Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers.

BACKGROUND: Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. METHODS: This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. RESULTS: Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001). CONCLUSIONS: The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.

Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review.

BACKGRUOUND: Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). METHODS: Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. RESULTS: In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. CONCLUSION: AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Predicting suicidal ideation using multiple serum biomarkers in patients with acute coronary syndrome.

BACKGROUND: Biomarkers for suicidal behavior in patients with acute coronary syndrome (ACS) have yet to be elucidated. This study aimed to identify a panel of serum biomarkers associated with suicidal ideation (SI) in patients with ACS. METHODS: The study evaluated 969 patients within 2 weeks of ACS (acute phase) and 711 patients 12 months later (chronic phase). The evaluation included 14 serum biomarkers covering 7 functional systems, socio-demographic/clinical characteristics, and SI assessed by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. Logistic regression models were used to analyze the data. The results showed that 195 patients (20.1 %) had SI in the acute phase, and 87 patients (12.2 %) had SI in the chronic phase. RESULTS: A combination of five serum biomarkers (tumor necrosis factor-α, interleukin-1ß, folate, troponin I, and creatine kinase-MB) was significantly associated with SI in the acute phase, and a combination of three serum biomarkers (tumor necrosis factor-α, interleukin-1ß, and folate) was significantly associated with SI in the chronic phase in a clear dose-dependent manner (all P-values < 0.001) after adjustment for relevant covariates. DISCUSSION: These findings suggest that the application of a combination of multiple serum biomarkers could improve the predictability of SI in patients with ACS at both acute and chronic phases.

Association between Weight Change and Incidence of Dyslipidemia in Young Adults: A Retrospective Cohort Study of Korean Male Soldiers.

Background: Recent lifestyle changes have increased the prevalence of dyslipidemia in Korea. Young men are known to have a low awareness of dyslipidemia and a lack of motivation to maintain their weight. However, the association between weight change and dyslipidemia in young adults has not been thoroughly examined. Methods: Data from the Armed Forces Medical Command Defense Medical Information System database were used. In this study, 15,068 soldiers who underwent private and corporal health examinations between May 2020 and April 2022 were included. The difference in weights between the two different health examinations was used to quantify weight change. Four components of the lipid profile were used to assess dyslipidemia during the corporal health examination. Results: After adjusting for relevant covariates, weight gain was associated with increased risk of dyslipidemia (adjusted odds ratio [OR], 1.38 [95% confidence interval, CI, 1.15 to 1.64] for the 5% to 10% weight gain group; and OR, 2.02 [95% CI, 1.59 to 2.55] for the ≥10% weight gain group), whereas weight loss was associated with decreased risk (adjusted OR, 0.82 [95% CI, 0.68 to 0.98] for the 5% to 10% weight loss group; and OR, 0.38 [95% CI, 0.27 to 0.53] for the ≥10% weight loss group). In subgroup analysis based on the participants' baseline body mass index, smoking status, regular exercise habits, and hypertension status, there were no significant differences between the subgroups. Conclusion: Weight change was associated with dyslipidemia in Korean male soldiers. The findings suggest that limiting weight gain in young adults by encouraging a healthy lifestyle may help prevent dyslipidemia.

Use of Serum Biomarkers to Aid Antidepressant Selection in Depressive Patients.

Objective: : This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. Methods: : This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3-12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. Results: : Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1ß and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. Conclusion: : Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.

A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review.

BACKGRUOUND: There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB. METHODS: Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers. RESULTS: Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate. CONCLUSION: FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients' medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Early Thyroid Volume Reduction in Subacute Thyroiditis Can be a Potential Indicator for Hypothyroidism.

Background: Thyroid volume has been reported to decrease significantly after episodes of subacute thyroiditis (SAT); however, the relationship between thyroid volume and hypothyroidism remains unclear. This study assessed the association between thyroid volume changes and the hypothyroid phase in patients with SAT, a condition that can progress to persistent hypothyroidism. Methods: This retrospective study evaluated 37 patients diagnosed with SAT at the Department of Endocrinology and Metabolism of Chonnam National University Hwasun Hospital (CNUHH) between 2016 and 2021. Since we could not determine the clinical characteristics of patients with SAT before their episodes, 120 healthy individuals who underwent thyroid ultrasonography during regular check-ups from 2019 to 2021 at CNUHH were selected for comparison. Subgroup analyses were performed on patients with SAT with and without the hypothyroid phase during their clinical course. Results: Thyroid volume was significantly greater in SAT patients at the first visit than in controls (p<0.05), and it decreased constantly throughout the follow-up period. Subgroup analysis showed that the initial thyroid volumes were similar in patients with SAT with and without the hypothyroid phase. However, SAT patients with the hypothyroid phase had significantly smaller thyroid volumes at the 1 month (p=0.025) and 3 month (p=0.006) follow-up visits. The reduction rate of the thyroid volume was significantly different within the first month (p=0.009). Conclusion: A greater reduction in thyroid volume in SAT patients within 1 month of episode had a higher chance of developing a subsequent hypothyroid phase, which can lead to persistent hypothyroidism. Serial thyroid ultrasonography in patients with SAT, especially within the first month, may help in predicting the disease course of SAT.

