Search Results (4,372)

Familial hypercholesterolemia (FH) is a common genetic disorder with a fairly constant worldwide prevalence of 1 case per 311 individuals worldwide. It is characterized by severe hypercholesterolemia from birth, early atherosclerosis and death from cardiovascular disease at a young age. Diagnosis and treatment from childhood are essential to reduce cardiovascular mortality. Many countries have developed a strategy of implementing pediatric screening, which has led to an increase in diagnoses. This paper evaluates the screening strategies implemented in different countries worldwide. First, we examined which schemes were preferred in various national contexts in Europe. Next, we evaluated the screening methods used in the US, Canada, Australia and Japan. Finally, we researched the screening strategies proposed in some low-resource countries, discovering the difficulties and limitations they face. We have highlighted a wide range of realities, from small-scale pilot studies to cutting-edge proposals. We have also emphasized that, while the topic is certainly of interest, it is burdened by multiple difficulties and unresolved questions. Full article

Background/Objectives: Appendiceal cancer (AC) is a rare and understudied malignancy with limited genomic data available to guide clinical interventions. Historically treated as a subtype of colorectal cancer, AC is now recognized as a distinct disease with unique histologic subtypes and molecular features. This review aims to consolidate current genomic data across AC subtypes and explore the clinical relevance of recurrent mutations. Methods: A systematic literature review was performed in accordance with general Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. Using search engines such as PubMed and Web of Science, we selected studies based on relevance to AC genomics using search terms such as “appendix cancer”, “appendiceal cancer”, “pseudomyxoma peritonei”, “sequencing”, “mutation”, and “genotype”. Results: AC comprises five major histologic subtypes—appendiceal neuroendocrine neoplasms (ANENs), mucinous appendiceal neoplasms (MANs), goblet cell adenocarcinomas (GCAs), colonic-type adenocarcinomas (CTAs) and signet ring cell adenocarcinomas (SRCs)—each with unique clinical behaviors and mutational profiles. Low-grade tumors, such as ANENs and MANs, frequently harbor KRAS and GNAS mutations, while high-grade subtypes, such as CTAs and SRCs, are enriched for TP53, APC, and SMAD gene alterations. GCA tumors exhibit a distinct mutational spectrum involving chromatin remodeling genes such as ARID1A and KMT2D. Compared to colorectal cancer, AC demonstrates lower frequencies of APC and TP53 mutations and a higher prevalence of GNAS mutations, consistent with a pathological divergence from CRC. Conclusions: The genomic heterogeneity of AC is commensurate with its histological complexity and has important implications for diagnosis, prognosis and treatment. While certain actionable mutations are present in a subset of tumors, large-scale genomic characterization efforts and development of subtype-specific models will be essential for advancing precision medicine in AC. Full article

Objective: Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. Although immunotherapy has transformed MCC management, published data remain limited. This comprehensive review evaluates current evidence on immune checkpoint inhibitors (ICIs) in MCC, in relation to other treatment modalities such as surgery and radiotherapy. Methods: Peer-reviewed articles published between January 2000 and August 2025 were searched manually in four databases: Scopus, ScienceDirect, PubMed and MEDLINE, using the keywords “Merkel cell carcinoma” AND “immunotherapy” AND “immune checkpoint inhibitors”. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology was employed. Results: ICIs can be given in different settings: (A) Neoadjuvant: The CheckMate 358 trial reported a 54.5% response rate among 33 radiologically evaluable patients treated with nivolumab, each showing over 30% tumor reduction. (B) Adjuvant: (1) The ADMEC-O phase II trial demonstrated improved disease-free survival with adjuvant nivolumab. (2) The ADAM phase III trial evaluates adjuvant avelumab in node-positive patients post-surgery/radiation, with common side effects including nausea, fatigue, and itching. (3) STAMP, a phase III trial, investigates pembrolizumab in stage I–III MCC. Both ADAM and STAMP have completed accrual and results are pending. (C) Primary therapy: KEYNOTE-017 and JAVELIN trials reported a 60% overall response rate and ~40% 3-year progression-free survival with first-line pembrolizumab or avelumab. Both agents also show promise as salvage therapies. Conclusions: ICIs demonstrate encouraging outcomes in MCC across various treatment stages. Continued research is essential to optimize treatment timing and integrate multimodal therapies. Full article

