Uptake of cage-free egg production in China remains limited, and many food companies have yet to meet their 2025 cage-free commitments. As the fulfilment of cage-free commitments potentially stimulates the growth of cage-free production, it is important to understand the factors influencing corporates' implementation. Drawing on seven semi-structured interviews with representatives from international food businesses and certification bodies operating in China, this study explores the enablers and challenges to implementing 2025 cage-free egg commitments and the role of certification schemes in supporting supply chain transitions. The findings show that access to cage-free certification schemes has supported the development of cage-free egg production and procurement. However, limited traceability and the absence of government regulation on animal welfare and product labelling remain challenges. Key enablers identified include the establishment of cage-free commitments, internal alignment and organisational buy-in, and phased implementation strategies. Despite this, major constraints persist, including high procurement costs, the complexity of transitioning multi-tier supply chains, and concerns about supply stability and continuity. While long-term interventions, such as policy development, producer capacity building, and consumer education, are essential, short-term market-based mechanisms, particularly the cage-free egg credits scheme, may offer a practical interim solution. These schemes can help companies fulfil their commitments and provide financial incentives for producers, thereby accelerating the transition to cage-free production and advancing animal welfare in China.
Expanding access to naloxone is an essential strategy in addressing the overdose crisis in the US. In March 2023, the US Food and Drug Administration approved the first over-the-counter (OTC) naloxone nasal spray, representing a substantial shift in public health policy and pharmacy practice. To assess the same-day availability of naloxone without a prescription across US retail pharmacies and examine pharmacy and neighborhood factors associated with access following OTC approval. This cross-sectional study used a secret shopper design to assess availability of naloxone in retail pharmacies in the US from January 15 to April 30, 2024. Participants included a stratified random sample of 1108 pharmacies from the 7 largest corporate pharmacy chains and an eighth stratum incorporating other retail pharmacies. Pharmacy characteristics (chain size, type, and affiliation) and neighborhood sociodemographic indicators (racial and ethnic composition and area deprivation index). Same-day naloxone availability without a prescription, location of naloxone within the store, price, and alternative access suggestions. Among the 1108 pharmacies contacted, an estimated 61.40% (95% CI, 57.34%-65.46%) of those with naloxone in stock reported it was available without a prescription. Naloxone was located at the pharmacy counter (estimate, 58.14% [95% CI, 53.59%-62.68%]), self-service aisles (estimate, 31.74% [95% CI, 27.59%-35.89%]), and front checkout areas (estimate, 8.99% [95% CI, 6.64%-11.34%]). The mean (SE) cost was $52.07 ($1.50) (95% CI, $49.12-$55.02). Among pharmacies without same-day naloxone (estimate, 38.60% [95% CI, 34.54%-42.66%]), respondents equally referred callers to another pharmacy or had no suggestions (estimate, 45.84% [95% CI, 37.77%-53.91%]), 4.46% (95% CI, 0.70%-8.21%) offered other suggestions (hospital, public service agencies, online service, or cannabis dispensary), 3.87% (95% CI, 0.48%-7.25%) suggested the public health department, and 0.06% (95% CI, 0.00%-0.17%) suggested syringe service programs. Pharmacies classified as food and/or mass merchandisers, independent, or medical affiliated had a lower odds ratio of offering same-day naloxone compared with corporate chains. In separate analyses, pharmacies located in areas with higher proportions of White residents were more likely to offer naloxone. Area deprivation index-defined neighborhood disadvantage, which does not include race in its calculation, was not associated with naloxone availability. In this cross-sectional study of pharmacies across the US, same-day naloxone availability and price remained uneven following OTC approval. As an initial national evaluation of same-day naloxone availability and price after OTC approval, the findings showed differences in implementation across pharmacy types and community demographic features. Although enactment of the OTC policy was necessary, its intended benefits were not realized equally in practice. Expanding pharmacist education and targeting support for independent and medical-affiliated pharmacies may help improve naloxone access, especially in rural and underserved areas.
