Coronary computed tomography angiography-derived total coronary plaque burden associated with subsequent cardiovascular outcomes following percutaneous coronary intervention.

OBJECTIVE: To investigate the association of coronary plaque burden variables derived from coronary computed tomography angiography (CCTA) before patients underwent their first percutaneous coronary intervention (PCI) procedure and major adverse cardiovascular events (MACEs) after PCI. METHODS: Patients who underwent CCTA before their first PCI were included retrospectively. A radiologist and a cardiologist analyzed CCTA images on a dedicated workstation. The coronary plaque burden variables included total plaque volume, total percent atheroma volume, volumes and fractions of total low-attenuation plaque, total fibrous plaque, and total calcified plaque. The primary outcomes were MACEs, a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unscheduled coronary revascularization. RESULTS: A total of 230 patients were included in the final analysis. During a median follow-up of 4.8 years, 67 MACEs occurred. Total plaque volume, total percent atheroma volume, volumes of total low-attenuation plaque and total fibrous plaque but not their fractions were independent predictors for MACEs. Compared with the first tertiles, the hazard ratio of the third tertile of total plaque volume, total percent atheroma volume, total low-attenuation plaque volume, and total fibrous plaque volume were 2.06 (95% CI: 1.03-4.15), 2.15 (95% CI: 1.02-4.51), 3.04 (95% CI: 1.45-6.36), and 2.23 (95% CI: 1.11-4.46), respectively. Neither total calcified plaque volume nor fraction was associated with MACEs independently. CONCLUSION: Selected pre-PCI CCTA-derived variables, including total percent atheroma volume, volumes of total plaque, total low-attenuation plaque and total fibrous plaque, were significantly associated with MACEs after PCI, suggesting that CCTA before PCI reveals the residual risk after revascularization. CLINICAL RELEVANCE STATEMENT: The coronary plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention are independently associated with major adverse cardiovascular events, which could be instrumental in optimizing patient management. KEY POINTS: Coronary plaque burden is associated with cardiovascular events in patients with coronary artery disease. Selected total plaque burden variables derived from coronary computed tomography angiography before percutaneous coronary intervention were associated with poor prognosis. Routine coronary computed tomography angiography before percutaneous coronary intervention might be helpful in reducing future risks.

Differential airway resistome and its correlations with clinical characteristics in Haemophilus- or Pseudomonas-predominant microbial subtypes of bronchiectasis.

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.

Clinical characteristics and therapeutic strategy of granulomatous mastitis accompanied by Corynebacterium kroppenstedtii: a retrospective cohort study.

BACKGROUND: Increasing evidence has suggested that Corynebacterium kroppenstedtii is associated with some cases of granulomatous mastitis, mostly based on pathology or microbiology. We aimed to identify the clinical characteristics and treatment regimens for granulomatous mastitis with Corynebacterium kroppenstedtii infection. Understanding these clinical features is essential for patient care. METHODS: We retrospectively collected data on 201 patients who were pathologically diagnosed with granulomatous mastitis and had microbiological results of either Corynebacterium kroppenstedtii or no bacterial growth and recorded and analysed their demographics, clinical characteristics, and clinical outcomes. RESULTS: There were 107 patients in the CK group and 94 patients in the negative group. Sinus formation (x2 = 13.028, p = 0.000), time to complete remission at the first treatment period (Z = -3.027, p = 0.002), diameter of breast mass at first-time medical consultancy (Z = -2.539, p = 0.011) and recurrence (x2 = 4.953, p = 0.026) were statistically significant. Age (Z = -1.046, p = 0.295), laterality (x2 = 4.217, p = 0.121), time to presentation since the last delivery (x2 = 0.028, p = 0.868), BMI (Z = -0.947, p = 0.344), lactation time (Z = -1.378, p = 0.168), parity (x2 = 1.799, p = 0.180), gravida (Z = -0.144, p = 0.885), history of lactational mastitis or abscess (x2 = 0.115, p = 0.734), local trauma (x2 = 0.982, p = 0.322), hyperprolactinemia (x2 = 0.706, p = 0.401), erythema nodosum (x2 = 0.292, p = 0.589), and nipple discharge (x2 = 0.281, p = 0.596) did not demonstrate statistical significance. Regarding recurrence related to therapeutic strategy, except for surgery combined with immunosuppressants (x2 = 9.110, p = 0.003), which was statistically significant, none of the other treatment regimens reached statistical significance. The recurrence rate of patients in the CK group using rifampicin in their treatment course was 22.0% (x2 = 4.892, p = 0.027). CONCLUSIONS: Granulomatous mastitis accompanied by Corynebacterium kroppenstedtii more easily forms sinuses and has a higher recurrence rate. Both of the clinical characteristics may indicate that Corynebacterium kroppenstedtii plays an important role in the development and progression of granulomatous mastitis. Lipophilic antibiotics may be essential for granulomatous mastitis with Corynebacterium kroppenstedtii infection.

