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Summary: Background: Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. Objectives: To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. Methods: We conducted a cross‐sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. Results: The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4–4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7–7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4–13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1–5·7; P = 0·038) and tumour stages III–IV (vs. I–II) (OR 3·4, 95% CI 1·6–7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. Conclusions: T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis. What is already known about this topic?Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma, at least in men, in addition to protective antitumoral activity as a result of metformin treatment. What does this study add?This multicentric study of a large series of prospectively recruited and well‐characterized patients with cutaneous melanoma shows, for the first time, that the presence of underlying T2DM, rather than metformin treatment, is associated with markers of increased tumour aggressiveness independently of confounders.Patients with melanoma and T2DM constitute a more aggressive phenotype of this tumour, unrelated to treatment with metformin.Melanoma prevention should be strengthened in patients with T2DM to minimize the negative impact of this metabolic disorder on melanoma aggressiveness. Linked Comment: A.E. Cust. Br J Dermatol 2021; 185:692–693. Plain language summary available online [ABSTRACT FROM AUTHOR]

Context: Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear.Objective: To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA.Design, Setting, and Patients: Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009.Intervention: Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice.Main Outcome Measures: Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).Results: Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20).Conclusions: In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference.Trial Registration: clinicaltrials.gov Identifier: NCT00127348. [ABSTRACT FROM AUTHOR]

RATIONALE: Home respiratory polygraphy (HRP) is an alternative to polysomnography (PSG) for sleep apnea-hypopnea syndrome (SAHS) diagnosis. However, therapeutic decision-making is a different process than diagnosis. OBJECTIVES: This study aimed to determine the agreement between HRP and in-hospital PSG for therapeutic decision-making in a large sample. METHODS: Patients with an intermediate or high SAHS suspicion were included in a multicenter study (eight sleep centers) and assigned to home and hospital protocols in a random order. Therapeutic decisions (continuous positive airway pressure, no continuous positive airway pressure, or impossible decision) were made by an investigator in each center, based on using either HRP or PSG and a single set of auxiliary clinical variables. Patients and diagnostic methods (HRP and PSG) were assessed in random order using an electronic database. After a month the same therapeutic decision-making procedure was repeated with the same method. MEASUREMENTS AND MAIN RESULTS: Of 366 randomized patients, 348 completed the protocol. The 'impossible decision' case was not observed with either PSG or HRP. Therapeutic decisions using HRP had a sensitivity of 73%, a specificity of 77%, and an agreement level (sum of true positives and negatives) of 76%. Patients with higher HRP apnea-hypopnea index (AHI) scores (>= 30; 41% of the total sample) had a sensitivity of 94%, a specificity of 44%, and the agreement level was 91%. CONCLUSIONS: The HRP-based therapeutic decision was adequate when AHI was high, but deficient in the large population of patients with mild to moderate AHI. Therefore, both selecting patients with a high suspicion and severity of SAHS and future prospective cost-effectiveness studies are necessary. [ABSTRACT FROM AUTHOR]

RATIONALE: Continuous positive airway pressure (CPAP) is the current treatment for patients with symptomatic obstructive sleep apnea (OSA). Its use for all subjects with sleep-disordered breathing, regardless of daytime symptoms, is unclear. Objectives: This multicenter controlled trial assesses the effects of 1 year of CPAP treatment on blood pressure (BP) in nonsymptomatic, hypertensive patients with OSA. METHODS: We evaluated 359 patients with OSA. Inclusion criteria consisted of an apnea-hypopnea index (AHI) greater than 19 hour(-1), an Epworth Sleepiness Scale score less than 11, and one of the following: under antihypertensive treatment or systolic blood pressure greater than 140 or diastolic blood pressure greater than 90 mm Hg. Patients were randomized to CPAP (n = 178) or to conservative treatment (n = 181). BP was evaluated at baseline and at 3, 6, and 12 months of follow-up. MEASUREMENTS AND MAIN RESULTS: Mean (SD) values were as follows: age, 56 +/- 10 years; body mass index (BMI), 32 +/- 5 kg x m(-2); AHI, 45 +/- 20 hour(-1); and Epworth Sleepiness Scale score, 7 +/- 3. After adjusting for follow-up time, baseline blood pressure values, AHI, time with arterial oxygen saturation less than 90%, and BMI, together with the change in BMI at follow-up, CPAP treatment decreased systolic blood pressure by 1.89 mm Hg (95% confidence interval: -3.90, 0.11 mm Hg; P = 0.0654), and diastolic blood pressure by 2.19 mm Hg (95% confidence interval: -3.46, -0.93 mm Hg; P = 0.0008). The most significant reduction in BP was in patients who used CPAP for more than 5.6 hours per night. CPAP compliance was related to AHI and the decrease in Epworth Sleepiness Scale score. CONCLUSIONS: In nonsleepy hypertensive patients with OSA, CPAP treatment for 1 year is associated with a small decrease in BP. This effect is evident only in patients who use CPAP for more than 5.6 hours per night. Clinical trial registered with www.clinicaltrials.gov (NCT00127348). [ABSTRACT FROM AUTHOR]

