Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Cytomolecular trends in Chamaecrista Moench (Caesalpinioideae, Leguminosae) diversification.

Chamaecrista is a Pantropical legume genus of the tribe Cassieae, which includes six other genera. In contrast to most of the other Cassieae genera, Chamaecrista shows significant variability in chromosome number (from 2n = 14 to 2n = 56), with small and morphologically similar chromosomes. Here, we performed a new cytomolecular analysis on chromosome number, genome size, and rDNA site distribution in a molecular phylogenetic perspective to interpret the karyotype trends of Chamaecrista and other two genera of Cassieae, seeking to understand their systematics and evolution. Our phylogenetic analysis revealed that Chamaecrista is monophyletic and can be divided into four major clades corresponding to the four sections of the genus. Chromosome numbers ranged from 2n = 14, 16 (section Chamaecrista) to 2n = 28 (sections Absus, Apoucouita, and Baseophyllum). The number of 5S and 35S rDNA sites varied between one and three pairs per karyotype, distributed on different chromosomes or in synteny, with no obvious phylogenetic significance. Our data allowed us to propose x = 7 as the basic chromosome number of Cassieae, which was changed by polyploidy generating x = 14 (sections Absus, Apoucouita, and Baseophyllum) and by ascending dysploidy to x = 8 (section Chamaecrista). The DNA content values supported this hypothesis, with the genomes of the putative tetraploids being larger than those of the putative diploids. We hypothesized that ascending dysploidy, polyploidy, and rDNA amplification/deamplification are the major events in the karyotypic diversification of Chamaecrista. The chromosomal marks characterized here may have cytotaxonomic potential in future studies.

Air quality modeling in the metropolitan area of São Paulo, Brazil: A review.

Numerous studies have used air quality models to estimate pollutant concentrations in the Metropolitan Area of São Paulo (MASP) by using different inputs and assumptions. Our objectives are to summarize these studies, compare their performance, configurations, and inputs, and recommend areas of further research. We examined 29 air quality modeling studies that focused on ozone (O3) and fine particulate matter (PM2.5) performed over the MASP, published from 2001 to 2023. The California Institute of Technology airshed model (CIT) was the most used offline model, while the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was the most used online model. Because the main source of air pollution in the MASP is the vehicular fleet, it is commonly used as the only anthropogenic input emissions. Simulation periods were typically the end of winter and during spring, seasons with higher O3 and PM2.5 concentrations. Model performance for hourly ozone is good with half of the studies with Pearson correlation above 0.6 and root mean square error (RMSE) ranging from 7.7 to 27.1 ppb. Fewer studies modeled PM2.5 and their performance is not as good as ozone estimates. Lack of information on emission sources, pollutant measurements, and urban meteorology parameters is the main limitation to perform air quality modeling. Nevertheless, researchers have used measurement campaign data to update emission factors, estimate temporal emission profiles, and estimate volatile organic compounds (VOCs) and aerosol speciation. They also tested different emission spatial disaggregation approaches and transitioned to global meteorological reanalysis with a higher spatial resolution. Areas of research to explore are further evaluation of models' physics and chemical configurations, the impact of climate change on air quality, the use of satellite data, data assimilation techniques, and using model results in health impact studies. This work provides an overview of advancements in air quality modeling within the MASP and offers practical approaches for modeling air quality in other South American cities with limited data, particularly those heavily impacted by vehicle emissions.

Effects of urbanization and accessibility to sanitation services on water quality in urban streams in Uruguay.

The world's urban population is growing rapidly, and threatening natural ecosystems, especially streams. Urbanization leads to stream alterations, increased peak flow frequencies, and reduced water quality due to pollutants, morphological changes, and biodiversity loss, known as the urban stream syndrome. However, a shift towards recognizing urban streams as valuable natural systems is occurring, emphasizing green infrastructure and nature-based solutions. This study in Uruguay examined water quality in various watersheds with different urbanization levels and socio-environmental characteristics along a precipitation gradient. Using Geographic Information Systems (GIS) and in situ data, we assessed physicochemical parameters, generated territorial variables, and identified key predictors of water quality. We found that urbanization, particularly urban areas, paved areas, and populations without sanitation, significantly influenced water quality parameters. These factors explained over 50% of the variation in water quality indicators. However, the relationship between urbanization and water quality was non-linear, with abrupt declines after specific urban intensity thresholds. Our results illustrate that ensuring sanitation networks and managing green areas effectively are essential for preserving urban stream water quality. This research underscores the importance of interdisciplinary teams and localized data for informed freshwater resource management.

