Journal of Personalized Medicine最新文献

Background: Comprehensive genomic profiling (CGP) identifies genetic alterations and patterns that are crucial for therapy selection and precise treatment development. In Colombia, limited access to CGP tests underscores the necessity of documenting the prevalence of treatable genetic alterations. This study aimed to describe the somatic genetic profile of specific cancer types in Colombian patients and assess its impact on treatment selection.

Methods: A retrospective cohort study was conducted at Clínica Colsanitas S.A. from March 2023 to June 2024. Sequencing was performed on the NextSeq2000 platform with the TruSight Oncology 500 (TSO500) assay, which simultaneously evaluates 523 genes for DNA analysis and 55 for RNA; additionally, analyses were performed with the SOPHiA DDM software. The tumor mutational burden (TMB), microsatellite instability (MSI), and programmed cell death ligand 1 (PDL1) were assessed.

Results: Among 111 patients, 103 were evaluated, with gastrointestinal (27.93%), respiratory (13.51%), and central nervous system cancers (10.81%) being the most prevalent. TP53 (37%), KMT2C (28%), and KRAS (21%) were frequent mutations. Actionable findings were detected in 76.7% of cases, notably in digestive (20 patients) and lung cancers (8 patients). MSI was stable at 82.52% and high at 2.91%, whilst TMB was predominantly low (91.26%).

Conclusions: The test has facilitated access to targeted therapies, improving clinical outcomes in Colombian patients. This profiling test is expected to increase opportunities for personalized medicine in Colombia.

Introduction: Reconstructing long bone defects in the upper limbs, particularly the radius and ulna, poses significant challenges. These defects, resulting from trauma, tumors, infections, or congenital anomalies, require precise surgical intervention for functional restoration. Traditional non-vascularized autogenous bone grafts have limitations, such as resorption and limited biological activity. To address these challenges, free vascularized fibular grafts (FVFGs) have been developed, offering enhanced recovery by supplying nutrients and structural support, particularly in large defects or compromised vascularity.

Materials and methods: This retrospective study reviewed patients with significant forearm skeletal defects treated with FVFGs at our institution from January 2008 to January 2019. Included were patients with radius or ulna defects exceeding 8 cm due to trauma, tumor excision, or non-union fractures. Data on demographics, clinical details, surgical techniques, and outcomes-including graft union time, complications, range of motion, and the disabilities of the arm, shoulder and hand (DASH) scores-were analyzed.

Results: Eight patients, with a mean age of 27.6 years and an average defect length of 9.8 cm, were included. All patients achieved graft union within an average of 4 months, with no tumor recurrence or significant complications. Functional outcomes showed mean forearm pronation of 56.9 degrees, supination of 52.5 degrees, and a mean DASH score of 17.7.

Conclusions: FVFG is a safe and effective technique for managing complex forearm bone defects, providing high union rates and good functional outcomes. It should be considered a primary option for large forearm skeletal defects.

Knee osteoarthritis (KOA) is a musculoskeletal disorder characterized by articular cartilage degeneration and chronic inflammation, affecting one in five people over 40 years old. The purpose of this study was to provide an overview of traditional and novel minimally invasive treatment options and role of artificial intelligence (AI) to streamline the diagnostic process of KOA. This literature review provides insights into the mechanisms of action, efficacy, complications, technical approaches, and recommendations to intra-articular injections (corticosteroids, hyaluronic acid, and plate rich plasma), genicular artery embolization (GAE), and genicular nerve ablation (GNA). Overall, there is mixed evidence to support the efficacy of the intra-articular injections that were covered in this study with varying degrees of supported recommendations through formal medical societies. While GAE and GNA are more novel therapeutic options, preliminary evidence supports their efficacy as a potential minimally invasive therapy for patients with moderate to severe KOA. Furthermore, there is evidentiary support for the use of AI to assist clinicians in the diagnosis and potential selection of treatment options for patients with KOA. In conclusion, there are many exciting advancements within the diagnostic and treatment space of KOA.

