Combined pulmonary fibrosis and emphysema.

PURPOSE OF REVIEW: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by upper lobe emphysema with lower lobe fibrosis. We aim to bring some clarity about its definition, nature, pathophysiology, and clinical implications. RECENT FINDINGS: Although multiple genetic and molecular pathways have been implicated in the development of CPFE, smoking is considered the most prevalent risk factor. CPFE is most prevalent in middle-aged men with more than 40 pack-years of smoking and can be seen in about 8% of all chronic obstructive pulmonary disease (COPD) patients. Given its nature, it is a radiological diagnosis, better defined by computed tomography (CT). Spirometry can be normal despite severe disease or can have restrictive or obstructive patterns, but the diffusing capacity of the lungs (DLCO) is consistently low regardless of the spirometry pattern. The disease is progressive, with high occurrences of lung cancer and pulmonary hypertension, complications that limit survival. Unfortunately, there is no treatment found to be beneficial other than supportive care and guideline-directed medical therapy. SUMMARY: CPFE is best described as a clinical and radiological syndrome where smokers are particularly at greater risk. Although simplistic, the earliest definition based chiefly on radiographic findings can identify a patient population with similar physiology. The most recent consensus proposes the definition based on mainly radiological findings with impaired gas exchange.

Asbestos-associated pulmonary disease.

PURPOSE OF REVIEW: Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma. RECENT FINDINGS: Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma. SUMMARY: Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.

A New Model of Hemoglobin Oxygenation.

The study of hemoglobin oxygenation, starting from the classical works of Hill, has laid the foundation for molecular biophysics. The cooperative nature of oxygen binding to hemoglobin has been variously described in different models. In the Adair model, which better fits the experimental data, the constants of oxygen binding at various stages differ. However, the physical meaning of the parameters in this model remains unclear. In this work, we applied Hill's approach, extending its interpretation; we obtained a good agreement between the theory and the experiment. The equation in which the Hill coefficient is modulated by the Lorentz distribution for oxygen partial pressure approximates the experimental data better than not only the classical Hill equation, but also the Adair equation.

Unprecedented: the toxic synergism of Covid-19 and climate change.

PURPOSE OF REVIEW: To review and compare the constellations of causes and consequences of the two current pandemics, Covid-19 and climate change. RECENT FINDINGS: There has been a transient counterbalancing, in which the response to Covid-19 has briefly mitigated pollution and greenhouse gasses. This divergence belies multiple commonalities of cause and effect. SUMMARY: The convergence of these two pandemics is unprecedented. Although at first glance, they appear to be completely unrelated, they share striking commonalities. Both are caused by human behaviors, and some of those behaviors contribute to both pandemics at the same time. Both illustrate the fact that isolation is not an option; these are global issues that inescapably affect all persons and all nations. Both incur prodigious current and anticipated costs. Both have similar societal impacts, and disproportionately harm those with lesser resources, widening the gap between the 'haves and the have-nots.' One can only hope that the devastation caused by these unprecedented pandemics will lead to increased awareness of how human beings have helped to create them and how our responses can and will shape our future.

Enhanced external counterpulsation: A unique treatment for the "No-Option" refractory angina patient.

WHAT IS KNOWN AND OBJECTIVES: Coronary artery disease (CAD) is the leading cause of death in the United States. For patients on whom guideline-driven measures have been tried, enhanced external counterpulsation (EECP) is the only truly noninvasive and safe intervention for which a reduction of angina symptoms and nitrate use, increased exercise tolerance, and improvement in myocardial ischaemia have been shown. The objective of this study was to demonstrate, by way of literature review, the efficacy of EECP as a treatment modality for the relief of refractory angina and improvement in quality of life in CAD patients. METHODS: This article reviewed the safety and efficacy of EECP in patients with refractory angina, by conducting a sweeping search and analysis of existing published literature. RESULTS AND DISCUSSION: Critical review of a multitude of studies revealed that EECP consistently reduces angina pectoris, extends time to exercise-induced ischaemia, decreases dependency on nitroglycerine for frequent chest pain, increases maximum workload, and improves the quality of life in patients with symptomatic stable angina. The literature reviewed also indicated that EECP is well-tolerated by the vast majority of patients, with relatively few adverse events reported. CONCLUSION: The present study suggests that EECP is a safe and likely best available method of treatment for patients presenting with symptomatic CAD not amenable to further revascularization.