Simultaneous and divergent evolution of resistance to cephalosporin/ß-lactamase inhibitor combinations and imipenem/relebactam following ceftazidime/avibactam treatment of MDR Pseudomonas aeruginosa infections.

OBJECTIVES: To describe and characterize the emergence of resistance to ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam in a patient receiving ceftazidime/avibactam treatment for an MDR Pseudomonas aeruginosa CNS infection. METHODS: One baseline (PA1) and two post-exposure (PA2 and PA3) isolates obtained before and during treatment of a nosocomial P. aeruginosa meningoventriculitis were evaluated. MICs were determined by broth microdilution. Mutational changes were investigated through WGS. The impact on ß-lactam resistance of mutations in blaPDC and mexR was determined through cloning experiments and complementation assays. RESULTS: Isolate PA1 showed baseline resistance mutations in DacB (I354A) and OprD (N142fs) conferring resistance to conventional antipseudomonals but susceptibility to ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. Post-exposure isolates showed two divergent ceftazidime/avibactam-resistant phenotypes associated with distinctive mutations affecting the intrinsic P PDC ß-lactamase (S254Ins) (PA2: ceftolozane/tazobactam and ceftazidime/avibactam-resistant) or MexAB-OprM negative regulator MexR in combination with modification of PBP3 (PA3: ceftazidime/avibactam and imipenem/relebactam-relebactam-resistant). Cloning experiments demonstrated the role of PDC modification in resistance to ceftolozane/tazobactam and ceftazidime/avibactam. Complementation with a functional copy of the mexR gene in isolate PA3 restored imipenem/relebactam susceptibility. CONCLUSIONS: We demonstrated how P. aeruginosa may simultaneously develop resistance and compromise the activity of new ß-lactam/ß-lactamase inhibitor combinations when exposed to ceftazidime/avibactam through selection of mutations leading to PDC modification and up-regulation of MexAB-OprM-mediated efflux.

Efficacy of Crohn's disease exclusion diet in treatment -naïve children and children progressed on biological therapy: a retrospective chart review.

BACKGROUND: Recent trials suggested that the Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) is a safe and effective strategy in remission induction of paediatric-onset CD. However, real-world evidence regarding the safety and efficacy of the CDED plus PEN approach is still lacking. The present case-series study reported our experience with the outcomes of CDED plus PEN in the paediatric-onset CD at disease onset and after the loss of response to biologics. METHODS: We conducted a retrospective chart review on children who were treated with CDED plus PEN through the period from July 2019 and December 2020. Clinical and laboratory data were retrieved and compared at baseline, 6, 12, and 24 weeks of treatment. The primary endpoint of the present study was the rate of clinical remission. RESULTS: The present study retrieved the data from 15 patients. Of them, nine patients were treatment naïve at the time of initiation of CDED plus PEN (group A) and the remaining patients relapsed on biologics before treatment. All patients in groups A and B exhibited clinical remission in week six, which was sustained until week 12. At the end of the follow-up, the clinical remission rate was 87% and 60% in groups A and B, respectively. No side effects were observed in both groups. In group A, the faecal calprotectin (FC) and albumin improved at week six, week 12, and week 24 (p < 0.05). The erythrocyte sedimentation rate (ESR) improved significantly at week 12 (p = 0.021) and week 24 (p = 0.027). At the same time, the haemoglobin and iron levels showed significant improvement only at week 24. For group B, only FC showed numerical reductions over time that did not reach the level of statistical significance. CONCLUSION: Treatment with CDED plus PEN was well tolerated and achieved an excellent clinical remission rate in treatment-naive patients. However, the benefit of CDED plus PEN was less in patients who initiated the strategy after losing the response to biologics.

Methylsiloxanes from Vehicle Emissions Detected in Aerosol Particles.

