Responder Group Research Articles

Predicting response to CCRT for esophageal squamous carcinoma by a radiomics-clinical SHAP model

BackgroundRadical concurrent chemoradiotherapy (CCRT) is frequently used as the first-line treatment for patients with locally advanced esophageal cancer. Unfortunately, some patients respond poorly. To predict response to radical concurrent chemoradiotherapy in pre-treatment patients with esophageal squamous carcinoma (ESCC), and compare the predicting efficacies of radiomics features of primary tumor with or without regional lymph nodes, we developed a radiomics-clinical model based on the positioning CT images. Finally, SHapley Additive exPlanation (SHAP) was used to explain the models.MethodsThis retrospective study enrolled 105 patients with medically inoperable and/or unresectable ESCC who underwent radical concurrent chemoradiotherapy (CCRT) between October 2018 and May 2023. Patients were classified into responder and non-responder groups with RECIST standards. The 11 recently admitted patients were chosen as the validation set, previously admitted patients were randomly split into the training set (n = 70) and the testing set (n = 24). Primary tumor site (GTV), the primary tumor and the uninvolved lymph nodes at risk of microscopic disease (CTV) were identified as Regions of Interests (ROIs). 1762 radiomics features from GTV and CTV were respectively extracted and then filtered by statistical differential analysis and Least Absolute Shrinkage and Selection Operator (LASSO). The filtered radiomics features combined with 13 clinical features were further filtered with Mutual Information (MI) algorithm. Based on the filtered features, we developed five models (Clinical Model, GTV Model, GTV-Clinical Model, CTV Model, and CTV-Clinical Model) using the random forest algorithm and evaluated for their accuracy, precision, recall, F1-Score and AUC. Finally, SHAP algorithm was adopted for model interpretation to achieve transparency and utilizability.ResultsThe GTV-Clinical model achieves an AUC of 0.82 with a 95% confidence interval (CI) of 0.76–0.99 on testing set and an AUC of 0.97 with a 95% confidence interval (CI) of 0.84–1.0 on validation set, which are significantly higher than those of other models in predicting ESCC response to CCRT. The SHAP force map provides an integrated view of the impact of each feature on individual patients, while the SHAP summary plots indicate that radiomics features have a greater influence on model prediction than clinical factors in our model.ConclusionGTV-Clinical model based on texture features and the maximum diameter of lesion (MDL) may assist clinicians in pre-treatment predicting ESCC response to CCRT.

Early Prediction of Radiation Treatment Response via Longitudinal Analysis of CBCT Radiomic Features for Locally Advanced Rectal Cancer.

Patients respond to the same radiation treatment course differently due to inter- and intra- patient variability in radiosensitivity. Despite widespread use of AI/ML in radiation oncology, there is a lack of monitoring strategies used during treatment courses to evaluate early predictors of treatment response in a systematic fashion. This work advances a straightforward, yet effective, method for the early detection of treatment response through systematically analyzing daily CBCT radiomic features. The goal is to aid clinicians in assessing the treatment efficacy routinely with a view towards optimizing personalized treatment. We included a cohort of 30 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant fractionated radiation treatment (RT) with a prescription dose of 50.4 Gy (28 fractions), followed by total mesorectal excision surgery after completion of ChemoRT. Daily IGRT imaging was acquired prior to each fraction resulting in a total of 840 CBCTs. Patients were divided into responder (14 patients) and non-responder (16 patients) groups based on post-RT pathological response. Mutual information algorithms were utilized to rigorously register daily CBCT images to the planning CT, and longitudinal radiomic features of the target were extracted from the daily CBCTs during the entire treatment course. All longitudinal features for a given patient were standardized with Z-Score normalization, followed by linear fitting using the least square method, resulting in radiomic feature trends (RFT) represented by slope values. Statistical significance was established via a two-sample U test and P-value with a threshold of 0.05. Logistic regression was performed to eliminate RFT with accuracy rates lower than 0.5. The final trending model was developed using random forest. For each patient at fraction N, our investigation involved independent 27 group experiments, where each experiment considered image group from fraction #1 to N, to confirm the effectiveness and stability of the model. The proposed RFT demonstrated a high level of precision and consistency for post-RT response based on longitudinal CBCT images for LARC patients. The trending model yielded an accuracy of 0.9556, 95% CI (0.94, 0.972) when each daily image was considered, the prediction consistency was 0.964. Given the first 14 experiments (considering group images of fraction #1-15), the prediction accuracy was 0.9357, 95% CI (0.915, 0.956) and the prediction consistency was 0.952. A strategy for monitoring and early prediction of LARC patients' radioresponse was evaluated via longitudinal CBCT assessment. Our trending models demonstrate a significant difference between the responder vs non-responder groups as early as the 15th fraction. Our strategy achieved superior accuracy and consistency to predict post-RT response of LARC patients.

Epigenetic Marks as Predictors of Metabolic Response to Bariatric Surgery: Validation from an Epigenome Wide Association Study.

Little is known about the potential role of epigenetic marks as predictors of the resolution of obesity-related comorbidities after bariatric surgery. In this study, 20 patients were classified according to the metabolic improvement observed 6 months after sleeve gastrectomy, based on the diagnosis of metabolic syndrome, into responders if metabolic syndrome reversed after bariatric surgery (n = 10) and non-responders if they had metabolic syndrome bariatric surgery (n = 10). Blood DNA methylation was analyzed at both study points using the Infinium Methylation EPIC Bead Chip array-based platform. Twenty-six CpG sites and their annotated genes, which were previously described to be associated with metabolic status, were evaluated. Cg11445109 and cg19469447 (annotated to Cytochrome P450 2E1 (CYP2E1) gene) were significantly more hypomethylated in the responder group than in the non-responder group at both study points, whilst cg25828445 (annotated to Nucleolar Protein Interacting With The FHA Domain Of MKI67 Pseudogene 3 (NIFKP3) gene) showed to be significantly more hypermethylated in the non-responder group compared to the responder group at both study points. The analysis of the methylation sites annotated to the associated genes showed that CYP2E1 had 40% of the differentially methylated CpG sites, followed by Major Histocompatibility Complex, Class II, DR Beta 1 (HLA-DRB1) (33.33%) and Zinc Finger Protein, FOG Family Member 2 (ZFPM2) (26.83%). Cg11445109, cg19469447 and cg25828445 could have a role in the prediction of metabolic status and potential value as biomarkers of response to bariatric surgery.

THE ROLE OF LUTEINIZING HORMONE (LH) RECEPTOR IN THE REGULATION OF OOCYTE MATURATION: A SYSTEMATIC LITERATURE REVIEW

The hormone luteinizing hormone (LH) is an important glycoprotein hormone that controls the activity of the gonadal organs, which in turn affects the physiology of the menstrual cycle. For LH to exert its effects, its specific receptor (LHR) must be expressed by cumulus cells. Objective: To determine the role of LH receptors (Luteinizing Hormone) in the regulation of human oocyte maturation processes Method:Systematic Literature Review (SLR). Data collection was conducted by documenting all articles based on predefined inclusion and exclusion criteria. A total of 10 national and international journal articles were retrieved from databases such as Google Scholar, PubMed, and Science Direct, using specific keywords related to the role of LH receptors and oocyte maturation. The literature search and study selection process followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results:The highest expression of Luteinizing Hormone Receptor (LHR) observed in preovulatory follicles. Cumulus cell maturation, covering 100% of the oocytes, was 74%. FSHR and LHR mRNA expression levels increased with an increase in LH concentration in the in vitro maturation (IVM) medium. After 24 hours of IVM, there was a significant downregulation in the expression of LHR and FSHR.The mRNA and protein levels of FSHR and LHR in the cumulus-oocyte complex gradually decreased with increasing doses of FRBI in the IVM media compared to the control group. Majority of the cumulus cells from MII oocytes had RGS2/B2M gene expression of more than 50%. LH receptor expression in granulosa cells positively correlated with morphology, oocyte maturity, and fertility rate in the poor responder group. Granulosa cells from an agonist-triggered cycle with recombinant human chorionic gonadotropin (rhCG) for 24 hours were observed to increase viability, regulate mRNA expression of 3β-HSD, LH receptor, VEGF, and BCL-L2. More than 50% of the oocytes are matured after hCG injectionat an hCG concentration of 119.8 mIU/mL. Conclusion:LH needs receptor binding and expression for proper function, resulting in improved oocyte maturation with optimal LHR concentration which is 10 µg/mL LH. LHR expression is highest in preovulatory follicles. LHR expression increases during antral follicle growth. Supplementing media with hCG improves oocyte maturity with a 77 mIU/mL cutoff value. Supplementation with FRBI reduce LHR expression in COCs. The number of cumulus cells can also indicate the level of oocyte maturity, where cumulus cells covering 100% of the oocytes show the highest oocyte maturation.

