Responder Group Research Articles

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.

Association of Glutathione S-Transferase P1 (GSTP1) Gene Polymorphism with the Response to Platinum Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Abstract Background Lung cancer is one of the most commonly diagnosed cancers and despite therapeutic advances, mortality remains high. Platinum based chemotherapy remains the mainstay of adjuvant or first line chemotherapy in non small cell lung cancer (NSCLC) treatment, pathophysiological features along with genetic background significantly influence therapeutic efficacy of platinum-based chemotherapy. GSTP1 gene is a member of the cytosolic superfamily of glutathione-S-transferases, which is responsible for phase II detoxification enzymes that convert various reactive metabolites to more water-soluble and less harmful forms by conjugating them with glutathione. The genetic polymorphism GSTP1 rs1695 is associated with decreased substrate specific catalytic activity and the reduced enzyme activity which may reduces platinum detoxification, thus promoting better response rates to platinum-based chemotherapy. Aim of the Work In the present study was aimed to investigate the association of GSTP1 gene polymorphism with the response to platinum based chemotherapy in patients with NSCLC in order to prevent the non necessary exposure to the toxic effect of chemotherapy. Patients and Methods The study was a retrospective cross sectional study conducted on 50 NSCLC patients who were recruited from the Oncology clinic in Ain Shams University Hospitals, twenty of them were responders to platinum based chemotherapy and the other 30 were not responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the GSTP1 rs1695 (A/G) polymorphism by real-time PCR was done for both the responders and the non responders group. Results There was no statistically significant difference between the responders’ and non responders’ groups regarding the genotypic distribution (p &amp;gt; 0.05). However, the G allele was significantly higher in the responders’ group compared to the non responders’ group with p value &amp;lt; 0.05. Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies of the GSTP1 rs 1695 among the responders and the non responders group, but despite that it showed that the A allele was significantly higher in the non responders’ group compared to the responders’ group. However, the G allele was significantly higher in the responders’ group compared to the non responders’ group. Further studies with higher sample size are needed to clarify the association.

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Background: Previous studies have pointed out the disproportionate action of clopidogrel in inhibiting platelet aggregation due to smoking more than ten cigarettes per a day. This study was designed to examine whether smoking enhances clopidogrel responsiveness in patients who are clinically diagnosed with coronary artery disease (CAD), following percutaneous coronary intervention (PCI). Methods: A total of 324 IHD participants were enrolled in a case-control study. Platelet function test was performed to all participants two hours before PCI procedure to measure clopidogrel response. Participants were then categorized into a non-responder group (case group n = 111) and responder group (control group n = 213). Each group was subdivided into a smoker group and a non-smoker group. All participants received clopidogrel loading dose equivalent to 600 mg and scheduled for elective PCI. Participants’ age, gender, family history of chronic illnesses was recorded in this study. Results: Smoking participants displayed a significant higher level of hemoglobin as compared to the non-smoking participants among the responder and the non-responder study groups (14.6±0.55 vs. 13.12±0.38, P &lt; 0.029; 14.3±0.31 versus 12.96±0.39, P &lt; 0.033) but lower AUC level (17±9 vs. 45±6, P &lt; 0.005; 62±3 vs. 95±7, P &lt; 0.008). Additionally, smoking intensity enhanced clopidogrel responsiveness by odd’s ratio 0.4213 at 95% C.I. (0.259 - 0.684), P &lt; 0.0002. Conclusions: Current smokers had a good response to clopidogrel therapy which exerted a beneficial effect when undergoing PCI as compared to non-smokers. The marked difference in AUC between smokers and non-smokers could be related to the variance in hemoglobin level. The smokers’ paradox needs further justification to confirm this concept.

