Long-term quality of life after conservative treatment versus surgery for different stages of acute sigmoid diverticulitis.

PURPOSE: It is controversial whether patients fare better with conservative or surgical treatment in certain stages of acute diverticulitis (AD), in particular when phlegmonous inflammation or covered micro- or macro-perforation are present. The aim of this study was to determine long-term quality of life (QoL) for AD patients who received either surgery or conservative treatment in different stages. METHODS: We included patients treated for AD at the University Hospital Grosshadern, Munich, Germany, between January 1, 2000, and December 31, 2010. Patients were classified by the Hansen and Stock (HS) classification, the modified Hinchey classification, and the German classification of diverticular disease (CDD). Pre-therapeutic staging was based on multidetector computed tomography. Long-term QoL was assessed by the Cleveland Global Quality of Life (CGQL) questionnaire, the Short Form 36 (SF-36), and the Gastrointestinal Quality of Life Index (GIQLI). Data are mean ± SEM. RESULTS: Patients with phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) had a better long-term QoL on the GIQLI when they were operated (78.5 ± 2.5 vs. 70.7 ± 2.1; p < 0.05). Patients with micro-abscess (CDD 2a) had a better long-term QoL on the GIQLI, CGQL, and the "Role Physical" scale of the SF-36 when they were not operated (GIQLI 86.9 ± 2.1 vs. 76.8 ± 1.0; p = 0.10; CGQL 82.8 ± 5.1 vs. 65.3 ± 11.0; p = 0.08; SF-36/Role Physical 100 ± 0.0 vs. 41.7 ± 13.9; p < 0.001). Patients with macro-abscess (CDD 2b) had a better long-term QoL when they were operated (GIQLI 89.3 ± 1.4 vs. 69.5 ± 4.5; p < 0.01; CGQL 80.3 ± 7.6 vs. 60.5 ± 5.8; p < 0.05; SF-36/Role Physical 95.8 ± 4.2 vs. 47.9 ± 13.6; p < 0.001). CONCLUSION: Considering long-term QoL, phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) should be treated conservatively. In patients with covered perforation, abscess size should guide the decision on whether to perform surgery later on or not. In the light of long-term quality of life, patients fare better after elective sigmoid colectomy when abscess size exceeds 1 cm.

Microbiota of high-pressure-processed Serrano ham investigated by culture-dependent and culture-independent methods.

The microbiota of Serrano dry-cured ham of different chemical composition, subjected or not to high-pressure processing (HPP), was investigated using culture-dependent and culture-independent methods. Microbial counts were submitted to analysis of variance with physicochemical parameters (aw, NaCl concentration, salt-in-lean ratio and intramuscular fat content) or HPP as main effects. In untreated hams, physicochemical parameters significantly affected counts of aerobic mesophiles, psychrotrophs, and moulds and yeasts. NaCl concentration and fat content influenced the levels of four and three of the five studied microbial groups, respectively, whereas no influence of aw was stated. The HPP treatment had a significant effect on counts of all investigated microbial groups. Culture-independent methods showed the presence of bacteria such as Staphylococcus equorum, Staphylococcus succinus, Bacillus subtilis and Cellulosimicrobium sp., moulds like Penicillium commune, Aspergillus fumigatus, Sclerotinia sclerotiorum, Eurotium athecium and Moniliella mellis, and yeasts like Debaryomyces hansenii and Candida glucosophila. Absence of B. subtilis bands and weaker bands of E. athecium were recorded for HPP-treated hams. The higher microbial levels found in lean ham might result in a quicker deterioration. HPP treatment confirmed its suitability as a procedure to control spoilage microorganisms. DGGE did not seem to be sensitive enough to highlight changes caused by HPP treatment in the microbiota of ham, but contributed to the detection of microbial species not previously found in ham.

Hartmann's procedure or primary anastomosis?

