Adjuvant Therapy Research Articles

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma

BackgroundSinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC.MethodsMedical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria.ResultsTotal 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506).ConclusionNAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Driving Abilities and Wearing-Off in Parkinson’s Disease: A Driving Simulation Study

Background/Objectives: Driving abilities require the synchronized activity of cerebral networks associated with sensorimotor integration, motricity, and executive functions. Drivers with Parkinson’s disease (DwP) have impaired driving ability, but little is known about the impact of “wearing-off” and therapies in addition to L-DOPA on driving capacities. This study aimed to (i) compare driving performance between DwP during different motor states and healthy controls and (ii) assess the impact of add-on therapies on driving abilities. Methods: DwP (n = 26) were enrolled as individuals experiencing wearing-off symptoms and treated (within 6 months before the enrollment) with add-on therapies to L-DOPA, including MAO inhibitors for DwP-A (n = 12) or opicapone for DwP-B (n = 14). Age- and sex-matched controls (CON, n = 12) were also enrolled. DwP received two driving assessments in a driving simulator during their “best-on” time and during their wearing-off time on different days. An anamnestic driving questionnaire was collected with the assistance of partners. A Virtual Driving Rating Scale (VDRS) was calculated, as well as learning curves (LCs) for driving items calculated in minutes. Results: DwP reported worse driving performance than CON at the driving questionnaire. In line with this, DwP showed worse VDRS (p < 0.01) and LC (p = 0.021) than CON. Lower VDRS was associated with wearing-off (p < 0.01), but DwP-B had better driving performance while in their “best-on” time (p = 0.037) and more items improving with LCs (7 vs. 3) than DwP-A. Conclusions: DwP demonstrated impaired driving compared to controls. Wearing-off symptoms can also affect driving ability, but therapies (opicapone more so than MAO inhibitors) may play a role in preserving specific driving skills, possibly through maintaining learning abilities.

Prognostic Significance of Angiogenesis in invasive ductal carcinoma

Background: Angiogenesis is essential for tumor growth and metastasis. Axillary lymphnode status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Microvessel density in invasive ductal carcinoma (measures of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. Objective: To correlate intratumoral and peritumoral angiogenic microvessel density with lymphnode metastasis in invasive ductal carcinoma. Material and Methods: It is a cross sectional observational study, carried out at the department of Pathology, BSMMU from January 2016 to December 2017. A total 48 mastectomy samples with axillary nodes from histologically confirmed invasive ductal carcinoma were included in this study. Weidner method was used for calculating micro vessels density. Sections examined to evaluate the density of angiogenic vessels by immuohistological stain with vWF expression in invasive breast cancer. Correlation between angiogenic vessels density with or without lymphnode metastasis was taken. Results: In this study angiogenic vessel count is more in the intratumoral area than peritumoural area. There was a positive significant correlation between lymphnode metastasis with micro vessel density in both peritumoral and intratumoral areas in Weidner method in vWF stain. J Shaheed Suhrawardy Med Coll 2023; 15(1): 59-65

Impact of semaglutide on weight and functional outcomes among obese heart failure patients: a propensity scores matching analysis