Management of Granulomatous Lobular Mastitis and Risk Factors Associated with Recurrence.

BACKGROUND: Granulomatous lobular mastitis (GM), an inflammatory breast lesion with unknown etiology, is prone to recur. There is no global consensus on the optimal treatment at present. This study was conducted to show our step-by-step systemic procedure and discuss the recurrence risk factors of GM. METHODS: The medical record database was retrospectively searched for patients with GM treated in our hospital between January 2015 and September 2021. Patients were divided into non-recurrence group (group A) and recurrence group (group B). Demographic and clinical characteristics, treatment and follow-up were collected and analyzed. RESULTS: A total of 885 GM patients were included in our study, all of whom received step-by-step systemic management. The mean age was 33.2 ± 5.2 years. There were 760 (85.9%) patients in group A and 125 (14.1%) in group B. Univariate analysis showed that there was no statistically significant difference between the two groups in size of mass, pregnancy, hyperprolactinemia, bacterial cultures, erythema nodosum. Multivariate analysis showed that patients with purulent nipple discharge, skin lesion, bilateral disease and patients who need the combination of surgery and medication to achieve complete remission had higher risk of recurrence. CONCLUSIONS: We built a step-by-step systemic procedure for GM, and the recurrence rate was 14.1%. Prolactin level and microbiological results are important for the management of GM. Purulent nipple discharge, skin lesion, bilateral disease and patients who need the combination of surgery and medication to achieve complete remission are associated with GM recurrence. Prolonged maintenance therapy may secure a better prognosis.

A case management model for patients with granulomatous mastitis: a prospective study.

BACKGROUND: Granulomatous mastitis (GM) is a chronic inflammatory mastitis disease that requires long-term treatment and has a high recurrence rate. Case management has been proven to be an effective mechanism in assisting patients with chronic illness to receive regular and targeted disease monitoring and health care service. The aim of this study was to investigate the application of a hospital-to-community model of case management for granulomatous mastitis and explore the related factors associated with its recurrence. METHODS: This was a prospective study on patients with granulomatous mastitis based on a case management model. Data on demographic, clinical and laboratory information, treatment methods, follow-up time, and recurrence were collected and analyzed. The eight-item Morisky Medication Adherence Scale (MMAS-8) was used to investigate patients' adherence to medications. Logistic regression models were built for analysis of risk factors for the recurrence of granulomatous mastitis. RESULTS: By October 2021, a total of 152 female patients with a mean age of 32 years had undergone the entire case management process. The mean total course of case management was 24.54 (range 15-45) months. Almost all the patients received medication treatment, except for one pregnant patient who received observation therapy, and approximately 53.9% of the patients received medication and surgery. The overall recurrence rate was 11.2%, and "high" medication adherence (RR = 0.428, 95% CI 0.224-0.867, P = 0.015) was significantly associated with a lower rate of recurrence, while the rate of recurrence with a surgical procedure + medication was higher than that with medication alone (RR = 4.128, 95% CI 1.026-16.610, P = 0.046). CONCLUSION: A case management model for patients with granulomatous mastitis was applied to effectively monitor changes in the disease and to identify factors associated with disease recurrence. "Low" medication adherence was a significant risk factor for the recurrence of granulomatous mastitis. Patients treated with medication and surgery were more likely to experience recurrence than those treated with medication alone. The optimal treatment approach should be planned for granulomatous mastitis patients, and patient medication adherence should be of concern to medical staff.

Methotrexate and low-dose corticosteroid: An effective alternate against corticosteroid-resistant granulomatous lobular mastitis.