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Background: Obesity hypoventilation syndrome (OHS) is associated with high morbidity and mortality. There are few data on whether there are gender differences in outcomes., Research Question: Do women with OHS experience worse outcomes in ambulatory and hospitalized settings compared to men?, Study Design and Methods: Post hoc analyses were performed on two separate OHS cohorts: (1) stable ambulatory patients from the two Pickwick randomized controlled trials; and (2) hospitalized patients with acute-on-chronic hypercapnic respiratory failure from a retrospective international cohort. We first conducted bivariate analyses of baseline characteristics and therapeutics between genders. Variables of interest from these analyses were then grouped into linear mixed effects models, Cox proportional hazards models, or logistic regression models to assess the association of gender on various clinical outcomes., Results: The ambulatory prospective cohort included 300 patients (64% self-identified as women), and the hospitalized retrospective cohort included 1,162 patients (58% self-identified as women). For both cohorts, women were significantly older and more obese than men. Compared with men, baseline Paco 2 was similar in ambulatory patients but higher in hospitalized women. In the ambulatory cohort, in unadjusted analysis, women had increased risk of emergency department visits. However, gender was not associated with the composite outcome of emergency department visit, hospitalization, or all-cause mortality in the fully adjusted model. In the hospitalized cohort, prescription of positive airway pressure was less prevalent in women at discharge. In unadjusted analysis, hospitalized women had a higher mortality at 3, 6, and 12 months following hospital discharge compared with men. However, after adjusting for age, gender was not associated with mortality., Interpretation: Our findings indicate that although the diagnosis of OHS is established at a more advanced age in women, gender is not independently associated with worse clinical outcomes after adjusting for age. Future studies are needed to examine gender-related health disparities in diagnosis and treatment of OHS., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Pulmonary surfactant, the primary substance lining the epithelium of the human Lower Respiratory Tract (LRT), is rich in lipids, with dipalmitoyl-phosphatidylcholine (DPPC) being the most abundant. Although surfactants are known to have antifungal activity against some yeast species, the significant presence of species like Malassezia restricta in the lung mycobiome suggests that these yeasts may exhibit some level of lipo-tolerance or even lipo-affinity for pulmonary lipids. This study explored the affinity and tolerance of yeasts, identified as significant members of the lung microbiome, to pulmonary lipids through culture-based methods. Eleven species from the genera Malassezia, Candida (including the new genera Nakaseomyces and Meyerozyma), and Cryptococcus were tested for their growth on media containing pulmonary lipids such as DPPC and commercial porcine surfactant and in other culture medium that contain non-pulmonary lipids such as glycerol monostearate and tweens. The yeasts' lipo-affinity or lipo-tolerance was assessed based on their growth on these lipids compared to standard media, specifically Modified Leeming Notman Agar (MLNA) for Malassezia species and Sabouraud Dextrose Agar (SDA) for the other genera. The addition of DPPC or surfactant to the media enhanced the growth of most Malassezia yeasts and some Cryptococcus species. C. parapsilosis, Meyerozyma guilliermondii and Cryptococcus neoformans s.s. showed similar growth to that on the standard media, while the other yeasts primarily demonstrated lipo-tolerance without lipo-affinity for these compounds. To our knowledge, this is the first report on the influence of pulmonary lipids on the in vitro growth of Malassezia spp. and other yeast members of the lung mycobiome. Some yeasts, such as Malassezia restricta, commonly found in the lower respiratory tract (LRT), exhibit specific affinity for lung lipids like DPPC and commercial porcine surfactant. This finding suggests that lung lipids may play a significant role in shaping the LRT mycobiome., Competing Interests: Declarations. Conflict of interest: None., (© 2024. The Author(s).)

Respiratory diseases and cardiovascular diseases (CVDs) have high prevalence and share common risk factors. In some respiratory diseases such as sleep apnoea and COPD, the evidence of their negative impact on the prognosis of CVDs seems clear. However, in other diseases it is less evident whether there is any direct relationship. With this in mind, our objective was to provide information that may be helpful to better understand the relationship between respiratory pathology and CVDs. There are different reasons for this relationship, such as shared risk factors, common pathophysiological mechanisms, side effects of treatment and the direct effect in the heart and great vessels of respiratory diseases. Indeed, aging and smoking are risk factors for CVDs and also for respiratory diseases such as obstructive sleep apnea (OSA), COPD and interstitial lung diseases (ILD). Furthermore, there are common pathophysiological mechanisms that affect both respiratory diseases and CVDs, such as accelerated atherosclerosis, microvascular dysfunction, endothelial dysfunction, inflammation, hypoxemia and oxidative stress. Besides that, it is well known that lung cancer, sarcoidosis and amyloidosis may directly affect the heart and great vessels. Finally, side effects of drugs for respiratory diseases and the discontinuation of treatments that are necessary for CVDs, such as β-blockers and aspirin, may have a deleterious impact on the cardiovascular system. In conclusion, the coexistence of respiratory diseases and CVDs is very common. It makes modifying diagnostic and therapeutic management necessary and is also a relevant prognostic factor., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Rationale: Although obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated., Objective: To characterize the molecular pathways that relate OSA with CVE recurrence., Methods: This post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea-hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology., Results: Proteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m 2 ). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes., Conclusion: A specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)