Background & objectivesObesity is a common comorbidity in heart failure, yet effective pharmacological options for weight loss in these patients are limited. Semaglutide, a glucagon-like peptide 1 receptor agonist, has shown promise for weight reduction in obese adults. This study aims to evaluate semaglutide’s impact on weight loss, functional status, and clinical outcomes in obese patients with heart failure.MethodsA retrospective analysis was conducted on all consecutive obese (BMI > 30 kg/m²) patients with heart failure at the University Hospital Bonn outpatient clinic from July 2019 to July 2022. Propensity score matching paired patients receiving semaglutide as an add-on therapy (SEMA) with those on medical therapy alone (Control).ResultsAmong 1,942 patients with heart failure screened, 26 matched pairs were identified. At one year, the SEMA group exhibited significant weight loss, with a mean BMI reduction of -2.91 kg/m² (95% CI: -4.27 to -1.55; p < 0.001), while the control group showed a non-significant mean change of -0.41 kg/m² (95% CI: -1.08 to 0.26; p = 0.22). The difference in BMI between the two groups was statistically significant (mean difference: 3.42 kg/m², 95% CI: 1.43 to 5.42; p = 0.001). Improvements by at least one NYHA class were observed in 65% of the SEMA group (p < 0.001) compared to 15% of the control group (p = 0.18). The SEMA group also showed a significant increase in 6-minute walk distance (6MWD), with a mean difference of 75 m between the groups at one year (95% CI: 0.53 to 150.02; p = 0.049). NT-proBNP levels significantly decreased in the SEMA group (p < 0.001) compared to the control group (p = 0.78), with a statistically significant difference in NT-proBNP between the groups (p = 0.048). Both improvements in 6MWD and reductions in NT-proBNP were significantly correlated with BMI percentage reductions.ConclusionsSemaglutide was associated with significant weight reduction in obese patients with heart failure, accompanied by improved NYHA classification and 6-minute walk distance. Larger, multi-center trials and prospective, randomized controlled trials are warranted. These studies should focus on assessing long-term outcomes, optimizing dosage, and exploring the potential cardiovascular benefits beyond weight reduction.

Molecular Targets of Plant-Derived Bioactive Compounds in Oral Squamous Cell Carcinoma

Background: With a significant increase in both incidence and mortality, oral cancer—particularly oral squamous cell carcinoma (OSCC)—is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. Methods: This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Results: Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. Conclusions: This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential.

An Overview of Reviews on Predictors of Neurorehabilitation in Surgical or Non-Surgical Patients with Brain Tumours

(1) Background. People suffering from brain cancer, regardless of histological tumour characteristics, often experience motor disturbances, cognitive–behavioural difficulty, language impairments, and functional and social limitations. The current treatment approach entails surgery and adjuvant therapy such as chemotherapy and radiotherapy combined with intensive rehabilitation. The primary focus of rehabilitation is usually motor and functional recovery, without specifically addressing the patient’s quality of life. The present systematic review identifies and evaluates the predictors of functional and cognitive rehabilitation outcomes and their influence on quality of life in adult patients with brain cancer. (2) Methods. Three electronic databases (PubMed, Elsevier, Cochrane) were searched for reviews about functional, cognitive, and quality-of-life outcomes in patients with central nervous system tumours, including articles published between January 2018 and May 2024. (3) Results. The search retrieved 399 records, 40 of which were reviewed. Five main areas of predictive factors were identified: diagnosis, therapy, complications, outcomes (in the motor, cognitive, and quality-of-life categories), and tailored rehabilitation. (4) Conclusions. These indicators may inform integrated care pathways for patients with primary central nervous system tumours.

Sex differences in recovery from postoperative sarcopenia during adjuvant CAPOX therapy for colorectal cancer

BackgroundWomen are predisposed to develop intolerance to cancer chemotherapy. Sarcopenia and chemotherapy are mutually related. Women are generally intolerable to chemotherapeutics such as 5-fluorouracil. Although adjuvant oxaliplatin-based chemotherapy, e.g. CAPOX is commonly used to treat colorectal cancer, its effects on patients in terms of sarcopenia and sex remain unknown. We investigated sex disparities in the impacts of CAPOX on body composition in this study.MethodsWe conducted a prospective study on diagnostic metrics used for sarcopenia in colorectal cancer patients receiving adjuvant CAPOX. Evaluations of the nutritional status by the Mini-Nutritional Assessment (MNA), gait speed, grip strength, skeletal muscle mass, fat mass, and bone mineral content using a body composition analyzer were performed in the first, fourth, and eighth cycles of CAPOX (first, second, and third measurements, respectively).ResultsAmong 80 eligible patients, 61 completed four CAPOX cycles. The median differences in MNA, gait, grip strength, muscle mass, fat mass, and bone mineral content between the first and second measurements for men (n = 35) and women (n = 26) were + 10.5% and + 2.9% (p = 0.067), + 4.5% and − 2.6% (p = 0.16), + 1.8% and + 2.8% (p = 0.66), + 2.7% and + 1.3% (p = 0.021), + 4.5% and + 3.5% (p = 0.59), and + 3.3% and + 0.0% (p = 0.006), There were no sex differences in comparisons of the above metrics between the first and third measurements in 34 patients who completed eight CAPOX cycles (19 wen and 15 women).ConclusionsEarly cycles of adjuvant CAPOX may have a negative impact on the postoperative recovery of several metrics for diagnosing sarcopenia in women.