Methylsiloxanes have gained growing attention as emerging pollutants due to their toxicity to organisms. As man-made chemicals with no natural source, most research to date has focused on volatile methylsiloxanes from personal care or household products and industrial processes. Here, we show that methylsiloxanes can be found in primary aerosol particles emitted by vehicles based on aerosol samples collected in two tunnels in São Paulo, Brazil. The aerosol samples were analyzed with thermal desorption-proton transfer reaction-mass spectrometry (TD-PTR-MS), and methylsiloxanes were identified and quantified in the mass spectra based on the natural abundance of silicon isotopes. Various methylsiloxanes and derivatives were found in aerosol particles from both tunnels. The concentrations of methylsiloxanes and derivatives ranged 37.7-377 ng m-3, and the relative fractions in organic aerosols were 0.78-1.9%. The concentrations of methylsiloxanes exhibited a significant correlation with both unburned lubricating oils and organic aerosol mass. The emission factors of methylsiloxanes averaged 1.16 ± 0.59 mg kg-1 of burned fuel for light-duty vehicles and 1.53 ± 0.37 mg kg-1 for heavy-duty vehicles. Global annual emissions of methylsiloxanes in vehicle-emitted aerosols were estimated to range from 0.0035 to 0.0060 Tg, underscoring the significant yet largely unknown potential for health and climate impacts.

Is myocardial fibrosis appropriately assessed by calibrated and 2D strain derived integrated backscatter?

AIMS: Increased collagen content of the myocardium modifies tissue reflectivity and integrated backscatter (IBS) indexes are suggested as markers of myocardial fibrosis (MF). We sought to assess the correlation between calibrated (c) IBS and bidimensional (2D) strain derived IBS with left ventricular (LV) MF in patients with severe aortic stenosis (AS). METHODS AND RESULTS: We made a prospective observational cohort study including 157 patients with severe AS referred for surgical aortic valve replacement (AVR), with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of surgery. Two groups of 30 patients were specifically evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak from both parasternal long axis (PLAX) and apical-three-chamber (AP3C) views and measured in decibels (dB). Whole-cardiac cycle IBS at basal anterior septum was obtained from 2D longitudinal strain. Correlation analysis of reflectivity indexes was performed with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) (Masson´s Trichrome). IBS values were compared in both group of patients (LGE + vs. LGE -). 60 patients (74 [36-74] years, 45% male) with high gradient (mean gradient: 63 ± 20mmHg), normal flow (45 ± 10mL/m2) AS and preserved left ventricular ejection fraction (60 ± 9%) were included. Basal septum cIBS was - 17.45 (-31.2-10.95) and - 9.17 ± 9.45dB from PLAX and A3C views, respectively. No significant correlations were found between IBS and both non-invasive CMR tissue characterization and CVF: median MF of 9.7(2.1-79.9)%. Acoustic indexes were not significantly different according to the presence of pre-operative LGE. CONCLUSION: In this group of patients with classical severe AS, IBS reflectivity indexes are of no added value to discriminate the presence of MF.

Peak left atrial longitudinal strain is associated with all-cause mortality in patients with ventricular functional mitral regurgitation.

PURPOSE: Chronic mitral regurgitation promotes left atrial (LA) remodeling. However, the significance of LA dysfunction in the setting of ventricular functional mitral regurgitation (FMR) has not been fully investigated. Our aim was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in patients with FMR and reduced left ventricular ejection fraction (LVEF). METHODS: Patients with at least mild ventricular FMR and LVEF < 50% under optimized medical therapy who underwent transthoracic echocardiography at a single center were retrospectively identified in the laboratory database. PALS was assessed by 2D speckle tracking in the apical 4-chamber view and the study population was divided in two groups according to the best cut-off value of PALS, using receiver operating characteristics (ROC) curve analysis. The primary endpoint-point was all-cause mortality. RESULTS: A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 - 40%) and median effective regurgitant orifice area (EROA) was 15mm2 (IQR: 9 - 22mm2). According to current European guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 - 6.6), 148 patients died. The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS. On multivariable analysis, PALS remained independently associated with all-cause mortality (adjusted hazard ratio 1.052 per % decrease; 95% CI: 1.010 - 1.095; P = 0.016), even after adjustment for several (n = 14) clinical and echocardiographic confounders. CONCLUSION: PALS is independently associated with all-cause mortality in patients with reduced LVEF and ventricular FMR.

