Pulmonary Asbestos Fiber Burden Is Related to Patient Survival in Malignant Pleural Mesothelioma.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with poor prognosis and is strongly associated with occupational asbestos exposure. Given the importance of asbestos exposure in MPM pathogenesis, we retrospectively analyzed the types and concentrations of asbestos fibers within the lung tissues of patients with MPM and investigated their effects on all-cause mortality. METHODS: We formed a national data set of patients with MPM identified from the Finnish Cancer Registry and Statistics Finland. These data were merged with pulmonary asbestos fiber analysis results received from the Finnish Institute of Occupational Health. RESULTS: We identified 590 patients with MPM who underwent pulmonary asbestos fiber analysis. The median asbestos concentration within dry lung tissue was 3.20 million fibers/gram (range: 0 - 1700 million fibers/gram). Crocidolite and anthophyllite were the most prevalent asbestos fiber types detected in lung tissue. The multivariable risk of death analyses, where changes over time were accounted for, revealed that total asbestos fiber concentration was associated with increased mortality. Nevertheless, no difference in mortality was noted between different fiber types. CONCLUSIONS: Our study revealed that pulmonary fiber concentrations correlated with the manner of asbestos usage. Anthophyllite was identified as the sole fiber in a sizable proportion of cases, supporting its independent role in the pathogenesis of MPM. Our findings suggest that asbestos fiber burden, but not fiber type, may have an impact on the prognosis of MPM.

Correction to "Metastable Nanobubbles".

[This corrects the article DOI: 10.1021/acsomega.0c05384.].

Comment on "On the thermodynamic stability of bubbles, immiscible droplets, and cavities" by G. S. Manning, Phys. Chem. Chem. Phys., 2020, 22, 17523.

In this comment, the thermodynamic analysis of the stability of nanobubbles is discussed in reference to the recent paper by Manning (G. S. Manning, On the Thermodynamic Stability of Bubbles,Immiscible Droplets, and Cavities, Phys. Chem. Chem. Phys., 2020, 22, 17523-17531). It is argued that Manning's critcism on the classical Epstein-Plesset model of bubble stability is unwarranted, and that the Young-Laplace-equation must be understood as a fundamental law of the pressure difference across a curved interface regardless of the reaction of the gas in the bubble. Consequently, the internal pressure and the radius of a bubble are inherently linked, so that the net force considered in Manning's stability analysis does not exist.

Metastable Nanobubbles.

Water containing suspended nanobubbles is utilized in various applications. The observed lifetime of suspended nanobubbles is several weeks, whereas, according to the classical theory of bubble stability, a nanosized bubble should dissolve within microseconds. Explanations for the longevity of nanosized bubbles have been proposed but none of them has gained general acceptance. In this study, we derive an explanation for the existence of metastable nanobubbles solely from the thermodynamic principles. According to our analysis, the dissolution of nanosized aqueous bulk bubbles is nonspontaneous below 180 nm diameter due to the energy requirement of gas dissolution. Hydrophobic surfaces have a further stabilizing effect, and the dissolution becomes nonspontaneous in surface nanobubbles having a diameter below 600 nm.

Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival. MATERIALS AND METHODS: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists. RESULTS: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time. CONCLUSION: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.

Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival.

Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.

Did malpractice claims for failed dental implants decrease after introduction of CBCT in Finland?

OBJECTIVES: To examine the role of cone beam computed tomography (CBCT) in preventing failures in implant treatment. We hypothesize that the number of malpractice claims related to dental implant treatment would decrease after the first CBCT device came available in 2002 in Finland. MATERIAL AND METHODS: Data concerning malpractice claims related to dental implant treatment during the years 1997-2011 were collected from the Finnish Patient Insurance Centre (N = 330 subjects). We selected the cases that might have benefitted from the use of CBCT examination. These cases (n = 131) led to financial compensation due to permanent inferior alveolar nerve injury, improper implant position, or insufficient amount of bone for the implant. The annual total number of inserted dental implants, CBCT devices, and CBCT examinations in Finland were drawn from the national registers and used to estimate the impact of CBCT in preventing treatment failures. RESULTS: The most common reason for all failures (n = 268 implants) was an improper implant position (46.3%). The most common area of malpractices was upper front teeth (34%). We have noticed a fall in the rate of compensable malpractice cases concerning implant failure, simultaneously with CBCT technology emerging on the market. CONCLUSIONS: There may be an association between the increasing availability of CBCT equipment and the reducing frequency of compensable malpractice claims. CLINICAL RELEVANCE: It is possible that the use of CBCT may result in fewer compensable malpractice claims.

