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Rationale: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity.Objectives: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients.Methods: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 microg/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery.Measurements and Main Results: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients.Conclusions: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients. [ABSTRACT FROM AUTHOR]

Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia., Study Design: Open-label randomized parallel 3-arm design., Settings & Participants: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control., Interventions: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control)., Outcomes: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months., Results: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group ( P  = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group ( P  = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups., Limitations: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements., Conclusions: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group., (© 2024 The Authors.)

Non-ionic surfactants are commonly used in parenteral protein formulations and include polysorbate 20, polysorbate 80 and poloxamer188. Recently, quantification and characterization of surfactants has generated considerable interest due to their connection to visible particle formation, a critical quality attribute for parenteral formulations. Typically, surfactant quantification is performed by mixed mode chromatography with evaporative light scattering detection (ELSD) or charged aerosol detection (CAD). However, these methods often suffer from loss of specificity in highly concentrated protein formulations. Here we present a mixed mode chromatography method using single quad mass detection, overcoming current limitations for highly concentrated proteins. In addition to content determination of intact surfactants, this method allows to quantify and characterize the predominant degradation patterns of polysorbates within a single measurement. Formulations with up to 200 mg/mL active pharmaceutical product (API) containing surfactant levels between 0.16 and 0.64 mg/mL were tested during method qualification. The obtained results for linearity (r > 0.99), precision (max. 3.8 % RSD) and accuracy (96-116 % recovery) meet current requirements for pharmaceutical products as defined in ICH Q2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The Body Composition Monitor (BCM) (Fresenius Medical Care) measures body impedances in alternating currents to subsequently calculate fat and lean tissue mass, fluid compartments, and overhydration (OH). The aim of this study was to investigate differences between two versions of the BCM (an older version, 3.2.5, and a newer version, 3.3.3)., Methods: Between September 2021 and December 2021, 28 hemodialysis patients were included to undergo BCM measurements before each of 14 consecutive dialysis sessions with versions 3.2.5 and 3.3.3 devices. Measurements were performed according to instructions provided by the manufacturer. Differences between BCM devices were tested for statistical significance using paired Wilcoxon tests, neglecting clustering., Results: A total of 288 measurement pairs of 27 patients were left after exclusion of 43 flawed data points. The mean difference in OH between both BCM devices was 0.548 L (higher for version 3.2.5). Analysis of impedance data revealed differences in the high-frequency spectrum, quantifiable by the intracellular resistance, R i (median R i version 3.2.5  = 1750.3 Ω; R i version 3.3.3  = 1612.45 Ω; P < 0.001), and the time delay, T d (median T d version 3.2.5  = 1.85 ns; T d version 3.3.3  = 8.88 nanoseconds; P < 0.001)., Conclusions: This study finds that results between the two versions of the BCM differed in a clinically meaningful fashion and that the newer version 3.3.3 device had a bias toward less OH. Circulating BCM devices should be checked for versions and only devices of the same version should be used for each patient to ensure better within-patient consistency., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Nephrotoxicity is frequent in cisplatin-based chemoradiation of head and neck squamous cell carcinoma (HNSCC). Toxicity outcomes and achieved cisplatin-doses after change of departmental hydration policy are presented., Methods: We performed a retrospective time-series analysis of HNSCC patients undergoing chemoradiation with conventional hydration (CH) between 01/2017 and 09/2018 versus shorter hydration with mannitol (SHM) between 09/2018 and 08/2019 to compare the rate of acute kidney injury (AKI) and cumulative cisplatin dose., Results: Among 113 HNSCC patients, SHM (n = 35) in comparison to CH (n = 78) correlated with less AKI (54.3% vs. 74.4%; p = 0.034) and higher cisplatin doses (82.9% vs. 61.5% ≥200 mg/m 2 ; p = 0.025). AKI ≥grade 2 was lower with SHM (2.9% vs. CH: 22.8%; p = 0.01). AKI occurred more frequently in females (92.6% vs. males: 60.5%, p = 0.002). Females received lower cumulative cisplatin doses (51.9% vs. males: 73.3%; p = 0.037)., Conclusions: We observed less AKI and higher cumulative chemotherapy doses with SHM. Female patients were at higher risk of AKI., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Introduction: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI)., Methods: This retrospective analysis comprised 77 patients who had their dialysate bolus-based absolute blood volume extracted routinely with an automated method. Patient-specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two-group comparisons, and correlation analyses., Findings: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (r s  = -0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (r s  = -0.299, p = 0.008)., Discussion: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus-based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs., (© 2023 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