Deepfake and other synthetic-media harms create a civil-liability problem that ordinary tort doctrine does not easily resolve: harmful content may be generated, amplified, monetised, and redistributed through a chain of actors in which no single participant controls the whole causal process. The objective of this article is to develop a layered civil-liability framework for that problem. It examines the Saudi and Jordanian civil-liability regimes as the principal doctrinal focus, while using selected EU, US, UAE, and Chinese materials as comparative reference points. The article remains private-law centred. It asks how civil-liability doctrine can respond when reputational, identity-based, corporate, and non-material harm is produced through the combined conduct of generative-model developers, prompting users, online platforms, and secondary distributors. The analysis identifies three pressure points: the natural-person wording of Article 138(2) of the Saudi Civil Transactions Law, which narrows moral-harm protection in relation to corporate and institutional injury; the persistence of a single-wrongdoer model in Saudi and Jordanian doctrine, despite the layered actor structure of deepfake production; and the evidential asymmetry created by opaque algorithmic causation. The article's main contribution is a calibrated model of layered civil liability: clearer protection for juridical-person reputation, a custody-based rule for algorithmic systems, cautious burden shifting where relevant information is controlled by platforms or developers, stronger private-law links to data-protection regimes, and targeted transparency duties for synthetic-media systems. The contribution is not to replace civil law with AI regulation, but to show how both fields must work together if deepfake-induced harm is to be remedied in a legally coherent way.
This ethnographic study examines the role of pharmaceutical companies in the era of precision medicine. Focusing on PD-L1 biomarker testing for cancer immunotherapy under Taiwan's National Health Insurance reimbursement policy, we trace how these diagnostics are introduced, adopted, and governed within the policy regime that frames therapeutic access. We propose the concept of "diagnostic infrastructuring" to describe how corporate entities act as "infrastructural architects," actively remodeling material platforms and clinical practices to facilitate the routinization of biomarker tests. Extending Sergio Sismondo's discourse on "assemblage marketing," this study reveals a shift toward material and practice governance. In this model, firms mobilize technical objects, standardize practices, and negotiate interpretive discretion and leniency to align with rigid policy frameworks, thereby bridging infrastructural gaps. By governing diagnostic routines, companies embed commercial interests directly into the clinical and reimbursement infrastructures of precision medicine. Ultimately, this industry-driven infrastructuring illuminates an evolving political economy where the capacity to deliver precision medicine is contingent upon the power to configure biomarker diagnostic practice.
Veterans are vulnerable to housing instability and/or homelessness (HUH) and may encounter unique challenges that affect their healthcare. While research has noted connections between major psychiatric disorders and HUH, few studies have examined personality disorders (PD) and their sex-specific relationships with HUH and healthcare use among aging veterans. We examined sex differences in the epidemiology of PD and their impact on healthcare service use among aging HUH veterans. A cross-sectional study involving 6,042,426 veterans (5,722,344 males and 320,082 females) was conducted using linked U.S. Department of Veterans Affairs (VA) Homeless Operations Management and Evaluation System and Corporate Data Warehouse among veterans ≥ 50 years who sought VA healthcare services over a twelve-month period between 2016 and 2024. Regression modeling was applied to identify predictors of PD and healthcare service use. PD prevalence was estimated at 0.46% (1.65% among females, and 0.39% among males). PD-diagnosed veterans experienced HUH more frequently than their counterparts, and this association was stronger in male vs. female veterans. Age < 65y, non-Black race, unmarried status, military sexual trauma, and self-directed violence were associated with PD among HUH-experienced veterans. Among HUH-experienced veterans, those with vs. without PD had greater odds of using healthcare services, with higher average number of healthcare encounters, especially among females for primary care, and among males for acute care. Although more frequently diagnosed among female veterans, PD were more strongly related to HUH among male veterans. Sex-specific patterns of healthcare use emerged according to PD among aging HUH-experienced veterans.
Development of organ dysfunction or death is still common in patients undergoing cardiac surgery. Yet, current risk stratification tools fail to adequately incorporate both preoperative vulnerability and immediate postoperative physiological derangements. This study aims to develop a predictive model integrating these critical timepoints to identify high-risk patients for presence of organ dysfunction or death 48 hours after surgery. This is a post hoc analysis of an international, multicenter, randomized, controlled trial in patients undergoing cardiac surgery (n=1394). Prespecified patient characteristics (age, Clinical Frailty Scale, at nutrition risk, combined procedures, urgent surgery, moderate-severe chronic kidney disease, left ventricular ejection fraction, European System for Cardiac Operative Risk Evaluation II, cardiopulmonary bypass duration, sex, Charlson Comorbidity Index, and Sequential Organ Failure Assessment score) were included in logistic regression models employing bootstrap validation. A total of 434 (31.1%) patients had organ dysfunction or died 48 hours after surgery. The preoperative model identified Clinical Frailty Scale, nutrition risk, urgent surgery and European System for Cardiac Operative Risk Evaluation II as significant predictors of organ dysfunction or death 48 hours after surgery (optimism-corrected area under the receiver operating characteristic curve, 0.644 [95% CI, 0.610-0.678]). Incorporation of postoperative variables (Sequential Organ Failure Assessment score at intensive care unit admission, and cardiopulmonary bypass duration) improved predictive performance (area under the receiver operating characteristic curve, 0.773 [95% CI, 0.745-0.801]). Incorporation of variables collected the day of surgery substantially improved the ability to predict organ dysfunction or death 48 hours after surgery compared with using presurgical variables only. This pragmatic, clinically actionable model may enable targeted resource allocation and personalized interventions and may provide a stratification tool for future research. URL: clinicaltrials.gov; Unique Identifier: NCT02002247.
The History of Medicine Library at the Royal Australasian College of Physicians is now one of the leading comprehensive research collections on the history of medicine of Australasia. This is a far cry from the founding fellows' original proposition in 1938, when they felt the need for a 'scientific library' to ensure the academic standards of their fledgling college. The present library has been made possible by donations from many personal and corporate collections. The first was a gift from the Royal College of Physicians of London in 1954, which redirected the focus to the history of medicine, followed in 1978 by the first munificent gift from Sir Edward Ford of his personal collection of Australiana. In the concluding decades of the 20th century, the value of all traditional history of medicine libraries worldwide was brought into question. Our library has survived the threat of dispersal on several occasions. The library and the extensive heritage collection of archives, artefacts, artwork and an image library have adapted to the challenges of the digital age, with greater visibility and accessibility through digital platforms. Our library, with its own unique history, has never looked so vibrant.
The bacterial strain Chryseobacterium endophyticum Cas268 was isolated from tobacco rhizosphere soil in China. In this study, we report the draft genome sequence of this strain. The genome measures 4,299,272 bp in length and has a G + C content of 39.56%.
There's a saying in the management world, popularized by NASA administrator Daniel Goldin in the 1990s, that the goal of technological improvements is to make products faster, better, and cheaper. Although this strategy had some success in the aerospace industry, the zealots of artificial intelligence (AI) have been making the same argument regarding how it will transform work, claiming that so little human effort will be required that humanity will enter an era of radical abundance, free from disease, drudgery, and danger, among other benefits, leaving society with more time for creative pursuits. But history tells a different story. When machines began to increase productivity during the second industrial revolution, American engineer Frederick Winslow Taylor's The Principles of Scientific Management encouraged corporations to use surveillance to get employees to work harder and longer, an approach that exhausted and discouraged workers and led to the transfer of knowledge and any decision-making from workers to management, while enriching the profits for only those at the top. Yet, it remains foundational to the American economic enterprise. Indeed, scientific publishing is starting to experience some Taylorism with the insertion of AI. Rigorous human checking of AI-generated research papers is creating bottlenecks as publishers strive to maintain the integrity of the scientific record. The challenge is requiring even more human effort, making the whole endeavor slower and more expensive.
Esketamine nasal spray (NS) is an established treatment for patients with treatment resistant depression (TRD). To further optimise real-world outcomes, consensus is needed regarding strategies to enhance patient outcomes and decision-making factors for pivotal timepoints in esketamine NS treatment. This modified Delphi panel (3 rounds) established expert consensus (≥80% agreement) from 30 European psychiatrists experienced in management of patients with TRD receiving esketamine NS. During the acute phase (4-12 weeks), modest/subjective reductions in core symptoms important to both patients and physicians supported esketamine NS continuation, especially with long disease course/resistance to multiple therapies. Consensus was reached that such a modest improvement during the acute phase should justify esketamine NS continuation (and supplementation of other treatment modalities with esketamine NS). Esketamine NS dose/frequency maximisation (84 mg weekly) was advocated for, to enhance acute phase outcomes, alongside strategies reflective of individual clinical characteristics. Monitoring in the continuation phase (6-9 months) should prioritise residual/fluctuating symptoms, changes in symptom severity, functional recovery status and comorbidity management/emergence. Should residual symptoms persist, dose/frequency escalation, among other all-phase options, were supported. Prolonging maintenance phase treatment (≥12 months) depended on the degree of clinical worsening when tapering, the risks/consequences of relapse, chronicity of the last depressive episode, residual symptoms and recurrence history. Across all phases, recommended treatment plans included integration of psychotherapy, optimisation of concomitant antidepressants/augmentation strategies, comorbidity management and strengthening support networks. Overall, the consensus advocated for an approach reflective of TRD complexities, prioritising meaningful outcomes for individual patients.
Contact lenses are a cornerstone of vision correction for ametropia and can be of particular value for management of irregular astigmatism and corneal ectasia. Beyond objective measures of visual acuity and corneal health, patient-reported outcomes and vision-related quality of life (VR-QoL) have emerged as critical endpoints. This review aimed to synthesize evidence on VR-QoL outcomes with contact lenses. We conducted a narrative review of studies published between 2000 and 2025 on the influence of various contact lens modalities including soft conventional lenses, rigid gas-permeable (RGP) lenses, scleral and mini-scleral lenses, orthokeratology, and specialty designs on VR-QoL across myopia, keratoconus, dry-eye disease, and other conditions. Descriptive tables were developed for all identified studies, and a synthesis of the impact of contact lenses on VR-QoL findings is presented. Evidence for VR-QoL measurement and instrumentation, special considerations for pediatric/adolescent populations, and barriers/limitations to sustained contact lens wear were also appraised. VR-QoL evaluations using validated instruments demonstrate favorable findings with contact lenses. VR-QoL gains with contact lenses are more favorable compared with spectacle correction, particularly in appearance, activities, peer perception, and psychological domains. In keratoconus, RGP and scleral lenses dramatically improve NEI-VFQ-25 composite scores, even in cases of advanced disease. Barriers to sustained wear of contact lenses mostly relate to lens discomfort and dry eye due to ocular surface complications, although studies in patients with ocular surface disease/dry eye still derive VR-QoL benefits with contact lenses. There is a lack of head-to-head trials for certain modalities (eg, an absence of studies directly comparing multifocal contact lenses to spectacles for fall rates). Contact lenses provide significant and clinically meaningful gains in VR-QoL among adult and pediatric patients with refractive error, keratoconus, ocular surface disease or dry eye, and other indications. The VR-QoL benefits of contact lenses may exceed those achieved with spectacles. The goals of vision correction are to improve patients’ functional vision as well as their quality of life (QoL). Vision-related quality of life (VR-QoL) includes visual function, social and emotional well-being, convenience, appearance, and independence from optical aids. Measuring VR-QoL among contact lens wearers is important because it has been shown that using the objective clinical measures alone (ie, functional vision) does not capture the full patient experience and does not predict long-term success and satisfaction with contact lenses. We conducted a review of published medical literature to summarize studies that evaluated VR-QoL with contact lenses from 2000 to 2025. Despite some gaps in evidence (for example, studies comparing bifocal contact lenses to bifocal glasses), this literature review demonstrated that there are substantial data showing the significant and clinically meaningful improvements in VR-QoL with contact lenses among adults and children with refractive error (myopia, hyperopia, astigmatism, and presbyopia), keratoconus and irregular corneal conditions, ocular surface disease/dry eye, amblyopia, photophobia, post-corneal crosslinking, and allergy. Contact lenses may improve VR-QoL more than glasses. Our research provides a comprehensive summary of published evidence for the impact of contact lenses on VR-QoL.
IntroductionPrevious studies found associations between cancer and the gut microbiome. Thus, we aimed to investigate the gut microbiome composition in adults with and without cancer to try to identify specific microbes that may be associated with cancer in a cross-sectional, observational, and retrospective study.MethodsStool samples from sixty participants, n=20 controls, n=25 with aggressive cancer, and n=15 with non-aggressive cancer were analyzed using Metagenomic Next Generation Sequencing. Mann-Whitney U test tests were used to examine differences in the relative abundances of bacterial genera.ResultsCompared to controls, aggressive cancer patients had statistically significantly lower levels of gut Bifidobacterium, Faecalibacterium, and Collinsella, (all p≤0.05), while they had higher levels of gut Bacteroides (p=0.015). Non-aggressive cancer patients had lower levels of gut Bifidobacterium compared to controls, an association that was approaching statistical significance (p=0.054).ConclusionAggressive-cancer patients showed significantly altered levels of key gut microbes compared to controls. These are preliminary associations, and thus further larger studies are needed to confirm these findings.
Hypnotic suggestibility may moderate treatment outcomes, but evidence in depression is limited and inconsistent. This analysis examined whether baseline hypnotic suggestibility moderated changes in depressive symptoms over time and whether this effect differed between groups. This exploratory secondary analysis used data from the HypnoDeep trial, a randomized, controlled, pilot trial. Patients with mild to moderate depressive symptoms were randomized to group hypnosis, progressive muscle relaxation (PMR), or control. Hypnotic suggestibility was assessed with the Harvard Group Scale of Hypnotic Susceptibility, Form 5 (HGSHS-5:G) and the Creative Imagination Scale (CIS) at baseline. Depressive symptoms were measured at baseline and at 6 weeks using the Beck Depression Inventory-II. Linear mixed-effects models examined whether baseline suggestibility moderated depressive symptom changes and whether this association differed between groups, adjusting for age and sex. Separate models were estimated for HGSHS-5:G and CIS. A post hoc power analysis contextualized detectable effect sizes. Ninety-four participants were included (mean age 39.2 years, SD 12.0; women: n = 67 [71.3%], men: n = 25 [26.6%], diverse: n = 2 [2.1%]). Baseline hypnotic suggestibility assessed with the HGSHS-5:G ranged from 0 to 5 (mean 2.9, SD 1.6), and CIS scores ranged from 2 to 35 (mean 17.6, SD 7.7). Baseline hypnotic suggestibility was not associated with differential change in depressive symptoms over time in the control group for either the HGSHS-5:G or the CIS, and there was no indication that this association differed in the hypnosis or PMR group compared with the control group (HGSHS-5:G: hypnosis β = 2.05, 95% CI -2.21 to 6.31, p = 0.350; PMR β = -0.97, 95% CI -5.14 to 3.20, p = 0.651; CIS: hypnosis β = 3.06, 95% CI -1.36 to 7.48, p = 0.179; PMR β = -0.44, 95% CI -4.49 to 3.61, p = 0.833). Post hoc power analysis indicated that complete-case group sizes were insufficient to reliably detect small-to-moderate associations. Exploratory analyses did not indicate that hypnotic suggestibility moderated changes in depressive symptoms across groups. Given limited statistical power, findings are preliminary and hypothesis-generating. Larger studies are needed to clarify treatment-response moderators.