Partial Substitution of Fish Oil with Microalgae (Schizochytrium sp.) Can Improve Growth Performance, Nonspecific Immunity and Disease Resistance in Rainbow Trout, Oncorhynchus mykiss.

The price of fish oil has reached a historical peak due to a consistent downward production trend, and therefore, the search for sustainable alternative sources has received great attention. This research was conducted to evaluate dietary micro-algae, Schizochytrium sp. (SC) as fish oil (FO) replacer in rainbow trout, Oncorhynchus mykiss. In the first trial, apparent digestibility coefficient (ADC) was 92.4% for dry matter, 91.4% for crude protein, and 94.2% for crude lipid in rainbow trout. In the second trial, six diets were formulated to replace FO at 0% (CON), 20% (T20), 40% (T40), 60% (T60), 80% (T80), and 100% (T100) with SC in the rainbow trout (3.0 ± 0.4 g, mean ± SD) diet. After eight weeks' feeding trial, weight gain (WG), specific growth rate (SGR), and feed efficiency (FE) of fish fed the T20 diet were significantly higher than those of fish fed other diets (p < 0.05). However, there were no significant differences in these parameters among those of fish fed CON, T40, T60, and T80 diets. Lysozyme activity of fish fed the T20 diet was significantly higher than those of fish fed other experimental diets (p < 0.05). After 10 days of disease challenge testing with pathogenic bacteria (Lactococcus garvieae 1 × 108 CFU/mL), the cumulative survival rate of fish fed the T20 diet was significantly higher than those of fish fed the CON, T80, and T100 diets. Therefore, these results suggest dietary microalgae SC is well-digested and could replace up to 80% of fish oil in the diet of rainbow trout without negative effects on growth and immune responses.

Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy.

Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3-12 week) phase (N = 1086), and in 3-month steps during the continuation (6-12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.

Interaction effect of the serum interleukin-6 level and anxiety on the 12-week pharmacotherapeutic responses of patients with depressive disorders.

BACKGROUND: Despite the pathogenic role played by interleukin-6 (IL-6) signaling in depression, the association between baseline peripheral IL-6 signaling and the antidepressant treatment responses noted in clinical studies remains controversial. We investigated the effects of the baseline serum IL-6 (sIL-6) level and anxiety symptoms on the 12-week remission rate of depressed outpatients who received stepwise antidepressant treatments. METHODS: At baseline, sIL-6 levels were measured, and anxiety symptoms were evaluated using the Hospital Anxiety Depression Scale-Anxiety subscale (HADS-A), in 1094 patients. All received stepwise antidepressant treatment. Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7, was assessed. RESULTS: The individual and interaction effects of the sIL-6 level (as a binary [low vs. high, based on the median value of 1.65 pg/mL] or continuous variable) and the HADS-A score (as a binary [<12 vs. ≥12] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. Patients with both low sIL-6 levels (<1.65 pg/mL) and HADS-A scores <12 had the highest 12-week remission rate; a significant interaction effect was also apparent. This effect was significant even when the data were analyzed as continuous variables. CONCLUSIONS: Our study suggests that the sIL-6 level can serve as a biomarker predicting the outcome of antidepressant treatment according to the severity of anxiety symptoms.

Amiodarone-Induced Multi-Systemic Toxicity Involving the Liver, Lungs, Thyroid, and Eyes: A Case Report.

Objectives: Amiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes. Case Presentation: A 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 µIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months. Conclusions: This case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis.

Small Amphiphilic Peptides: Activity Against a Broad Range of Drug-Resistant Bacteria and Structural Insight into Membranolytic Properties.

