Asymptomatic esophageal perforation discovered after elective cardiac surgery: the importance of clinical awareness.

Transesophageal echocardiography (TEE) has become an indispensable part of cardiothoracic surgery at present and is considered to be a safe procedure, rarely associated with complications. However, TEE may cause serious and life threatening complications, as presented in this case report. We describe a patient who developed an empyema after elective cardiac surgery due to an esophageal perforation caused by TEE, without any clinical symptoms. Risk factors for TEE-related complications, identified in recent literature, will be discussed as well as the remarkable absence of clinical symptoms in this particular patient.

[Assessment of exo- and endocrine function of pancreas following distal pancreatectomy].

AIM: The assessment of pancreatic resection volume influence on exo- and endocrine pancreatic functions. MATERIALS AND METHODS: The resected pancreatic volume influence was assessed in 47 patients: 31 (66%) patients after resections of pancreatic body and tail, and 16 (34%) patients after distal resections. The exocrine pancreatic function was assessed by pancreatic fecal elastase 1 as well as endocrine pancreatic function was assessed by C-peptide level measurement. Computed tomography with intravenous contrast enhancement and postprocessing was used for pre- and postoperative pancreatic volume assessment. All tests were performed before and 1, 3, and 6 months after surgery. RESULTS: Type of surgery had no influence on C-peptide and pancreatic fecal elastase 1 levels (p>0.05). Exo- and endocrine pancreatic functions markers tended to decrease in 1st month after surgery with consequent functions restoration towards 6 months after surgery. There were 15 (35.7%) patients from 42 patients with normal exocrine pancreatic function with a fecal elastase 1 level decrease to 114.7±61.8 µg/g; exocrine insuficiency remained only in 2 (4.8%) patients after 6 months after surgery. C-peptide concentration decrease before surgery to less than 1.1 ng/ml was noticed only in 8 (17%) patients. C-peptide concentration decreased in 30 (63.8%) patients in 1st month after surgery, but after 6 months after surgery, C-peptide level decrease was only in 7 (14.9%) patients. CONCLUSION: The exo- and endocrine function of the pancreas is restored in more than 80% of patients after DR. Probably it could be associated with the activation of the pancreatic compensatory abilities.

Characterizing Determinants of Near-Road Ambient Air Quality for an Urban Intersection and a Freeway Site.