(1) Background: Young-onset colorectal adenomas (YOAs) are precursors to early-onset colorectal cancer, a growing concern among individuals under 50 years old. This study investigated the association between surrogate markers of insulin resistance (IR) and YOAs occurrence. (2) Methods: A retrospective cross-sectional analysis was conducted on 4467 individuals aged 20 to 49 years who underwent their first screening colonoscopy at Dong-A University Hospital from 2018 to 2022. IR was assessed using the triglyceride-glucose (TyG) index, triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for insulin resistance (METS-IR). (3) Results: Individuals with YOAs exhibited significantly higher median TyG index (8.51 ± 0.71 vs. 8.32 ± 0.61, p < 0.001), TG/HDL-C ratio (2.78 ± 3.05 vs. 2.12 ± 1.85, p < 0.001), and METS-IR (35.72 ± 8.37 vs. 33.44 ± 9.11, p < 0.001) values than controls. The adjusted odds ratios for YOAs were 1.064 (95% CI: 1.22-2.23, p = 0.021) for the TyG index, 1.067 (95% CI: 1.031-1.105, p < 0.001) for the TG/HDL-C ratio, and 1.011 (95% CI: 1.002-1.021, p = 0.023) for METS-IR values, indicating a strong association between higher IR marker values and the presence of YOAs. (4) Conclusions: Elevated IR marker values are strongly associated with the occurrence of YOAs in individuals under 50 years old.

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial disease with unknown etiology and no effective cure, posing a great health burden to society. Erythropoietin (EPO) has been demonstrated to have protective roles in various tissues such as brain, spinal cord, heart, kidney and lung tissues. In this study, we investigate the specific anti-inflammatory, antioxidant and antiapoptotic effects of erythropoietin on lung tissue in a bleomycin-induced rat model of idiopathic pulmonary fibrosis.

Methods: Recombinant human EPO or saline was injected, and the animals were monitored for 14 days after bleomycin instillation. Their hematocrit and serum EPO levels were determined. Histological and immunohistochemical analyses were performed.

Results: The extent of tissue injury, determined through morphometric analysis, was significantly decreased in size in animals treated with erythropoietin. An immunohistochemical analysis of the expression of cyclooxygenase-2 (COX-2), inducible synthase of nitric oxide (i-NOS), metalloproteinase-9 (MMP-9), erythropoietin receptor (EPO-R), and cytochrome-C (cyt-C) found these enzymes to be decreased in a statistically significant manner in animals treated with erythropoietin when compared to a non-treated group.

Conclusions: The reduced expression of COX-2, i-NOS, MMP-9, EPO-R, and i-NOS in the lung tissues of animals treated with EPO indicates the anti-inflammatory, antioxidant and antiapoptotic action of erythropoietin, suggesting its potential therapeutic role in pulmonary fibrosis.

Background: Perforator mapping is a mandatory tool for the preoperative planning of a microsurgical free flap, especially in breast reconstruction. Numerous methods for mapping have been described. In this study, we investigate the combined use of Dynamic Infrared Thermography (DIRT) and Colour Doppler Ultrasonography (CDUS) only to see whether it can eliminate the need for Computed Tomography Angiography (CTA). Methods: A prospective study was conducted on 33 patients with deep inferior epigastric perforator (DIEP) flaps for breast reconstruction. DIRT, followed by CDUS and CTA, was performed preoperatively and perforators were confirmed intraoperatively. Results: From 135 hot spots found on DIRT, 123 perforators were confirmed by CDUS (91.11%). A total of 86.66% of the perforator vessels detected on CTA have their correspondent on DIRT, while 95.12% have their correspondent on CDUS. No statistically significant difference (p > 0.05) was found comparing DIRT vs. CTA and CDU vs. CTA. The average DIRT time was 121.54 s and CDUS 232.09 s. The mean sensitivity for DIRT was 95.72% and 93.16% for CDUS. Conclusion: DIRT combined with CDUS can precisely and efficiently identify suitable perforators without the need for CTA in DIEP breast reconstruction.

Sjögren's syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren's syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren's syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud's phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS.

Background: The Autotaxin (ATX)-lysophosphatidic acid (LPA) axis is involved in decreasing radiation sensitivity of breast tumor cells. This study aims to further elucidate the effect of irradiation on the ATX-LPA axis and cytokine secretion in different breast cancer cell lines to identify suitable breast cancer subtypes for targeted therapies.

Methods: Different breast cancer cell lines (MCF-7 (luminal A), BT-474 (luminal B), SKBR-3 (HER2-positive), MDA-MB-231 and MDA-MB-468 (triple-negative)) and the breast epithelial cell line MCF-10A were irradiated. The influence of irradiation on LPA receptor (LPAR) expression, ATX expression, and Interleukin (IL)-6 and IL-8 secretion was analyzed. Further, the effect of IL-6 and IL-8 on ATX expression of adipose-derived stem cells (ADSC) was investigated.

Results: Irradiation increased ATX and LPAR2 expression in MDA-MB-231 cells. Additionally, IL-6 secretion was enhanced in MDA-MB-231, and IL-8 secretion in MDA-MB-231 and MDA-MB-468. Stimulation of ADSC with IL-6 and IL-8 increased ATX expression in ADSC.

Conclusions: Targeting ATX or its downstream signaling pathways might enhance the sensitivity of triple-negative breast cancer cells to radiation. Further exploration of the interplay between irradiation, the ATX-LPA axis, and inflammatory cytokines may elucidate novel pathways for overcoming radioresistance and improving individual treatment outcomes.

Background: Bilateral cleft lip palate is a severe congenital birth defect of the mouth and face. Immunity factors modulate immune response, inflammation, and healing; therefore, they are vital in the assessment of the immunological status of the patient. The aim of this study is to assess the distribution of Gal-10, CD-163, IL-4, IL-6, IL-10, HBD-2, HBD-3, and HBD-4 in tissue of the bilateral cleft lip palate in primary dentition children.

Methods: Five patients underwent cheiloplasty surgery, where five tissue samples of lip were obtained. Immunohistochemical staining, semi-quantitative evaluation, and non-parametric statistical analysis were used.

Results: A statistically significant increase in HBD-2, HBD-3, and HBD-4 was found in skin and mucosal epithelium, hair follicles, and blood vessels. A notable increase was also noted in IL-4, IL-6, and IL-10 in the mucosal epithelium and CD163 in blood vessels. The connective tissue of patients presented with a statistically significant decrease in Gal-10, IL-10, and HBD-3. Spearman's rank correlation revealed multiple significant positive and negative correlations between the factors.

Conclusions: Upregulation of CD163 points to increased angiogenesis but the increase in IL-4 and IL-10 as well as the decrease in Gal-10 points to suppression of excessive inflammatory damage. Decreased connective tissue healing and excessive scarring are suggested by the decrease in HBD-3 and IL-10 and the increase in IL-6.

The COVID-19 pandemic underscores the need for accurate prognostic tools to predict patient outcomes. This study evaluates the effectiveness of four prominent COVID-19 prediction scores-PAINT, ISARIC4C, CHIS, and COVID-GRAM-at two critical time points: at admission and seven days post-symptom onset, to assess their utility in predicting mortality among hospitalized patients. Conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, this retrospective analysis included adult patients hospitalized with confirmed SARS-CoV-2 infection. Eligible patients had complete data for the scores at both time points. Statistical analysis involved ROC curves and logistic regression to assess the scores' predictive accuracy for mortality. The study included 215 patients, split into 139 survivors and 76 non-survivors. At admission, the PAINT, ISARIC4C, CHIS, and COVID-GRAM scores significantly differentiated between the survival outcomes (p < 0.0001). The best cutoff values at admission were 6.26 for PAINT, 7.95 for ISARIC4C, 5.58 for CHIS, and 0.63 for COVID-GRAM, corresponding to sensitivities of 85.47%, 80.56%, 88.89%, and 83.33% and specificities of 77.34%, 82.12%, 75.01%, and 78.45%, respectively. By day seven, the cutoff values increased, indicating deteriorating conditions in patients who eventually succumbed to the virus. The hazard ratios at admission for exceeding these cutoffs were significant: PAINT (HR = 3.45), ISARIC4C (HR = 2.89), CHIS (HR = 4.02), and COVID-GRAM (HR = 3.15), highlighting the scores' abilities to predict severe outcomes. One week post symptom onset, these scores' predictive values and corresponding hazard ratios increased, further validating their prognostic significance over time. The evaluated COVID-19 prediction scores robustly predict mortality at admission and become more predictive by the seventh day of symptom onset. These findings support the use of these scores in clinical settings to facilitate early identification and intervention for high-risk patients, potentially improving patient outcomes during the ongoing global health crisis.