Efficacy and safety of a novel polytetrafluoroethylene-coated self-expandable metal stent for distal malignant biliary obstruction.

Background: Stent migration and sludge formation remain significant problems associated with covered self-expandable metal stents (CSEMSs). The EGIS biliary stent fully covered flare type (EGIS biliary stent), a new type of polytetrafluoroethylene-coated self-expandable metal stent with low axial force and an anti-migration system, was developed to overcome these disadvantages. We conducted this study to evaluate the efficacy and safety of this stent in comparison with conventional CSEMS (c-CSEMS). Methods: We retrospectively analyzed consecutive patients with unresectable pancreatic cancer who received initial CSEMS for distal malignant biliary obstruction. The primary outcome was time to recurrent biliary obstruction (RBO). Secondary outcomes included technical success rate, functional success rate, stent-related adverse events, causes of RBO, and re-intervention. Results: A total of 40 patients were included (EGIS group: 20; c-CSEMS group: 20). The technical and functional success rates were similar between the two groups. Stent-related adverse event rates (20% vs. 15%, p > 0.99) and overall RBO rates (56% vs. 50%, p > 0.99) were not significantly different between the two groups. Stent migration was the most common cause of RBO in the EGIS group, while stent occlusion was in the c-CSEMS group. The median time to RBO (102 vs. 434 days, p = 0.10) was not significantly different between the two groups. Endoscopic transpapillary re-intervention was successful in most patients in both groups. Conclusions: The EGIS biliary stent was not associated with a longer time to RBO compared to c-CSEMS. Further improvements, especially against stent migration, are needed to improve its efficacy.

Antibiotic heteroresistance and persistence: an additional aid in hospital acquired infections by Enterococcus spp.?

Enterococcus, particularly E. faecium and E. faecalis, are responsible for many hospital-acquired infections. With their intrinsic antibiotic resistance and ability to form biofilms, enterococcal infections are already challenging to manage. However, when heterogenous populations are present, such as those exhibiting heteroresistance and persistence, the complexity of these infections increases exponentially not only due to their treatment but also due to their difficult diagnosis. In this study, we provide a summary of the current understanding of both heteroresistance and persistence in terms of mechanisms, diagnosis and treatment and subsequently review recent literature pertaining to these susceptibility types specifically in enterococci.

Some bacteria are common causes of illness among hospital patients. Some of these infections are very difficult to treat, as the bacteria can respond differently to antibiotics. This review looks at how a type of bacteria called Enterococcus can respond differently to antibiotics, and how we can diagnose or kill them more easily.

Human microbiome: Impact of newly approved treatments on C. difficile infection.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice. SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies. CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.

The Effect of Recurrent Heart Failure Hospitalizations on the Risk of Cardiovascular and all-Cause Mortality: a Systematic Review and Meta-Analysis.

INTRODUCTION: Heart failure (HF) is a significant worldwide concern due to its substantial impact on mortality rates and recurrent hospitalizations. The relationship between recurrent hospitalizations and mortality in individuals diagnosed with heart failure has been the subject of conflicting findings in previous studies. A meta-analysis was conducted to investigate the association between recurrent heart failure hospitalizations (HFHs) and mortality. METHODS: We conducted a systematic search across various online databases, such as PubMed, Embase, Web of Science, ProQuest, Scopus, Science Direct, and Google Scholar, to locate studies that examined the connection between recurrent HFHs and cardiovascular (CV) mortality as well as all-cause mortality until January 2023. To evaluate the heterogeneity among the studies, we employed I2 and Cochran's Q test. RESULTS: In total, 143,867 participants from seven studies were included in the analysis. Recurrent HFHs were found to be strongly associated with elevated risks of both cardiovascular (CV) mortality and all-cause mortality. The pooled hazard ratios (HRs) indicated a non-significant association for CV mortality (HR = 4.28, 95% CI: 0.86-7.71) but a significant association for all-cause mortality (HR = 2.76, 95% CI: 2.05-3.48). Subgroup analyses revealed a reduction in heterogeneity when stratified by factors such as quality score, sample size, hypertension comorbidity, number of recurrent HFHs, and follow-up time. A clear correlation was observed between the frequency of HFH and the mortality risk. Various subgroups, including those with diabetes, atrial fibrillation, and chronic kidney disease, showed significant associations between recurrent HFHs and all-cause mortality. Additionally, recurrent HFHs were significantly associated with CV mortality in subgroups such as heart failure with reduced ejection fraction (HFrEF), atrial fibrillation, and diabetes. CONCLUSION: This meta-analysis provides evidence of an association between recurrent HFH and elevated risk of both CV mortality and all-cause mortality. The findings consistently indicate that a higher frequency of HFH is strongly associated with an increased likelihood of mortality.