INTRODUCTION: Near-road ambient air pollution concentrations that are affected by vehicle emissions are typically characterized by substantial spatial variability with respect to distance from the roadway and temporal variability based on the time of day, day of week, and season. The goal of this work is to identify variables that explain either temporal or spatial variability based on case studies for a freeway site and an urban intersection site. The key hypothesis is that dispersion modeling of near-road pollutant concentrations could be improved by adding estimates or indices for site-specific explanatory variables, particularly related to traffic. Based on case studies for a freeway site and an urban intersection site, the specific aims of this project are to (1) develop and test regression models that explain variability in traffic-related air pollutant (TRAP) ambient concentration at two near-roadway locations; (2) develop and test refined proxies for land use, traffic, emissions and dispersion; and (3) prioritize inputs according to their ability to explain variability in ambient concentrations to help focus efforts for future data collection and model development.The key pollutants that are the key focus of this work include nitrogen oxides (NOx), carbon monoxide (CO), black carbon (BC), fine particulate matter (PM2.5; PM ≤ 2.5 µm in aerodynamic diameter), ultrafine particles (UFPs; PM ≤ 0.1 µm in aerodynamic diameter), and ozone (O3). NOx, CO, and BC are tracers of vehicle emissions and dispersion. PM2.5 is influenced by vehicle table emissions and regional sources. UFPs are sensitive to primary vehicle emissions. Secondary particles can form near roadways and on regional scales, influencing both PM2.5 and UFP concentrations. O3 concentrations are influenced by interaction with NOx near the roadway. Nitrogen dioxide (NO2), CO, PM2.5, and O3 are regulated under the National Ambient Air Quality Standards (NAAQS) because of demonstrated health effects. BC and UFPs are of concern for their potential health effects. Therefore, these pollutants are the focus of this work. METHODS: The methodological approach includes case studies for which variables are identified and assesses their ability to explain either temporal or spatial variability in pollutant ambient concentrations. The case studies include one freeway location and one urban intersection. The case studies address (1) temporal variability at a fixed monitor 10 meters from a freeway; (2) downwind concentrations perpendicular to the same location; (3) variability in 24-hour average pollutant concentrations at five sites near an urban intersection; and (4) spatiotemporal variability along a walking path near that same intersection.The study boundary encompasses key factors in the continuum from vehicle emissions to near-road exposure concentrations. These factors include land use, transportation infrastructure and traffic control, vehicle mix, vehicle (traffic) flow, on-road emissions, meteorology, transport and evolution (transformation) of primary emissions, and production of secondary pollutants, and their resulting impact on measured concentrations in the near-road environment. We conducted field measurements of land use, traffic, vehicle emissions, and near-road ambient concentrations in the vicinity of two newly installed fixed-site monitors. One is a monitoring station jointly operated by the U.S. Environmental Protection Agency (U.S. EPA) and the North Carolina Department of Environmental Quality (NC DEQ) on I-40 between Airport Boulevard and I-540 in Wake County, North Carolina. The other is a fixed-site monitor for measuring PM2.5 at the North Carolina Central University (NCCU) campus on E. Lawson Street in Durham, North Carolina. We refer to these two locations as the freeway site and the urban site, respectively. We developed statistical models for the freeway and urban sites. RESULTS: We quantified land use metrics at each site, such as distances to the nearest bus stop. For the freeway site, we quantified lane-by-lane total vehicle count, heavy vehicle (HV) count, and several vehicle-activity indices that account for distance from each lane to the roadside monitor. For the urban site, we quantified vehicle counts for all 12 turning movements through the intersection. At each site, we measured microscale vehicle tailpipe emissions using a portable emission measurement system.At the freeway site, we measured the spatial gradient of NOx, BC, UFPs, and PM, quantified particle size distributions at selected distances from the roadway and assessed partitioning of particles as a function of evolving volatility. We also quantified fleet-average emission factors for several pollutants.At the urban site, we measured daily average concentrations of nitric oxide (NO), NOx, O3, and PM2.5 at five sites surrounding the intersection of interest; we also measured high resolution (1-second to 10-second averages) concentrations of O3, PM2.5, and UFPs along a pedestrian transect. At both sites, the Research LINE-source (R-LINE) dispersion model was applied to predict concentration gradients based on the physical dispersion of pollution.Statistical models were developed for each site for selected pollutants. With variables for local wind direction, heavy-vehicle index, temperature, and day type, the multiple coefficient of determination (R2) was 0.61 for hourly NOx concentrations at the freeway site. An interaction effect of the dispersion model and a real-time traffic index contributed only 24% of the response variance for NOx at the freeway site. Local wind direction, measured near the road, was typically more important than wind direction measured some distance away, and vehicle-activity metrics directly related to actual real-time traffic were important. At the urban site, variability in pollutant concentrations measured for a pedestrian walk-along route was explained primarily by real-time traffic metrics, meteorology, time of day, season, and real-world vehicle tailpipe emissions, depending on the pollutant. The regression models explained most of the variance in measured concentrations for BC, PM, UFPs, NO, and NOx at the freeway site and for UFPs and O3 at the urban site pedestrian transect. CONCLUSIONS: Among the set of candidate explanatory variables, typically only a few were needed to explain most of the variability in observed ambient concentrations. At the freeway site, the concentration gradients perpendicular to the road were influenced by dilution, season, time of day, and whether the pollutant underwent chemical or physical transformations. The explanatory variables that were useful in explaining temporal variability in measured ambient concentrations, as well as spatial variability at the urban site, were typically localized real-time traffic-volume indices and local wind direction. However, the specific set of useful explanatory variables was site, context (e.g., next to road, quadrants around an intersection, pedestrian transects), and pollutant specific. Among the most novel of the indicators, variability in real-time measured tailpipe exhaust emissions was found to help explain variability in pedestrian transect UFP concentrations. UFP particle counts were very sensitive to real-time traffic indicators at both the freeway and urban sites. Localized site-specific data on traffic and meteorology contributed to explaining variability in ambient concentrations. HV traffic influenced near-road air quality at the freeway site more so than at the urban site. The statistical models typically explained most of the observed variability but were relatively simple. The results here are site-specific and not generalizable, but they are illustrative that near-road air quality can be highly sensitive to localized real-time indicators of traffic and meteorology.

Performance and reading time of lung nodule identification on multidetector CT with or without an artificial intelligence-powered computer-aided detection system.

AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.

Imaging of head and neck mucosa-associated lymphoid tissue lymphoma (MALToma).

Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALToma) arises in extranodal sites in the head and neck. Chronic inflammatory, infectious or autoimmune conditions are implicated in its pathogenesis. Within the head and neck, MALToma is often multifocal and indolent and the imaging appearances may be mistaken for non-malignant disease in the head and neck. The aim of this article is to illustrate the varied radiological and clinical features of MALToma in the head and neck, an awareness of which is needed for timely and correct diagnosis to guide subsequent disease management.

Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.

Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76-280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.

Current and future perspectives on allogeneic transplantation using ex vivo expansion or manipulation of umbilical cord blood cells.

In patients with hematologic malignancies, the outcome of umbilical cord blood transplantation has improved and is now comparable to that of matched unrelated donor transplantation. However, the limitation of using umbilical cord blood has been a delay in both hematopoietic and immunologic recovery. Strategies have been proposed to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.

Perception of the risk of tobacco use in pregnancy and factors associated with tobacco use in rural areas of Myanmar.

INTRODUCTION: Tobacco use is recognized as the most important preventable risk factor for pregnancy complications and undesirable fetal outcomes. This study examined the reported prevalence of tobacco use among married men and women residing in rural areas, and their knowledge on the risks of tobacco use during pregnancy and the factors associated with tobacco use. METHODS: A cross-sectional study was conducted within 32 villages in the delta region of Myanmar, randomly selected through multistage sampling procedure by using a pre-tested structured questionnaire during 2016. In all, 617 people participated in the household survey. RESULTS: About 80% of current smokers (109/128) smoked at home, of whom 16% reported the presence of a pregnant woman in their smoking area. Less than 25% of the respondents were aware of the negative impacts of tobacco use on pregnancy outcomes. Men had significantly lower perceived risk towards smoking on some pregnancy outcomes. Multivariate analysis confirmed the significant influence of male gender (adjusted OR, AOR=12.62; 95% CI: 6.30-25.29) and the age of women <35 years (AOR=3.51; 95% CI: 1.97-6.26) on current tobacco use, when controlling for other variables. CONCLUSIONS: Men in the study villages and those with a low level of education had poor knowledge on the risks of tobacco on pregnancy outcomes. However, good knowledge and perceived risk of undesirable impacts on pregnancy did not have any influence on tobacco use.

Trends in the total numbers of HBV and HCV carriers in Japan from 2000 to 2011.

We estimated the total number of undiagnosed HBV and HCV carriers and patients with hepatitis virus-related disease in Japan according to 6 different groups classified by their natural histories during 2011. In 2011, the total number of carriers and patients infected with HBV or HCV was estimated according to 6 groups using government reports and reports from the hepatitis epidemiology research group of The Ministry of Health, Labor and Welfare in Japan. In 2011, the total number of hepatitis virus carriers was estimated to be 2 090 128-2 840 128 in which the estimated number of undiagnosed HCV and HBV carriers was 776 826 (HBV: 481 470; HCV: 295 356). The total number of treated patients, as either inpatients or outpatients, was estimated to be 811588 (HBV: 303 366; HCV: 520 600) in 2011. It is presumed that many carriers shirk consultation for many reasons, such as patients' misunderstanding, lack of awareness and forgetfulness of their positive status. The numbers of infected patients who did not seek treatment increased gradually to 501 714-1 251 714 (HBV: 333 791-483 791; HCV: 167 923-767 923) in 2011. Compared to 2000, the number of undiagnosed carriers was significantly reduced in 2011 probably because of the well-organized, effective national hepatitis virus screening system that has been launched by the Japanese government since 2002. Moreover, the increase in the number of untreated persons who are aware of their positive status shows that more effort should be invested in improving the referral system from screening centres to core hospitals.

Well-differentiated papillary mesothelioma of tunica vaginalis testis of unknown malignant potential: Sonographic appearance.

Paratesticular mesothelioma is a rare differential diagnosis in the presence of scrotal hydrocele. A 17-year-old boy presented with a 3-year history of progressive hydrocele. Sonography revealed a large left paratesticular mass within the hydrocele. Serum tumor markers were negative. Left hydrocelectomy was performed and pathological analysis of the epididymal mass revealed a well-differentiated papillary mesothelioma. We discuss the sonographic and pathological findings of this rare neoplasm.

Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study.

PURPOSE: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients. METHODS: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution's ethical research committee. RESULTS: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2). CONCLUSIONS: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.

[CIRCADIAN DEPENDENCE OF PARACETAMOL HEPATOTOXICITY IN RATS.]

Results of chronopharmacological study of the circadian dependence of paracetamol toxicity and the extrapolation of obtained results to determine peculiarities in the daily activity of metabolic processes in rat liver are reported. The study was conducted on the model of acute paracetamol-induced hepatitis in both male and female rats in four diual periods: 03.00 a.m., 09.00 a.m., 15.00 p.m., and 21.00 p.m. The toxicity of paracetamol and the functional activity of liver were estimated by changes in markers of cytolytic activity of alanine aminotransferase (AIAT) and aspartate aminotransferase (AsAT) in blood serum, and the content of reduced glutathione (RG) in liver tissue. It is established that the degree of paracetamol toxicity and the level of hepatocyte RG are mutually dependent: the higher the content of RG in cells, the less pronounced toxic effect of xenobiotic is and vice versa, which is confirmed by correlation analysis (r = 0.43 - 0.94, depending on the circadian system of animals from control group). Extrapolation of results on the toxicity of paracetamol was used to reveal periods of the maximum and minimum functional activity of the liver. Acrophase of the functional activity of liver in rats corresponds to 15.00, and the antiphase of this activity in humans, to 01 - 03.

