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1.
Diseases ; 12(7)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39057104

ABSTRACT

BACKGROUND: Patients with peripheral artery disease (PAD) have 40-70% higher three-year mortality after lower limb amputation compared to non-amputees. In this study, we examined the consequences of delayed treatment for patients with PAD during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study employed a retrospective single-centre cohort design at a large tertiary care hospital. We compared amputees with PAD during the initial COVID-19 outbreak period in 2020 with a control group of amputees from 2019 after a three-year follow-up. RESULTS: In total, 134 amputees with PAD were included due to unsuccessful revascularization (n = 84 in 2020 vs. n = 50 in 2019). Patients in 2020 were significantly younger than those in 2019 (p = 0.01) and mostly admitted with advanced stages of PAD (p < 0.03). The proportion of major limb amputations increased significantly in 2020 (p = 0.03). Non-COVID-19-related deaths among patients in 2020 were more than twice as many as those in 2019, and long-term mortality in 2020 was 49% compared to 39% in 2019 (p = 0.04). Diabetes and renal insufficiency had a significantly negative impact on the survival of amputees with PAD (p < 0.01). CONCLUSIONS: Delayed treatment in patients with PAD leads to high long-term mortality risk after amputation, especially in PAD patients with diabetes and renal insufficiency. Therefore, in future pandemics, continuously monitoring patients with PAD will be crucial to prevent delayed treatment and severe short-term and long-term consequences.

2.
Wien Klin Wochenschr ; 135(15-16): 399-405, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36472709

ABSTRACT

BACKGROUND: Sacral neuromodulation (SNM) is a widely accepted treatment for pelvic floor disorders, including constipation and fecal incontinence (FI). In 2017, a standardized electrode placement method, the H technique, was introduced to minimize failure rates and improve clinical outcomes. We aimed to investigate the technical feasibility and functional outcome of the procedure. METHODS: In this prospective study, we evaluated the first 50 patients who underwent SNM according to the H technique between 2017 and 2020 at a tertiary care hospital. Patient demographic and clinical data were collected, and the impact of various factors on patients' postoperative quality of life (QoL) was assessed after a follow-up of 40 months. Functional outcome was monitored prospectively using a standardized questionnaire. RESULTS: Of 50 patients, 36 (72%) reported greater than 50% symptom relief and received a permanent implant (95% CI: 58.3-82.5). We observed 75% success in relieving FI (95% CI: 58.9-86.3) and 64% in constipation (95% CI: 38.8-83.7). Complication occurred in five (10%) patients. Preoperative vs. postoperative physical and psychological QoL, Vaizey score, and obstructed defecation syndrome (ODS) scores revealed significant improvements (all p < 0.01). Male gender was significantly associated with postoperative complications (p = 0.035). CONCLUSION: We provide evidence for the technical feasibility and efficacy of the SNM implantation using the H technique. The medium-term results are promising for patients with FI and constipation. Male patients and those with a BMI > 25 are more prone to perioperative complications.


Subject(s)
Electric Stimulation Therapy , Fecal Incontinence , Humans , Male , Treatment Outcome , Quality of Life , Prospective Studies , Fecal Incontinence/surgery , Constipation/therapy , Constipation/diagnosis , Electric Stimulation Therapy/methods
3.
Oral Oncol ; 124: 105634, 2022 01.
Article in English | MEDLINE | ID: mdl-34844042

ABSTRACT

BACKGROUND: Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial. METHODS: Platinum-resistant R/M HNSCC patients received DTX 75 mg/m^2 plus P 200 mg for up to six cycles followed by P maintenance therapy. The primary endpoint was overall response rate (ORR) and safety. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS). RESULTS: Twenty-two patients were enrolled. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. The ORR was 22.7% (95% CI 10.1%-43.4%) and one (4.5%) complete response was achieved. The DCR was 54.6% (95% 34.7%-73.1%). The median PFS was 5.8 months (95% CI 2.7-11.6) and the median OS 21.3 months (95% CI 6.3-31.1). The 1-year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune-related AEs were grade skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia. CONCLUSION: DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients.


Subject(s)
Head and Neck Neoplasms , Neoplasm Recurrence, Local , Antibodies, Monoclonal, Humanized , Docetaxel , Head and Neck Neoplasms/chemically induced , Head and Neck Neoplasms/drug therapy , Humans , Neoplasm Recurrence, Local/pathology , Prospective Studies , Squamous Cell Carcinoma of Head and Neck/drug therapy
4.
Cancers (Basel) ; 12(11)2020 Oct 25.
Article in English | MEDLINE | ID: mdl-33113874

ABSTRACT

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.

