Pulmonary Disease Research Articles

YAP/TAZ activation mediates PQ-induced lung fibrosis by sustaining senescent pulmonary epithelial cells.

Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms of PQ-induced pulmonary fibrosis and whether pulmonary epithelial cell senescence is involved in the process remain elusive. In this study, PQ-induced pulmonary epithelial cell senescence and Hippo-YAP/TAZ activation were observed in both C57BL/6 mice and human epithelial cells. PQ-induced senescent pulmonary epithelial cells promoted lung fibroblast transformation through secreting senescence-associated secretory phenotype (SASP) factors. Yap/Taz knockdown in mice lungs significantly decreased the expression of downstream profibrotic protein Ctgf and senescent markers p16 and p21, and alleviated PQ-induced pulmonary fibrosis. Interfering YAP/TAZ in senescent human pulmonary epithelial cells resulted in decreased expression of the anti-apoptosis protein survivin and elevated level of apoptosis. In conclusion, our findings reveal a novel mechanism by which the involvement of Hippo-YAP/TAZ activation in pulmonary epithelial cell senescence mediates the pathogenesis of PQ-induced pulmonary fibrosis, thereby offering novel insights and potential targets for the clinical management of PQ poisoning as well as providing the mechanistic insight of the involvement of Yap/Taz activation in cell senescence in pulmonary fibrosis and its related pulmonary disorders. The YIN YANG balance between cell senescence and apoptosis is important to maintain the homeostasis of the lung, the disruption of which will lead to disease.

Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Factors associated with severe respiratory syncytial virus infection among hospitalized children in Thammasat University Hospital

Background Respiratory syncytial virus (RSV) is one of the most significant respiratory pathogens that causes acute lower respiratory tract infections (LRTI) early in life. Most children have a history of RSV infection within 24 months of age, and recurrent infections are common throughout life. Methods Children under five years of age were identified through a review of medical records with a diagnosis of RSV-LRTI between 2016 and 2020. Severe RSV-LRTI was defined as a prolonged length of stay (> 7 days), admission to the intensive care unit, need for mechanical ventilation, non-invasive positive pressure ventilation, or in-hospital mortality. Factors associated with severe RSV-LRTI were investigated using univariate and multivariate analyses. Results During the study period, 620 patients were diagnosed with RSV-LRTI and 249 (40.16%) patients had severe RSV-LRTI. In the multivariable logistic regression analysis, the factors for severe RSV-LRTI were being under 3 months (aOR 2.18 CI 1.39-3.43, p0.001), cardiovascular disease (aOR 3.55 CI 1.56-8.06, p0.002), gastrointestinal disease (aOR 5.91 CI 1.90-18.46, p0.002), genetic disease (aOR 7.33 CI 1.43-37.54, p0.017), and pulmonary disease (aOR 9.50, CI 4.56-19.80, p<0.001). Additionally, the presence of ≥ 2 co-morbidities (aOR 6.23 CI 2.81-14.81, p<0.016), experiencing illness for more than 5 days (aOR 3.33 CI 2.19-5.06, p<0.001), co-detection of influenza (aOR 8.62 CI 1.49-38.21, p0.015), and nosocomial RSV infection (aOR 9.13 CI 1.98-41.30, p0.012), markedly increased the risk of severe RSV-LTRI. The severe RSV-LRTI group demonstrated higher hospitalization expenses (median, US $720.77 vs $278.00, respectively; p<0.001), and three infants died in-hospital. Conclusion Children at high risk for RSV-LRTI due to underlying genetic and gastrointestinal diseases are at an increased risk for severe RSV-LRTI. Further studies to determine the cost-effectiveness of RSV immunization in these potential co-morbidities should be initiated to prioritize RSV immunization, especially in resource-constrained regions with limited availability of nirsevimab.

Pediatric three-dimensional quantitative cardiovascular computed tomography.