The role of local inflammation in complications associated with intubation in pediatric patients: A narrative review.

Although the most important primary local inflammatory response factor to intubation is not yet clear, it is known that it may be directly attributed to the presence of trauma during intubation or the response of oral bacterial flora present in the trachea. It is known that prolonged intubation is associated with worse outcomes, but other underlying systemic issues, such as sepsis and trauma, are also associated with this result. Likewise, patients who require advanced airway management and excessive manipulation are more likely to experience complications. There are various inflammatory mediators that are generated during orotracheal intubation, many of which can be considered targets for therapies to help reduce inflammation caused by intubation. However, there is little evidence on the management of the inflammatory response induced by orotracheal intubation in pediatric patients. Therefore, the aim of this narrative review is to highlight the intubation associated complications that can arise from poorly controlled inflammation in intubated pediatric patients, review the proposed pathophysiology behind this, and discuss the current treatments that exist. Finally, taking into account the discussion on pathophysiology, we describe the current therapies being developed and future directions that can be taken in order to create more treatment options within this patient population.

Proteomics as a New-Generation Tool for Studying Moulds Related to Food Safety and Quality.

Mould development in foodstuffs is linked to both spoilage and the production of mycotoxins, provoking food quality and food safety concerns, respectively. The high-throughput technology proteomics applied to foodborne moulds is of great interest to address such issues. This review presents proteomics approaches useful for boosting strategies to minimise the mould spoilage and the hazard related to mycotoxins in food. Metaproteomics seems to be the most effective method for mould identification despite the current problems related to the bioinformatics tool. More interestingly, different high resolution mass spectrometry tools are suitable for evaluating the proteome of foodborne moulds able to unveil the mould's response under certain environmental conditions and the presence of biocontrol agents or antifungals, being sometimes combined with a method with limited ability to separate proteins, the two-dimensional gel electrophoresis. However, the matrix complexity, the high ranges of protein concentrations needed and the performing of multiple steps are some of the proteomics limitations for the application to foodborne moulds. To overcome some of these limitations, model systems have been developed and proteomics applied to other scientific fields, such as library-free data independent acquisition analyses, the implementation of ion mobility, and the evaluation of post-translational modifications, are expected to be gradually implemented in this field for avoiding undesirable moulds in foodstuffs.

Effect of selected agents for ochratoxin A biocontrol on the colour, texture and volatile profile of dry-cured fermented sausages.

BACKGROUND: Traditional dry-cured fermented sausages favour the growth of an autochthonous microbial population, which plays an important role in their sensory aspects. However, some moulds can produce mycotoxins such as ochratoxin A (OTA). The biocontrol agents (BCAs) Debaryomyces hansenii FHSCC 253H and Staphylococcus xylosus FHSCC Sx8 have been demonstrated to reduce OTA production in dry-cured meat products, but their influence in the sensory characteristics of sausages has to be tested. The aim of this study was to evaluate the effect of these BCAs on the colour, texture and volatile profile of dry-cured fermented sausages. RESULTS: D. hansenii caused few differences in the tested parameters with respect to the control batch. S. xylosus modified the texture and colour, although the values found were within the range expected for dry-cured fermented sausages 'salchichón'. Additionally, the volatile profile revealed the potential antioxidant effect of both BCAs and their ability to produce compounds associated with the ripened aroma that could increase product acceptability. CONCLUSION: The results indicate that there were no inconveniences in implementing both BCAs during the processing of dry-cured fermented sausages 'salchichón'. Moreover, D. hansenii FHSCC 253H could improve the volatile profile of this product. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Sex workers' peer support during the COVID-19 pandemic: Lessons learned from a study of a Portuguese community-led response.