We report the synthesis and antibacterial activities of a series of amphiphilic membrane-active peptides composed, in part, of various nongenetically coded hydrophobic amino acids. The lead cyclic peptides, 8C and 9C, showed broad-spectrum activity against drug-resistant Gram-positive (minimum inhibitory concentration (MIC) = 1.5-6.2 µg/mL) and Gram-negative (MIC = 12.5-25 µg/mL) bacteria. The cytotoxicity study showed the predominant lethal action of the peptides against bacteria as compared with mammalian cells. A plasma stability study revealed approximately 2-fold higher stability of lead cyclic peptides as compared to their linear counterparts after 24 h of incubation. A calcein dye leakage experiment revealed the membranolytic effect of the cyclic peptides. Nuclear magnetic resonance spectroscopy and molecular dynamics simulation studies of the interaction of the peptides with the phospholipid bilayer provided a solid structural basis to explain the membranolytic action of the peptides with atomistic details. These results highlight the potential of newly designed amphiphilic peptides as the next generation of peptide-based antibiotics.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 µg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98-0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48-4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41-4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

Predictive values of tumor necrosis factor-α for depression treatment outcomes: effect modification by hazardous alcohol consumption.

Inflammation is potentially associated with poor antidepressant treatment outcomes. Pro-inflammatory cytokines are influenced by hazardous alcohol consumption. The aim of the present study was to investigate the effects of the serum tumor necrosis factor-α (sTNF-α) level on antidepressant treatment outcomes in terms of the 12-week and 12-month remission rates and 24-month relapse rate, and to investigate the potential modifying effects of alcohol consumption on these associations in patients with depressive disorders. At baseline, sTNF-α was measured and alcohol-related data from the Alcohol Use Disorders Identification Test (AUDIT) and consumption history were collected from 1094 patients. Patients received stepwise antidepressant treatment. Remission at 12 weeks and 12 months was defined as a Hamilton Depression Rating Scale (HAMD) score ≤ 7. Relapse (HAMD score ≥ 14) was identified until 24 months for those who had initially responded (HAMD score <14) at 12 weeks. Higher sTNF-α levels were found to have significant effects on the 12-week and 12-month non-remission and 24-month relapse rates. These effects were more prominent in those with low levels of alcohol consumption (AUDIT score ≤ 8 or no current alcohol consumption); the effects were not significant in those exhibiting hazardous alcohol consumption (AUDIT score > 8 or current drinking). Significant interactions were found for the 12-month non-remission and relapse rates, although the interaction was not statistically significant for 12-week remission. In conclusion, baseline sTNF-α levels may be a useful predictor for both short- and long-term antidepressant treatment outcomes, and the consideration of alcohol consumption status may increase predictability, in particular for long-term outcomes.

A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.

BACKGROUND: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION: A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION: We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Surgery is a safe, effective first-line treatment modality for noninvasive prolactinomas.

PURPOSE: Dopamine agonists (DAs) have long been the recommended first-line treatment for prolactinoma. Given the remarkable developments in surgical techniques, however, surgery is on the rise. We compared the treatment outcomes of patients with noninvasive prolactinomas receiving two different initial treatments (DAs and transsphenoidal surgery). METHODS: We reviewed 745 patients with hyperprolactinemia or pituitary tumors treated from 2004 to 2020 at Chonnam National University Hwasun Hospital and identified 310 with prolactinomas. After selecting patients who had pituitary tumors with Knosp grade 0 to 1 with follow-up period over 1 year, 70 patients (29 who underwent surgery and 41 who received DAs as the initial treatment) were finally included for a comparative study. RESULTS: The surgery group exhibited better outcomes in terms of DA-free remission and the structural response, although the tumor size was significantly larger than in the DA group. The groups exhibited comparable results in terms of symptom control and the biochemical response. Univariate and multivariate analyses indicated that surgery as the initial treatment modality provided significantly better clinical outcomes in terms of DA-free remission. In the surgery group, a postoperative prolactin level < 10 ng/mL was the only significant predictor of DA-free remission. CONCLUSIONS: Transsphenoidal surgery showed comparable clinical outcomes in patients with prolactinomas, and low complication rates. The decision regarding the first-line treatment modality for non-invasive prolactinomas should be made on an individual basis.

Reverse remodelling by sacubitril/valsartan predicts the prognosis in heart failure with reduced ejection fraction.

AIMS: Despite well-established benefits of sacubitril/valsartan for cardiac reverse remodelling and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), there are some patients with limited therapeutic response, even with optimal therapy. We assessed the treatment response to sacubitril/valsartan in patients with HFrEF, focusing on the association between reverse remodelling and the prognosis. METHODS AND RESULTS: Using a retrospective cohort of consecutive patients with HFrEF treated with sacubitril/valsartan, we compared the time trajectory of cardiac function in 415 patients (1258 echocardiograms), according to the occurrence of cardiovascular death and hospitalization for HF during a median follow-up of 19.1 (interquartile range, 10.9-27.6) months. A higher sacubitril/valsartan dose was associated with a better prognosis, whereas advanced age, diabetes, left ventricular (LV) hypertrophy, left atrial enlargement, and pulmonary hypertension were associated with a worse prognosis. Patients without an event (n = 337; 81.2%) showed LV reverse remodelling (LV ejection fraction ≥45% or LV end-systolic volume reduction by 15% from baseline), which was typically observed within 6 months of sacubitril/valsartan treatment. Reverse remodelling achievement was significantly associated with a better prognosis. However, patients without reverse remodelling had a worse prognosis, as poor as that in patients with HFrEF not treated with sacubitril/valsartan. CONCLUSIONS: In patients with HFrEF treated with sacubitril/valsartan, LV reverse remodelling reflects the treatment response and predicts the prognosis, whereas a lack of reverse remodelling indicates the lack of treatment benefits. Prediction and assessment of reverse remodelling may facilitate the selection of patients with greater benefits by sacubitril/valsartan.