Malignant pleural mesothelioma in Finland: regional and gender variation.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care. METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland. RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months. CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate. IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.

Computed tomography in the evaluation of malignant pleural mesothelioma-Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival.

OBJECTIVES: Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. MATERIALS AND METHODS: As part of our study that included all MPM patients diagnosed in Finland 2000-2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. RESULTS: The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. CONCLUSION: In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses.

Chronic low back pain in relation to Modic changes, bony endplate lesions, and disc degeneration in a prospective MRI study.

PURPOSE: To clarify the significance of Modic changes, bony endplate lesions, and disc degeneration as predictors of chronic low back pain (LBP) during 1-year follow-up. METHODS: 49 patients with severe, non-specific, chronic LBP, and Modic 1 lesion (M1) were prospectively studied with MRI and questionnaire. Changes in grade of disc degeneration, severity of Modic changes, Schmorl lesions, and bony endplate irregularities were evaluated and changes assessed in LBP intensity on numeric rating scale 0-10 and severity with Oswestry disability index 0-100 (ODI). Association between change in MRI findings and symptoms was computed using generalized estimating equations analysis. RESULTS: Although pain decreased in most patients during 1-year follow-up, it increased or persisted in 36 %. Change in M1, M2, bony endplate lesions, and signal intensity (SI) and height of the disc associated with change of pain intensity, while change in M1, bony endplate lesions, and disc height associated with change of ODI. Not only persistent M1s, increasing bony endplate lesions, decreasing disc height, and M2s, but also new M2s predicted persistence of pain, while decrease of M1s and SI of the disc and increase of size of M2s predicted decrease of pain. Changes in disc bulges did not associate with pain. CONCLUSIONS: In patients with chronic non-specific LBP, persisting M1, decreasing disc height, and increasing bony endplate lesions associated with persisting pain while decrease of SI of the disc with decrease of pain. Such changing MRI findings in the same disc space have earlier been shown to progress abnormally fast. They may be signs or biomarkers of a prolonged pain causing, deforming degenerative process, and should lead to considering early intervention or specific treatments to affect that process.

Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities.

The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.

Relationships (I) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with the ILO International Classification of Radiographs of Pneumoconioses for parenchymal abnormalities.

The International Classification of High-resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) has been developed for the screening, diagnosis, and epidemiological reporting of respiratory diseases caused by occupational hazards. This study aimed to establish a correlation between readings of HRCT (according to the ICOERD) and those of chest radiography (CXR) pneumoconiotic parenchymal opacities (according to the International Labor Organization Classification/International Classification of Radiographs of Pneumoconioses [ILO/ICRP]). Forty-six patients with and 28 controls without mineral dust exposure underwent posterior-anterior CXR and HRCT. We recorded all subjects' exposure and smoking history. Experts independently read CXRs (using ILO/ICRP). Experts independently assessed HRCT using the ICOERD parenchymal abnormalities grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). The correlation between the ICOERD summed grades and ILO/ICRP profusions was evaluated using Spearman's rank-order correlation. Twenty-three patients had small opacities on CXR. HRCT showed that 21 patients had RO; 20 patients, IR opacities; and 23 patients, EM. The correlation between ILO/ICRP profusions and the ICOERD grades was 0.844 for rounded opacities (p<0.01). ICOERD readings from HRCT scans correlated well with previously validated ILO/ICRP criteria. The ICOERD adequately detects pneumoconiotic micronodules and can be used for the interpretation of pneumoconiosis.

