Are Questionnaires Helpful To Predict Exercise-Induced Bronchoconstriction (EIB) And Exercise-Induced Laryngeal Obstruction (EILO)?

OBJECTIVE: Exercise induced laryngeal obstruction (EILO) is an important differential diagnosis to exercise induced bronchoconstriction (EIB) and diagnosed via continuous laryngoscopy while exercising (CLE). However, availability of CLE is limited to specialized centres. And without CLE EILO is often misdiagnosed as EIB. Therefore it is essential to carefully preselect potential EILO candidates. Aim of this study was to investigate whether two short questionnaires -Asthma Control Test (ACT) and Dyspnea Index (DI) evaluating upper airway-related dyspnea- can differentiate between EIB and EILO. METHODS: Patients with dyspnea while exercising were analysed with an exercise challenge in the cold chamber (ECC) to diagnose EIB in visit 1 (V1), as appropriate a CLE in visit 2 (V2, 4-6 weeks after V1) and ACT and DI in V1 and V2. EIB patients were treated with asthma medication after V1. RESULTS: Complete dataset of 36 subjects were gathered. The ACT showed lower values in V2 in EILO compared to EIB patients. A lack of improvement in ACT in V2 after asthma medication of EIB patients is suspicious for additional EILO diagnosis. The DI showed higher values in V1 in EILO compared to EIB patients. A score≥30 can predict a positive CLE reaction. CONCLUSION: ACT and DI are valuable tools in preselecting CLE candidates to assure timely diagnostic despite limited diagnostic capabilities.

Donor-type red blood cell transfusion to deplete isoagglutinins prior to allogeneic stem cell transplantation from ABO major incompatible bone marrow donors.

ABO incompatibility affects approximately 40% of allogeneic stem cell transplants in Caucasian patient populations. Because bone marrow (BM), the preferred graft from paediatric sibling donors and for non-malignant diseases, has a red blood cell (RBC) content similar to blood, anti-donor isoagglutinins must either be depleted from the recipient or RBCs removed from the graft. To achieve tolerability of unmanipulated BM grafts, we used controlled infusions of donor ABO-type RBC units to deplete isoagglutinins before the transplant. This retrospective study evaluates the outcomes of 52 ABO major incompatible BM transplants performed at our centre between 2007 and 2019. The use of donor-type RBC transfusions was well tolerated. They effectively reduced isoagglutinins levels, typically achieving target titres after one (60%) or two (29%) transfusions. The approach allowed for successful and uneventful infusions of unmanipulated BM which provided timely engraftment. The transplant outcomes were not inferior to those of a matched-pair control group of patients with ABO-identical donors.

Severe bronchial hyperresponsiveness along with house dust mite allergy indicates persistence of asthma in young children.

BACKGROUND: Significant risk factors for persistence of asthma later in life are family history of allergies, early allergic sensitization and bronchial hyperresponsiveness (BHR). The evolution of BHR in young children without allergic sensitization and with house dust mite allergy (HDM) was investigated. METHODS: In this retrospective analysis, electronic charts of 4850 young children with asthma and wheezy bronchitis between 2005 and 2018 were reviewed in order to study all patients ≤6 years with BHR assessed by methacholine provocation tests (MCT) at least once (n = 1175). Patients with more than two follow-up measurements were divided in group 1 (no allergic sensitization; n = 110) and group 2 (HDM allergy; n = 88). Additionally, skin prick test, exhaled nitrite oxide (eNO), and asthma treatment were analyzed. RESULTS: Forty-seven patients of group 1 aged median 4.3 years and 48 patients of group 2 aged median 4.7 years showed initially severe BHR <0.1 mg. At follow-up, patients with HDM were more likely to show persistence of severe BHR than non-sensitized patients (severe BHR group 1: n = 5 (10.6%) vs. group 2: n = 21 (43.8%), p < .001). In addition, 89.4% of group 1 had mild to moderate or no BHR, compared to only 56.2% of group 2. There was a significant difference in eN0 (median group 1: 9 ppb vs. group 2: 26 ppb, p < .001), at last follow-up. Age, sex, and asthma therapy had no effect on BHR. CONCLUSION: In young children without sensitization BHR normalizes, whereas HDM allergy indicates a persistence of asthma beyond infancy.

Aerosol measurement identifies SARS-CoV 2 PCR positive adults compared with healthy controls.

