Src Kinase Is Biphosphorylated at Y416/Y527 and Activates the CUB-Domain Containing Protein 1/Protein Kinase C δ Pathway in a Subset of Triple-Negative Breast Cancers.

Targeted therapeutics are needed for triple-negative breast cancer (TNBC). In this study, we investigated the activation of Src family of cytoplasmic tyrosine kinases (SFKs) and two SFK substrates-CUB-domain containing protein 1 (CDCP1) and protein kinase C δ (PKCδ)-in 56 formalin-fixed, paraffin-embedded (FFPE) TNBCs. Expression of SFK phosphorylated at Y416 (SFK_pY416+) in tumor cells was strongly associated with phosphorylation of CDCP1 and PKCδ (CDCP1_ pY743+ and PKCδ_pY311+), as assessed by immunohistochemistry, indicating increased SFK activity in situ. To enable biochemical analysis, protein extraction from FFPE tissue was optimized. Cleaved CDCP1 isoform (70 kDa) was expressed to a varying degree in all samples but only phosphorylated in TNBC tumor cells that expressed SFK_pY416. Interestingly, active SFK was found to be biphosphorylated (SFK_pY416+/pY527+). Biphosphorylated active SFK was observed more frequently in forkhead box protein A1 (FOXA1)- TNBCs. In addition, in SFK_pY416- samples, FOXA1+ TNBC tended to be SFK_pY527+ (classic inactive SFK), and FOXA1- TNBC tended to be SFK_pY527- (SFK poised for activation). Strong SFK_pY416 staining was also observed in tumor-infiltrating lymphocytes in a subset of TNBCs with high tumor-infiltrating lymphocyte content. This report will facilitate protein biochemical analysis of FFPE tumor samples and justifies the development of therapies targeting the SFK/CDCP1/PKCδ pathway for TNBC treatment.

Anti-HLA alloantibodies of the IgA isotype in re-transplant candidates part II: Correlation with graft survival.

We reported previously on the widespread occurrence of anti-HLA alloantibodies of the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re-tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx patients, we now extended our earlier findings by examining the impact of the presence and donor specificity of anti-HLA IgA on graft survival. We observed frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter collective of 694 kidney re-tx patients. This subgroup displayed significantly reduced graft survival as evidenced by the median time to first dialysis after transplantation (TTD 77 months) compared to patients carrying either anti-HLA IgG or IgA (TTD 102 and 94 months, respectively). In addition, donor specificity of anti-HLA IgA had a significant negative impact on graft survival (TTD 74 months) in our study. Taken together, our data strongly indicate that presence of anti-HLA IgA, in particular in conjunction with anti-HLA-IgG, in sera of kidney re-tx patients is associated with negative transplantation outcome.

Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non-response to Previous Hepatitis B Vaccination.

Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies. We re-assessed their anti-HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)-γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non-response to HBV vaccination (HLA-DRB1*03 and HLA-DQB1*02) were over-represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti-HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti-HBs antibodies ≥10 IU/l (10-264), in four HBV-specific lymphocyte proliferation (stimulation index of 2.6-8.7) and in one specific IFN-γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix™ could already induce HBV-specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.

[Influence of Fissure Sealants on Dental Health of Elementary School Children in Weimar - A Longitudinal Observational Study under Real-life Conditions]. / Einfluss der Fissurenversiegelung auf die Zahngesundheit von Weimarer Grundschülern ­ Eine longitudinale Beobachtungsstudie unter Alltagsbedingungen.

The aim of the present observational study was to assess the effect of the number and timing of placing fissure sealants (FS) on caries prevalence in elementary school children under real-life conditions. Methods: Oral health data from 7- to 10-year-old elementary school children (n=505) attending 4 consecutive annual checkups between 2004 and 2009 was extracted from the public health service database. The number of intact FS and the number of teeth affected by caries was scored according to WHO standard (1997). Results: 34.9% pupils had at least one, 10% 4 FS. Children without FS had a higher dental caries rate compared to peers with FS (0.2 DT/0.4 DMFT vs. 0.1 DT/0.2 DMFT). Pupils with 4 FS showed the lowest number of teeth with caries (0 DT/0 DMFT). Children with an early application of FS had a lower D-component than children with a later or missing application (0.1 DT vs. 0.2 DT). Pupils with less than 4 FS had a higher risk of developing caries in their permanent dentition compared to peers with 4 FS (OR 4.36). Conclusion: FS is an effective caries preventive measure under real-life conditions. Early application and sealing of all 4 molars can optimize the prevention of caries in the permanent dentition.

