Two-step versus three-step proctocolectomy for ulcerative colitis: a comparative study on nutritional status, immunosuppressive therapy, and long-term outcome.

BACKGROUND: Despite novel medical therapies, rates of surgery in ulcerative colitis remain relevant. While various surgical approaches for multistep proctocolectomy are available, overall evidence is low and robust recommendations are lacking for individual procedures especially in case of refractory inflammation and signs of malnutrition. METHODS: All patients who received multistep proctocolectomy between 2010 and 2021 for ulcerative colitis were evaluated and divided into two groups (two-step/2-IPAA [ileal pouch-anal anastomosis] versus three-step/3-IPAA proctocolectomy). Patient characteristics as well as short- and long-outcomes were individually analyzed. RESULTS: Surgical techniques were explained in detail. Fifty patients were included in the study with 27 patients receiving 2-IPAA and 23 patients 3-IPAA. Rates of postoperative complications were comparable for both groups. While patients receiving 2-IPAA were more often suffering from malignancy, 3-IPAA resulted in a significant increase of hemoglobin and albumin levels as well as a reduction of immunosuppressive medication. Rates of stoma reversal trended to be reduced for 3-IPAA compared to 2-IPAA (52.2% vs. 77.8%, p = 0.06). CONCLUSION: Three-step proctocolectomy with creation of sigmoidostomy is a safe procedure and reasonable surgical approach in patients with preoperatively high dosages of immunosuppressive medication or risk factors such as persistent active inflammation and anemia.

Community-acquired pneumonia: use of clinical characteristics of acutely admitted patients for the development of a diagnostic model - a cross-sectional multicentre study.

OBJECTIVES: This study aimed to describe the clinical characteristics of adults with suspected acute community-acquired pneumonia (CAP) on hospitalisation, evaluate their prediction performance for CAP and compare the performance of the model to the initial assessment of the physician. DESIGN: Cross-sectional, multicentre study. SETTING: The data originated from the INfectious DisEases in Emergency Departments study and were collected prospectively from patient interviews and medical records. The study included four Danish medical emergency departments (EDs) and was conducted between 1 March 2021 and 28 February 2022. PARTICIPANTS: A total of 954 patients admitted with suspected infection were included in the study. PRIMARY AND SECONDARY OUTCOME: The primary outcome was CAP diagnosis assessed by an expert panel. RESULTS: According to expert evaluation, CAP had a 28% prevalence. 13 diagnostic predictors were identified using least absolute shrinkage and selection operator regression to build the prediction model: dyspnoea, expectoration, cough, common cold, malaise, chest pain, respiratory rate (>20 breaths/min), oxygen saturation (<96%), abnormal chest auscultation, leucocytes (<3.5×109/L or >8.8×109/L) and neutrophils (>7.5×109/L). C reactive protein (<20 mg/L) and having no previous event of CAP contributed negatively to the final model. The predictors yielded good prediction performance for CAP with an area under the receiver-operator characteristic curve (AUC) of 0.85 (CI 0.77 to 0.92). However, the initial diagnosis made by the ED physician performed better, with an AUC of 0.86 (CI 84% to 89%). CONCLUSION: Typical respiratory symptoms combined with abnormal vital signs and elevated infection biomarkers were predictors for CAP on admission to an ED. The clinical value of the prediction model is questionable in our setting as it does not outperform the clinician's assessment. Further studies that add novel diagnostic tools and use imaging or serological markers are needed to improve a model that would help diagnose CAP in an ED setting more accurately. TRIAL REGISTRATION NUMBER: NCT04681963.

Improving diagnostics using extended point-of-care testing during in-home assessments of older adults with signs of emerging acute disease: a prospective observational non-randomised pilot and feasibility study.

