Implementation of a multidisciplinary infections conference affects the treatment plan in prosthetic joint infections of the hip: a retrospective study.

INTRODUCTION: Establishing a systematic multidisciplinary approach in the treatment of prosthetic joint infections (PJI) of the hip and analyzing its effect on clinical decision-making. PATIENTS AND METHODS: Forty-six patients diagnosed with PJI of the hip were included in the retrospective study. The treatment plan was either established by a single-discipline approach (n = 20) or by a weekly multidisciplinary infections conference (n = 26) consisting of at least an orthopedic surgeon, microbiologist and pathologist. Recorded data included the length of hospital stay, number and type of surgeries, medical complications, recovered organisms as well as the number of applied antibiotics. RESULTS: Patients discussed in the multidisciplinary infections conference showed a significantly shorter in-hospital stay (29 vs 62 days; p < 0.05), a significant reduction in surgeries (1.8 vs 5.1; p < 0.05) and a smaller number of antibiotics required (2.8 vs 4.2; p < 0.05). No significant difference could be found comparing inpatient complications between the two groups. Staphylococcus aureus and coagulase-negative staphylococci were the most frequently recovered organisms in both patient groups. CONCLUSION: This study demonstrates the successful implementation of a weekly infections conference as an instrument to introduce a multidisciplinary approach to PJI of the hip. Implementation of these conferences significantly improves the treatment plan compared to a single-discipline approach, which we therefore highly recommend for other institutions. Multidiscipline may even affect clinical outcome which needs to be further investigated.

Psychometric evaluation of a motor control test battery of the craniofacial region.

The primary objective of this study was to determine the structural and known-group validity as well as the inter-rater reliability of a test battery to evaluate the motor control of the craniofacial region. Seventy volunteers without TMD and 25 subjects with TMD (Axes I) per the DC/TMD were asked to execute a test battery consisting of eight tests. The tests were video-taped in the same sequence in a standardised manner. Two experienced physical therapists participated in this study as blinded assessors. We used exploratory factor analysis to identify the underlying component structure of the eight tests. Internal consistency (Cronbach's α), inter-rater reliability (intra-class correlation coefficient) and construct validity (ie, hypothesis testing-known-group validity) (receiver operating curves) were also explored for the test battery. The structural validity showed the presence of one factor underlying the construct of the test battery. The internal consistency was excellent (0.90) as well as the inter-rater reliability. All values of reliability were close to 0.9 or above indicating very high inter-rater reliability. The area under the curve (AUC) was 0.93 for rater 1 and 0.94 for rater two, respectively, indicating excellent discrimination between subjects with TMD and healthy controls. The results of the present study support the psychometric properties of test battery to measure motor control of the craniofacial region when evaluated through videotaping. This test battery could be used to differentiate between healthy subjects and subjects with musculoskeletal impairments in the cervical and oro-facial regions. In addition, this test battery could be used to assess the effectiveness of management strategies in the craniofacial region.

Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.

Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.

Sunitinib for metastatic renal cell cancer patients: observational study highlighting the risk of important drug-drug interactions.

WHAT IS KNOWN AND OBJECTIVE: Sunitinib, a CYP3A4 substrate, is standard of care treatment in metastatic renal cell carcinoma (mRCC) and is administered orally as a single dose of 50 mg, in a 4 weeks on/2 weeks off regimen. Frequently, dose reduction is necessary because of toxicity, as is the association of comedication to treat side effects. In addition, existing comorbidities in these patients necessitate the intake of various classes of chronic medication. Only limited data are available on the risk of drug-drug interactions (DDI). The objective of our paper was to evaluate prescribed dose, comedication, risk of drug-drug interactions and outcome among patients with mRCC treated with sunitinib. METHODS: A single-centre, retrospective analysis was performed for patients with mRCC treated with sunitinib. The drug interaction databases 'Clinical Pharmacology' and 'Lexicomp' were used to screen for possible interactions. RESULTS AND DISCUSSION: The hospital files of 36 patients with mRCC were evaluated. Twenty-two patients received sunitinib as first-line treatment. Progression-free survival (PFS) in this first-line group was longer for patients that started with full-dose sunitinib (21·1 months; n = 12) than for patients started on reduced dose (3·5 months; n = 10). In the whole group of 36 patients, an average of 6·8 comedications was taken. Possible pharmacodynamic drug-drug interactions were most frequently found (47%) and reported as major interactions (QT prolongation). Risk of pharmacokinetic interactions due to co-administration of CYP inhibitors, CYP inducers, CYP substrates and PgP substrates was reported for 8%, 11%, 53% and 19%, respectively. These interactions were reported as major or moderate. WHAT IS NEW AND CONCLUSION: Patients with mRCC under treatment with sunitinib at a reduced starting dose had a decreased PFS compared with patients started with full-dose sunitinib. Due to adverse drug reactions and comorbidity, patients under sunitinib, a CYP3A4 substrate, took an average of 6·8 comedications provoking an important risk of major-to-moderate drug-drug interactions. With the help of a multidisciplinary team, avoidance of drug-drug interactions could be obtained. Moreover, serial ECG monitoring is recommended for patients at high risk of QT prolongation.

