Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Tissue specific stem cell therapy for airway regeneration.

Secondary atrophic rhinitis (AR), a consequence of mucosal damage during nasal surgeries, significantly impairs patient quality of life. The lack of effective, lasting treatments underscores the need for alternative therapeutic strategies. A major impediment in advancing research is the scarcity of studies focused on secondary AR. Our study addresses this gap by developing an animal model that closely mirrors the histopathological changes observed in patients with secondary AR. These changes include squamous metaplasia, goblet cell hyperplasia, submucosal fibrosis, and glandular atrophy. Upon administering human nasal turbinate stem cells embedded in collagen type I hydrogel in these models, we observed ciliary regeneration. This finding suggests the potential therapeutic benefit of this approach. Our animal models not only emulate the clinical manifestations of secondary AR but also serve as valuable tools for evaluating the efficacy of cell-based biotechnological interventions.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

Human Nasal Inferior Turbinate-Derived Neural Stem Cells Improve the Niche of Substantia Nigra Par Compacta in a Parkinson's Disease Model by Modulating Hippo Signaling.

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer's disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells. METHODS: Dopaminergic neuron-like cells were differentiated from SH-SY5Y cells (DA-Like cells) and treated with 1-Methyl-4-phenylpyridinium iodide to stimulate Reactive oxidative species (ROS) production. A transwell assay was conducted to validate the effect of hNTSCs on the Hippo pathway. We generated an MPTP-induced PD mouse model and transplanted hNTSCs into the substantia nigra of PD mice via stereotaxic surgery. After five weeks of behavioral testing, the brain samples were validated by immunoblotting and immunostaining to confirm the niche control of hNTSCs. RESULTS: In-vitro experiments showed that hNTSCs significantly increased cell survival and exerted anti-inflammatory effects by controlling ROS-mediated ER stress and hippocampal signaling pathway factors. Similarly, the in-vivo experiments demonstrated an increase in anti-inflammatory effects and cell survival rate. After transplantation of hNTSCs, the PD mouse model showed improved mobility and relief from PD symptoms. CONCLUSION: hNTSCs improved the survival rate of dopaminergic neurons by manipulating the hippocampal pathway through Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ) by reducing inflammatory cytokines. In this study, we found that controlling the niche of hNTSCs had a therapeutic effect on PD lesions.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Fibroblast function recovery through rejuvenation effect of nanovesicles extracted from human adipose-derived stem cells irradiated with red light.

Fibroblasts (hDFs) are widely employed for skin regeneration and the treatment of various skin disorders, yet research were rarely investigated about restoration of diminished therapeutic efficacy due to cell senescence. The application of stem cell and stem cell-derived materials, exosomes, were drawn attention for the restoration functionality of fibroblasts, but still have limitation for unintended side effect or low yield. To advance, stem cell-derived nanovesicle (NV) have developed for effective therapeutic reagents with high yield and low risk. In this study, we have developed a method using red light irradiated human adipose-derived stem cells (hADSCs) derived NV (R-NVs) for enhancing the therapeutic efficacy and rejuvenating hDFs. Through red light irradiation, we were able to significantly increase the content of stemness factors and angiogenic biomolecules in R-NVs. Treatment with these R-NVs was found to enhance the migration ability and leading to rejuvenation of old hDFs to levels similar to those of young hDFs. In subsequent in vivo experiments, the treatment of old hDFs with R-NVs demonstrated a superior skin wound healing effect, surpassing that of young hDFs. In summary, this study successfully induced rejuvenation and leading to increased therapeutic efficacy to R-NVs treated old hDFs previously considered as biowaste.

Sinonasal Outcomes of the Combined Transseptal/Transnasal Approach with Unilateral Nasoseptal Rescue Flap in Endoscopic Endonasal Transsphenoidal Surgery: A Propensity Score Matching Analysis.