To respond to the consequences felt by the COVID-19 pandemic, a community-led intervention was developed by the Portuguese national Movement of Sex Workers. With this exploratory study, we aimed to document their work and analyze their perceptions of this impact. To do so, we interviewed them individually, between May and August of 2020. Additionally, we analysed an Excel Sheet that contained the needs assessment and the support provided by the Movement. The content analysis of both suggests that the impact of the pandemic might have been exacerbated by the social inequalities caused by the prostitution stigma and characteristics such as gender, migration status, race, and socioeconomic status. This study calls for the inclusion of sex workers' voices in the design of policies and responses related to the commerce of sex. The consolidation of a Portuguese Movement of Sex Workers is also noted.

Effectiveness of anti-obesity medications approved for long-term use in a multidisciplinary weight management program: a multi-center clinical experience.

BACKGROUND AND AIMS: Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings. METHODS: We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020. INTERVENTION: We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation. RESULTS: The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects. CONCLUSIONS: AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials.

Chikungunya in Brazil: An epidemic of high cost for private healthcare, 2017.

OBJECTIVE: We evaluated the impact of direct and indirect medical costs incurred through chikungunya infections in patients treated in Fortaleza, Brazil. METHODS: Cross-sectional study about the cost of illness. The valuation method of medical costs was based on the micro-costing approach (bottom-up). The study was carried out in a large general hospital of the private health network. The study population consisted of patients treated as suspected cases of chikungunya and hospital professionals who applied for sick leave due to chikungunya. RESULTS: In 2017, there were 2683 patients treated at this hospital who incurred an estimated cost of $383,514.40. From this amount, $174,322.91 (45.5%) were expended on emergency care, $194,700.59 (50.8%) on hospitalisations. 123 hospital professionals were infected with chikungunya and sick leave duration ranged between 1 and 19 days. Health professionals generated 746 days of absence and an amount of $14,490.90 due to absenteeism from work related to chikungunya. 31 symptoms were reported, especially arthralgia (91.1%) and fever (79.4%). There was a predominance of females (58.8%) and the age group of 20-39 years (42.1%). CONCLUSION: The average cost of admissions was over $2400. Considering the epidemic potential of chikungunya, our data indicate the huge economic burden of this disease to healthcare units in the presence of epidemics. Economic factors, added to the loss of life and the consequences of chronic chikungunya, make this disease a real scourge for countries with fewer material resources.

An in vitro assay of the effect of lysine oxidation end-product, α-aminoadipic acid, on the redox status and gene expression in probiotic Lactobacillus reuteri PL503.

This study was designed to gain information about the underlying mechanisms of the effects of a food-occurring free oxidized amino acid, α-aminoadipic acid (AAA), on the probiotic Lactobacillus reuteri PL503. This bacterium was incubated in colonic-simulated conditions (37 °C for 24 h in microaerophilic conditions) and exposed to three food-compatible AAA concentrations, namely, 1 mM, 5 mM, and 10 mM. A control group with no AAA exposure was also considered. Each of the four experimental conditions was replicated three times and samplings were collected at 12, 16, 20, and 24 h. The downregulation of the uspA gene by AAA (0.5-fold decrease as compared to control) suggests that AAA is identified as a potential chemical threat. The dhaT gene, implicated in the antioxidant defense, was found to be upregulated in bacteria treated with 1 and 5 mM AAA (up to twofold increase, as compared to control), which suggest the ability of the oxidized amino acid to impair the redox status of the bacterium. In fact, AAA caused an increased production of reactive oxygen species (ROS) and the accretion of post-translational changes (protein carbonylation) in L. reuteri (up to 13 nmol allysine/mg protein vs 1.8 nmol allysine/mg protein in control). These results suggest that probiotic bacteria identify oxidized amino acids as harmful species and activate mechanisms that may protect themselves and the host against their noxious effects.

Severe hypoxemia in a patient with right ventricular myocardial infarction and SARS-CoV-2 infection.