[Current therapy of polyarticular forms of juvenile idiopathic arthritis]. / Aktuelle Therapie der polyartikulären Verlaufsform der juvenilen idiopathischen Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.

Determination of unacceptable HLA antigen mismatches in kidney transplant recipients: recommendations of the German Society for Immunogenetics.

One of the major tasks of histocompatibility and immunogenetics laboratories is the pretransplant determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients. In this procedure, human leucocyte antigen (HLA) specificities are defined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM and the potential donor's complete HLA typing, prediction of the crossmatch result, the so called 'virtual crossmatch', is possible. Currently, the laboratories are using different algorithms for the determination of UAM, and depending on the algorithm, more or fewer organ offers are excluded for patients with a similar antibody profile. In order to bring homogeneity into the allocation of organs to immunized patients in Germany, the German Society for Immunogenetics established, on the basis of current knowledge, recommendations for the determination of UAM. The UAM recommendations, which are thought to serve as a common tool for responsible physicians at different transplant centers, contain technical issues that need to be considered and are individualized for sensitized patients with a high or intermediate risk of antibody-mediated rejection. The present review contains these recommendations and puts them into perspective to current international practice.

A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation. SUBJECTS AND METHODS: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility. Clinical status was evaluated at 1 day, 7-10 days, and 2 weeks after ablation. CE-MRI was performed 25-40 days after ablation, followed by surgical resection within 5 days. RESULTS: Ultrasound-guided cryoablation was uniformly technically successful, and postablation clinical status was good to excellent in all participants. Cryoablation was not clinically successful in 15% (three of 20 patients). Three participants had residual cancer at the periphery of the cryoablation site. Two participants had viable nonmalignant tissue within the central zone of cryoablation-induced necrosis. Postablation CE-MRI had a sensitivity of 0% (0/3) and specificity of 88% (15/17). The predictive value of negative findings on CE-MRI was 83% (15/18). Correlations between cancer characteristics, cryoablation procedural variables, postablation CE-MRI findings, and surgical specimen features were not statistically significant. There were also no significant differences in participants with or without residual cancer. CONCLUSION: In our pilot experience, ultrasound-guided cryoablation of invasive ductal carcinomas up to 15 mm has a clinical failure rate of 15% but is technically feasible and well tolerated by patients. The majority of cryoablation failures are manifest as DCIS outside the cryoablation field. Postablation CE-MRI does not reliably predict cryoablation outcome.

Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany.

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.

[Multimodal document management in radiotherapy]. / Multimodales Dokumentenmanagement in der Strahlentherapie.

BACKGROUND AND PURPOSE: After incorporating treatment planning and the organisational model of treatment planning in the operating schedule system (BAS, "Betriebsablaufsystem"), complete document qualities were embedded in the digital environment. The aim of this project was to integrate all documents independent of their source (paper-bound or digital) and to make content from the BAS available in a structured manner. As many workflow steps as possible should be automated, e.g. assigning a document to a patient in the BAS. Additionally it must be guaranteed that at all times it could be traced who, when, how and from which source documents were imported into the departmental system. Furthermore work procedures should be changed that the documentation conducted either directly in the departmental system or from external systems can be incorporated digitally and paper document can be completely avoided (e.g. documents such as treatment certificate, treatment plans or documentation). It was a further aim, if possible, to automate the removal of paper documents from the departmental work flow, or even to make such paper documents superfluous. In this way patient letters for follow-up appointments should automatically generated from the BAS. Similarly patient record extracts in the form of PDF files should be enabled, e.g. for controlling purposes. METHOD: The available document qualities were analysed in detail by a multidisciplinary working group (BAS-AG) and after this examination and assessment of the possibility of modelling in our departmental workflow (BAS) they were transcribed into a flow diagram. The gathered specifications were implemented in a test environment by the clinical and administrative IT group of the department of radiation oncology and subsequent to a detailed analysis introduced into clinical routine. RESULTS: The department has succeeded under the conditions of the aforementioned criteria to embed all relevant documents in the departmental workflow via continuous processes. Since the completion of the concepts and the implementation in our test environment 15,000 documents were introduced into the departmental workflow following routine approval. Furthermore approximately 5000 appointment letters for patient aftercare per year were automatically generated by the BAS. In addition patient record extracts in the form of PDF files for the medical services of the healthcare insurer can be generated.

