Intraabdominal infections and gut origin sepsis

Intraabdominal postoperative or posttraumatic infections remain a major threat to life in spite of generation after generation of increasingly effective antimicrobial drugs indicating the importance of immunological host defense failure following major trauma or surgical complications. The spectrum of infectious postoperative or posttraumatic complications can, in part, be explained by pathogenic factors inherent to the methodology of modern surgical intensive care and techniques. This report presents a survey of the historical background as well as current concepts of the multiple systems organ failure syndrome as related to postoperative or posttraumatic intraabdominal infectious complications. The pathophysiology of nosocomial infectious complications in the intensive care unit setting is analyzed. The concept of gut origin sepsis is presented and possible preventive and therapeutic actions discussed. A judicious use of antimicrobial drugs on strict indications is emphasized as is the importance of increased knowledge of the interactions between the gut flora, antibiotics, and absence of enteral nutrition.

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Resumen Las infecciones intraabdominales postoperatorias o postraumáticas siguen representando una amenaza grave para la vida a pesar de generación tras generación de drogas antimicrobianas de creciente efectividad, lo cual señala la importancia de la falla de los mecanismos inmunes de defensa del huésped que se presenta después de trauma mayor o acompanando las complicaciones quirúrgicas. El espectro de las complicaciones infecciosas postoperatorias o postraumáticas puede ser explicado en parte por factores patogénicos inhérentes a la tecnología y metodología del moderno cuidado intensivo del paciente en estado crítico. El presente informe reporta una revisión de los antecedentes históricos y de los conceptos actuales sobre el sindrome de falla orgánica multisistémica relacionado con complicaciones infecciosas intraabdominales postoperatorias o postraumáticas. Se analiza la patofisiología de las complicaciones infecciosas nosocomiales en el marco de la unidad de cuidado intensivo. Se hace énfasis sobre el uso juicioso de drogas antimicrobianas según indicaciones estrictas, asi como sobre la importancia de un mayor conocimiento sobre las interacciones entre la flora intestinal, los antibióticos, y la ausencia de nutrición enterai.

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Résumé Les infections intra-abdominales postopératoires ou post-traumatiques continuent de menacer le pronostic vital malgré une amélioration constante des antibiotiques ce qui met l'accent sur l'échec des moyens de défense immunologiques après les traumatismes majeurs ou les complications chirurgicales. Le spectre des complications infectieuses postopératoires ou post-traumatiques peut, en partie, être expliqué par des facteurs pathogéniques inhérents à la méthode des soins intensifs et techniques modernes. Ce travail présente l'historique et les concepts actuels de défaillance polyviscérale en rapport avec des complications infectieuses intra-abdominales postopératoires ou post-traumatiques. La pathophysiologie des complications infectieuses nosocomiales dans l'unité des soins intensifs est analysée. La conception de sepsis d'origine intestinale est présentée et les actions préventive et thérapeutique sont discutées. L'utilisation judicieuse des antibiotiques est soulignée, ainsi que les interactions entre la flore intestinale, les antibiotiques et l'absence de nutrition entérale.

     

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Immediate Obturation of the Surgical Defect after Partial Maxillectomy in the Endentulous Patient

Closure of the surgical defect immediately after partial maxillectomy is the treatment of choice. The advantages are: maintaining facial contour, rapid re-establishment of speech, swallowing and mastication. A number of methods for the fixation of the immediate obturator in patients without teeth have been described. A new technique is reported where a transnasal wire holds the existing denture in position after partial maxillectomy. The method has been carried out on 7 patients with sino-nasal cancer during the period 1978-1994. The advantages of the technique are that the wire acts as an axis of rotation which together with the sponge in the cavity provide good stability of the denture. There is minimal preoperative laboratory work and simplification in replacing the surgical dressing.     

Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia.

PURPOSE: Cloretazine (VNP40101M) is a novel sulfonylhydrazine alkylating agent with significant antileukemia activity. A phase I study of cloretazine combined with cytarabine (1-beta-d-arabinofuranosylcytosine, ara-C) was conducted in patients with refractory disease. DESIGN: Ara-C was given i.v. at a fixed dose of 1.5 gm/m(2)/d by continuous infusion for 4 days (patients ages <65 years at time of diagnosis) or 3 days (patients ages > or =65 years). Cloretazine was given i.v. over 15 to 60 minutes on day 2 at a starting dose of 200 mg/m(2), with escalation in 100 mg/m(2) increments in cohorts of three to six patients until a maximum tolerated dose was established. The DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) was measured at baseline. RESULTS: Forty patients, including 32 with acute myeloid leukemia, received 47 courses of treatment. Complete responses were seen at cloretazine dose levels of > or =400 mg/m(2) in 10 of 37 (27%) evaluable patients, and in this patient subset, AGT activity was significantly lower in patients that responded to treatment than in patients who did not (P < or = 0.027). Dose-limiting toxicities (gastrointestinal and myelosuppression) were seen with 500 and 600 mg/m(2) of cloretazine combined with the 4-day ara-C schedule but not seen with the 3-day schedule. CONCLUSION: The recommended cloretazine dose schedule for future studies is 600 mg/m(2) combined with 1.5 gm/m(2)/d continuous infusion of ara-C for 3 days. The cloretazine and ara-C regimen has significant antileukemic activity. AGT activity may be a predictor of response to cloretazine.     

Disseminated Bartonella henselae disease mimicking Langerhans’ cell histiocytosis

Bartonella henselae, the causative agent of cat‐scratch disease, has been recognized to be responsible for a broad range of clinical syndromes. We report the case of a patient with disseminated B. henselae infection mimicking Langerhans cell histiocytosis at presentation and its successful management with neurosurgery, prolonged antibacterial therapy, and observation.     

Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.     

Functional parcellation of the inferior frontal and midcingulate cortices in a flanker‐stop‐change paradigm

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within‐trial response change of the initiated response (keep response vs. stop‐change). We used event‐related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole‐brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition‐related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop‐change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

The emerging EU quality of care policy: From sharing information to enforcement

Despite the fact that Member States and many citizens of the EU like to keep healthcare a foremost national competence and the EU treaties state that Member States remain primarily responsible for the organization and delivery of health care services, the European Union (EU) has expanded its involvement in healthcare policy over the last twenty years. Based on interviews and document and literature analysis we show that the scope of EU involvement has widened from public health and access to care, to quality of care. In this paper we concentrate on the latter. Focusing on the recent EU initiatives regarding the quality systems of the Member States and the quality of services, this paper shows how the depth of EU interference has increased from sharing information to standardization and even to the first signs of enforcement. We argue that at this stage, reflection on the feasibility and desirability of the EU's involvement is clearly needed, also considering the differences in quality of care policies between and within EU Member States. Both arguments in favour and against further EU involvement are discussed in this paper.     

Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.