High-resolution, isotropic, 3-dimensional (D) data from pediatric cardiovascular computed tomography (CT) offer great potential for the accurate quantitative evaluation of pediatric cardiovascular and pulmonary vascular diseases. Recent pilot studies using pediatric 3-D cardiovascular CT have shown promising results in assessing cardiac function in conditions such as tetralogy of Fallot, cardiac defects with a hypoplastic ventricle, Ebstein anomaly, and in quantifying myocardial mass. In addition, the quantitative assessment of pulmonary vascularity is useful for evaluating differential right-to-left pulmonary vascular volume ratio, the effectiveness of pulmonary angioplasty, and predicting pulmonary hypertension. These initial experiences could broaden the role of pediatric cardiovascular CT in clinical practice. Furthermore, the current barriers to its widespread use, pertinent solutions to these problems, and new applications are discussed. In this review, the 3-D quantitative evaluations of cardiac function and pulmonary vascularity using high-resolution pediatric cardiovascular CT data are illustrated.

Management of Pulmonary Vascular Disease Associated with Congenital Left to Right Shunts: A Single Center Experience.

To describe the course and outcomes of children under 18 with left-to-right (LR) shunts and pulmonary arterial hypertension (PAH) undergoing one of two management approaches: PAH treatment prior to LR shunt repair (Treat First) and LR shunt repair first, with or without subsequent PAH treatment (Repair First). Retrospective single center study, conducted from September 2015 to September 2021, of children LR shunts and PAH (defined as indexed pulmonary vascular resistance (PVRi) ≥ 4WU*m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, PAH management, LR shunt repair, and outcomes were reviewed. Of 768 patients evaluated for LR shunt closure, 51 (6.8%) had LR shunt associated PAH [median age 1.1 (0.37,5) years, median PVRi 6 (5.2,8.7) WU*m2]. Of the "Treat First" group (n=33, 65%), 27 (82%) underwent LR shunt closure and 6 (18%) did not respond to PAH therapy and did not undergo LR shunt closure. In the "Repair First" group (n=18, 35%), 12 (67%) received PAH therapy and 6 (33%) did not. Mortality rates were 6% in "Treat First" and 11% in "Repair First", follow-up of 3.4 and 2.5 years, respectively. After LR shunt closure, there was no significant change in PVRi over a median follow-up of 2 years after surgery (p=0.77). In children with LR shunts and associated PAH, treatment with PAH-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to PAH-targeted therapy before shunt closure persists 2-3 years post-closure, providing valuable insights into the long-term management of these patients.

Associations between chronic obstructive pulmonary disease and ten common cancers: novel insights from Mendelian randomization analyses.

Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15-1.77, FDR = 6.37 × 10-3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03-2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7-26.1%), 36.1% (24.9-33.2%), 35.9% (25.7-34.9%), and 35.5% (26.2-34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

COPD Self-Management: A Patient-Physician Perspective.

This article is co-authored by five patients living with chronic obstructive pulmonary disease (COPD), and a primary care physician who has over 30 years of clinical experience and is involved in educating healthcare professionals. The first section of this article is authored by the patients, who describe their experiences of living with COPD. The section that follows is authored by the physician, who discusses the management of COPD in the context of the patients' experiences.

Association between preoperative anxiety states and postoperative complications in patients with esophageal cancer and COPD: a retrospective cohort study