AIM: Granulomatous lobular mastitis (GM) is an inflammatory breast disease with unknown etiology. Studies showed that some patients could achieve complete remission with corticosteroids and excisional surgery. However, some patients would suffer from corticosteroid resistance. We aim to report our single-center experience with the highest number of corticosteroid-resistant GM patients treated by methotrexate and low-dose corticosteroid. METHODS: The medical record database in our center was searched retrospectively for GM patients between January 2015 and January 2022. Patients suffered corticosteroid resistance and received methotrexate-containing regimen were included in this study. The clinical characteristics, management and outcomes were collected and analyzed. RESULTS: Eighty-one patients with the median follow-up of 18 months (range 5-61 months) were included. The median age was 30 years old (range 21-48 years). The common initial complaints were breast mass, pain, and erythema. The initial treatment of 80 (98.8%) patients was methylprednisolone. Patients were switched to methotrexate and low-dose corticosteroid due to corticosteroid resistance. Complete remission was achieved in 61 (75.3%) patients who received methotrexate and low-dose corticosteroid with or without segmental dissection. Nineteen methotrexate-resistant patients were referred for antimycobacterial treatment with the exception that one patient was lost during follow-up. Thirteen of them achieved complete remission, and the other five gained partial remission and received segmental dissection. None of these methotrexate-resistant patients recured. CONCLUSION: An approach with methotrexate and low-dose corticosteroid should be considered as an alternative method to corticosteroid-resistant GM patients.

Controlling and optimizing the morphology and microstructure of 3D interconnected activated carbons for high performance supercapacitors.

For an active electrode material, the morphology, microstructure and the effective specific surface area derived from them, have a dominant effect for the high performance supercapacitors. In this study, 3D interconnected activated carbons with controlled and optimized morphologies and porous structures were prepared from accessible carbon source and graphene oxide by a hydrothermal carbonization and following an activation method. Through optimizing the ratios of the precursors and reaction conditions, an electrode material with excellent specific surface area of 2318 m2 g-1, meso-/macro-pore ratio of 63.2% (meso-/macro-pore volume reached to 0.83 cm3 g-1), as well as an outstanding electrical conductivity of 46.6 S m-1, was obtained. The materials exhibit superior double-layer capacitive performances on a symmetric supercapacitor, delivering superior specific capacitance of 157 F g-1 in organic electrolyte system at current density of 0.5 A g-1, excellent energy density of 37.6 W h kg-1 with a power density of 7.1 kW kg-1 and good cycling stability of capacitance retention of 94% over 7000 cycles. These results offer a practical method to prepare the desired carbon electrode materials with controlled morphology and structure for high efficiency electrochemical energy storage devices.

Effective inhibition of Cbf-14 against Cryptococcus neoformans infection in mice and its related anti-inflammatory activity.

Cbf-14 (RLLRKFFRKLKKSV), a designed peptide derived from cathelicidin family AMP, has proven to be potent against drug-resistant bacteria. In the present study, we investigated the anti-cryptococcal activity of Cbf-14 in vitro and in a pulmonary infection mouse model. Sensitivity test indicated that Cbf-14 possessed effective antifungal activity against Cryptococcus neoformans with an MIC of 4-16 µg/ml, and killing experiments showed that fungicidal activity was achieved after only 4 h treatment with Cbf-14 at 4× MIC concentrations in vitro. Meanwhile, Cbf-14 was effective at prolonging the survival of infected mice when compared with controls, and significantly inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, suggesting its anti-inflammatory activity against fungal infections. As a positively charged peptide, Cbf-14 was proven to neutralize the negative zeta potential of the fungal cell surface, disrupt the capsule polysaccharide of fungi, and further damage cell membrane integrity. These results were confirmed by flow cytometry analysis of the fluorescence intensity after PI staining, while cell membrane damage could be clearly observed by transmission electron microscopy after Cbf-14 (4× MIC) treatment for 1 h. In addition, Cbf-14 increased the IL-10 levels in cultured RAW 264.7 cells, which were stimulated by C. neoformans infection. The obtained data demonstrated that Cbf-14 could rapidly kill C. neoformans cells in vitro, effectively inhibit C. neoformans induced-infection in mice, and inhibit inflammation in vitro / vivo. Therefore, Cbf-14 could potentially be used for the treatment of fungal infections clinically.

A study on the relationship between chemotherapy-induced cognitive impairment and age in patients with breast cancer.

