Search Results (109)

Background/Objectives: Mass-forming chronic pancreatitis (MFP) and pancreatic ductal adenocarcinoma (PDAC) can present with overlapping radiological, clinical, and serological features in patients with underlying chronic pancreatitis (CP), making differential diagnosis particularly challenging. Current diagnostic tools, including CA19-9 and endoscopic ultrasound (EUS) imaging, often lack the specificity needed to reliably distinguish between these conditions. The objective of this study was to investigate whether the proteomic profiling of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples could provide molecular-level discrimination between MFP and PDAC in patients with CP. Methods: Thirty CP patients with solid pancreatic lesions were prospectively enrolled: 15 with histologically confirmed PDAC and 15 with MFP. Traditional diagnostic parameters, including CA19-9 levels and EUS characteristics, were recorded but found insufficient for differentiation. EUS-FNA samples were analyzed using label-free mass spectrometry. A total of 928 proteins were identified in PDAC samples and 555 in MFP samples. Differential abundance analysis and pathway enrichment were performed. Results: Overall, 88 proteins showed significant differential abundance between PDAC and MFP samples, of which 26 met stringent statistical thresholds. Among these, Carboxylesterase 2 (CES2), Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1), Lumican (LUM), Transmembrane Protein 205 (TMEM205), and NAD(P)H Quinone Dehydrogenase 1 (NQO1) emerged as key discriminatory proteins. Pathway enrichment analysis revealed distinct biological processes between the groups, including mitochondrial fatty acid β-oxidation, Rho GTPase signaling, and platelet degranulation. Conclusions: Proteomic signatures derived from EUS-FNA samples offer a promising molecular approach to distinguish inflammatory pseudotumoral lesions from malignant pancreatic tumors in CP patients. This minimally invasive strategy could enhance diagnostic accuracy where current methods fall short. Further validation in larger, multicenter cohorts is warranted to confirm these findings and evaluate their clinical applicability. Full article

Cell-free DNA (cfDNA), shed by malignant tumor cells into extracellular fluid, provides valuable epigenetic information indicative of cancer status. Nipple aspirate fluid (NAF), a noninvasive liquid biopsy from at-risk women, contains nucleic acid and protein biomarkers from adjacent cancer cells, showing promise for breast cancer (BrC) detection. However, despite its potential, the application of cfDNA in NAF for BrC screening is still underexplored. Here, we report a proof-of-concept study for using cfDNA bisulfite sequencing (cfBS) to assess tumor DNA methylation signatures from NAF samples. For four healthy individuals and three BrC patients, cfBS achieved greater than 20× sequencing depth with an average coverage of 26.5× on the genome. A total of 7471 differentially methylated regions were identified, with significant hypermethylation in BrC samples compared to healthy controls. Gene set enrichment analysis indicated that the differentially methylated genes (DMGs) were significantly associated with epithelial–mesenchymal transition (EMT). By developing a novel EMT scoring metric, we found that BrC samples had more of a mesenchymal phenotype than samples from healthy individuals. CDH1, WNT2, and TRIM29 were hypermethylated near the promoter region, while COL5A2 was hypermethylated in the coding region. The DNA methylation and EMT changes were validated through The Cancer Genome Atlas Breast Invasive Carcinoma study, which confirmed that DMGs were associated with gene expression change and that our methylation-based EMT score reliably distinguished tumors from healthy controls. Our findings support the utilization of the NAF cfDNA cfBS methylation profile for noninvasive BrC screening and pave the way for enhanced early detection of this disease. Full article

Intravascular aspiration thrombectomy catheters are widely used to treat stroke, pulmonary embolism, and deep venous thrombosis. However, their performance is frequently compromised by clot material becoming lodged within the catheter tip. To address this, we develop a novel ultrasound-enhanced aspiration catheter approach that generates cavitation within the tip to mechanically degrade clots, with a view to facilitate extraction. The design employs hollow cylindrical transducers that produce inwardly propagating cylindrical waves to generate sufficiently high pressures to perform histotripsy. This study investigates the feasibility of self-sensing cavitation detection by analyzing voltage signals across the transducer during treatment. Experiments were conducted for two transmit pulse lengths at varying driving voltages with water or clot in the lumen. Cavitation clouds within the lumen were assessed using 40 MHz ultrasound imaging. Changes in the signal envelope during the pulse body and ringdown phases occurred above the cavitation threshold, the latter being associated with more rapid wave damping in the presence of bubble clouds within the lumen. In the frequency domain, voltage-dependent cavitation signals—subharmonics, ultra-harmonics, and broadband—emerged alongside transmit pulses. This work demonstrates a highly sensitive, sensor-free method for detecting cavitation within the lumen, enabling feedback control to further improve histotripsy-assisted aspiration. Full article