Endoscopic Ultrasonography-Derived Maximum Tumor Thickness and Tumor Shrinkage Rate as Independent Prognostic Factors in Locally Advanced Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy

Neoadjuvant chemoradiotherapy (NCRT) is increasingly used in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Endoscopic ultrasonography (EUS)-derived maximum tumor thickness (MTT) before and after standard NCRT for LA-ESCC indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT. We retrospectively enrolled patients with LA-ESCC who underwent EUS examination pre- and post-NCRT from 2017 to 2021. MTT was measured using EUS. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cut-off value defining the EUS response was determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier (KM) curves were used to calculate overall survival (OS) and progression-free survival (PFS). Data from another center were also used for external validation testing. The median follow-up period was 30.6 months.230 patients with LA-ESCC who underwent EUS pre- or post-NCRT were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the re-examined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. In the whole group the 1-year and 3-year OS rates were 93.9% and 67.9%, and PFS rates were 77.7% and 54.1%, respectively. Thinner post-MTT (≤8.8 mm) and EUS-responders (tumor shrinkage rate≥52%) were independently associated with better OS. The result of EUS-respond was an independent prognostic factor could be confirmed in the external validation group. Among LA-ESCC patients with initial ultrasonic T2-3 staging and T4 staging, no statistically differences were observed between the responder and non-responder groups (P = 0.082; P = 0.190). EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT. Initial tumor infiltration beyond esophageal adventitial layer on ultrasound effect could not, however, predict the long-term prognosis.

Long-Term Results of Induction Chemotherapy for Esophageal Squamous Cell Carcinoma Receiving Concurrent Chemoradiotherapy

This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with esophageal squamous cell carcinoma (ESCC). Between 2008 and 2022, 271 ESCC patients who received definitive CCRT (IC followed by CCRT, n = 72; CCRT alone, n = 199) were enrolled. Radiotherapy technique included intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). Through a propensity score matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone, according to age, gender, performance status, tumor length, and pre-treatment TN stage. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. The IC + CCRT group had no improvement in 5-year overall survival (OS) rate (39.0% vs 29.3%, p = 0.360), recurrence-free survival (RFS) rate (39.0% vs 26.9%, p = 0.142), and distant metastasis-free survival (DMFS) rate (33.6% vs 27.2%, p = 0.515) compared with the CCRT group. The overall clinical response rate was 45.1% after IC in the IC + CCRT group. The IC responders (CR + PR + SD) group showed more favorable 5-year OS (41.7% vs. 14.3% vs. 29.3%, p < 0.001), RFS (41.7% vs. 14.3% vs. 26.9%, p < 0.001) and DMFS (37.3% vs. 0% vs. 27.2%, p < 0.001) compared with the IC non-responders (PD) group and the CCRT group. Besides, the 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders (CR + PR) were significantly higher than that of the IC poor responders (SD + PD) and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and AJCC stage (Ⅲ/Ⅳ) were independent predictive factors of OS, RFS and DMFS. Besides, age was an independent predictive factor of DMFS. No significant difference was observed in the rates of grades 3-4 toxicities between both groups. Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without increase in toxicities.

Cardiac Magnetic Resonance in Patients with Suspected Tachycardia-Induced Cardiomyopathy: The Impact of Late Gadolinium Enhancement and Epicardial Fat Tissue.

