Clinical Efficacy In Patients Research Articles

Population-pharmacokinetic/pharmacodynamic model of atractylodes lancea (Thunb.) DC. administration in patients with advanced-stage intrahepatic cholangiocarcinoma: a dosage prediction

BackgroundA recent phase 2A clinical study of Atractylodes lancea (Thunb.) DC. (AL) in patients with advanced-stage intrahepatic cholangiocarcinoma (iCCA) demonstrated significant reduction of the risk of tumor progression and mortality with a dose ranging from 1,000 to 2,000 mg. The present study aimed to determine the potential dosage regimen of AL for further phase 2B clinical study.MethodsPlasma-concentration time profiles of total AL bioactivity and clinical efficacy in patients with advanced-stage iCCA were obtained from Phase 2 A study. The population pharmacokinetic (pop-PK) model was developed. The pop-PK model and Monte-Carlo (MC) simulation, in conjunction with maximum concentration of AL (Cmax) as a cut-off criterion, was performed and validated with clinical data. The optimal model was used to simulate further dosage regimens and clinical efficacy of AL.ResultsThe pop-PK properties of total AL bioactivity were best described by a compartmental model with zero-order absorption (without delay) and linear clearance. None of the investigated covariates improved model accuracy.The developed pop-PK with MC simulations following once-daily dosing of 1,000 mg and 2,000 mg adequately predicted the clinical efficacy (tumor progression and mortality). The once-daily dose of 2,500 mg is recommended for further phase 2B clinical study due to its relatively high efficacy on tumor progression inhibition (73%) and mortality rate reduction (71%) without excessive number of the administered capsules (23 capsules) and low risk of toxicities (<5%).ConclusionsThe applied pop-PK model with MC simulation, along with the appropriate cut-off pharmacokinetic parameters, can be used as a potential tool for supporting dosage prediction and selection for clinical studies, and thus reducing the rate of drug development failures.Trial registrationwww.thaiclinicaltrials.org, WHO ICTRP search, TCTR20210129007, Registed 29 January 2021.

Mechanical Thrombectomy for Treatment of Acute Cerebral Infarction due to Distal Medium Vessel Occlusions: A Retrospective Cohort Study.

Mechanical thrombectomy (MT) is standard of care for acute cerebral infarction (ACI) due to large vessel occlusions. However, its clinical efficacy in patients with ACI due to distal medium vessel occlusions (DMVOs) remains unclear. This study evaluates the efficacy and safety of MT in patients with ACI due to DMVOs. Totally, 306 patients with ACI at a very early stage were assigned into DMVOs-MT, M1-MT, and DMVOs-intravenous thrombolysis (IVT) groups. These groups were compared regarding baseline data, recanalization rate, location of vessel occlusions, number of thrombectomy, first-pass recanalization, mRS scores, NIHSS scores, 90-day mRS scores, incidence of adverse events, and mortality. Risk factors for poor prognosis of patients with DMVOs following MT were analyzed. DMVOs-MT and M1-MT groups showed comparable first-pass recanalization rates, recanalization rates, and NIHSS score reduction ratios, with marked differences in location of vessel occlusions. Versus DMVOs-IVT, DMVOs-MT had increased differences between pre- and post-treatment NIHSS scores and between pre-treatment NIHSS scores and NIHSS scores at discharge and elevated NIHSS reduction ratios. The poor prognosis rate of DMVOs-MT group was insignificantly different from that of M1-MT group but lower than that of DMVOs-IVT group. Adverse events and mortality incidences were comparable among the three groups. Diabetes, first-pass recanalization, and pre-treatment NIHSS scores were independent risk factors for poor prognosis in DMVO patients after MT. MT is as effective and safe in patients with DMVOs as in patients with M1 occlusions. In patients with DMVOs, MT has higher efficacy and safety than IVT.

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study.

Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH)2-vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

Enhanced bone cement distribution in percutaneous vertebroplasty using a curved guide wire: a propensity score matching analysis

BackgroundOsteoporotic vertebral compression fractures (OVCF) severely affect the quality of life in the aged population. Percutaneous vertebroplasty (PVP) alleviates pain and stabilizes vertebrae, but suboptimal bone cement distribution can cause complications. Hence, this study aimed to clarify whether a new technique for PVP, using a curved guide wire, enhances the distribution of bone cement and improves clinical outcomes in patients with OVCF.MethodsPatients with single-segment OVCF underwent PVP or curved guide wire percutaneous vertebroplasty (C-PVP). Propensity score matching (PSM) was employed to balanced the baseline characteristics. The primary outcomes were the visual analog scale (VAS) and Oswestry disability index (ODI) scores. The secondary outcomes included assessments of bone cement distribution, bone cement injection volume, radiological parameters, and general clinical results. Additionally, Complications and adverse events were documented.ResultsAfter PSM analysis, each group comprised 54 patients, which significantly reduced baseline differences. The C-PVP group showed better clinical outcomes compared to the traditional PVP group. One month after surgery, the C-PVP group had significantly lower VAS and ODI scores (p < 0.001). These improvements persisted at six months and the final follow-up. Additionally, bone cement distribution scores were better (p < 0.001), injection volume was higher (p = 0.03), leakage was less frequent (p = 0.02), and adjacent vertebral fractures occurred less frequently (p = 0.04) in the C-PVP group. Radiological parameters and overall clinical outcomes revealed no significant differences between the two groups.ConclusionThe use of curved guide wire in PVP significantly improves bone cement distribution and injection volume, resulting in better clinical efficacy in patients with OVCF.

CD27-Armored BCMA CAR T Cell Therapy (CBG-002) for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial.

B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term response has yet to be established. We investigated the feasibility of CBG-002, an CD27-armored BCMA CAR T therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events(AEs). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), while no patients experienced grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%) and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8-21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T therapy, demonstrated safety and clinical efficacy in patients with RRMM.

Effectiveness and efficiency of aquatic therapy on independence in activities of daily living and mobility in post-acute spinal cord injury: A matched case-control study.

Aquatic therapy (AT), though potentially effective, lacks studies on clinical efficacy in patients with spinal cord injury (SCI). A recent study analyzing interviews with rehabilitation professionals on its clinical application reported that the scarce evidence of AT benefits was one of the actual barriers to its successful integration into clinical practice. We seek to provide evidence by comparing independence in activities of daily living (ADLs) and functional ambulation capacity in patients following rehabilitation which included AT and matched controls who followed rehabilitation without AT (non-AT). Functional Independence Measure (FIM), Spinal Cord Independence Measure (SCIM-III), Walking Index for Spinal Cord Injury (WISCI-II) and its minimal clinically important difference (WISCI-II/MCID) were assessed. The AT group followed the Halliwick concept. We performed nonparametric nearest-neighbor k:1 matching for age, time since injury to admission, FIM at admission, level of injury (paraplegia/tetraplegia), completeness and cause of injury (traumatic, non-traumatic). The rehabilitation program comprised four daily hours of intensive treatment from the multidisciplinary team. Both groups received the same total number of rehabilitation hours at the same specialized clinical center and were admitted to follow inpatient rehabilitation within 2months after injury. A total of 29 patients with SCI who followed AT (admitted between 2017 and 2023) were compared to historical matches selected from 551 inpatients with SCI (admitted between 2014 and 2023). For k=1, the groups showed no significant differences in gains, efficiency, or effectiveness in FIM and SCIM-III; significant differences were observed in WISCI-II gain (p=0.018) and WISCI-II efficiency (p=0.046) in favor of the AT group; the proportion of patients achieving WISCI-II/MCID was significantly higher for the AT group (75.9% vs. 48.3%) (p=0.030). These results were confirmed for k=2. The AT group performed similarly in independence for performing ADLs and significantly better in ambulation than the matched historical controls.

Validation of a genome-based model for adjusting radiotherapy dose (GARD) in patients with locally advanced rectal cancer