Extracorporeal lung support includes the risk of hemolysis due to suction pressures. Manufacturers measure the negative suction pressure across drainage cannulas for their products in vitro using water. Clinical experience suggests that hemolysis occurs in vivo already at much lower flow rates. The aim of this study was to analyze the in vivo suction pressure for veno-venous extracorporeal membrane oxygenation (VV-ECMO) cannulas. Prospective, observational study at a tertiary-care intensive care unit: 15 patients on VV-ECMO for severe ARDS were prospectively included. In vitro , the 25 Fr drainage cannula pressure drops below a critical level of around -100 mm Hg at a flow rate of 7.9 L/min, the 23 Fr drainage cannula at 6.6 L/min. In the clinical setting, critical suction pressures were reached at much lower flow rates (5.5 and 4.7 L/min; p < 0.0001, nonlinear regression). The in vitro data largely overestimate the safely achievable flow rates in daily clinical practice by 2.4 L/min (or 44%, 25 Fr) and 1.9 L/min (or 41%, 23 Fr). In vivo measurement of suction pressure of venous drainage cannulas differed significantly from in vitro derived measurements as the latter largely underestimate the resulting suction pressure., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Purpose: Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy., Methods: Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72 Gy, single fraction 1.8-2 Gy) in 572 patients and HF (total dose 62.5-63.75 Gy, single fraction 2.5-2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis., Results: There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001)., Conclusion: For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited., (© 2022. The Author(s).)

Importance: Fewer than 50% of kidney transplant recipients (KTRs) develop antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine. Preliminary data suggest that a heterologous vaccination, combining mRNA and viral vector vaccines, may increase immunogenicity., Objective: To assess the effectiveness of a third dose of an mRNA vs a vector vaccine in KTRs who did not have antibodies against the SARS-CoV-2 spike protein after 2 doses of an mRNA vaccine., Design, Setting, and Participants: This was a single center, single-blinded, 1:1 randomized clinical trial of a third dose of vaccine against SARS-CoV-2, conducted from June 15 to August 16, 2021, in 201 KTRs who had not developed SARS-CoV-2 spike protein antibodies after 2 doses of an mRNA vaccine. Data analyses were performed from August 17 to August 31, 2021., Interventions: mRNA (BNT162b2 or mRNA-1273) or vector (Ad26COVS1) as a third dose of a SARS-CoV-2 vaccine., Main Outcomes and Measures: The primary study end point was seroconversion after 4 weeks (29-42 days) following the third vaccine dose. Secondary end points included neutralizing antibodies and T-cell response assessed by interferon-γ release assays (IGRA). In addition, the association of patient characteristics and vaccine response was assessed using logistic regression, and the reactogenicity of the vaccines was compared., Results: Among the study population of 197 kidney transplant recipients (mean [SD] age, 61.2 [12.4] years; 82 [42%] women), 39% developed SARS-CoV-2 antibodies after the third vaccine. There was no statistically significant difference between groups, with an antibody response rate of 35% and 42% for the mRNA and vector vaccines, respectively. Only 22% of seroconverted patients had neutralizing antibodies. Similarly, T-cell response assessed by IGRA was low with only 17 patients showing a positive response after the third vaccination. Receiving nontriple immunosuppression (odds ratio [OR], 3.59; 95% CI, 1.33-10.75), longer time after kidney transplant (OR, 1.44; 95% CI, 1.15-1.83, per doubling of years), and torque teno virus plasma levels (OR, 0.92; 95% CI, 0.88-0.96, per doubling of levels) were associated with vaccine response. The third dose of an mRNA vaccine was associated with a higher frequency of local pain at the injection site compared with the vector vaccine, while systemic symptoms were comparable between groups., Conclusions and Relevance: This randomized clinical trial found that 39% of KTRs without an immune response against SARS-CoV-2 after 2 doses of an mRNA vaccine developed antibodies against the SARS-CoV-2 spike protein 4 weeks after a third dose of an mRNA or a vector vaccine. The heterologous vaccination strategy with a vector-based vaccine was well tolerated and safe but not significantly better than the homologous mRNA-based strategy., Trial Registration: EudraCT Identifier: 2021-002927-39.

Purpose: This study's objective was the comparison of external beam radiotherapy (EBRT) and I‑125 seed brachytherapy regarding clinical outcome and development of side effects., Patients and Methods: In all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seed brachytherapy or EBRT with a dose of 74 or 78 Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed., Results: Patients were followed up yearly with a median follow-up of 54 (3-192) months. Observed bNED rates for 74 Gy, 78 Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74 Gy (p = 0.81) and 78 Gy (p = 0.19), as well as between 74 and 78 Gy (p = 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥ 2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥ 2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time., Conclusion: Favorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78 Gy) or permanent interstitial seed brachytherapy., (© 2021. The Author(s).)

Purpose: The goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects., Patients and Methods: 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds., Results: Patients were followed up yearly with a median follow-up of 70 (3-192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time., Conclusion: Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.