Tachycardia-induced cardiomyopathy (TIC) is a reversible subtype of dilated cardiomyopathy (DCM) resulting from sustained supraventricular or ventricular tachycardia and diagnosed by the normalization of left ventricular ejection fraction (LVEF) after stable sinus rhythm restoration. The aim of this study was to determine the contribution of cardiac magnetic resonance (CMR) to the differential diagnosis of TIC and DCM with persistent atrial arrythmias in patients hospitalized for the first time with heart failure (HF) with reduced LVEF of nonischemic origin. A total of 29 patients (age: 58.2 ± 16.9 years; males: 65.5%; average EF: 37.0 ± 9.5%) with persistent atrial tachyarrhythmia and first decompensation of HF without known coronary artery diseases were included in this study. The patients successfully underwent cardioversion and were observed for 30 days. The study population was divided into groups of responders (TIC patients; N = 16), which implies achieving FF > 50% or its increase > 10% in 30 days of TIC, and non-responders (N = 13). The increase in left ventricle (LV) volumes measured using CMR was significantly higher in the non-responder group when compared with the responders (114.8 mL ± 25.1 vs. 68.1 mL ± 10.5, respectively, p < 0.05). Non-responders also demonstrated decreased interventricular septum thickness (9.1 ± 0.8 vs.11.5 ± 1.3, respectively, p < 0.05). Late gadolinium enhancement (LGE) was observed in 12 patients (41.4%). The prevalence of LGE was increased in the non-responder group (25.0% vs. 65.1%, respectively, p = 0.046). Notably, a septal mid-wall LGE pattern was found exclusively in the non-responders. Epicardial adipose tissue thickness was decreased in the non-responder group versus the TIC patients. Conclusion: Patients with TIC were found to have smaller atrial and ventricular dimensions in comparison to patients with DCM. In addition, LGE was more common in DCM patients.

The Use of Phentermine for Obesity in Psychiatric Patients With Antipsychotics.

Phentermine is a commonly used weight-loss agent in the United States, but there is a little information about the use of phentermine for patients with obesity taking antipsychotic medications. We gathered 57 patients with obesity taking antipsychotic medications whose phentermine treatment was simultaneous with or after any type of antipsychotic exposure and collected data of clinical information, initial/follow-up anthropometric variables, and adverse events (AEs) for the 6-month study period. In total, the mean body weight reduction (BWR) was 4.45 (7.04) kg, and the mean BWR percent (BWR%) was 3.92% (6.96%) at 6 months. Based on the response to phentermine, the patients were classified into two groups: the responder (n=25; BWR% ≥5%) and nonresponder (n=32; BWR% <5%) groups. The responder group's mean BWR and BWR% were 10.13 (4.43) kg and 9.35% (4.09%), respectively, at 6 months. The responders had higher rates of anticonvulsant combination therapy (ACT; responder, 72.0% vs. non-responder, 43.8%; p=0.033) and a shorter total antipsychotic exposure duration (responder, 23.9 [16.9] months vs. non-responder, 37.2 [27.6] months; p= 0.039). After adjusting age, sex, and initial body weight, ACT maintained a significant association with phentermine response (odds ratio=3.840; 95% confidence interval: 1.082-13.630; p=0.037). In the final cohort, there was no report of adverse or new-onset psychotic symptoms, and the common AEs were sleep disturbances, dry mouth, and dizziness. Overall, phentermine was effective and tolerable for patients with obesity taking antipsychotic medications, and ACT (predominantly topiramate) augmented the weight-loss effect of phentermine.

Predictive Factors of Intra-articular Corticosteroid Injections With Ultrasound-Guided Posterior Capsule Approach for Patients With Primary Adhesive Capsulitis.

Adhesive capsulitis affects the shoulder joint, causing pain and limiting motion. In clinical practice, the effectiveness of injections varies, and the factors influencing their success remain unclear. This study investigates the predictors of effective corticosteroid injections in patients with primary adhesive capsulitis. This retrospective study enrolled adhesive capsulitis patients older than 35 yrs who received intra-articular corticosteroid injections. The response was determined based on patients' pain and range of motion 3 mos after the injection. Demographic data, medical comorbidities, and radiographic parameters (critical shoulder angle and acromial index) were compared between the effective and noneffective groups. Receiver operating characteristic curves and logistic regression were used to identify the predictors of injection effectiveness. This study included 325 patients with primary adhesive capsulitis, who were divided into responder (189 patients, 58.2%) and nonresponder (136 patients, 41.8%) groups. The receiver operating characteristic curve revealed that the acromial index score indicated favorable discrimination for predicting a poor response to injections, whereas the critical shoulder angle score did not. Logistic regression revealed that the pain period, diabetes mellitus, and acromial index are predictors of nonresponders to injections. Long pain duration, the presence of diabetes mellitus, and an acromial index score greater than 0.711 were predictors of nonresponse to corticosteroid injections for primary adhesive capsulitis patients.