Neoadjuvant radiotherapy is the standard care of locally advanced rectal cancer. Although a majority of patients received the same dose, the curative efficacy varies among individuals. In recent years, cancer treatment has entered the era of precise medical care, and how to identify patients for proper treatment by molecular signature is an important path of individualized therapy. This study aimed to establish and validate a genome-based model for adjusting radiation dose (GARD) for Chinese locally advanced rectal cancer through gene expression microarrays, and to evaluate the response of the GARD model in predicting the efficacy of neoadjuvant radiotherapy. Fresh-frozen primary tumor from 64 patients with locally advanced rectal cancer undergoing neoadjuvant radiotherapy from 2015 to 2018 were included. The gene expression profile was analyzed using Affymetrix 3000Dx gene-chip scanner. The radiosensitivity index (RSI) and GARD were calculated using the pGRT™ algorithm. Neoadjuvant rectal cancer score (NAR) was selected as efficacy evaluation indicators. Patients were divided into high and low NAR scoring groups, and two-sample t-test was used to analyze the differences in GARD values between different NAR subgroups. ROC curves were used to calculate the cut-off values and the area under the curve (AUC) for assessing the validity of the GARD models. The personalized radiation dose ( pGRT dose )can be computed using the formula nd = GARD / (α + βd). Among patients, 1.5% T2, 46.3% T3, and 52.2% T4. Wherein pCR (n = 10; 15.6%) and no pCR (n = 54; 84.4%). The median NAR is 8.43 (rang from 0 to 50.34, IQR 3.75–14.98). NAR > 8.43 (n = 27; 42.2%) and NAR ≤ 8.43 (n = 37; 57.8%), suggesting that there are significant individual differences in clinical efficacy of patients with similar tumor stages and under the same treatment conditions. The median RSI is 0.48 (rang from 0.22 to 0.92, IQR 0.41–0.55). Median GARD was 18.40 rang from (rang from 2.26 to 37.52, IQR 14.94–22.28) within tumor tissue, suggesting individual differences in the efficacy of radiation therapy. The RSI value was significantly lower in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (0.44 vs. 0.54, p = 0.0003). The GARD value was significantly higher in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (21.01 vs. 15.88, p = 0.0004). Using the Receiver Operating Characteristic (ROC) curve analysis, a GARD threshold of 17 was identified as optimal, covering 37.5% of the 64-patient sample, with an area under the curve (AUC) of 0.75. In the external validation cohort, the high GARD score group demonstrated superior DFS compared to the low GARD score group(p < 0.001). Only 17% of patients had pGRT dose within the guideline recommended dose (45–50 Gy). The differences in NAR values among LARC patients receiving standard neoadjuvant radiotherapy suggest significant individual differences in clinical outcomes among patients with similar tumor stage and the same treatment conditions. Patients with a GARD value exceeding 17 exhibit a more favorable prognosis. Our results suggest that the gene expression-based pGRT™ algorithm has good efficacy prediction performance in preoperative concurrent radiotherapy for locally advanced rectal cancer, suggesting the potential clinical application of this method to guide the designation of individualized radiotherapy doses.

Bixie Fenqing decoction in the treatment of chronic prostatitis: A systematic review and meta-analysis.

Traditional Chinese medicine (TCM) posits that chronic prostatitis is associated with the accumulation of damp-heat pathogenic factors in the lower jiao. The Bixie Fenqing decoction (BFD) eliminates damp-heat pathogenic factors in the body, thereby alleviating inflammation and improving symptoms. Databases such as CNKI, WanFang, VIP, CBM, ClinicalKey, PubMed, Embase, and the Cochrane Library were searched. The search time ranged from the establishment of the database until March 30, 2024. RCTs that used BFD for chronic prostatitis were screened. The methodological quality of the studies was evaluated using the Cochrane Scoring System. Meta-analysis of outcome indicators was performed using RevMan 5.4 software, and Egger analysis of publication bias for the primary outcome indicators was conducted using Stata 16 software. This analysis included 1104 patients. Meta-analysis showed that BFD significantly improved clinical efficacy in patients with chronic prostatitis, with a total effective rate (RR = 1.20, 95% CI: 1.13 to 1.26, P < .00001) and cure rate (RR = 1.52, 95% CI: 1.24 to 1.86, P < .00001). It significantly reduced the NIH-CPSI (National Institutes of Health-Chronic Prostatitis Symptom Index) scores, levels of inflammatory factors, white blood cell counts, and TCM syndrome scores in patients with chronic prostatitis. Specifically, the NIH-CPSI total scores (MD = -4.41, 95% CI: -5.27 to -3.55, P < .00001), NIH-CPSI pain scores (MD = -2.08, 95% CI: -2.93 to -1.23, P < .00001), NIH-CPSI urinary symptom scores (MD = -1.13, 95% CI: -1.69 to -0.57, P < .0001), NIH-CPSI quality of life scores (MD = -1.25, 95% CI: -1.76 to -0.75, P < .00001), levels of inflammatory factors TNF-α (MD = -11.18, 95% CI: -13.84 to -8.53, P < .00001) and IL-10 (MD = -20.60, 95% CI: -26.82 to -14.37, P < .00001) in prostatic fluid, white blood cell counts in prostatic fluid (MD = -2.91, 95% CI: -5.46 to -0.36, P = .03), and TCM syndrome scores (MD = -7.01, 95% CI: -8.13 to -5.90, P < .00001) were all significantly improved. BFD has a definite effect on the treatment of chronic prostatitis.