Lipocalin-2 (LCN2) is an immunomodulatory protein holding major metabolic and immune functions. It is involved in several inflammatory processes and induced by cytokines of the interleukin-1 family known as contributors to the morbidity in graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). The possible role of LCN2 in predicting outcome and course of illness has never been elucidated in patients undergoing HSCT for hematologic malignancies. We conducted a prospective cohort study including 40 patients following autologous or allogeneic HSCT by collecting plasma samples at seven time points with respect to GVHD, relapse, and outcome. LCN2 levels were significantly increased in acute patients with GVHD compared with autologous and healthy controls (125.7 ng/mL vs. 65.9 and 71.4 ng/mL) and correlated with its severity. Similarly, LCN2 levels were significantly elevated in chronic GHVD compared with autologous and healthy controls (295.0 ng/mL vs. 54.9 and 76.5 ng/mL). Moreover, LCN2 correlated with mortality. The suspected role of LCN2 as a predictive parameter for outcome and prognosis needs to be further investigated., (Copyright © 2019. Published by Elsevier Inc.)

Background: The aim of this clinical investigation was to determine the outcomes of an outpatient videoendoscopic diode laser polypectomy (DLPE) and subsequent topical high-dose corticosteroid application in chronic rhinosinusitis with recurrent nasal polyposis (NP)., Methods: After ineffective revision sinus surgery and prolonged mometasone furoate application, 19 consecutive mild and moderate NP patients suffering from nasal obstruction (NO) and olfactory dysfunction (OD) were prospectively entered into the study to undergo DLPE under topical anesthesia. Beginning 1 week postoperatively, 250 microg of beclomethasone dipropionate aerosol spray (BDPAS) was self-administered into each nostril twice a day. Treatment efficacy was assessed after 1, 6, and 12 weeks and at quarterly long-term follow-ups based on objective parameters (videoendoscopic photodocumentation and rhinomanometry) and subjective evaluation of NO, OD, and satisfaction (visual analog scales [VASs])., Results: VASs indicated very low values for intraoperative pain and discomfort and high postoperative satisfaction. After 6 weeks, subjective and objective data revealed a significant improvement of NO and OD (p < 0.0005). Topical BDPAS application was well tolerated. At a median follow-up of 32 months (range, 1-4 years), 21% of the patients developed NP disappearance, 53% had a stable disease, and 26% had a progressive disease., Conclusion: In therapy-refractory NP, endonasal DLPE represents a minimally invasive, symptom-oriented, safe and easily reapplicable outpatient treatment option that provides effective improvement of NO and OD. Compared with the pre-DLPE period, the proposed long-term quarterly follow-up combined with high-dose topical BDPAS application might reduce or delay the need for major surgery and appears to be suitable for disease control.

Purpose: Pilot study to evaluate a new ultrasound (US) technique for differentiating parotid cystadenolymphoma (CL) from pleomorphic adenoma (PA)., Materials and Methods: 27 patients presenting with a palpable lesion of the parotid gland were examined by B-mode US. All patients underwent US examination with administration of 2.4 ml US contrast medium (USCM). The intratumoral time-to-peak was determined. The contrast medium inflow curves from the tumor and parotid parenchyma were compared by using AUC analysis and compared with histology., Results: Histology demonstrated cystadenolymphoma in 9 cases (CL group) and pleomorphic adenoma in 9 (PA group). The intratumoral time-to-peak in the PA group was markedly longer than in the CL group (26.8 +/- 11.1 sec versus 22.6 +/- 5.1 sec, p < 0.05). AUC analysis for the tumor area demonstrated a significant difference between the PA group (30.3 +/- 24.3 dB/area) and the CL group (77.4 +/- 45.6 dB/area, p < 0.05)., Conclusion: The standardized analysis of USCM inflow curves has the potential to differentiate cystadenolymphoma and pleomorphic adenoma. More patient numbers, perhaps with blinded readers, would allow reliable diagnostic determination for future studies.

Background: The larynx bypass (LB) is the only device capable of providing laryngectomy patients with the ability to smell. Our findings regarding one-time and long-term use did reveal an improved olfactory function in these patients. Because the LB is difficult to use, however, it is not appropriate for everyday use. Therefore, we devised a new instrument: the scent-diffusing ventilator (SV)., Methods: Between January 2006 and February 2007, we researched the olfactory function of 16 patients who had undergone a laryngectomy (13 men/3 women; median age, 63 years) by using the LB and the SV. Their olfactory function was measured with the Sniffin' Sticks test battery. Further practicability of both methods was determined through a visual analog scale (1-10)., Results: The patients' olfactory function significantly improved (SV median 8 versus LB median 7; p < 0.002). In addition, the SV was much easier to use than the LB (median, 6 versus 5; p < 0.001)., Conclusion: Further technical improvements are necessary to make the SV an established part of the rehabilitation of the olfactory function after laryngectomy.

