Search Results (148)

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Background: Accurate and rapid diagnosis of drug-resistant tuberculosis is essential for initiating appropriate treatment and preventing the transmission of these strains. This study compares phenotypic and genotypic methods of drug susceptibility testing for Mycobacterium tuberculosis (M. tuberculosis). Methods: Resistance to first-line drugs, as well as resistance to second-line drugs (fluoroquinolones and aminoglycosides), was assessed using the Löwenstein–Jensen medium phenotypic method and the GenoType MTBDRplus genotypic method and analyzed. Results: The phenotypic resistance rate was 84.85% for INH (n = 56), 46.97% for RIF (n = 31), 48.48% for STR (n = 32), and 30.30% for EMB (n = 20). Of the MDR-TB isolates (n = 29), 41.37% were resistant to fluoroquinolones (n = 12) and 31.03% were resistant to both fluoroquinolones and injectable aminoglycosides, being classified as XDR-TB (n = 9). In addition, 22.73% of the MDR-TB isolates were resistant to all four first-line drugs (n = 15). The overall concordance between the line probe assay method and phenotypic testing was 94.74% for RIF and 95.16% for INH. Discordances were identified in three cases for RIF and two cases for INH, where isolates were reported as susceptible by GenoType MTBDRplus, but phenotypically resistant. Conclusions: Genotypic testing using GenoType MTBDRplus provides rapid and accurate results, but some cases of phenotypic resistance are not detected by this method. The results highlight the importance of using combined phenotypic and genotypic methods for accurate diagnosis of MDR-TB, as well as the need to integrate genomic sequencing to improve diagnostic accuracy. Full article

Background/Objectives: Prostate cancer (PCa) is diagnosed at an earlier median age, more advanced stage, and has worse clinical outcomes in African American (AA) men compared to European Americans (EA). Methods: To investigate the role of aberrant DNA methylation in tumor-adjacent stroma (TAS), methyl binding domain sequencing (MBD-seq) was performed on AA (n = 17) and EA (n = 15) PCa patients. This was independently confirmed using the long interspersed nuclear element-1 (LINE-1) assay. Pathway analysis was performed on statistically significantly differentially methylated genes for AA and EA TAS. DNA methylation profiles of primary cultured AA and EA carcinoma-associated fibroblasts (CAFs) were compared with AA and EA TAS. AA and EA CAFs were treated with demethylating agent 5-Azacytidine (5-AzaC). Results: AA TAS exhibited higher global DNA methylation than EA TAS (p-value < 0.001). Of the 3268 differentially methylated regions identified (DMRs, p-value < 0.05), 85% (2787 DMRs) showed increased DNA methylation in AA TAS, comprising 1648 genes, of which 1379 were protein-coding genes. Based on DNA methylation levels, two AA subgroups were identified. Notably, AA patients with higher DNA methylation were predominantly those with higher Gleason scores. Pathway analysis linked methylated genes in AA TAS to several key signaling pathways (p-value < 0.05), including immune response (e.g., IL-1, IL-15, IL-7, IL-8, IL-3, and chemokine), Wnt/β-catenin, androgen, PTEN, p53, TGF-β, and circadian clock regulation. A total of 168 concordantly methylated genes were identified, with 109 genes (65%) showing increased methylation in AA CAFs and TAS (p-value < 0.05). Treatment with 5-AzaC significantly reduced DNA methylation of concordant genes in AA CAFs (p-value < 0.001). Conclusions: These findings suggest a distinct stromal methylome in AA, providing a foundation for integrating demethylating agents into standard therapies. This approach targets the tumor microenvironment, potentially addressing PCa disparities in AA men. Full article

Evolving technologies available to clinical laboratories and laboratory-related updates to clinical guidelines both drive the need for clinical laboratories to keep their test menu updated and in line with current technological and clinical developments. Our laboratory has developed a targeted Illumina-based amplicon next-generation sequencing (NGS) assay to interrogate the hsp65 and erm(41) genes of Mycobacterium spp. for the purposes of providing species-level ± subspecies-level identification of Mycobacterium spp. organisms in clinical samples and genotypic predictions for inducible macrolide resistance (in the case of M. abscessus complex members). The developed assay demonstrated 100% sensitivity and specificity for M. tuberculosis and M. abscessus complex cultured organisms, 98% ID overall concordance relative to the available reference identification, and a nearly 60% “rescue” rate for primary samples that could not be identified using our previous method. There was 94.6% concordance between genotypic and phenotypic results for inducible macrolide resistance. The developed assay was successfully implemented in our clinical laboratory and has been accredited for clinical use. Full article

