Successful Therapy Research Articles

Analysis of interventional treatment options of the common femoral artery - a retrospective single center experience.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

Inflammation and cancer: friend or foe?

Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.

The efficiency of stem cell differentiation into functional beta cells for treating insulin-requiring diabetes: Recent advances and current challenges.

In recent years, the potential of stem cells (SCs) to differentiate into various types of cells, including β-cells, has led to a significant boost in development. The efficiency of this differentiation process and the functionality of the cells post-transplantation are crucial factors for the success of stem cell therapy in diabetes. Herein, this article reviews the current advances and challenges faced by stem cell differentiation into functional β-cells for diabetes treatment. In vitro, researchers have sought to enhance the differentiation efficiency of functional β-cells by mimicking the normal pancreatic development process, using gene manipulation, pharmacological and culture conditions stimulation, three-dimensional (3D) and organoid culture, or sorting for functional β-cells based on mature islet cell markers. Furthermore, in vivo studies have also looked at suitable transplantation sites, the enhancement of the transplantation microenvironment, immune modulation, and vascular function reconstruction to improve the survival rate of functional β-cells, thereby enhancing the treatment of diabetes. Despite these advancements, developing stem cells to produce functional β-cells for efficacious diabetes treatment is a continuous research endeavor requiring significant multidisciplinary collaboration, for the stem-cell-derived beta cells to evolve into an effective cellular therapy.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Role of Nasal Surgery in Adult Obstructive Sleep Apnea: A Systematic Review

Abstract Objective To perform a systematic review to determine if isolated nasal surgery has any impact on subjective or objective parameters in adult obstructive sleep apnea (OSA) patients. Materials and Methods From December 2022 to March 2023, we conducted a search on the PubMed, Cochrane, Scopus, and Web of Science databases. Two independent investigators performed a study selection according to the established criteria, as well as data collection, including the study design, the subjective and objective parameters addressed, the type of intervention, and the outcomes, considering the methodological quality and risk of bias. Results In total, 25 studies met the selection criteria, and they showed that there is a significant improvement in sleep quality, sleepiness, nasal resistance, and snoring after isolated nasal surgery. Still, there is no relevant modification of other polysomnographic parameters. It also reduces the required titration pressures of continuous positive airway pressure (CPAP) and increases the duration of its use. Conclusion Isolated nasal surgery is not a primary treatment for OSA. Still, it improves the subjective parameters and can lead to CPAP therapy success by enhancing its effectiveness and long-term compliance.

The Unprecedented Success of Chimeric Antigen Receptor T-Cell Therapy in the Treatment of Hematological Malignancies

The Unprecedented Success of Chimeric Antigen Receptor T-Cell Therapy in the Treatment of Hematological Malignancies

Nutritional support is an effective tool in the hands of an oncologist

As part of the XXVII Russian Oncology Congress, a section “Nutritional support — an underestimated tool in the hands of an oncologist. How to ensure successful continuous antitumor therapy?” was held. The presented message outlines the abstracts of the reports of the section participants. Report by A.R. Gevorkov concerned the relevance of nutritional support in oncology, the negative impact of nutritional deficiency on the results of surgical, drug and radiation treatment of cancer patients at all stages. Report by O.A. Obukhova was devoted to the effectiveness of nutritional support during surgical treatment of cancer patients, based on the results of well-planned and executed clinical studies, including the first domestic prospective multicenter randomized trial of perioperative high-protein enteral nutrition NUTRILUNC. Report by M.Yu. Kukosh reflected the role of rehabilitation in the continuity of antitumor treatment and the place of nutritional support in the corresponding rehabilitation program. The authors concluded that nutritional support at all stages of antitumor treatment is relevant, effective and safe, and called on oncologists to widely introduce artificial nutrition into clinical practice.

Establishment of dry-chemistry-based reference intervals of routine liver function tests for the adult population of Gandaki Province, Nepal.