Objectives The authors applied surgical techniques acquired during the use of endoscopic combined transseptal/transnasal approach to reduce approach-related morbidity and improve sinonasal outcomes. Study Design This is a retrospective cohort study of a prospectively collected database. Setting The study setting involves a tertiary referral center. Participants A total of 86 patients who underwent endoscopic endonasal transsphenoidal surgery for newly diagnosed pituitary adenomas from April 2018 to March 2021 were included. Patients treated via the combined transseptal/transnasal approach served as the study group ( n = 18); those treated via the bilateral transnasal approach comprised the control group ( n = 68). From the control group, propensity score matching (PSM) analysis was further performed to account for potential confounders and selection bias. Main Outcome Measures Paired analysis was performed for pre- and 6-month-postoperative time points in study group, control group, and PSM control group. Olfactory function was evaluated by Connecticut Chemosensory Clinical Research Center (CCCRC) test, Cross-Cultural Smell Identification Test (CCSIT), and sinonasal outcomes were assessed by Sino-Nasal Outcome Test-22 (SNOT-22). Results In the study group, CCCRC ( p = 0.517) and CCSIT ( p = 0.497) did not show any significant difference before and after surgery. There was some improvement in the symptom score of SNOT-22, but it was not statistically significant ( p = 0.115). In the control group adjusted with PSM, a significant decrease in olfaction ( p = 0.047) was observed using CCCRC. The CCSIT score was also decreased but not significant ( p = 0.163). Also, there was no difference in the improvement of SNOT-22 ( p = 0.781). Conclusion Our new surgical method preserves olfactory function without compromising surgical outcomes.

Empowering the Vehicular Network with RIS Technology: A State-of-the-Art Review.

Reconfigurable intelligent surfaces (RIS) are expected to bring about a revolutionary transformation in vehicular networks, thus paving the way for a future characterized by connected and automated vehicles (CAV). An RIS is a planar structure comprising many passive elements that can dynamically manipulate electromagnetic waves to enhance wireless communication by reflecting, refracting, and focusing signals in a programmable manner. RIS exhibits substantial potential for improving vehicle-to-everything (V2X) communication through various means, including coverage enhancement, interference mitigation, improving signal strength, and providing additional layers of privacy and security. This article presents a comprehensive survey that explores the emerging opportunities arising from the integration of RIS into vehicular networks. To examine the convergence of RIS and V2X communications, the survey adopted a holistic approach, thus highlighting the potential benefits and challenges of this combination. In this study, we examined several applications of RIS-aided V2X communication. Subsequently, we delve into the fundamental emerging technologies that are expected to empower vehicular networks, encompassing mobile edge computing (MEC), non-orthogonal multiple access (NOMA), millimeter-wave communication (mmWave), Artificial Intelligence (AI), and visible light communication (VLC). Finally, to stimulate further research in this domain, we emphasize noteworthy research challenges and potential avenues for future exploration.

Sinonasal microbiome and inflammatory profiles in fungal ball and chronic rhinosinusitis.

OBJECTIVE: Fungal balls (FB) are the main form of non-invasive fungal rhinosinusitis found in immunocompetent hosts. Bacterial coinfection affects clinical symptoms. We investigated the sinonasal microbiome and inflammatory profiles in FB and chronic rhinosinusitis (CRS) patients. METHODS: Thirty-three participants were prospectively recruited. Nasal swab samples and sinonasal tissues were collected from controls, and FB and CRS patients. DNA extraction and microbiome analysis using V3-V4 region 16S rRNA sequencing were performed. Inflammatory cytokine levels in the sinonasal tissues, blood eosinophil counts, and serum total IgE were measured. RESULTS: No significant differences were observed in species richness or evenness measures. The phylogenetic tree demonstrated that the FB samples were different from the controls. The sinus bacteria composition differed among the groups. At the phylum level, Firmicutes in FB were significantly depleted compared with those in CRS, while Proteobacteria were more enriched in FB than that in controls and CRS. At the genus level, in FB, Staphylococcus and Corynebacterium were significantly decreased compared to those in the controls. The prevalence of Haemophilus was the highest in FB. Blood eosinophil counts and IL-5 and periostin levels in the sinonasal tissue of the FB group were significantly lower than those in the CRS group. CONCLUSIONS: FB patients had different microbiome compositions and fewer type 2 inflammatory profiles than CRS patients did. However, whether these findings cause FB or result from bacterial and/or fungal infection remains unclear. Further studies are needed to reveal how these differences occur and affect the development of FB and clinical symptoms.

Evaluation of Post-Intervention Outcomes in Patients with Empty Nose Syndrome.

