Optimal Regimen Research Articles

Evaluation of Efficacy and Safety of Different Doses of Eladis® in the Therapy of Cough Against Acute Respiratory Viral Infection

Aim. Justification of the optimal dosage regimen regarding the efficacy and safety of Eladis®, film-coated tablets, 10 mg (Valenta Pharm JSC, Russia) in comparison with placebo in patients with non-productive cough due to acute respiratory viral infection (ARVI). Material and methods. A double-blind placebo-controlled randomized multicenter study was conducted in which 141 patients with non-productive cough on the background of acute respiratory viral infection took part. The study participants were randomized into 4 groups. Patients from the first group took 1 tablet of Eladis® 2 times a day (daily dose of 20 mg); patients from the second group took 2 tablets of Eladis® 2 times a day (daily dose of 40 mg); patients from the third group took 4 tablets of Eladis® 2 times a day (daily dose of 80 mg). Patients in the fourth group received placebo tablets in quantities corresponding to the first three groups. For this purpose, 3 subgroups of 12 people were allocated within group 4. The duration of therapy was 7–14 days. The effectiveness of therapy was assessed based on monitoring the frequency of cough attacks, changes in values on the day and night cough scales, a digital rating scale (DRS), and the time to achieve clinical cure of cough and ARVI symptoms was also taken into account. The safety of the studied drug was assessed based on monitoring of vital signs, laboratory parameters, and electrocardiogram (ECG) data. The number and severity of adverse events (AEs) and serious adverse events (SAEs) were assessed. Results. Analysis of data on the primary endpoint (reduction of cough attack frequency by ;)50% by the 5th day relative to the 1st visit) showed the superiority of Eladis® over placebo at a daily dose of 80 mg (P=0.00003). At the same time, the proportion of patients who reached the primary endpoint by day 5 when receiving Eladis® at a dose of 80 mg per day was 71.43%, while in the combined placebo group it was 22.22%. Conclusion. Evaluation of various dosage regimens of Eladis® has shown that a daily dose of 80 mg is optimal for the treatment of non-productive cough in patients with ARVIs, as it provides the greatest effectiveness with a safety profile comparable to other studied doses.

Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma.

Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3IDHmt/Codel) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens. The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3IDHmt/Codel. We included patients with histologically proven O3IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathological review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model. 305 newly diagnosed patients with O3IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025). In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study

ABSTRACT Background This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir. Methods A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations. Results The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0–59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir. Conclusions PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.

Acupuncture and Related Therapies for Endometriosis: A Network Meta-Analysis of Randomized Controlled Trials.

Acupuncture and related therapies are effective and safe ways to relieve the pain, and improve the health and quality of life in women with endometriosis-related pain. However, it is still unclear which treatment is the most effective. Our study aims to summarize the evidence and determine the most effective and safe method to treat the endometriosis. We searched PubMed, EMBASE, Cochrane Library, and Web of science, China Biology Medicine, China National Knowledge Infrastructure, Wan fang Data, Chinese Scientific Journal Database and conducted manual searches of relevant papers, summarized randomized clinical trials of acupuncture-related therapies for endometriosis from database inception to 21 April 2024. After independent literature screening and data extraction that pain VAS was selected as the primary outcome measure. The quality evaluation was conducted by Review Manager 5.4. Perform network meta-analysis (NMA) used Stata 15.0 software. Forty-two eligible trials involving six acupuncture-related interventions and 3,635 participants were included in this NMA. Pairwise meta-analyses show that combination therapy was more efficacious than western medicine and Chinese herb medicine for pain VAS scores, serum CA125 level and response rate results. The NMA estimates indicated that: for pain VAS scores, acupuncture (SMD: -2.33; 95% CI: -4.37, -0.29) and combination therapy (SMD: 1.79 95% CI: 1.21, 2.41) were superior to western medicine. For serum CA125 level, acupoint application (SMD: -11.33 95% CI: -20.28, -2.97) and combination therapy (SMD: 6.20; 95% CI: 1.60, 10.75) were associated with better efficacy when considered alongside western medicine. For response rate, combination therapy (SMD: 0.20; 95% CI: 0.14, 0.29) and auricular therapy (SMD: 8.01; 95% CI: 2.08, 45.37) were more efficacious than western medicine. The comprehensive ranking results show that acupoint catgut embedding was the best performing at lowering pain VAS scores, acupoint application was identified as the most effective in reducing serum CA125 level, and auricular therapy was ranked first in improving the response rate. Acupoint catgut embedding, auricular therapy, acupoint application and combination therapy may be the best solutions for the treatment of endometriosis. Additional trials are needed to develop higher-quality evidence and optimal regimens.