Ekstrak Daun Bandotan (Ageratum conyzoides lin) Memperbaiki Perilaku Depresi pada Mus Musculus

This study aims to assess immobility time in Sham group mice (Mus musculus), assess the effect of fluoxetine antidepressant on immobility time in mice (Mus musculus), assess the impact of bandotan leaf extract antidepressant (Ageratum conyzoides lin) on immobility time in mice (Mus musculus), evaluate the antidepressant effectiveness of the combination of bandotan leaf extract (Ageratum conyzoides lin) with fluoxetine on immobility time in mice (Mus musculus), and compare the efficacy of the four groups, namely group 1 (Sham), group 2 (fluoxetine), group 3 (bandotan leaf extract (Ageratum conyzoides lin)), and group 4 (Fluoxetine with bandotan leaf extract (Ageratum conyzoides lin)). This study uses a type of quantitative approach and pure experimental method (true experimental research) with Posttest only Control Group Design research design. The results showed that the mean immobility time in mice (Mus musculus) group 1 (Sham) was for 34 ± 22.1 seconds. The average immobility time in mice (Mus musculus) group 2 (Fluoxetine) is for 162.5 ± 44.43 seconds. The average immobility time in mice (Mus musculus) group 3 (Bandotan leaf extract) was 172.67 ± 40.5 seconds. The average immobility time in mice (Mus musculus) group 4 (Combination of fluoxetine with bandotan leaf extract) was 118.83 ± 24.1 seconds. The combination of fluoxetine with bandotan leaf extract has significance (p-value 0.039 &lt;0.05) as an antidepressant in reducing immobility time in mice so that bandotan leaves can act as adjuvant therapy.

Pregabalin as an Effective Adjunct in Postoperative Care following Third Molar Removal

Background: The surgical removal of impacted mandibular third molar is probably the most commonly performed procedure in oral &amp; maxillofacial surgery. This study aimed to evaluate the effectiveness of pregabalin as an adjunct to standard analgesia for managing postoperative pain, facial swelling, and trismus following mandibular third molar extraction.  Methods: A total of 136 patients undergoing bilateral extractions were included. Each patient served as their own control, receiving pregabalin with standard analgesia for one extraction and only standard analgesia for the other. Postoperative pain was assessed using the Visual Analogue Scale (VAS) at various intervals, while facial swelling and interincisal distance (IID) were measured on Days 1, 3, 7, and 14.  Results: VAS scores were higher in the control group; however, it was not statistically significant (P = 0.000) at any time interval. % facial swelling was significantly lower in the test group on postoperative day 1[2.32(1.77- 2.95) test; 2.32 (1.82-3.60) control; P = 0.009] and day 3 [6.67 (5.17-8.44) test; 7.49 (5.77-9.43) control; P = 0.004]. However, no significant differences were seen on postoperative day 7 and day 14. Similarly, no significant differences in mouth opening measurements were found.  Conclusion: Pregabalin is effective as an adjuvant therapy in reducing pain and facial swelling after third molar surgery. However, multicenter, randomized, double- blinded studies are recommended to confirm these findings.

Clinicopathologic characterization of secretory carcinoma of salivary gland

BackgroundTo investigate the clinicopathologic characteristics, therapeutic methods, and prognosis of secretory carcinoma of salivary gland (SCSG).MethodsThe clinicopathologic data of 13 patients with SCSG admitted to Shanxi Cancer Hospital from January 2018 to June 2023 were retrospectively analyzed, and a literature review was performed.ResultsA total of eight males and five females aged 22–78 years old were enrolled, and they commonly presented with painless masses in the parotid or submandibular gland. They all underwent surgical treatment, accompanied by typical pathological examinations postoperatively. Fluorescence in situ hybridization (FISH) was conducted in seven cases, the results were all positive, and no gene fusion other than ETV6-NTRK3 was found. Two patients developed local relapse during follow-up, both of which were in the surgical area. By the end of the follow-up, 12 patients survived and one patient died.ConclusionsSCSG is a rare low-grade malignancy with a good prognosis. Pathological and immunohistochemical characteristics are the key to secretory carcinoma (SC) diagnosis, and surgical excision is the major treatment means for SCSG. Whether to perform simultaneous cervical lymph node dissection and other adjuvant therapies should be determined based on the pathological stage and the presence or absence of high-risk factors.

The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.

Metabolism reprogramming is a crucial hallmark of malignant tumors. Tumor cells demonstrateenhanced metabolic efficiency, converting nutrient inputs into glucose, amino acids, and lipids essential for theirmalignant proliferation and progression. Metformin, a commonly prescribed medication for type 2 diabetes mellitus,has garnered attention for its potential anticancer effects beyond its established hypoglycemic benefits. This review adopts a comprehensive approach to delineate the mechanisms underlying metabolite abnormalities within the primary metabolic processes of malignant tumors. This review examines the abnormal activation of G protein-coupled receptors (GPCRs) in these metabolic pathways, encompassing aerobic glycolysis with increased lactate production in glucose metabolism, heightened lipid synthesis and cholesterol accumulation in lipid metabolism, and glutamine activation alongside abnormal protein post-translational modifications in amino acid and protein metabolism. Furthermore, the intricate metabolic pathways and molecular mechanisms through which metformin exerts its anticancer effects are synthesized and analyzed, particularly its impacts on AMP-activated protein kinase activation and the mTOR pathway. The analysis reveals a multifaceted understanding of how metformin can modulate tumor metabolism, targeting key nodes in metabolic reprogramming essential for tumor growth and progression. The review compiles evidence that supports metformin's potential as an adjuvant therapy for malignant tumors, highlighting its capacity to interfere with critical metabolic pathways. In conclusion, this review offers a comprehensive overview of the plausible mechanisms mediating metformin's influence on tumor metabolism, fostering a deeper comprehension of its anticancer mechanisms. By expanding the clinical horizons of metformin and providing insight into metabolism-targeted tumor therapies, this review lays the groundwork for future research endeavors aimed at refining and advancing metabolic intervention strategies for cancer treatment.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study

BackgroundThe evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE.MethodsA retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted.ResultsMultivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 − 7000 cGy, n = 1155 versus 6000 − 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578).ConclusionsFor OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600–7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Enhancing neonatal sepsis outcomes: the role of ascorbic acid and thiamine as adjuvant therapies

Enhancing neonatal sepsis outcomes: the role of ascorbic acid and thiamine as adjuvant therapies

Unraveling the Ferroptosis-inducing Potential of Methanol Leaves Extract of Prosopis Juliflora Via Downregulation of SLC7A11 and GPX4 mRNA Expression in A549 Lung Cancer Cells.

Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, Prosopis juliflora leaf methanol extract (PJME) has a promising future in the fight against lung cancer. It may also be used in conjunction with other treatments to effectively manage lung cancer. The main objective of this study was to explore the potential of PJME to inhibit lung cancer in A549 cells, along with its underlying mechanisms of action. The antiproliferative effects were determined using MTT and LDH tests. Apoptosis- inducing capacity was evaluated using the DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, and qRT-PCR. To investigate the mechanism of action of PJME in lung cancer, the levels of ROS, MMP, GSH, MDA, and specific ferroptosis indicators were measured. The experimental data of the current study indicated that exposure of A549 cells to PJME reduced cell viability and increased cellular cytotoxicity. The apoptosis-inducing ability of PJME in A549 cells was validated by enhanced nuclear condensation, level of the caspase- 3, cytochrome C, and PARP release. In addition, qRT-PCR investigations verified that the administration of PJME led to a decrease in the expression of anti-apoptotic gene Bcl2 while enhancing the mRNA level of pro-apoptotic genes, such as Bax and caspase-3, in A549 cells. The study also found that PJME has the ability to activate ferroptosis pathways, as evidenced by elevated reactive oxygen species (ROS) generation, changes in the levels of antioxidant markers (MDA and GSH), and decreased expression of SLC7A11 and GPX4. The results of the present study clearly showed that PJME inhibited the proliferation of A549 cells and induced ferroptosis by reducing the expression of the important targets SLC7A11 and GPX4. Further research is necessary to fully understand the clinical efficacy of PJME before it can be investigated as supplemental or adjuvant therapy for lung cancer.

Current Practice, Safety and Efficacy of Interventions for Recurrent Respiratory Papillomatosis: Evidence From a UK Registry.

To determine the current practice, safety and efficacy of interventions used in the management of recurrent respiratory papillomatosis (RRP) in the UK NHS. Prospective registry (recruitment between 1st April 2018 and 31st August 2022, retrospective data from 1st January 2015 permitted with consent). Sub-group data-linked to Hospital Episode Statistics for additional follow-up (until 31st July 2022). UK NHS hospitals treating RRP patients. Children and adults diagnosed with RRP and managed in an NHS hospital. Disease severity (Derkay, voice handicap and GRBAS scores), management (type and frequency of surgical and adjuvant intervention) and complications (cancer, death). Three hundred and thirty patients were entered into the registry; 304 (including 65 children) were eligible for analysis. Children had more severe disease than adults (median Derkay score 10 vs. 5). Microdebrider was the most common surgical intervention, particularly in children (86% of children, 49% of adults). Additionally, lasers (CO2, KTP and pulsed dye) were used in 34% of adults. Gardasil was the most common adjuvant therapy (21 children, 23 adults). Procedural complications were rare (10.8% children, 5.9% adults). Five patients developed laryngeal malignancy; there were six deaths during follow-up period. This is the largest UK RRP study to date. RRP is more aggressive in children than adults, and treatment choice differs between age groups. Overall, management was safe with minimal complications reported, and generally effective in maintaining a safe airway. Standardised reporting is required to objectively monitor disease progression and safety over time. NCT03465280, ISRCTN36100560.

Empagliflozin as a novel therapy for cirrhotic refractory ascites: a randomized controlled study

BackgroundCirrhotic refractory ascites (RA) patients have few alternatives for treatment. Empagliflozin is now known to have natriuretic and neurohormonal modulatory effects. This research investigated the safety and efficacy of empagliflozin in the management of RA when added to the standard of care (SoC) compared to SoC alone.MethodsPatients were randomized to receive either a fixed dose of 10 mg of empagliflozin plus standard of care (SoC) or SoC alone. Patients were followed up for 3 months. The primary endpoint was achieving no need for large-volume paracentesis (LVP).ResultsForty-two patients were randomized equally, and intention-to-treat was performed. There was a statistically significant decrease in the need for LVP in the empagliflozin group compared to the SoC group (100% in the SoC vs. 42.9% in the empagliflozin group, p < 0.001). By the end of the study, the total resolution of ascites was reported in approximately 24% of patients. Muscle cramps and newly developed hyponatremia were more common in the empagliflozin group, but they were mild. Acute kidney injury was more common in the SoC group.ConclusionsEmpagliflozin may be an effective option for use as an add-on therapy in the management of RA, with an accepted safety profile.Trial registrationThe trial was registered at www.clinicaltrials.gov under the identifier NCT05430243. The registration was submitted on 18/06/2022. It is available at https://clinicaltrials.gov/study/NCT05430243.Graphical

The Mechanism and Inflammatory Markers Involved in the Potential Use of N-acetylcysteine in Chronic Pain Management

N-acetylcysteine (NAC) has established use as an antidote for acetaminophen overdose and treatment for pulmonary conditions and nephropathy. It plays a role in regulating oxidative stress and interacting with various cytokines including IL-1β, TNFα, IL-8, IL-6, IL-10, and NF-κB p65. The overexpression of reactive oxygen species (ROS) is believed to contribute to chronic pain states by inducing inflammation and accelerating disease progression, favoring pain persistence in neuropathic and musculoskeletal pain conditions. Through a comprehensive review, we aim to explore the mechanisms and inflammatory pathways through which NAC may manage neuropathic and musculoskeletal pain. Evidence suggests NAC can attenuate neuropathic and musculoskeletal pain through mechanisms such as inhibiting matrix metalloproteinases (MMPs), reducing reactive oxygen species (ROS), and enhancing glutamate transport. Additionally, NAC may synergize with opioids and other pain medications, potentially reducing opioid consumption and enhancing overall pain management. Further research is needed to fully elucidate its therapeutic potential and optimize its use in pain management. As an adjuvant therapy, NAC shows potential for chronic pain management, offering significant benefits for public health.

Gastrointestinal stromal tumor in Carney’s triad with laparoscopic total gastrectomy: a case report

IntroductionCarney's triad is a rare syndrome characterized by the co-occurrence of gastric gastrointestinal stromal tumor (GIST), pulmonary chondroma, and extra-adrenal paraganglioma. We present a case of a young woman with GISTs associated with this triad.Case presentationA 28-year-old woman was identified with multiple gastric tumors and a right lung nodule during a routine health check-up. CT scans and upper gastrointestinal endoscopy revealed a 50 mm mass on the lesser curvature of the stomach, along with two additional gastric lesions and a 20 mm nodule in the right lung. The patient had a history of right middle lobectomy at the age of 19 for pulmonary chondroma. During surgery, enlarged lymph nodes were observed, indicating metastasis, which necessitated a total gastrectomy with radical (D2) lymph node dissection. Pathological examination confirmed seven GISTs, with immunohistochemical staining positive for KIT (+), DOG1 (+), and negative for SDHB (−). The postoperative course was uneventful, and the patient was discharged on the seventh postoperative day. Despite opting out of adjuvant imatinib therapy, she remains disease-free 2 years postoperatively.ConclusionsThis case underscores the necessity of total gastrectomy with lymph node dissection due to the high incidence of metastasis in GISTs associated with Carney's triad. Further research is required to determine the optimal extent of lymph node dissection in such cases.

Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update.

Gastrointestinal stromal tumor (GIST) is characterized by well-defined oncogenes. Despite the significant improvement in treatment outcomes with adjuvant imatinib therapy for patients, drug resistance remains a major challenge for GIST therapy. This review focuses on the mechanisms contributing to drug resistance phenotype in GIST, such as primary imatinib-resistant mutants, secondary mutations, non-covalent binding of TKI to its target, tumor heterogeneity, re-activation of pro-survival/proliferation pathways through non-KIT/PDGFRA kinases, and loss of therapeutic targets in wild-type GIST. Corresponding suggestions are proposed to overcome drug-resistance phenotype of GIST. This review also summarizes the suitability of currently approved TKIs on different KIT/PDGFRA mutations and updates related clinical trials. Recent potent drugs and emerging strategies against advanced GISTs in clinical trials are presented. Additionally, metabolic intervention offers a new avenue for clinical management in GIST. A landscape of metabolism in GIST and metabolic changes under imatinib treatment are summarized based on currently published data. The OXPHOS pathway is a promising therapeutic target in combination with TKI against sensitive KIT/PDGFRA mutants. Comprehensive understanding of the above resistance mechanisms, experimental drugs/strategies and metabolic changes is critical to implement the proper therapy strategy and improve the clinical therapy outcomes for GIST.