evaluation and for Escherichia coli at Day 1. Gingipain activity was less in Sr-functionalized wafers, compared to control wafers, and the qPCR showed that P. gingivalis remained below detection levels at Sr-functionalized wafers, while it consisted of 15% of the total biofilm on control wafers at Day 6.
CONCLUSION
Sr functionalization displayed promising antimicrobial potential, possessing bactericidal and bacteriostatic ability against bacteria associated with peri-implantitis grown either as mono-species or mixed in a multispecies consortium with several common oral microorganisms
Cut From the Same Cloth? The Problem of Male Supremacy and Deradicalization
No full textIn this short essay, we show that, despite the recent turn to including masculinity and male supremacist ideology into Preventing and Countering Violent Extremism programming (P/CVE), current deradicalization approaches often remain based on ideas about male victimhood and gender hierarchies that are eerily similar to those that are at the core of male supremacist ideology and (interpersonal and political) misogynist violence. We argue that to effectively address male supremacist radicalization, P/CVE approaches must challenge and disrupt their own underlying male supremacist views of gender relations
High prevalence of short telomeres in idiopathic porto-sinusoidal vascular disorder.
Get PDFBACKGROUND
Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD).
METHODS
As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD.
RESULTS
This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel.
CONCLUSIONS
Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD
Early Versus Late Initiation of Endovascular Therapy in Patients with Severe Cerebral Venous Sinus Thrombosis.
Get PDFBACKGROUND
Endovascular therapy (EVT) for severe cerebral venous sinus thrombosis (CVST) is controversial in terms of indication and clinical benefit. The impact of delay of EVT on functional recovery is unclear. This study aimed to investigate the effect of early versus late initiation of EVT in severe CVST.
METHODS
From prospective EVT and CVST registries, patients with CVST diagnosed between January 2010 and December 2022 were retrospectively identified for this multicenter collaboration. EVT was considered in severe CVST with features prone to a poor prognosis. We compared early ( 24 h) initiation of EVT after the presentation in the emergency department and subsequent CVST diagnosis. Outcome parameters included functional independence (modified Rankin Scale [mRS] score 0-2) at 90 days, mRS score at discharge, in-hospital mortality, and mortality at 3 months.
RESULTS
Of 363 patients with CVST, 45 (12.4%; 31 [early EVT] vs. 14 [late EVT]) were included in this study. We found a higher proportion of patients with functional independence at 3 months among early versus late EVT (66.7% vs. 27.3%; odds ratio [OR] 5.3; 95% confidence interval 1.02-25; p = 0.036). In multivariate logistic regression, late EVT was inversely correlated with functional independence (OR 0.17 [0.04-0.83]; p = 0.011). The mortality rate was 16.7% versus 36.4% (mRS 6 at 3 months, OR 0.34, 95% confidence interval 0.07-1.75; p = 0.217) at 90 days for early versus late EVT.
CONCLUSIONS
We observed a higher rate of functional independence in patients with early EVT. These preliminary findings must be confirmed in subsequent randomized controlled trials evaluating a "time-is-brain" paradigm for EVT in CVST
Validity of different algorithmic methods to identify hospital readmissions from routinely coded medical data.
Get PDFBACKGROUND
Hospital readmission rates are used for quality and pay-for-performance initiatives. To identify readmissions from administrative data, two commonly employed methods are focusing either on unplanned readmissions (used by the Centers for Medicare & Medicaid Services, CMS) or potentially avoidable readmissions (used by commercial vendors such as SQLape or 3 M). However, it is not known which of these methods has higher criterion validity and can more accurately identify actually avoidable readmissions.
OBJECTIVES
A manual record review based on data from seven hospitals was used to compare the validity of the methods by CMS and SQLape.
METHODS
Seven independent reviewers reviewed 738 single inpatient stays. The sensitivity, specificity, positive predictive value (PPV), and F1 score were examined to characterize the ability of an original CMS method, an adapted version of the CMS method, and the SQLape method to identify unplanned, potentially avoidable, and actually avoidable readmissions.
RESULTS
Both versions of the CMS method had greater sensitivity (92/86% vs. 62%) and a higher PPV (84/91% vs. 71%) than the SQLape method, in terms of identifying their outcomes of interest (unplanned vs. potentially avoidable readmissions, respectively). To distinguish actually avoidable readmissions, the two versions of the CMS method again displayed higher sensitivity (90/85% vs. 66%), although the PPV did not differ significantly between the different methods.
CONCLUSIONS
Thus, the CMS method has both higher criterion validity and greater sensitivity for identifying actually avoidable readmissions, compared with the SQLape method. Consequently, the CMS method should primarily be used for quality initiatives
Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.
Get PDFDeficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders
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