Effect of Probiotic Supplementation on Disease Activity in Rheumatoid Arthritis Patients

Abstract Background Rheumatoid arthritis (RA), a prevalent inflammatory arthritis with a global incidence of 0.5–1%, is characterized by autoimmune-driven articular pain, cartilage degradation, bone destruction, and functional disability. Emerging evidence suggests a potential link between alterations in gastrointestinal microflora and the development of autoimmune diseases, including RA. Probiotic bacteria have gained attention as a potential adjunctive therapy due to their immunomodulatory properties, offering promise for improving clinical and metabolic outcomes in RA patients. Aim of the Work To study the effects of probiotic supplementation on clinical status of patients with RA. Patients and Methods Sixty Egyptian RA patients aged 18-60 years, diagnosed and screened in the Rheumatology department at Ain Shams University Hospital, were enrolled in this study. The patients were divided into two groups: group A received daily probiotic supplementation for 8 weeks, while group B served as the control. Detailed clinical assessments and laboratory investigations were conducted. Results There were no significant differences in age, sex distribution, disease duration, or disease- modifying antirheumatic drugs (DMARDs) usage between the two groups, consistent with previous research. The probiotic regimen included Lactobacillus acidophilus and Bifidobacterium animalis. Conclusion Probiotic supplementation in RA patients yielded mixed results in this study, with improvements in TJC and ESR but no significant changes in SJC, CRP, or disease activity scores. Further research is needed to elucidate the complex relationship between gut microbiota and RA pathogenesis and to determine the optimal probiotic regimen for improving clinical outcomes in RA patients.

Postprandial Glucose Following High Glycemic Index Meals in Children and Adolescents with Type 1 Diabetes on Insulin Pump Therapy

Abstract Background Achieving postprandial normoglycemia is the most challenging part in the management of type 1 diabetes. Meal timing and meal composition affect glycemic outcomes. Nutritional properties of food, including protein, fat and glycemic index significantly impact postprandial glycemic excursions. Objective To assess efficacy of continuous subcutaneous insulin infusion (CSII) in optimizing postprandial glycemic excursions following the consumption of a high-glycemic index (high-GI) carbohydrate. Methods The current study is a non-blinded single arm randomized controlled trial including 24 participants with type1 diabetes regularly following up at the Pediatric and Adolescent Diabetes Unit (PADU), Pediatrics Hospital, Ain Shams University. All recruited children and adolescents were using the MiniMed® Paradigm Revel TM 523/723. The same high-GI breakfast with standardization of fat and protein content (cereal- cornflakes (contains 50 g carbohydrates, GI = 81±6) and skimmed milk (contains 0.5 g fats, 9 g carbohydrates, 6 g proteins) was given to all participants and prandial insulin dosage was individualized according to participants’ insulin-carb ratio. Insulin was delivered upfront as a standard bolus, given 15 minutes before consuming the test meal. Postprandial glycemic excursions were assessed using flash glucose monitoring system at 1, 2 and 3 hours post meal. Results The standard bolus didn’t control the early postprandial excursions, with highly significant postprandial excursions at 60 min and 120 min following consumption of the tested meal. The mean blood glucose level significantly increased from 101.79 ± 19.73 mg/dl at baseline to 167.50 ± 16.64 mg/dl at 60 min (P = 0.000). Similarly, at 120 min after consumption of the test meal, the mean glucose significantly increased to 183.83 ± 19.90 (P = 0.001) Conclusion High-GI carbohydrates modifies postprandial glycemic response causing early sharp glycemic rise, which was not controlled by the standard bolus of insulin delivery. Further studies are needed to define the optimal insulin delivery regimen required to optimize postprandial glycemia following the consumption of high-GI carbohydrates.