BACKGROUND: Refractory hypoxemia after right ventricular myocardial infarction and concomitant SARS-CoV-2 infection represents an uncommon, yet particularly challenging clinical scenario. We report a challenging diagnostic case of refractory hypoxemia due to right-to-left shunt highlighting contemporary challenges and pitfalls in acute cardiovascular care associated with the current COVID-19 pandemic. CASE PRESENTATION: A 52-year-old patient admitted for inferior acute myocardial infarction developed rapidly worsening hypoxemia shortly after primary percutaneous coronary intervention. RT-PCR screening for SARS-CoV-2 was positive, even though the patient had no prior symptoms. A computed tomography pulmonary angiogram excluded pulmonary embolism and showed only mild interstitial pulmonary involvement of the virus. Transthoracic echocardiogram showed severe right ventricular dysfunction and significant right-to-left shunt at the atrial level after agitated saline injection. Progressive improvement of right ventricular function allowed weaning from supplementary oxygen support. Patient was latter discharged with marked symptomatic improvement. CONCLUSION: Refractory hypoxemia after RV myocardial infarction should be carefully addressed, even in the setting of other more common and tempting diagnoses. After exclusion of usual etiologies, right-to-left shunting at the atrial level should always be suspected, as this may avoid unnecessary and sometimes harmful interventions.

TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy.

BACKGROUND: While BRAF mutations seem important for early melanomagenesis, mutations in the TERT promoter (TERTp) are related to metastasis. Yet, in conventional melanoma management, risk stratification does not depend on molecular biomarkers that can indicate the stage of progression, but rather on clinical, pathological, sentinel lymph node (SLN), and radiologic evaluation. The aim of this work was to evaluate the frequency and prognostic impact of TERTp mutations, comparing their predictive value to those of conventional procedures in melanoma management. METHODS: Mutational analysis of a series of 91 cases was performed. The correlations between TERTp and BRAF mutational status and clinicopathological features were assessed. RESULTS: The mutation rate was 33% for TERTp and 30% for BRAF. There was 68% concordance between primary and metastatic samples for TERTp mutations and 92% for BRAF mutations. TERTp mutations are significantly associated with the presence of BRAF mutations, features of worse prognosis, and a reduced disease-free survival. Also, TERTp mutational status was similar to SLN biopsy as a predictive factor of cutaneous melanoma recurrence and metastasis. CONCLUSIONS: The predictive value of TERTp mutations may be similar to that of SLN biopsy and its integration in the management algorithm of melanoma patients should be considered.

Pectoralis major muscle quantification by cardiac MRI is a strong predictor of major events in HF.

Clinical overt cardiac cachexia is a late ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The main goal of this study was to assess the feasibility and prognostic significance of muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF. HF patients with LVEF < 40% (HFrEF) referred for CMR were retrospectively identified in a single center. Key exclusion criteria were primary muscle disease, known infiltrative myocardial disease and intracardiac devices. Pectoralis major muscles were measured on standard axial images at the level of the 3rd rib anteriorly. Time to all-cause death or HF hospitalization was the primary endpoint. A total of 298 HF patients were included (mean age 64 ± 12 years; 76% male; mean LVEF 30 ± 8%). During a median follow-up of 22 months (IQR: 12-33), 67 (22.5%) patients met the primary endpoint (33 died and 45 had at least 1 HF hospitalization). In multivariate analysis, LVEF [Hazard Ratio (HR): 0.950; 95% Confidence Interval (CI): 0.917-0.983; p = 0.003), NYHA class I-II vs III-IV (HR: 0.480; CI: 0.272-0.842; p = 0.010), creatinine (HR: 2.653; CI: 1.548-4.545; p < 0.001) and pectoralis major area (HR: 0.873; 95% CI: 0.821-0.929; p < 0.001) were independent predictors of the primary endpoint, when adjusted for gender and NT-pro-BNP levels. Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies to establish appropriate age and gender-adjusted cut-offs of muscle areas are needed to identify high-risk subgroups.

The many paths to diagnose diaphragmatic paralysis: Cardiopulmonary ultrasound on stage.

Abnormal diaphragmatic motion (ADM) due to phrenic nerve injury is a recognized complication of cardiac surgery and several diagnostic techniques can be used to determine the diagnosis. Due to its relationship with the diaphragm, cardiac kinetics is affected by the abnormal movement of the diaphragm in cases of left hemidiaphragm paralysis. The authors present a case of diaphragmatic paralysis in which the initial diagnosis is made through echocardiography.