Negative pressure wound therapy in burns: a prospective, randomized-controlled trial.

BACKGROUND: Negative-pressure-wound-therapy (NPWT) has become a widely used tool for the coverage and active treatment of complex wounds, including burns. This study aimed to evaluate the effectiveness of NPWT in acute burns of upper and lower extremities and to compare results to the standard-of-care (SOC) at our institution. METHODS: Patients that were admitted to our institution between May 2019 and November 2021 with burns on extremities between 0.5 % and 10 % of the total body surface area (%TBSA) were included and randomized to either NPWT or SOC (polyhexanide gel, fatty gauze, and cotton wool). Treatment was performed until complete wound healing. Patients that required skin grafts, received additional NPWT after grafting independent on the initial group allocation. RESULTS: Sixty-five patients suffering from burn injury between May 2019 and November 2021 were randomized into treatment with NPWT (n = 33) or SOC (n = 32); of these, 33 patients (NPWT) and 28 patients (SOC) had complete data sets and were included in the analysis. Both groups were similar regarding age (39.8 ± 13.7 vs. 44.8 ± 16.2 years,p = 0.192), total burn size (3.1 ± 2.3 vs. 3.4 ± 2.8 %TBSA,p = 0.721) and treated wound size (1.9 ± 1.2 vs. 1.5 ± 0.8 %TBSA,p = 0.138). We found no differences regarding healing time (11.0 ± 4.9 vs. 8.6 ± 3.8,p = 0.074, and significant differences in a number of dressing changes throughout the study (2.4 ± 1.5 vs 4.2 ± 1.9,p < 0.001). The Kaplan-Meier time-to-event analysis exhibited no statistically significant difference in the time to healing or skin grafting (p = 0.085) in NPWT group compared with SOC group. The median time to healing or skin grafting was 10(8-11) days for NPWT and 9(7-11) days for SOC. The hazard ratio for healing or skin graft was HR= 0.64(0.38-1.08). The results of the time-to-event analysis as well as the Kaplan-Meier curve on the PPS confirmed this result. We found no differences in secondary surgical operations 15.2 vs 21.4 % pain or functional outcomes. CONCLUSIONS: In this study, we found no significant difference between the two groups in terms of time to detect wound healing. We also found no difference regarding further operations for wound closure, pain and/or scarring. However, dressing changes were significantly less frequent for patients that were treated with NPWT, which may be a psychological and logistical advantage.

Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis.

OBJECTIVES: A considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA. METHODS: Adult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1. RESULTS: Among 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07-1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96-1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66-1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33-0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11-2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings. CONCLUSIONS: These real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Virucidal efficacy of an ozone-generating system for automated room disinfection.

Besides conventional prevention measures, no-touch technologies based on gaseous systems have been introduced in hospital hygiene for room disinfection. The whole-room disinfectant device Sterisafe Pro, which creates ozone as a biocidal agent, was tested for its virucidal efficacy based on Association Française de Normalisation Standard NF T 72-281:2014. All test virus titres were reduced after 150 and 300 min of decontamination, with mean reduction factors ranging from 2.63 (murine norovirus) to 3.94 (simian virus 40). These results will help to establish realistic conditions for virus inactivation, and assessment of the efficacy of ozone technology against non-enveloped and enveloped viruses.

Prevalence of untreated and uncontrolled cardiovascular risk factors in survivors of allogeneic cell transplantation.

Cardiovascular risk factors (CVRF) are frequent among long-term survivors after allogeneic hematopoietic cell transplantation (HCT) but prospective data on CVRF are sparse. We conducted a cross-sectional single center study including patients who underwent a first HCT mostly for hematologic malignancies at our center between 2000 and 2016, surviving at least 1 year. 260 patients (median age 54 years [range 19-78], 40% female) who were median 6 years (range 1-16) after transplantation were included. Most patients (232, 89%) had peripheral blood stem cell transplantation. cGVHD was present in 41% at the time of study inclusion. Prevalence of hypertension, dyslipidemia, and diabetes was 58%, 63% and 9%, respectively. Untreated hypertension, dyslipidemia and diabetes was found in 15%, 35% and 2%. Among patients with treated hypertension, 38% did not have blood pressure controlled to levels ≤140/90 mmHg. 36% patients under lipid-lowering therapy did not reach their LDL target. Multivariable logistic regression analyses showed that age and diabetes increased the likelihood for hypertension and dyslipidemia, whereas body mass index, cGVHD and male sex predicted hypertension only. In summary, CVRF in long-term survivors are frequent and persisting after cessation of immunosuppression. A large proportion of CVRF are either untreated or uncontrolled.

Parallel PRC2/cPRC1 and vPRC1 pathways silence lineage-specific genes and maintain self-renewal in mouse embryonic stem cells.