BackgroundEsophageal cancer brings emotional changes, especially anxiety to patients. Co-existing anxiety makes the surgery difficult and may cause complications. This study aims to evaluate effects of anxiety in postoperative complications of esophageal cancer patients with chronic obstructive pulmonary disease (COPD).MethodsPatients with esophageal cancer and co-existing COPD underwent tumor excision. Anxiety was measured using Hospital Anxiety and Depression Scale (HAD) before surgery. Clavien-Dindo criteria were used to grade surgical complications. A multiple regression model was used to analyze the relationship between anxiety and postoperative complications. The chi-square test was used to compare the differences in various types of complications between the anxiety group and the non-anxiety group. A multinomial logistic regression model was used to analyze the influencing factors of mild and severe complications.ResultsThis study included a total of 270 eligible patients, of which 20.7% had anxiety symptoms and 56.6% experienced postoperative complications. After evaluation by univariate analysis and multivariate logistic regression models, the risk of developing complications in anxious patients was 4.1 times than non-anxious patients. Anxious patients were more likely to develop pneumonia, pyloric obstruction, and arrhythmia. The presence of anxiety, surgical method, higher body mass index (BMI), and lower preoperative oxygen pressure may increase the incidence of minor complications. The use of surgical methods, higher COPD assessment test (CAT) scores, and higher BMI may increase the incidence of major complications, while anxiety does not affect the occurrence of major complications (P = 0.054).ConclusionPreoperative anxiety is associated with postoperative complications in esophageal cancer patients with co-existing COPD. Anxiety may increase the incidence of postoperative complications, especially minor complications in patient with COPD and esophageal cancer.

Platelet Activation and Severe Bleeding During Extracorporeal Carbon Dioxide Removal in Chronic Obstructive Pulmonary Disease Patients.

Platelet Activation and Severe Bleeding During Extracorporeal Carbon Dioxide Removal in Chronic Obstructive Pulmonary Disease Patients.

Antibiotic treatment for patients with exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundAlthough respiratory tract infection is a significant factor that triggers exacerbation of chronic obstructive pulmonary disease (COPD), the benefit of antibiotics for patients with COPD exacerbation remains controversial. It is necessary to evaluate the efficacy and safety of antibiotics versus placebo in such patients. MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials of antibiotics versus placebo for the treatment of COPD exacerbation, and compared the frequencies of treatment failure, mortality, and adverse events between patients treated with antibiotics and those treated with placebo. ResultsA total of six studies were included in this meta-analysis. The frequency of treatment failure was significantly lower in the antibiotic-treated patients compared to the placebo-treated patients (odds ratios [OR] 0.50, 95% confidence intervals [CI] 0.35–0.71, p = 0.0001). There was no significant difference between the two groups in mortality (OR 0.44, 95% CI 0.05–3.76, p = 0.45) or frequency of adverse events (OR 1.05, 95% CI 0.75–1.48, p = 0.78). ConclusionIn the current systematic review and meta-analysis, we found that antibiotics were superior to placebo in patients with exacerbated COPD, as shown by the lower treatment failure rate.

Testosterone replacement therapy in patients with cachexia: a contemporary review of the literature.

Patients with long-term chronic illnesses frequently present with hypogonadism, which is primarily managed through exogenous testosterone. These same patients also experience a high degree of cachexia, a loss of skeletal muscle and adipose tissue. To perform a contemporary review of the literature to assess the effectiveness of testosterone replacement therapy (TRT) for managing chronic disease-associated cachexia. We performed a PubMed literature search using MeSH terms to identify studies from 2000 to 2022 on TRT and the following cachexia-related chronic medical diseases: cancer, COPD, HIV/AIDS, and liver cirrhosis. From the literature, 11 primary studies and 1 meta-analysis were selected. Among these studies, 3 evaluated TRT on cancer-associated cachexia, 3 on chronic obstructive pulmonary disease, 4 on HIV and AIDS, and 2 on liver cirrhosis. TRT showed mixed results favoring clinical improvement on each disease. Cachexia is commonly observed in chronic disease states. Its occurrence with hypogonadism, alongside the shared symptoms of these 2 conditions, points toward the management of cachexia through the administration of exogenous testosterone. Robust data in the literature support the use of testosterone in increasing lean body mass, improving energy levels, and enhancing the quality of life for patients with chronic disease. However, the data are variable, and further studies are warranted on the long-term efficacy of TRT in patients with cachexia.

Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.

