Efficient Rescue of Retinal Degeneration in Pde6a Mice by Engineered Base Editing and Prime Editing.

Retinitis pigmentosa (RP) is a complex spectrum of inherited retinal diseases marked by the gradual loss of photoreceptor cells, ultimately leading to blindness. Among these, mutations in PDE6A, responsible for encoding a cGMP-specific phosphodiesterase, stand out as pivotal in autosomal recessive RP (RP43). Unfortunately, no effective therapy currently exists for this specific form of RP. However, recent advancements in genome editing, such as base editing (BE) and prime editing (PE), offer a promising avenue for precise and efficient gene therapy. Here, it is illustrated that the engineered BE and PE systems, particularly PE, exhibit high efficiency in rescuing a target point mutation with minimal bystander effects in an RP mouse model carrying the Pde6a (c.2009A > G, p.D670G) mutation. The optimized BE and PE systems are first screened in N2a cells and subsequently assessed in electroporated mouse retinas. Notably, the optimal PE system, delivered via dual adeno-associated virus (AAV), precisely corrects the pathogenic mutation with average 9.4% efficiency, with no detectable bystander editing. This correction restores PDE6A protein expression, preserved photoreceptors, and rescued retinal function in Pde6a mice. Therefore, this study offers a proof-of-concept demonstration for the treatment of Pde6a-related retinal degeneration using BE and PE systems.

Aging of drinking water transmission pipes during long-term operation as a potential source of nano- and microplastics.

Microplastics (MPs) and nanoplastics (NPs) released into drinking water from transmission pipes can pose a potential health risk to consumers. This paper presents the results of a comprehensive study of PE and PVC pipes after long-term operation in drinking water distribution networks, which confirmed that degradable polymers can be a significant source of MPs. Both plastics age relatively quickly, and the degree of damage to the pipe surface depends on the time and operating conditions. During aging, polymer chains deteriorate, leading to a weakening of the structure and increased amorphousness of the plastics. As a result, the surfaces of PE and PVC crack and peel, resulting in the formation of particles with sizes corresponding to NP and MP with high potential for release into water. The magnitude of the phenomenon increases as the diameter of the pipes decreases, indicating that the most vulnerable customers are those at the ends of the network to which drinking water is supplied through small-diameter pipes. Aging PE and PVC pipes should be considered a real and very important source of MPs and NPs in drinking water, and water quality in this aspect should be monitored by manufacturers.

PE/PPE Proteome and ESX-5 Substrate Spectrum in Mycobacterium marinum.

PE/PPE proteins secreted by the ESX-5 type VII secretion system constitute a major protein repertoire in pathogenic mycobacteria and are essential for bacterial survival, pathogenicity, and host-pathogen interaction; however, little is known about their expression and secretion. The scarcity of arginine and lysine residues in PE/PPE protein sequences and the high homology of their N-terminal domains limit protein identification using classical trypsin-based proteomic methods. This study used endoproteinase AspN and trypsin to characterize the proteome of Mycobacterium marinum. Twenty-seven PE/PPE proteins were uniquely identified in AspN digests, especially PE_PGRS proteins. These treatments allowed the identification of approximately 50% of the PE/PPE pool encoded in the genome. Moreover, EspG5 pulldown assays retrieved 44 ESX-5-associated PPE proteins, covering 85% of the PPE pool in the identified proteome. The identification of PE/PE_PGRS proteins in the EspG5 interactome suggested the presence of PE-PPE pairs. The correlation analysis between protein abundance and phylogenetic relationships found potential PE/PPE pairs, indicating the presence of multiple PE/PE_PGRS partners in one PPE. We validated that EspG5 interacted with PPE31 and PPE32 and mapped critical residues for complex formation. The modified proteomic platform increases the coverage of PE/PPE proteins and elucidates the expression and localization of these proteins.

The influence of patient sex on pulmonary embolism evaluation, treatment modality, and outcomes.