The Relationship between Depressive Symptoms, Quality of Life and miRNAs 8 Years after Bariatric Surgery.

(1) Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. (2) Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into "good responders" and "non-responders" depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. (3) Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning-physical, role functioning-emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. (4) Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS.

Role of radionuclide assessment of global and regional mechanical dyssynchrony of the heart in prognosis of cardiac resynchronization therapy in patients with heart failure

Aim. To determine the prognostic significance of cardiac regional mechanical dyssynchrony (MD), assessed by radionuclide equilibrium ventriculography (REVG) in candidates for cardiac resynchronization therapy (CRT).Material and methods. The study included 65 patients with indications for CRT according to current guidelines. Prior to CRT, all patients underwent REVG to assess cardiac contractile function and MD. According to the phase analysis, indicators of global and regional cardiac MD were evaluated: phase standard deviation (PSD), histogram band width (HBW), entropy, and interventricular dyssynchrony. The regional assessment included an evaluation of phase histograms obtained from the analysis of the contraction of certain walls: left ventricular (LV) anterior, lateral, posterior wall, right ventricular (RV) free wall, and the interventricular septum. To evaluate the effectiveness of treatment 6 months after CRT, all patients underwent echocardiography, on the basis of which patients were divided into groups of responders and non-responders.Results. REVG revealed significant differences in the initial regional MD values between the groups of responders and non-responders: in responders, MD values of RV free wall (PSD: 39 (28-67) vs 28 (20-50), p=0,03) and LV anterior wall (PSD: 28,5 (16-40) vs 14 (11-24), p=0,0005) were higher, and the LV lateral wall was lower (PSD: 10 (7-14) vs 15 (9-26), p=0,007) than in non-responders. Multivariate logistic regression found following independent predictors of a positive response to CRT: heart failure of ischemic origin, LV HBW, RV free wall PSD, anterior wall PSD, LV lateral wall HBW (p&lt;0,001). The sensitivity and specificity of the model was 93% and 91%, respectively.Conclusion. Regional MD scintigraphy parameters increase the predictive value of REVG in CRT candidates. The most informative in this regard are the PSD of RV free wall and LV anterior wall, as well as the HBW of LV lateral wall.

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors.

Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method. In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression. PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group. Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.

Intracellular Fusobacterium nucleatum infection attenuates antitumor immunity in esophageal squamous cell carcinoma

Currently, the influence of the tumor microbiome on the effectiveness of immunotherapy remains largely unknown. Intratumoural Fusobacterium nucleatum (Fn) functions as an oncogenic bacterium and can promote tumor progression in esophageal squamous cell carcinoma (ESCC). Our previous study revealed that Fn is a facultative intracellular bacterium and that its virulence factor Fn-Dps facilitates the intracellular survival of Fn. In this study, we find that Fn DNA is enriched in the nonresponder (NR) group among ESCC patients receiving PD-1 inhibitor and that the serum antibody level of Fn is significantly higher in the NR group than in the responder (R) group. In addition, Fn infection has an opposite impact on the efficacy of αPD-L1 treatment in animals. Mechanistically, we confirm that Fn can inhibit the proliferation and cytokine secretion of T cells and that Fn-Dps binds to the PD-L1 gene promoter activating transcription factor-3 (ATF3) to transcriptionally upregulate PD-L1 expression. Our results suggest that it may be an important therapeutic strategy to eradicate intratumoral Fn infection before initiating ESCC immunotherapies.