The transcriptional repressors Polycomb repressive complex 1 (PRC1) and PRC2 are required to maintain cell fate during embryonic development. PRC1 and PRC2 catalyze distinct histone modifications, establishing repressive chromatin at shared targets. How PRC1, which consists of canonical PRC1 (cPRC1) and variant PRC1 (vPRC1) complexes, and PRC2 cooperate to silence genes and support mouse embryonic stem cell (mESC) self-renewal is unclear. Using combinatorial genetic perturbations, we show that independent pathways of cPRC1 and vPRC1 are responsible for maintenance of H2A monoubiquitylation and silencing of shared target genes. Individual loss of PRC2-dependent cPRC1 or PRC2-independent vPRC1 disrupts only one pathway and does not impair mESC self-renewal capacity. However, loss of both pathways leads to mESC differentiation and activation of a subset of lineage-specific genes co-occupied by relatively high levels of PRC1/PRC2. Thus, parallel pathways explain the differential requirements for PRC1 and PRC2 and provide robust silencing of lineage-specific genes.

Effects of anti-androgens cyproterone acetate, linuron, vinclozolin, and p,p'-DDE on the reproductive organs of the copepod Acartia tonsa.

The study was performed to detect the effects of anti-androgenic compounds on the reproduction. In this paper alterations observed in the marine calanoid copepod Acartia tonsa exposed to environmental concentrations of cyproterone acetate (CPA), linuron (LIN), vinclozolin (VIN), and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) for 21 days covering a full life cycle are described. Histological alterations were studied with a focus on reproductive organs, gonad and accessory sexual glands. Exposure to ≥1.2 µg L(-1) CPA caused degeneration of spermatocytes and deformation of the spermatophore in males. In a single male exposed to 33 µg L(-1) CPA, an ovotestis was observed. In CPA exposed females, enhancement of oogenesis, increase in apoptosis and a decrease in proliferation occurred. Exposure of males to ≥12 µg L(-1) LIN caused degenerative effects in spermatogonia, spermatocytes and spermatids, and at 4.7 µg L(-1) LIN, the spermatophore wall displayed an irregular formation. In LIN exposed females, no such structural alterations were found; however, the proliferation index was reduced at 29 µg L(-1) LIN. At an exposure concentration of ≥100 µg L(-1) VIN, distinct areas in male gonad were stimulated, whereas others displayed a disturbed spermatogenesis and a deformed spermatophore wall. In VIN exposed female A. tonsa, no effects were observed. Male A. tonsa exposed to p,p'-DDE displayed an impairment of spermatogenesis in all stages with increased degrees of apoptosis. In p,p'-DDE-exposed females, a statistical significant increase of the proliferation index and an intensification of oogenesis were observed at 0.0088 µg L(-1).

Prognostic impact of systemic inflammatory diseases in elderly patients with congestive heart failure.

BACKGROUND AND AIMS: Inflammation is part of the pathophysiology of congestive heart failure (CHF). However, little is known about the impact of the presence of systemic inflammatory disease (SID), defined as inflammatory syndrome with constitutional symptoms and involvement of at least two organs as co-morbidity on the clinical course and prognosis of patients with CHF. METHODS AND RESULTS: This is an analysis of all 622 patients included in TIME-CHF. After an 18 months follow-up, outcomes of patients with and without SID were compared. Primary endpoint was all-cause hospitalization free survival. Secondary endpoints were overall survival and CHF hospitalization free survival. At baseline, 38 patients had history of SID (6.1%). These patients had higher N-terminal pro brain natriuretic peptide and worse renal function than patients without SID. SID was a risk factor for adverse outcome [primary endpoint: hazard ratio (HR) = 1.73 (95% confidence interval: 1.18-2.55, P = 0.005); survival: HR = 2.60 (1.49-4.55, P = 0.001); CHF hospitalization free survival: HR = 2.3 (1.45-3.65, P < 0.001)]. In multivariate models, SID remained the strongest independent risk factor for survival and CHF hospitalization free survival. CONCLUSION: In elderly patients with CHF, SID is independently accompanied with adverse outcome. Given the increasing prevalence of SID in the elderly population, these findings are clinically important for both risk stratification and patient management.

Effects of methyltestosterone, letrozole, triphenyltin and fenarimol on histology of reproductive organs of the copepod Acartia tonsa.