BACKGROUND: SARS-CoV-2 is spread primarily through droplets and aerosols. Exhaled aerosols are generated in the upper airways through shear stress and in the lung periphery by 'reopening of collapsed airways'. Aerosol measuring may detect highly contagious individuals ("super spreaders or super-emitters") and discriminate between SARS-CoV-2 infected and non-infected individuals. This is the first study comparing exhaled aerosols in SARS-CoV-2 infected individuals and healthy controls. DESIGN: A prospective observational cohort study in 288 adults, comprising 64 patients testing positive by SARS CoV-2 PCR before enrollment, and 224 healthy adults testing negative (matched control sample) at the University Hospital Frankfurt, Germany, from February to June 2021. Study objective was to evaluate the concentration of exhaled aerosols during physiologic breathing in SARS-CoV-2 PCR-positive and -negative subjects. Secondary outcome measures included correlation of aerosol concentration to SARS-CoV-2 PCR results, change in aerosol concentration due to confounders, and correlation between clinical symptoms and aerosol. RESULTS: There was a highly significant difference in respiratory aerosol concentrations between SARS-CoV-2 PCR-positive (median 1490.5/L) and -negative subjects (median 252.0/L; p < 0.0001). There were no significant differences due to age, sex, smoking status, or body mass index. ROC analysis showed an AUC of 0.8918. CONCLUSIONS: Measurements of respiratory aerosols were significantly elevated in SARS-CoV-2 positive individuals, which helps to understand the spread and course of respiratory viral infections, as well as the detection of highly infectious individuals.

Methacholine and FeNO Measurement in Patients with Habit Cough.

BACKGROUND: Chronic cough is one of the most common symptoms in childhood. Making a definite diagnosis is a challenge for all pediatricians especially in patients when cough is without an organic cause like in habit cough. PATIENTS AND METHODS: In this retrospective analysis, all electronic outpatient charts of the Division of Allergology and Pneumology, between January 1, 2010 and December 31, 2019 were reviewed in order to study all children with potential habit cough. All children underwent the following diagnostic algorithms, skin prick test (SPT), measurement of fractional exhaled nitric oxide (FeNO), spirometry and methacholine challenge test (MCT). The value of a normal MCT and FeNO measurement for diagnosing habit cough was investigated. RESULTS: The chart review revealed 482 patients with chronic cough>4 weeks. Of these, 99 (20.5%) with suspected habit cough were collected. 13 patients had to be excluded for other diagnosis and a complete data set was available in 55 patients. 33 (60.0%) of 55 patients were SPT negative and 22 (40.0%) had sensitization to common allergens. Five patients had elevated FeNO≥20 ppb and three showed severe bronchial hyperresponsiveness<0.1 mg methacholine, challenging the diagnosis of habit cough. CONCLUSION: A normal FeNO and MCT can help confirm the clinical diagnosis of habit cough. However, in patients with positive MCT and/or elevated FeNO habit cough can be present. Especially in patients with elevated FeNO and severe BHR cough variant asthma and eosinophilic bronchitis have to be ruled out.

Outcome of esophageal atresia: inborn versus outborn patients.

Esophageal atresia (EA) is a rare congenital disease which is usually not of the detected prenatally. Due to the lack of prenatal diagnosis, some newborns with EA are born outside of specialized centers. Nevertheless, centralized care of EA has been proposed, even if a clear volume-outcome association in EA management remains unconfirmed. Furthermore, whether outcomes differ between outborn and inborn patients with EA has not been systematically investigated. Therefore, this single-center, retrospective study aimed to investigate EA management and outcomes with a special focus on inborn versus outborn patients. The following data were extracted from the medical records of infants with EA from 2009 to 2019: EA type, associated anomalies, complications, and long-term outcome. Patients were allocated into inborn and outborn groups. Altogether, 57 patients were included. Five patients were excluded (referral before surgery, loss of data, death before surgery [n = 1], and incorrect diagnosis [diverticulum, n = 1]). Among all patients, the overall survival rate was 96%, with no mortalities among outborn patients. The overall hospitalization period was shorter for outborn patients. The median follow-up durations were 3.8 years and 3.2 years for inborn and outborn patients, respectively. Overall, 15% of patients underwent delayed primary anastomosis (long-gap atresia [n = 4] and other reasons [n = 4]). Early complications included three anastomotic leakages and one post-operative fistula; 28% of patients developed strictures, which required dilatation, and 38% of patients showed relevant gastroesophageal reflux, which required fundoplication, without any differences between the groups. The two groups had comparable low mortality and expected high morbidity with no significant differences in outcome. The outborn group showed nonsignificant trends toward lower morbidity and shorter hospitalization periods, which might be explained by the overall better clinical status.