Is cancer a pure growth curve or does it follow a kinetics of dynamical structural transformation?

BACKGROUND: Unperturbed tumor growth kinetics is one of the more studied cancer topics; however, it is poorly understood. Mathematical modeling is a useful tool to elucidate new mechanisms involved in tumor growth kinetics, which can be relevant to understand cancer genesis and select the most suitable treatment. METHODS: The classical Kolmogorov-Johnson-Mehl-Avrami as well as the modified Kolmogorov-Johnson-Mehl-Avrami models to describe unperturbed fibrosarcoma Sa-37 tumor growth are used and compared with the Gompertz modified and Logistic models. Viable tumor cells (1×105) are inoculated to 28 BALB/c male mice. RESULTS: Modified Gompertz, Logistic, Kolmogorov-Johnson-Mehl-Avrami classical and modified Kolmogorov-Johnson-Mehl-Avrami models fit well to the experimental data and agree with one another. A jump in the time behaviors of the instantaneous slopes of classical and modified Kolmogorov-Johnson-Mehl-Avrami models and high values of these instantaneous slopes at very early stages of tumor growth kinetics are observed. CONCLUSIONS: The modified Kolmogorov-Johnson-Mehl-Avrami equation can be used to describe unperturbed fibrosarcoma Sa-37 tumor growth. It reveals that diffusion-controlled nucleation/growth and impingement mechanisms are involved in tumor growth kinetics. On the other hand, tumor development kinetics reveals dynamical structural transformations rather than a pure growth curve. Tumor fractal property prevails during entire TGK.

Health inequalities by socioeconomic characteristics in Spain: the economic crisis effect.

BACKGROUND: An economic crisis can widen health inequalities between individuals. The aim of this paper is to explore differences in the effect of socioeconomic characteristics on Spaniards' self-assessed health status, depending on the Spanish economic situation. METHODS: Data from the 2006-2007 and 2011-2012 National Health Surveys were used and binary logit and probit models were estimated to approximate the effects of socioeconomic characteristics on the likelihood to report good health. RESULTS: The difference between high and low education levels leads to differences in the likelihood to report good health of 16.00-16.25 and 18.15-18.22 percentage points in 2006-07 and 2011-12, respectively. In these two periods, the difference between employees and unemployed is 5.24-5.40 and 4.60-4.90 percentage points, respectively. Additionally, the difference between people who live in households with better socioeconomic conditions and those who are in worse situation reaches 5.37-5.46 and 3.63-3.74 percentage points for the same periods, respectively. CONCLUSIONS: The magnitude of the contribution of socioeconomic characteristics to health inequalities changes with the economic cycle; but this effect is different depending on the socioeconomic characteristics indicator that is being measured. In recessive periods, health inequalities due to education level increase, but those linked to individual professional status and household living conditions are attenuated. When the joint effects of individuals' characteristics are considered, the economic crisis brings about a slight increase in the inequalities in the probability of reporting good health between the two extreme profiles of individuals. The design of public policies aimed at preventing any worsening of health inequalities during recession periods should take into account these differential effects of socioeconomic characteristics indicators on health inequalities.

Diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis.

BACKGROUND: Patent foramen ovale (PFO) is a remnant of the fetal circulation present in 20% of the population. Right-to-left shunting (RLS) through a PFO has been linked to the pathophysiology of stroke, migraine with aura, and hypoxemia. While different imaging modalities including transcranial Doppler, intra-cardiac echo, and transthoracic echo (TTE) have often been used to detect RLS, transesophageal echo (TEE) bubble study remains the gold standard for diagnosing PFO. The aim of this study was to determine the relative accuracy of TEE in the detection of PFO. METHODS AND RESULTS: A systematic review of Medline, using a standard approach for meta-analysis, was performed for all prospective studies assessing accuracy of TEE in the detection of PFO using confirmation by autopsy, cardiac surgery, and/or catheterization as the reference. Search results revealed 3105 studies; 4 met inclusion criteria. A total of 164 patients were included. TEE had a weighted sensitivity of 89.2% (95% CI: 81.1-94.7%) and specificity of 91.4% (95% CI: 82.3-96.8%) to detect PFO. The overall positive likelihood ratio (LR+) was 5.93 (95% CI: 1.30-27.09) and the overall negative likelihood ratio (LR-) was 0.22 (95% CI: 0.08-0.56). CONCLUSION: While TEE bubble study is considered to be the gold standard modality for diagnosing PFO, some PFOs may still be missed or misdiagnosed. It is important to understand the limitations of TEE and perhaps use other highly sensitive screening tests, such as transcranial doppler (TCD), in conjunction with TEE before scheduling a patient for transcatheter PFO closure.