OBJECTIVES: To conduct a systematic review and meta-analysis of published articles to assess the impact of inferior turbinate/meatus augmentation in patients diagnosed with empty nose syndrome (ENS). DATA SOURCES: PubMed, Cochrane database, Embase, Web of Science, SCOPUS, and Google Scholar. REVIEW METHODS: Six databases were searched to December 2022. We retrieved studies evaluating improvements in refractory ENS-related symptoms based on various patient-reported outcome measures after inferior turbinate/meatus augmentation. RESULTS: As a result of meta-analysis, Sinonasal Outcome Test, Empty Nose Syndrome 6-Item Questionnaire (ENS6Q), and depression scores were measured at 1 week; 1, 3, and 6 months; and later than 12 months after intervention for patients with ENS. All scores revealed significant symptom improvement. By reference to the minimal clinically important difference of the ENS6Q (6.25), inferior turbinate/meatus augmentation relieved the nasal symptoms of ENS in the long term. Although the improvements in anxiety scores at 1 week (0.4133 [-0.3366; 1.1633], 0.00, I2 = NA) and 1 month (0.4525 [-0.0529; 0.9579], I2 = 0.0%) were not statistically significant, the scores differed significantly at 3 months (0.7351 [0.4143; 1.0559], I2 = 28.4%), 6 months (0.8297 [0.6256; 1.0337], I2 = 37.2%), and longer than 12 months (0.7969 [0.4768; 1.1170], I2 = 0.0%). CONCLUSION: These data and analysis suggest that performing inferior turbinate/meatus augmentation on ENS patients may improve not only nasal symptom scores but also accompanying psychological problems such as anxiety and depression. Laryngoscope, 134:2005-2011, 2024.

Effectiveness of temperature-controlled radiofrequency neurolysis of the posterior nasal nerve to treat chronic rhinitis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluates the effect of TRNP on rhinitis-related symptoms. METHODS: We reviewed studies retrieved from PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database to June 2023. Studies that evaluated quality-of-life and rhinitis-related symptom scores before and after treatment were analyzed, as was one sham-treatment-controlled study. RESULTS: In total, 406 patients evaluated in five studies were analyzed. TRNP significantly improved rhinitis-related symptoms-congestion, itching, rhinorrhea, and sneezing-for up to 12 months after treatment, compared to before treatment. The most significant symptom decreases were those of rhinorrhea and nasal congestion. Rhinitis-related symptoms had improved significantly at 3 months after TRNP, compared to sham surgery. TRNP improved disease-specific quality-of-life scores on the Rhinoconjunctivitis Quality of Life Questionnaire at 6 months after treatment, compared to before treatment. The rates of clinical improvement in terms of all nasal symptoms (reduction > 30% from baseline) and in quality of life (minimal clinically important difference > 0.4) after TRNP were 79% and 84% respectively. There was no severe adverse event associated with either device use or the overall procedure. CONCLUSIONS: TRNP treatment improved subjective symptoms related to rhinitis, especially rhinorrhea and nasal congestion, and also improved disease-specific quality-of-life scores.

Percutaneous insertion of long-covered biliary stents in patients with malignant duodenobiliary stricture.

OBJECTIVE: To investigate the technical feasibility, safety, and efficacy of a long-covered biliary stent in patients with malignant duodenobiliary stricture. METHODS: This retrospective study enrolled 57 consecutive patients (34 men, 23 women; mean age, 64 years; range, 32-85 years) who presented with malignant duodenobiliary stricture between February 2019 and November 2020. All patients were treated with a long (18 or 23 cm)-covered biliary stent. RESULTS: The biliary stent deployment was technically successful in all 57 patients. The overall adverse event rate was 17.5% (10 of 57 patients). Successful internal drainage was achieved in 55 (96.5%) of 57 patients. The median patient survival and stent patency times were 99 days (95% confidence interval [CI], 58-140 days) and 73 days (95% CI, 60-86 days), respectively. Fourteen (25.5%) of the fifty-five patients presented with biliary stent dysfunction due to sludge (n = 11), tumor overgrowth (n = 1), collapse of the long biliary stent by a subsequently inserted additional duodenal stent (n = 1), or rapidly progressed duodenal cancer (n = 1). A univariate Cox proportional hazards model did not reveal any independent predictor of biliary stent patency. CONCLUSIONS: Percutaneous insertion of a subsequent biliary stent was technically feasible after duodenal stent insertion. Percutaneous insertion of a long-covered biliary stent was safe and effective in patients with malignant duodenobiliary stricture. CLINICAL RELEVANCE STATEMENT: In patients with malignant duodenobiliary stricture, percutaneous insertion of a long-covered biliary stent was safe and effective regardless of duodenal stent placement. KEY POINTS: • Percutaneous insertion of long-covered biliary stents in patients with malignant duodenobiliary stricture is a safe and effective procedure. • Biliary stent deployment was technically successful in all 57 patients and successful internal drainage was achieved in 55 (96.5%) of 57 patients. • The median patient survival and stent patency times were 99 days and 73 days, respectively, after placement of a long-covered biliary stent in patients with duodenobiliary stricture.