Comparison between Preoperative Ultrasound Guided TAP Block and Caudal Block in Inguinal Hernia Repair in Paediatrics for Intraoperative and Postoperative Analgesia

Abstract Background Inguinal hernia repair is the most common scheduled sub-umbilical surgery done in day case paediatric surgical units. Using optimal analgesic regimens is essential to provide safe and effective analgesia, reduce postoperative stress response and accelerate recovery from surgery. Regional anaesthetic techniques are commonly used to facilitate pain control in paediatric surgical procedures. Aim of the Work To compare the effectiveness and safety of US guided TAP versus caudal block for postoperative analgesia in paediatric patients undergoing Unilateral Inguinal hernia repair. Patients and Methods The study was conducted on 40 randomly chosen patients in Ain Shams University Hospitals after approval of the medical ethical committee. Patients were divided randomly into two groups, each group consisted of 20 patients. After preoperative assessment and obtaining baseline vital data, all patients received general anaesthesia followed by the block at the beginning of the operation. Results the study revealed that US guided TAP block provided significantly prolonged postoperative analgesia and reduced the postoperative analgesic requirements as compared with caudal block in paediatric patients and also demonstrated that both analgesic techniques are safe. Conclusion From our study we can conclude that Ultrasound-guided transversus abdominis plane block and caudal epidural block are effective analgesics in children undergoing inguinal hernia repair surgery, with transversus plane block providing longer analgesic effect and decreased pain scores.

Bupivacaine vs Bupivacaine with Dexmedetomidine for the Caudal Epidural Block as an Adjuvant to General Anesthesia in Lumbosacral Surgeries

Abstract Background A caudal epidural block can be incorporated as a part of multimodal analgesia for lumbosacral spine surgeries. Utilizing a combination of different analgesic modalities, achieving better pain relief, sparing opioids and decreasing their adverse effects, it is a simple and safe technique that can be easily performed under fluoroscopy in the prone position. Using an optimal analgesic regimen provides safe and effective analgesia, reduces postoperative pain, and accelerates recovery from surgery. Aim of the Work to compare the effectiveness and safety of Bupivacaine vs. Bupivacaine and Dexmedetomidine in the fluoroscopy-guided caudal epidural block for postoperative analgesia in patients undergoing lumbosacral surgeries combined with general anesthesia. Patients and Methods The study was conducted on 60 randomly chosen patients in Ain Shams University Hospitals after approval of the medical ethical committee. Patients were divided randomly into two groups; each group consisted of 30 patients. Results revealed that Fluoroscopy-guided caudal epidural block using Bupivacaine and Dexmedetomidine provided significantly prolonged postoperative analgesia and reduced the postoperative analgesic requirements as compared with Bupivacaine only in patients undergoing lumbosacral surgeries and demonstrated that both analgesic techniques are safe. Conclusion Bupivacaine and Dexmedetomidine provided significantly prolonged postoperative analgesia and reduced the postoperative analgesic requirements as compared with Bupivacaine alone in patients undergoing lumbosacral surgeries under general anesthesia and also demonstrated that both analgesic drugs are safe.

Effect of Dexamethasone as an adjuvant to Bupivacaine in caudal block for Postoperative Analgesia in Pediatric Patients undergoing Orchidopexy

Abstract Background Regional anesthetic techniques are commonly used to facilitate pain control in pediatric surgical procedures. The most commonly used technique in pediatrics is caudal block. Urogenital surgeries are one of the most frequently performed surgical procedures in the pediatric population. Using optimal analgesic regimen provides safe and effective analgesia, reduce postoperative stress response and accelerate recovery from surgery. Aim of the Work to evaluate the analgesic effect of dexamethasone when given as an adjuvant to caudal block in children undergoing orchidopexy surgery. Patients and Methods The study was conducted on 40 randomly chosen patients in Ain Shams University Hospitals after approval of the medical ethical committee. Patients were divided randomly into two groups; each group consisted of 20 patients. Results revealed that dexamethasone 0.1 mg/kg, when used as an adjuvant to caudal anesthesia, can significantly prolong the duration of postoperative analgesia. It is better than bupivacaine alone in caudal block at similar doses in controlling postoperative pain. Conclusion we can conclude that adding 0.1 mg/kg of dexamethasone to 0.5 ml/kg of 0.25% bupivacaine effectively improves the analgesic duration in single-shot caudal anesthesia.