Stability of the CAG Tract in the ATXN2 Gene Depends on the Localization of CAA Interruptions.

It is known that the presence of CAA codons in the CAG tract affects the nature and time of disease onset caused by the expansion of trinucleotide repeats. The mechanisms leading to the occurrence of these diseases should be sought not only at the level of the physiological role of the ATXN2 protein, but also at the DNA level. These mechanisms are associated with non-canonical configurations (hairpins) that can form in the CAG tract. The tendency of hairpins to slide along the corresponding threads is usually considered important to explain the expansion of the CAG tract. At the same time, hairpins occur in areas of open states. Previous studies on the role of CAA interruptions have suggested that, under certain conditions, they can stabilize the dynamics of the hairpin, preventing the expansion of the CAG tract. We calculated the probability of additional open state zones occurrence in the CAG tract using an angular mathematical model of DNA. The calculations made it possible to establish that CAA interruptions affect the stability of the CAG tract, and this influence, depending on the localization of the interruption, can both increase and decrease the stability of the CAG tract.

Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length.

Hereditary ataxias are one of the «anticipation diseases¼ types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22-23 CAG trinucleotides. Mutations that increase the length of CAG repeats can cause severe neurodegenerative and neuromuscular disorders known as trinucleotide repeat expansion diseases. The mechanisms causing such diseases are associated with non-canonical configurations that can be formed in the CAG repeat region during replication, transcription or repair. This makes it relevant to study the zones of open states that arise in the region of CAG repeats under torque. The purpose of this work is to study, using mathematical modeling, zones of open states in the region of CAG repeats of the ATXN2 gene, caused by torque. It has been established that the torque effect on the 1st exon of the ATXN2 gene, in addition to the formation of open states in the promoter region, can lead to the formation of additional various sizes open states zones in the CAG repeats region. Moreover, the frequency of additional large zones genesis increases with increasing number of CAG repeats. The inverse of this frequency correlates with the dependence of the disease onset average age on the CAG repeats length. The obtained results will allow us to get closer to understanding the genetic mechanisms that cause trinucleotide repeat diseases.

Effect of Salt Mist Ageing on the Physical and Mechanical Properties of Two Ignimbrites from the Canary Islands (Spain).

The aim of this research work is to study the effect of salt mist ageing on the physico-mechanical properties of two ignimbrites from the Canary Islands (Spain). Due to their insular nature and extensive coastlines, these regions are highly susceptible to atmospheric salt aerosols, which is a significant weathering agent for building materials. The ignimbrites analysed are marketed under the names "Azul Lomo Tomás de León" and "Marrón de Abades" and are widely used as building stones. Petrographic, mineralogical and chemical properties were obtained via polarisation microscopy, X-ray diffraction and X-ray fluorescence. The samples were subjected to 60 cycles of a salt mist environment, following relevant European standards. Scanning electron microscopy images of the specimens were analysed along with physical properties, including apparent density, open porosity, water absorption, colourimetry and ultrasound propagation velocity, initially and after every 20 cycles, allowing us to assess their evolution during the ageing test. Mechanical properties were evaluated using uniaxial compressive strength and flexural strength under concentrated load tests on two groups of specimens: one unaged and the other subjected to 60 ageing cycles. With the exception of apparent density, the other properties show a decrease between 5% and 30%. However, open porosity increases and is one of the properties most affected by the ageing test.

Mathematical models describing oxygen binding by hemoglobin.