Implementation of a multidisciplinary infections conference improves the treatment of spondylodiscitis.

Establishing a multidisciplinary approach regarding the treatment of spondylodiscitis and analyzing its effect compared to a single discipline approach. 361 patients diagnosed with spondylodiscitis were included in this retrospective pre-post intervention study. The treatment strategy was either established by a single discipline approach (n = 149, year 2003-2011) or by a weekly multidisciplinary infections conference (n = 212, year 2013-2018) consisting of at least an orthopedic surgeon, medical microbiologist, infectious disease specialist and pathologist. Recorded data included the surgical and antibiotic strategy, complications leading to operative revision, recovered microorganisms, as well as the total length of hospital and intensive care unit stay. Compared to a single discipline approach, performing the multidisciplinary infections conference led to significant changes in anti-infective and surgical treatment strategies. Patients discussed in the conference showed significantly reduced days of total antibiotic treatment (66 ± 31 vs 104 ± 31, p < 0.001). Moreover, one stage procedures and open transpedicular screw placement were more frequently performed following multidisciplinary discussions, while there were less involved spinal segments in terms of internal fixation as well as an increased use of intervertebral cages instead of autologous bone graft (p < 0.001). Staphylococcus aureus and Staphylococcus epidermidis were the most frequently recovered organisms in both patient groups. No significant difference was found comparing inpatient complications between the two groups or the total in-hospital stay. Implementation of a weekly infections conference is an effective approach to introduce multidisciplinarity into spondylodiscitis management. These conferences significantly altered the treatment plan compared to a single discipline approach. Therefore, we highly recommend the implementation to optimize treatment modalities for patients.

Rapid identification of the vanA/vanB resistance determinant in Enterococcus sp. from blood cultures using the Cepheid Xpert vanA/vanB cartridge system.

Especially in immunocompromised and intensive care patients VRE sepsis is associated with high mortality. The GeneXpert vanA/vanB assay is marketed for fast molecular surveillance of VRE colonization in peri-anal and rectal swabs. The aim of this study was to evaluate this assay for its usefulness for rapid identification of the vanAB determinant from positive blood cultures. During an evaluation phase, 33/34 blood cultures (negative = 13; vanA = 1; and vanB = 19) were correctly identified. In the validation phase 205/211 blood cultures were correctly identified (negative, n = 160; vanA, n = 2; vanB, n = 43). Sensitivity and specificity calculated from valid tests was 100% (95% CI: 90.2-100%) and 100% (95% CI: 97.1-100%), respectively. The error rate was 2.8%. The Xpert vanA/vanB cartridge is a reliable tool in the rapid molecular identification of the vanA and vanB determinant from positive blood cultures with moderate inhibition rates (2.8%) and high PPV and NPV. However, additional methods for species identification are required.

IgG4-related cholangitis: Case report and literature review.