Background: Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty. The debridement, antibiotics, irrigation, and implant retention (DAIR) procedure is commonly employed to treat acute, early-stage infections, but its success is highly variable, influenced by factors such as pathogen virulence and antibiotic susceptibility profiles. This study aimed to evaluate the impact of pathogens responsible for these infections on the outcome of DAIR. Methods: This retrospective, single-center study analyzed the microbiological profiles of 116 patients (66 hips and 50 knees) treated for acute periprosthetic joint infections (PJIs) with DAIR between 2018 and 2022. Acute PJI was defined as a duration of symptom less than three weeks, according to the criteria established by the Tsukayama and Izakovicova classification. Preoperative joint aspirations, intraoperatively collected tissue samples, and sonication of the exchanged mobile parts were analyzed for each case. We differentiated between monomicrobial PJI, polymicrobial PJI (defined as the identification of more than one microorganism from preoperative joint fluid aspiration or intraoperative samples), and difficult-to-treat (DTT) pathogens. Results: In this cohort, the following pathogen profiles were identified: culture-negative cases accounted for 11.1% of infections, while 64.2% were attributed to Gram-positive bacteria, 19.8% to Gram-negative bacteria, and 4.9% to fungal pathogens. Among the identified microorganisms, coagulase-negative staphylococci (CNS) were the most frequently detected, exhibiting a notable oxacillin resistance rate of 52.9% and rifampicin resistance rate of 28.7%. Additionally, no significant difference in revision-free implant survival was found between patients with DTT pathogens and/or polymicrobial PJI and those without such infections. Conclusions: This study highlights that pathogens in prosthetic joint infections (PJIs) do not solely determine outcomes, as patient-specific factors (comorbidities, implant type) may also play a key role. Regional variations in pathogens and antibiotic resistance patterns should guide empirical therapy. For instance, this study found a high reliance on vancomycin due to high oxacillin resistance in CNS, the most frequent causative pathogen. Full article

Against a backdrop of severe and long-standing teacher shortages, in this paper we present analyses of over 60,000 survey responses collected via a cross-sectional cohort study that sampled young people in England over a period of 11 years; at ages 10/11, 12/13, 13/14, 15/16, 17/18, and 21/22. These methods allow us to explore how common teaching aspirations are amongst young people at different ages, and who aspires to become a teacher as a future career. Analysing both free-text and Likert-scale data, we find that many more young people express an interest in becoming a teacher than is reflected in teacher recruitment data, and that teaching aspirations are patterned by gender and ethnicity. Girls and young women, as well as young people who identified as White, were significantly more likely to be open to teaching than their peers. Our findings suggest that teaching is a common back-up, or second-choice career aspiration, and that many individuals who report an earlier interest in teaching do not go on to become teachers. We end the paper with reflections on how these findings might be used to increase and diversify teacher recruitment, as well as recommendations for future research. Full article

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Background: Papillary thyroid microcarcinoma (PTMC), a subtype of papillary thyroid carcinoma ≤ 1 cm in diameter, has shown a marked increase in incidence in recent decades, largely due to the widespread use of neck ultrasonography and fine needle aspiration cytology. Despite its generally indolent course, optimal management of PTMC remains controversial, with treatment strategies ranging from active surveillance to total thyroidectomy. Methods: This retrospective study analyzes five years of experience at a single tertiary care center, including 130 patients diagnosed with PTMC following thyroid surgery between July 2018 and December 2023. Clinical, cytological, and pathological data were collected and analyzed to identify factors influencing surgical decision-making and postoperative outcomes. Patients underwent either total thyroidectomy or hemithyroidectomy, with central and lateral lymph node dissection performed as indicated. Follow-up included clinical and biochemical surveillance for a mean duration of 3 years. Results: Total thyroidectomy was performed in 89.3% of patients, while hemithyroidectomy was limited to 10.7%. Multifocality was observed in 26.1% of cases, with bilateral involvement in 17.7%. Occult lymph node metastases were found in 14.6% (central compartment) and 3.8% (lateral neck). Postoperative radioactive iodine therapy was administered in 23.8% of patients. At final follow-up, 90.7% were disease-free. No significant predictors of recurrence or adverse outcomes were identified, though multifocality and lymph node involvement influenced surgical planning. Conclusions: Our findings support a risk-adapted surgical approach to PTMC, favoring total thyroidectomy in patients with suspicious or multifocal disease to avoid reoperation. While active surveillance and minimally invasive techniques are emerging, total thyroidectomy remains a safe and effective strategy in selected cases. Prospective, multicenter studies are needed to further refine management guidelines for this increasingly common thyroid malignancy. Full article