BACKGROUND: Delayed recognition of acute disease among older adults hinders timely management and increases the risk of hospital admission. Point-of-Care testing, including Focused Lung Ultrasound (FLUS) and in-home analysis of biological material, may support clinical decision-making in suspected acute respiratory disease. The aim of this study was to pilot test the study design for a planned randomised trial, investigate whether in-home extended use of point-of-care testing is feasible, and explore its' potential clinical impact. METHODS: A non-randomised pilot and feasibility study was conducted during September-November 2021 in Kolding Municipality, Denmark. A FLUS-trained physician accompanied an acute community nurse on home-visits to citizens aged 65 + y with signs of acute respiratory disease. The acute community nurses did a clinical assessment (vital signs, capillary C-reactive protein and haemoglobin) and gave a presumptive diagnosis. Subsequently, the physician performed FLUS, venipuncture with bedside analysis (electrolytes, creatinine, white blood cell differential count), nasopharyngeal swab (PCR for upper respiratory pathogens), and urine samples (flow-cytometry). Primary outcomes were feasibility of study design and extended point-of-care testing; secondary outcome was the potential clinical impact of extended point-of-care testing. RESULTS: One hundred consecutive individuals were included. Average age was 81.6 (SD ± 8.4). Feasibility of study design was acceptable, FLUS 100%, blood-analyses 81%, PCR for upper respiratory pathogens 79%, and urine flow-cytometry 4%. In addition to the acute community nurse's presumptive diagnosis, extended point-of-care testing identified 34 individuals with a condition in need of further evaluation by a physician. CONCLUSION: Overall, in-home assessments with extended point-of-care testing are feasible and may aid to identify and handle acute diseases in older adults.

The Diagnostic Accuracy of Procalcitonin, Soluble Urokinase-Type Plasminogen Activator Receptors, and C-Reactive Protein in Diagnosing Urinary Tract Infections in the Emergency Department-A Diagnostic Accuracy Study.

Background: Urinary tract infections (UTIs) are a leading bacterial infection in the emergency department (ED). Diagnosing UTIs in the ED can be challenging due to the heterogeneous presentation; therefore, fast and precise tests are needed. We aimed to evaluate the diagnostic precision of procalcitonin (PCT), soluble urokinase plasminogen activator receptors (suPARs), and C-reactive protein (CRP) in diagnosing UTIs, grading the severity of UTIs, and ruling out bacteremia. Methods: We recruited adults admitted to three Danish EDs with suspected UTIs. PCT, suPAR, and CRP were used in index tests, while blood cultures, expert panel diagnosis, and severity grading were used in the reference tests. Logistic regression and area under the receiver operator characteristic curves (AUROCs) were utilized to evaluate the models and determine the optimal cut-offs. Results: We enrolled 229 patients. PCT diagnosed UTI with an AUROC of 0.612, detected severe disease with an AUROC of 0.712, and ruled out bacteremia with an AUROC of 0.777. SuPAR had AUROCs of 0.480, 0.638, and 0.605, while CRP had AUROCs of 0.599, 0.778, and 0.646. Conclusions: The diagnostic performance of PCT, suPAR, or CRP for UTIs or to rule out severe disease was poor. However, PCT can safely rule out bacteremia in clinically relevant numbers in ED patients suspected of UTI.

Urine Flow Cytometry and Dipstick Analysis in Diagnosing Bacteriuria and Urinary Tract Infections among Adults in the Emergency Department-A Diagnostic Accuracy Trial.

Urinary tract infections (UTIs) are a leading infectious cause of emergency department admission. Early UTI diagnosis is challenging, and a faster, preferably point-of-care urine analysis is necessary. We aimed to evaluate the diagnostic accuracy of urine flow cytometry (UFC) and urine dipstick analysis (UDA) in identifying bacteriuria and UTIs. This study included adults suspected of an infection admitted to three Danish emergency departments. UFC and UDA were the index tests, and urine culture and an expert panel diagnosis were the reference tests. We used logistic regression and receiver operator characteristics curves to find each test's optimal model and cut-off. We enrolled 966 patients and performed urine cultures on 786. Urine culture was positive in 337, and 200 patients were diagnosed with a UTI. The UFC model ruled out bacteriuria in 10.9% with a negative predictive value (NPV) of 94.6% and ruled out UTI in 38.6% with an NPV of 97.0%. UDA ruled out bacteriuria in 52.1% with an NPV of 79.2% and UTI in 52.8% with an NPV of 93.9%. Neither UFC nor UDA performed well in ruling out bacteriuria in our population. In contrast, both tests ruled out UTI safely and in clinically relevant numbers.