PURPOSE: To investigate the correlation of chemotherapy-induced cognitive impairment (CICI) with age in patients with triple-negative breast cancer (TNBC). METHODS: A total of 120 breast cancer patients with different ages and receiving chemotherapy were selected as breast cancer group, and another 120 healthy subjects were enrolled as healthy control group. Breast cancer group included 60 TNBC patients (TNBC group) and 60 patients without TNBC (non-TNBC group). Both breast cancer and healthy control group were further divided into young group (n=40), middle-aged group (n=40) and elderly group (n=40). For TNBC group and non-TNBC group, each age group had 20 patients. Then, mini-mental state examination (MMSE), retrospective memory (RM) and prospective memory (PM) questionnaires were performed separately. RESULTS: There were statistically significant differences in MMSE, RM and PM scale scores between breast cancer group and healthy control group (p<0.001). In breast cancer group, the MMSE score was negatively correlated with age (r=-0.614, p<0.001), and the RM scale and PM scale scores were positively related to age (r=0.527, 0.439, p<0.001). The differences in MMSE, RM and PM scale scores were statistically significant between TNBC group and non-TNBC group (p<0.05). Moreover, the scores of MMSE, RM scale and PM scale were statistically significant among the young, middle-aged and elderly group in both TNBC group and non-TNBC group (p<0.001). In young group, there were statistically significantly differences in scores of MMSE, RM scale and PM scale between TNBC group and non-TNBC group (p<0.001). In middle-aged and elderly group, the scores of MMSE, PM scale and RM scale also had statistically significant differences between TNBC group and non-TNBC group (p<0.001). Multivariate logistic regression analyses revealed that TNBC [odds ratio (OR)=3.659, p=0.004] and age (OR =1.128, p<0.001) were risk factors for the occurrence of cognitive impairment in patients with breast cancer. CONCLUSIONS: Patients receiving chemotherapy for breast cancer suffer from varying degrees of cognitive impairment. The cognitive impairment in TNBC patients is more severe than that in patients without TNBC, the difference being mainly detected in young patients. In addition, both TNBC and age are risk factors for CICI in breast cancer.

Clinical analysis of bronchoscopic cryotherapy in 156 pediatric patients.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of bronchoscopic cryotherapy for pediatric poor ventilation. METHODS: A total of 156 pediatric patients with airway stenosis and obstruction as well as pulmonary atelectasis received bronchoscopic cryotherapy. Treatment efficacy was evaluated on bronchoscopy Before cryotherapy and after the last cryotherapy treatment. Pulmonary atelectasis was assessed according to range of atelectasis on chest computed tomography (CT), and tracheobronchial stenosis according to pulmonary function, tidal volume analysis and dyspnea index. RESULTS: The 154 patients with effective treatment had patent airway, smooth mucosa and resolved atelectasis. In the two patients with ineffective treatment, however, the airway was not smooth and the range of pulmonary atelectasis was reduced by <30%. Among the 156 patients, 136 had markedly effective treatment, with CT pulmonary atelectasis recovery >70%. The width of the main airway significantly increased approximately 50% and the tidal volume or capacity increased 100%. Effective treatment was identified in 18 patients (18/156), with CT pulmonary atelectasis area reduced 30-70%. Ineffective treatment was noted in two patients, with CT pulmonary atelectasis area reduced by <30%. No complications were noted in any patients during or after operation. No recurrence was noted on follow up of 2-24 months. CONCLUSION: Bronchoscopic cryotherapy is effective and safe for dyspnea caused by airway obstruction, and wide application in clinic is recommended.

A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge.

Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated with nipple discharge. This study investigated the relationships between ductoscopic image-based indicators and breast cancer risk, and developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge. A total of 879 consecutive inpatients (916 breasts) with nipple discharge who underwent selective duct excision for intraductal neoplasms detected by MD from June 2008 to April 2014 were analyzed retrospectively. A nomogram was developed using a multivariate logistic regression model based on data from a training set (687 cases) and validated in an independent validation set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for the diagnosis of breast cancer. Color of discharge, location, appearance, and surface of neoplasm, and morphology of ductal wall were independent predictors for breast cancer in multivariate logistic regression analysis. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.36. Area under the curve values of 0.812 (95 % confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was obtained in the training and validation sets, respectively. The accuracies of the nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 % in the validation set. We developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge based on MD image findings. This model may aid individual risk assessment and guide treatment in clinical practice.

Recombinant expression of glpK and glpD genes improves the accumulation of shikimic acid in E. coli grown on glycerol.