Effects of Bacillus subtilis WB60 and Lactococcus lactis on Growth, Immune Responses, Histology and Gene Expression in Nile tilapia, Oreochromis niloticus.

An eight-week feeding trial was conducted to evaluate the effects of a basal control diet (CON), Bacillus subtilis at 107 (BS7) and at 108 CFU/g diet (BS8), Lactococcus lactis at 107 CFU/g (LL7) and at 108 CFU/g diet (LL8), and oxytetracycline (OTC) at 4 g/kg diet on Nile tilapia. Fish with initial body weight of 2.83 ± 0.05 g (mean ± SD) were fed two times a day. Weight gain, specific growth rate, feed efficiency, protein efficiency ratio and lysozyme activity of fish fed BS8, LL8 and LL7 diets were significantly higher than those of fish fed CON diet (p < 0.05). Superoxide dismutase and myeloperoxidase activity of fish fed BS8, LL8, BS7, LL7 and OTC diets were significantly higher than those of fish fed CON diet. Intestinal villi length and muscular layer thickness of fish fed BS8, LL8 and LL7 diets were significantly higher than those of fish fed CON and OTC diets. Also, heat shock protein 70 (HSP70), interleukin (IL-1ß), interferon-gamma (IFN-γ) and tumour necrosis factor (TNF-α) gene expression of fish fed BS8 and LL8 diets were significantly higher than those of fish fed CON diet. After 13 days of challenge test, cumulative survival rate of fish fed BS8 and LL8 diets were significantly higher than those of fish fed CON, BS7 and OTC diets. Based on these results, B. subtilis and L. lactis at 108 (CFU/g) could replace antibiotics, and have beneficial effects on growth, immunity, histology, gene expression, and disease resistance in Nile tilapia.

Differential impact of smoking on cardiac or non-cardiac death according to age.

Tobacco smoking causes cardiovascular diseases, lung disease, and various cancers. Understanding the population-based characteristics associated with smoking and the cause of death is important to improve survival. This study sought to evaluate the differential impact of smoking on cardiac or non-cardiac death according to age. Data from 514,866 healthy adults who underwent national health screening in South Korea were analyzed. The participants were divided into three groups: never-smoker, ex-smoker or current smoker according to the smoking status. The incidence rates and hazard ratios (HRs) of cardiac or non-cardiac deaths according to smoking status and age groups during the 10-year follow-up were calculated to evaluate the differential risk of smoking. Over the follow-up period, 6,192 and 24,443 cardiac and non-cardiac deaths had occurred, respectively. The estimated incidence rate of cardiac and non-cardiac death gradually increased in older age groups and was higher in current smokers and ex-smokers than that in never-smokers among all age groups. After adjustment of covariates, the HRs for cardiac death of current smokers compared to never-smokers were the highest in individuals in their 40's (1.82; 95% CI, 1.45-2.28); this gradually decreased to 0.96 (95% CI, 0.67-1.38) in individuals >80 years. In contrast, the HRs for non-cardiac death peaked in individuals in their 50's, (HR 1.69, 95% CI 1.57-1.82) and was sustained in those >80 years (HR 1.40, 95% CI 1.17-1.69). Ex-smokers did not show elevated risk of cardiac death compared to never-smokers in any age group, whereas they showed significantly higher risk of non-cardiac death in their 60's and 70's (HR, 1.29; 95% CI, 1.19-1.39; HR 1.22, 95% CI, 1.12-1.32, respectively). Acute myocardial infarction and lung cancer showed patterns similar to those of cardiac and non-cardiac death, respectively. Smoking was associated with higher relative risk of cardiac death in the middle-aged group and non-cardiac death in the older age group. Ex-smokers in the older age group had elevated risk of non-cardiac death. To prevent early cardiac death and late non-cardiac death, smoking cessation should be emphasized as early as possible.

Development of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets.

Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10-20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection.