Impact of maternal social vulnerability and timing of prenatal care on outcome of prenatally detected congenital heart disease.

OBJECTIVES: Early prenatal detection of congenital heart disease (CHD) allows mothers to plan for their pregnancy and delivery; however, the effect of certain sociodemographic and fetal factors on prenatal care has not been investigated thoroughly. This study evaluated the impact of maternal and fetal characteristics on the timing of prenatal diagnosis of CHD and fetal and postnatal outcomes. METHODS: This retrospective multicenter cohort study included women with a fetal echocardiographic diagnosis of CHD between 2010 and 2019. Women were grouped into quartiles of social vulnerability (quartiles 1-4; low-high) using the 2014 social vulnerability index (SVI) provided by the Centers for Disease Control and Prevention. A fetal disease severity score (range, 1-7) was calculated based on a combination of CHD severity (mild = 1; moderate = 2; severe, two ventricles = 3; severe, single ventricle = 4 points) and prenatally diagnosed genetic abnormality, non-cardiac abnormality and fetal hydrops (1 point each). Late diagnosis was defined as a fetal echocardiographic diagnosis of CHD after 24 weeks' gestation. Univariate and multivariable regression analyses were used to identify factors associated with late diagnosis, termination of pregnancy (TOP), postnatal death, prenatal-postnatal discordance in CHD diagnosis and severity and, for liveborn infants, to identify which prenatal variables were associated with postnatal death or heart transplant. RESULTS: Among 441 pregnancies included, 94 (21%) had a late diagnosis of CHD. Late diagnosis was more common in the most socially vulnerable quartile, 38% of women in this group having diagnosis > 24 weeks, compared with 14-18% in the other three quartile groups. Late diagnosis was also associated with Catholic or other Christian religion vs non-denominational or other religion and with a lower fetal disease severity score. There were 93 (21%) TOP and 26 (6%) in-utero fetal demises. Factors associated with TOP included early diagnosis and greater fetal disease severity. Compared with the other quartiles, the most socially vulnerable quartile had a higher incidence of in-utero fetal demise and a lower incidence of TOP. Among the 322 liveborn infants, 49 (15%) died or underwent heart transplant during the follow-up period (range, 0-16 months). Factors associated with postnatal death or heart transplant included longer delay between obstetric ultrasound examination at which CHD was first suspected and fetal echocardiogram at which CHD was confirmed and greater fetal disease severity. CONCLUSIONS: High social vulnerability, Catholic or other Christian religion and low fetal disease severity are associated with late prenatal CHD diagnosis. Delays in CHD diagnosis are associated with fewer TOPs and worse postnatal outcome. Therefore, efforts to expedite fetal echocardiography following abnormal obstetric screening, particularly for at-risk women (e.g. those with high SVI), have the potential to impact pregnancy and postnatal outcome among the prenatally diagnosed CHD population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Experimental demonstration of accurate Bragg peak localization with ionoacoustic tandem phase detection (iTPD).

Accurate knowledge of the exact stopping location of ions inside the patient would allow full exploitation of their ballistic properties for patient treatment. The localized energy deposition of a pulsed particle beam induces a rapid temperature increase of the irradiated volume and leads to the emission of ionoacoustic (IA) waves. Detecting the time-of-flight (ToF) of the IA wave allows inferring information on the Bragg peak location and can henceforth be used forin-vivorange verification. A challenge for IA is the poor signal-to-noise ratio at clinically relevant doses and viable machines. We present a frequency-based measurement technique, labeled as ionoacoustic tandem phase detection (iTPD) utilizing lock-in amplifiers. The phase shift of the IA signal to a reference signal is measured to derive theToF. Experimental IA measurements with a 3.5 MHz lead zirconate titanate (PZT) transducer and lock-in amplifiers were performed in water using 22 MeV proton bursts. A digital iTPD was performedin-silicoat clinical dose levels on experimental data obtained from a clinical facility and secondly, on simulations emulating a heterogeneous geometry. For the experimental setup using 22 MeV protons, a localization accuracy and precision obtained through iTPD deviates from a time-based reference analysis by less than 15µm. Several methodological aspects were investigated experimentally in systematic manner. Lastly, iTPD was evaluatedin-silicofor clinical beam energies indicating that iTPD is in reach of sub-mm accuracy for fractionated doses < 5 Gy. iTPD can be used to accurately measure theToFof IA signals online via its phase shift in frequency domain. An application of iTPD to the clinical scenario using a single pulsed beam is feasible but requires further development to reach <1 Gy detection capabilities.

Reconsidering statistical methods for assessing replication.

Recent empirical evaluations of replication in psychology have reported startlingly few successful replication attempts. At the same time, these programs have noted that the proper way to analyze replication studies is far from a settled matter and have analyzed their data in several different ways. This presents 2 challenges to interpreting the results of these programs. First, different analysis methods assess different operational definitions of replication. Second, the properties of these methods are not necessarily common knowledge; it is possible for a successful replication to be deemed a failure by nearly all of the metrics used, and it is not always immediately clear how likely such errors are to occur. In this article, we describe the methods commonly used in replication research and how they imply specific operational definitions of replication. We then compute the probability of false failure (i.e., a successful replication is concluded to have failed) and false success determinations. These are shown to be high (often over 50%) and in many cases uncontrolled. We then demonstrate that errors are probable in the data to which these methods have been applied in the literature. We show that the probability that some reported conclusions about replication are incorrect can be as high as 75-80%. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Deliberating performance targets workshop: Potential paths for emerging PM2.5 and O3 air sensor progress.

The United States Environmental Protection Agency held an international two-day workshop in June 2018 to deliberate possible performance targets for non-regulatory fine particulate matter (PM2.5) and ozone (O3) air sensors. The need for a workshop arose from the lack of any market-wide manufacturer requirement for Ozone documented sensor performance evaluations, the lack of any independent third party or government-based sensor performance certification program, and uncertainty among all users as to the general usability of air sensor data. A multi-sector subject matter expert panel was assembled to facilitate an open discussion on these issues with multiple stakeholders. This summary provides an overview of the workshop purpose, key findings from the deliberations, and considerations for future actions specific to sensors. Important findings concerning PM2.5 and O3 sensors included the lack of consistent performance indicators and statistical metrics as well as highly variable data quality requirements depending on the intended use. While the workshop did not attempt to yield consensus on any topic, a key message was that a number of possible future actions would be beneficial to all stakeholders regarding sensor technologies. These included documentation of best practices, sharing quality assurance results along with sensor data, and the development of a common performance target lexicon, performance targets, and test protocols.

Particulate matter chemical component concentrations and sources in settings of household solid fuel use.

Particulate matter (PM) air pollution derives from combustion and non-combustion sources and consists of various chemical species that may differentially impact human health and climate. Previous reviews of PM chemical component concentrations and sources focus on high-income urban settings, which likely differ from the low- and middle-income settings where solid fuel (ie, coal, biomass) is commonly burned for cooking and heating. We aimed to summarize the concentrations of PM chemical components and their contributing sources in settings where solid fuel is burned. We searched the literature for studies that reported PM component concentrations from homes, personal exposures, and direct stove emissions under uncontrolled, real-world conditions. We calculated weighted mean daily concentrations for select PM components and compared sources of PM determined by source apportionment. Our search criteria yielded 48 studies conducted in 12 countries. Weighted mean daily cooking area concentrations of elemental carbon, organic carbon, and benzo(a)pyrene were 18.8 µg m-3 , 74.0 µg m-3 , and 155 ng m-3 , respectively. Solid fuel combustion explained 29%-48% of principal component/factor analysis variance and 41%-87% of PM mass determined by positive matrix factorization. Multiple indoor and outdoor sources impacted PM concentrations and composition in these settings, including solid fuel burning, mobile emissions, dust, and solid waste burning.

The impact of biogas and fuelwood use on institutional kitchen air quality in Kampala, Uganda.

Experts have suggested that microscale biogas systems offer a source of renewable energy that improves indoor air quality, but such impacts have not been directly measured. This study documented cooking behaviors and measured 2.5-µm particulate matter (PM2.5 ), carbon monoxide (CO), and sulfur dioxide (SO2 ) concentrations within 14 institutional kitchens in Kampala, Uganda, that prepare meals using biogas (n=5), a mixture of biogas and fuelwood (n=3), and fuelwood (n=6). Small institutions (10-30 people) with biogas kitchens had 99% lower concentrations of PM2.5 (21 µg/m3 ) than fuelwood kitchens (3100 µg/m3 ). Larger institutions (>100 people) had biogas systems that produced insufficient gas and relied on fuelwood to meet over 90% of their energy needs. PM2.5 concentrations in these biogas-firewood kitchens were equivalent to concentrations in fuelwood kitchens. Although concentrations of hydrogen sulfide (H2 S) in biogas were as high as 2000 ppm, 75% of systems had undetectable H2 S levels (<100 ppm) in the biogas. Kitchens using biogas with high H2 S had correspondingly higher SO2 concentrations in the kitchen air. However, even the highest SO2 concentration in biogas kitchens (150 µg/m3 ) was lower than SO2 concentration in fuelwood kitchens (390 µg/m3 ). The results suggest that biogas systems can offer air quality improvements if sized properly for energy demands.

Sources, evolution and impacts of EC and OC in snow on sea ice: a measurement study in Barrow, Alaska.

Based on the field measurements in Barrow, Alaska within the period of April-May 2015, we investigate the sources and variations of elemental carbon (EC) and organic carbon (OC) in the surface layer of snowpack on sea ice, and estimate their effects on the sea ice albedo. Results show that the snow OC in Barrow are from natural sources (e.g. terrestrial higher plants and micro-organisms) mainly, as well as biomass burning (e.g. forest fires and straw combustion) as an important part. Both EC and OC can accumulate at the snow surface with snow melt. The variations in EC and OC and liquid water content in the snow layer are well consistent during the snow-melting period. A higher rate of snow melt implied a more efficient enrichment of EC and OC. In the last phase of snow melt, the concentration increased to a maximum of 16.2 ng/g for EC and 128 ng/g for OC, which is ∼10 times larger than those before snow melt onset. Except for the dominant influence of melt amplification mechanism, the variation in concentrations of EC and OC could be disturbed by the air temperature fluctuation and snowfall. Our study indicates that the light-absorbing impurities contributed 1.6%-5.1% to the reduction in sea ice albedo with melt during the measurement period. The significant period of light-absorbing impurities influencing on sea ice albedo begins with the rapid melting of overlying snow and ends before the melt ponds formed widely, which lasted for about 10 days in Barrow, 2015.

The discoloration of the Taj Mahal due to particulate carbon and dust deposition.

The white marble domes of the Taj Mahal are iconic images of India that attract millions of visitors every year. Over the past several decades the outer marble surfaces of the Taj Mahal have begun to discolor with time and must be painstakingly cleaned every several years. Although it has been generally believed that the discoloration is in some way linked with poor air quality in the Agra region, the specific components of air pollution responsible have yet to be identified. With this in mind, ambient particulate matter (PM) samples were collected over a one-year period and found to contain relatively high concentrations of light absorbing particles that could potentially discolor the Taj Mahal marble surfaces, that include black carbon (BC), light absorbing organic carbon (brown carbon, BrC), and dust. Analyses of particles deposited to marble surrogate surfaces at the Taj Mahal indicate that a large fraction of the outer Taj Mahal surfaces are covered with particles that contain both carbonaceous components and dust. We have developed a novel approach that estimates the impact of these deposited particles on the visible light surface reflectance, which is in turn used to estimate the perceived color by the human eye. Results indicate that deposited light absorbing dust and carbonaceous particles (both BC and BrC from the combustion of fossil fuels and biomass) are responsible for the surface discoloration of the Taj Mahal. Overall, the results suggest that the deposition of light absorbing particulate matter in regions of high aerosol loading are not only influencing cultural heritage but also the aesthetics of both natural and urban surfaces.

Temporal constraints on hydrate-controlled methane seepage off Svalbard.

Methane hydrate is an icelike substance that is stable at high pressure and low temperature in continental margin sediments. Since the discovery of a large number of gas flares at the landward termination of the gas hydrate stability zone off Svalbard, there has been concern that warming bottom waters have started to dissociate large amounts of gas hydrate and that the resulting methane release may possibly accelerate global warming. Here, we corroborate that hydrates play a role in the observed seepage of gas, but we present evidence that seepage off Svalbard has been ongoing for at least 3000 years and that seasonal fluctuations of 1° to 2°C in the bottom-water temperature cause periodic gas hydrate formation and dissociation, which focus seepage at the observed sites.

[Therapy of functional abdominal pain in childhood. Concept, acceptance and preliminary results of a short hypnotherapeutic-behavioural intervention]. / Therapie funktioneller Bauchschmerzen bei Kindern. Konzept, Akzeptanz und erste Pilotergebnisse einer hypnotherapeutisch-behavioralen Kurzintervention.

OBJECTIVE: Recurrent abdominal pain is one of the most frequent pain syndromes in childhood and is accompanied by notable functional impairment and unfavourable long-term outcome. Psychotherapeutic approaches are promising, but not widely used in Germany. The concept of a multimodal short-term intervention and its acceptance are described and preliminary results are reported. METHOD: A total of 21 children aged 6-12 years and their parents participated in a hypnotherapeutic-behavioural short intervention program. Preliminary results on efficacy up to 3 months are reported. RESULTS: Participating children showed a decrease in pain frequency and daily impairment. Health-related quality of life also increased and associated mental problems could be reduced. Content and conditions of the intervention were rated as helpful by children and parents. CONCLUSION: Preliminary results indicate that even short psychotherapeutic interventions might help affected children effectively and lower the burden felt by parents. Further investigations using a randomized controlled trial design and focussing on children suffering more severely should follow to allow major conclusions.

Patterns and predictors of personal exposure to indoor air pollution from biomass combustion among women and children in rural China.

UNLABELLED: Indoor air pollution (IAP) from domestic biomass combustion is an important health risk factor, yet direct measurements of personal IAP exposure are scarce. We measured 24-h integrated gravimetric exposure to particles < 2.5 µm in aerodynamic diameter (particulate matter, PM2.5) in 280 adult women and 240 children in rural Yunnan, China. We also measured indoor PM2.5 concentrations in a random sample of 44 kitchens. The geometric mean winter PM2.5 exposure among adult women was twice that of summer exposure [117 µg/m³ (95% CI: 107, 128) vs. 55 µg/m³ (95% CI: 49, 62)]. Children's geometric mean exposure in summer was 53 µg/m³ (95% CI: 46, 61). Indoor PM2.5 concentrations were moderately correlated with women's personal exposure (r=0.58), but not for children. Ventilation during cooking, cookstove maintenance, and kitchen structure were significant predictors of personal PM2.5 exposure among women primarily cooking with biomass. These findings can be used to develop exposure assessment models for future epidemiologic research and inform interventions and policies aimed at reducing IAP exposure. PRACTICAL IMPLICATIONS: Our results suggest that reducing overall PM pollution exposure in this population may be best achieved by reducing winter exposure. Behavioral interventions such as increasing ventilation during cooking or encouraging stove cleaning and maintenance may help achieve these reductions.

Organic compound characterization and source apportionment of indoor and outdoor quasi-ultrafine particulate matter in retirement homes of the Los Angeles Basin.

UNLABELLED: Quasi-ultrafine (quasi-UF) particulate matter (PM(0.25)) and its components were measured in indoor and outdoor environments at four retirement communities in Los Angeles Basin, California, as part of the Cardiovascular Health and Air Pollution Study (CHAPS). The present paper focuses on the characterization of the sources, organic constituents and indoor and outdoor relationships of quasi-UF PM. The average indoor/outdoor ratios of most of the measured polycyclic aromatic hydrocarbons (PAHs), hopanes, and steranes were close to or slightly lower than 1, and the corresponding indoor-outdoor correlation coefficients (R) were always positive and, for the most part, moderately strong (median R was 0.60 for PAHs and 0.74 for hopanes and steranes). This may reflect the possible impact of outdoor sources on indoor PAHs, hopanes, and steranes. Conversely, indoor n-alkanes and n-alkanoic acids were likely to be influenced by indoor sources. A chemical mass balance model was applied to both indoor and outdoor speciated chemical measurements of quasi-UF PM. Among all apportioned sources of both indoor and outdoor particles, vehicular emissions was the one contributing the most to the PM(0.25) mass concentration measured at all sites (24-47% on average). PRACTICAL IMPLICATIONS: Although people (particularly the elderly retirees of our study) generally spend most of their time indoors, a major portion of the PM(0.25) particles they are exposed to comes from outdoor mobile sources. This is important because, an earlier investigation, also conducted within the Cardiovascular Health and Air Pollution Study (CHAPS), showed that indoor-infiltrated particles from mobile sources are more strongly correlated with adverse health effects observed in the elderly subjects living in the studied retirement communities compared with other particles found indoors (Delfino et al., 2008).

[Impulse oscillometry in the diagnosis of the severity of obstructive pulmonary disease]. / Die Impulsoszillometrie in der Schweregraddiagnostik obstruktiver Lungenerkrankungen.

Impulse oscillometry (IOS) is a computer-supported method for the measurement of complex mechanical airway characteristics. The aim of this study was to evaluate the applicability of IOS in the diagnosis of obstructive airway diseases in comparison to the standard methods of spirometry, pneumotachymetry, and bodyplethysmography. 244 patients (age 61.5 +/- 13.6 years; 61 % men) with bronchial asthma (n = 65) and chronic obstructive pulmonary disease (COPD) (n = 179) were retrospectively analysed. By means of body plethysmography (Srtot < 120%pred) an obstruction was diagnosed in 94%, by pneumotachymetry (FEV1 < 80%pred) in 78 %, and by IOS depending on the parameter chosen in 87-94% of patients. Mild and medium obstructions could be identified by means of all IOS parameters except for R20: severe obstructions, however, were better detected by means of the frequency-dependent resistance FDR and reactance at 5 Hz, X5. The parameters R5, X5, and Zrs, however, showed a tendency to underestimate the degree of obstruction. Bronchial obstruction can reliably be diagnosed by IOS when, in cases of severe obstruction, more complex parameters like FDR and X5 are included. The parameters of the standard methods (body plethysmography and pneumotachymetry) show relatively low correlations due to the different measurement methods not only in comparison to IOS but also to one another. In summary, IOS is a convenient method for patients with a low dependency on cooperation for the evaluation of obstructive airway diseases complementary to the established standard methods and, in addition, is useful as a sensitive screening tool for the early detection of bronchial obstruction.

Treatment of invasive pulmonary aspergillosis in neutropenic patients by additional bronchoscopic amphotericin B instillation.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy. OBJECTIVES: This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA. METHODS: Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan. RESULTS: The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients). CONCLUSIONS: Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.

Antenatal ultrasonographic appearance of isolated fetal ascites. A case report of sinus urogenitalis.

BACKGROUND: Isolated fetal ascites can be caused by many heterogeneous disorders and is associated with a variety of conditions. Cloacal anomalies are rare abnormalities with a highly variable array of sonographic symptoms, which make them difficult to diagnose antenatally. We present a case with isolated fetal ascites without hydronephrosis caused by a cloacal malformation. CASE: A 28-year-old woman, gravida 2, para 1, was referred to our unit at 18 weeks gestation with a hyperdense structure in the fetal liver. Cordocentesis revealed a normal karyotype and negative viral titers. Isolated fetal ascites occurred for the first time at 23 weeks gestation. Serial ultrasounds showed progressive fetal ascites with no hydronephrosis at any time and no other malformations apart from the previously diagnosed hyperechogenic liver structure. After the insertion of an abdomino-amniotic shunt, a temporary reduction of the sonographically detectable ascites could be achieved. Cesarean delivery was necessary due to a pathological CTG at 33 weeks of gestation. The baby was born with a markedly distended abdomen. Postnatal radiologic examination showed two fistulae between the cloaca and the notedly dilated vagina and the rectum respectively. At the age of 3 months a vaginoplasty was performed, which involved creating a correctly positioned vaginal opening, reconstruction of the urethra and rectum as well as occlusion of the two fistulae. CONCLUSION: In view of the examinations, performed before and after delivery, it has to be assumed that fetal urine drained via the cloaca through the fallopian tubes into the abdomen. In contrast to usual appearance of cloacal malformations no hydronephrosis was detected and the kidney function was normal at all times. To our knowledge, this is the first published case of isolated fetal ascites without hydronephrosis caused by a cloacal malformation.

Atmospheric mercury speciation in Yellowstone National Park.

Atmospheric concentrations of elemental mercury (Hg(0)), reactive gaseous Hg (RGM), and particulate Hg (pHg) concentrations were measured in Yellowstone National Park (YNP), U.S.A. using high resolution, real time atmospheric mercury analyzers (Tekran 2537A, 1130, and 1135). A survey of Hg(0) concentrations at various locations within YNP showed that concentrations generally reflect global background concentrations of 1.5-2.0 ng m(-3), but a few specific locations associated with concentrated geothermal activity showed distinctly elevated Hg(0) concentrations (about 9.0 ng m(-3)). At the site of intensive study located centrally in YNP (Canyon Village), Hg(0) concentrations did not exceed 2.5 ng m(-3); concentrations of RGM were generally below detection limits of 0.88 pg m(-3) and never exceeded 5 pg m(-3). Concentrations of pHg ranged from below detection limits to close to 30 pg m(-3). RGM and pHg concentrations were not correlated with any criteria gases (SO(2), NO(x), O(3)); however pHg was weakly correlated with the concentration of atmospheric particles. We investigated three likely sources of Hg at the intensive monitoring site: numerous geothermal features scattered throughout YNP, re-suspended soils, and wildfires near or in YNP. We examined relationships between the chemical properties of aerosols (as measured using real time, single particle mass spectrometry; aerosol time-of-flight mass spectrometer; ATOFMS) and concentrations of atmospheric pHg. Based on the presence of particles with distinct chemical signatures of the wildfires, and the absence of signatures associated with the other sources, we concluded that wildfires in the park were the main source of aerosols and associated pHg to our sampling site.

[Matrix metalloproteinases and their inhibitors in lung cancer with malignant pleural effusion]. / Matrix-Metalloproteinasen und deren Inhibitoren bei Lungenkarzinomen mit malignem Pleuraerguss.

UNLABELLED: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play a crucial role in physiological and pathological matrix turnover. This study aimed to determine the occurrence of MMP and TIMP in lung cancer patients with malignant pleural effusions (CA). METHODS: MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF) patients and in plasma of 18 healthy controls (CON). RESULTS: MMP-2, TIMP-1, and TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p < 0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p < 0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p < 0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p < 0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA vs. CON plasma (p < 0.05). CONCLUSIONS: MMP-2, TIMP-1, and TIMP-2 accumulate in the pleural compartment in CA and CHF, probably reflecting an unspecific pleural reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to differentiate CHF from CA effusions.

Vascular endothelial growth factor in pleural effusions of different origin.

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.

Bosentan therapy for portopulmonary hypertension.

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported. In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for >1 yr with bosentan. After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310+/-102 m at baseline to 388+/-81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6+/-3.5 to 16.6+/-2.8 mL.min(-1).kg(-1). Pulmonary vascular resistance fell from 944+/-519 to 635+/-321 dynes.s.L(-1). The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury. In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.

[Unexpected cause of a tarsal destruction in a diabetic patient]. / Unerwartete Ursache einer Fusswurzeldestruktion bei einem Diabetiker.

HISTORY: A 56-year-old male patient has suffered from increasing pain in the left foot which limited the ability of walking since 18 months. There was a soft and painful swelling below the left inner ankle. In addition the patient reported back pain, but no neurological symptoms. Insulin dependent diabetes type II was known for 20 years, and a diabetic foot syndrome was suspected. 6 months prior the patient consulted his physician because of repeated acute bronchitis with expectoration and no improvement following antibiotic therapy. INVESTIGATIONS: Osteolytic destruction of the left middle foot and the tarsal with soft tissue infiltration according to MR, a spondylodiscitis of the lumbar vertebra I and II (MR) and mixed interstitial/alveolar infiltrates throughout the lung with a predominance in both upper lobes were found. The microbiological examination of sputum and biopsy of inflamed soft tissue of the left ankle revealed infection with mycobacterium tuberculosis. DIAGNOSIS: Open lung tuberculosis with concomitant bone tuberculosis and tuberculous arthritis of the left middle foot and spondylodiscitis. THERAPY AND CLINICAL COURSE: The antibiotic therapy consisted of a combination of five antibiotic drugs for 2 weeks and of a four drug combination for further 3.5 months. After that there will be a consolidation therapy with a two drug regime for 6 months. An orthopaedist is also involved. Surgical procedures with respect to the left foot will not be considered as long as the antibiotic therapy has not been finished. CONCLUSION: A combination of symptoms resulting from inflammatory bone processes and pulmonary symptoms is always suspicious for a hematogenic dissemination of a pulmonary tuberculosis.