Increased Body Mass Index Correlates with Less Favorable Postoperative Outcomes After Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea: A Retrospective Cohort Study

Obstructive sleep apnea is associated with high morbidity. Hypoglossal nerve stimulation (HNS) has become a novel (neuro-) surgical treatment strategy for obstructive sleep apnea, demonstrating good success rates. Beyond predefined inclusion and exclusion criteria, no precise data are available, enabling individual preoperative risk assessment. To improve preoperative risk stratification, this study analyzed individual patient factors that affect outcomes of HNS. Fourteen patients treated with unilateral HNS were analyzed retrospectively. Assessed risk factors included: hypertension, diabetes mellitus, depression, smoking, alcohol consumption, body mass index (BMI), and disease duration. Treatment success was defined as a reduction in the postoperative apnea-hypopnea index (AHI) to≤20 events/hour, with a relative reduction of at least 50% compared to baseline. A significant reduction in the postoperative apnea-hypopnea index was observed in all patients (P < 0.0001). BMI correlated significantly with postoperative AHI scores (95% confidence interval, 0.1519-0.8974; P= 0.018). Significant treatment success was observed in 50% of patients. Compared with the "Excellent Responder group," the "Responder group" demonstrated a significantly higher BMI (95% confidence interval, 1.174-6.226; P= 0.0078). Diabetes, hypertension, disease duration, smoking, depression, and alcohol consumption were not significantly associated with AHI reduction. Our findings suggest that BMI may be an independent risk factor for the response to HNS, with patients who had less benefit from therapy having significantly higher BMI than "Excellent Responders." Therefore, carefully selecting patients is crucial in obtaining optimal outcomes with HNS therapy, especially those with a high BMI.

Reproductive Hormones and Female Mental Wellbeing

Fluctuating hormone levels during the menstrual cycle and major reproductive cycle stages have been linked to mood changes, mental health conditions, and an increased likelihood of psychotic episodes. This knowledge could potentially be used for the predictive modeling of exacerbations and mood deterioration through the collection and analysis of data from wearables and apps. A literature search for a narrative review has been conducted using selected keywords in Pubmed, Embase and Google Scholar. Based on published data, it can be seen that hormonal changes affect the severity of symptoms in several mental health conditions, including depression, PMDD, PTSD, bipolar disorder and schizophrenia. The influence of FSH, LH, testosterone, and other hormone precursors has also been investigated, but there is less information available regarding their impact. E2 levels have been measured as a treatment–response biomarker and have demonstrated significant predictive ability for treatment responder groups. On the other hand, FSH has been demonstrated to be helpful in predicting treatment non-responder groups in schizophrenia. Monitoring reproductive hormones in combination with wearables or digital solutions has the potential to predict mood changes more effectively. Precise and frequent hormone measurements might prove to be more effective than relying on absolute threshold levels. Further research is needed to validate the utility and precision of hormone use in the field of mental health.

Does the decrease in E2 levels between the trigger of ovulation and embryo transfer affect the reproductive outcome in IVF-ICSI cycles?

This study aimed to evaluate the effect of the rate of decline in serum estradiol (E2) levels between hCG injection and the day of embryo transfer (ET) on the success of assisted reproductive technology (ART) in women with infertility of different etiologies. Women 20-45 years of age who underwent a standard GnRH antagonist or long agonist protocol and fresh ET during day 3 of their first ART cycle were included. Group 1 was diagnosed with low ovarian reserve, group 2 comprised high ovarian responders, and group 3 consisted of normal responders. Both groups were divided into four subgroups according to the decrease in E2 levels between the day of hCG injection and the day of ET. Subgroup A patients had a decrease of <20%, subgroup B a decrease of 20-40%, subgroup C a decrease of 41-60%, and subgroup D a decrease >60%. The primary outcome measure was the effect of an E2 decline, based on the measurement of E2 on the day of hCG administration and day of ET, on the implantation rate. The secondary outcome was the change in E2 values in these three groups. The study was conducted on 1.928 women. Of these, 639 were poor responders (group 1), 502 were high responders (group 2), and 787 women had a normal ovarian response (group 3). Patients with a 60% decrease in their E2 levels on the ET day after hCG had a lower live birth rate (LBR) and higher miscarriage rate (MCR), except normoresponders, in whom a similar decline was significant only with respect to MCR. We indicate that high ovarian responders who underwent fresh ET cycles with a 60% decrease in their E2 levels on the ET day after human chorionic gonadotropin had lower LBRs and higher miscarriage. However, in normoresponder women, this decline was only significant in miscarriage.

Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study.