[Integration of the radiotherapy irradiation planning in the digital workflow]. / Integration der Bestrahlungsplanung in den volldigitalen Workflow.

BACKGROUND AND PURPOSE: At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. METHOD: After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. RESULTS AND CONCLUSION: The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

16(th) IHIW: anti-HLA alloantibodies of the of IgA isotype in re-transplant candidates.

In this multicentre study, sera from 803 retransplant candidates, including 775 kidney transplant recipients, were analysed with regard to the presence and specificity of anti-HLA alloantibodies of the IgA isotype using a modified microsphere-based platform. Of the kidney recipients, nearly one-third (n = 237, 31%) had IgA alloantibodies. Mostly, these antibodies were found in sera that also harboured IgG alloantibodies that could be found in a total of 572 (74%) of patients. Interestingly, IgA anti-HLA antibodies were preferentially targeting HLA class I antigens in contrast to those of the IgG isotype, which targeted mostly both HLA class I and II antigens. Donor specificity of the IgA alloantibodies could be established for over half of the 237 patients with IgA alloantibodies (n = 124, 52%). A further 58 patients had specificities against HLA-C or HLA-DP, for which no information regarding donor typing was available. In summary, these data showed in a large cohort of retransplant candidates that IgA alloantibodies occur in about one-third of patients, about half of these antibodies being donor specific.

Inheritance of moyamoya disease in a Caucasian family.

BACKGROUND AND PURPOSE: Moyamoya disease is a very rare occlusive cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial portion of the internal carotid artery and proximal cerebral arteries with an extensive network of fine collaterals. The aetiology and genetic susceptibility of moyamoya disease, especially in Caucasians, still remains unclear. METHODS AND RESULTS: We describe the cases of affected German father, daughter and son with juvenile stroke because of idiopathic moyamoya disease. The rare existing literature is reviewed and discussed. CONCLUSIONS: This is the first report on a father-to-child inheritance pattern in Caucasian patients with idiopathic Moyamoya disease (MMD). Our cases indicate possible genetic risk factors for the genesis of Caucasian Moyamoya disease.

Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection.

BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A.

Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate- data of the German BIKER registry.

BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. METHODS: Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. RESULTS: From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. CONCLUSIONS: Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.

Definition of a drilling protocol for mini dental implants in different bone qualities.

Mini dental implants (MDI) have proven to be a good alternative of the conventional implants to support lower overdentures in elderly edentulous patients with narrow residual ridge. The aim of the present study was to define drilling protocols for each diameter of the MDI in each bone quality. The number and the diameter of the drilling bur and the drilling depth was investigated. A total of 48 MDIs with a ball head and transgingival collar were used to the drilling protocol in four different bone qualities (Q1-Q4). All available four diameters of the implants were included: 1.8mm, 2.1mm, 2.4mm, and 2.9mm. The length of all implants was 15mm. Three different protocols were prepared for each of the four bone qualities and for each implant diameter. The insertion torques and the primary stability of the implants were measured in their final position. Regardless of implant diameter and bone quality, the insertion torque was significantly higher using drilling protocol 1 than 3 and using drilling protocol 2 than 3 as well. The insertion torque was significantly higher in bone quality Q1 than in Q2-Q4. The unscrewing resulted in considerably increase in the torque, which exceeded the insertion torques by up to two times. This repeatedly led to the bending and fractures of implants.