EP.12A.02 What is the Optimal First-Line Regimen for EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis

EP.12A.02 What is the Optimal First-Line Regimen for EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis

Non-pharmacological interventions of traditional Chinese medicine in treating polycystic ovary syndrome: a group consensus

ObjectiveTo make a group consensus about non-pharmacological interventions of traditional Chinese medicine in treating polycystic ovary syndrome based on the previous guidelines, literature, and expert viewpoints. MethodsOrganized by Chinese Integrative Medicine & Traditional Chinese Medicine Academy, Chinese Maternal and Child Health Association, China, 29 experts from 18 Chinese provinces and 2 international experts, who specialize in gynecology, obstetrics, pediatrics, endocrinology, cardiovascular, psychology, reproductive genetics, nursing, acupuncture and tuina, traditional Chinese medicine, integrative medicine, and other disciplines, discussed and revised the recommendations one by one through in-person or online communication. Each recommendation was approved by ≥90% of the experts before it could be established. Main outcome measure(s)An optimal clinical regimen for addressing the requirements of women with PCOS and improving their quality of life. Result(s)The writing panel drafted the initial report, following a consensus process via adequate communication, which was then reviewed and revised by the consensus panel. This consensus provides 12 non-pharmacological interventions (including acupuncture, thumbtack needle, thread-embedding therapy, TEAS, AA, acupoint hot compress, cupping, acupressure, moxibustion, five elements music, aromatherapy, traditional Chinese exercises) for 8 phenotypes of PCOS, resulting in 34 items of clinical practice recommendations. Conclusion(s)The consensus provides 12 non-pharmacological interventions of traditional Chinese medicine for 8 phenotypes of PCOS, resulting in 34 items of clinical practice recommendations, which may be improved by more high-quality multicenter clinical trials.

Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome.

The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model. We evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in Scn1aA1783V/WT mice. Clobazam, N-desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry for the combinations deemed effective against hyperthermia-induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin. Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in Scn1aA1783V/WT mice. In Scn1aWT/WT mice, brain clobazam and N-desmethyl clobazam concentrations were higher in the triple-drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple-drug therapy than when given alone. A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug-drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.

An Insight into the Mechanism, Safety and Efficacy for Photoprotection and Dermatological Conditions of Polypodium leucotomos Extract

Abstract: Numerous photoprotective techniques have been employed to successfully shield against the harmful effects of ultraviolet radiation. Current photoprotective techniques have limitations due to the amount of topical application, insufficient physical protection, and adverse responses to topical agents. A newer option that offers a promising defense against solar radiation is systemic agents, the well-researched Polypodium leucotomos is significant in this category, and several studies have found to be effective ―oral sunscreenǁ. Polypodium leucotomos (PL) extract has gained significant attention as a potential therapeutic agent in the field of dermatology, particularly in the photoprotection and management of various dermatological conditions. This abstract provides a comprehensive overview of the mechanism, safety, and efficacy of Polypodium leucotomos extract in relation to photoprotection and dermatological conditions. Our primary aim is to review Polypodium leucotomos' photoprotective results from studies that are currently available, and our secondary goal is to describe Polypodium leucotomos' applications in different dermatological conditions. Articles discussing Polypodium leucotomos uses in photoprotection and dermatologic conditions are searched and downloaded from publicly available databases such as PubMed, JSTOR, PLOS, Science Direct, DOAJ, Google Scholar, and Web of Science and evaluate the outcomes of the Polypodium leucotomos effect. Firstly, we delve into the mechanisms underlying the photoprotective properties of PL extract. Extensive research has demonstrated that PL extract exerts its protective effects through multiple pathways, including antioxidant activity, DNA repair stimulation, immunomodulation, and inhibition of inflammatory mediators. These mechanisms collectively contribute to the prevention of photodamage, such as sunburn, DNA damage, and photoaging. Furthermore, we explore the safety profile of PL extract, emphasizing its remarkable tolerability and minimal adverse effects reported in clinical studies. The absence of systemic absorption and its compatibility with other treatments make PL extract a promising option for long-term use in photoprotection and dermatological care. A promising alternative to traditional photoprotection may be Polypodium leucotomos. Additional thorough clinical trials are necessary to ascertain its role and effectiveness more accurately. The efficacy of PL extract in managing various dermatological conditions is also discussed. Multiple studies have demonstrated its beneficial effects in conditions such as vitiligo, melasma, psoriasis, and atopic dermatitis. The anti-inflammatory and immunomodulatory properties of PL extract have shown promise in reducing disease severity, improving skin symptoms, and enhancing the quality of life for patients. Additionally, the abstract highlights the potential future directions and areas of research for PL extract. Investigating its combination therapy with other photoprotective agents, exploring optimal dosage regimens, and further elucidating the molecular mechanisms are areas that warrant attention. In conclusion, this abstract provides an insightful overview of the mechanisms, safety, and efficacy of PL extract in photoprotection and dermatological conditions. The remarkable properties of PL extract, combined with its favorable safety profile, position it as a promising therapeutic intervention in dermatology. Further research and clinical trials are needed to fully exploit its potential and establish its place in the management of various skin conditions.