BACKGROUND: Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality, accounting for 100,000 deaths per year in the United States. Although sex-based disparities have previously been described in this population, it is unclear if these differences have persisted with the expansion of PE evaluation and treatment approaches. The purpose of this study is to investigate sex-based differences in the evaluation, management, and outcomes of patients with acute PE. METHODS: We performed a retrospective analysis of patients enrolled in the national Pulmonary Embolism Response Team (PERT) Consortium database between October 2015 and October 2022. We evaluated patient demographics, clinical characteristics, diagnostic imaging performed, treatment at several phases of care (pre-PERT, PERT recommendations, and post-PERT), and clinical outcomes. RESULTS: A total of 5722 patients with acute PE (2838 [49.6%] women) from 35 centers were included. There were no differences in PE risk category between male and female patients. Women were less likely to undergo echocardiography (76.9% vs 73.8%) and more likely to receive no anticoagulation prior to PERT evaluation (35.5% vs 32.9%). PERT teams were more likely to recommend catheter-based interventions for men (26.6% vs 23.1%), and men were more likely to undergo these procedures (21.9% vs 19.3%). In a multivariable analysis, female sex was a predictor of in-hospital mortality (OR 1.53, 95% CI 1.06 to 2.21). CONCLUSIONS: In this analysis, we identified sex-based differences in the evaluation and management of patients presenting with acute PE. Subsequently, women presenting with acute PE were at higher risk of in-hospital mortality.

Risk factors and mortality associated with venous thromboembolism in the elderly US population with chronic lymphocytic leukemia.

BACKGROUND: Venous thromboembolism (VTE) causes morbidity and mortality in cancer patients. The association of VTE with known risk factors in chronic lymphocytic leukemia (CLL) is not known. OBJECTIVE: To examine risk factors and mortality associated with VTE in White, Black, and Asian CLL patients. METHODS: The United States SEER-Medicare database (2000-2015) was used for CLL patients ≥ 65 years. Logistic regression was used to examine VTE risk factors and Cox proportional regression was used to evaluate the effect of VTE on mortality in White, Black, and Asian CLL patients. RESULTS: Among 34,075 CLL patients, VTE was diagnosed in 11.6 % of 31,395 White, 14.6 % of 2062 Black and 6.3 % of 618 Asian patients. Risk of having VTE was, ORa = 1.2 (95 % CI, 1.0-1.4) for Black patients and ORa = 0.5 (95 % CI, 0.4-0.7) for Asian patients compared to White patients. Anemia and heart failure were associated with VTE in all three racial cohorts and were the only risk factors in Asian patients. Other risk factors in White patients were the same as in the overall population, including hypertension, obesity, COPD, kidney disease, diabetes, hyperlipidemia, myocardial infarction, and chemotherapy. In Black patients, other risk factors were hypertension, and chemotherapy. Mortality was slightly higher with VTE in the overall population and in White patients. CONCLUSION: There was difference in VTE risk factors in White, Black, and Asian patients. VTE was marginally associated with mortality in CLL patients. Our findings may help to identify patients at higher risk of VTE in racially diverse CLL populations.

Chemo-Enzymatic Depolymerization of Functionalized Low-Molecular-Weight Polyethylene.

Polyethylene (PE) is the most commonly used plastic type in the world, contributing significantly to the plastic waste crisis. Microbial degradation of PE in natural environments is unlikely due to its inert saturated carbon-carbon backbones, which are difficult to break down by enzymes, challenging the development of a biocatalytic recycling method for PE waste. Here, we demonstrated the depolymerization of low-molecular-weight (LMW) PE using an enzyme cascade that included a catalase-peroxidase, an alcohol dehydrogenase, a Baeyer Villiger monooxygenase, and a lipase after the polymer was chemically pretreated with m-chloroperoxybenzoic acid (mCPBA) and ultrasonication. In a preparative experiment with gram-scale pretreated polymers, GC-MS and weight loss determinations confirmed ~27% polymer conversion including the formation of medium-size functionalized molecules such as ω-hydroxy acids and α,ω-carboxylic acids. Additional polymer property analyses using AFM showed that enzymatic depolymerization reduced the particle sizes of this mCPBA- and enzyme-treated LMWPE. This multi-enzyme catalytic concept with distinct chemical steps represents a unique starting point for future development of bio-based recycling methods for polyolefin waste.

The efficacy of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. METHODS: PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). CONCLUSION: This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. LEVEL OF EVIDENCE: Level I.

Biodegradation of low-density polyethylene by mixed fungi composed of Alternaria sp. and Trametes sp. isolated from landfill sites.

With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In this study, we isolated a series of LDPE-degrading fungi from landfill sites and carried out LDPE degradation experiments by combining highly efficient degrading fungi in pairs. The results showed that the mixed microorganisms composed of Alternaria sp. CPEF-1 and Trametes sp. PE2F-4 (H-3 group) had a greater degradation effect on heat-treated LDPE (T-LDPE). After 30 days of inoculation with combination strain H-3, the weight loss rate of the T-LDPE film was approximately 154% higher than that of the untreated LDPE (U-LDPE) film, and the weight loss rate reached 0.66 ± 0.06%. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) were used to further investigate the biodegradation impacts of T-LDPE, including the changes on the surface and depolymerization of the LDPE films during the fungal degradation process. Our findings revealed that the combined fungal treatment is more effective at degrading T-LDPE than the single strain treatment, and it is expected that properly altering the composition of the microbial community can help lessen the detrimental impact of plastics on the environment.

20 years clinical application of the vacuum bell for conservative treatment of pectus excavatum-past, present, future.

Background: For decades, open surgical repair was the only available method to treat pectus excavatum (PE). In 1998 Donald Nuss described first time a minimally invasive repair of pectus excavatum (MIRPE), and today MIRPE is performed with increasing frequency worldwide. However, despite its minimally invasive approach, with the widespread use of MIRPE the character and number of complications have increased. 20 years ago, non-surgical measures such as vacuum bell therapy (VBT) were introduced as a useful complement for specific treatment of PE patients. However, until today there are no existing validated guidelines concerning VBT. Methods: The study includes the results of an online survey submitted to the members of Chest Wall International Group (CWIG), a selective review of the English spoken current literature with focus on VBT and an analysis of our own previous studies concerning VBT. Results: Seventy-two percent of the CWIG members practicing in 47 different institutions confirmed to use VBT for PE patients. Furthermore, within the last 10 to 15 years an increasing number of studies were identified reporting on successful use of VBT for PE. However, a recently published study stated that the effect of VBT is predominantly because of thickening of the chest wall by increasing pre-sternal adipose tissue. There was one study comparing VBT to MIRPE but no randomized and/or prospective studies comparing conservative treatment vs. surgical repair or conservative treatment vs. no specific therapy. Variables predictive of an excellent outcome could be identified. Especially in younger PE patients, VBT is reported with increasing frequency in the survey as well as in the literature. However, validated guidelines concerning VBT are still not available. Conclusions: Non-operative treatment of PE with VBT proved to be safe and a potential alternative to surgical repair in carefully selected PE patients. Patient's age at diagnosis and severity of the PE represents relevant variables to decide which kind of therapy might be successful to correct PE. Especially in PE patients under the age of 10 years, VBT seems to represent the first step of specific therapy.

Best Practices for Optimizing Patients Undergoing Surgical Procedures to Prevent Postoperative Venous Thromboembolism: A Quality Improvement Project.

Introduction Current studies suggest that both chemical and mechanical venous thromboembolism (VTE) prophylaxis is underused, which is concerning due to the potential lethality of VTEs. The Caprini risk score is a preoperative VTE risk assessment that determines a patient's risk of enduring a VTE. The objective of this study was to examine postoperative cases of VTE to determine if accurate VTE risk stratification was performed and whether appropriate VTE prophylaxis was administered. Methods A retrospective analysis was conducted on 23 reported cases of VTE that occurred at a Central Florida hospital from April 1, 2021, to March 31, 2022. Relevant demographic and medical information was gathered from each patient chart to calculate an individual Caprini risk score and determine the type of chemical VTE prophylaxis that was received. Results Out of 23 reported cases of VTE in surgical patients, 17 were ultimately determined to have suffered VTE associated with their hospitalization and surgery. Thirteen out of 17 (76%) received appropriate perioperative chemical deep vein thrombosis (DVT) prophylaxis based on the calculated Caprini risk score and corresponding recommendations. Four out of 17 (24%) were determined to have received insufficient perioperative chemical DVT prophylaxis. Conclusion Consistent utilization of a DVT/pulmonary embolism (PE) risk stratification tool, such as the Caprini risk score calculator, is essential in the prevention of postoperative VTE. Hospitals can improve the utilization of such a tool and thereby reduce the number of embolic events by making it more visible and accessible to the overseeing provider in the electronic medical record (EMR).