Perforation following acute diverticulitis is a typical scenario during the first attack. Different classification systems exist to classify acute perforated diverticulitis. While the Hinchey classification, which is based on intraoperative findings, is internationally best known, the German Hansen-Stock classification which is based on CT scan is widely accepted within Germany. When surgery is necessary, sigmoid colectomy is the standard of care. An important question is whether patients should receive primary anastomosis or a Hartmann procedure subsequently. A priori there are several arguments for both procedures. Hartmann's operation is extremely safe and, therefore, represents the best option in severely ill patients and/or extensive peritonitis. However, this operation carries a high risk of stoma nonreversal, or, when reversal is attempted, a high risk in terms of morbidity and mortality. In contrast, primary anastomosis with or without loop ileostoma is a slightly more lengthy procedure as normally the splenic flexure needs to be mobilized and construction of the anastomosis may consume more time than the Hartmann operation. The big advantage of primary anastomosis, however, is that there is no need for the potentially risky stoma reversal operation. The most interesting question is when to do the Hartmann operation or primary anastomosis. Several comparative case series were published showing that primary anastomosis is feasible in many patients. However, no randomized trial is available to date. It is of note, that all non-randomized case series are biased, i.e. that patients in better condition received anastomosis and those with severe peritonitis underwent Hartmann's operation. This bias is undoubtedly likely to be present, even if not obvious, in the published papers! Our own data suggest that this decision should not be based on the extent of peritonitis but rather on patient condition and comorbidity. In conclusion, sigmoid colectomy and primary anastomosis is feasible and safe in many patients who need surgery for perforated diverticulitis, particularly when combined with loop ileostomy. Based on our own published analysis, however, we recommend performing Hartmann's operation in severely ill patients who carry substantial comorbidity, while the extent of peritonitis appears not to be of predominant importance.

Comparative protective effects of recombinant DNA and Mycobacterium bovis bacille Calmette-Guérin vaccines against M. avium infection.

A range of strategies are being explored to develop more effective vaccines against mycobacterial infection, including immunization with DNA plasmids encoding single mycobacterial bacterial genes and the use of recombinant live vectors based on the current vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG). We have compared these two approaches using a model of virulent M. avium infection, and the gene for the immunodominant 35 kDa protein which is shared by M. avium and M. leprae, but absent from BCG. Recombinant BCG over-expressing the M. avium 35 kDa protein (BCG-35) induced strong antigen-specific proliferative and interferon-gamma (IFN-gamma)-secreting T cell responses. These were comparable to those induced by a single immunization with a plasmid expressing the same antigen (DNA-35); however, repeat DNA-35 immunization evoked the strongest IFN-gamma release. Immunization with BCG-35 significantly reduced the growth of virulent M. avium, although this effect was similar to that induced by wild-type BCG. Immunization with DNA-35 resulted in significantly greater (2 x log(10)) reduction in the growth of M. avium. Prime-boost strategies combining DNA-35 and BCG-35 increased the protective effect above that achieved by BCG-35, but they were not more protective than DNA-35 alone. Therefore, recombinant BCG-35 and BCG induced similar levels of protection in this model, and maximal protection against M. avium infection was attained by immunization with DNA encoding the 35 kDa protein.

DNA encoding a single mycobacterial antigen protects against leprosy infection.

The continuing incidence of leprosy infection around the world and the inability of Mycobacterium bovis bacille Calmette-Guérin (BCG) to protect certain populations clearly indicates that an improved vaccine against leprosy is needed. The immuno dominant 35 kDa protein, shared by Mycobacterium leprae and Mycobacterium avium, but not Mycobacterium tuberculosis or BCG, is recognised by >90% of leprosy patients, making it an ideal candidate antigen for a subunit vaccine. Immunization of outbred Swiss Albino mice with a DNA-35 vaccine stimulated specific T cell activation and IFN-gamma production. DNA-35 immunization induced significant levels of protection against M. leprae footpad infection, comparable to that produced by BCG. Therefore, DNA immunization with the 35 kDa antigen is effective against M. leprae infection and genetic immunization with a combination of antigens holds the potential for an improved vaccine against leprosy.

Protection against virulent Mycobacterium avium infection following DNA vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting CD4(+) T cells.

Mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of M. avium varies from that of Mycobacterium tuberculosis, with the immunodominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this M. avium 35-kDa antigen (DNA-35) induces protective immunity against virulent M. avium infection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-gamma) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4(+) T-cell response, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and an increase in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vaccination with Mycobacterium bovis BCG and significantly greater than that for previous treated infection with M. avium. These results illustrate the importance of the 35-kDa protein in the protective response to M. avium infection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronic M. avium infection.

Immunoprophylaxis against Mycobacterium leprae infection with subunit vaccines.

We have investigated the effect of subunit vaccines against infection with Mycobacterium leprae, employing DNA plasmids as the vaccine vectors, and the immunodominant 35 kDa protein of M. leprae as the candidate antigen. A DNA vaccine that expresses the M. leprae 35 kDa protein both stimulated interferon-gamma (IFN gamma)-secreting T cells in mice, and demonstrated protection against M. leprae-infection of mice.

Immunity to intracellular bacteria

Immunity to intracellular bacteria including Mycobacterium tuberculosis. Mycobacterium leprae, and Listeria monocytogenes depends on specific T cells. Evidence to be described suggests that CD4 (alpha/beta)T cells which interact with each other and with macrophages contribute to acquired resistence against as well as pathogenesis of intracellular bacterial infections