Background: Osteotomies around the knee aim to correct varus or valgus malalignment and improve biomechanics. However, little is known about their effect on knee phenotypes, as defined by the Coronal-Plane-Alignment-of-the-Knee (CPAK) and Hirschmann’s functional classification. This study evaluated pre- and postoperative phenotypes in patients undergoing high-tibial-osteotomy (HTO) or distal-femoral-osteotomy (DFO). Methods: We retrospectively analysed 214 osteotomies around the knee (HTO: 145; DFO: 69) of 188 patients from our institutional registry. Radiographic parameters were measured using a validated artificial intelligence software, with phenotypes classified by CPAK and Hirschmann classification. Preoperative osteotomy planning was compared to postoperative alignment. Regression was used to assess the influence of demographic and radiographic factors. Results: CPAK types changed in 95.3% of cases. Medial opening HTOs most frequently shifted from CPAK type I (73.8%) to VI (42.3%), while medial closing DFOs transitioned from type III (81.5%) to V (24.1%). Concordance between planned and achieved CPAK types was highest for types III, IV, and V. Postoperative angles were generally smaller than planned for joint-line-obliquity (JLO), lateral-distal-femur-angle, and medial-proximal-tibial-angle (p < 0.001). Neutral JLO was restored in only 48.1%. Preoperative phenotypes NEUmLDFA0° (40.1%) and VARmMPTA3° (32.3%) were most common, while postoperative phenotypes included VALmLDFA3° (52.4%) and VALmMPTA3° (37.7%). Age, sex, and BMI significantly influenced alignment outcomes. Conclusions: Postoperative CPAK classifications shifted significantly across all osteotomy types, with minimal retention of preoperative types. Although most procedures achieved correction within the target HKA range, restoration of a neutral JLO was observed in only half of the cases, emphasizing the importance of phenotype-specific planning and highlight potential limitations of CPAK classification. Full article

The development of alternative methods that link cellular and predictive toxicity to high-level toxicity is a key focus of current research within the framework of the 3Rs in animal experimentation. In this context, this study aimed to evaluate the previously developed in vitro approach using the zebrafish liver cell line (ZFL) for assessing bioaccumulation and biotransformation of the compound BDE-47, which is more hydrophobic than phenanthrene, and is the compound used in the previous study. For this purpose, experimentally, the internal concentrations in the cells (C_cell) and the exposure medium of both BDE-47 and its main metabolites were quantified at different exposure times by GC-MS. Additionally, the free bioavailable concentration (C_free) was determined with a solid-phase microextraction (SPME) experiment. With the aim of refine models, C_cell and C_free were also estimated using a predictive chemical distribution model (MBM). Bioconcentration factors (BCFs) were determined by relating all these values, as well as by toxicokinetic fitting and by in vitro–in vivo extrapolation modelling (IVIVE). The results showed a high concordance with the values obtained in vivo. Moreover, the study highlighted the importance of experimentally determining C_free and C_cell, as the predicted values can vary depending on the chemical, thereby influencing the BCF outcome. This variation occurs because models do not account for the absorption and biotransformation kinetics of the compounds. The data presented may contribute to refining predictive models. Full article

Background: We reviewed outcomes of short and long-term chemotherapy with or without breaks in pancreatic ductal adenocarcinoma (PDAC) patients. Methods: PDAC patients receiving ≥3 chemotherapy cycles between 2019 and 2024 at three institutions were included. Progression-free survival after first-line chemotherapy (PFS1), overall survival (OS) and best overall response (BOR) to chemotherapy were assessed using the Wilcoxon test, Kaplan–Meier test, and univariate and multivariate Cox regression models. Results: We screened 237 patients, and 135 patients met the study criteria. Among these patients, 25 had resectable disease, and 110 had unresectable/metastatic disease (13% borderline resectable (BRPC), 20% locally advanced (LAPC), 10% localised developing metastases, 57% de novo metastatic). Ten patients (7%) underwent genetic profiling; KRAS aberrations (N = 4), actionable PLAB2/BRCA2/FGFR2 mutations (N = 3), ATM/BRIP1 alteration (N = 1). Two patients were managed with PARP inhibitors after receiving multiple lines of chemotherapy. Median PFS1 and OS were concordant with the published literature, but select patient groups achieved prolonged survival outcomes. Among the 36 BRPC/LAPC patients, we observed >1-year PFS1 in 9 (25%) patients and >2-year OS in 3 (8%) patients. Among the 63 de novo metastatic patients, we observed >1-year PFS1 and >2-year OS in 6 (10%) patients. Among patients with localised disease, smoking history was a poor prognostic factor with respect to OS (p = 0.03). Improved PFS1 and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥3.66 months, and local treatment after first chemotherapy (p < 0.05 for all). Stereotactic body radiotherapy following first-line chemotherapy was delivered in N = 6 (27%) and N = 1 (7%) of patients with LAPC and BRPC, respectively. Chemotherapy interruption duration, but not number, was associated with PFS1 and OS only in the localised cohort (p < 0.05). In patients with de novo metastatic disease, prevalence of type 2 diabetes was adversely associated with OS (p = 0.03). Improved PFS and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥4.37 months, and BOR to it (only in this cohort) (p < 0.05 for all). A favourable OS was associated with >1 line of chemotherapy (p = 0.003). Conclusion: Despite challenges, extended chemotherapy and multiple treatment lines may improve survival, with localised treatments benefiting select patients. Full article