Steroids in severe community-acquired pneumonia.

There is conflicting evidence regarding the use of steroids in severe community-acquired pneumonia (CAP), with previous randomised controlled trials limited by small sample sizes. ESCAPe and CAPE COD are two recently published large trials on steroids in severe CAP. ESCAPe assessed the initiation of methylprednisolone within 72-96 h of hospital admission, while CAPE COD studied the use of hydrocortisone within 24 h of the development of severe CAP. ESCAPe did not show any differences in all-cause 60-day mortality or any of its secondary outcomes. CAPE COD showed that hydrocortisone improved all-cause 28-day mortality and reduced the risk of intubation or vasopressor-dependent shock. Important differences between the trials included the steroid regimens used, timing of steroid administration and baseline characteristics, with more diabetic patients included in ESCAPe. The results of CAPE COD support the initiation of hydrocortisone within 24 h of developing severe CAP, but more research is needed to evaluate long-term outcomes and optimum dosing regimens for steroids in severe CAP.

Neoadjuvant Chemotherapy for Borderline Resectable Head and Neck Cancers: A Comparative Study of Three-Drug and Two-Drug Regimens in a Low- and Middle-Income Country (LMIC) Context.

Background Borderline resectable head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge, particularly in low- and middle-income countries (LMICs) like India. Neoadjuvant chemotherapy (NACT) aims to downstage tumors to achieve operability, but the optimal regimen remains controversial due to varying efficacy and toxicity profiles. This study compares the efficacy and toxicity of a three-drug regimen (TPF: docetaxel, cisplatin, and 5-fluorouracil) with a two-drug regimen (taxane and platinum) in patients with borderline resectable HNSCC in an LMIC setting. Methods In this retrospective cohort study, a total of 90 patients with borderline resectable HNSCC were included. Forty-three patients received the TPF regimen (Arm A), while 47 received the taxane + platinum regimen (Arm B). The outcomes measured included conversion to operability, stage-specific outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Statistical analyses included chi-square tests for categorical variables, Kaplan-Meier survival analysis, and Cox proportional hazards modeling for multivariate analysis. Results The conversion to operability was significantly higher in the TPF group (72% vs. 51%, p=0.03). Patients in Arm A also exhibited a trend toward higher pathological complete response (pCR) rates compared to Arm B (60% vs. 43%, p=0.08). The overall survival and progression-free survival were improved in the TPF group, although the study did not reach statistical significance in these endpoints due to the limited sample size. However, the TPF regimen was associated with significantly higher toxicity. Grade 3-4 neutropenia occurred in 55% of the patients in Arm A compared to 32% in Arm B (p=0.01), and mucositis was observed in 47% of Arm A patients compared to 19% in Arm B (p=0.002). Febrile neutropenia was also more frequent in the TPF group (28% vs. 13%, p=0.04). Multivariate analysis identified the chemotherapy regimen (HR=1.45, 95% CI 1.05-2.01, p=0.02) and baseline nutritional status (HR=1.78, 95% CI 1.12-2.82, p=0.01) as independent predictors of overall survival. Conclusion While the TPF regimen offers superior efficacy in terms of tumor downstaging and conversion to operability, its higher toxicity profile limits its applicability in resource-constrained settings, such as LMICs. The taxane + platinum regimen, although less effective in downstaging, presents a more favorable toxicity profile, making it a viable alternative for patients with comorbidities or poor performance status. The choice between these regimens should be individualized, considering the patient's overall health, nutritional status, and the availability of supportive care. Further research is warranted to optimize NACT strategies for patients in LMICs.