5.
Surg Obes Relat Dis ; 16(3): 372-380, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31959564

ABSTRACT

BACKGROUND: Homocysteine is an important independent risk factor for predicting cardiovascular disease (CVD). However, changes in the homocysteine levels after bariatric surgery remain controversial. OBJECTIVES: Modeling differences in homocysteine after bariatric surgery. SETTING: University Hospital, Austria. METHODS: Seven hundred eight consecutive bariatric surgery patients (78% female, 22% male, mean body mass index 41 kg/m2 preoperatively) underwent laparoscopic long-limb Roux-en-Y gastric bypass in a 6-year period and were retrospectively evaluated for changes in their preoperative homocysteine levels, at 3, 6, 9, 12, 18, 24, 36, 48, 60, and 72 months postoperatively. Furthermore, a postal and telephone screening for postoperative CVD with a follow-up of 71% was conducted. RESULTS: Hyperhomocysteinemia was present in 11.8% preoperatively (normal range: <15 µmol/L). The median plasma homocysteine level was 10.4 preoperatively, 12.1 at 3, 11.2 at 6, 10.0 at 9, 9.8 at 12, 8.9 at 18, 8.7 at 24, 8.6 at 36, 9.1 at 48, 9.8 at 60, and 10.0 µmol/L at 72 months postoperatively. After subdividing the study population in morbidly obese (n = 509, body mass index 40-50 kg/m2) and super-obese (n = 199, body mass index >50 kg/m2) patients, the short-term increase into homocysteine levels remained. Overall, newly onset CVD risk was 4.2%. After subdividing the CVD risk into risk for myocardial infarction, stroke, and risk for deep vein thrombosis/pulmonary embolism the distribution was as follows: .2% myocardial infarction, .59% stroke, and 2.97% deep vein thrombosis/pulmonary embolism (median 36 [interquartile range 36-48] mo postoperatively). CONCLUSION: Laparoscopic Roux-en-Y gastric bypass leads to increased homocysteine levels in the early postoperative period. However, there was no relationship between increased homocysteine levels and CVD event onset.


Subject(s)
Gastric Bypass , Laparoscopy , Obesity, Morbid , Body Mass Index , Female , Follow-Up Studies , Gastric Bypass/adverse effects , Homocysteine , Humans , Male , Obesity, Morbid/surgery , Plasma , Postoperative Complications/etiology , Postoperative Period , Retrospective Studies , Treatment Outcome , Weight Loss
8.
J Eval Clin Pract ; 24(4): 708-712, 2018 08.
Article in English | MEDLINE | ID: mdl-29790230

ABSTRACT

The difference between the pth quantiles of 2 survival functions can be used to compare patients' survival between 2 therapies. Setting p = 0.5 yields the median survival time difference. Varying p between 0 and 1 defines the quantile survival time difference curve which can be straightforwardly estimated by the horizontal differences between 2 Kaplan-Meier curves. The estimate's variability can be visualized by adding either a bundle of resampled bootstrap step functions or, alternatively, approximate bootstrap confidence bands. The user-friendly SAS software macro %kmdiff enables the straightforward application of this exploratory graphical approach. The macro is described, and its application is exemplified with breast cancer data. The advantages and limitations of the approach are discussed.


Subject(s)
Kaplan-Meier Estimate , Software , Biomedical Research/methods , Breast Neoplasms/therapy , Computer-Aided Design , Humans , Models, Statistical , Survival Analysis , Time Factors
9.
Burns ; 44(4): 784-792, 2018 06.
Article in English | MEDLINE | ID: mdl-29395408

ABSTRACT

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.


Subject(s)
Bacteremia/epidemiology , Burns/epidemiology , Candidiasis/epidemiology , Fungemia/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Pseudomonas Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/mortality , Body Surface Area , Burn Units , Candidiasis/mortality , Child , Cohort Studies , Critical Care , Drug Resistance, Multiple, Bacterial , Enterococcus , Female , Fungemia/mortality , Gram-Positive Bacterial Infections/mortality , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Pseudomonas Infections/mortality , Retrospective Studies , Risk Factors , Trauma Severity Indices , Young Adult
10.
Wien Klin Wochenschr ; 129(11-12): 398-403, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28204968

ABSTRACT

BACKGROUND: After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2­year survival, we present an update of the disease-specific and disease-free survival after 5 years. PATIENTS AND METHODS: A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease. RESULTS: Since the 2­year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5­year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients. CONCLUSION: We present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.