First record of a possible trypanotolerant cattle breed in Latin America: Parasitological, serological, and clinical aspects.

Trypanosoma vivax infections are endemic in Africa, where they provoke trypanosomosis against which some local taurine breeds are tolerant and are thus named trypanotolerant. In Latin America, T. vivax was imported in 1919, since when it has been responsible for periodic outbreaks of the disease. This study assessed whether a South American taurine breed resilient to several parasitic and infectious diseases (Curraleiro Pé-Duro-CPD) can meet trypanotolerant criteria (control parasite proliferation, prevent anemia, survive without treatment, and maintain productivity). Three groups were established, each consisting of six animals (Group 1: CPD-infected; Group 2: Holstein/Gyr-infected; Group 3: Holstein/Gyr-uninfected, negative control). Groups 1 and 2 were infected with T. vivax on Day 0 and evaluated until day 532. Throughout the experimental period, parasitological (Woo and Brener), molecular (cPCR), serological (enzyme-linked immunosorbent assay - ELISA, indirect fluorescent antibody test - IFAT, immunochromatographic assay - IA), and clinical (hemogram, fever, weight loss) aspects were evaluated. During the acute phase of the disease, T. vivax was initially detected in Holstein/Gyr. Notably, the CPD animals restored their packed cell volume (PCV) values to the normal range 74 days after inoculations. In the chronic phase, two of the six CPD animals were positive by cPCR until D + 522 following immunosuppression with dexamethasone. Regarding serological aspects, the two CPD animals had positive tests until D + 532. The absence of T. vivax in blood during the chronic phase did not correspond to "self-cure". Holstein/Gyr animals exhibited fever on more evaluation days than CPD animals. Both breeds experienced weight loss, with Holstein/Gyr animals losing significantly more weight. On D + 25, the Holstein/Gyr group required treatment. During the 532 days, none of the CPD animals required treatment, even after being sensitized with dexamethasone. Animals from Group 3 tested negative for T. vivax throughout the experiment. This study demonstrated that CPD cattle fulfill the mentioned trypanotolerant criteria.

Isolation of marine polyethylene (PE)-degrading bacteria and its potential degradation mechanisms.

Microbial degradation of polyethylene (PE) offers a promising solution to plastic pollution in the marine environment, but research in this field is limited. In this study, we isolated a novel marine strain of Pseudalkalibacillus sp. MQ-1 that can degrade PE. Scanning electron microscopy and water contact angle results showed that MQ-1 could adhere to PE films and render them hydrophilic. Analyses using X-ray diffraction, fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy showed a decrease in relative crystallinity, the appearance of new functional groups and an increase in the oxygen-to­carbon ratio of the PE films, making them more susceptible to degradation. The results of gel permeation chromatography and liquid chromatography-mass spectrometry indicated the depolymerization of the long PE chains, with the detection of an intermediate, decanediol. Furthermore, genome sequencing was employed to investigate the underlying mechanisms of PE degradation. The results of genome sequencing analysis identified the genes associated with PE degradation, including cytochrome P450, alcohol dehydrogenase, and aldehyde dehydrogenase involved in the oxidative reaction, monooxygenase related to ester bond formation, and esterase associated with ester bond cleavage. In addition, enzymes involved in fatty acid metabolism and intracellular transport have been identified, collectively providing insights into the metabolic pathway of PE degradation.

Causal association of sex hormone-binding globulin on gestational hypertension and pre-eclampsia: a two-sample Mendelian randomization study.