Enhanced clindamycin delivery using chitosan-coated niosomes to prevent Toxoplasma gondii strain VEG in pregnant mice: an experimental study

BackgroundCongenital toxoplasmosis occurs when a pregnant woman becomes infected with Toxoplasma gondii (T. gondii) for the first time. Treatment typically involves antimicrobial medications, with spiramycin commonly used to prevent transmission. However, spiramycin's effectiveness is limited due to poor placental penetration. Clindamycin, another antibiotic, can cross the placenta but reaches the fetus at only half the maternal concentration. Encapsulating the drug in chitosan-coated niosomes (Cs-Nio) could enhance its effectiveness by targeting specific organs and ensuring sustained release. To address the challenges of using clindamycin, a niosome-coated chitosan system was investigated for treating congenital toxoplasmosis caused by the VEG strain of T. gondii in an animal model.MethodsPregnant mice were infected with VEG strain of T. gondii on the 12th day of pregnancy, followed by treatment with various drugs across six groups. The treatments included chitosan-coated niosomes loaded clindamycin (Cs-Nio-Cli) and other controls. Parasitological evaluations (microscopic examination and real-time PCR), along with histopathological and immunological assessments were conducted to assess treatment efficacy. Finally, statistical analysis was conducted using GraphPad Prism 8.0 and SPSS 26, comparing test and control groups with T test and Mann–Whitney test. A p ≤ 0.05 was considered statistically significant.ResultsThe study found that treatment with Cs-Nio-Cli significantly reduced the number of T. gondii cysts in the brain and eyes (97.59% and 92.68%, respectively) compared to the negative control group. It also mitigated inflammatory changes, prevented cell death, and reduced vascular cuffs in the brain. In addition, Cs-Nio-Cli treatment decreased bleeding, placental thrombosis, and inflammatory cell infiltration in the placenta while improving eye tissue health by reducing retinal folds and bleeds. Immunologically, nanoclindamycin treatment resulted in lower TNF-α cytokine levels and higher IL-10 levels, indicating an enhanced anti-inflammatory response.ConclusionsAlthough Cs-Nio-Cli demonstrates promise in reducing the transmission of congenital toxoplasmosis and mitigating the effects of congenital toxoplasmosis, additional research is necessary to determine the optimal treatment regimens for the complete eradication of the parasite in the fetus.

Patterns of failure and the subsequent treatment after progression on first-line immunotherapy monotherapy in advanced non-small cell lung cancer: a retrospective study

BackgroundImmune checkpoint inhibitors (ICIs) have become the recommended first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, data on the failure patterns of first-line ICIs monotherapy is limited, and the optimal strategy for subsequent treatment remains controversial.MethodsAdvanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and October 2021 were identified. The progressive sites were recorded to analyze failure patterns. Post-progression survival (PPS) was compared between different treatment regimens.ResultsA total of 121 patients receiving first-line ICIs monotherapy were identified, with a median progression-free survival of 8.6 months. Sixty-five patients had available imaging at diagnosis as well as progressive disease, with 56.9% showing oligoprogression. For those with progression in existing lesions, the most common sites were the liver (77.8%) and lung parenchyma (62.5%), while progression with new lesions frequently occurred in the liver (32.0%). Fifty patients with recorded subsequent treatment were included in the analysis of subsequent treatment patterns. Patients treated with anti-angiogenesis therapy could get better PPS (HR: 0.275, P = 0.013). Isolated oligoprogression occurred most often in the lung parenchyma and intracranial lesions. More than half of these patients continued immunotherapy after local treatment, with a 2.5-year PPS rate of 51.4%.ConclusionThe liver was the most common site of progression on first-line ICIs monotherapy. Anti-angiogenesis-based therapy might be an optimal regimen at the time of progression. Patients with isolated oligoprogressive could still benefit from immunotherapy after local treatment.