Subject(s)
Chemoradiotherapy/mortality , Neoplasm Recurrence, Local/mortality , Oropharyngeal Neoplasms/epidemiology , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/epidemiology , Papillomavirus Infections/therapy , Aged , Aged, 80 and over , Austria/epidemiology , Chemoradiotherapy/statistics & numerical data , Disease-Free Survival , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Prognosis , Retrospective Studies , Risk Factors , Survival , Treatment Outcome
11.
Eur J Obstet Gynecol Reprod Biol ; 191: 51-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26073262

ABSTRACT

OBJECTIVE: We performed a randomised controlled trial of percutaneous tibial nerve stimulation (PTNS) versus tolterodine for treating treatment naïve women with overactive bladder (OAB). STUDY DESIGN: 36 patients with symptoms of OAB were randomised to 3 months of treatment with weekly PTNS or tolterodine (2mg bid p.o.). The primary outcome measure was the difference of micturitions per 24h. The secondary outcome measure was the impact on quality of life (QoL) measured with a visual analogue scale (VAS) between baseline and after 3 months of therapy. RESULTS: Micturition frequencies did not decline significantly (p=0.13) over time and there were no significant treatment differences (p=0.96). QoL was significantly dependent from its level at baseline (p=0.002) and showed improvement over time compared to baseline measurements but no significant differences between both treatment groups (p=0.07). Incontinence episodes per 24h depended significantly on the level at baseline (p=0.0001) and declined significantly (p=0.03) during 3 months of therapy in both therapy groups. However no significant treatment differences on the reduction of incontinence episodes in 24h could be shown between both therapy groups (p=0.89). PTNS had fewer side effects than tolterodine (p=0.04). CONCLUSION: PTNS and tolterodine were both effective in reducing incontinence episodes and improving QoL in patients with OAB but not micturition frequencies. PTNS had fewer side effects.


Subject(s)
Cholinergic Antagonists/therapeutic use , Quality of Life , Tibial Nerve/physiopathology , Tolterodine Tartrate/therapeutic use , Transcutaneous Electric Nerve Stimulation , Urinary Bladder, Overactive/therapy , Urological Agents/therapeutic use , Adult , Aged , Aged, 80 and over , Austria , Cholinergic Antagonists/adverse effects , Female , Follow-Up Studies , Germany , Humans , Middle Aged , Patient Dropouts , Pilot Projects , Severity of Illness Index , Tolterodine Tartrate/adverse effects , Transcutaneous Electric Nerve Stimulation/adverse effects , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/physiopathology , Urinary Incontinence, Urge/etiology , Urinary Incontinence, Urge/prevention & control , Urological Agents/adverse effects , Young Adult
12.
PLoS One ; 9(6): e99008, 2014.
Article in English | MEDLINE | ID: mdl-24905750

ABSTRACT

Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM) with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID)-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both) and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively), and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as novel prognostic marker which is superior to clinicopathological parameters. Findings emphasize anti-tumoral role of B cell-driven mechanism(s) and thus indicate a new way of thinking about potential treatment strategies for CRCLM patients.


Subject(s)
B-Lymphocytes/cytology , B-Lymphocytes/immunology , Colorectal Neoplasms/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Algorithms , Antigens, CD/metabolism , B-Lymphocytes/metabolism , Female , Humans , Liver Neoplasms/secondary , Macrophages/immunology , Male , Middle Aged , Prognosis
13.
Br J Nurs ; 21(2): 98, 100-2, 2012.
Article in English | MEDLINE | ID: mdl-22306640

ABSTRACT

Pruritus ani is a hidden but frequently occurring clinical condition, with a large impact on patients' quality of life. Currently, therapeutic options are scarce, offering mainly limited success. The authors performed a prospective, open-label, two-centre pilot study to analyse the efficacy and safety of a liquid-film forming acrylate cream for the treatment of pruritus ani and peri-anal skin irritation. A total of 28 patients were included and applied the cream to the cleansed anal and peri-anal skin once daily for a study period of 3-4 weeks. The primary outcome measure was the reduction of pruritis ani, comparing day 0 to day 28 results. For this purpose, a visual analog scale (VAS) was used. Secondary parameters included the physician global assessment score (PGA) of peri-anal skin condition, assessment of patients' quality of life using a specifically designed quality of life scoring tool, and patient satisfaction with the treatment regimen. The application of the acrylate skin protection cream resulted in a fast and substantial improvement of all study parameters, with a high score for patient satisfaction. The cream was well tolerated without any adverse events noted during the study period. The authors' pilot study has generated initial evidence that the acrylate skin protection cream may be effective for the treatment of pruritus ani. However, further randomized controlled studies are needed to confirm the authors' findings.


Subject(s)
Acrylates/administration & dosage , Emollients/administration & dosage , Pruritus Ani/drug therapy , Administration, Topical , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pilot Projects , Pruritus Ani/nursing , Skin Care/methods , Young Adult
14.
Ann Surg Oncol ; 19(2): 519-26, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21743980

ABSTRACT

INTRODUCTION: Our study aims to determine whether patients with lobular-type breast cancer have significantly improved rates of breast conservation (BCT) after neoadjuvant chemotherapy (nCT). METHODS: Patients who received nCT and surgery within three prospective trials between 1995 and 2007 at the Medical University of Vienna were retrospectively analyzed. RESULTS: 325 patients had median follow-up of 53 months; 21% had lobular cancer, and 70% of these women were initially scheduled for mastectomy (MX). Twenty-one finally received BCT, yielding a MX-BCT turnover rate of 45%. Of patients primarily scheduled for BCT, 20% had to finally undergo MX in lobular cancer. The 256 patients with ductal-type breast cancer finally had a MX-BCT turnover rate of 52% (p = 0.561 versus lobular) and a BCT-MX turnover rate of 15% (p = 0.933 versus lobular). Secondary MX after initial BCT was necessary in 2% (ductal) and 10% (lobular, p = 0.110). There was no difference in local recurrence in lobular- as compared with ductal-type breast cancer patients after BCT (2.7% versus 10%, p = 0.135), nor was a difference seen in lobular breast cancer patients when comparing BCT with MX (2.7% versus 3.4%, p = 0.795). Tumor type was not an independent predictor for either BCT or local recurrence. CONCLUSION: We do not suggest excluding patients with lobular-type breast cancer who are primarily scheduled for MX from nCT, since BCT rates may still increase by 45% without influencing the oncologic outcome.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Lobular/drug therapy , Mastectomy, Segmental , Neoadjuvant Therapy , Adult , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/mortality , Carcinoma, Lobular/surgery , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prospective Studies , Survival Rate , Treatment Outcome
15.
Wien Klin Wochenschr ; 123(7-8): 215-21, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21448626

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the incidence and clinical significance of HPV (Human papilloma virus) infection in patients with head and neck cancer who had received radiotherapy in Eastern Austria. PATIENTS AND METHODS: 88 patients with head and neck cancer including 26 patients with oral cavity cancer, 45 patients with oropharyngeal cancer, seven patients with laryngeal carcinoma and ten patients with carcinoma of the hypopharynx were screened for high risk HPV by immunohistochemistry, PCR (Polymerase Chain Reaction) and in-situ hybridization. 29 out of 45 patients with a squamous cell carcinoma of the oropharynx received radiotherapy alone, radiotherapy in combination with cisplatin or cetuximab. RESULTS: Of the investigated 29 patients with oropharyngeal cancer receiving conservative treatment, 11 had a HPV-positive and 18 a HPV-negative tumor. Patients received radiation ± cisplatin or cetuximab, where the HPV-positive patients had a significant better response to treatment and overall survival (p = 0.015) as well as disease-free survival (p = 0.001) after therapy. CONCLUSION: Patients with oropharyngeal carcinoma and a positive HPV status respond considerably better to radiochemotherapy than patients with HPV-negative tumors. HPV screening is a simple procedure and can easily be implemented in routine pathology investigations and should be included in standard operational procedures for the diagnosis and therapy of head and neck cancer patients.


Subject(s)
Chemotherapy, Adjuvant/mortality , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/mortality , Radiotherapy, Adjuvant/mortality , Adult , Aged , Aged, 80 and over , Austria/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Papillomavirus Infections/therapy , Prevalence , Risk Assessment , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome , Young Adult
16.
Clin Cancer Res ; 17(1): 122-33, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21208906