Extended use of point-of-care technology versus usual care for in-home assessment by acute community nurses in older adults with signs of potential acute respiratory disease: an open-label randomised controlled trial protocol.

BACKGROUND: Due to ageing-related physiological changes, diagnosing older adults is challenging. Delayed disease recognition may lead to adverse health outcomes and increased hospitalisation, necessitating the development of new initiatives for timely diagnosis and treatment of older adults. Point-of-care technology, such as focused lung ultrasound scan and bedside analysis of blood samples (leucocytes with differential count, electrolytes, and creatinine) conducted in the patients' home, may support clinical decision-making, and potentially reduce acute hospital admissions. We present the protocol for a randomized controlled trial, which aims at assessing the effect of focused lung ultrasound scan and bedside blood analysis during in-home assessments among older adults with signs of potential acute respiratory disease on hospital admissions. METHOD: We will use a parallel open-label, individually randomised controlled trial design in an acute community healthcare setting. The trial will initiate on October 2022 and is expected to end one year later. The study population will include older adults (65 + year), with at least one of the following inclusion criteria: Cough, dyspnoea, fever, fall, or rapid functional decline. Expected study sample will comprise 632 participants. Participants in the control group will receive usual care, while the intervention group will undergo extended point-of-care technology (focused lung ultrasound scan and bedside venous blood analysis), in addition to usual care. The primary outcome is acute hospital admission within 30 days follow-up. Secondary outcomes include readmissions, mortality, length of hospital stay, hospital-free days, complications during hospital admission, treatment initiations or changes, functional level, re-referrals to the acute community healthcare service, and contacts to the primary care physician. A tertiary outcome is the diagnostic accuracy of Acute Community Nurses for conducting focused lung ultrasound compared with a specialist. Outcomes will be analysed as intention-to-treat. DISCUSSION: To our knowledge, this is the first randomised controlled trial examining the effect of extended use of point-of-care technology conducted in an in-home setting. We expect that the results may contribute to the development of new interventions aiming to improve timely diagnostics, treatment decisions, and reduce acute hospital admissions. TRIAL REGISTRATION: www. CLINICALTRIALS: org NCT05546073 (Date of registration: September 19th, 2022).

Antibiotic Guideline Adherence at the Emergency Department: A Descriptive Study from a Country with a Restrictive Antibiotic Policy.

BACKGROUND: Denmark has a low level of antimicrobial resistance (AMR). Patients hospitalized with suspected infection often present with unspecific symptoms. This challenges the physician between using narrow-spectrum antibiotics in accordance with guidelines or broad-spectrum antibiotics to compensate for diagnostic uncertainty. The aim of this study was to investigate adherence to a restrictive antibiotic guideline for the most common infection in emergency departments (EDs), namely community-acquired pneumonia (CAP). METHOD: This multicenter descriptive cross-sectional study included adults admitted to Danish EDs with a suspected infection. Data were collected prospectively from medical records. RESULTS: We included 954 patients in the analysis. The most prescribed antibiotics were penicillin with beta-lactamase inhibitor at 4 h (307 (32.2%)), 48 h (289 (30.3%)), and day 5 after admission (218 (22.9%)). The empirical antibiotic treatment guidelines for CAP were followed for 126 (31.3%) of the CAP patients. At 4 h, antibiotics were administered intravenously to 244 (60.7%) of the CAP patients. At day 5, 218 (54.4%) received oral antibiotics. CONCLUSION: Adherence to CAP guidelines was poor. In a country with a restrictive antibiotic policy, infections are commonly treated with broad-spectrum antibiotics against recommendations.

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.

Vancomycin-sensitive Enterococcus faecium bacteraemia - hospital transmission and mortality in a Danish University Hospital.