Quantitative in vitro to in vivo extrapolation (QIVIVE) utilizes in vitro data to predict in vivo toxicity. However, there may be differences between reported nominal concentrations and the biologically effective free concentrations in media or cells. This study evaluated the performance of four in vitro mass balance models for predicting free media or cellular concentrations. Comparing model predictions to experimentally measured values for a wide range of chemicals and test systems, we found that predictions of media concentrations were more accurate than those for cells, and that the Armitage model had slightly better performance overall. Through sensitivity analyses, we found that chemical property-related parameters were most influential for media predictions, while cell-related parameters were also important for cellular predictions. Assessing the impact of these models on QIVIVE accuracy for a small dataset of 15 chemicals with both in vitro and regulatory in vivo points-of-departure, we found that incorporating in vitro and in vivo bioavailability resulted in at best modest improvements to in vitro–in vivo concordance. Based on these results, we conclude that a reasonable first-line approach for incorporating in vitro bioavailability into QIVIVE would be to use the Armitage model to predict media concentrations, while prioritizing accurate chemical property data as input parameters. Full article

The degree of tree curvature exerts a significant influence on the utilization of forestry resources. This study proposes an enhanced quantitative structural modeling (QSM) method, founded upon terrestrial laser scanning (TLS) point cloud data, for the precise extraction of 3D curvature characteristics of tree trunks. The conventional approach operates under the assumption that the tree trunk constitutes an upright rotating body, thereby disregarding the tree trunk’s true curvature morphology. The proposed method is founded on the classical QSM algorithm and introduces two zoom factors that can dynamically adjust the fitting parameters. This improvement leads to enhanced accuracy in the representation of tree trunk curvature and reduced computational complexity. The study utilized 146 sample trees from 13 plots in Jixi, Anhui Province, which were collected and pre-processed by TLS. The study combines point cloud segmentation, manual labeling of actual curvature and dual-factor experiments, and uses quadratic polynomials and simulated annealing algorithms to determine the optimal model factors. The validation results demonstrate that the enhanced method exhibits a greater degree of concordance between the predicted and actual curvature values within the validation set. In the regression equation, the coefficient of the two-factor method for fitting a straight line is 0.95, which is substantially higher than the 0.75 of the one-factor method. Furthermore, the two-factor model has an R² of 0.21, indicating that the two-factor optimization method generates a significantly smaller error compared to the one-factor model (with an R² of 0.12). In addition, this study discusses the possible reasons for the error in the results, as well as the shortcomings and outlook. The experimental results demonstrate the augmented method’s capacity to accurately reconstruct the 3D curvature of tree trunks in most cases. This study provides an efficient and accurate method for conducting fine-grained forest resource measurements and tree bending studies. Full article

The diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging due to their heterogeneous etiologies and overlapping clinical and radiographic patterns. A confident diagnosis often necessitates histopathological sampling, particularly when high-resolution computed tomography and serologic assessments are inconclusive. While surgical lung biopsy (SLB) has long been considered the diagnostic gold standard, its invasiveness, associated morbidity, and limited feasibility in high-risk patients have driven the pursuit of less invasive alternatives. Here, we review the current applications, diagnostic yield, procedural techniques, and complications of several bronchoscopic modalities. Bronchoalveolar lavage (BAL) aids in characterizing inflammatory profiles and differentiating among conditions such as hypersensitivity pneumonitis, sarcoidosis, and eosinophilic pneumonia. Endobronchial biopsies (EBBs) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) are valuable in diagnosing granulomatous diseases with lymphadenopathy. Transbronchial lung biopsy (TBLB) is effective for peribronchial and centrilobular diseases but is limited by small sample size and tissue distortion. Transbronchial lung cryobiopsy (TBC) enables acquisition of larger, well-preserved parenchymal tissue samples from the peripheral lung. Over recent years, studies have demonstrated that TBC, when interpreted within a multidisciplinary discussion (MDD), achieves diagnostic concordance rates with SLB exceeding 75%, and up to 95% in cases where high diagnostic confidence is reached. When performed in experienced centers using standardized protocols, TBC is considered a viable first-line histopathologic tool in the diagnostic evaluation of ILD. Adequate training and standardization of the TBC procedure are needed to ensure low complication rates and a high yield. Full article

The role of blind endometrial sampling, in the era of hysteroscopy-guided biopsy, can be only considered as a screening tool or a first-line approach if a hysteroscopy cannot be performed for whatever reason. Several devices are available, with Perma (a sharp-edged spatula sliding inside a flexible cannula) being one of them. Objectives: The aims of this study were to compare the concordance of blind to visual endometrial sampling, and the influence of operators’ experience on the results. Materials and Methods: Women undergoing hysteroscopy were invited to undergo a Perma biopsy as well. If accepted, a Perma sampling was performed before the hysteroscopy and only if there was no cervical dilatation (as an office setting). The operator was randomly chosen between expert (two staff members) and non-expert (two residents) operators. All cases were collected at the AOU Maggiore della Carità, Novara, Italy. Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD. The association between categorical variables was evaluated using Fisher’s exact test. Clinical outcomes were analyzed, and the results were first compared within the same patient and subsequent within the doctors’ group (inter- and intra-variation) in terms of Cohen’s Kappa. Results: 82 women performed both hysteroscopy and Perma. A sensitivity of 81.8% and specificity of 100% was found when Perma was compared to hysteroscopy (the gold standard). The comparison between valid vs. invalid samples in terms of sufficient evaluable tissue was not significant (p = 0.583). There are no statistical associations with body mass index, parity, or previous intrauterine surgery related to the outcomes of hysteroscopy and Perma. Cohen’s Kappa between non-experts was 0.43 (moderate), between experts was 0.30 (fair), with the highest concordance being between one non- and one expert (0.68 = substantial). Perma represents a pragmatic diagnostic tool, which could also be used in outpatient. Full article

Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in the infected erythrocyte. We had previously proposed an extracellular vesicle (EV) export model of ART resistance in P. falciparum. This model predicts that EV abundance will be altered by ART exposure and that the peptide cargo of EVs from the ART-exposed condition will be enriched with aggregation-prone peptides. We tested the predictions of the EV export hypothesis in this study using in vitro culture assays of an ART-resistant transgenic line engineered on a 3D7 background (R561H) and a 3D7 knock-out line (PfVps60KO) with deficient EV production phenotype. EV enrichment was obtained from in vitro parasite culture supernatants via a series of ultracentrifugation and filtration steps, followed by size exclusion chromatography. A quality check on EVs was performed using dynamic light scattering. Liquid chromatography with tandem mass spectrometry was used to determine the proteome cargo from extracted EVs, and parasite peptides were queried for aggregation-prone tendency using open-access software. We report that dihydroartemisinin (DHA) exposure was positively correlated with EV abundance (coefficient estimate = 1038.58, confidence interval of 194.86–1882.30, and p-value = 0.018) and suggests that EV biogenesis is part of the parasite’s response to DHA/ART. Furthermore, our findings suggest the expression of a non-constitutive DHA-induced alternate EV biogenesis pathway as the PfVps60KO was observed to produce the highest number of EVs under DHA exposure. Finally, we show that EVs from both ART-susceptible and resistant parasites under DHA exposure carry a cargo of Chorein N-terminal domain-containing protein (PF3D7_1021700) with a high aggregation-prone index (prion-like domain [PrLD] score = 26.5) out of nine identified parasite peptides. The former of these findings is in concordance with the EV export hypothesis, which posits that the removal of DHA/ART-induced aggregated and/or misfolded peptides is critical to the parasite’s survival under DHA/ART exposure. This observation further implicates EVs in the development of the ART-resistant phenotype. However, the finding of one aggregation-prone peptide out of the nine parasite proteins in the EV cargo does not sufficiently support the EV export hypothesis. Future replicates of this study and further interrogations of the EV export hypothesis are needed. Full article