A Case Report With Dual Diagnosis of Candidiasis in a Patient With Uncontrolled Diabetes Mellitus.

Chronic hyperglycemia is a hallmark of diabetes mellitus (DM), one of the most common endocrine illnesses affecting millions of people globally. A key issue for diabetes patients is a compromised immune system, which impairs their capacity to fight off invading microbes and increases their susceptibility to infections. Compared to the healthy population, those with DM experience noticeably longer recovery from illnesses or injuries. Individuals suffering from DM are more susceptible to Candida albicans colonizing their oral and/or vaginal mucosa and urinary system. The present article presented a case of a 52-year-old female patient who reported recurrent multiple plaque-like lesions with the underlying condition of hyperglycemia. The oral lesions were treated using the local application of clotrimazole gel and the discomfort subsided with Aceclofenac. The underlying condition was treated by a general physician who prescribed the tablet metformin 500mg. The patient was educated about the predisposing condition, and motivated to make some lifestyle changes and to maintain a proper diet.

Clinical value of thromboelastography in predicting the risk of recurrence of acute ischemic stroke.

Background: Thromboelastography (TEG) can objectively reflect the formation, development and rupture process of thrombosis in patients, but there are limited data on whether TEG can be used as a predictive tool for recurrence in patients with acute ischemic stroke. Objective: To explore the TEG risk of recurrence in patients with acute ischemic stroke predictive value. Methods: A total of 441 patients with acute ischemic stroke who met the research criteria in the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2020 to December 2021 were selected as the research objects. TEG was measured in all patients, and the main parameters of TEG (R value, indicating coagulation reaction time; K value and Angle, the rate of blood clot formation; MA value, indicating the maximum amplitude). The primary outcome of this study was ischemic stroke recurrence. Recurrent events included cerebral infarction, cerebral hemorrhage, TIA, and were determined by combining imaging events and clinical events. Logistic regression analysis was used to explore the influencing factors of recurrence in patients with acute ischemic stroke. Results: Fifty-six patients (12.7%) had recurrence. Multivariate Logistic regression analysis showed that: Age [OR = 1.078, 95%CI(1.024, 1.135)], triglyceride [OR = 1.541, 95%CI(1.033, 2.298)], glycosylated hemoglobin [OR = 1.401, 95%CI(1.097, 1.790)], history of hypertension [OR = 16.046, p < 0.05], 95%CI(4.726, 54.489), R value [OR = 0.533, 95%CI(0.351, 0.809)], MA value [OR = 1.399, 95%CI(1.004, 1.949)] were independent influencing factors for hemorrhagic transformation in patients with acute ischemic stroke. Conclusion: TEG has some value in predicting recurrence in patients with acute ischemic stroke, and the MA value in TEG [AUC = 0.806 (95%CI:0.747-0.867), with a sensitivity of 78.6% and a specificity of 70.4%], predicted the most significant efficiency of AIS recurrence.

A self-fused peptide-loaded hydrogel with injectability and tissue-adhesiveness for preventing postoperative peritoneal adhesions.

Peritoneal adhesions commonly occur following abdominal or pelvic surgery and can cause serious complications. Currently, physical barriers are the primary approach used in clinical practice to prevent adhesion, although their effectiveness is frequently inadequate. In this study, we developed an injectable peptide-loaded hydrogel with multiple functions, including self-fusion, tissue-adhesiveness, anti-inflammation, anti-cell adhesion and anti-angiogenesis. To assess the effectiveness of these hydrogels, which are stabilized by dynamic imine bonds and acetal connections, in preventing postoperative abdominal adhesions, we utilized both a rat abdominal adhesion model and a rat model simulating repeated-injury adhesions. In comparison to the commercially available HA hydrogel, as-prepared hydrogels exhibited significant reductions in inflammation, fibrosis, and angiogenesis, leading to an obvious decrease in peritoneal adhesions. Moreover, this peptide-loaded hydrogel demonstrated an ideal degradation time, maintaining an in vivo viability for about 10 days. We believe this peptide-loaded hydrogel presents a promising solution for the challenging clinical issue of postoperative abdominal adhesions.

