RSV-CLASS -Clinical Assessment Severity Score: An easy-to-use clinical disease severity score for respiratory syncytial virus infection in hospitalized children.

Respiratory syncytial virus (RSV) is the most common cause of acute respiratory tract infection in infants and young children often leading to severe disease requiring hospitalization. However, validated tools for systematic assessment of disease severity are lacking. This study aimed at creating and validating a standardized, simple-to-use disease severity score for RSV infection in children-the RSV-CLASS (Clinical Assessment Severity Score). Therefore, data from over 700 RSV-infected children over six winter seasons (2014-2020) was analyzed using univariate and multiple regression analyses for the prediction of lower respiratory tract infection (LRTI) as a proxy for a severe course of the disease. Testing a broad range of respiratory symptoms, they eventually yielded seven items. Performing stepwise selection, these were reduced to the final four items: cough, tachypnea, rales, and wheezing, each receiving one point in the proposed score named RSV-CLASS. The score was calculated for children in two cohorts A and B, one for development and one for validation, with an area under the curve of 0.90 and 0.87, respectively. With a score value of 3 or 4, 97.8% and 100% of the children, respectively, were admitted with LRTI and classified correctly. The RSV-CLASS is a disease severity score based on a neutral, analytical approach using prospective data from a large study cohort. It will contribute to systematically assessing the disease severity of RSV infection and can be used for evidence-based clinical decision-making as well as for research settings.

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography.

PURPOSE: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. METHODS: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. RESULTS: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. CONCLUSION: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

Mixed reality for the assessment of aortoiliac anatomy in patients with abdominal aortic aneurysm prior to open and endovascular repair: Feasibility and interobserver agreement.

OBJECTIVES: The objective is to evaluate the feasibility and interobserver agreement of a Mixed Reality Viewer (MRV) in the assessment of aortoiliac vascular anatomy of abdominal aortic aneurysm (AAA) patients. METHODS: Fifty preoperative computed tomography angiographies (CTAs) of AAA patients were included. CTAs were assessed in a mixed reality (MR) environment with respect to aortoiliac anatomy according to a standardized protocol by two experienced observers (Mixed Reality Viewer, MRV, Brainlab AG, Germany). Additionally, all CTAs were independently assessed applying the same protocol by the same observers using a conventional DICOM viewer on a two-dimensional screen with multi-planar reconstructions (Conventional viewer, CV, GE Centricity PACS RA1000 Workstation, GE, United States). The protocol included four sets of items: calcification, dilatation, patency, and tortuosity as well as the number of lumbar and renal arteries. Interobserver agreement (IA, Cohen's Kappa, κ) was calculated for every item set. RESULTS: All CTAs could successfully be displayed in the MRV (100%). The MRV demonstrated equal or better IA in the assessment of anterior and posterior calcification (κMRV: 0.68 and 0.61, κCV: 0.33 and 0.45, respectively) as well as tortuosity (κMRV: 0.60, κCV: 0.48) and dilatation (κMRV: 0.68, κCV: 0.67). The CV demonstrated better IA in the assessment of patency (κMRV: 0.74, κCV: 0.93). The CV also identified significantly more lumbar arteries (CV: 379, MRV: 239, p < 0.01). CONCLUSIONS: The MRV is a feasible imaging viewing technology in clinical routine. Future efforts should aim at improving hologram quality and enabling accurate registration of the hologram with the physical patient.

Pilot evaluation of an objective structured assessment of technical skills tool for chest tube insertion.

Background: Chest tube insertion is a standard intervention for management of various injuries of the thorax. Efficient clinical training of this and similar bed-side procedures is equally demanded and improvable. Here, we propose a nouveau means of assessment and feedback using an Objective Structured Assessment of Technical Skills (OSATS) tool. The modified OSATS for chest drain insertion is evaluated in a pilot trial focusing on chest drain insertion. Methods: Participants in the pilot trial were medical students (3rd-6th year of studies, n=9), junior residents (1st-3rd post-graduate year, n=12), senior residents (4th-6th post-graduate year, n=14), and attending surgeons (n=6) from Heidelberg University. Chest drain insertions on a cadaveric porcine model were rated by experts with the modified OSATS score. Participants' performances were videotaped and subsequently rated by two remote experts (video rating). Primary aim was to assess criterion validity of the OSATS to distinguish experience levels. Results: Kruskal-Wallis test showed significant differences between means of scores between four groups stratified by previous experience in chest tube insertion (level 0: 22.1±3.2 vs. level 1: 26.8±2.8 vs. level 2: 35.4±2.2 vs. level 3: 41.0±2.0; p=0.002; p1,3=0.049, p0,3=0.005). However, if groups were stratified by formal professional level, no statistically significant distinction could be made using OSATS. Hence, the OSATS tool showed criterion validity for differentiation between experience levels. Conclusion: In the pilot study, the modified OSATS for chest tube insertion was apt to standardize expert rating and could be used to measure skill and to depict different experience levels. The OSATS will help facilitate training and assessment of chest drain insertion and could therefore improve surgical training for trauma situations. According to our data, the OSATS might be integrated into modern curricula.