Despite the fact that the investigation of the structural and functional properties of hemoglobin dates back more than 150 years, the topic has not lost its relevance today. The most important component of these studies is the development of mathematical models that formalize and generalize the mechanisms determining the cooperative binding of ligands based on data on the structural and functional state of the protein. In this work, we review the mathematical relationships describing oxygen binding by hemoglobin, ranging from the classical Hüfner, Hill, and Adair equations to the Szabo-Karplus and tertiary two-state mathematical models based on the Monod-Wyman-Changeux and Koshland-Némethy-Filmer concepts. The generality of the considered equations as mathematical functions, bearing in their basis a power dependence, is demonstrated. The problems and possible solutions related to approximation of experimental data by the oxygenation equations with correlated fitting parameters are noted. Attention is paid to empirical equations, extended versions of the Hill equation, where the coefficient of cooperation is modulated by Gauss and Lorentz distributions as functions of partial oxygen pressure.

A 72-Year-Old Woman With Dyspnea, Multiple Pulmonary Nodules, and Mediastinal Lymphadenopathy.

CASE PRESENTATION: A 72-year-old woman presented to our institution with gradually worsening shortness of breath and bilateral lower extremity edema of 3 weeks' duration. She had associated complaints of cough and intermittent hemoptysis. Her medical history was significant for hypertension and hypothyroidism. She was a former cigarette smoker with a 35 pack-year smoking history. She had no recent travel history and had a pet dog at home. Six months before the current hospitalization, evaluation for cough had revealed mediastinal lymphadenopathy at an outside institution. She underwent evaluation with an endobrachial ultrasound procedure at an outside facility 8 weeks before the current admission. The procedure demonstrated both acute and chronic inflammation, with one specimen showing few atypical cells on cytopathology and no growth on bacterial, fungal, and mycobacterial cultures. She was treated empirically with oral steroids for presumed sarcoidosis. However, this did not result in clinical benefit, and because of progressive symptoms, she presented to our institution.

A 34-Year-Old Man With Lightheadedness and Dyspnea.

CASE PRESENTATION: A 34-year-old man presented to our institution with lightheadedness and dyspnea on exertion. His medical history included chronic pancreatitis, juvenile rheumatoid arthritis (JRA), gastroesophageal reflux disease, hypertension, lumbar degenerative disc disease, seizure disorder, anterior uveitis, and multiple vertebral fractures. In addition, he was a cigarette smoker with a 10-pack-year smoking history.

Proposal for the functional assessment of acute inflammatory neuropathy (FAAIN) in Guillain-Barré syndrome.

BACKGROUND: Guillain Barré syndrome (GBS) functional assessment is necessary in clinical practice, research and clinical trials. Existing instruments are not sensitive to change and are not applicable to the current GBS clinical spectrum. OBJECTIVE: To construct a functional assessment for acute inflammatory neuropathies (FAAIN-GBS), inclusive for current GBS spectrum that assesses extension and intensity separately. METHODS: FAAIN-GBS subscales were constructed. Its structure and interpretation were defined. It was validated using data from medical record of 167 GBS patients admitted to the Institute of Neurology and Neurosurgery. Cronbach α was used for items reduction and reliability analysis. Bartlett sphericity test was performed. Exploratory factor analysis (EFA) of the main components, with varimax rotation, was applied to evaluate dimensionality and content validity. Hughes scale was used as gold standard for criterion validity. Sensitivity, specificity and area under the receiver operating characteristic curves (AUROC), were calculated. Construct validity was assessed by confirmatory factor analysis (CFA). RESULTS: FAAIN-GBS is made up of two subscales (extension and intensity). The final score is obtained by averaging both dimensions. Internal consistency was acceptable (Cronbach 0.745). EFA showed three dimensions: intensity, spinal extension and cranial extension. Spearman correlation between FAAIN-GBS and Hughes scale was 0.463. Sensitivity (0.714) and specificity (0.986) values showed the good behavior of the scale; AUROC was 0.93. CONCLUSION: FAAIN-GBS was constructed and a first step of validation was made, showing good internal consistency and validity. New prospective studies with large populations will be necessary to perfect this instrument that could be useful in neurological practice.

[Probable association between preeclampsia/eclampsia and paternal age: a pilot study]. / Posible asociación entre preeclampsia-eclampsia y la edad paterna: estudio piloto.