The Arthroscopically Guided Bristow-Latarjet Procedure With Cortical Button Fixation: A Minimum 10-Year Follow-up.

BACKGROUND: Despite improved visualization, the use of arthroscopic surgery to perform the Latarjet procedure has not decreased the rates of complications and glenohumeral osteoarthritis (OA) in the long term. Many of the reported complications are related to the use of screws for bone block fixation with freehand drilling. PURPOSE: To evaluate the long-term (at a minimum 10-year follow-up) clinical and radiological outcomes of the arthroscopic Bristow-Latarjet procedure using a posterior guided drilling technique and suture button for coracoid bone graft fixation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Consecutive patients who underwent the arthroscopic Bristow-Latarjet procedure with suture button fixation between 2011 and 2013 were reviewed by 2 independent evaluators. Complications and revision surgery were recorded, and we evaluated patient-reported outcomes including subjective scores, recurrence of shoulder instability (dislocation or subluxation), range of motion limitations, and return to sports. Patients had radiographs taken at least 10 years after surgery to assess glenohumeral OA according to the Samilson-Prieto classification system and computed tomography scans to assess bone block positioning and healing. RESULTS: A total of 65 consecutive patients (68 shoulders) with a mean follow-up of 135 months (range, 120-156 months) were included. The mean age at the time of surgery was 25 ± 8 years; 7 patients had previous failed Bankart repair. At follow-up, 94% (64/68) of the shoulders had no recurrence of instability. The 4 cases of instability recurrence were traumatic and occurred at 3 weeks (a fall), 4 months, 2 years, and 7 years after surgery. No hardware failures, coracoid fractures, or neurological complications were observed. Overall, 61 patients (94%) were still participating in sports, with 44 (68%) at the same or higher level. Range of motion showed nonsignificant restrictions in external rotation with the arm at the side (7° ± 9°) and with the arm at 90° of abduction (9° ± 10°) compared with the contralateral side. Additionally, 11 shoulders (16%) had some residual anterior apprehension on clinical examination. At last follow-up, 77% (47/61) of the shoulders had no OA development or progression. Previous failed Bankart repair was a risk factor for the development of OA. Patients with OA had significantly lower Subjective Shoulder Value scores (79% vs 91%, respectively; P = .01) and decreased external rotation with the arm at the side (40° vs 65°, respectively; P = .001) compared with patients with no or little OA. CONCLUSION: The arthroscopically guided Bristow-Latarjet procedure with suture button fixation is a safe and durable surgical treatment method for recurrent anterior shoulder instability, allowing a high rate of return to sports without significant motion restrictions and no or little OA in the long term.

MNSFß promotes LPS-induced TNFα expression by increasing the localization of RC3H1 to stress granules, and the interfering peptide HEPN2 reduces TNFα production by disrupting the MNSFß-RC3H1 interaction in macrophages.

Abnormally elevated tumor necrosis factor-α (TNFα) levels at the maternal-fetal interface can lead to adverse pregnancy outcomes, including recurrent miscarriage (RM), but the mechanism underlying upregulated TNFα expression is not fully understood. We previously reported that the interaction between monoclonal nonspecific suppressor factor-ß (MNSFß) and RC3H1 upregulates TNFα expression, but the precise mechanisms are unknown. In this study, we found that MNSFß stimulated the LPS-induced TNFα expression by inactivating the promoting effect of RC3H1 on TNFα mRNA degradation rather than directly inhibiting the expression of RC3H1 in THP1-Mϕs. Mechanistically, the 81-326 aa region of the RC3H1 protein binds to the 101-133 aa region of the MNSFß protein, and MNSFß facilitated stress granules (SGs) formation and the translocation of RC3H1 to SGs by interacting with RC3H1 and fragile X mental retardation 1 (FMR1) in response to LPS-induced stress. The SGs-localization of RC3H1 reduced its inhibitory effect on TNFα expression in LPS-treated THP1-Mϕs. The designed HEPN2 peptide effectively reduced the LPS-induced expression of TNFα in THP1-Mϕs by interfering with the MNSFß-RC3H1 interaction. Treatment with the HEPN2 peptide significantly improved adverse pregnancy outcomes, including early pregnancy loss (EPL) and lower fetal weight (LFW), which are induced by LPS in mice. These data indicated that MNSFß promoted TNFα expression at least partially by increasing the localization of RC3H1 to SGs under inflammatory stimulation and that the HEPN2 peptide improved the adverse pregnancy outcomes induced by LPS in mice, suggesting that MNSFß is a potential pharmacological target for adverse pregnancy outcomes caused by abnormally increased inflammation at early pregnancy.