The marine calanoid copepod Acartia tonsa was exposed to methyltestosterone (MET, 1.6-126 µg L(-1)), letrozole (LET, 10-1000 µg L(-1)), triphenyltin chloride (TPT, 0.0014-0.0088 µg L(-1) TPT-Sn) and fenarimol (FEN, 2.8-105 µg L(-1)) for 21 d covering a full life-cycle. All four compounds investigated are known to act as androgens in vertebrates. The digestive tract, musculature, nervous system, reproductive organs, gonad and accessory sexual glands were examined by light microscopy after routine staining and immune-labelling for detection of apoptosis and determination of proliferation activities. MET induced an inhibition of oogenesis, oocyte maturation and yolk formation, respectively, which was most pronounced at the lowest concentrations tested. In LET exposed males, spermatogenesis was enhanced with very prominent gamete stages; in some stages apoptosis occurred. The spermatophore was hypertrophied and displayed deformations. In females, LET induced a disorder of oogenesis and disturbances in yolk synthesis. TPT stimulated the male reproductive system at 0.0014 and 0.0035 µg TPT-SnL(-1), whereas inhibiting effects were observed in the female gonad at 0.0088 µg TPT-SnL(-1). In FEN exposed females proliferation of gametes was reduced and yolk formation showed irregular features at 2.8-105 µgL(-1). In FEN exposed males an elevated proliferation activity was observed. No pathological alterations in other organ systems, e.g. the digestive tract including the hindgut acting as respiratory organ, the nervous system, or the musculature were seen. This indicates that the effects on gonads might be caused rather by disturbance of endocrine signalling or interference with hormone metabolism than by general toxicity.

Induction of immediate early genes in the mouse auditory cortex after auditory cued fear conditioning to complex sounds.

Immediate early genes (IEGs) are widely used as markers to delineate neuronal circuits because they show fast and transient expression induced by various behavioral paradigms. In this study, we investigated the expression of the IEGs c-fos and Arc in the auditory cortex of the mouse after auditory cued fear conditioning using quantitative polymerase chain reaction and microarray analysis. To test for the specificity of the IEG induction, we included several control groups that allowed us to test for factors other than associative learning to sounds that could lead to an induction of IEGs. We found that both c-fos and Arc showed strong and robust induction after auditory fear conditioning. However, we also observed increased expression of both genes in any control paradigm that involved shocks, even when no sounds were presented. Using mRNA microarrays and comparing the effect of the various behavioral paradigms on mRNA expression levels, we did not find genes being selectively upregulated in the auditory fear conditioned group. In summary, our results indicate that the use of IEGs to identify neuronal circuits involved specifically in processing of sound cues in the fear conditioning paradigm can be limited by the effects of the aversive unconditional stimulus and that activity levels in a particular primary sensory cortical area can be strongly influenced by stimuli mediated by other modalities.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. CONCLUSION: In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Physical illness and schizophrenia: a review of the literature.

OBJECTIVE: The lifespan of people with schizophrenia is shortened compared to the general population. We reviewed the literature on comorbid physical diseases in schizophrenia to provide a basis for initiatives to fight this unacceptable situation. METHOD: We searched MEDLINE (1966 - May 2006) combining the MeSH term of schizophrenia with the 23 MeSH terms of general physical disease categories to identify relevant epidemiological studies. RESULTS: A total of 44 202 abstracts were screened. People with schizophrenia have higher prevalences of HIV infection and hepatitis, osteoporosis, altered pain sensitivity, sexual dysfunction, obstetric complications, cardiovascular diseases, overweight, diabetes, dental problems, and polydipsia than the general population. Rheumatoid arthritis and cancer may occur less frequently than in the general population. Eighty-six per cent of the studies came from industrialized countries limiting the generalizability of the findings. CONCLUSION: The increased frequency of physical diseases in schizophrenia might be on account of factors related to schizophrenia and its treatment, but undoubtedly also results from the unsatisfactory organization of health services, from the attitudes of medical doctors, and the social stigma ascribed to the schizophrenic patients.

Gene expression of brain natriuretic peptide in isolated atrial and ventricular human myocardium: influence of angiotensin II and diastolic fiber length.

BACKGROUND: We studied the effects of angiotensin II (Ang II) and diastolic overstretch on the induction of cardiac growth in isometrically contracting muscle preparations from human right atria and left ventricles. We used the gene expression of brain natriuretic peptide (BNP) as a molecular marker of cardiac hypertrophy. METHODS AND RESULTS: Northern blot analysis was performed in human atrial muscle preparations, which were either incubated in 10(-6) mol/L Ang II for 45 minutes or diastolically stretched to 120% of optimum muscle length. Similar experiments were performed with human left ventricular muscle preparations. Results were as follows: (1) BNP gene expression increased in human atrial myocardium 4-fold when stimulated by Ang II (n=7, P<0.001). (2) Diastolic overstretch increased BNP expression in a time-dependent manner. The linear regression equations for the BNP/GAPDH ratio as a function of time (hours) were y=1.21+0.62x (P:<0.001) for overstretched preparations and y=1.07-0.01x (P:=NS) for atrial preparations kept at physiological muscle length. (3) In left ventricular human muscle preparations, diastolic overstretch and Ang II increased BNP gene expression as well. (4) In addition, the Ang II subtype 1 receptor blocker losartan was able to block the effects of Ang II and diastolic overstretch. CONCLUSIONS: Cardiac hypertrophy can be induced in isolated human atrial and left ventricular intact myocardium by Ang II and diastolic overstretch but not by isometric afterload. The fact that the induction of cardiac growth is inhibited by the blockade of Ang II subtype 1 receptors is of scientific and clinical importance.