Effects of mandibular advancement devices on upper airway dimensions in obstructive sleep apnea: responders versus non-responders

Study objectivesTo compare the effects of mandibular advancement device (MAD) therapy on upper airway dimensions between responders and non-responders with mild to moderate obstructive sleep apnea (OSA).MethodsThirty-one participants (21 men and 10 women) with a mean ± SD apnea-hypopnea index (AHI) of 16.6 ± 6.7 events/h, and aged 48.5 ± 13.9 years, were included in this study. Polysomnographic recordings and cone beam computed tomography (CBCT) scans in supine position were performed for every participant at baseline and at 3-month follow-up with their MAD in situ. Responders were defined as having ≥ 50% reduction in baseline AHI with a residual AHI < 10 events/h. The primary outcome variable was the minimal cross-sectional area of the upper airway (CSAmin).ResultsNo significant differences were found between responders (n = 15) and non-responders (n = 16) in age, gender distribution, body mass index, and neck circumference (P = 0.06–0.93), nor in AHI and CSAmin (P = 0.40 and 0.65, respectively) at baseline. The changes of the CSAmin with MAD in situ in the responder group were not significantly different compared to those in the non-responder group (P = 0.06).ConclusionWithin the limitations of this study, we conclude that the changes of the upper airway dimensions induced by MADs are not significantly different between responders and non-responders with mild to moderate OSA.Trial registrationClinicalTrials.gov Identifier: NCT02724865. https://clinicaltrials.gov/ct2/show/NCT02724865

Experience with agomelatine therapy for non-psychotic depression with a single and recurrent course

Therapy of depression is a current problem in psychiatry. Agomelatine is not inferior to other modern drugs in terms of antidepressant efficacy (response and remission rates) and is characterized by the best tolerability.Objective: to evaluate the efficacy and safety of agomelatine in the treatment of nonpsychotic depression with a single and recurrent course.Material and methods. Patients (n=37) with a current depressive episode (DE; F32 according to ICD-10), mean age 41.2±2.07 years, were studied. Clinical psychopathological and psychometric methods were used in the study (Hamilton Hospital Depression Scale – HAMD-17; Spielberger–Khanin Anxiety Self-Assessment Scale, Sheehan Anxiety Scale, Clinical Global Impression Scale – CGI-I). A single DE was diagnosed in 62.2% of patients, and recurrent depressive disorder in 37.8%. Stress-related onset of current DE was found in 56.8% of cases, autochthonous in 43.2%.Results. 94.6% of patients were responders, including 68.6% who went into remission. A statistically significant decrease in scores on the HAMD-17 scale was noted in the remission group from the 7th day of agomelatine therapy (p&lt;0.05), in the responder group – from the 14th day of therapy (p&lt;0.05). According to the Sheehan scale, a statistically significant decrease in scores was noted at the end of the first week of therapy (p&lt;0.05), according to the Spielberger–Khanin scale – in the second week (p&lt;0.05) in all patients. According to the CGI-I scale, the condition at the end of therapy improved in 57.1% of patients, significantly in 42.9%. Clinical predictors of therapeutic response in patients with remission included significantly higher frequency of a single DE (p&lt;0.02), moderate severity of current depression (p&lt;0.02), dizziness among autonomic disorders (p&lt;0.01), a significantly lower representation of the melancholic type of depression (p&lt;0.05), a symptom of a gloomy and pessimistic vision of the future (p&lt;0.05), sleep disturbances (p&lt;0.04), a factor of personal significance in the form of a threat in patients with stress-provoked onset of the current DE (p&lt;0.05).Adverse events occurred in the first week of treatment with agomelatine in 14.3% of cases (nausea – 8.6%, headache and dizziness – 2.9% each), they were mild and did not require discontinuation of the drug. Two patients taking agomelatine at a dose of 50 mg discontinued the study: in one case persisted social phobia, increased fatigue, motor retardation, and persistent modern insomnia; in the other case – a pronounced senestoalgic syndrome with cerebral localization.Conclusion. Agomelatine therapy has been shown to be highly effective and well tolerated in nonpsychotic depression.

Delhi Model: A New Tool for Predicting Response to Terlipressin in Hepatorenal Syndrome—Acute Kidney Injury