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The association between pregnancy and the risk of symptomatic hemorrhage (SH) in brainstem cavernous malformations remains uncertain. We aimed to quantify the risk of pregnancy-associated SH in women with brainstem cavernous malformations. We analyzed women with brainstem cavernous malformations in a prospective registry (2016-2022) experiencing pregnancy after enrollment. Follow-up was divided into pregnancy-associated segments (pregnancy plus ≤6 weeks postpartum or postabortion) and nonpregnant segments. Primary analysis used case-crossover models; propensity score-matched analyses assessed robustness. Among 63 women (median age, 30.0 years), 53 (84.1%) had bled before enrollment, including 45 (71.4%) with SH in the preceding year. Prospectively, they contributed 72 pregnancies and 371.7 patient-years, observing 34 SHs. The pregnancy annual SH rate was 20.4% versus 7.2% nonpregnant (adjusted incidence rate ratio: 2.56, 95% CI, 1.11-5.93; P=0.028). Trimester-specific and postpartum annual SH rates were 5.9%, 16.8%, 34.6%, and 38.3%; risk significantly increased only during the third trimester (P=0.004) and postpartum (P=0.007). This pregnancy effect was confined to segments with SH in the preceding year (annual SH rates 46.7% versus 9.4%; P=0.007), which was an independent risk factor. Propensity score-matched analyses yielded consistent results. Pregnancy is associated with an elevated SH risk in women with brainstem cavernous malformations, specifically among those with SH in the preceding year. Because of selection bias, generalizability to asymptomatic or incidental lesions is limited, warranting cautious extrapolation. URL: www.chictr.org.cn; Unique Identifier: ChiCTR-POC-17011575.
This study investigates the 2024 cholera outbreak in Gujarat, India, utilizing combined whole-genome analysis of clinical Vibrio cholerae isolates and wastewater surveillance. A total of, 69 V. cholerae isolates were recovered from affected patients, predominantly belonging to the O1 serogroup (51 isolates). Antimicrobial susceptibility test (AST) of 34 isolates revealed complete resistance to ampicillin and partial resistance to cotrimoxazole, whereas all isolates were susceptible to doxycycline, ciprofloxacin, chloramphenicol, tetracycline, and gentamicin. Whole-genome sequencing of 20 selected isolates revealed that the isolates belong to the seventh pandemic El Tor (7PET) lineage, sequence type ST69. Phylogenomic analyses using a multi-method approach, core genes, Composition Vector (CV) Tree, SNPs, and multilocus sequence typing (MLST) showed tight clustering with limited diversity among the isolates. All isolates contained 13-15 antimicrobial resistance genes, with high consistency between genotype-phenotype for most antibiotics, although discordance was observed for ciprofloxacin, cotrimoxazole, and chloramphenicol. Sixteen genes were identified as virulence factors, and 11 isolates also had ctxA/ctxB. All isolates also had two to four integrative conjugative elements (ICEs) containing antimicrobial resistance genes (ARGs) and important Vibrio cholerae pathogenicity islands (VPI-1, VPI-2) and Vibrio cholerae seventh pandemic islands (VSP-1, VSP-2). The pangenome analysis highlights extensive genomic flexibility within species, likely driven by horizontal gene transfer and ecological adaptation; however, further outbreak-specific investigations are required to determine their direct role in current outbreak. The detection of ctxA-positive signals in wastewater, 20% (28/140) of the samples, suggests a possible surveillance signal during the outbreak. These results highlight the presence of antimicrobial-resistant 7PET O1 El Tor strains in Gujarat outbreaks and support continued genomic monitoring to guide focused public health interventions in endemic areas. Furthermore, this study also underscores the importance of wastewater surveillance for monitoring V. cholerae.
Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.
To compare tissue-level (TL) and bone-level X (BLX) implants regarding peri-implant bone level alterations, survival, and complication rates over a 3-years. In this retrospective, non-interventional clinical study, patients that had received either TL or BLX implants (both: Straumann AG), with at least one clinical follow-up (minimum 6 months), were included. Bone-level alterations and bone peaks were evaluated at baseline (implant placement) and at follow-ups from dental radiographs. In addition, clinical follow-ups included the recording of the presence of keratinized mucosa and the registration of technical complications (e.g., chipping fractures). For statistics, descriptive analyses, t-tests, and a random-effects linear regression analysis were applied. A total of 146 implants (73 TL and 73 BLX) were included. TL implants showed a survival rate of 100%, whereas BLX implants showed a survival rate of 98% after 3 years. TL implants showed significant mesial bone gain (0.08 mm, p = 0.018) between 2- and 3-year follow-ups, with a notable difference (0.21 mm, p = 0.041) compared to BLX implants. At distal bone levels, TL implants showed initial bone loss (0.12 mm, p = 0.020) at 6 months but gained bone (0.07 mm, p < 0.001) between 2 and 3 years, whereas BLX implants showed significant distal bone loss (0.15 mm, p = 0.038) over 3 years. The number of complications was higher in BLX implants. BLX implants with a band of keratinized mucosa > 2 mm showed smaller bone level alterations. Both TL and BLX implants performed similarly in terms of clinical and radiological outcomes. However, at the mesial aspect, bone level alterations in TL implants were smaller than in BLX implants, and complications were less frequent. Keratinized mucosa seems especially beneficial in BLX implants. As implant selection was based on clinical indication, the two groups differed in baseline characteristics, and this should be considered when interpreting the between-group comparisons.
In chronic myeloid leukemia in chronic phase (CML-CP), BCR::ABL1T315I commonly leads to treatment resistance, worse patient outcomes, and limited subsequent treatment options. By targeting the ABL1 myristoyl pocket, asciminib maintains activity against BCR::ABL1T315I. We report final long-term safety, tolerability, and efficacy results with asciminib in 48 patients with T315I-mutated CML-CP who received asciminib 200 mg twice daily in the phase 1, nonrandomized trial (NCT02081378). After a median exposure of 3.5 years, 52.1% of patients continued to receive asciminib via posttrial access. Of 45 evaluable patients, 24 (53.3%) achieved major molecular response (MMR); 20 of 24 maintained or deepened their response by the cutoff. The Kaplan-Meier estimated proportion of patients maintaining their first MMR for at least 144 weeks (2.8 years) was 86% (95% CI: 71.9-100.0%). The safety profile showed no new or worsening safety signals. With 1.4 years' additional exposure since the previous analysis, the incidence of grade ≥3 adverse events (AEs) (60.4%) did not increase. Four patients (8.3%) discontinued due to AEs. The exposure-adjusted incidence rate of first all-grade AOEs was 4.4 cases per 100 patient-years. With up to approximately 6 years of exposure, this final analysis confirms asciminib as a treatment option for patients with T315I-mutated CML-CP.
Therapeutic phlebotomy maintains hematocrit (Hct) <45% in patients with polycythemia vera (PV) and reduces thrombotic risks. However, frequent phlebotomy can induce iron deficiency. Ropeginterferon alfa-2b (ropeg) is a new-generation interferon therapy that induces durable complete hematologic and molecular responses through reduction of the Janus kinase 2 (JAK2)-mutated clone. Two dosing regimens have been investigated: the FDA-approved slow-titration regimen and a higher initial dose and accelerated titration (HIDAT) regimen. A cross-analysis of three prospective trials showed that ropeg achieved sustained Hct control and reduction of phlebotomy dependence in PV patients, including high-risk and hydroxyurea-resistant/intolerant patients. In exploratory cross-study comparisons, the HIDAT regimen was associated with more rapid phlebotomy-free Hct response rates, lower mean annualized phlebotomy frequency, higher overall hematologic response rates and deeper JAK2V617F allele burden reduction than slow titration. Both regimens were safe and well tolerated. Ropeg treatment provides durable Hct control and phlebotomy-independence in a broad PV population, including high-risk patients.