Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

Adverse reactions during voluntary donation of blood and/or blood components. A statistical-epidemiological study

Background

Voluntary donors normally tolerate blood donation very well, but, occasionally, adverse reactions of variable severity may occur during or at the end of the collection. Aim of this study was to estimate and possibly avoid the cause of unwanted reactions.

Materials and methods

The study was conducted over a period of 6 months, from 24^th October, 2005 to 24^th April 2006. The donor population analysed consisted of 4,906 donors (3,716 male and 1,190 female). In total, 3,983 (81%) voluntaries have donated whole blood, 851 (17%) plasma from apheresis, 64 (1.3%) experienced multicomponent donation, and 8 (0.1%) were donors of plasma-platelet apheresis.

Results

Only 63 donors (1.2% of all the volunteers) suffered some kind of adverse reaction: 59 (1.08% of the subjects) had mild reactions (agitation, sweating, pallor, cold feeling, sense of weakness, nausea), and only 4 (3 males and 1 female, 0.2%) had more severe disorders, including vomiting, loss of consciousness, and convulsive syncope.

Conclusions

Although the number of donors who developed disturbances during or at the end of blood donations was very low, it is nevertheless desirable to reduce risks to a minimum. A set of advices is provided for preventing problems.     

Diagnosis and management of glutaric aciduria type I �C revised recommendations

Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline.     

MEFV-Mutationsspektrum bei famili?rem Mittelmeerfieber (FMF)

Objectives

Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disorder, is characterized by recurrent, self-limiting fever and serositis which is frequently seen in Mediterranean populations. In this study, we retrospectively evaluated the MEFV gene mutation distribution of 883 citizens of the Aegean region with preliminary diagnosis of FMF who were referred to the Tepecik Research and Education Hospital??s Tissue Typing and Molecular Diagnostic Laboratory (Izmir, Turkey) between 2006 and 2009.

Methods

The FMF Strip Assay? (ViennaLab Diagnostics, Vienna, Austria) was used to determine the 12 most common MEFV gene mutations in patients prediagnosed with FMF.

Findings

Allelic frequencies of the major mutations in the mutation positive groups, including M694V, E148Q, M680I(G>C), and V726A, accounted for 48.4, 16.5, 13.5, and 9.7%, respectively.

Conclusion

The M694V mutation was found to be the most common mutation among FMF patients in the Aegean region, which is in accordance with mutation studies reported from other regions of the country and different ethnic populations. An English full-text version of this article is available at SpringerLink as supplemental.     

S3-Leitlinie: Analabszess

Background

Anal abscesses are relatively frequent and most common in young men.

Methods

A systematic review of the literature has been undertaken.

Results

The origin of the abscess is usually the proctodeal gland in the intersphincteric space. There are different types of abscesses: intersphincteric, ischioanal and supralevatory abscesses. Anamnesis and clinical examination are sufficient to indicate surgery. Further examinations such as endosonography or magnetic resonance tomography (MRT) should be considered in recurrent or supralevatory abscesses. The timing of surgical intervention depends on clinical symptoms, whereas the acute abscess is an emergency indication. Surgery is the primary therapy approach for anal abscess. Surgical access (transrectal or perianal) depends on the localization of the abscess. The aim of surgery is to broadly drain the infection and protect anal sphincter structures. The wound should be rinsed regularly (showering with clear water). Treatment with local antiseptics carries the risk of zytotoxicity. Antibiotic treatment is necessary only in selected cases. Any attempt to locate a fistula intraoperatively should be undertaken with great care; proven evidence of a fistula is not mandatory. Although the risk of recurrent abscess or secondary fistula is low, these may be caused by insufficient drainage. The primary fistulotomy of superficial fistulas should only be performed by an experienced surgeon. In the case of ambiguous findings or high fistulas, treatment should be carried out in a second surgical procedure.

Conclusion

For the first time in Germany, this clinical S3 guideline provides instructions for the diagnosis and treatment of anal abscesses based on a systematic review of the literature.     

Early intervention during imatinib therapy in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a study of the Spanish PETHEMA group

Background

Despite the favorable results of imatinib front line in chronic-phase chronic myeloid leukemia there is room for improvement.

Design and Methods

Early intervention during imatinib therapy was undertaken in 210 adults with chronic-phase chronic myeloid leukemia less than three months from diagnosis (Sokal high risk: 16%). Patients received imatinib 400 mg/day. At three months, dose was increased if complete hematologic response was not achieved. At six months, patients in complete cytogenetic response were kept on 400 mg and the remainder randomized to higher imatinib dose or 400 mg plus interferon-alfa. At 18 months, randomized patients were switched to a 2^nd generation tyrosine kinase inhibitor if not in complete cytogenetic response and imatinib dose increased in non-randomized patients not in major molecular response.