Introduction. The emergence of vancomycin-resistant Enterococcus faecium (VREfm) has left the vancomycin-sensitive E. faecium (VSEfm) strains almost unnoticed.Hypothesis. Molecular characteristics, hospital transmission patterns and clinical impact of VSEfm have changed, and VSEfm is a predictor of VREfm introduction.Aim. We wanted to do a molecular characterization of VSEfm to identify hospital transmissions and links between VSEfm and VREfm, and to investigate the demographics, treatment and impact on mortality of VSEfm bacteraemia.Methodology. VSEfm and VREfm blood culture isolates from Odense University Hospital, Denmark, from 2015 to 2019 were characterized using whole-genome sequencing and core-genome multilocus sequence typing (cgMLST). Clonal shifts and diversity of the VREfm isolates were compared to the VSEfm isolates. Hospital records were used for clinical data and transmission investigation of VSEfm cases.Results. Six-hundred and thirty VSEfm isolates from 599 patients belonged to 42 sequence types (STs) and 131 complex types (CTs) in several clusters. Multiple types were involved in putative transmission, occurring over the entire period. Twenty-seven VREfm bacteraemia cases were included. No correlation between the VSEfm and VREfm clones was identified. The 30 day mortality was 40 %, but only in 6.3 % of the cases, VSEfm bacteraemia was the likely cause of death.Conclusion. The molecular types of VSEfm bacteraemia isolates are changing and diverse. No direct correlation between VSEfm and the introduction of VREfm was found, but widespread hospital transmission indicates a presence of risk factors that could facilitate transmission of other micro-organisms as well. VSEfm bacteraemia is rarely the cause of death, indicating that 30 day mortality does not reflect the cause of death.

Carrier prevalence of Clostridioides difficile in emergency departments and the association of prior antibiotic consumption: a combined cross-sectional and nested case-control study.

INTRODUCTION: Clostridioides difficile infection is an urgent public health threat, and the incidence has been increasing over the last decades. Knowledge of the prevalence of C. difficile in acutely admitted patients and risk factors for colonization with C. difficile assists emergency departments (EDs) in prioritizing preventive initiatives. This national study aimed to describe prevalence and risk factors for C. difficile carriers acutely admitted to EDs, focusing on the impact of earlier antibiotic prescription. METHODS: We conducted a nationwide analytic cross-sectional study with prospective data collection combined with a nested case-control study with retrospective data collection. All adults visiting one of eight Danish EDs were interviewed and examined for C. difficile. Using a national register, we collected the antibiotic history within the 2 years prior to enrolment. The primary outcome was the prevalence of C. difficile colonization, and secondary outcomes were related to risk factors and prior antibiotic prescription. Multivariate analyses examined the association between earlier antibiotic prescription and C. difficile colonization. RESULTS: Of 5019 participants, 89 were colonized with C. difficile (prevalence of 1.8%). A significant and exposure-dependent association was found for penicillins [DDD/person-year(PY) > 20; OR 4.93 (95% CI 2.22-10.97)] and fluoroquinolones [DDD/PY > 20; OR 8.81 (95% CI 2.54-30.55)], but not macrolides. Timing of the prescription did not affect the association. CONCLUSIONS: One out of 55 patients visiting a Danish ED were colonized with C. difficile. Risk factors for colonization included high age, comorbidity and prior prescription of fluoroquinolones and penicillins.

Predictive value of computed tomography on surgical resectability in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: Results from a prospective, multicentre phase 2 trial (NEOLAP-AIO-PAK-0113).