OBJECTIVES: Pre-eclampsia (PE) and gestational hypertension (GH) are two different categories of hypertensive disorders of pregnancy. Given earlier observational research, the relationship between sex hormone-binding globulin (SHBG) and a higher risk of GH/PE is still up for dispute. Hence, the present investigation aimed to examine the possible link between SHBG and the likelihood of GH/PE. METHODS: As a first stage, single nucleotide polymorphisms from summary-level genome-wide association studies were tightly screened using quality-control techniques. Afterward, we utilized a two-sample Mendelian randomization (MR) study to examine the causal impact of SHBG on the likelihood of GH/PE. There was no indication of a relationship between blood SHBG level (n = 214,989) and GH/PE (1864 cases and 461,069 controls) in the initial study. Consensus results were obtained from the replicated analysis, which utilized MR estimates based on serum SHBG level(n = 214,989) for GH (4255 cases and 114,735 controls). RESULTS: The findings did not indicate any proof of a cause-and-effect connection between SHBG and the likelihood of GH/PE (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.999 - 1.00, p = .34). Replicate analysis also revealed similar patterns (OR = 0.92, 95%CI = 0.82-1.05, p = .21). The above findings were demonstrated to have a strong level of robustness. CONCLUSIONS: The findings of this research did not offer definitive proof to endorse the idea that SHBG has a direct causal impact on the likelihood of GH/PE, which goes against numerous widely accepted observational studies. To ascertain the potential processes behind the relationships seen in observational studies, more investigation is needed.

Age-related differences in the prevalence of premature ejaculation: taking a second and more detailed look.

Background: Research indicates an inconsistent relationship between age and the prevalence of premature ejaculation (PE), with studies reporting an increase, decrease, or no change with age. Aim: To reexamine the possible relationship between age and PE prevalence, implementing methodological improvements that enhance the likelihood of detecting real effects. Methods: From a sample of 2772 men, we analyzed a subset of 418 classified as having probable or definite PE based on the Premature Ejaculation Diagnostic Tool. We not only analyzed men with lifelong PE (LPE; n = 316) and acquired PE (APE; n = 102) separately but assessed prevalence differences across age groups using an omnibus measure to establish PE status and specific PE diagnostic criteria, individually and in multifactorial combination. Outcome: Prevalence of PE in younger vs older men. Results: LPE, but not APE, showed age-related differences in prevalence, with LPE being lower in the higher age group. This pattern was most discernible when a multifactorial approach was used to establish PE status. Clinical Translation: Older men may be less distressed about their dysfunction or may benefit from diminishing ejaculatory function with age. Strengths and Limitations: This cross-sectional study used an improved methodology to detect age-related differences in PE prevalence. Future studies would benefit from a larger sample size that enables a breakdown of prevalence using a greater number of age categories. Conclusion: According to an improved methodology, men with LPE showed a decline in prevalence with aging. A methodology aimed at exploring this relationship should-at the very least-not only distinguish between LPE and APE subtypes but also consider using a multifactorial method of determining PE status that includes a measure of bother/distress.

Task-specific relationships between error-related ERPs and behavior: Flanker, Stroop, and Go/Nogo tasks.

Performance monitoring has been widely studied during different forced-choice response tasks. Participants typically show longer response times (RTs) and increased accuracy following errors, but there are inconsistencies regarding the connection between error-related event-related brain potentials (ERPs) and behavior, such as RT and accuracy. The specific task in any given study could contribute to these inconsistencies, as different tasks may require distinct cognitive processes that impact ERP-behavior relationships. The present study sought to determine whether task moderates ERP-behavior relationships and whether these relationships are robustly observed when tasks and stimuli are treated as random effects. ERPs and behavioral indices (RTs and accuracy) recorded during flanker, Stroop, and Go/Nogo tasks from 180 people demonstrated a task-specific effect on ERP-behavior relationships, such that larger previous-trial error-related negativity (ERN) predicted longer RTs and greater likelihood of a correct response on subsequent trials during flanker and Stroop tasks but not during Go/Nogo task. Additionally, larger previous-trial error positivity (Pe) predicted faster RTs and smaller variances of RTs on subsequent trials for Stroop and Go/Nogo tasks but not for flanker task. When tasks and stimuli were treated as random effects, ERP-behavior relationships were not observed. These findings support the need to consider the task used for recording performance monitoring measures when interpreting results across studies.