International club of ascites (ICA) has introduced revised criteria for hepatorenal syndrome-acute kidney injury (HRS-AKI) with an aim to improve the response rate to treatment. We lack prospective trials to assess its positive impact on the response rate and factors influencing response rate. Thus, we conducted this study with the primary aim of identifying independent factors that predict treatment response to terlipressin. We prospectively included patients of HRS-AKI as per the revised ICA criteria. All were treated with terlipressin and albumin according to the defined protocol and were followed for 90 days, death or liver transplantation. Baseline parameters, as well as delta serum creatinine (sCr) at day 4 (DCD4), were investigated as predictive factors influencing response to terlipressin (primary endpoint). Secondary endpoints were the overall response rate to terlipressin, response in various subgroups of acute-on-chronic liver failure (ACLF) patients, need for readmission, and 90 days survival. The study included 114 patients with a median age of 52 years (83% males). 70 (61%) patients responded to terlipressin. Response rate among ACLF1, ACLF2, and ACLF3 were 62%, 48%, and 35%, respectively. On multivariate analysis, baseline creatinine (odds ratio [OR] 7.889, 95% confidence interval [CI] 3.335, 18.664), Child Turcotte Pugh (CTP) score (OR 1.470, 95% CI 1.026, 2.106), and the DCD4 (OR 0.048, 95% CI 0.015, 0.158) were independently predicting response. We also created a Delhi Model (DM) with an excellent predictive ability for response prediction at day 4 with an AUROC of 0.940 (95% CI 0.897, 0.982). Among responder group, 50% of patients required readmission within three months.The 90-days survival among responder and non-responder groups were 68.5% and 9% (Pvalue<0.01), respectively. Baseline creatinine, CTP score, and DCD4 independently predict response to terlipressin in HRS-AKI. The DM may guide terlipressin treatment in HRS-AKI but need further validation.

The relationship between inadequate response to physical therapy and central sensitization in patients with knee osteoarthritis: A prospective cohort study.

Objectives: This study aims to investigate the relationship between physical therapy response and the presence of central sensitization (CS) in patients with painful knee osteoarthritis (OA). Patients and methods: Between May 2019 and March 2020, a total of 84 patients with knee OA (12 males, 72 females; mean age: 60.7±7.7 years; range 50 to 74 years) and 30 age and sex-matched controls (6 males, 24 females; mean age: 59.2±8.9 years; range 50 to 75 years) were included in this study. Knee pain and functional status were evaluated by Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Structural damage was assessed by knee radiography. The Central Sensitization Inventory (CSI), Beck Depression Inventory (BDI), Insomnia Severity Index (ISI), Pain Catastrophizing Scale (PCS), and PainDETECT Questionnaire (PDQ) were applied at baseline. Pain pressure thresholds (PPTs) of the patients were measured and compared with the control group. All patients underwent a total of 15 sessions of physical therapy program for five sessions/weekly. After treatment, the patients were divided into two groups as responders and non-responders according to the Osteoarthritis Research Society International (OARSI) criteria. Results: The CSI score of the patients in non-responder group was significantly higher compared to the responder group (p=0.004). Using a cut-off value of ≥40, the proportion of patients with CSI scores of ≥40 was significantly lower in the responder group compared to non-responder group (p=0.021). The PPT measurement values were significantly lower in the non-responder group compared to the responder and control groups (p <0.01). There was a significant difference in the frequency of hyperalgesia between the groups (p=0.021). Central sensitization and depression were the most significant predictors of non-response to physical therapy (p=0.045 and p=0.024, respectively). Conclusion: Our study results suggest the presence of CS and depression may result in an inadequate response to physical therapy in patients with knee OA. Clinicians should consider the findings of CS and depression in treatment planning.

The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs

Gastric cancer (GC) is the fifth most frequent malignancy and the fourth leading cause of worldwide cancer-related death. Despite the usage of multimodal perioperative chemotherapy (pCT), GC progressively gains chemoresistance, thereby, the identification of suitable targets to overcome drug resistance is fundamental. Amongst the potential biomarkers, carbonic anhydrase IX (CAIX) - associated with a poor prognosis of several solid cancers - has gained the most attention. In a cohort of GC patients who received perioperative FLOT (i.e., Leucovorin, 5-Fluouracil, Docetaxel, and Oxaliplatin) or FOLFOX (i.e., Leucovorin, 5-Fluouracil, and Oxaliplatin), non-responder patients showed an increased expression of tumor CAIX compared to responder group. Moreover, GC cell lines induced to be resistant to 5-Fluouracil, Paclitaxel, Cisplatin, or the combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel, overexpressed CAIX compared to the control. Accordingly, CAIX-high-expressing GC cells showed increased therapy resistance compared to low-expressing cells. Notably, SLC0111 significantly improved the therapy response of both wild-type and resistant GC cells.Overall, these data suggest a correlation between CAIX and GC drug resistance highlighting the potential of SLC-0111 in re-sensitizing GC cells to pCT.