In chronic obstructive pulmonary disease (COPD), inflammation gives rise to protease-mediated degradation of the key extracellular matrix protein, elastin, which causes irreversible loss of pulmonary function. Intervention against proteolysis has met with limited success in COPD, due in part to our incomplete understanding of the mechanisms that underlie disease pathogenesis. Peptidyl arginine deiminase (PAD) enzymes are a known modifier of proteolytic susceptibility, but their involvement in COPD in the lungs of affected individuals is underexplored. In this study, we showed that enzyme isotypes PAD2 and PAD4 are present in primary granules of neutrophils and that cells from people with COPD release increased levels of PADs when compared with neutrophils of healthy control subjects. By examining bronchoalveolar lavage and lung tissue samples of patients with COPD or matched smoking and nonsmoking counterparts with normal lung function, we reveal that COPD presents with markedly increased airway concentrations of PADs. Ex vivo, we established citrullinated elastin in the peripheral airways of people with COPD, and invitro, elastin citrullination significantly enhanced its proteolytic degradation by serine and matrix metalloproteinases, including neutrophil elastase and matrix metalloprotease-12, respectively. These results provide a mechanism by which neutrophil-released PADs affect lung function decline, indicating promise for the future development of PAD-based therapeutics for preserving lung function in patients with COPD.

Combined Lifestyle Interventions in the Prevention and Management of Asthma and COPD: A Systematic Review

(1) Background: A healthy lifestyle has a protective role against the onset and management of asthma and chronic obstructive pulmonary disease (COPD). Therefore, combined lifestyle interventions (CLIs) are a potentially valuable prevention approach. This review aims to provide an overview of existing CLIs for the prevention and management of asthma or COPD. (2) Methods: A systematic literature search was conducted using PubMed, EMBASE, and PsycInfo. Studies were included if CLIs targeted at least two lifestyle factors. (3) Results: Among the 56 included studies, 9 addressed asthma and 47 addressed COPD management, with no studies focusing on prevention. For both conditions, the most prevalent combination of lifestyle targets was diet and physical activity (PA), often combined with smoking cessation in COPD. The studied CLIs led to improvements in quality of life, respiratory symptoms, body mass index/weight, and exercise capacity. Behavioural changes were only measured in a limited number of studies and mainly showed improvements in dietary intake and PA level. (4) Conclusions: CLIs are effective within asthma and COPD management. Next to optimising the content and implementation of CLIs, these positive results warrant paying more attention to CLIs for persons with an increased risk profile for these chronic respiratory diseases.

The 3'UTR Polymorphisms in the NLRP3 Gene Associated with the Risk of COPD and Their Putative Effects on the microRNA Mechanism.

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.

Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary disease.

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.

The Superiority of Fine-tuning over Full-training for the Efficient Diagnosis of COPD from CXR Images

This research investigates the use of deep learning for diagnosing lung diseases like Chronic Obstructive Pulmonary Disease (COPD) using Chest X-rays (CXR). The study compares the impact of deep learning on improving these diagnoses by comparing the performance of models trained from the scratch with those enhanced through fine-tuning established architectures like InceptionV3, ResNet50, and VGG-19. The study revealed that fine-tuning pre-trained models offers significant benefits: faster convergence, improved stability, and increased accuracy. Data augmentation techniques were found to be particularly useful when dealing with limited or unbalanced datasets. A custom CNN model, Iyke-Net, showed promising results when fine-tuned. Interestingly, it was observed that models using grayscale images outperformed those using colour images in disease classification, suggesting that colour information might be less critical than previously thought for certain diagnostic procedures. The study emphasizes the importance of balancing model complexity with computational efficiency and diagnostic accuracy. It advocates for refining existing deep learning models for COPD diagnosis from CXR images, paving the way for further innovations in AI-enhanced medical diagnostics.

Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study.

Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent. A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period. Secondary thoracic cancer care. Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment. With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible. ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

A worldwide look into Long COVID-19 management: an END-COVID survey

BackgroundLong COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide.MethodsA survey-based study investigating Long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID, PATS). A global analysis of the results is provided here, alongside with sub-population analysis based on continents, national income levels, type of involved healthcare professionals and inclusion or exclusion of paediatric patients.Findings1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated Long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in Long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre.InterpretationLong COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included.FundingERS has received funding to conduct this study by AstraZeneca UK Limited, Novartis Pharma AG, F. Hoffmann-La Roche Ltd, and Boehringer Ingelheim International GmbH.

A NEGLECTED RARE DISORDER: IGG4 RELATED DISEASE

Abstract IgG4–related disease (IgG4–RD) is an autoimmune disorder characterized by infiltration of plasma cells with IgG4. Almost any organ could be affected. Common presentations include lung manifestation, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. Cardiovascular involvement is less frequent. Corticosteroids are first line therapy, with or without anti–rheumatic drugs. Long–term prognosis of IgG4–RLD remains unknown. We present the case of a 65–years old woman, with a previuos diagnosis of IgG4–RD with mediastinal involvement. In the meantime she was recovered for pyelonephritis with high fever and positive blood coltures (S. hominis). We were called to perform a transthoracic echocardiogram to rule out infective endocarditis. The exam showed normal size of cardiac chambers, normal biventricular systolic function, absence of relevant valvular disease. In apical view we noticed a hyperechogenic ovalar imagine in the right atrium, not visible in all the projections. A first differential diagnosis included a mass with site of implantation at the top of the right atrium or something external but contiguous to heart structures. To clear this doubt the patient performed a thoracic CT with stunning results. The CT highlighted parietal encasement of chardiac structures and, particularly, of the superior vena cava at the confluence in right atrium, explaining the image we saw with transthoracic echo. The exam also showed encasement of ascending aorta, aortic arch and descending aorta with maximum thickness of 18 mm. CT also reported encasement of right pulmonary arthery. The CT highlighted a progression of the disease with indication to more aggressive therapy. In fact IgG4–RD of the cardiovascular system results in serious complications that need to be recognized and treated. Aortic involvement in IgG4–RD is extremely rare and tipically affects the infrarenal abdominal aorta. Cardiovascular IgG4–RD could also lead to aortitis, medium–vessel arteritis, pulmonary vascular disease, phlebitis, valvulopathy, pericarditis and myocardial disease. These forms of Igg4–RD are often underdiagnosed as clinical presentations is similar to cardiovascular disease due to more common aetiologies. Regarding our case the patient began methotrexate based on the results of the CT. This was a really interesting case for our working group to deepen this little–known disease. “The eyes see only what the mind is prepared to comprehend”.

The Association between Oxaliplatin-Induced Peripheral Neuropathy, Sociodemographic, and Clinical Characteristics with Falls in Older Adults with Colorectal Cancer.

Our purpose was to investigate the associations between oxaliplatin-induced peripheral neuropathy (OIPN), sociodemographic, and clinical characteristics of older colorectal cancer patients with falls. The study population consisted of older adults diagnosed with colorectal cancer obtained from the Surveillance, Epidemiology, and End Results database combined with Medicare claims. OIPN was defined using specific (OIPN 1) and broader (OIPN 2) definitions of OIPN, based on diagnosis codes. Extensions of the Cox regression model to accommodate repeated events were used to obtain overall hazard ratios (HR) with 95% confidence intervals and the cumulative hazard of fall. The unadjusted risk of fall for colorectal cancer survivors with vs. without OIPN 1 at 36 months of follow-up was 19.6% vs. 14.3%, respectively. The association of OIPN with time to fall was moderate (OIPN 1, HR = 1.37, 95% CI: 1.04, 1.79) to small (OIPN 2, HR = 1.24, 95% CI: 1.01, 1.53). Memantine, opioids, cannabinoids, prior history of fall, female sex, advanced age and disease stage, chronic liver disease, diabetes, and chronic obstructive pulmonary disease all increased the hazard rate of fall. Incorporating fall prevention in cancer care is essential to minimize morbidity and mortality of this serious event in older colorectal cancer survivors.