Patients who undergo laryngectomy typically lose their sense of smell. One device that has been used to rehabilitate olfactory function in these patients is the larynx bypass. We conducted a long-term study of the larynx bypass in 16 laryngectomized patients. After undergoing objective and subjective baseline evaluations, patients were asked to use the device at home for at least 30 minutes each day for 3 months. They were also asked to record in a diary subjective ratings of their sense of smell and the practicability of using the device every day. At study's end, patients experienced a statistically significant improvement (p < 0.001) in olfactory function on objective measurement (Sniffin' Sticks testing). Subjective improvement was seen after 1 week (p < 0.001) and maintained throughout the study. Practicability scores improved statistically (p = 0.003), but the device remained difficult to use. The long-term use of the larynx bypass has not been studied previously, and we hope that our findings will serve as a basis for further investigation.

Purpose: There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble., Methods: Fourteen patients with different tumour entities were enrolled. A mixture of (99m)Tc-nanocolloid and a dissolved superparamagnetic iron oxide was injected interstitially. Dynamic, sequential static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan data sets were fused and evaluated with special regard to the topographical location of SLNs. The day after injection, nine patients underwent SLN biopsy and, in the presence of SLN metastasis, an elective lymph node dissection., Results: Twenty-five SLNs were localised in the 14 patients examined. A 100% fusion correlation was achieved in all patients. The anatomical sites of SLNs detected during surgery showed 100% agreement with those localised on the multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom had nodal metastasis., Conclusion: Our novel approach of multimodal fusion imaging for targeted SLN management in primary tumours with lymphatic drainage to anatomically difficult regions enables SLN biopsy even in patients with lymphatic drainage to obscure regions. Currently, we are testing its validity in larger patient groups and other tumour entities.

Background: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excessive intra-alveolar accumulation of surfactant lipids and proteins. Therapeutic whole lung lavages are currently the principle therapeutic option in adults. Not much is known on the kinetics of the wash out process, especially in children., Methods: In 4 pediatric and 6 adult PAP patients 45 therapeutic half lung lavages were investigated retrospectively. Total protein, protein concentration and, in one child with a surfactant protein C mutation, aberrant pro-SP-C protein, were determined during wash out., Results: The removal of protein from the lungs followed an exponential decline and averaged for adult patients 2-20 g and <0.5 to 6 g for pediatric patients. The average protein concentration of consecutive portions was the same in all patient groups, however was elevated in pediatric patients when expressed per body weight. The amount of an aberrant pro-SP-C protein, which was present in one patient with a SP-C mutation, constantly decreased with ongoing lavage. Measuring the optical density of the lavage fluid obtained allowed to monitor the wash out process during the lavages at the bedside and to determine the termination of the lavage procedure at normal protein concentration., Conclusion: Following therapeutic half lung lavages by biochemical variables may help to estimate the degree of alveolar filling with proteinaceous material and to improve the efficiency of the wash out, especially in children.

In the present study, one- and two-dimensional gel electrophoresis combined with high resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) have been applied as powerful approaches for the proteome analysis of surfactant proteins SP-A and SP-D, including identification of structurally modified and truncation forms, in bronchoalveolar lavage fluid from patients with cystic fibrosis, chronic bronchitis and pulmonary alveolar proteinosis. Highly sensitive micropreparation techniques were developed for matrix-assisted laser desorption/ionization (MALDI) FT-ICR MS analysis which provided the identification of surfactant proteins at very low levels. Owing to the high resolution, FT-ICR MS was found to provide substantial advantages for the structural identification of surfactant proteins from complex biological matrices with high mass determination accuracy. Several protein bands corresponding to SP-A and SP-D were identified by MALDI-FT-ICR MS after electrophoretic separation by one- and two-dimensional gel electrophoresis, and provided the identification of structural modifications (hydroxy-proline) and degradation products. The high resolution mass spectrometric proteome analysis should facilitate the unequivocal identification of subunits, aggregations, modifications and degradation products of surfactant proteins and hence contribute to the understanding of the mechanistic basis of lung disease pathogenesis.

Background: OMFT are nearly always benign, usually presented in soft tissue, of uncertain origin and tend to relapse. They are regarded as neoplasms of the adult, only three cases of children have been reported so far., Patient: A case of a 12-year-old boy is presented, for the first time, with an OMFT in the nasal cavity and the paranasal sinus. The diameter measured 9 centimetres. Histologically the tumor consisted of a myxoid matrix and showed areas of metaplastic bone. Most of the cells showed a spindleform and sometimes polymorphic hyperchromatic nuclei. The tumor expressed S-100 protein and vimentin. The cellularity was moderately high, the mitotic rate was very low., Conclusions: OMFT are rare neoplasms, the diagnosis should be verified histopathologically. Complete excision should be performed. A clinical follow-up is necessary.