Tetanus in adults: results of the multicenter ID-IRI study.

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

Liver involvement in patients with brucellosis: results of the Marmara study.

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n = 73), doxycycline plus rifampicin (n = 71), doxycycline plus rifampicin and an aminoglycoside (n = 27). The duration of ALT normalization differed significantly in three treatment groups (p < 0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p < 0.05). However, the length of hospital stay did not differ significantly between these three combinations (p > 0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.

Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthritis and osteoarthritis.

Changes in the expression of repellent factors, i.e., Netrins and their receptors, may be responsible for the invasive behavior of the synovial tissue cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This study was carried out to analyze the expression of Netrins and their receptors in synovial cells of patients with RA, OA, and control subjects without synovial inflammation. Quantitative RT-PCR was performed to measure the expression of Netrin-1, -3, -4, Neogenin, DCC, UNC5A-D. The influence of Netrin-1 on synovial fibroblasts (SF) was analyzed by determining proliferation, migration, and their ability to organize collagen. SF expressed all repellent factors of the Netrin family. When comparing SF of healthy donors to patients with RA and OA, a stronger expression of UNC5B (4 fold) and UNC5C (769 fold) in RA and OA was found, whereas expression of the other molecules revealed no significant differences. Treating the SF-cells with recombinant Netrin-1 resulted in inhibition of migration of RA- and OA-SFs whereas control cells were not affected. The stronger expression of UNC5B and UNC5C receptors might contribute to the disordered phenotype of RA- and OA-SFs. Addition of Netrin-1 reduces the migratory ability of SFs, potentially by repulsion, as seen in neuronal cells in embryonic development. Due to its function, Netrin-1 may constitute a novel target in the treatment of OA and RA.

NF-kappaB transcription factors: critical regulators of hematopoiesis and neuronal survival.

The Rel/NF-kappaB family of transcription factors has been implicated in the regulation of genes involved in immune and inflammatory responses, and of processes such as cell survival, apoptosis, development, differentiation, cell growth and neoplastic transformation. In this report we will summarize recent findings which highlight critical roles of NF-kappaB in different processes in hematopoietic and neuronal cells.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Signal-specific and phosphorylation-dependent RelB degradation: a potential mechanism of NF-kappaB control.

RelB is an unusual member of the Rel/NF-kappaB family of transcription factors which are involved in oncogenic processes. Due to a relaxed control by the IkappaBs, the cytosolic NF-kappaB inhibitors, RelB is constitutively expressed in the nuclei of lymphoid cells. We show here that RelB is inducibly degraded upon activation of T cells in a fashion similar to the IkappaBs. However, RelB degradation differs from that of IkappaBs since it is not induced by TNFalpha but only by T cell receptor or TPA/ionomycin stimulation. Moreover, RelB degradation occurs in three steps: (i) after stimulation RelB is rapidly phosphorylated at amino acids Thr84 and Ser552 followed by (ii) an N-terminal cut and, finally, (iii) the complete degradation in the proteasomes. Since mutation of the two phosphoacceptor sites to non-acceptor sites abolished RelB phosphorylation in vivo and led to the stabilization of the mutated RelB(DM), site-specific phosphorylation appears to be a necessary prerequisite for RelB degradation. RelB is a crucial regulator of NF-kappaB-dependent gene expression. Thus, the signal-induced degradation of RelB should be an important control mechanism of NF-kappaB activity.

The effect of EUSOMA certification on quality of breast cancer care.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

Hepatocyte growth factor (HGF) in patients with hepatitis B and meningitis.

OBJECTIVES: The present study investigates serum hepatocyte growth factor (HGF) levels in patients with acute and chronic hepatitis B and the relation between these levels and intrahepatic inflammatory markers of the liver and fibrosis, as well as the cerebrospinal fluid (CSF) HGF levels in patients with meningitis and the relation between these levels and CSF findings. To our knowledge this is the first study regarding CSF HGF levels in tuberculous meningitis. PATIENTS AND METHODS: The study consisted of 35 patients with chronic hepatitis B (HbeAg and HBV-DNA positive), 20 with acute hepatitis B, 20 with acute bacterial meningitis and 15 having tuberculous meningitis. HGF levels in the serum and CSF samples were measured by using the ELISA method. RESULTS: The mean serum HGF levels in acute hepatitis B group were found statistically significantly higher than those in the control group and chronic hepatitis B group (p<0.0001). It was established that serum HGF levels in patients with chronic hepatitis B were significantly correlated with serum alanine aminotransferase (ALT) and HBV-DNA levels (r: 0.816, 0.951; p<0.05, respectively). Similarly, serum HGF levels of patients with chronic hepatitis B were correlated with fibrosis score and hepatic activity index of the liver histopathology (r: 0.750, 0.459; p<0.05, respectively). The mean CSF HGF levels of patients with acute bacterial meningitis and tuberculous meningitis were higher than those in the control group (p<0.05). In addition, it was observed that mean CSF HGF levels in patients suffered from tuberculous meningitis were statistically significantly higher than those in acute bacterial meningitis (p<0.05). CONCLUSIONS: We suggest that serum HGF level in patients with chronic hepatitis B might reflect viral load, necro-inflammatory activity in the liver and the degree of structural progression. Our findings have demonstrated that tuberculous meningitis cause increased HGF concentrations in CSF. It is, therefore, suggested that examination of HGF levels in CSF may provide additional information in the differential diagnosis.