Enhancing microplastic removal from natural water using coagulant aids.

Microplastic (MP) pollution poses a significant environmental challenge, underscoring the need for improved water treatment methods. This study investigates the effectiveness of coagulation, flocculation, and sedimentation processes for removing microbeads, focusing on key factors that influence removal efficiency. Among the coagulants tested, polyaluminium chloride (PAC) demonstrated superior performance by enhancing the aggregation of microplastics with flocs. Optimal treatment conditions were determined to be 0.4 mmol/L PAC and 3 mg/L polyacrylamide (PAM) at pH 8 (before adding PAC), with rapid stirring at 240 rpm for 1 min, followed by slow stirring at 35 rpm for 13 min, and a sedimentation period of 25 min. Under these conditions, removal efficiencies exceeded 95 % for a range of microbeads (10-1000 µm: Polystyrene (PS), Polypropylene (PP), Polyvinyl chloride (PVC), Polyamide (PA), Polyethylene (PE), and Polyurethane (PU)) from natural water samples. Without PAM, PAC alone achieved a 97 % removal rate for PS microbeads. The addition of PAM maintained high removal efficiency, while aluminium sulphate and ferric chloride were less effective, with removal rates of 67 % and 48 % for PS microbeads, respectively. PAM enhanced MP removal across various coagulants and microbead types, with maximum efficiency observed at PAM concentrations of ≥3 mg/L. The treatment also demonstrated that organic matter in Regent's Park pond water could further improve MP removal. Size significantly impacts removal efficiency: larger microbeads (1 mm to >250 µm) were removed more effectively (95 %) compared to smaller ones (10 to <250 µm), which had a lower removal rate of 49 %. Denser microbeads like PVC (density 1.38 g/cm³) settled more efficiently than lighter microbeads such as PE (density 0.97 g/cm³). These findings suggest a need for advanced technologies to better remove lighter, smaller MPs from water.

E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients. CONCLUSION: These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient's need for Colchicine treatment. WHAT IS KNOWN: • The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation. • The prevalence of MEFV variants can vary significantly among different ethnic groups. WHAT IS NEW: • The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment. • The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.

Double-bar technique for the correction of asymmetric pectus excavatum.

Background: Minimally invasive repair of pectus excavatum (MIRPE) improves clinical outcomes and chest wall morphology. However, asymmetry in patients with pectus excavatum (PE) remains as an important issue, even after surgery. Here, we evaluated the benefit of double-bar technique in achieving a symmetric chest wall. Methods: This retrospective study included 79 patients with PE who underwent MIRPE between 2017 and 2021. The patients were divided into the double- or non-double-bar groups. Asymmetric degree (AD) and sternal rotation angle (SRA) were used to assess the severity of asymmetry based on computed tomography (CT) images. The primary outcome was the change in radiologic parameters. Secondary outcomes were clinical results, including hospital stay, pain scores, and complication rates. Subgroup analysis of patients with preoperative asymmetric PE was performed. Results: Patients in the double-bar group (n=23) were younger than those in the non-double-bar group (n=56). Additionally, the double-bar group exhibited lower pain scores and shorter hospital stay. Based on radiological assessments, the double-bar group demonstrated a greater decrease in AD without compromising improvement in the Haller index (HI). The benefit of the double-bar technique was more obvious among patients with asymmetry with a preoperative AD >5%, resulting in a significant reduction in AD. In this subgroup, a better correction of sternal rotation was observed. Conclusions: The double-bar technique may be a promising option for correcting asymmetry in patients with PE. Simplified AD and SRA radiologic assessments can be used to evaluate improvements in chest wall configuration.

The early and long-term occurrence of symptomatic venous thromboembolism after lung cancer surgery without extended thromboprophylaxis-a single center experience with 435 patients.