PURPOSE: To assess the role of current imaging-based resectability criteria and the degree of radiological downsizing in locally advanced pancreatic adenocarcinoma (LAPC) after multiagent induction chemotherapy (ICT) in multicentre, open-label, randomized phase 2 trial. METHOD: LAPC patients were prospectively treated with multiagent ICT followed by surgical exploration within the NEOLAP trial. All patients underwent CT scan at baseline and after ICT to assess resectability status according to national comprehensive cancer network guidelines (NCCN) criteria and response evaluation criteria in solid tumors (RECIST) at the local study center and retrospectively in a central review. Imaging results were compared in terms of local and central staging, downsizing and pathological resection status. RESULTS: 83 patients were evaluable for central review of baseline and restaging imaging results. Downstaging by central review was rarely seen after multiagent ICT (7.7%), whereas tumor downsizing was documented frequently (any downsizing 90.4%, downsizing to partial response (PR) according to RECIST: 26.5%). Patients with any downsizing showed no significant different R0 resection rate (37.3%) as patients that fulfilled the criteria of PR (40.9%). The sensitivity of any downsizing for predicting R0 resection was 97% with a negative predictive value (NPV) of 0.88. ROC-analysis revealed that tumor downsizing was a predictor of R0 resection (AUC 0.647, p = 0.028) with a best cut-off value of 22.5% downsizing yielding a sensitivity of 65% and a specificity of 61%. CONCLUSIONS: Imaging-based tumor downsizing and not downstaging can guide the selection of patients with a realistic chance of R0-resection in LAPC after multi-agent ICT.

[Surgical strategies for hereditary colorectal cancer]. / Operative Strategien bei hereditären kolorektalen Karzinomen.

Hereditary colorectal cancer (hCRC) represents a major diagnostic and therapeutic challenge. In addition to the usual diagnostic methods, the family history, histological confirmation and mutation analysis play an important role in identifying the type of hereditary CRC. The diagnosis and classification of hCRC are carried out based on the anamnesis, clinical presentation and histology and the further treatment is determined depending on the underlying type of hCRC. For familial adenomatous polyposis (FAP) coloproctomucosectomy after the end of puberty is always recommended, whereas the treatment recommendations for other forms, such as attenuated FAP (aFAP), MUTYH-associated polyposis (MAP) and hereditary nonpolyposis colon cancer (HNPCC, Lynch syndrome), range from close surveillance and endoscopic control, through segmental resection up to colectomy. Irrespective of the type of hCRC, the treatment regimens necessitate an individualized approach and require close interdisciplinary cooperation. When colorectal resection is performed, minimally invasive procedures should principally be prioritized and some studies could demonstrate a potential benefit of robotic surgery compared to laparoscopy.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Gram Stain and Culture of Sputum Samples Detect Only Few Pathogens in Community-Acquired Lower Respiratory Tract Infections: Secondary Analysis of a Randomized Controlled Trial.

Identification of the bacterial etiology of lower respiratory tract infections (LRTI) is crucial to ensure a narrow-spectrum, targeted antibiotic treatment. However, Gram stain and culture results are often difficult to interpret as they depend strongly on sputum sample quality. We aimed to investigate the diagnostic yield of Gram stain and culture from respiratory samples collected by tracheal suction and expiratory technique from adults admitted with suspected community-acquired LRTI (CA-LRTI). In this secondary analysis of a randomized controlled trial, 177 (62%) samples were collected by tracheal suction, and 108 (38%) by expiratory technique. We detected few pathogenic microorganisms, and regardless of sputum quality, there were no significant differences between the sample types. Common pathogens of CA-LRTI were identified by culture in 19 (7%) samples, with a significant difference between patients with or without prior antibiotic treatment (p = 0.007). The clinical value of sputum Gram stain and culture in CA-LRTI is therefore questionable, especially in patients treated with antibiotics.

In vitro and in vivo immunogenicity assessment of protein aggregate characteristics.

The immunogenicity risk of therapeutic protein aggregates has been extensively investigated over the past decades. While it is established that not all aggregates are equally immunogenic, the specific aggregate characteristics, which are most likely to induce an immune response, remain ambiguous. The aim of this study was to perform comprehensive in vitro and in vivo immunogenicity assessment of human insulin aggregates varying in size, structure and chemical modifications, while keeping other morphological characteristics constant. We found that flexible aggregates with highly altered secondary structure were most immunogenic in all setups, while compact aggregates with native-like structure were found to be immunogenic primarily in vivo. Moreover, sub-visible (1-100 µm) aggregates were found to be more immunogenic than sub-micron (0.1-1 µm) aggregates, while chemical modifications (deamidation, ethylation and covalent dimers) were not found to have any measurable impact on immunogenicity. The findings highlight the importance of utilizing aggregates varying in few characteristics for assessment of immunogenicity risk of specific morphological features and may provide a workflow for reliable particle analysis in biotherapeutics.