Genitourinary brucellosis: results of a multicentric study.

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

Carotenoid-based bill colour as an indicator of immunocompetence and sperm performance in male mallards.

Female mate choice is often based on exaggerated sexual traits, signals of male qualities that females cannot assess directly. Two such key qualities are male immune and/or sexual competence, whereby honesty in signalling could be maintained by physiological trade-offs. Carotenoid-based ornaments likely constitute such honest signals, as there is direct competition for (limited) carotenoids between ornament deposition and anti-oxidant support of immune or sperm functioning. Using spectrometry, we assessed the potential signalling function of the yellow, carotenoid-based colour of the bill of male mallards, a target of female mate choice. Here we demonstrate that bill reflectance varied with plasma carotenoid level, indicating antioxidant reserves. Moreover, lower relative UV reflectance during autumn pairing predicted immune responsiveness and correlated positively with sperm velocity during breeding, a trait that affects fertility. Our data provide support for current theories that females could use carotenoid-based sexual signals to detect immune vigour and fertilizing ability of prospective mates.

[Biophysical study of coronary stents: which factors influence the dilatation and recoil behavior?]. / Biophysikalische Prüfung koronarer Stents: Welche Faktoren beeinflussen das Dilatations- und Recoilverhalten?

In Europe more than fifty stents are currently available for the therapy of coronary artery disease. Nonetheless it is unknown whether material and design influence the stent's behavior. We have studied the recoil and dilatation behavior of five currently available stainless steel (316L) stents compared to stent prototypes made of pure titanium. Furthermore we have investigated how the behavior is influenced by the process of crimping. The aim of this work was to determine material and design characteristics, which influence the recoil and dilatation behavior. The 316L stents showed a homogeneous behavior (plateau pressure min. 1.15 +/- 0.01 atm, max. 0.26 +/- 0.03 atm, recoil min. 0.15 +/- 0.03%, max. 0.26 +/- 0.03%). The titanium stent showed a linear response to the balloon expansion. This was seen in a significantly lower plateau pressure (0.43 +/- 0.15 atm, p < 0.001). Despite the material characteristics of titanium, there were no significant differences in the recoil behavior (0.28 +/- 0.02%). Crimping leads to stent alterations which result in a significantly higher plateau pressure (1.9 +/- 0.07 atm vs. 2.7 +/- 0.58 atm, p < 0.001) and a reduced end-diameter (3.6 +/- 0.02 mm vs. 3.54 +/- 0.05 mm, p < 0.005). The presented data show that the dilatation behavior is relying on the stent material while the recoil is strongly influenced by the stent design.

Pneumopericardium and subcutaneous emphysema of the neck. An unusual manifestation of colonoscopic perforation.

Subcutaneous neck emphysema has been reported infrequently following colonoscopic perforation and only a single case of pneumopericardium has been previously reported. The successful management of these patients in the literature has largely been non-operative. We report a case of colonoscopic perforation which presented with subcutaneous neck emphysema, pneumopericardium, and pneumoperitoneum that required operative intervention.

Activation of NF-kappa B via the Ikappa B kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells.

Activation of the transcription factor NF-kappaB is necessary for full expression of tumor necrosis factor alpha (TNF-alpha)-inducible endothelial chemokines and adhesion molecules. However, a detailed analysis regarding contribution of the different NF-kappaB upstream components to endothelial activation has not been performed yet. We employed a retroviral infection approach to stably express transdominant (TD) mutants of IkappaBalpha, IkappaBbeta, or IkappaBepsilon and dominant negative (dn) versions of IkappaB kinases (IKK) 1 or 2 as well as a constitutively active version of IKK2 in human endothelial cells. TD IkappaBalpha, IkappaBbeta, and IkappaBepsilon were not degraded upon TNF-alpha exposure, and each prevented NF-kappaB activation. These TD IkappaB mutants almost completely inhibited the induction of monocyte chemoattractant protein-1, interleukin-8, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression by TNF-alpha, whereas interferon-gamma-mediated up-regulation of intercellular adhesion molecule-1 and HLA-DR was not affected. Expression of dn IKK2 completely blocked TNF-alpha-induced up-regulation, whereas dn IKK1 showed a partial inhibition of expression of these molecules. Importantly, expression of constitutively active IKK2 was sufficient to drive full expression of all chemokines and adhesion molecules in the absence of cytokine. We conclude that the IKK/IkappaB/NF-kappaB pathway is crucial and sufficient for proinflammatory activation of endothelium.