The effect of different surgical methods and timing of surgery on the clinical efficacy in patients with hypertensive intracerebral hemorrhage in basal ganglia

Objective: To explore the effect of different surgical methods and timing on the clinical efficacy of patients with hypertensive intracerebral hemorrhage (HICH) in basal ganglia. Methods: A total of 200 patients with HICH in basal ganglia were divided into traditional craniotomy (TC) group, small bone window craniotomy (SBWC) group and neuroendoscopic minimally invasive surgery (NMIS) group. And they were also divided into ultra-early group, early group and delayed group, depending on the timing of surgery. The operation time, intraoperative blood loss, hematoma clearance rate and incidence of complications among different groups were recorded and analyzed. The National Institutes of Health Stroke Scale (NIHSS) and Glasgow outcome scale (GOS) were used to evaluate the neurological function and prognosis. Results: The NMIS group was superior to the TC group and SBWC group in terms of operation time, and intraoperative blood loss, hematoma clearance rate, complication 6-months NIHSS scores and the GOS scores (P&lt;0.05). There was no significant differences in operation time, intraoperative blood loss, hematoma clearance rate and complication among the ultra-early group, the early group and the delayed group (P&gt;0.05). While the ultra-early group was superior to the early group and the delayed group in terms of 6-month NIHSS scores and the GOS scores. Conclusion: NMIS could reduce the operation time, intraoperative blood loss, and complications, and improve the hematoma clearance rate and prognosis of patients with HICH in basal ganglia. And the ultra-early surgical treatment improved the prognosis of patients with IHCH in basal ganglia.

Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study

BackgroundTreatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.MethodsCancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed.ResultsFifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8–26.9) months.ConclusionTofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast.

Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

Optimization and clinical evaluation of hyaluronic acid proniosome loaded in-situ gel for the management of recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is a frequent unpleasant oral condition that causes ulcers. Hyaluronic acid (HY) is an inherent polymer owing antioxidant, anti-inflammatory, and anti-bacterial patterns. D-optimal response surface design was used to investigate the impact of surfactant type (Span 80 or Brij®35) and the concentration of HY (0.5 % or 1), on three selected dependent variables: zeta potential (ζ, ZP, R1), particle size (PS, R2), and entrapment efficiency (%EE, R3). The optimized HYPN was then loaded in thermosensitive in-situ gel. The clinical efficacy in patients with RAS was evaluated by measuring the improvement in pain levels (using the Visual Analog Scale), reduction in ulcer size, enhancement in quality of life (measured by OHIP-14 scores), and analysis of pro-inflammatory Tumor Necrosis Factor Alpha (TNF-α) and total antioxidant capacity (TAC) in saliva samples. The optimized formula obtained a mucoadhesive strength of 26 ± 1.76 N/m2. A burst release of 38 ± 1.56 % after 2 h was obtained followed by 80 ± 2.21 % till 24 h, with a transbuccal flux (Jss) 425 ± 7.9 μg/h.cm2. Clinically, a significant difference (P ≤ 0.001) in pain scores, ulcer diameter, OHIP-14 scores, TAC, and TNF-α between the in-situ gel containing HYPN and the placebo gel was found. The mean values for the number of recurrences at 6 months follow-up were 2.55 ± 1.13 and 4.63 ± 1.75, respectively, before and after treatment. The thermosensitive mucoadhesive in-situ gel seems to be a promising therapeutic choice for RAS treatment.

Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure.

Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

Effects of the combination of red yeast rice-containing commercial Chinese polyherbal preparation with statins for dyslipidemia: a systematic review and meta-analysis.