Background and Objectives: Sesamoiditis is a painful and functionally limiting condition that affects the sesamoid bones of the hallux, frequently seen in athletic populations. Despite its clinical relevance, there are no standardised guidelines for its conservative management. This systematic review aims to evaluate the effectiveness of conservative treatments for sesamoiditis by summarising individual-level data from published studies. Materials and Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ISI/Web of Science, and PEDro (Physiotherapy Evidence Database) up to December 2024 in accordance with PRISMA 2020 guidelines and following a protocol specifically devised for rare or underrepresented medical conditions. Eligible studies included case reports and case series involving patients aged ≥16 years who were conservatively treated for clinically and/or radiologically diagnosed sesamoiditis. Data on patient demographics, diagnosis, type and duration of treatment, pain- (Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS)) and function-related (Foot and Ankle Ability Measure (FAAM) and Foot and Ankle Outcome Score (FAOS)) outcomes, and return to activity were extracted. Study quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Pooled effect sizes were computed where applicable. Results: Out of 2380 initial records, 11 studies comprising 59 patients (29 females) were included. Treatments varied widely, including orthotics, corticosteroid injections, physical therapy, and biologic approaches such as concentrated bone marrow aspirate (CBMA). VAS scores improved in 66% of cases. NRS scores returned to baseline in some patients after initial improvement, revealing recurrence. FAAM and FAOS subscales showed functional improvements, particularly in sports-specific domains. Return to activity varied: in a case series, 45.4% resumed pain-free sports participation, while others remained symptomatic. Conclusions: Conservative treatment options for sesamoiditis showed variable effectiveness with promising outcomes in selected patients. Corticosteroid injections and orthotics appeared beneficial, but high recurrence and limited functional recovery persisted in some cases. Standardised treatment protocols and high-quality prospective studies are needed to improve clinical decision-making and optimise non-surgical management. Full article

The aims of the present study were to analyze the taxonomic profile and to evaluate the functional effects of sheep FF cultivable microbiota on prepubertal lamb oocytes PLOs developmental potential. Ovarian FFs were recovered from slaughtered adult sheep via the aspiration of developing follicles and used for microbiota propagation. Bacterial pellets underwent 16S rRNA gene sequencing and targeted culturomics, whereas cell-free supernatants were used as supplements for the in vitro maturation (IVM) of slaughtered PLOs. For the first time, bacteria presence in adult sheep FF was detected, with the first report of Streptococcus infantarius subsp. infantarius (as a species) and Burkholderia cepacia (as a genus and species) in either animal or human FF. The short- and long-term effects of bacterial metabolites on PLO maturation and embryonic development were demonstrated. As short-term effects, the addition of FF microbiota metabolites did not affect the oocyte nuclear maturation and mitochondria distribution pattern, except in one of the examined supernatants, which reduced all quantitative bioenergetic/oxidative parameters. As long-term effects, one of them reduced the total cleavage rate after in vitro embryo culture (IVC). In conclusion, microbiota/bacteria are present in adult sheep FF and may influence reproductive outcomes in vitro. Future studies may reveal the beneficial in vitro effects using the microbiome from preovulatory follicles. Full article

Background: Interdigitating dendritic cell sarcoma (IDCS) is a very rare haematologic malignant tumour that arises from antigen-presenting cells. While it primarily affects the lymph nodes, extranodal manifestations have been observed, and there is a slight male predominance. Due to its rarity, diagnosing IDCS can be challenging, as illustrated in our case report of a 61-year-old woman. Methods: In this case presentation, the oncological management of a patient suspected of having malignant melanoma metastasis in the neck lymph nodes is discussed. This includes otorhinolaryngological examinations, fine needle aspiration biopsy, PET CT imaging, and histological analysis with immunohistochemistry. Results: The patient’s medical history included the excision of a pigmented lesion from the left ala of her nose, which was diagnosed as malignant melanoma. After surgical treatment, she experienced a tumour-free period of one year; however, during a follow-up ultrasonography three pathological lymph nodes were detected on the left side of her neck. Initially, a nodal metastasis of melanoma was suspected. Yet, fine needle aspiration cytology revealed myofibroblastic tumour invasion, and a re-biopsy showed no signs of malignancy. To further investigate, PET-CT scans were conducted, and a modified radical neck dissection was performed based on the findings. The histological analysis of the lymph nodes revealed an IDCS, a second independent tumour distinct from the initially diagnosed malignant melanoma, originating from the submandibular, upper jugular, and mid-jugular lymph nodes. Conclusions: This case highlights the diagnostic difficulties associated with IDCS. Initially, the clinical suspicion of malignant melanoma was considered, necessitating further examinations and a multidisciplinary approach to reach a final diagnosis and provide the patient with appropriate treatment. Full article