Background/Objectives: Ustekinumab (UST) and upadacitinib (UPA) are molecules that have been used in patients with ulcerative colitis (UC) since 2019 and 2022, respectively. Both agents are generally preferred for biologically experienced UC patients. However, the number of head-to-head studies comparing the efficacy and adverse events of UST and UPA in this patient group is limited. Methods: This was a retrospective cohort study evaluating the efficacy and safety of UST (n = 57) and UPA (n = 32) in biologically experienced UC patients during the induction and 24-week maintenance treatment periods. Most patients in both groups had received prior anti-TNF treatment (98.2% and 96.9%, respectively). Clinical response and remission rates were determined based on the partial Mayo score (PMS). Additionally, patients’ pre-treatment laboratory parameters were compared with their results at week 24. Results: During the induction phase, clinical response and remission were achieved in 84.2% and 43.9% of the UST group and 93.8% and 50% of the UPA group, respectively (OR [95% CI] = 2.81 [0.57–6.87] and 1.28 [0.54–3.05]). At week 24, the clinical response and remission rates in the UST and UPA groups were similar (77.1% vs. 80% and 58.3% vs. 63.3%, respectively). No statistically significant difference was found between the groups (p > 0.05). Both UST and UPA provided a marked reduction in fecal calprotectin and CRP levels. Regarding safety, UPA treatment led to increased total, LDL, and HDL cholesterol levels, whereas UST did not. In both groups, glucose; HbA1c; and thyroid, renal, and liver functions remained stable. No serious adverse events were observed in either group. At week 24, treatment continuation rates were 68.4% (n = 39) for UST and 78.2% (n = 25) for UPA (OR = 0.61 [0.22–1.66]). Conclusions: In biologically experienced ulcerative colitis, both UST and UPA are effective and safe treatment options. This study did not statistically demonstrate the superiority of UPA over UST. Given the preliminary nature and limited patient numbers of this investigation, our findings require confirmation through future multicenter, large-scale, and long-term prospective studies. Full article

Background and Clinical Significance: The occurrence of acute myeloid leukemia (AML) in pregnancy represents a diagnostic and management challenge in the attempt to balance and achieve both maternal and fetal wellbeing. Pregnancy-specific manifestations mimic the initial symptoms of leukemia and may lead to a delay in diagnosis, especially during the first trimester of pregnancy. Decision-making strategies involve the patient and couples counseling with a multidisciplinary team of hematologists, obstetricians, neonatologists and psychologists. Maternal outcome depends on the disease subtype, progression and response to medication. Fetal outcome depends on other potential pregnancy complications, possible teratogenicity, gestational age at delivery and sometimes iatrogenic prematurity. Case Presentation: We present the case of a 38-year-old multiparous patient with a late first trimester, with an AML diagnosis presenting with hyperemesis gravidarum-like symptoms. Genetic testing revealed the presence of an Fms-like tyrosine kinase 3-internal tandem duplication mutation (FLT3-ITD). Following that, a repeatedly refused termination of pregnancy and rapid disease progression with azacitidine therapy was initiated. Elective cesarean delivery was performed at 34 weeks of gestation due to progressive leukocytosis, which persisted postpartum, requiring the use of first-, second-, and eventually third-line chemotherapy. Fetal outcome was favorable at 3 months postpartum. Conclusions: Cases of AML in pregnancy require a tailored approach according to guidelines, but also patient/couple preferences, while the choice of chemotherapy is limited considering its potential teratogenic effects. This is a case with a misleading first presentation and a challenging therapeutic choice due to its genetic subtype and maternal treatment postponement. Full article