Refractory shock, which fails to respond to conventional vasopressor therapy, is a common complication of sepsis. Methylene blue has emerged as a potential adjunctive treatment option for reversing refractory shock in sepsis. The aim of this study was to evaluate the impact of intravenous methylene blue infusion on hemodynamic improvement and mortality in patients with refractory shock. This was an observational prospective study for the duration of six months conducted at intensive care a medical college and teaching hospital including 76 patients with a diagnosis of septic shock requiring vasopressor therapy. Intravenous (IV) methylene blue was infused as a bolus dose with 2 mg/kg dose in 20 minutes and its response to mean arterial blood pressure, decrease in vasopressor therapy, lactate level, and urine output was recorded in next 2 hours. Patients with improvement in mean arterial pressure (MAP) by 10% or decrease in vasopressor therapy in the next 2 hours were leveled as responder. The length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of acute kidney injury (AKI), and mortality were compared between responder and non-responder. A total of 76 patients with refractory shock were included in the study. With the use of IV methylene blue, 41 (53.9%) patients showed significant improvement in MAP within 2 hours (70.17 ± 8.30 vs 64.28 ± 11.84, p = 0.005). Responders were 4.019 times more likely to have vasopressor-free time within 24 hours (18.4% vs 5.3%, p = 0.020, odds ratio 4.019, 95% confidence interval, 1.180-13.682). However, there was no significant difference in terms of mortality, length of ICU stay, ventilator free days, and incidence of AKI. In the responder group, there was a significant increase in the MAP and decrease in vasopressor requirement pre- and post-infusion of methylene blue (p < 0.05). Responder had shorter vasopressor-free days as compared with non-responder (5.34 vs 6.79, p = 0.008) while the mean survival time was longer with responders (21.97 vs 15.93 days, p = 0.024). The use of IV methylene blue in refractory shock as an adjuvant therapy significantly improved the mean arterial blood pressure and decreased the requirement of vasopressor therapy as well as improvement in the survival time. However, there was no change in the mortality, length of ICU stay, ventilator-free days, or incidence of AKI in the patients. Rajbanshi LK, Bajracharya A, Arjyal B, Devkota D. Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study. Indian J Crit Care Med 2023;27(9):669-674.

Exploring novel genetic and hematological predictors of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Introduction: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). To select patients who would benefit the most from nCRT, there is a need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of post-nCRT response. Materials and methods: In silico analysis of published transcriptomics datasets was conducted to identify candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC were prospectively included between June 2020-January 2022. Patients were assessed for tumor response in week 8 post-nCRT with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested ("watch and wait" approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. Results: Responders group comprised 35 patients (46.6%) and NR group 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p < 0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p < 0.01). According to MRI findings, non-responders more often presented with extramural vascular invasion (p < 0.05). Conclusion: Based on logistic regression model, factors associated with favorable response to nCRT were tumor morphology and hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.

Tumor-derived exosomes RNA expression profiling identifies the prognosis, immune characteristics, and treatment in HR+/HER2-breast cancer.

Exosomes play crucial roles in intercellular communication and are involved in the onset and progression of various types of cancers, including breast cancer. However, the RNA composition of breast cancer-derived exosomes has not been comprehensively explored. We conducted microarray assays on exosomes isolated from breast cancer and healthy breast epithelial cells from three patients with hormone receptor (HR) +/ human epidermal growth factor receptor (HER2) - breast cancer and identified 817 differentially expressed genes (DEGs). Among these, 315 upregulated tumor-derived exosome genes (UTEGs) were used to classify HR+/HER2- breast cancers into two categories, revealing a difference in survival rates between the groups. We developed and validated a novel prognostic exosome score (ES) model consisting of four UTEGs that provides a refined prognosis prediction in HR+/HER2-breast cancer. ES reflects various immune-related features, including somatic variation, immunogenicity, and tumor immune infiltrate composition. Our findings indicate a considerable positive correlation between the ES and drug sensitivity values for vincristine, paclitaxel, and docetaxel. However, ES was remarkably higher in the endocrine therapy non-responder group than in the responder group. Immunohistochemistry confirmed the remarkable expression of the four model genes in tumor tissues, and their expression in MCF-7 cell exosomes was higher than that in MCF10A cells, as verified via qPCR. In summary, tumor-derived exosome genes provide novel insights into the subtyping, prognosis, and treatment of HR+/HER2-breast cancer.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics

BackgroundPsoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown.MethodWe assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay.ResultsWe first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets.ConclusionIn this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.