An indirect comparative analysis of two posterior nasal nerve ablation techniques for treating chronic rhinitis: A systemic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis evaluates and compares the effects of two treatments that ablate the posterior nasal nerves for rhinitis-related symptoms: cryotherapy and radiofrequency neurolysis. METHODS: We reviewed studies retrieved from PubMed, SCOPUS, Embase, the Web of Science and the Cochrane database up to June 2023. Papers reporting quality-of-life and rhinitis-related symptom scores before and after cryotherapy, and sham-controlled studies, were analyzed. RESULTS: In total, 738 patients enrolled in 10 studies were evaluated. Both cryotherapy and radiofrequency neurolysis significantly improved rhinitis-related symptoms including congestion, itching, rhinorrhea, and sneezing, and quality of life during 12 months of follow-up. Radiofrequency neurolysis was significantly more effective than cryotherapy in terms of reducing total nasal symptom scores at up to 12 months postoperatively. In terms of individual symptoms, itching, rhinorrhea, and congestion were significantly alleviated or tended to be reduced more by radiofrequency neurolysis than by cryotherapy. The improvements in the minimal clinically important difference in total nasal symptom scores (1.0 point) after 3 months of cryotherapy and radiofrequency therapy were 81.8 % and 92.7 %, respectively. CONCLUSIONS: Cryotherapy and radiofrequency neurolysis both improved rhinitis-symptom and quality-of-life scores. Especially, radiofrequency neurolysis showed the better effectiveness for improving the nasal symptoms related to the rhinitis than cryotherapy.

Outcomes of allogeneic hematopoietic stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a currative treatment modality for diffuse large B-cell lymphoma (DLBCL) because of the intrinsic graft-versus-lymphoma effect. However, limited information is available regarding which patients with relapsed or refractory DLBCL are likely to benefit from allo-HSCT. We retrospectively analyzed data from 1268 DLBCL patients who received allo-HSCT. The overall survival and progression-free survival (PFS) rates were 30.3% and 21.6% at 3 years, respectively. Multivariate analysis revealed that stable or progressive disease at transplantation, male patient, poorer performance status at transplantation, and shorter intervals from previous transplantation were associated independently with a lower PFS. Four prognostic factors were used to construct a prognostic index for PFS, predicting 3-year PFS of 55.4%, 43.7%, 20.4% and 6.6%, respectively. The prognostic model predicted relapse rates following allo-HSCT accordingly (P < 0.0001), whereas did not predict transplantation-related mortality (P = 0.249). The prognostic index can identify a subgroup of DLBCL patients who benefit from allo-HSCT and it is worthwhile to evaluate whether this model is also applicable to patients undergoing allo-HSCT in cases of relapse after chimeric antigen receptor engineered T-cell therapy, although the application of allo-HSCT has been declining with the increase of novel immunotherapies.

Hypoglossal Nerve Stimulation Effects on Obstructive Sleep Apnea Over Time: A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to determine the efficacy of hypoglossal nerve stimulation (HGS) in the treatment of obstructive sleep apnea. DATA SOURCES: PubMed, Cochrane database, Embase, Web of Science, SCOPUS, and Google Scholar. REVIEW METHODS: Five databases were reviewed to identify relevant studies that measured polysomnography parameters such as the apnea-hypopnea index (AHI) and oxygen desaturation index, as well as quality of life and functional outcomes of sleep questionnaire scores, before and after HGS. RESULTS: In total, 44 studies involving 8670 patients met the inclusion criteria. At 12 months after treatment, approximately 47%, 72%, and 82% of patients achieved AHI values of <5, < 10, and <15, respectively. The reported clinical success rates according to Sher criteria were 80% within 12 months and 73% between 12 and 36 months. While the favorable effects exhibited a gradual reduction up to 12 months postimplantation, they generally maintained a consistent level between the 12th and 36th months, as assessed by AHI < 5, <15, and success rate according to Sher criteria. CONCLUSION: HGS can enhance quality of life scores and polysomnography outcomes in obstructive sleep apnea patients. Although the positive effects gradually decreased until 12 months after implantation, they generally remained consistent between 12 and 36 months.

Scoring system for optimal cord blood unit selection for single cord blood transplantation.