Every clinical laboratory should ideally establish its own population-specific reference intervals (RIs) to promote precision and evidence-based medicine. However, clinical laboratories in Nepal find it easier to follow external RIs than establish their own, leading to a lack of RIs specific to the local population. This study thus aimed to establish RIs of routine LFTs for the adult population of Gandaki Province, Nepal, and compare them with the current RIs used by our laboratory. We established the dry-chemistry-based reference intervals of 11 common LFT parameters for the adult population of Gandaki Province, Nepal using the direct priori-based method. The combined and sex-specific 95% double-sided RIs of total protein, albumin, globulin, A/G ratio, bilirubin, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), AST/ALT ratio, and alkaline phosphatase (ALP) were established using non-parametric percentile method. The new RIs were also compared with the currently used RIs that were adopted from the reagent kit inserts. The newly established RIs for each LFT were: Total proteins: 68.0-69.0g/L, albumin: 39.0-52.0g/L; globulin: 27.0-42.0g/L; A/G ratio: 1.1-1.8; total bilirubin: 5.13-25.65μmol/L (0.30-1.50mg/dl); unconjugated bilirubin: 1.71-17.10μmol/L (0.10-1.00mg/dl); conjugated bilirubin: 0.00-10.26 μmol/L (0.00-0.60mg/dl); AST: 20.0-43.2U/L; ALT: 11.0-53.0 U/L; AST/ALT ratio: 0.7-2.1; ALP: 42.0-135.4U/L. The RIs of albumin, globulin, A/G ratio, AST, ALT, and AST/ALT ratio differed significantly (p < 0.05) between males and females. Moreover, calculated out-of-range values showed that up to 4-40% of apparently healthy adults were classified as having abnormal test results based on current RIs. The newly established RIs fulfil the need for population and platform-specific RIs for the adult population of Gandaki Province of Nepal and bring more conformity and accuracy in interpreting the LFT results, diagnosis of hepatobiliary diseases, clinical decision-making, monitoring the success of therapy and future liver specific biomedical researches within the Gandaki Province of Nepal.

Effect of Base Type Variation on Physicochemical Properties of Ambon Banana Peel (Musa Paradisiaca L) Methanol Extract Nanoemulsions Ointment

Ambon banana peel (Musa Paradisiaca L) contains flavonoids, tannins, terpenoids and saponins which have potential to be in the wound healing process. One of topical preparations suitable for wound healing is ointment. The ointment base can affect the release of active substances and absorption in the skin layers, since the release of the drug from its base is an important factor in the success of therapy. The aim of this study was to analyze the effect of base type variations on the physicochemical properties of ointments from banana peel methanol extract nanoemulsions. Ambon banana peel extract was obtained by maceration using methanol solvent and made in the form of a nanoemulsion. Ambon banana peel extract nanoemulsion is then added to the ointment preparation with water-soluble, absorption and hydrocarbon base types. Ointments with variations in base types were observed for physicochemical properties including organoleptic, homogeneity, viscosity, pH and spreadability. The data obtained were analyzed statistically using One Way ANOVA. The results showed that variations in base type affected on organoleptic appearance, viscosity and spreadability but had no effect on the pH value and homogeneity. The absorption base produces a formula that meets the requirements for ointment preparations.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

BackgroundTherapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA).MethodsIntubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients.ResultsLinezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L.ConclusionsLinezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection “lung”. Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

HPV prevalence and genotype distribution among Vietnamese cervical cancer patients in the northern region of Vietnam, from 2018 – 2020

Background/purposeHPV infection is the primary cause of cervical cancer, and genotype distribution varies according to geographical location and carcinogenicity. Therefore, identifying HPV genotype and its association with cervical cancer features is critical for screening, diagnosis, and therapy. MethodsData from Vietnamese women with HPV-positive cervical cancer were collected from the northern region. The HPV genotype was identified using the Cobas®®4800 HPV system, whereas the nucleotide sequences of the E6, E7, and L1 genes were used to identify lineages and sublineages using DNASTAR, Bioedit, ATGC 7.2, and MEGA 11.0.10 softwares. ResultsOf the 180 patients infected with HPV, 82.8 % revealed single infections, and 17.2 % showed multiple infections. HPV16 (64.4 %), HPV18 (28.9 %), and other HPVs (6.7 %) were the most prevalent HPV genotypes. HPV16 lineages included European (sublineage A1 (11.2 %), A2 (1.72 %), and A3 (25.86 %); Asian (sublineage A4 (53.85 %); African-American (sublineage D1 (5.17 %); and Asian-American (sublineage D3 (2.59 %). The HPV18 lineage includes Asian-Ameridian (sublineages A1 (100 %)). HPV18 revealed a higher rate of cervical cancer, cervicitis, warts, and ulcers than HPV16 and other high-risk genotypes in the 35–54–year–old group, but did not show a difference in cancer stages. ConclusionsHPV16 and HPV18 genotypes are common in cervical cancer in northern Vietnam, with European, Asian, and Asian–Amerindian lineages predominating. HPV18 causes cervical cancer at a higher rate than other genotypes in the 35–54–year–old age group; thus, early identification of the genotype is critical for more successful therapy.

HER2 mutation as an emerging target in advanced breast cancer.

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2-targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2-targeted drugs in HER2-mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges.

Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.

Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging. Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails (n = 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC90) of Trichophyton rubrum, the fold differences between the MIC90 and the antifungal concentrations in the nails (the multiplicity of the MIC90) were calculated overall and for the keratin-unbound fractions. Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3h following terbinafine treatment was 1414μg/g of tissue (equivalent to 4.9mM) compared with 780μg/g (2.5mM) following amorolfine treatment (not significantly different; p = 0.878). The median multiplicity of the MIC90 was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48; p = 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8; p = 0.002). In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC90 values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success.

Can failure be predicted in methotrexate treatment with the modified parameter?

The objective of the study was to increase the prediction of success of single-dose methotrexate therapy in ectopic pregnancy patients with modified parameters obtained from complete blood count and beta-human chorionic gonadotropin (β-hCG) parameters. In this way, it was aimed to predict patients whose methotrexate treatment may fail and rupture, to avoid unnecessary methotrexate treatment, to shorten the duration of hospital stay and to reduce patient mortality. 233 patients diagnosed with ectopic pregnancy between January 1, 2017, and March 01, 2022, in the obstetrics and gynecology service of a tertiary center were included in the study. The mean of β-hCG was 1976 in the methotrexate group and 2358 in the surgery group (p < 0.05). The ROC curve determined the effect of BW (β-hCGxWBC/1000) and BP (β-hCGx1000/PLT) markers in diagnosing patients who will need surgery in ectopic pregnancy. The areas under the ROC curve for β-hCG, BW and BP were 0.86, 0.99 and 0.94, respectively (p < 0.05). β-hCG > 2139.03, BW > 30.96 and BP > 10.17 values were significantly associated with the need for surgery in ectopic pregnancy patients (p < 0.05). Logistic regression analysis revealed that a 1-unit increase in BP caused a statistically significant 1.77-fold increase in surgical need in patients with ectopic pregnancy. In contrast, a 1-unit increase in BW caused a 2.34-fold increase in surgical need (p < 0.05). The study results showed that BW and BP values together with β-hCG are effective in predicting ectopic pregnancy patients who may undergo surgery.

The value of biomarkers in the therapy of CRSwNP with biologicals-a long-term follow-up of dupilumab therapy.

Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. The follow-up was performed with 104 patients retrospectively up to 22months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. There was substantially improvement in all clinical parameters up to 1year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5billion/L) had a trend of better SNOT-22 development after 1year (- 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. Dupilumab has considerably reduced symptoms and disease severity even beyond 1year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings.

Nanotechnology-Powered Meningitis Therapies: Lipid Nanoparticles Lead the Way.

The meninges serve as a protective layer, and the fluid around the brain and spinal cord can become inflamed, known as meningitis. Lipid-based pharmaceutical formulations, by their high lipophilicity, can negotiate the Blood-Brain Barrier (BBB). The current mode of treatment of meningitis is mainly through antibiotics, which, at best, is partially effective. The success of antibiotic therapy depends on several factors, for example, the difficulty of reaching the infection site, maintaining proper concentrations of the drug after crossing the BBB, and finally, its efficacy in preventing recurrent infection. In this context, interest has focused on organic and inorganic nanostructures for meningitis and transporting antibiotics to the selected region through the BBB. A focus has also been placed on several polymeric nanotechnology techniques for detecting various types of meningitis. This review focuses on nano interventions and their most recent meningitis treatments using nanotechnology.

Factors influencing TSH suppression efficacy in postoperative papillary thyroid carcinoma patients: a retrospective cohort study

ObjectivesWhile surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC.MethodsThis study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy.ResultsThere were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P < 0.05), and the ROC curve analysis indicated that the area under the curve for the preoperative TSH index was 0.610 (P < 0.05). The proportion of patients in the TSH level conforming group who took oral levothyroxine sodium tablets at a dose of ≥ 1.4 µg/kg·d after surgery was higher (P < 0.05). The postoperative levels of FT3 and FT4 were higher in the TSH level conforming group (P < 0.05). The results of binary logistic regression analysis indicated that factors “Postoperative TSH level ≥ 2 mU/L”, “Levothyroxine sodium tablet dose<1.4 µg/kg·d”, and “Combined with Hashimoto thyroiditis” were significantly associated with an elevated risk of postoperative TSH levels failing to reach the target (P < 0.05).ConclusionOptimal thyroid function in patients with PTC post-surgery is best achieved when adjusting the dose of levothyroxine sodium in a timely manner to reach the target TSH level during follow-up visits.

Neutrophil-activating secretome characterizes palbociclib-induced senescence of breast cancer cells

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation.