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.

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.

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.

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.

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.

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.

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.

Cardio-Oncology: A Myriad of Relationships Between Cardiovascular Disease and Cancer.

Cardiovascular disease (CVD) and cancer are the leading causes of death worldwide. With an increasing number of the elderly population, and early cancer screening and treatment, the number of cancers cases are rising, while the mortality rate is decreasing. However, the number of cancer survivors is increasing yearly. With the prolonged life span of cancer patients, the adverse effects of anti-tumor therapy, especially CVD, have gained enormous attention. The incidence of cardiovascular events such as cardiac injury or cardiovascular toxicity is higher than malignant tumors' recurrence rate. Numerous clinical studies have also shifted their focus from the study of a single disease to the interdisciplinary study of oncology and cardiology. Previous studies have confirmed that anti-tumor therapy can cause CVD. Additionally, the treatment of CVD is also related to the tumors incidence. It is well established that the increased incidence of CVD in cancer patients is probably due to an unmodified unhealthy lifestyle among cancer survivors or cardiotoxicity caused by anti-cancer therapy. Nevertheless, some patients with CVD have a relatively increased cancer risk because CVD and malignant tumors are highly overlapping risk factors, including gender, age, hypertension, diabetes, hyperlipidemia, inflammation, and obesity. With advancements in the diagnosis and treatment, many patients simultaneously suffer from CVD and cancer, and most of them have a poor prognosis. Therefore, clinicians should understand the relationship between CVD and tumors, effectively identify the primary and secondary prevention for these diseases, and follow proper treatment methods.

Pregnancy Associated Granulomatous Mastitis: Clinical Characteristics, Management, and Outcome.

Background: We have already known that idiopathic granulomatous mastitis (IGM) is a rare benign chronic inflammatory disorder that can clinically mimic breast carcinoma, especially affects parous women of childbearing age, but there is little literature to report about pregnancy associated granulomatous mastitis (PAGM). The aim of our study is to report and describe the clinical signs, managements, clinical course, and clinical outcomes after treatment of PAGM in our hospital. Methods: We retrospectively analyzed 15 pregnant patients who were diagnosed as PAGM in our hospital collected from December 2018 to December 2020 by reviewing medical records and questionnaire survey, including the patients' characteristics, clinical presentations, microbiological workups, tissue pathology, treatment modalities, outcomes, and follow-up data. Results: The mean age of these patients at diagnosis was 30.5 (range 24-35) years. All patients had one birth before, and had at least two gravida times, 6 of them (40%) had three gravida times, and only one of them had four gravida times at diagnosis. The mean weeks of gestational age were 23.7 (range 4-37) weeks. Two patients' BMI were greater than 30, which were considered obese. The mean time to presentation since last delivery was 38.4 (range 19-78) months. All patients had a history of breastfeeding; the average breastfeeding time was 12.97 months. Just 2 of them were diagnosed with lactational mastitis before. One patient smoked before, 1 patient had oral contraceptive pills before, 4 patients had breast trauma recently, 5 patients had positive bacterial culture of pyogenic fluids, 3 patients had nipple retraction, 6 patients had abnormal humoral immunity, shown as elevated C3 or C4, and 2 patients had elevated serum prolactin. All patients presented as a breast mass with pain; two of them had erythema nodosum and oligoarthritis. Nearly all patients had unilateral lesion. The mean follow-up was 11 (range 1-24) months. Thirteen patients gave birth to a healthy baby, and all babies had a healthy growth and development. Almost all patients chose observation during pregnancy. Nine patients demonstrated complete remission, five of them underwent surgery after steroids and/or antibiotics, one patient had observation alone, two chose postpartum steroids alone, and the last one chose postpartum antibiotics alone. The average time to complete remission was 11.2 (range 7-18) months. Conclusions: In general, PAGM is a much rare disorder which has onset during pregnancy, and mainly happens in the second trimester and the third trimester. PAGM patients were all parous women and generally within 5 years of their last pregnancy, also with uncertain etiology and pathogenesis. Observational therapy during pregnancy for PAGM is reliable and feasible.

Decreased Systemic and Airway Sirtuin 1 Expression in Adults With Bronchiectasis.

Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation. Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium. Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05). Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.

Clinical Analysis of Congenital Deficient Tracheal Cartilage Rings: Six Case Reports and a Literature Review.

Congenital deficiency of tracheal rings is a rare tracheal malformation that can cause central airway obstruction. Herein we reported the clinical data of six patients with symptomatic congenital deficient tracheal rings. There were five cases, with isolated short-segment absent cartilage ring located on the distal trachea (three cases), cervical trachea (one case), and distal trachea combined with bilateral bronchi (one case). Among them, four (4/5) received surgical tracheal resection, three fully recovered, and one died of severe infection. Besides that, one patient, who could not be weaned off the mechanical ventilation, died after rejecting surgery. One case had episodes of recurrent dyspnea and extubation failure due to long-segment tracheomalacia after repair of esophageal atresia and tracheoesophageal fistula. For this patient, deficient cartilage rings were suspected and confirmed at the age of 26 months. Moreover, the clinical characteristics of 12 cases with congenital deficient tracheal cartilage rings reported in previous literature were reviewed. The different characteristics between short- and long-segment deficient cartilage rings were discussed.

The Role of Epstein-Barr Virus in Adults With Bronchiectasis: A Prospective Cohort Study.

BACKGROUND: Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. METHODS: We collected induced sputum in healthy controls and spontaneous sputum at 3-6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. RESULTS: We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1ß (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor-α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. CONCLUSIONS: Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression.

Cardiac biomarkers of heart failure in chronic kidney disease.