CASE PRESENTATION: We describe a case of a patient who presents with jaundice, elevated cholestatic liver enzymes, an extreme weight loss and a midcholedochal stricture very suspect for a cholangiocarcinoma. In the conviction of malignancy, although the absence of anatomopathological prove, the patient underwent a choledochal resection. The anatomopathological specimen revealed no malignancy. In the year following resection, the patient keeps presenting with bile duct strictures and further weight loss. Ultimately the diagnosis of Ig G4-related cholangitis is withheld. Therapy with corticosteroids is initiated with a spectacular clinical, biochemical and radiographical result. DISCUSSION: IgG4-related cholangitis is the biliary presentation of IgG4-related disease, a recently discovered entity of fibroinflammatory masses which can affect virtually every organ in the body. It is characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis and a presence of > 30 IgG4-positive plasma cells per high power field. Main differential diagnosis contains cholangiocarcinoma and primary sclerosing cholangitis. Corticoids are cornerstone of therapy, with azathioprine frequently used as a maintenance in case of relapse. CONCLUSIONS: With this case we want to draw the attention to a rather uncommon cause of biliary obstruction, easily mistaken for a cholangiocarcinoma.

Guidelines for measuring and reporting environmental parameters for experiments in greenhouses.

BACKGROUND: The importance of appropriate, accurate measurement and reporting of environmental parameters in plant sciences is a significant aspect of quality assurance for all researchers and their research. There is a clear need for ensuring research across the world can be compared, understood and where necessary replicated by fellow researchers. A common set of guidelines to educate, assist and encourage comparativeness is of great importance. On the other hand, the level of effort and attention to detail by an individual researcher should be commensurate with the particular research being conducted. For example, a researcher focusing on interactions of light and temperature should measure all relevant parameters and report a measurement summary that includes sufficient detail allowing for replication. Such detail may be less relevant when the impact of environmental parameters on plant growth and development is not the main research focus. However, it should be noted that the environmental experience of a plant during production can have significant impact when subsequent experiments investigate plants at a molecular, biochemical or genetic level or where species interactions are considered. Thus, researchers are encouraged to make a critical assessment of what parameters are of primary importance in their research and these parameters should be measured and reported. CONTENT: This paper brings together a collection of parameters that the authors, as members of International Committee on Controlled Environment Guidelines (ICCEG) in consultation with members of our three parent organizations, believe constitute those which should be recorded and reported when publishing scientific data from experiments in greenhouses. It provides recommendations to end users on when, how and where these parameters should be measured along with the appropriate internationally standardized units that should be used.

Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.

BACKGROUND: Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). RESULTS: Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50. CONCLUSIONS: The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

Lithopedion: case report and ultrastructural study of the skeletal muscle.

A case of lithopedion (lythokelyphopedion) is reported in a 69 year old woman who had carried a nearly full term dead fetus for at least 20 years. The fine structure of the skeletal muscle was in an astonishingly good state of preservation with contractile elements and myosin molecules identifiable. The conditions and modifying factors that may play a role in the development of a lithopedion are discussed, and x-ray, histologic, and electron microscopic studies are described.

Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer.

To assess high-dose carboplatin chemotherapy with or without paclitaxel with filgrastim mobilized peripheral blood progenitor cell (PBPC) support in a phase I/II study, a total of 21 patients with mostly chemonaive disease received four cycles of high-dose chemotherapy. Cycle 1 (cyclophosphamide, 6 g/m2) was followed by two cycles of carboplatin (1600 mg/m2 or 1800 mg/m2). Cycle 4 consisted of carboplatin (1600 mg/m2), etoposide (1600 mg/m2), and melphalan (140 mg/m2). Further chemotherapy intensification was achieved by adding paclitaxel (175 mg/m2) to all cycles with a fixed carboplatin dose (1600 mg/m2). Ototoxicity was dose-limiting for escalation of sequential cycles of carboplatin. Grade 2 and grade 3 ototoxicity, hearing loss not requiring a hearing aid, or hearing loss correctable with a hearing aid, was observed with carboplatin at 1800 mg/m2. The maximum tolerated dose (MTD) of sequential carboplatin, therefore, was identified in this study as 1600 mg/m2. After cycles 1, 2, 3 and 4 the median duration of leukopenia (<1.0x10(9)/l) was 7, 4, 4 and 6 days. Severe grade 3 and 4 infections were seen in only 7% of cycles. Of the 21 patients evaluable for disease response, 57% had complete remissions and 43% experienced partial remissions resulting in an overall response rate of 100%. The median progression-free survival is 25 (15-36) months, the median overall survival 36.5 (15-38) months. Most patients were suboptimally debulked or had bulky residual disease at the start of chemotherapy. Sequential high-dose chemotherapy to a maximum dose of 1600 mg/m2 carboplatin is effective and feasible. A randomized, prospective trial comparing sequential high-dose chemotherapy with optimal standard chemotherapy is now warranted.