Significant challenges are associated with the pharmacological management of dyslipidemia, an important risk factor for cardiovascular disease. Limited reliable evidence exists regarding the efficacy of red yeast rice (RYR)-containing commercial Chinese polyherbal preparation (CCPP), despite their widespread use in China. We aimed to investigate the efficacy of RYR-containing CCPPs combined with statins in treating dyslipidemia. Eight databases were searched for relevant randomized controlled trials (RCTs) from database inception date to November 2023. Outcome measures, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), clinical efficacy, and adverse reactions, were assessed. The Cochrane Handbook for Systematic Reviews of Interventions was used for quality evaluation, and the meta-analysis was conducted using RevMan 5.3 and Stata 15.1. Thirty-three studies involving 4,098 participants were included. The combination of RYR-containing CCPP, such as Xuezhikang (XZK), Zhibitai (ZBTAI), or Zhibituo (ZBTUO) with statins had a significant effect on the increase in clinical efficacy [RR:1.16, 95%CI (1.13, 1.19), p < 0.00001]. In addition, they also improved blood lipid profile parameters by increasing HDL-C levels [MD:0.21, 95%CI(0.17, 0.25), p < 0.00001], and decreasing TC [MD: 0.60, 95%CI(-0.76, -0.45), p < 0.00001], TG [MD: 0.33, 95%CI(-0.39, -0.26), p < 0.00001] and LDL-C levels [MD: 0.45, 95%CI(-0.54, -0.36), p < 0.00001]. No significant adverse reactions was observed in the RYR-containing CCPPs. Notably, ZBTAI and XZK significantly reduced the incidence of gastrointestinal disturbances and muscular adverse reactions. However, subgroup analyses suggested that the type of CCPPs, dose, and treatment duration might affect the efficacy of RYR-containing CCPPs. RYR-containing CCPPs combined with statins appears to improve lipid profiles and clinical efficacy in patients with dyslipidemia. However, due to the poor quality of the included studies, and some studied showing negative findings was unpublished. The results should be interpreted with caution until further confirmation by well-designed RCTs. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=487402, identifier CRD42023487402.

Mitigating infection risks: The promise and challenge of bispecific antibodies in haematological malignancies.

Bispecific antibodies have shown significant clinical efficacy in patients with relapsed/refractory B-cell non-Hodgkin lymphomas and multiple myeloma, expanding treatment options for these patients. While these advancements are promising, it is important to be aware of associated side effects, such as cytokine release syndrome, neutropenia and infections. Gonugunta etal. provide valuable insights into the infection risks linked to the use of bispecific antibodies in haematological malignancies, drawing on both clinical trial data and real-world experiences. Commentary on: Gonugunta etal. Risk of infections with bispecific antibodies in B-cell non-Hodgkin lymphomas and multiple myeloma-The current state. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19633.

Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke.

Eighty percent of stroke patients develop upper limb dysfunction, especially hand dysfunction, which has a very slow recovery, resulting in economic burden to families and society. To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke. Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group, each with 50 cases. The control group underwent head acupuncture plus routine upper limb rehabilitation training (acupuncture therapy). In addition to acupuncture and rehabilitation, the observation group underwent upper limb task-oriented training (30 min). Each group underwent treatment 5 d/wk for 4 wk. Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Wolf Motor Function Rating Scale (WMFT), modified Barthel Index (MBI), and Canadian Occupational Performance Measure (COPM). Quality of life was evaluated using the Short-Form 36-Item Health Survey (SF-36). Clinical efficacy of the interventions was also evaluated. Before intervention, no significant differences were observed in the FMA-UE, MBI, and WMFT scores between the two groups (P > 0.05). After intervention, the FMA-UE, WMFT, MBI, COPM-Functional Mobility and Satisfaction, and SF-36 scores increased in both groups (P < 0.05), with even higher scores in the observation group (P < 0.05). The observation group also obtained a higher total effective rate than the control group (P < 0.05). Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility, quality of life, and clinical efficacy in patients with early stroke.

Analysis of the efficacy of hyperbaric oxygen therapy for disorders of consciousness: A retrospective cohort study.

To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment. A retrospective study was carried out on patients with disorders of consciousness (DOC) receiving HBO treatment from January to January 2022 in the Second Department of Rehabilitation Medicine of the Second Hospital of Hebei Medical University, China. HBO therapy improved the Glasgow Coma Scale (GCS) and Chinese Nanjing Persistent Vegetative State Scale (CNPVSS), as well as the clinical efficacy in patients with DOC. The comparison of GCS and CNPVSS scores in patients with DOC before and after HBO treatment was all statistically significant, with 325 patients (67.1%) showing effective results and 159 patients (32.9%) having unchanged outcomes. Univariate analysis indicated that there were statistically significant differences in age, HBO intervention time, HBO treatment times, pre-treatment GCS score, and etiology and underlying diseases between the good and poor prognoses groups. Multivariate regression analysis showed that HBO intervention time ≤7 days, HBO treatment ＞ times, high GCS score before HBO treatment, and brain trauma were independent influencing factors in achieving a good prognosis for patients with DOC. Low pre-treatment GCS scores were an independent risk factor for a poor prognosis in patients with brain trauma while being male, late HBO intervention time, fewer HBO treatment times, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after a stroke. Being ≥50 years of age, late HBO intervention time, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after hypoxic-ischaemic encephalopathy. HBO therapy can improve the GCS, CNPVSS scores and clinical efficacy in patients with DOC, and the timing of HBO intervention ≤7 days, times of HBO treatment, high pre-treatment GCS score, and brain trauma were the independent influencing factors of good prognosis in patients with DOC.

Unlocking the Therapeutic Symphony: A Systematic Review Exploring the Role of Levosimendan in the Management of Heart Failure.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emergedas a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminalpro-B-typenatriuretic peptide (NT-ProBNP) innon-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

Serabelisib, sapanisertib (PIKTOR) and paclitaxel: A combinatorial approach to improve PI3K/mTOR/AKT pathway inhibition and treatment response in solid tumors.

e15134 Background: Despite high mutation rates in genes of the PI3K/mTOR/AKT pathway in cancer, therapeutic strategies to inhibit this pathway featuring single targeted therapies have achieved limited clinical success. An alternate approach inhibiting multiple parts of the pathway simultaneously demonstrated improved activity (Starks et al, GynOnc 2022). The Phase 1 study combined the targeted PI3K-alpha and mTOR inhibitors serabelisib and sapanisertib (PIKTOR) with paclitaxel showing reasonable safety and promising clinical efficacy in patients with advanced endometrial, breast and ovarian tumors that had progressed on prior taxane. The ORR was 47% including 3 complete responses, with a PFS of 11 months in 15 evaluable subjects (NCT03154294). We sought to better understand the mechanistic basis for the efficacy of this triplet drug combination in models of endometrial and breast cancer to support successful clinical development of this regimen. Methods: Signaling activity in PI3K/mTOR/AKT pathway was probed by western blot for phospho-S6 and phospho-4EBP1 in human endometrial and breast cancer cell lines with PI3K/mTOR/AKT mutations. Single and combinatorial dose-response curves were established for serabelisib, sapanisertib and paclitaxel versus FDA-approved pathway inhibitors. Mechanisms of cytotoxicity and paclitaxel sensitization were probed with cell death assays. The impact of single and combined agents on tumor growth was assessed with in vivo xenograft studies. Results: In human endometrial and breast cancer cell lines, the combination of serabelisib and sapanisertib achieved markedly improved PI3K/mTOR/AKT pathway inhibition versus FDA-approved single agents. Serabelisib and sapanisertib increased the cytotoxicity of paclitaxel, supporting prior work that identifies PI3K/mTOR/AKT pathway activation as a key mediator of taxane resistance. Further, interrogation of a range of clinically relevant doses and scheduling led to an optimized regimen in which serabelisib and sapanisertib substantially improved the response to paclitaxel in vivo. Conclusions: Simultaneous inhibition of PI3K-alpha, mTORC1 and mTORC2 with PIKTOR offers potential for superior PI3K/mTOR/AKT pathway inhibition, suggesting that rational drug combination approaches may offer two important benefits: (1) more complete PI3K/mTOR/AKT pathway inhibition by targeting multiple signaling nodes, and (2) greater tumor cell cytotoxicity by sensitization to taxanes. These data, combined with the promising efficacy and safety signal from PIKTOR plus paclitaxel in a Phase 1 trial (NCT03154294), provide a compelling rationale for further clinical investigation. Future studies will focus on tumors known to have high rates of PI3K mutations including gynecologic tumors where there is a high unmet need.