Ferritin is associated with neural differentiation of bone marrow-derived mesenchymal stem cells under extremely low-frequency electromagnetic field.

Extremely low-frequency electromagnetic field (ELFEF) is a well-known mechanical stimulation that induces neural differentiation. It is potentially an effective treatment for neurodegenerative diseases. In a previous study, ferritin light chain was upregulated in ELFEF-exposed human bone marrow-derived mesenchymal stem cells (BM-MSCs). Ferritin light chain is a component of ferritin, a highly conserved iron-binding protein. In this study, to identify molecules associated with ferritin during neural differentiation of BM-MSCs, we performed reverse transcription polymerase chain reaction (RT-PCR), western blotting, and ATP analysis. Our data indicated that ELFEF triggers the upregulation of ferritin light chain (FLC) and ferritin heavy chain (FHC) in BM-MSCs. The elevated levels of FLC and FHC correlated positively with the differentiation of BM-MSCs into neural cells. Moreover ELFEF induced the activation of iron regulatory protein-1 (IRP-1) and cofilin, which are downstream targets of ferritin. These results suggest that ELFEF induces neural differentiation through activation of a ferritin-regulated mechanism.

The accuracy of current methods in determining the timing of epiphysiodesis.

We compared the accuracy of the growth remaining method of assessing leg-length discrepancy (LLD) with the straight-line graph method, the multiplier method and their variants. We retrospectively reviewed the records of 44 patients treated by percutaneous epiphysiodesis for LLD. All were followed up until maturity. We used the modified Green-Anderson growth-remaining method (Method 1) to plan the timing of epiphysiodesis. Then we presumed that the other four methods described below were used pre-operatively for calculating the timing of epiphysiodesis. We then assumed that these four methods were used pre-operatively. Method 2 was the original Green-Anderson growth-remaining method; Method 3, Paley's multiplier method using bone age; Method 4, Paley's multiplier method using chronological age; and Method 5, Moseley's straight-line graph method. We compared 'Expected LLD at maturity with surgery' with 'Final LLD at maturity with surgery' for each method. Statistical analysis revealed that 'Expected LLD at maturity with surgery' was significantly different from 'Final LLD at maturity with surgery'. Method 2 was the most accurate. There was a significant correlation between 'Expected LLD at maturity with surgery' and 'Final LLD at maturity with surgery', the greatest correlation being with Method 2. Generally all the methods generated an overcorrected value. No method generates the precise 'Expected LLD at maturity with surgery'. It is essential that an analysis of the pattern of growth is taken into account when predicting final LLD. As many additional data as possible are required.

Mitochondrial modulation decreases the bortezomib-resistance in multiple myeloma cells.

Multiple myeloma (MM) is an incurable hematological malignancy that causes most patients to eventually relapse and die from their disease. The 20S proteasome inhibitor bortezomib has emerged as an effective drug for MM treatment; however, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. We evaluated the involvement of mitochondria in resistance to bortezomib-induced cell death in two different MM cell lines (bortezomib-resistant KMS20 cells and bortezomib-sensitive KMS28BM cells). Indices of mitochondrial function, including membrane potential, oxygen consumption rate and adenosine-5'-triphosphate and mitochondrial Ca(2+) concentrations, were positively correlated with drug resistance of KMS cell lines. Mitochondrial genes including CYPD, SOD2 and MCU were differentially expressed in KMS cells. Thus, changes in the expression of these genes lead to changes in mitochondrial activity and in bortezomib susceptibility or resistance, and their combined effect contributes to differential sensitivity or resistance of MM cells to bortezomib. In support of this finding, coadministration of bortezomib and 2-methoxyestradiol, a SOD inhibitor, rendered KMS20 cells sensitive to apoptosis. Our results provide new insight into therapeutic modalities for MM patients. Studying mitochondrial activity and specific mitochondrial gene expression in fresh MM specimens might help predict resistance to proapoptotic chemotherapies and inform clinical decision-making.

SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen.

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-ß in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

Four cases of possible human infections with Delftia lacustris.

We report four cases of possible human infections with Delftia lacustris. D. lacustris isolates, which were isolated from blood cultures and bile fluid of patients with underlying diseases such as empyema, renal injury, hepatocellular carcinoma, and renal infarction, were identified using 16S rRNA gene sequencing and biochemical tests. Four D. lacustris isolates did not show the same antimicrobial susceptibility profiles and enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) patterns, indicating their non-clonality.