Background: The incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), after lung cancer resections varies in the literature, and there is limited evidence regarding the optimal duration of thromboprophylaxis. This study aimed at determining the early and long-term occurrence of thromboembolic complications in patients who received in-hospital thromboprophylaxis and underwent resective surgery for lung cancer. Methods: The study included all patients who underwent lung cancer surgery at Tampere University Hospital between 2004 and 2016. Postoperative thromboprophylaxis was administered for the duration of the hospitalization. Data on subsequent episodes of VTE and survival were obtained from national registries. The results were compared to a demographically matched reference population. Results: The study comprised 435 patients and 4,338 individuals in the reference population. The overall occurrence of VTE in patients and the reference group was 0.3% vs. 0.2% at 90 days (P=0.56), 3.5% vs. 0.7% at 1 year (P<0.001), 9.2% vs. 2.2% at 3 years (P<0.001), and 18.7% and 3.9% at 5 years (P<0.001), respectively. The majority of cases represented PE. The overall mortality at 5 years was 44.4% vs. 11.6% (P<0.001). No associations between patient characteristics and the occurrence of VTE during follow-up were detected. Conclusions: Patients undergoing lung cancer surgery and who receive in-hospital medical thromboprophylaxis do not seem to be in high risk for symptomatic VTE during the early postoperative period. However, during long-term follow-up the occurrence of symptomatic VTE was significant.

Revision after prior failed pectus excavatum repair: higher risks and greater complications than primary surgery.

Background: Revision of a prior failed pectus excavatum (PE) repair is occasionally required. These procedures may be technically more complex and have a greater risk of complications. This study was performed to evaluate the outcomes of adult patients undergoing revision procedures. Methods: A retrospective review of adult patients who underwent revision of a prior PE repair from 2010 to 2023 at Mayo Clinic Arizona was performed. Patients were classified by prior procedure [minimally invasive repair of pectus excavatum (MIRPE), Open/Ravitch, and both] and the type of revision procedure performed [MIRPE, hybrid MIRPE, complex hybrid reconstruction, or complex reconstruction of acquired thoracic dystrophy (ATD)]. Outcomes and complications of these groups were analyzed and compared. Results: In total, 190 revision cases were included (mean age was 33±10 years; 72.6% males, mean Haller Index: 4.4±1.8). For the initial repair procedure, 90 (47.4%) patients had a previous MIRPE, 87 (45.8%) patients a prior open repair, and thirteen (6.8%) patients had both. Furthermore, 30 (15.8%) patients had two or more prior interventions. Patients having had a prior MIRPE were able to be repaired with a revision MIRPE in 82.2% of the cases. Conversely, patients with a prior open repair (including those who had both prior MIRPE and open repairs) were much more likely to require complex reconstructions (85%) as none of the ATD patients in this group had an attempted MIRPE. Operative times were shortest in the MIRPE redo approach and longest in the complex reconstruction of the ATD patients (MIRPE 3.5±1.3 hours, ATD 6.9±1.8 hours; P<0.001). The median length of hospital stay was 5 days [interquartile range (IQR), 3.0 days] with the shortest being the MIRPE approach and the longest occurring in the complex reconstruction of the ATD patients [MIRPE 4 days (IQR, 3.0 days); ATD 7 days (IQR, 4.0 days); P<0.001]. Major and minor complications were more frequent in the ATD complex reconstruction group. Preoperative chronic pain was present in over half of the patients (52.6%). Although resolution was seen in a significant number of patients, significant pain issues persisted in 8.8% of the patients postoperatively. Overall, persistent, long term chronic pain was greatest in the post open/Ravitch patient group (open 13.6% vs. MIRPE 3.6%, P=0.02). Conclusions: Revision of a prior failed PE repair can be technically complex with a high risk of complications, prolonged duration of surgery, and lengthy hospitalization. Chronic pain is prevalent and its failure to completely resolve after surgery is not uncommon. The initial failed repair will influence the type of procedure that can be performed and potentially subsequent complications. Even when some recurrences after previous PE surgeries can be repaired with acceptable results, this study demonstrates the importance of proper primary repair due to these increased risks.