ABSTRACT

PURPOSE: Heat shock protein-90 (HSP-90), a molecular chaperone required by numerous oncogenic kinases [e.g., HER-2, epidermal growth factor receptor (EGFR), Raf-1, v-Src, and AKT] for conformational stability, has attracted wide interest as a novel target for cancer therapy. HSP-90 inhibition induces degradation of HSP-90 client proteins, leading to a combinatorial inhibition of multiple oncogenic signaling pathways with consecutive growth arrest and apoptosis. MET, a tyrosine kinase that is constitutively active in tumor cells with MET oncogene amplification, has recently been identified as another HSP-90 client. EXPERIMENTAL DESIGN: The aim of our study was to assess the efficacy of SNX-2112, a synthetic HSP-90 inhibitor, in 3 different MET-amplified tumor cell lines (GTL-16, MKN-45, and EBC-1) as well as PR-GTL-16 cells, a GTL-16 subline selected for resistance to the highly selective MET kinase inhibitor PHA-665752. RESULTS: In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT, as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest. SNX-5542, an orally bioavailable prodrug of SNX-2112, displayed significant antitumor efficacy in vivo in nude mice bearing MET-amplified tumor xenografts. Importantly, HSP-90 inhibition maintained its antitumor efficacy in PR-GTL-16 cells both in vitro and in vivo, suggesting that HSP-90 inhibition could be a particularly valuable strategy in MET-amplified tumors that have acquired resistance to MET kinase inhibition. CONCLUSIONS: Our study provides evidence for the efficacy of HSP-90 inhibition in MET-amplified cancer cells, particularly when MET kinase inhibitor resistance has emerged.


Subject(s)
Antineoplastic Agents/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Heterocyclic Compounds, 4 or More Rings/pharmacology , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Humans , Indoles/pharmacology , Mice , Mice, Inbred BALB C , Mice, Nude , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-met/metabolism , Structure-Activity Relationship , Sulfones/pharmacology
17.
World J Surg ; 34(7): 1702-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20372901

ABSTRACT

BACKGROUND: Mesh graft infection after prosthetic hernia repair is a challenging complication usually treated by mesh removal. The aim of this study was to identify risk factors associated with mesh infection and to assess the efficacy of conservative wound therapy in preserving an infected mesh. METHODS: We performed a retrospective analysis of 476 consecutive patients with incisional hernia who received mesh graft repair between February 1, 2000 and February 28, 2005 at our institution using chart review and clinical investigation. RESULTS: Thirty-one of 476 (6.5%) patients developed a deep surgical site infection involving the implanted mesh graft. Upon multivariate analysis, operation time was the only significant risk factor associated with mesh infection (p = 0.0038). Seventeen (55%) of 31 infected mesh grafts were preserved by conservative means. There was a significant association between the type of mesh graft used and the probability of mesh preservation in case of infection: While conservative therapy led to preservation of 100% of infected polyglactin/polypropylene meshes, only 20% of infected polypropylene and 23% of infected PTFE/polypropylene meshes could be salvaged using conservative means (p < 0.0001). In none of the patients with preserved mesh graft was hernia recurrence at the former site of infection observed. CONCLUSIONS: Operation time is the only significant risk factor associated with mesh graft infection following incisional hernia repair. Conservative treatment should be applied in case of infection of absorbable mesh grafts such as polypropylene/polyglactin, while nonabsorbable meshes such as PTFE/polypropylene or pure polypropylene are much less amenable to conservative treatment, usually requiring early surgical removal.


Subject(s)
Hernia, Abdominal/surgery , Prosthesis-Related Infections/epidemiology , Surgical Wound Infection/epidemiology , Aged , Female , Humans , Male , Middle Aged , Negative-Pressure Wound Therapy , Prosthesis-Related Infections/surgery , Prosthesis-Related Infections/therapy , Retrospective Studies , Risk Factors , Surgical Mesh
18.
Crit Care ; 13(4): R127, 2009.
Article in English | MEDLINE | ID: mdl-19646229

ABSTRACT

INTRODUCTION: The usefulness of CPR training in schools has been questioned because young students may not have the physical and cognitive skills needed to correctly perform such complex tasks correctly. METHODS: In pupils, who received six hours of CPR training from their teachers during a standard school semester at four months post training the following outcome parameters were assessed: CPR effectiveness, AED deployment, accuracy in checking vital signs, correctness of recovery position, and whether the ambulance service was effectively notified. Possible correlations of age, gender, body mass index (BMI), and outcome parameters were calculated. RESULTS: Of 147 students (mean age 13 +/- 2 years), 86% performed CPR correctly. Median depth of chest compressions was 35 mm (inter quartile range (IQR) 31 to 41), and the median number of compressions per minute was 129 bpm (IQR 108 to 143). Sixty nine percent of the students tilted the mannequin head sufficiently for mouth to mouth resuscitation, and the median air volume delivered was 540 ml (IQR 0 to 750). Scores on other life supporting techniques were at least 80% or higher. Depth of chest compressions showed a correlation with BMI (r = 0.35; P < 0.0001), body weight (r = 0.38; P < 0.0001), and body height (r = 0.31; P = 0.0002) but not with age. All other outcomes were found to be unrelated to gender, age, or BMI. CONCLUSIONS: Students as young as 9 years are able to successfully and effectively learn basic life support skills including AED deployment, correct recovery position and emergency calling. As in adults, physical strength may limit depth of chest compressions and ventilation volumes but skill retention is good.


Subject(s)
Adolescent Behavior , Child Behavior , First Aid , Adolescent , Austria , Cardiopulmonary Resuscitation , Child , Humans , Prospective Studies , Self Efficacy
19.
Wien Klin Wochenschr ; 121(1-2): 41-6, 2009.
Article in English | MEDLINE | ID: mdl-19263013

ABSTRACT

BACKGROUND AND AIM: Chest compressions are crucial in cardiopulmonary resuscitation (CPR), although the optimal number, rate and sequence are unknown. The 2005 CPR guidelines of the European Resuscitation Council (ERC) brought major changes to the basic life support algorithm. One of the major aims of the ERC was to decrease hands-off time in order to improve perfusion of the coronary vessels and the brain. Using a manikin model of basic life support in simulated cardiac arrest, we compared hands-off time and total number of chest compressions according to the guidelines of 2000 and those of 2005. METHODS: A total of 50 volunteers performed CPR according to the guidelines of 2000 (Group 2000) and 2005 (Group 2005) in a randomized unblinded cross-over study. Volunteers received 10 min of standardized teaching and 10 min of training, including corrective feedback, for each set of guidelines before performing 5 min of basic life support on a manikin. We compared hands-off time as the primary outcome parameter and the total number of chest compressions as the secondary outcome parameter. RESULTS: Fifty volunteers were enrolled in the study, one individual dropped out after randomization. In Group 2005, hands-off time was significantly lower (mean 107 +/- 19 [SD] s vs. 139 +/- 15 s in Group 2000 (P < 0.0001) and the total number of chest compressions was significantly higher (347 +/- 64 compressions vs. 233 +/- 51 compressions; P < 0.0001). CONCLUSION: In this manikin setting, both hands-off time and the total number of chest compressions improved with basic life support performed according to the ERC guidelines of 2005.


Subject(s)
Algorithms , Cardiopulmonary Resuscitation/standards , Heart Massage/standards , Adult , Austria , Cardiopulmonary Resuscitation/education , Female , Humans , Male , Manikins , Practice Guidelines as Topic , Quality Assurance, Health Care/standards , Red Cross , Time and Motion Studies
20.
Ann Surg ; 247(3): 470-6, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18376192

ABSTRACT

OBJECTIVE: To analyze whether breast-conserving therapy (BCT) may be an oncologically safe approach and result in a good cosmesis in patients with centrally located breast cancer (CLBC). SUMMARY BACKGROUND DATA: Only underpowered, retrospective, single-arm studies have suggested that oncoplastic BCT for CLBC may be oncologically safe and may result in a good cosmesis. METHODS: The authors retrospectively analyzed the overall and recurrence-free survival in 1485 patients with breast cancer undergoing BCT comparing CLBC with non-CLBC. Moreover, the authors described 4 different oncoplastic techniques for BCT in patients with CLBC and compared the cosmetic results with simple lumpectomy according to a recently elaborated objective cosmetic evaluation system, the Breast Symmetry Index. RESULTS: Kaplan-Meier curves show no significant difference in a 5-year overall, local, or distant recurrence-free survival between patients with CLBC and non-CLBC after BCT (94% vs. 96%; 100% vs. 98%; 92% vs. 90%; median follow-up, 35.3 months). The cosmetic outcome after oncoplastic BCT compared with simple lumpectomy differed significantly (Breast Symmetry Index: 22 +/- 6%d vs. 44 +/- 12%d; P < 0.05). CONCLUSIONS: The results demonstrate that BCT for CLBC is oncologically safe and that oncoplastic techniques improve cosmesis.


Subject(s)
Breast Neoplasms/surgery , Mastectomy, Segmental , Breast Neoplasms/mortality , Esthetics , Female , Humans , Retrospective Studies , Survival Rate , Treatment Outcome
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