Biochemical analysis of a lithopedion.

Lithopedions are very rare; the medical literature mentions 330 cases. In the present case, a calcified lithopedion was found in the abdominal cavity of a 69-year-old woman who had died of unrelated causes. In general, the different organs of the lithopedion were easily distinguishable macroscopically. Microscopic examination detected reasonably well preserved structure only in skeletal muscle. Dry weight studies showed a definite dehydration (mummification) had taken place. Chemical analysis revealed a shell consisting mostly of inorganic constituents. Quantitative inorganic analysis of tissues was done and results compared to normal tissues. These results showed significant decrease of K and Cl, significant increase in Mg, P, Na and enormous increase in Ca. These data are compatible with the histologically observed calcification of the tissues. Under proper conditions, presumably dormant enzymes were reactivated in brain, liver, and muscle, although the total activity was low. Discernible LDH isoenzymes were found in liver and muscle. Discernible CK isoenzymes were found in brain and muscle.

Chronic anterior tibial compartment syndrome. A light-microscopic, histochemical and electronmicroscopic analysis.

A case of chronic anterior tibial compartment syndrome is reported where the entity was accompanied with a primary neurogenic type of muscle atrophy. Histology, histochemistry and electronmicroscopy indicated the diagnosis. The authors concluded that in a moderate case of leg trauma with peroneal nerve involvement, when it is complicated by intermittent arterial spasm, the anterior tibial compartment syndrome may develop chronically.

[The information value of roentgen computerized tomography in atrial tumors of the heart]. / Informationswert der Röntgencomputertomographie bei Vorhoftumoren des Herzens.

The symptoms of intracavitary masses are usually not characteristic and are often confused with those of mitral valve disease. It is therefore necessary to employ all possible diagnostic measures. Like echo cardiography, computer tomography is a non-invasive method which provides accurate information concerning the size, position and shape of the mass. Angiocardiography can confirm these findings, but provides extra information only if there are additional abnormalities or coronary disease. Early diagnosis is important, since the patient is at risk from complications such as cardiac failure, emboli and arrhythmias, and since operative removal of the tumour carries a good prognosis.

Report on the Hungarian Military Health Service Support (a former Soviet dominion).

The author describes the structure and organization of the Health Service Support of the Hungarian Armed Forces. The differences and similarities between the U.S. and the Hungarian Military Medical Services are highlighted. The potential for inter-operability is examined. The importance of such considerations is marked by the ongoing hostilities in the former Yugoslav Republic.

Al Eskan disease: Persian Gulf syndrome.

This article examines the potential relationship between Al Eskan disease and the Persian Gulf syndrome. Al Eskan disease, reported in Military Medicine in 1992, is a novel and previously unreported condition triggered by the exceptionally fine sand dust of the Central and Eastern Saudi Arabian peninsula. We repeat our study of the pathogenesis of Al Eskan disease to include the ultrastructural and microanalytical study of the sand, aerobiological studies of the Kingdom of Saudi Arabia, and the etiology, symptoms, and prevalence of the disease. We conclude that immunodepression resulting from the continued presence of sand particles less than 1 micron in diameter in the lungs and bodies of Persian Gulf veterans explains not only the symptoms of the hyperegic lung condition of phase I and the symptoms of phase II of Al Eskan disease, but also provides an important clue to a common factor in most cases of Persian Gulf illnesses. We include a discussion of most of the commonly suspected agents in the Persian Gulf syndrome. In this case, we conclude that each of these factors, such as oil well fires, old-world diseases, or depleted uranium, are probably adjuvant or contributing causes. The only common exposure that would lead to recognition of the Persian Gulf syndrome as a single medical condition, rather than a catch-all phrase for unrelated conditions, appears to be exposure to the ubiquitous, fine sand of the area, and a resulting immunosuppression that is aggravated by opportunistic infections and other nonmicrobial ailments.