Youth sport participation provides undeniable physical, emotional, and social benefits. However, the current landscape of pediatric athletics has shifted toward early sports specialization (ESS), year-round training, and heightened competitive pressures. This has led to an increased prevalence of overuse-related traumatic injuries in adolescent patients, as well as increased risk of worsening mental health due to burnout, depression, suicide, and general psychological distress. There are numerous innovations and solutions aimed at addressing the increased risk of injury associated with current sporting trends, such as neuromuscular training programs, delayed specialization, promotion of free play, and pediatric specific surgical techniques mindful of future growth, such as those seen for anterior cruciate ligament reconstruction (ACL-R). However, the social factors associated with an injury remain problematic and are not adequately addressed; these include social isolation, depression, anxiety, and academic decline. Sport psychology is a promising solution to address many risk factors associated with poor performance, address the challenges associated with injury, and increase return-to-play in adolescent sports medicine. Integrating sport psychology into pediatric sports medicine offers the ability to directly address the emotional and cognitive demands of injury and recovery. Emphasizing mental health support and redefining success in youth sports—prioritizing enjoyment, personal growth, and long-term health over scholarships and professional aspirations—are key steps in preserving the overall benefits of pediatric sport participation. Yet sport psychology remains often underutilized and has been slow to gain traction, particularly in youth sports. This editorial serves to highlight the current state of mental health advocacy in pediatric sports medicine and how sport psychology can help young athletes manage the mental stress of high-performance athletics and mitigate the detrimental effect of injury and delayed return to sport. Full article

Background/Objective: Early pregnancy loss is often caused by chromosomal abnormalities, necessitating accurate diagnostic tools. While product of conception (POC) chromosomal testing is commonly used, it can be limited by culture failure or an inability to obtain fetal tissue due to spontaneous expulsion. Cell-free fetal DNA (cff DNA) analysis provides a non-invasive alternative; however, its effectiveness in early pregnancy loss, particularly in cases where fetal components are still minimal, has not been fully established. The objective of this study was to evaluate the accuracy of pre- and postoperative cff DNA analysis for detecting fetal aneuploidy by comparing the results to those of POC chromosomal testing. Methods: In this single-center prospective cohort study, 50 women undergoing manual vacuum aspiration for pregnancy loss before 12 weeks of gestation were enrolled (February 2022–December 2024). Cff DNA analysis was performed on maternal blood samples collected pre- and postoperatively. The primary outcome was concordance between the cff DNA and POC results. Sensitivity, specificity, and factors affecting concordance were also assessed. Results: Eight participants were excluded due to unsuccessful POC culture (n = 3), suspected maternal tissue contamination in the POC sample (n = 1), mosaicism (n = 3), or triploidy (n = 1), resulting in 42 evaluable cases. Preoperative cff DNA analysis showed 88.1% concordance with POC (sensitivity 86.4% and specificity 90.0%). Postoperative analysis showed 78.6% concordance (sensitivity 72.7% and specificity 85.0%). Conclusions: The Cff DNA analysis of preoperative and postoperative maternal blood samples showed generally good concordance with conventional POC chromosomal testing in detecting fetal aneuploidy in early pregnancy loss. Full article

This article explores the challenges associated with practicing Buddhist non-attachment as a layperson and whether its application in everyday life represents a puzzle. In Buddhism, practicing non-attachment implies becoming free of desires, as prescribed by Mahāyāna Buddhist philosophy in pursuit of liberation. This raises a critical challenge to form and maintain friendships in this increasingly competitive and demanding environment. To thrive, one must pursue beneficial goals to ensure a meaningful existence. A layperson, therefore, cannot entirely detach from their goals and aspirations without potentially abandoning the Buddhist path to enlightenment. Thus, non-attachment presents a dilemma for laypersons, creating a challenge in reconciling Buddhist philosophy with the realities of worldly existence. Full article

Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment. Full article