Objectives: Hamstring strain injuries are common in elite athletes and affect return-to-sport timelines. Although magnetic resonance imaging (MRI) is the gold-standard method for assessing injury severity, ultrasonography (US) is a more accessible and cost-effective alternative. This study aimed to evaluate the agreement between US and MRI in the diagnosis of hamstring injuries and their prognostic value in predicting recovery. Methods: This retrospective study included elite athletes who sustained acute first-time hamstring strains and underwent both MRI and US within five days after injury. The injuries were classified according to location (muscle belly, musculotendinous junction, or tendon) and severity (modified Peetron’s classification). The agreement between the imaging findings and return-to-sports timelines was analyzed. Results: US demonstrated a 70% agreement with MRI in identifying injury locations, showing the highest concordance for muscle belly injuries (90%), followed by musculotendinous junction (80%) injuries, but a lower accuracy for tendon injuries (60%). Recovery times differed significantly by location and severity (p < 0.01), with tendon grade 3 injuries requiring the longest recovery (383 days) and muscle belly injuries requiring the shortest recovery (16 days). Musculotendinous junction grade 2, tendon grade 1, and tendon grade 2 injuries had similar recovery durations (57–65 days). Conclusions: High-resolution US is a reliable diagnostic tool for muscle belly and musculotendinous junction injuries. However, MRI remains essential for high-grade tendon injuries. US serves as the first-line imaging modality, with MRI reserved for cases that require a detailed prognostic assessment. These findings provide guidance for optimizing imaging strategies for hamstring injury management. Full article

The cognitive ability of the elderly significantly influences evacuation performance in urgent situations. Despite its importance, many fire evacuation studies overlook the impact of cognitive ability on elderly evacuation performance. To address this gap, this study employs multicriteria decision-making to identify nudging factors that enhance the cognitive abilities of the elderly during fire evacuations in long-term care facilities. Based on a literature review, key nudging factors include guidance lights, guide lines, handrails, and guidance equipment, with sub-criteria such as location, color, size, and intervals. Experts from academic and practical fields analyzed the nudging factors, followed by a hybrid analytic hierarchy process (AHP–TOPSIS) analysis. The findings emphasize the necessity of providing auditory information through guidance equipment (e.g., voice evacuation system) in high-level scenarios (practice experts AHP: 0.31) and visual information through the continuous installation of guide lines in strategic locations (academic experts AHP: 0.35) to facilitate efficient evacuation. As a result, this study confirms both the differing and concordant opinions among expert groups while recognizing the absolute necessity of elderly evacuation research and considering the unique challenges that prevent actual evacuation experiments with elderly individuals. By synthesizing these perspectives, the study derives the weights and ranks of nudging factors based on urgent-level circumstances, thereby conducting a quantitative assessment of factors that enhance cognitive ability during elderly evacuation. The findings of this study can serve as a basis for future evacuation policy formulation for elderly-related facilities and, as a derivative effect, contribute to ensuring the life safety of elderly individuals within the local community. Full article

Background: Ovarian cancers harboring inactivating mutations in BRCA1 or BRCA2 demonstrate increased sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPis). BRCA1 promoter methylation could serve as a more precise biomarker for therapy response, as it reflects a dynamic mechanism, compared with genomic scarring, which remains persistent and lacks real-time prediction of sensitivity after prior lines of treatment. Additionally, the BRCA1 promoter methylation may provide a more precise biomarker for identifying homologous recombination deficiency compared to genomic scars. In this study, we describe the validation of a pyrosequencing method to assess BRCA1 promoter methylation status. Methods: Tumor DNA from high-grade serous ovarian carcinoma was tested targeting 11 CpG sites adjacent to the BRCA1 transcription start site. All cases had concordant results compared with TCGA methylation data or real-time PCR results. To determine the sensitivity of this assay, we performed a dilution series experiment using seven mixtures of methylated DNA and unmethylated genomic DNA (100%, 50%, 25%, 12.5%, 6.25%, 3.125%, and 1.56%). Results: We observed a high degree of correlation (R² = 0.9945) between predicted and observed results. Intra- and inter-run reproducibility was established by performing six cases in triplicate in the same run and in three different runs. Conclusions: By applying 10% as the cutoff for detection of methylation, the PyroMark Q24 pyrosequencing assay demonstrated 100% concordance across all the ovarian cancer cases included in this validation. This assay has been approved by the New York State Department of Health as a laboratory-specific assay for clinical use. Full article