Cervical and lumbar pain and radiological degeneration among fighter pilots: a systematic review and meta-analysis.

To assess the associations of acceleration force indicators (aircraft type and flight hours) with cervical and lumbar pain and radiological degeneration among fighter pilots. The PubMed, Embase, Scopus and Web of Science databases were searched until October 2013. Twenty-seven studies were included in the review and 20 in the meta-analysis. There were no differences in the prevalence of neck pain (pooled OR=1.07, 95% CI 0.87 to 1.33), cervical disc degeneration (OR=1.26, CI 0.81 to 1.96), low back pain (OR=0.80, CI 0.47 to 1.38) or lumbar disc degeneration (OR=0.87, CI 0.67 to 1.13) between fighter pilots and helicopter or transport/cargo pilots. Moreover, the prevalence of cervical (OR=1.14, CI 0.61 to 2.16) or lumbar (OR=1.05, CI 0.49 to 2.26) disc degeneration did not differ between fighter pilots and non-flying personnel. Most studies did not control their estimates for age and other potential confounders. Among high-performance aircraft pilots, exposure to the highest G-forces was associated with a higher prevalence of neck pain compared with exposure to lower G-forces (pooled OR=3.12, CI 2.08 to 4.67). The studies on the association between flight hours and neck pain reported inconsistent findings. Moreover, looking back over the shoulder (check six) was the most common posture associated with neck pain. Fighter pilots exposed to high G-forces may be at a greater risk for neck pain than those exposed to low G-forces. This finding should be confirmed with better control for confounding. Awkward neck posture may be an important factor in neck pain among fighter pilots.

Variations in the TNFα gene and their interactions with the IL4R and IL10 genes in relation to hand osteoarthritis.

BACKGROUND: The development of osteoarthritis (OA) involves inflammation, but the evidence for participation of genes propagating or inhibiting inflammation in the OA process is inconsistent. We investigated the associations of common variants in the TNFα gene, and their interactions with other cytokine genes, with hand OA among Finnish women. METHODS: This cross-sectional study was based on bilateral hand radiographs of 542 female dentists and teachers which were classified according to the presence of OA (radiographic K-L score ≥ 2 in ≥ 3 joints) using reference images. The genotypes were determined by PCR-based methods. The degree of pairwise linkage disequilibrium (LD) and haplotypes were constructed and analyzed by the SNPStats software. The associations between four TNFα SNPs and hand OA were tested using logistic regression adjusting for age, occupation, and BMI, and fitting a log-additive model of inheritance. Gene-gene interactions of TNFα SNPs with IL4R and IL10 SNPs were examined by stratified logistic regression analyses. Possible interactions of the TNFα SNPs with variants in the previously reported IL1ß and IL6 genes in influencing hand OA were also explored. RESULTS: Two TNFα polymorphisms ("-1031" and "-863") were associated with hand OA (OR = 1.45, 95% CI 1.01-2.07 and 1.55, 1.06-2.25, respectively). These associations retained when adjusting further for IL1ß "3954" and IL6 "174". The TNFα G-A-G haplotype was associated with an increased risk of hand OA (1.61, 1.10-2.37, p = 0.01). Interactions were observed between TNFα "-1031" and IL4R Ser503Pro, TNFα "-1031" and IL10 "-1082", and TNFα "-863" and IL10 "-1082" SNPs with regard to hand OA (p = 0.012, p = 0.0068, and p = 0.02, respectively). The carriage of the TNFα "-1031" minor allele doubled the risk (2.01, 1.26 - 3.22) only in women with the IL4R Ser/Ser genotype. Similarly, the TNFα "-1031" and "-863" minor alleles were associated with an increased risk of hand OA only in IL10 G/G or A/A homozygotes (2.54, 1.45-4.47 and 2.60, 1.46-4.62, respectively) but not in heterozygotes (G/A). CONCLUSIONS: Our results suggest that the TNFα gene variants play a role in the etiology of hand OA. In addition, the findings are suggestive of a gene-gene interaction of the TNFα with IL4R and IL10 genes.