Molecular diagnostic yield of exome sequencing in a Chinese cohort of 512 fetuses with anomalies.

BACKGROUND: Currently, whole exome sequencing has been performed as a helpful complement in the prenatal setting in case of fetal anomalies. However, data on its clinical utility remain limited in practice. Herein, we reported our data of fetal exome sequencing in a cohort of 512 trios to evaluate its diagnostic yield. METHODS: In this retrospective cohort study, the couples performing prenatal exome sequencing were enrolled. Fetal phenotype was classified according to ultrasound and magnetic resonance imaging findings. Genetic variants were analyzed based on a phenotype-driven followed by genotype-driven approach in all trios. RESULTS: A total of 97 diagnostic variants in 65 genes were identified in 69 fetuses, with an average detection rate of 13.48%. Skeletal and renal system were the most frequently affected organs referred for whole exome sequencing, with the highest diagnostic rates. Among them, short femur and kidney cyst were the most common phenotype. Fetal growth restriction was the most frequently observed phenotype with a low detection rate (4.3%). Exome sequencing had limited value in isolated increased nuchal translucency and chest anomalies. CONCLUSIONS: This study provides our data on the detection rate of whole exome sequencing in fetal anomalies in a large cohort. It contributes to the expanding of phenotypic and genotypic spectrum.

Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens. Case descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0. She underwent chemoradiation and presented three months after primary treatment completion with recurrence of squamous cell carcinoma and positive PD-L1 expression with a CPS score of 20. Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type. She underwent open radical hysterectomy, bilateral salpingectomy, bilateral oophorepexy, and bilateral pelvic lymph node dissection with subsequent adjuvant chemoradiation. Her initial pathology demonstrated positive PDL1 expression with CPS score of 15. She presented six months after completion of primary treatment with recurrence of endocervical adenocarcinoma, mucinous type and negative PD-L1 expression with a CPS score of < 1. Regardless of this discrepancy, pembrolizumab was added to cycle five of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She initially demonstrated a mixed response; however, ultimately progressed after eight cycles and was transitioned to tisotumab vedotin. Discussion: To our knowledge, discrepancies in PD-L1 expression in a matched setting between primary and metastatic tumors has only been reported once. This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.

Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.

Aims: We aimed to elucidate the mechanism leading to polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA). Background: PCOS is an endocrine disorder. Patients with RSA also have a high incidence rate of PCOS, implying that PCOS and RSA may share the same pathological mechanism. Objective: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) and RSA GSE113790 and GSE178535) were downloaded from the Gene Expression Omnibus (GEO) database. Methods: Datasets of PSCO and RSA patients were retrieved from the Gene Expression Omnibus (GEO) database. The "WGCNA" package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the "DAVID" database. The GSEA analysis was performed in "clusterProfiler" package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Results: The modules related to PCOS and RSA were sectioned by weighted gene co-expression network analysis (WGCNA) and positive correlation modules of PCOS and RSA were all enriched in angiogenesis and Wnt pathways. The GSEA further revealed that these biological processes of angiogenesis, Wnt and regulation of cell cycle were significantly positively correlated with the PCOS and RSA phenotypes. The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples. Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway. Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells. Conclusion: This study revealed the common pathological mechanisms between PCOS and RSA and explored the role of the PI3K-AKT signaling pathway in the two diseases, providing a new direction for the clinical treatment of PCOS and RSA.

Comparison of cold snare endoscopic mucosal resection and hot snare endoscopic mucosal resection for small colorectal polyps: a randomized controlled trial.

