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Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD).Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.
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Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.
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Purpose@#YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. @*Results@#In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.
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Background@#Risk assessment for pulmonary resection in patients with early-stage non– small-cell lung cancer (NSCLC) is important for minimizing postoperative morbidity. Depletion of skeletal muscle mass is closely associated with impaired nutritional status and limited physical ability. We evaluated the relationship between skeletal muscle depletion and early postoperative complications in patients with early-stage NSCLC. @*Methods@#Patients who underwent curative lung resection between 2016 and 2018 and who were diagnosed with pathological stage I/II NSCLC were included, and their records were retrospectively analyzed. The psoas volume index (PVI, cm3/m3) was calculated based on computed tomography images from routine preoperative positron emission tomography- computed tomography. Early postoperative complications, defined as those occurring within 90 days of surgery, were compared between the lowest sex-specific quartile for PVI and the remaining quartiles. @*Results@#A strong correlation was found between the volume and the cross-sectional area of the psoas muscle (R2=0.816). The overall rate of complications was 57.6% among patients with a low PVI and 32.8% among those with a normal-to-high PVI. The most common complication was prolonged air leak (low PVI, 16.9%; normal-to-high PVI, 9.6%), followed by pneumonia (low PVI, 13.6%; normal-to-high PVI, 7.9%) and recurrent pleural effusion (low PVI, 11.9%; normal-to-high PVI, 6.8%). The predictors of overall complications were low PVI (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.07–4.09; p=0.03), low hemoglobin level (OR, 0.686; 95% CI, 0.54–0.87; p=0.002), and smoking history (OR, 3.93; 95% CI, 2.03–7.58; p<0.001). @*Conclusion@#Low PVI was associated with a higher rate of early postoperative complications in patients with early-stage NSCLC.
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Background@#Accurate intraoperative assessment of mediastinal lymph nodes is a critical aspect of lung cancer surgery. The efficacy and potential for upstaging implicit in these dissections must therefore be revisited in the current era of uniportal video-assisted thoracoscopic surgery (VATS). @*Methods@#A retrospective study was conducted in which 544 patients with stage I (T1abc–T2a, N0, M0) primary lung cancer were analyzed. To assess risk factors for nodal upstaging and to limit any imbalance imposed by surgical choices, we constructed an inverse probability of treatment-weighted (IPTW) logistic regression model (in addition to non-weighted logistic models). We also evaluated risk factors for early locoregional recurrence using IPTW logistic regression analysis. @*Results@#In the comparison of uniportal and multiportal VATS, the resected lymph node count (14.03±8.02 vs. 14.41±7.41, respectively; p=0.48) and rate of nodal upstaging (6.5% vs. 8.7%, respectively; p=0.51) appeared similar. Predictors of nodal upstaging included tumor size (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.12–2.70), carcinoembryonic antigen level (OR, 1.11; 95% CI, 1.04–1.18), and histologically confirmed pleural invasion (OR, 3.97; 95% CI, 1.89–8.34). The risk factors for locoregional recurrence within 1 year were found to be number of resected N2 nodes, age, and nodal upstaging. @*Conclusion@#Uniportal and multiportal VATS appear similar with regard to accuracy and thoroughness, showing no significant difference in the extent of nodal dissection.
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Objectives@#Sleep misperception is the underestimation of perceived total sleep time compared to actual total sleep time. It is observed in approximately 50% of patients with insomnia. Insomnia patients with sleep misperception report significantly higher depression than those without sleep misperception. Depression is one of the most consistent risk factors for predicting insomnia. Therefore, this study attempted to confirm the mediating effect of depression in exacerbating insomnia. @*Methods@#This study included 77 male and female aged 18–40 years who met diagnostic criteria for insomnia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Depression and insomnia severity were measured using self-report questionnaires, and actigraphy data were collected for 1 week. The sleep misperception index was calculated using the sleep diary and actigraphy. @*Results@#The Pearson correlation analysis was performed to examine the relationships between sleep misperception, insomnia, and depression. Sleep misperception was positively associated with depression (r=0.399, p<0.01). There was also a significant positive correlation between depression and insomnia severity (r=0.591, p<0.01). However, there was no significant correlation between sleep misperception and insomnia severity (r=0.210, p=0.07). Depression was found to have a full mediating effect on the relationship between sleep disturbance and severity of insomnia (n=77, B=6.1688, 95% confidence interval=2.9960, 10.4562). @*Conclusions@#This study verified the mediating effect of depression on the relationship between sleep misperception and insomnia severity. The results highlight the importance of considering depression and sleep misperception in insomnia treatment.
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Objectives@#Sleep misperception is the underestimation of perceived total sleep time compared to actual total sleep time. It is observed in approximately 50% of patients with insomnia. Insomnia patients with sleep misperception report significantly higher depression than those without sleep misperception. Depression is one of the most consistent risk factors for predicting insomnia. Therefore, this study attempted to confirm the mediating effect of depression in exacerbating insomnia. @*Methods@#This study included 77 male and female aged 18–40 years who met diagnostic criteria for insomnia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Depression and insomnia severity were measured using self-report questionnaires, and actigraphy data were collected for 1 week. The sleep misperception index was calculated using the sleep diary and actigraphy. @*Results@#The Pearson correlation analysis was performed to examine the relationships between sleep misperception, insomnia, and depression. Sleep misperception was positively associated with depression (r=0.399, p<0.01). There was also a significant positive correlation between depression and insomnia severity (r=0.591, p<0.01). However, there was no significant correlation between sleep misperception and insomnia severity (r=0.210, p=0.07). Depression was found to have a full mediating effect on the relationship between sleep disturbance and severity of insomnia (n=77, B=6.1688, 95% confidence interval=2.9960, 10.4562). @*Conclusions@#This study verified the mediating effect of depression on the relationship between sleep misperception and insomnia severity. The results highlight the importance of considering depression and sleep misperception in insomnia treatment.
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Atypical thymic carcinoid is an extremely rare tumor with a poor prognosis. In addition to its known association with multiple endocrine neoplasia type 1, its hallmark characteristics include local invasion and early distant metastasis. In this report, we share our experience treating atypical thymic carcinoid in a patient with Zollinger-Ellison syndrome.
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PURPOSE: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established. MATERIALS AND METHODS: Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy. RESULTS: Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progression-free survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response. CONCLUSION: The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to first- or second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.
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Humanos , Carcinoma Pulmonar de Células não Pequenas , Intervalo Livre de Doença , Tratamento Farmacológico , Éxons , Incidência , Coreia (Geográfico) , Mutagênese Insercional , Proteínas Tirosina Quinases , Receptores ErbB , Estudos RetrospectivosRESUMO
Atypical thymic carcinoid is an extremely rare tumor with a poor prognosis. In addition to its known association with multiple endocrine neoplasia type 1, its hallmark characteristics include local invasion and early distant metastasis. In this report, we share our experience treating atypical thymic carcinoid in a patient with Zollinger-Ellison syndrome.
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Humanos , Tumor Carcinoide , Neoplasia Endócrina Múltipla Tipo 1 , Metástase Neoplásica , Tumores Neuroendócrinos , Prognóstico , Síndrome de Zollinger-EllisonRESUMO
Epidermal growth factor receptor (EGFR)‒tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a thirdgeneration EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female patient with metastatic NSCLC developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a preexisting T790M mutation (73%) in cis and an exon 19 deletion (87%). Another 53-year-old female patient developed systemic progression after 10 months of osimertinib. CancerSCAN of the lung biopsy identified an EGFR L718Q mutation at an allele frequency of 7%, concomitant PIK3CA E545K (12.90%) and preexisting EGFR L858R (38%), but loss of the T790M mutation. The heterogeneity of osimertinib resistance mechanisms warrants further investigation into novel or combination agents to overcome the rare acquired resistances.
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Feminino , Humanos , Pessoa de Meia-Idade , Biópsia , Carcinoma Pulmonar de Células não Pequenas , Éxons , Frequência do Gene , Fígado , Pulmão , Fosfotransferases , Características da População , Receptores ErbBRESUMO
PURPOSE: Congenital hypothyroidism (CH) is the most common endocrine disorder in children. Thyroid hormone deprivation results not only in mental retardation but also growth retardation. This study investigates the final height (FH) in Korean patients with CH detected by newborn screening and examines factors that may affect the FH. METHODS: The medical records of Korean CH patients (n=45) were reviewed. The FH was examined and target height (TH) was calculated based on mid-parental height. The FH z score (FHZ) and TH z score (THZ) were computed using the 2007 Korean National Growth Chart. The FHZ and THZ were compared with a Student t test. The impact of the etiology of CH (athyreosis, dyshormonogenesis, ectopic thyoid, hypoplastic thyroid), initial serum thyroid stimulating hormone (TSH) level, initial free thyroxine (T4) level, and time of therapy initiation based on FH was assessed. RESULTS: The mean FHZ was 0.10±1.01 for male patients and −0.11±1.09 for female patients. There were no significant differences between FHZ and THZ for both female (P=0.356) and male patients (P=0.237). No significant relationship was found between FH and the etiology of CH, initial TSH level, initial free T4 level, and the time of therapy initiation. CONCLUSION: Early intervention and satisfactory management do not appear to impede growth in Korean patients with CH. Thus, early detection and proper management of patients with CH detected by newborn screening program are necessary.
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Criança , Feminino , Humanos , Recém-Nascido , Masculino , Hipotireoidismo Congênito , Intervenção Educacional Precoce , Gráficos de Crescimento , Deficiência Intelectual , Programas de Rastreamento , Prontuários Médicos , Glândula Tireoide , Tireotropina , TiroxinaRESUMO
Mesenchymal stem cells (MSCs) isolated from various tissues have been well characterized for therapeutic application to clinical diseases. However, in contrast to MSCs from other animal species, the characteristics of feline MSCs have not been fully documented. In this study, we conducted extensive characterization of feline adipose tissue-derived MSCs (fAD-MSCs). Study fAD-MSCs were individually isolated from the intra-abdominal adipose tissues of six felines. The expression levels of cell surface markers and pluripotent markers were evaluated. Next, proliferation capacity was analyzed by performing cumulative population doubling level (CPDL) and doubling time (DT) calculation assays. Differentiation potentials of fAD-MSCs into mesodermal cell lineages were analyzed by examining specific staining and molecular markers. All fAD-MSCs positively expressed cell surface markers such as CD29, CD44, CD90, CD105, CD166, and MHC-I, while CD14, CD34, CD45, and CD73 were negatively expressed. The CPDL of the fAD-MSCs was maintained until passage 5 to 6 (P5 to P6), whereas DT increased after P3 to P4. Also, stem cell-specific pluripotent markers (Oct3/4, Nanog, and SSEA-4) were detected. Importantly, all fAD-MSCs demonstrated mesodermal differentiation capacity. These results suggest that fully characterized fAD-MSCs could be beneficial when considering the use of these cells in feline disease research.