Shikimic acid (SA) is an industrially important chiral compound used in diverse commercial applications, and the insufficient supply by isolation from plants and expensive chemical synthesis of SA has increased the importance of developing strategies for SA synthesis. In our previous studies, glycerol was observed to be an effective carbon source for SA accumulation in E. coli DHPYAAS-T7, where the PTS operon (ptsHIcrr) and aroL and aroK genes were inactivated, and the tktA, glk, aroE, aroF (fbr) , and aroB genes were overexpressed. For further investigation of the effects of glycerol aerobic fermentation on SA accumulation in E. coli BL21(DE3), the glpD, glpK genes and tktA, glk, aroE, aroF (fbr) , aroB genes were overexpressed simultaneously. The results indicated that SA production was increased 5.6-fold, while the yield was increased 5.3-fold over that of parental strain in shake flasks. It is demonstrated that the aerobic fermentation of glycerol associated with glpD and glpK gene overexpression increased glycerol flux, resulting in higher SA accumulation in E. coli BL21(DE3)-P-DK.

Comparing lycopene's impact on mortality in adults with or without obesity.

Objective: Given lycopene's anti-inflammatory and antioxidant properties, we investigated its mortality impact in individuals with and without obesity, confirming distinct effects. Methods: This study analyzes the National Health and Nutrition Examination Survey (NHANES) data from 2003-2006 and 2017-2018, linking lycopene levels to all-cause and cardiovascular mortality. Using various statistical methods, three models are sequentially adjusted for confounders, investigating the lycopene-outcome relationship. Results: We studied 11 737 adults for 162 months and found 1537 all-cause deaths (13.1%) and 443 cardiovascular deaths (3.8%). For those without obesity, serum lycopene had an "L" shape relationship with all-cause mortality, being harmful at very low levels but protective above a certain threshold. It consistently protects against cardiovascular mortality. In individuals with obesity, the relationship with all-cause mortality formed a "U" shape, with increased risk at very low and very high lycopene levels and protection in the middle range. Cardiovascular mortality showed a similar pattern in individuals with obesity. Interestingly, dietary lycopene intake had protective effects in both groups. Conclusion: This study reveals that lycopene exhibits distinct associations with all-cause and cardiovascular mortality in populations with or without obesity, emphasizing the importance of considering individual health profiles when assessing its benefits.

Refractory hypotension and coronary artery spasm induced by antipsychotic drugs: A challenging case and treatment consideration: A case report and literature review.

RATIONALE: Coronary artery spasms may result from supply-demand mismatch due to hypotension. Norepinephrine is more effective in ameliorating antipsychotic-induced refractory hypotension. PATIENT CONCERNS: Postoperative difficult-to-correct hypoperfusion occurs in patients with comorbid depression and coronary spasm; the use of norepinephrine and epinephrine for rapidly raising blood pressure needs to be considered. DIAGNOSES: Electrocardiogram is an auxiliary tool and Digital Substraction Angiography is the gold standard for the diagnosis. INTERVENTIONS: Surgery and correct choice of raising blood pressure are the main treatment methods. OUTCOMES: Hypotension induced by the use of antipsychotics after angiography is difficult to correct with dobutamine, and the above scenario is relatively rare in the clinic, where norepinephrine could be a potential therapeutic option. LESSONS: Based on the lessons learnt from this case, caution must be exercised when dealing with patients on multiple antipsychotics during the perioperative period, while pressor-boosting medications should not be limited to conventional drugs such as dopamine. Norepinephrine may be more effective in dealing with difficult-to-correct hypoperfusion.

COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, of which cardiovascular system diseases are one of the main manifestations, such as myocarditis, myocardial infarction, and arrhythmia, which threaten the infected population worldwide. These diseases threaten the cardiovascular health of infected populations worldwide. Although the prevalence of coronavirus disease 2019 (COVID-19) has slightly improved with virus mutation and population vaccination, chronic infection, post-infection sequelae, and post-infection severe disease patients still exist, and it is still relevant to study the mechanisms linking COVID-19 to cardiovascular disease (CVD). This article introduces the pathophysiological mechanism of COVID-19-mediated cardiovascular disease and analyzes the mechanism and recent progress of the interaction between SARS-CoV-2 and the cardiovascular system from the roles of angiotensin-converting enzyme 2 (ACE2), cellular and molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, and psychosocial factors, respectively. We also discussed the differences and mechanisms involved in cardiovascular system diseases combined with neocoronavirus infection in different populations and provided a theoretical basis for better disease prevention and management.

Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?

Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill patients need to be further improved and perfected. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator, and some studies have demonstrated its potential therapeutic use for COVID-19, severe respiratory distress syndrome, pulmonary infections, and pulmonary hypertension. In this article, we describe the biochemistry and basic characteristics of NO and discuss whether iNO can act as a "savior" for COVID-19 and related respiratory and cardiovascular disorders to exert a potent clinical protective effect.

Obesity, birth weight, and lifestyle factors for frailty: a Mendelian randomization study.

Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is uncertain. We conducted a two-sample Mendelian randomization study to investigate the associations. Genetic instruments associated with the exposures at the genome-wide significance level (p < 5 × 10-8) were selected from corresponding genome-wide association studies (n = 143,677 to 703,901 individuals). Summary-level data for the frailty index were obtained from the UK Biobank (n = 164,610) and Swedish TwinGene (n = 10,616). The ß of the frailty index was 0.15 (p = 3.88 × 10-9) for 1 standard deviation increase in the prevalence of smoking initiation, 0.19 (p = 3.54 × 10-15) for leisure screen time, 0.13 (p = 5.26 × 10-7) for body mass index and 0.13 (p = 1.80 × 10-4) for waist circumference. There was a suggestive association between genetically predicted higher birth weight and moderate-to-vigorous intensity physical activity with the decreased risk of the frailty index. We observed no causal association between genetically predicted age of smoking initiation and alcoholic drinks per week with the frailty index. This study supports the causal roles of smoking initiation, leisure screen time, overall obesity, and abdominal obesity in frailty. The possible association between higher birth weight, proper physical activity and a decreased risk of frailty needs further confirmation.

The association of blood ctDNA levels to mutations of marker genes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a deadly and commonly diagnosed cancer. Cell-free circulating tumor DNAs (ctDNA) have been used in the diagnosis and treatment of CRC, but there are open questions about the relationship between ctDNAs and CRC. Although mutations of genes detected by ctDNA in CRC have been studied, the quantitative relationship between ctDNA mutations and ctDNA concentration has not been addressed. AIMS: We hypothesized that there was an association between mutations of genes identified in ctDNAs and ctDNA concentration. His study examined this association in a population of CRC patients. METHODS: In 85 CRC patients, we sampled 282 mutations in 36 genes and conducted an association study based on a Random forest model between mutations and ctDNA concentrations in all patients. RESULTS: This association study showed that mutations on five genes, ALK, PMS2, KDR, MAP2K1, and MSH2, were associated with the ctDNA concentrations in CRC patients' blood samples. Because ctDNA mutations correlate with ctDNA level, we can infer the tumor burden or tumor size from ctDNA mutations, as well as the survival time for prognosis. CONCLUSION: Our findings shed light on the associations between mutations of genes identified in ctDNAs and ctDNA concentration in the blood of CRC patients. This discovery provides information regarding the tumor burden or tumor size based on ctDNA mutations.

Characteristics and Management of Granulomatous Lobular Mastitis Associated with Antipsychotics-Induced Hyperprolactinemia.

Background: Granulomatous lobular mastitis (GM) is a rare inflammatory breast disease. Reports focusing on GM caused by antipsychotic-induced hyperprolactinemia (HPRL) are very rare. Aim: To report a study of GM associated with antipsychotic-induced HPRL and discuss the mechanism and management. Materials and Methods: A retrospective review of patients with GM and psychiatric disorders were carried out. The clinical characteristics, management and outcome were collected and analyzed. The relationship between antipsychotics and GM was evaluated using the Naranjo Adverse Drug Reaction Probability Scale (Naranjo scale). Results: Nineteen female GM patients with psychiatric diseases, aged 21-39 years, who had received antipsychotics for 0.5-10.2 years were included. Most patients took multiple antipsychotics, and 10 (52.6%) took risperidone-containing regimens. Increased prolactin (PRL) was detected in all patients (range 35.15-200 ng/mL). The scores of Naranjo scale were 7-8, indicated the antipsychotics probably induced GM. All patients received systemic therapy, and were prescribed bromocriptine. Seven patients (36.8%) decreased the dose of antipsychotics, six (31.6%) switched antipsychotics, three (15.8%) continued the primary antipsychotics, and three (15.8%) discontinued antipsychotics. In addition, 14 patients (73.7%) received corticosteroid, 4 (21.1%) received antimycobacterials. PRL decreased to normal in 1 month. Seven patients (36.8%) received excisional surgery. After 12 months' follow-up (range 9-56 months), only three patients (15.8%) had a recurrence. Conclusion: Long-term use of antipsychotics may increase PRL levels, and lead to GM. It is vital to assess PRL level and reduce PRL to normal in patients with GM.