Salix suchowensis is an ideal model organism for investigating nitrogen (N) transport mechanisms due to its low N-input requirements. Accurate quantification of gene expression is essential for elucidating these processes, with quantitative real-time PCR (RT-qPCR) being the preferred method. However, the identification of stable reference genes for normalization in Salix suchowensis under varying N conditions remains unresolved. In this study, thirteen commonly employed candidate reference genes were evaluated across root, stem, and leaf tissues, under four N treatments (NH₄NO₃, NH₄⁺, NO₃⁻, and N deficiency). Five genes (UBQ1, UBQ3, 18S, H2A2, and H2B2) were excluded due to poor amplification efficiency or irregular melting curves. The remaining eight genes were further assessed for expression stability using the geNorm, NormFinder, and BestKeeper algorithms. Integrated ranking via RefFinder identified EF1α, EFβ, and αTUB as the most stable reference genes. GeNorm analysis suggested that two reference genes were sufficient for reliable normalization. Validation using the N-responsive gene SsAMT1 and SsNRT2 confirmed the stability of EF1α, EFβ, and αTUB as suitable reference genes. Based on comprehensive stability assessments and experimental validation, we recommended EF1α + αTUB as optimal reference gene pairs for RT-qPCR normalization under varying N conditions. Furthermore, the consistent expression of EF1α and αTUB across nine willow genotypes highlighted their broader applicability within Salix species. This study provides valuable methodological guidance for advancing molecular research on N transport in woody perennial plants. Full article

Background/Objectives: In early-stage oncology clinical trials, the use of endpoints beyond overall survival (OS), including recurrence-free survival (RFS) or event-free survival (EFS), is becoming more common. To understand whether these outcomes are important to patients, this study explored the perceived value of non-OS endpoints among Canadians treated for early-stage cancer or with curative intent. Methods: Canadians treated for early-stage breast, lung, or gastrointestinal cancer participated in semi-structured interviews. Participants provided perspectives on OS, RFS, disease-free survival (DFS), EFS, and pathological complete response (pCR) endpoints. Reflexive thematic analysis was used to explore patterns in responses and alignment of trial endpoints with patient treatment goals, priorities and preferences. Results: The mean age of the 33 participants was 54.8 years, and 21 were female; 28 reported prior surgery, and 21 were also treated with chemotherapy (11 specified as neo-adjuvant; 9 specified adjuvant). All participants valued OS, and most viewed non-OS endpoints as reflective of their treatment priorities, including maintaining health-related quality of life and getting back to ‘normal’. They also valued timely and equitable treatment access and equated having access to new treatments with better options. While participants considered efficacy data from clinical trials provided by non-OS endpoints sufficient to want access to new treatments, the relative importance of being disease- or recurrence-free versus maximizing length of life differed according to recurrence status, prognosis, cancer type and life stage. Conclusions: These findings support the relevance and importance of non-OS endpoints to Canadians with early-stage cancer and highlight participants’ desire for rapid approval of treatments with demonstrated improvements in non-OS endpoints. Full article

Background/Objectives: Patellar instability is a common orthopedic condition affecting pediatric and adolescent populations, particularly during periods of rapid growth and increased sports participation. Recurrent patellar dislocation in skeletally immature patients is frequently associated with underlying anatomical risk factors such as patella alta, trochlear dysplasia, or increased tibial tubercle–trochlear groove distance. Methods: This narrative review summarizes the current evidence on the epidemiology, diagnostic approach, and arthroscopic management of patellar instability in skeletally immature patients. Results: Arthroscopy has become an essential tool in both the diagnosis and treatment of patellar instability, allowing for minimally invasive assessment of patellofemoral alignment, chondral pathology, and ligament integrity. It also enables precise surgical interventions such as physeal-sparing medial patellofemoral ligament reconstruction, which remains the preferred stabilization technique for patients with open physes due to its safety and efficacy. Emerging innovations, including robotic-assisted tunnel placement, bioengineered scaffolds for cartilage repair, and three-dimensional modeling for surgical planning, have the potential to improve outcomes and arthroscopic surgical precision in this population. Despite these advances, major challenges such as a lack of pediatric-specific outcome measures, variability in surgical indications and rehabilitation protocols, and limited long-term follow-up data remain. Conclusions: Optimizing outcomes in pediatric and adolescent patients with patellar instability requires individualized growth-aware strategies and multidisciplinary collaborations. By integrating technological innovation with patient-centered care, clinicians can continue to refine the arthroscopic management of patellofemoral instability in young patients. Full article

Aortic stenosis (AS) is a common degenerative valvular disease in elderly patients, causing obstruction of left ventricular outflow and presenting with symptoms such as angina, syncope, and heart failure. Although surgical aortic valve replacement (SAVR) remains the gold standard, its high perioperative risk in frail patients has led to the adoption of transcatheter aortic valve implantation (TAVI) as a less invasive and effective alternative. The transfemoral (TF) access route is generally preferred, but severe peripheral arterial disease may limit its feasibility. We report the case of a 71-year-old woman with critical AS complicated by multiple comorbidities, including extensive vascular calcifications, a porcelain aorta, and significant subrenal abdominal aortic stenosis. Multimodal imaging, including computed tomography, was essential for procedural planning, revealing complex iliofemoral anatomy unsuitable for conventional device passage without intervention. Intravascular lithotripsy (IVL) was used to disrupt calcific plaques and facilitate safe vascular access. The TAVI procedure was successfully performed under local anesthesia via TF access using a 65 cm GORE® DRYSEAL Flex Introducer Sheath (W. L. Gore & Associates, Flagstaff, AZ, USA) (18-Fr). After balloon valvuloplasty performed over a SAFARI2™ Pre-Shaped TAVI Guidewire, Extra Small (Boston Scientific, Marlborough, MA, USA) Curve in the left ventricle, a self-expanding Medtronic Evolut™ FX 26 (Medtronic, Minneapolis, MN, USA)mm transcatheter valve was implanted. Postoperative imaging confirmed optimal valve function and vascular integrity without complications. This case highlights the role of IVL as an innovative adjunctive technique enabling TF-TAVI in patients with challenging vascular anatomy, thereby expanding treatment options for high-risk individuals with severe AS. Full article

Pre-fermentative treatments are essential in winemaking, as they significantly influence the quality and stability of white wines in particular. The synthesis of many compounds obtained from yeast, such as higher alcohols and esters, is influenced by the type and concentration of aromatic precursors present in the must, especially amino acids. Clarification has a positive effect on wine quality, mainly by improving organoleptic properties, with flavour being the most affected. In this study, the influences of different static settling times, different pressures during must extraction and the addition of different bentonite concentrations to the must on the aroma of wines from the autochthonous grape varieties Krstač and Žižak were investigated. The identification of aromatic compounds in the wine was performed using GC/FID-MS analysis. Wine subjected to the longest static settling time (30 h) showed the highest concentration of esters. Krstač wine, which underwent a 30 h of settling, was characterised by an increased concentration of esters, such as isoamyl acetate, ethyl decanoate and ethyl hexanoate, while Žižak wine was characterised by the presence of 2-phenylethyl acetate and isoamyl acetate. The total fatty acid content in Krstač wine obtained by pressing was higher (14.90 mg/L) than in wine produced from free-run juice (8.04 mg/L). Full article

Background/Objectives: Trigger finger is a common cause of hand pain and functional limitation. Although open A1 pulley release remains the standard surgical treatment, ultrasound-guided percutaneous needle release (UGPR) has emerged as a minimally invasive alternative. This study aimed to compare the clinical effectiveness and safety of UGPR with open surgery. Methods: In this prospective, randomized controlled trial, 146 patients with Green stage 2–4 trigger finger were randomly assigned to UGPR (n = 75) or open release (n = 71). Pain (VAS), functional status (QuickDASH), and symptom severity (Nirschl Phase Rating) were assessed preoperatively and at postoperative day 3, 1, 6, and 12 months. Grip strength was measured with a digital pinchmeter, and ultrasonographic evaluation of A1 pulley and flexor tendon thickness was performed preoperatively and at 12 months. Subgroup analyses were conducted to address the imbalance in thumb distribution. Results: Both groups showed significant postoperative improvements in VAS, QuickDASH, and Nirschl scores (p < 0.05 for intragroup comparisons), with no significant differences between groups at 12 months (p > 0.05). At the one-year follow-up, grip strength was significantly greater in the UGPR group (p = 0.008). Ultrasonographic evaluation revealed greater MCP tendon thickness in UGPR, without clinical impact. Subgroup analyses confirmed comparable functional outcomes in thumb-only and non-thumb cases. Four revisions occurred in the UGPR group (incomplete release, recurrent tenosynovitis, flexor tendon rupture, and neurovascular injury), while none were observed in the open group. Conclusions: UGPR and open release provide comparable long-term outcomes in the treatment of trigger finger. UGPR offers the advantages of being minimally invasive and preserving grip strength, although it carries a small risk of incomplete release and procedure-related complications. Patient preference, surgeon expertise, and digit type should guide treatment selection. Full article

Objectives: The study assessed knowledge, attitude, and practices of dentists towards treating pregnant patients. Methods: It was based on a cross-sectional, electronically administered survey of a convenience sample of Russian dentists conducted between March and April 2025. Our questionnaire was developed based on international guidelines and previously published surveys and validated through expert review and pilot testing. It contains four sections: Demographics, Knowledge, Attitude, and Practice. The overall knowledge and attitude scores were calculated and compared across subgroups based on gender, specialty, and experience using the Kruskal–Wallis and Dunn’s tests. Spearman’s coefficient was calculated to reveal pair-wise correlations between knowledge, attitude, and age of the participants. Results: Overall, 403 dentists completed the questionnaire. The majority of the participants (53%) demonstrated fair knowledge about providing dental care throughout pregnancy. Female dentists had a significantly higher median knowledge score compared with that of males; orthodontists and prosthetic dentists showed lower knowledge scores than other specialists. All participants demonstrated a positive attitude toward treating pregnant patients; however, a considerable number of dentists agreed that they do not feel comfortable treating pregnant women and prefer not to do that. A large majority of dental practitioners (83%) indicated that they had treated pregnant women. Liability concerns (42%) and a lack of knowledge (24%) were reported as the main barriers for providing dental care to pregnant patients. Conclusions: It can be concluded that insufficient knowledge influenced by gender and specialty is one of the key barriers to the dental treatment of pregnant women, despite generally positive attitudes of the practitioners. Full article

US food regulatory agencies have adopted a preference for researchers and testing labs to use ‘acid-adapted challenge cultures’ when performing inoculated validation studies of food processes that involve acidic treatments to accustom the cultures to acidic pH so that they will not be easily affected during processing. We evaluated acid adaptation in regard to the processing of South African style air-dried beef, notably biltong and droëwors, using a mixture of five serovars of Salmonella as well as a unique serovar isolated from dried beef (Salmonella Typhimurium 1,4,[5],12:i:-). Acid adaptation was obtained by growing cultures in tryptic soy (TS) broth containing 1% glucose. Non-adapted cultures were obtained by growth in TS broth without glucose or in TS broth with 1% glucose but buffered with 0.2 M phosphate buffer. Processes included biltong (dried solid beef) and droëwors (ground, sausage-style). Each trial was performed twice and triplicate samples were examined at each sampling point (i.e., n = 6). Statistical analysis was applied using analysis of variance (ANOVA) or one-way repeated measures (RM-ANOVA) and the Holm–Sidak test for pairwise multiple comparisons to determine significant differences (p < 0.05). We observed that in all processes examined (eight trials), treatments using acid-adapted cultures were more sensitive to the biltong and droëwors processes, giving greater reductions (5.3-log reduction) than when non-adapted cultures were used (3.8-log reduction). Acid adaptation leads to stressed conditions in Salmonella resulting in sensitization to the multiple hurdles found in biltong and droëwors processing (acid/vinegar, salt, desiccation). Based on our data, the use of non-adapted Salmonella cultures to achieve desired challenge culture process lethality could result in more robust processing conditions and a greater level of safety in these products as intended by US regulatory guidance. Full article

Cranberry (Vaccinium macrocarpon Ait.) is an herbaceous, evergreen, dwarf shrub of the genus Vaccinium in the family Ericaceae, often used as a functional food. Cranberries are primarily distributed in the northern United States—including Massachusetts, Wisconsin, and Maine—as well as in Quebec, Canada; the state of Columbia; Chile in South America; and northeastern Europe. They are also found in China’s Greater Khingan Range and Fuyuan City, Jiamusi, Heilongjiang Province. The plants thrive in cool environments and exhibit considerable adaptability to soil conditions, preferring acidic soils. Cranberries are rich in a variety of biologically active components, such as polyphenols (proanthocyanidins, chlorogenic acid, flavonols, anthocyanins, caffeic acid, etc.), triterpenoids, and other nutrients. Studies have shown that the chemical components extracted from cranberry fruit have pharmacological effects such as antioxidant, anti-inflammatory, anti-cancer, and urinary tract infection prevention and treatment, and are commonly used clinically in the treatment of cardiovascular diseases, the prevention of urinary tract infections, blood pressure lowering, and the fight against Helicobacter pylori, among other clinical diseases. Cranberries also play a huge role in daily nutrition, and they are named for their richness in a variety of mineral elements, trace elements and vitamins. This work uses information from Pubmed, Web of Science, Scopus, CNKI (China National Knowledge Infrastructure), and related papers. In this paper, a comprehensive review of the phytochemical composition, pharmacological mechanism of action, clinical application value and nutritional significance of cranberry was conducted in recent years to provide references for the further extraction of chemical components in cranberry and rational clinical application, which can help to guide people to rationalize their diets and promote the formation of healthy diets. Full article

Objective: This study aimed to compare the effectiveness and safety of vonoprazan–amoxicillin (VA) dual therapy with modified bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, and clarithromycin; EBAC) in treatment-naïve patients infected with Helicobacter pylori (H. pylori). Methods: In this single-center, open-label, randomized controlled trial conducted from July to December 2024, a total of 504 H. pylori-positive patients were randomly allocated to receive either VA (vonoprazan 20 mg and amoxicillin 1000 mg, twice daily for 14 days) or EBAC (esomeprazole 20 mg bid, bismuth potassium citrate 220 mg bid, amoxicillin 1000 mg bid, clarithromycin 500 mg bid, twice daily for 14 days). The primary endpoint was the H. pylori eradication rate, and the secondary endpoint was safety. Results: In the intention-to-treat (ITT) analysis, the eradication rates were 79.4% (200/252) in the VA group and 85.7% (216/252) in the EBAC group (p = 0.060). Per-protocol (PP) analysis showed comparable eradication rates between the two groups (92.1% [197/214] vs. 93.0% [213/229], p = 0.712), confirming the non-inferiority of VA compared to EBAC. The incidence of adverse events was significantly fewer in the VA group (27.2% vs. 42.7%, p < 0.001). Logistic regression identified medication adherence (≥80%) as the only independent predictor of successful eradication (OR 17.557, p < 0.001). Conclusions: VA dual therapy achieved comparable H. pylori eradication rates to EBAC, while offering better safety and a more convenient regimen, supporting it as a preferred first-line treatment for H. pylori infection. Full article