BACKGROUND: We conducted a retrospective study to categorize the cord blood unit (CBU)s to identify the optimal units. METHODS: A total of 8503 adults (female, n = 3592; male, n = 4911) receiving their first single cord blood transplantation (CBT) in 2000-2019 were analyzed. Factors associated with CBUs affecting overall survival (OS) and neutrophil engraftment were selected to create ranked categorization for each outcome, followed by comparison with transplantation using HLA-matched bone marrow (BMT)/peripheral blood stem cell (PBSCT) from unrelated (n = 6052) and related donors (n = 4546). RESULTS: Sex-mismatch, CD34+ cell and CFU-GM counts were selected in the OS analysis. Considering the strong interaction between sex mismatch and CD34+ cell counts, we analyzed females and males separately. For females, female CBU with CD34+ cell counts {greater than or equal to} 0.5 × 10e5/kg and CFU-GM counts {greater than or equal to} 15 × 10e3/kg offered the best OS (Group I), followed by other groups with any (Groups II-IV) or all (Group V) of the risk factors. Group I consistently showed favorable OS (Group IV: HR1.22, P = 0.027; Group V: HR1.31, P = 0.047), comparable to those of rBMT/PBSCT (OS: HR1.02, P = 0.654) and uBM/PBSCT in patients with higher rDRI (HR1.07, P = 0.353). Male patients lacked significant factors affecting OS. Categorization for neutrophil engraftment consisting of CD34+ cell and CFU-GM counts, sex-mismatch, presence of donor-specific antibodies, and the number of HLA-mismatches was effective but not predicted OS. CONCLUSION: Our ranked categorizations sufficiently predicted female OS and engraftment. The best-ranked CBUs offered preferable outcomes comparable to conventional BM/PB donors in female but not in male patients.

Effectiveness of the Posterior Nasal Nerve Cryoablation in Allergic and Non-Allergic Rhinitis.

OBJECTIVES: This study assessed the impact of cryoablation of the posterior nasal nerve on symptoms of rhinitis in individuals with allergic rhinitis (AR) and non-allergic rhinitis (NAR). DATA SOURCES: PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases for studies published up to June 2023. REVIEW METHODS: Studies that evaluated the quality of life and rhinitis-related symptom scores before and after cryotherapy treatment, as well as sham-controlled studies, were included. RESULTS: In total, 368 patients from seven studies were analyzed. Patients who underwent cryoablation showed a significant improvement in rhinitis-related symptoms in both NAR and AR. In particular, the most significant improvement was observed in symptoms of rhinorrhea and congestion. Furthermore, cryoablation improved the disease-specific quality of life evaluated using the Rhinoconjunctivitis Quality of Life Questionnaire. The rate of clinical improvement in the total nasal symptom score (total nasal symptom score [TNSS]; >30% reduction from baseline) after cryotherapy was 74%. The change in TNSS score significantly increased over time in NAR patients (p = 0.0041). Therefore, changes in the TNSS score after 12 months of cryotherapy treatment were greater in the NAR group than in the AR group (p = 0.0020), indicating that cryoablation is effective for both types of rhinitis and has better long-term efficacy in NAR than in AR. CONCLUSIONS: Subjective symptom scores related to rhinitis, particularly for rhinorrhea and congestion, decrease after cryoablation of the posterior nasal nerve. Furthermore, the symptom improvement was greater in NAR than AR. Laryngoscope, 2023.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Characteristics of Human Nasal Turbinate Stem Cells under Hypoxic Conditions.

This study investigated the influence of hypoxic culture conditions on human nasal inferior turbinate-derived stem cells (hNTSCs), a subtype of mesenchymal stem cells (MSCs). It aimed to discern how hypoxia affected hNTSC characteristics, proliferation, and differentiation potential compared to hNTSCs cultured under normal oxygen levels. After obtaining hNTSCs from five patients, the samples were divided into hypoxic and normoxic groups. The investigation utilized fluorescence-activated cell sorting (FACS) for surface marker analysis, cell counting kit-8 assays for proliferation assessment, and multiplex immunoassays for cytokine secretion study. Differentiation potential-osteogenic, chondrogenic, and adipogenic-was evaluated via histological examination and gene expression analysis. Results indicated that hNTSCs under hypoxic conditions preserved their characteristic MSC phenotype, as confirmed by FACS analysis demonstrating the absence of hematopoietic markers and presence of MSC markers. Proliferation of hNTSCs remained unaffected by hypoxia. Cytokine expression showed similarity between hypoxic and normoxic groups throughout cultivation. Nevertheless, hypoxic conditions reduced the osteogenic and promoted adipogenic differentiation potential, while chondrogenic differentiation was relatively unchanged. These insights contribute to understanding hNTSC behavior in hypoxic environments, advancing the development of protocols for stem cell therapies and tissue engineering.