Cost-Effectiveness of Carbon Ion Radiation Therapy for Skull Base Chordoma Utilizing Long-Term (10-Year) Outcome Data.

BACKGROUND/AIM: Carbon ion radiotherapy (CIRT) offers high conformality and ability to dose-escalate skull base chordomas, with promising clinical data. However, it is an imperative measure to economically justify the use of such high-priced new technologies. Herein, we investigated the cost-effectiveness of CIRT compared to photon radiotherapy (PRT) using 10-year outcome data extrapolated to a 34-year time frame. MATERIALS AND METHODS: Data regarding costs of PRT, as well as 10-year outcomes were obtained from published sources. Corresponding figures for CIRT were acquired from institutional and published sources. Adjustment was made in order to compare both cost figures, including elimination of additional financing and follow-up, so that only direct costs of treatment and the cost of progression were compared between both modalities. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between both modalities divided by the difference in 34-year quality-adjusted life-year (QALY) outcomes. The annual gross domestic product per capita cost-effectiveness threshold definition (as recommended by the WHO) was employed. RESULTS: The total cost of a complete course of CIRT (20-22 fractions) was €31,538.21. After removal of financing and follow-up costs, the adjusted direct cost of CIRT utilized for comparison was €18,957.78. In a previous publication, the cost of PRT was €4,700.00. ICERs were based upon these direct cost figures and the average of reported 10-year progression-free survival (PFS) values with PRT (41.1%) and CIRT (54%), as well as gained PFS years (10.66 years CIRT, 8.58 years PRT). QALYs were 6.65 for photon RT and 8.26 for CIRT, a difference of 1.61 discounted lifetime QALYs for patients treated with CIRT. The overall ICER was €8,855.76/QALY. If the cost of progression/recurrence treated with imatinib were included into the calculation, the total ICER was €170.61/QALY. CONCLUSION: CIRT is a highly cost-effective option to treat chordoma.

Selective contrast-enhanced computed tomography is appropriate in diffuse large B-cell lymphoma therapy response assessment.

OBJECTIVE: Although not the gold standard, contrast-enhanced CT of neck, thorax, and abdomen/pelvis is routinely performed in diagnosis and response assessment of DLBCL. PD during first-line treatment is a relatively rare event. The question arises if the imaging of initially involved regions only might be sufficient for response evaluation. METHOD: We retrospectively analyzed the data of 167 DLBCL patients who had an extensive contrast-enhanced CT scan at first diagnosis. The majority of patients (n = 128, 77%) was treated with R-CHOP. Therapy response was assessed as interim and end of treatment staging by contrast-enhanced CT. RESULTS: The overall response rate at the end of treatment was 94%. None of the patients showed involvement of new sites at interim staging. As a major finding, none of the patients showed an involvement of sites, which were not initially involved. Four patients developed PD during first-line chemotherapy/after mid-treatment staging and 31 relapsed. A conclusive comparison between initial and PD/relapse DLBCL involvement was possible in 27 patients: 8 patients did and 19 patients did not show additional/new sites of involvement compared to first diagnosis. CONCLUSION: Our retrospective analysis provides a rationale for selective imaging of initially involved DLBCL sites for therapy response assessment.

Assessment of renal function in routine care of people living with HIV on ART in a resource-limited setting in urban Zambia.

INTRODUCTION: Data on renal impairment in sub-Saharan Africa (SSA) remains scarce, determination of renal function is not part of routine assessments. We evaluated renal function and blood pressure in a cohort of people living with HIV (PLWH) on antiretroviral treatment (ART) in the Renal Care Zambia project (ReCaZa). METHODS: Using routine data from an HIV outpatient clinic from 2011-2013, we retrospectively estimated the glomerular filtration rate (eGFR, CKD-Epi formula) of PLWH on ART in Lusaka, Zambia. Data were included if adults had had at least one serum creatinine recorded and had been on ART for a minimum of three months. We investigated the differences in eGFR between ART subgroups with and without tenofovir disproxil fumarate (TDF), and applied multivariable linear models to associate ART and eGFR, adjusted for eGFR before ART initiation. RESULTS AND DISCUSSION: Among 1118 PLWH (63,3% female, mean age 41.8 years, 83% ever on TDF; median duration 1461 [range 98 to 4342] days) on ART, 28.3% had an eGFR <90 ml/min, and 5.5% <60 ml/min at their last measurement. Information on other conditions associated with renal impairment was not systematically documented. Fourteen per cent of the PLWH who later switched to TDF-free ART had an initial eGFR lower 60ml/min. Nineteen percent had first-time hypertensive readings at their last visit. The multivariable models suggest that physicians acted according to guidelines and replaced TDF-containing ART if patients developed moderate/severe renal impairment. CONCLUSIONS: Assessment of renal function in SSA remains a challenge. The vast majority of PLWH benefit from long-term ART, including improved renal function. However, approximately 5% of PLWH on ART may have clinically relevant decreased eGFR, and 27% hypertension. While a routine renal assessment might not be feasible, strategies to identify patients at risk are warranted. Targeted monitoring prior and during ART is recommended, however, should not delay ART access.

Ultrasound vs. MRI in the assessment of rotator cuff structure prior to shoulder arthroplasty.

BACKGROUND/AIMS: We compared the accuracy of US to 3 T Tesla MRI for the detection of rotator cuff and long biceps tendon pathologies before joint replacement. METHODS: 45 patients were prospectively included. RESULTS: For the supraspinatus tendon, the accuracy of US when using MRI as reference was 91.1%. For the infraspinatus tendon, the accuracy with MRI as reference was 84.4%. The subscapularis tendon was consistently assessed by US and MRI in 35/45 patients (accuracy 77.8%). For the long biceps tendon the accuracy was 86.7%. CONCLUSION: US detection of rotator cuff and biceps tendon integrity is comparable to MRI and should be preferred in revision cases.

Rescue stem cell mobilization with plerixafor economizes leukapheresis in patients with multiple myeloma.

While extensive data demonstrated that plerixafor improves stem cell harvest in difficult-to-mobilize patients, economic concerns limit a broader application. We retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ABSCT) and therefore received cyclophosphamide-based mobilization chemotherapy and consecutive stimulation with granulocyte colony-stimulating factor (G-CSF). Fifteen patients with poor stem cell harvest in the first leukapheresis session received plerixafor. Data were compared with a matched historic control group of 45 patients who also had a poor stem cell yield in the first apheresis session, but continued mobilization with G-CSF alone. Patients in the plerixafor group collected significantly more CD34+ cells in total (median 4.9 vs. 3.7 [range 1.6-14.1 vs. 1.1-8.0] × 10(6) CD34+ cells /kg bw; P < 0.05), and also more CD34+ cells per leukapheresis procedure (P < 0.001). Consequently, they required a significantly lower number of leukapheresis procedures to achieve the collection goal (median 2.0 vs. 4.0 [range 2-3 vs. 2-9] procedures; P < 0.001). The efficiency of the collected stem cells in terms of hematologic engraftment after ABSCT was found to be equal in both groups. These data demonstrate that rescue mobilization with plerixafor triggered by a low stem cell yield in the first leukapheresis session is effective. Although the actual economic benefit may vary depending on the local leukapheresis costs, the median saving of two leukapheresis procedures offsets most of the expenses for the substance in this setting. An exemplary cost calculation is provided to illustrate this effect.

Lower risk of decompression sickness after recommendation of conservative decompression practices in divers with and without vascular right-to-left shunt.

INTRODUCTION: A vascular right-to-left shunt (r/l shunt) is a well-known risk factor for the development of decompression sickness (DCS). No studies to date have examined whether divers with a history of DCS with or without a r/l shunt have a reduced risk of suffering recurrent DCS when diving more conservative dive profiles (CDP). METHODS: Twenty-seven divers with a history of DCS recommended previously to dive more conservatively were included in this study and retrospectively interviewed by phone to determine the incidence of DCS recurrence. RESULTS: Twenty-seven divers performed 17,851 dives before examination in our department and 9,236 after recommendations for conservative diving. Mean follow up was 5.3 years (range 0-11 years). Thirty-eight events of DCS occurred in total, 34 before and four after recommendation of CDP. Four divers had a closure of their patent foramen ovale (PFO). A highly significant reduction of DCS risk was observed after recommendation of CDP for the whole group as well as for the sub-groups with or without a r/l shunt. A significant reduction of DCS risk in respect to r/l shunt size was also observed. DISCUSSION: This study indicates that recommendations to reduce nitrogen load after DCS appear to reduce the risk of developing subsequent DCS. This finding is independent of whether the divers have a r/l shunt or of shunt size. The risk of suffering recurrent DCS after recommendation for CDP is less than or equal to an unselected cohort of divers. CONCLUSION: Recommendation for CDP seems to significantly reduce the risk of recurrent DCS.

To whom do the results of the multicenter, randomized, controlled INSECT trial (ISRCTN 24023541) apply?--assessment of external validity.

UNLABELLED: A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582. BACKGROUND: Existing evidence suggests that the transfer of results of randomized controlled trials into clinical practice may be limited. Potential reasons can be attributed to aspects of external validity. The aim of this study is to investigate issues related to the external validity of the INSECT trial. METHODS: All participating surgical departments were categorized and the clinical and baseline characteristics of randomized patients were evaluated. In addition, demographic and clinical data of all screened and randomized patients at the Departments of Surgery in Heidelberg and Erlangen were analyzed. RESULTS: Twenty-five centers enrolled a total of 625 patients. These centers included eight primary, 11 secondary, and six tertiary care centers. The tertiary care centers enrolled the most patients (n = 237, 38%) followed by the primary care centers (n = 199, 32%) and the secondary care centers (n = 189 patients; 30%). The mean number and baseline data of randomized patients did not differ between the three types of care centers (p = 0.09). Overall, the treatment according to protocol was at least 92%. At the Department of Surgery, University of Heidelberg, 307 patients were screened and 60 out of 130 eligible patients were randomized. There were no differences in demographic and clinical baseline data between included and non-included patients. In Erlangen, 351 patients were screened and 57 out of 106 eligible patients randomized. CONCLUSIONS: Results of the INSECT trial are applicable to a broad spectrum of patients treated at different hospital levels.

Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.

Limitations of the MELD score in predicting mortality or need for removal from waiting list in patients awaiting liver transplantation.

BACKGROUND: Decompensated cirrhosis is associated with a poor prognosis and liver transplantation provides the only curative treatment option with excellent long-term results. The relative shortage of organ donors renders the allocation algorithms of organs essential. The optimal strategy based on scoring systems and/or waiting time is still under debate. METHODS: Data sets of 268 consecutive patients listed for single-organ liver transplantation for nonfulminant liver disease between 2003 and 2005 were included into the study. The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores of all patients at the time of listing were used for calculation. The predictive ability not only for mortality on the waiting list but also for the need for withdrawal from the waiting list was calculated for both scores. The Mann-Whitney-U Test was used for the univariate analysis and the AUC-Model for discrimination of the scores. RESULTS: In the univariate analysis comparing patients who are still on the waiting list and patients who died or were removed from the waiting list due to poor conditions, the serum albumin, bilirubin INR, and CTP and MELD scores as well as the presence of ascites and encephalopathy were significantly different between the groups (p < 0.05), whereas serum creatinine and urea showed no difference. Comparing the predictive abilities of CTP and MELD scores, the best discrimination between patients still alive on the waiting list and patients who died on or were removed from the waiting list was achieved at a CTP score of >or=9 and a MELD score of >or=14.4. The sensitivity and specificity to identify mortality or severe deterioration for CTP was 69.0% and 70.5%, respectively; for MELD, it was 62.1% and 72.7%, respectively. This result was supported by the AUC analysis showing a strong trend for superiority of CTP over MELD scores (AUROC 0.73 and 0.68, resp.; p = 0.091). CONCLUSION: The long term prediction of mortality or removal from waiting list in patients awaiting liver transplantation might be better assessed by the CTP score than the MELD score. This might have implications for the development of new improved scoring systems.

The objective severity assessment of atopic dermatitis score: an objective measure using permeability barrier function and stratum corneum hydration with computer-assisted estimates for extent of disease.

OBJECTIVES: Clinical scores used to assess the severity of atopic dermatitis (AD) rely entirely on subjective criteria to evaluate the severity of lesions and the extent of involvement. The aim of this study was to develop an objective measure of AD severity by measuring stratum corneum (SC) functions and by using computer-assisted estimates of involved body surface areas (BSAs). DESIGN: Barrier function of the SC was assessed by measuring transepidermal water loss, and SC hydration was assessed by measuring capacitance. The extent of disease was assessed using a computer-assisted algorithm. PATIENTS: A total of 38 sequential volunteers aged 4 months to 18 years (25 girls, 13 boys) with mild to severe AD at a university outpatient pediatric dermatology clinic. MAIN OUTCOME MEASURES: The computer-assisted method for estimating BSA was compared with estimates using the "rule of nines." The Objective Severity Assessment of Atopic Dermatitis (OSAAD) score, derived from measurements of SC barrier function and SC hydration and normalized for extent of disease was compared with the Scoring Atopic Dermatitis (SCORAD) index. RESULTS: Measurements of epidermal permeability barrier function and SC hydration correlated with clinical estimates of disease severity. The computer-assisted measurements of the extent of disease correlated with estimates derived from the rule of nines. The OSAAD scores correlated with the currently used instrument for AD severity, the SCORAD index. CONCLUSION: The OSAAD is a new AD severity score that avoids the pitfalls of currently used subjective scoring systems by using objective measures.