Al Eskan disease: Desert Storm pneumonitis.

The authors observed an acute desert-related disease when the mixture of the fine Saudi sand dust and pigeon droppings triggered a hyperergic lung condition. It was further aggravated by various kinds of organic pathogenic components contributing to an opportunistic infection of the lung. These all lead to the recognition of a new clinicopathological entity, Desert Storm pneumonitis or Al Eskan disease. For the first time, the Saudi sand dust's elemental composition was studied by ultrastructural and microanalytical means. The authors concluded that, contrary to previous beliefs, sand particles less than 1 microns (0.1 microns to 0.25 microns) in diameter are present in substantial quantities in the Saudi sand and are pathogenic, causing hyperergia. Pathogenesis of the sand dust, induced hyperergia, and its immunopathologic background are highlighted.

Annual training medical support for a Reserve Separate Infantry Brigade (Mechanized).

The authors have combined their experience of recent changes in the Health Service Support of a separate mechanized infantry brigade during 10-day field training exercises conducted by the same population, in the same geographical area, and in the same season in 4 consecutive years. The development of Health Service Support and the reasons necessitating its evolution are discussed. The impact of MedForce activities on training effectiveness is highlighted. The intensive use of health care providers in the most forward field medical treatment facilities, to include the nursing pool from the training support reserve hospital and Army Medical Department augmentation pool doctors, can alleviate unit medical staff shortfalls and provide exceptional training for unit medics "in house." The deployment of medical assets far forward and the maximization of "in situ" treatment of casualties prevents significant loss of training time and can prevent loss of life in combat. The authors recommend changing the medical care doctrine of Vietnam, from the life-threatening "scoop and run" doctrine to the life-preserving "doc in the box" doctrine presented in this article.

Prevalence of injuries and illnesses of a Reserve Separate Infantry Brigade (Mechanized) during annual training.

Approximately 1,500 reserve soldiers conducted annual training in the same geographical location and in the same season during 4 consecutive years. This unique situation allowed the authors to collect data on the incidence of illnesses and injuries, and assess environmental and weather influences on readiness and training effectiveness during 10 days of field training exercises. The authors demonstrate that the health of the force and medical preventive countermeasures are decisive contributors to military success or failure.

The role of the sand in chemical warfare agent exposure among Persian Gulf War veterans: Al Eskan disease and "dirty dust".

The purpose of this paper is to inquire into the relationship between Al Eskan disease and the probable exposure to chemical warfare agents by Persian Gulf War veterans. Al Eskan disease, first reported in 1991, compromises the body's immunological defense and is a result of the pathogenic properties of the extremely fine, dusty sand located in the central and eastern region of the Arabian peninsula. The disease manifests with localized expression of multisystem disorder. Signs and symptoms of Al Eskan disease have been termed by the news media "Persian Gulf syndrome." The dust becomes a warfare agent when toxic chemicals are microimpregnated into inert particles. The "dirty dust" concept, that the toxicity of an agent could be enhanced by absorption into inactive particles, dates from World War I. A growing body of evidence shows that coalition forces have encountered Iraqi chemical warfare in the theater of operation/Persian Gulf War to a much greater extent than early U.S. Department of Defense information had indicated. Veterans of that war were exposed to chemical warfare agents in the form of direct (deliberate) attacks by chemical weapons, such as missiles and mines, and indirect (accidental) contamination from demolished munition production plants and storage areas, or otherwise. We conclude that the microimpregnated sand particles in the theater of operation/Persian Gulf War depleted the immune system and simultaneously acted as vehicles for low-intensity exposure to chemical warfare agents and had a modifying-intensifying effect on the toxicity of exposed individuals. We recommend recognition of a new term, "dirty sand," as a subcategory of dirty dust/dusty chemical warfare agents. Our ongoing research efforts to investigate the health impact of chemical warfare agent exposure among Persian Gulf War veterans suggest that Al Eskan disease is a plausible and preeminent explanation for the preponderance of Persian Gulf War illnesses.