Results

Seventy-two percent of patients started imatinib within one month from diagnosis. Median follow-up is 50.5 (range: 1.2–78) months. At three months 4 patients did not have complete hematologic response; at six months 73.8% were in complete cytogenetic response; among the remainder, 9 could not be randomized (toxicity or consent withdrawal), 17 were assigned to high imatinib dose, and 15 to 400 mg + interferon-alpha. The low number of randomized patients precluded comparison between the two arms. Cumulative response at three years was: complete hematologic response 98.6%, complete cytogenetic response 90% and major molecular response 82%. On an intention-to-treat basis, complete cytogenetic response was 78.8% at 18 months. At five years, survival was 97.5%, survival free from accelerated/blastic phase 94.3%, failure free survival 82.5%, and event free survival (including permanent imatinib discontinuation) 71.5%.

Conclusions

These results indicate the benefit of early intervention during imatinib therapy (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00390897","term_id":"NCT00390897"}}NCT00390897).     

Effect of hysterectomy on colonoscopy completion rate

BACKGROUND:

Several studies show that colonoscopies are technically more difficult to perform in women than men, especially in women who have undergone abdominal and gynecological surgeries. A review of the literature indicates an increased rate of noncompletion of colonoscopies in most cases; however, no studies have investigated the procedural complication rate, sedation requirements and perception of pain in colonoscopies.

OBJECTIVE:

To determine whether women who have undergone a previous hysterectomy have a higher noncompletion rate when undergoing a colonoscopy, and to assess whether there is a higher percentage of complications. Furthermore, the present study also aimed to ascertain whether these women required more sedation and whether their perception of pain is greater than that of women who did not undergo previous abdominal surgeries.

METHODS:

The present study was a prospective cohort study of women, 45 to 80 years of age, who underwent colonoscopy (n=508). A total of 229 patients were eligible for the study; they completed a questionnaire, and were subsequently divided into control and hysterectomy groups. Gastroenterologists performed all procedures. After colonoscopy, the patient and endoscopist completed a pain perception questionnaire. Cecal intubation rates were also recorded.

RESULTS:

No significant difference for cecal intubation rates were detected between the two groups (95.7% and 98.7% in hysterectomy and control groups, respectively; P=0.176). The crude OR for the success rate was 0.29 (95% CI 0.05 to 1.90). There was no significant difference between groups regarding sedation or the type of colonoscope. No correlation between the gastroenterologists’ evaluation of pain and patients’ pain was observed.

CONCLUSION:

Hysterectomy did not significantly diminish the cecal intubation rate, and there was no detectable difference in pain perception or sedative dose. Colonoscopy remains an excellent screening and diagnostic tool for all women.     

Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter?

Background  

Febrile neutropenic cancer patients represent a heterogeneous population with a limited proportion at risk of serious medical complications. The Multinational Association for Supportive Care in Cancer (MASCC) score has been developed and validated for identifying low-risk patients at the onset of febrile neutropenia. Since bacteremia, although not documented at baseline, is a predictor of pejorative outcome, the purpose of this study was to investigate the possible interaction between the MASCC score and bacteremic status and to assess whether, assuming that bacteremic status could be predicted at onset of febrile neutropenia, adding bacteremia as a covariate in a risk model would improve the accuracy of low-risk patients identification.     

Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases

Background

Familial hemophagocytic lymphohistiocytosis is a genetic disorder of lymphocyte cytotoxicity that usually presents in the first two years of life and has a poor prognosis unless treated by hematopoietic stem cell transplantation. Atypical courses with later onset and prolonged survival have been described, but no detailed analysis of immunological parameters associated with typical versus atypical forms of familial hemophagocytic lymphohistiocytosis has been performed.

Design and Methods

We analyzed disease manifestations, NK-cell and T-cell cytotoxicity and degranulation, markers of T-cell activation and B-cell differentiation as well as Natural Killer T cells in 8 patients with atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2.

Results

All but one patient with atypical familial hemophagocytic lymphohistiocytosis carried at least one splice-site mutation in UNC13D or STXBP2. In most patients episodes of hemophagocytic lymphohistiocytosis were preceded or followed by clinical features typically associated with immunodeficiency, such as chronic active Epstein Barr virus infection, increased susceptibility to bacterial infections, granulomatous lung or liver disease, encephalitis or lymphoma. Five of 8 patients had hypogammaglobulinemia and reduced memory B cells. Most patients had a predominance of activated CD8⁺ T cells and low numbers of Natural Killer T cells. When compared to patients with typical familial hemophagocytic lymphohistiocytosis, NK-cell cytotoxicity and NK-cell and CTL degranulation were impaired to a similar extent. However, in patients with an atypical course NK-cell degranulation could be partially reconstituted by interleukin-2 and cytotoxic T-cell cytotoxicity in vitro was normal.

Conclusions

Clinical and immunological features of atypical familial hemophagocytic lymphohistiocytosis show an important overlap to primary immunodeficiency diseases (particularly common variable immunodeficiency and X-linked lymphoproliferative syndrome) and must, therefore, be considered in a variety of clinical presentations. We show that degranulation assays are helpful screening tests for the identification of such patients.