[Prognostic factors for COPD patients with chronic hypercapnic respiratory failure and home ventilation]. / Prognosefaktoren bei Patienten mit COPD mit chronisch-hyperkapnischer respiratorischer Insuffizienz und ausserklinischer Beatmungstherapie.

The prevalence of patients with severe COPD and chronic hypercapnic respiratory failure (CHRF) receiving non-invasive home ventilation has greatly increased. With regard to disease severity, a multidimensional assessment seems indicated. Base excess (BE), in particular, reflects the long-term metabolic response to chronic hypercapnia and thus constitutes a promising, easily accessible, integrative marker of CHRF. Infact, BE as well as nutritional status and lung hyperinflation have been identified as independent predictors of long-term survival. In addition and in a review with the literature, a broad panel of indices including frequent comorbidities are helpful for assessment and monitoring purposes of patients with CHRF. Accordingly, in view of the patients' individual risk profile, the decision about the initiation of NIV should probably not rely solely on symptoms and chronic persistent hypercapnia but include a spectrum of factors that specifically reflect disease severity. Owing to the physiologically positive effects of NIV and according to retrospective data, patients with COPD and recurrent hypercapnic respiratory decompensation and patients with prolonged mechanical ventilation and/or difficult weaning could also be considered for long-term non-invasive ventilation. This, however, has to be corroborated in future prospective trials.

Synchronous recurrence of concurrent colon adenocarcinoma and dedifferentiated liposarcoma.

A 62-year-old man presented with concurrent sigmoid colon adenocarcinoma and small bowel mesenteric dedifferentiated liposarcoma. Following surgical resection of the colon cancer, complete excision of the mesenteric sarcoma and adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy, the patient demonstrated no radiological evidence of disease for more than 2 years. The patient then developed synchronous recurrence of both cancers: the colon cancer metastasised to the liver and a pelvic lymph node, and the liposarcoma recurred in the original location. The patient underwent additional chemotherapy with complete response of the metastatic colon cancer and stable disease for the liposarcoma. The recurrent mesenteric tumour was subsequently resected. Although concurrent cancers have been reported, this unique case of synchronous recurrence raises interesting hypotheses regarding host-tumour interaction and immune surveillance.

Nutritional depletion and its relationship to respiratory impairment in patients with chronic respiratory failure due to COPD or restrictive thoracic diseases.

OBJECTIVE: While malnutrition, especially fat-free mass index (FFMI), is a predictor for mortality in chronic obstructive pulmonary disease (COPD), less information on prevalence and mechanisms is available in patients with chronic respiratory failure (CRF) due to restrictive thoracic diseases (RTD). DESIGN AND SETTING: Cross-sectional study of patients consecutively admitted to an in-patient primary pulmonary centre. SUBJECTS: One hundred and thirty-two patients (30% RTD; 70% COPD) with CRF and intermittent non-invasive positive pressure ventilation. INTERVENTIONS: Malnutrition was quantified by bioelectrical impedance analysis or body mass index (BMI), and its relationship to laboratory, lung function, inspiratory muscle and blood gas parameters and 6-min walking distance (6-MWD) was assessed. RESULTS: Malnutrition in terms of BMI<20 kg/m(2) occurred in 16.1% of patients with COPD but none of those with RTD. FFMI<17.4 (<15.0 in female patients) kg/m(2) was found in 35.4 and 30.7%, respectively. FFMI was correlated with airway obstruction (sR(aw), r = -0.50; FEV(1)/VC, r = -0.28; P< or = 0.01 each) and lung hyperinflation (intrathoracic gas volume, r = -0.41; total lung capacity (TLC), r = -0.50; P< or = 0.001 each) in COPD, and with lung restriction in RTD (TLC, r=0.40; P=0.011). Furthermore, malnourished patients showed a higher inspiratory load (P (0.1)) and reduced 6-MWD in both groups. In COPD, only hyperinflation and P (0.1) were independently related to FFMI. CONCLUSIONS: Malnutrition as indicated by low FFMI was similarly prevalent in patients with CRF and COPD or RTD, but inadequately represented by BMI. The correlations between lung function impairments specific for the disease and FFMI emphasized the link between malnutrition and respiratory mechanical load irrespective of its aetiology.