Incomplete resection rates vary among endoscopists performing cold snare polypectomy. Cold snare endoscopic mucosal resection (CS-EMR) is the technique of cold resection after submucosal injection to reduce incomplete resection. This study aimed to evaluate the efficacy and safety of CS-EMR for small colorectal polyps compared to hot snare endoscopic mucosal resection (HS-EMR). Preplanned sample size required 70 polyps to CS-EMR group or HS-EMR group, respectively. Patients with polyps sized 6-9 mm were randomly allocated to either the CS-EMR or the HS-EMR group. The primary outcome was residual or recurrent adenoma (RAA) rate. A total of 70 and 68 polyps were resected using CS-EMR and HS-EMR, respectively. In the intention-to-treat population, the RAA rate was 0% in the CS-EMR group and 1.5% in the HS-EMR group (risk difference [RD], - 1.47; 95% confidence interval [CI] - 4.34 to 1.39). En bloc resection rate was 98.6% and 98.5% (RD, - 0.04; 95% CI - 4.12 to 4.02); the R0 resection rate was 55.7% and 82.4% (RD, - 27.80; 95% CI - 42.50 to - 13.10). The total procedure time was 172 s (IQR, 158-189) in the CS-EMR group and 186 s (IQR, 147-216) in the HS-EMR group (median difference, - 14; 95% CI - 32 to 2). Delayed bleeding was 2.9% vs 1.5% (RD, 1.37; 95% CI - 3.47 to 6.21) in both groups, respectively. CS-EMR was non-inferior to HS-EMR for the treatment of small colorectal polyps. CS-EMR can be considered one of the standard methods for the removal of colorectal polyps sized 6-9 mm.

Hybrid deep learning based prediction for water quality of plain watershed.

Establishing a highly reliable and accurate water quality prediction model is critical for effective water environment management. However, enhancing the performance of these predictive models continues to pose challenges, especially in the plain watershed with complex hydraulic conditions. This study aims to evaluate the efficacy of three traditional machine learning models versus three deep learning models in predicting the water quality of plain river networks and to develop a novel hybrid deep learning model to further improve prediction accuracy. The performance of the proposed model was assessed under various input feature sets and data temporal frequencies. The findings indicated that deep learning models outperformed traditional machine learning models in handling complex time series data. Long Short-Term Memory (LSTM) models improved the R2 by approximately 29% and lowered the Root Mean Square Error (RMSE) by about 48.6% on average. The hybrid Bayes-LSTM-GRU (Gated Recurrent Unit) model significantly enhanced prediction accuracy, reducing the average RMSE by 18.1% compared to the single LSTM model. Models trained on feature-selected datasets exhibited superior performance compared to those trained on original datasets. Higher temporal frequencies of input data generally provide more useful information. However, in datasets with numerous abrupt changes, increasing the temporal interval proves beneficial. Overall, the proposed hybrid deep learning model demonstrates an efficient and cost-effective method for improving water quality prediction performance, showing significant potential for application in managing water quality in plain watershed.

Unique Transligamentous Variant of the Recurrent Motor Branch of the Median Nerve.

This case report presents a 72-year-old female with a unique anatomical variation of the median nerve recurrent motor branch that has not been described in the literature. During her open carpal tunnel release, the recurrent motor branch was found to divide from the median nerve within the carpal tunnel, pierce the proximal aspect of the transverse carpal ligament in a transligamentous fashion, and then immediately divide into one branch that pierced the thenar muscles and another branch that traveled superficial to the transverse carpal ligament before piercing the thenar muscles more distal. This variation in anatomy stresses the importance of thoughtful incision design and direct visualization of all structures during carpal tunnel release.

Recurrent neural network for trajectory tracking control of manipulator with unknown mass matrix.

Real-world robotic operations often face uncertainties that can impede accurate control of manipulators. This study proposes a recurrent neural network (RNN) combining kinematic and dynamic models to address this issue. Assuming an unknown mass matrix, the proposed method enables effective trajectory tracking for manipulators. In detail, a kinematic controller is designed to determine the desired joint acceleration for a given task with error feedback. Subsequently, integrated with the kinematics controller, the RNN is proposed to combine the robot's dynamic model and a mass matrix estimator. This integration allows the manipulator system to handle uncertainties and synchronously achieve trajectory tracking effectively. Theoretical analysis demonstrates the learning and control capabilities of the RNN. Simulative experiments conducted on a Franka Emika Panda manipulator, and comparisons validate the effectiveness and superiority of the proposed method.

Effect of blue light emitting diode therapy on recurrent vulvovaginal candidiasis: A randomized assessor-blinded controlled trial.

OBJECTIVE: Vulvovaginal Candidiasis (VVC) is a prevalent genital infection in women of reproductive age and requires effective non-drug therapies. Therefore, this study aimed to investigate the effect of blue light emitting diode (LED) therapy as an alternative treatment for recurrent VVC due to its proven antimicrobial properties. The safety and non-invasiveness of LED therapy make it a promising option for sensitive tissue applications. MATERIALS AND METHODS: This randomized controlled trial recruited 60 women with culture-confirmed VVC. Participants were randomly allocated to two groups. Group A (control group) received standard antifungal treatment with Gynoconazol 0.8% vaginal cream for three consecutive nights (n = 30). Group B (study group) received the same antifungal treatment plus two 60-min sessions of blue LED therapy directed at the vagina and vulva, with the sessions separated by two days (n = 30). Candida count (via CHROMagar™ Candida) and vaginal pH (via AD110-AD111 m) were assessed at baseline and one week after initiating treatment. RESULTS: Post-treatment, group (B) demonstrated a significantly greater reduction in Candida count compared to group (A) (mean difference (MD) 8.267; 95% Confidence Interval (CI) 6.723-9.811; p = 0.0001). However, there was no statistically significant difference in vaginal pH between the groups (MD -0.03; 95% CI -0.244-0.178; p = 0.749). CONCLUSION: Blue LED therapy effectively reduces Candida count in women with recurrent VVC without adversely affecting the vaginal pH, highlighting its safety and efficacy as a treatment modality.

FibroScan compared to liver biopsy for accurately staging recurrent hepatic steatosis and fibrosis after transplantation for MASH.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the diagnostic accuracy in the post-LT setting of patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings. METHODS: This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1-year after LT. RESULTS: In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range [IQR]:16-46) and 26.0 (IQR: 16.8-41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0-5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients (n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients (n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa (n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post-LT hypertension (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 1.8-80.4, p = .010) and post-LT dyslipidaemia (OR: 7.9, 95% CI: 1.3-47.1, p = .024) with LSM (OR: 1.7, 95% CI: 1.1-2.8, p = .030) was independently associated with MASLD. CONCLUSIONS: Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis.

Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.

It has been recognized that oxidative stress (OS) is implicated in the etiology of recurrent pregnancy loss (RPL), yet the biomarkers reflecting oxidative stress in association with RPL remain scarce. The dataset GSE165004 was retrieved from the Gene Expression Omnibus (GEO) database. From the GeneCards database, a compendium of 789 genes related to oxidative stress-related genes (OSRGs) was compiled. By intersecting differentially expressed genes (DEGs) in normal and RPL samples with OSRGs, differentially expressed OSRGs (DE-OSRGs) were identified. In addition, four machine learning algorithms were employed for the selection of diagnostic markers for RPL. The Receiver Operating Characteristic (ROC) curves for these genes were generated and a predictive nomogram for the diagnostic markers was established. The functions and pathways associated with the diagnostic markers were elucidated, and the correlations between immune cells and diagnostic markers were examined. Potential therapeutics targeting the diagnostic markers were proposed based on data from the Comparative Toxicogenomics Database and ClinicalTrials.gov. The candidate biomarker genes from the four models were further validated in RPL tissue samples using RT-PCR and immunohistochemistry. A set of 20 DE-OSRGs was identified, with 4 genes (KRAS, C2orf69, CYP17A1, and UCP3) being recognized by machine learning algorithms as diagnostic markers exhibiting robust diagnostic capabilities. The nomogram constructed demonstrated favorable predictive accuracy. Pathways including ribosome, peroxisome, Parkinson's disease, oxidative phosphorylation, Huntington's disease, and Alzheimer's disease were co-enriched by KRAS, C2orf69, and CYP17A1. Cell chemotaxis terms were commonly enriched by all four diagnostic markers. Significant differences in the abundance of five cell types, namely eosinophils, monocytes, natural killer cells, regulatory T cells, and T follicular helper cells, were observed between normal and RPL samples. A total of 180 drugs were predicted to target the diagnostic markers, including C544151, D014635, and CYP17A1. In the validation cohort of RPL patients, the LASSO model demonstrated superiority over other models. The expression levels of KRAS, C2orf69, and CYP17A1 were significantly reduced in RPL, while UCP3 levels were elevated, indicating their suitability as molecular markers for RPL. Four oxidative stress-related diagnostic markers (KRAS, C2orf69, CYP17A1, and UCP3) have been proposed to diagnose and potentially treat RPL.