Heart failure remains a continuing threat to patients with chronic kidney disease (CKD). Although various heart failure biomarkers have been applied for early detection, diagnosis and prognosis in CKD, these are easily affected by renal insufficiency thus limiting use in these patients. In this review, the major four groups of heart failure biomarkers are explored. These include those associated with: myocardial stretch, ie, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP); myocyte injury, ie, high-sensitivity troponin T (hsTnT), heart-type fatty acid-binding protein (H-FABP); fibrosis, matrix remodelling and inflammation, ie, soluble growth stimulating gene 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15); and renal function, ie, neutrophil gelatinase-associated lipocalin (NGAL) kidney injury molecule-1 (KIM-1), cystatin C (CysC), urinary sodium and urinary albumin. This review highlights classic heart failure biomarkers with critical values adjusted to glomerular filtration rate, summarizes research progress of new heart failure biomarkers and future research directions. Because diagnostic and prognostic usefulness of a single time point biomarker is limited, biomarkers should be combined and monitored at multiple times for optimal clinical impact.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

BACKGROUND: Exacerbations are crucial events during bronchiectasis progression. OBJECTIVES: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. METHODS: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. RESULTS: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P<.05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P<.05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P=.019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. CONCLUSIONS: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

Background: Exacerbations are crucial events during bronchiectasis progression. Objectives: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. Methods: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. Results: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P < .05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P < .05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P = .019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. Conclusions: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

Contexto: Las exacerbaciones son eventos cruciales durante la progresión de la bronquiectasia. Objetivos: Analizar las asociaciones entre el aislamiento de bacterias, virus y virus y bacterias juntas y las exacerbaciones de las bronquiectasias. Métodos: En este estudio prospectivo se incluyó a 108 pacientes a los que se siguió cada 3-6 meses y al comienzo de las exacerbaciones entre marzo de 2017 y noviembre de 2018. La muestra de esputo espontáneo se dividió para la detección de bacterias (cultivo de rutina) y virus (reacción en cadena de la polimerasa cuantitativa). Se evaluaron los síntomas y la función pulmonar durante las exacerbaciones. Resultados: La mediana de la tasa de exacerbación fue de 2,0 (rango intercuartil: 1,0-2,5) por paciente/año. En cualquier visita, los aislamientos de virus (V+) tuvieron lugar con mayor frecuencia durante el inicio de las exacerbaciones (odds ratio [OR]: 3,28; intervalo de confianza del 95% [IC 95%]: 1,76-6,12), al igual que el aislamiento de nuevas bacterias (NB+) (OR: 2,52; IC 95%: 1,35-4,71) y los aislamientos de bacterias y virus juntos (OR: 2,24; IC 95%: 1,11-4,55). Mientras que la coriza parecía más común en las exacerbaciones con V+ que en las exacerbaciones sin aislamientos de patógenos y en aquellas con NB+, los síntomas de las vías respiratorias inferiores fueron más graves en las exacerbaciones con NB+ (p < 0,05). Los niveles de interleucina-1ß en el esputo fueron más altos en las exacerbaciones con NB+ que en las exacerbaciones sin aislamiento de patógenos, y aquellas con V+ (ambos p < 0,05). De manera significativa, más síntomas de coriza se correlacionaron con aislamientos de bacterias y virus juntos durante las exacerbaciones (p = 0,019). Comparados con los V+ en solitario, los aislamientos de bacterias con y sin virus tienden a producir síntomas más graves en las vías respiratorias inferiores, pero no alteran los niveles de citocinas en el esputo durante las exacerbaciones. Conclusiones: Los aislamientos de virus, el aislamiento de nuevas bacterias y el aislamiento de bacterias y virus juntos están asociados a las exacerbaciones de las bronquiectasias. Los síntomas de las exacerbaciones pueden proporcionar información a los médicos sobre los posibles patógenos responsables.

Sputum Exosomal microRNAs Profiling Reveals Critical Pathways Modulated By Pseudomonas aeruginosa Colonization In Bronchiectasis.

Background: Pseudomonas aeruginosa (PA) colonization confers poor prognosis in bronchiectasis. However, the biomarkers and biological pathways underlying these associations are unclear. Objective: To identify the roles of PA colonization in bronchiectasis by exploring for sputum exosomal microRNA profiles. Methods: We enrolled 98 patients with clinically stable bronchiectasis and 17 healthy subjects. Sputum was split for bacterial culture and exosomal microRNA sequencing, followed by validation with quantitative polymerase chain reaction. Bronchiectasis patients were stratified into PA and non-PA colonization groups based on sputum culture findings. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to explore biological pathways corresponding to the differentially expressed microRNAs (DEMs) associated with PA colonization. Results: Eighty-two bronchiectasis patients and 9 healthy subjects yielded sufficient sputum that passed quality control. We identified 10 overlap DEMs for the comparison between bronchiectasis patients and healthy subjects, and between PA and non-PA colonization group. Both miR-92b-5p and miR-223-3p could discriminate PA colonization (C-statistic >0.60) and independently correlated with PA colonization in multiple linear regression analysis. The differential expression of miR-92b-5p was validated by quantitative polymerase chain reaction (P<0.05), whereas the differential expression of miR-223 trended towards statistical significance (P=0.06). These DEMs, whose expression levels correlated significantly with sputum inflammatory biomarkers (interleukin-1ß and interleukin-8) level, were implicated in the modulation of the nuclear factor-κB, phosphatidylinositol and longevity regulation pathways. Conclusion: Sputum exosomal microRNAs are implicated in PA colonization in bronchiectasis, highlighting candidate targets for therapeutic interventions to mitigate the adverse impacts conferred by PA colonization.

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.