Enzymatic TherapyversusVATS for pleural infections: a systematic review and meta-analysis

QuestionParapneumonic pleural infections are frequently encountered, but the optimal treatment regimen remains controversial. The aim of this systematic review was to investigate whether immediate video-assisted thoracoscopic surgery (VATS) has advantages over intrapleural enzymatic therapy (IET).MethodsWe searched MEDLINE, Embase, and Web of Science Core Collection till November 2023 and included studies comparing IET and VATS in adult patients with parapneumonic pleural infections. Primary outcome was length of hospital stay (LOS), secondary outcomes included mortality and morbidity. Study quality was assessed using ROBINS-I and RoB 2. Inverse variance random-effects meta-analysis was performed.ResultsWe screened 2263 articles, eight were included in the final analysis, covering 1023 patients (n=465 IET (mostly single agent IET); n=558 VATS). Six were non-randomized studies (n=5 with serious risk of bias) comprising 964 patients, and two were small, randomized feasibility studies (n=1 with high risk of bias), comprising 59 patients. In the meta-analysis, LOS in non-randomized studies was shorter for patients treated by VATS (mean difference 4.2 days; 95%CI 1.5 to 7.0). However, no significant difference was reported in the randomized feasibility studies. Mortality and morbidity rates showed no significant difference.InterpretationIn this meta-analysis of non-randomized studies with a high risk of selection bias, VATS appears superior to IET regarding LOS in the treatment of parapneumonic pleural infections, without increased mortality and morbidity rate. Two recently published randomized feasibility studies failed to confirm this finding, but were not designed to detect a difference in LOS. This meta-analysis highlights the need for high quality studies.

Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents.

Postoperative Bleeding Complications are Common among Patients Undergoing Transcarotid Artery Revascularization

Current practice guidelines recommend dual antiplatelet therapy for at least 30days postoperatively after transcarotid artery revascularization (TCAR) to promote stent patency. However, many patients are already taking other antithrombotic medications. The optimal pharmacologic regimen in this patient population remains unclear, especially as it pertains to postoperative bleeding complications. All TCAR procedures performed at a large academic medical center from January 1, 2017, to April 30, 2023, were identified via current procedural terminology codes and retrospectively reviewed via electronic medical records. Data were collected on patient demographics, procedural details, postoperative complications, and antithrombotic regimen. Bleeding complications were categorized as surgical and nonsurgical, which included any bleeding diatheses that were not related to the neck incision, such as epistaxis, hematuria, melena, or noncervical hematoma. A total of 116 TCAR procedures were performed. The 30-day incidence of bleeding complications was 12.1% (n=14), which included 8 (6.9%) symptomatic neck hematomas and 6 (5.2%) nonsurgical site bleeding complications. Aside from patient age (median 72years [66-79] vs. 79years [70.5-88], P=0.03), demographics, medical comorbidities, surgical indication, risk-related indication for TCAR, and inpatient/outpatient status were similar between patients who experienced bleeding versus no bleeding complications. Patients who developed bleeding complications experienced higher 30-day hospital readmission (42.9% vs. 9.8%, P<0.001) and reintervention rates (21.4% vs. 2.0%, P<0.001) and trended toward longer postoperative length of stay (1.5days [1-3] vs. 1 [1-2] days, P=0.07). Reasons for readmission (n=16) included: epistaxis (1), hematuria (1), headache and melena (1), melena and myocardial infarction (1), fall (1), headache (1), dyspnea (5), delirium (1), diarrhea (1), atrial fibrillation (1), and neck hematoma (1); 1 patient did not have a readmission reason documented. Reinterventions (n=6) included neck hematoma evacuation (2), epistaxis cauterization (1), emergent cricothyroidotomy (1), and repeat carotid stenting (1). The management of antithrombotic medications during bleeding events were highly variable among providers (11 patients with nothing held, 1 apixaban held, 1 aspirin held, 1 clopidogrel held); however, no patients suffered carotid stent thrombosis. Bleeding complications are common within 30days of TCAR and frequently result in unplanned hospital readmission and reintervention. There is significant provider-level variability in management of antithrombotic medications during these events. These data highlight need for evidence-based guidelines for the optimal pharmacologic strategy for patients post-TCAR who develop bleeding complications.