Expiratory Technique versus Tracheal Suction to Obtain Good-Quality Sputum from Patients with Suspected Lower Respiratory Tract Infection: A Randomized Controlled Trial.

Microbiological diagnostics of good-quality sputum samples are fundamental for infection control and targeted treatment of lower respiratory tract infections (LRTI). This study aims to compare the expiratory technique and tracheal suction on the quality of sputa from adults acutely hospitalized with suspected LRTI. We performed an open-label, randomized controlled trial. Patients were randomized to sputum sampling by tracheal suction (standard care) or the expiratory technique. The primary outcome was quality of sputum evaluated by microscopy and was analysed in the intention-to-treat population. The secondary outcomes were adverse events and patients experience. In total, 280 patients were assigned to tracheal suction (n = 141, 50.4%) or the expiratory technique (n = 139, 49.6%). Sputum samples were collected from 122 (86.5%) patients with tracheal suction and 67 (48.2%) patients with expiratory technique. Good-quality sputa were obtained more often with tracheal suction than with expiratory technique (odds ratio 1.83 [95% CI 1.05 to 3.19]; p = 0.035). There was no statistical difference in adverse events (IRR 1.21 [95% CI, 0.94 to 1.66]; p = 0.136), but patient experience was better in the expiratory technique group (p < 0.0001). In conclusion, tracheal suction should be considered a routine procedure in emergency departments for patients with suspected LRTI.

[Ileal pouch after restorative coloproctectomy]. / Dünndarmpouch nach restaurativer Proktokolektomie.

The continuous development of pouch surgery has enabled continence-preserving treatment after coloproctectomy. The ileoanal J­pouch is nowadays the standard reconstruction after restorative coloproctectomy with excellent functional long-term results. Taking the relative contraindications and a suitable patient selection into consideration, pouch placement can be indicated not only for ulcerative colitis and familial adenomatous polyposis, but also for patients with nonfistular Crohn's disease. Due to a high treatment density with immunosuppressants, the surgical treatment regimen should be subdivided into a multistage procedure, whereby according to current data a modified two-stage procedure should be favored.

Optimizing laparoscopic training efficacy by 'deconstruction into key steps': a randomized controlled trial with novice medical students.

BACKGROUND: Simulator training is an effective way of acquiring laparoscopic skills but there remains a need to optimize teaching methods to accelerate learning. We evaluated the effect of the mental exercise 'deconstruction into key steps' (DIKS) on the time required to acquire laparoscopic skills. METHODS: A randomized controlled trial with undergraduate medical students was implemented into a structured curricular laparoscopic training course. The intervention group (IG) was trained using the DIKS approach, while the control group (CG) underwent the standard course. Laparoscopic performance of all participants was video-recorded at baseline (t0), after the first session (t1) and after the second session (t2) nine days later. Two double-blinded raters assessed the videos. The Impact of potential covariates on performance (gender, age, prior laparoscopic experience, self-assessed motivation and self-assessed dexterity) was evaluated with a self-report questionnaire. RESULTS: Both the IG (n = 58) and the CG (n = 68) improved their performance after each training session (p < 0.001) but with notable differences between sessions. Whereas the CG significantly improved their performance from t0 -t1 (p < 0.05), DIKS shortened practical exercise time by 58% so that the IG outperformed the CG from t1 -t2, (p < 0.05). High self-assessed motivation and dexterity associated with significantly better performance (p < 0.05). Male participants demonstrated significantly higher overall performance (p < 0.05). CONCLUSION: Mental exercises like DIKS can improve laparoscopic performance and shorten practice times. Given the limited exposure of surgical residents to simulator training, implementation of mental exercises like DIKS is highly recommended. Gender, self-assessed dexterity, and motivation all appreciably influence performance in laparoscopic training.