BACKGROUND: The preeclampsia is a multisystemic syndrome that occupied the first cause of maternal and fetal mortality around the world. Epidemiologic studies shown both mother and father contribute at the same risk for preeclampsia. OBJECTIVE: To determinate if there is an association between preeclampsia and paternal age. MATERIAL AND METHOD: Preeclampsia-eclampsia patients and couples were analyzed in agree to "National High Blood Pressure Education Program Working Group" classification, and a control group constituted by normal pregnant women and couples was included. RESULTS: There were 27 cases with mild preeclampsia and her couples, 13 cases with severe preeclampsia and her couples and 40 controls conformed by normal pregnant women and her couples. The statistical analysis of variance of the ages shown that men from preeclamptic group had a greater variance in contrast with man of control group (p < 0.001; valor of F = 5.084). CONCLUSIONS: Although is not clear how paternal age interview in preeclampsia risk, the interaction between paternal-maternal imprinting and spermatic senescence, followed by shortened telomeres of chromosome, could be produce the inactivity of a whole network of signals implicated in disease aetiology.

COVID-19 epidemic in The World Health Organization African Region (WHOAR): Situation and forecast.

To describe the dynamics and forecast the main parameters of the COVID-19 pandemic, the time series of daily cases in the World Health Organization African Region (WHOAR) from February 26th to December 29th, 2020 was analyzed. Estimates for expected values of parameters characterizing an epidemic (size of the epidemic, turning point, maximum value of daily cases, and basic reproductive number) were provided for both the first and the second wave, and for the entire ongoing pandemic in WHOAR. To this aim, the classical SIR (Susceptible-Infected-Removed) model and its approximations were applied to each identified wave. Our results suggest that the turning point of the COVID-19 first wave took place around July 20th, 2020. The first wave was expected to disappear by mid-December 2020, with a total of 1,200,000 expected cases. The second wave apparently started around August 19th, with an expected turning point by January 12th, 2021. The second wave is expected to end by August 9th, 2021, with 1,800,000 cumulative cases, and mounting up to 3,000,000 total cases between February 2020 and August 2021. Estimated basic reproduction numbers (R0) were 1.27 (first wave) and 1.15 (second wave); the expected total number of deaths is around 66,000 victims.

Robotic Bronchoscopy for Peripheral Pulmonary Lesion Biopsy: Evidence-Based Review of the Two Platforms.

Despite many advancements in recent years for the sampling of peripheral pulmonary lesions, the diagnostic yield remains low. Initial excitement about the current electromagnetic navigation platforms has subsided as the real-world data shows a significantly lower diagnostic sensitivity of ~70%. "CT-to-body divergence" has been identified as a major limitation of this modality. In-tandem use of the ultrathin bronchoscope and radial endobronchial ultrasound probe has yielded only comparable results, attributable to the limited peripheral reach, device maneuverability, stability, and distractors like atelectasis. As such, experts have identified three key steps in peripheral nodule sampling-navigation (to the lesion), confirmation (of the correct location), and acquisition (tissue sampling by tools). Robotic bronchoscopy (RB) is a novel innovation that aspires to improve upon these aspects and consequently, achieve a better diagnostic yield. Through this publication, we aim to review the technical aspects, safety, feasibility, and early efficacy data for this new diagnostic modality.

Chryseobacterium gleum Causing Healthcare-Associated Pneumonia in an Adult Male With Diffuse Large B Cell Lymphoma.

Chryseobacterium species are recognized as an emerging opportunistic bacterial pathogen in nosocomial settings especially in debilitated or immunosuppressed patients and neonates. The ubiquitous distribution in nature, ability to form biofilms with inherent resistance to broad-spectrum antimicrobials, and lack of clinical studies pose a further diagnostic and therapeutic challenge. This case report describes an elderly male with relapsed diffuse large B-cell lymphoma (DLBCL) status post-chemotherapy and radiation who acquired healthcare-associated pneumonia with sputum isolates showing Chryseobacterium gleum and Stenotrophomonas maltophila. It also includes a review of literature compiling all the previously reported cases with antibiotic susceptibilities, clinical picture, and treatment outcomes.

Migrating azygos vein and vanishing azygos lobe: MDCT findings.

OBJECTIVE: The purpose of this study was to describe six cases of migrating azygos vein and to explain the etiologic factors that contribute to the migration. Six patients with migrating azygos vein were studied by MDCT before and after migration. Five patients had right pneumothorax. All patients had repeated episodes of cough, vomiting, and a short mesoazygos. CONCLUSION: Pneumothorax, increased intrathoracic pressure, and a short mesoazygos, in combination or alone, are the main factors in azygos vein migration.