Evaluating Children and Adolescents with Suspected Exercise Induced Asthma: Real Life Data.

OBJECTIVE: Exercise-induced bronchoconstriction (EIB) occurs frequently in children and adolescents and may be a sign of insufficient asthma control. EIB is often evaluated by respiratory symptoms, spirometry, eNO measurement and methacholine testing (MCT) instead of time consuming exercise test. Aim of this study was to analyse the amount of patients for which an exercise challenge in a cold chamber (ECC) was needed for a clear EIB diagnosis, to characterize EIB phenotypes and the incidence of exercise induced laryngeal obstruction (EILO) in a large cohort of patients with EIB. METHODS: A retrospective analysis was performed in 595 children and adolescents (mean age 12.1 years) with suspected EIB from January 2014 to December 2018. Complete data sets of skin prick test, spirometry, eNO and MCT were available from 336 patients. RESULTS: An ECC to confirm the EIB diagnosis was performed in 125 (37.2%) of patients. Three EIB phenotypes were detected: group 1: EIB without allergic sensitization (n=159); group 2: EIB with other than house dust mite (HDM) sensitization (n=87) and group 3: EIB with HDM sensitization (n=90). MCT and eNO showed significant differences between the subgroups: An eNO>46 ppb and/or a MCT<0.1 mg was found in 23.9% vs. 50.6% vs. 57.8% in group 1-3, respectively. Significantly more patients suffered from EILO in group 1 compared to group 2 and 3 (n=13 vs. n=1). CONCLUSION: EIB without sensitization is as often as EIB with sensitization. In patients without sensitization, EILO has to be considered as a possible cause of symptoms during exercise.

Antibiotic Use in Paediatric Patients Hospitalized with Acute Severe Asthma.

BACKGROUND: Antibiotic use during asthma exacerbations in paediatric patients is not routinely recommended but common practise in out-patient and in-patient settings. Objective of this study was to analyse frequency of antibiotic use during acute severe asthma exacerbations, antibiotic classes utilized and clinical decision-making. METHODS: All in-patient admissions over 10 years in a single German Children's University hospital due to acute severe asthma were included in this retrospective analysis. Age, length of stay, oxygen supplementation, treatment, laboratory parameters and chest x-rays of all patients ranging from 1 to 17 years were analysed. RESULTS: 580 hospital admissions were included in this study. Overall antibiotic use was high but decreased with age (1-5 years 69,6%, 6-11 years 57,6% and 12-17 years 39,7%, p<0.001). Analysis of antibiotic treatment without clear indication showed a consistently lower treatment rate of 28.3%, with macrolides being the most common antibiotic class. Younger age significantly decreased, whereas, increase of CrP value, use of oxygen supplementation and concomitant fever all significantly increased the odds ratio (OR 0.967; 4.366, 2.472 and 2.011 respectively) of receiving antibiotic treatment without clear indication. CONCLUSION: Antibiotic treatment without clear indication during acute severe asthma is common in this German single-centre cohort. Clinical parameters of more severe disease affect clinician's decision to administer antibiotics despite evidence of bacterial infection or improved outcome.

Impulse oscillometry bronchodilator response in preschool children.

BACKGROUND: In preschoolers, performing an acceptable spirometry and measuring bronchodilator response (BDR) is challenging; in this context, impulse oscillometry (IOS) represents a valid alternative. However, more studies on the standardization of BDR for IOS in young children are required. OBJECTIVE: The objective of the study was to identify optimal thresholds to define a positive BDR test with IOS in preschoolers with suspected asthma. METHODS: Children aged 3-6 years with suspected asthma and their lung function investigated with both IOS and spirometry pre- and post-BDR were retrospectively analyzed. The spirometric BDR was defined as positive when the change of FEV1 was ≥12% or ≥200 mL. The oscillometric BDR was defined as positive in case of change of at least -40% in R5, +50% in X5, and -80% in AX. RESULTS: Among 72 patients, 36 (age 5.2 ± 1 years; 64% boys) were selected for the subsequent analysis according to ATS/ERS quality criteria of measurements; specifically, 19 patients did not meet IOS and 36 did not meet spirometry criteria. The spirometric BDR was found positive in seven subjects (19.4%); conversely, a positive oscillometric BDR was identified in four patients (11.1%). No patient presented a positive BDR response with both methods. In IOS, the mean decrease in R5 and AX was 19.9% ± 10% and 44% ± 22.1%, and the mean increase in X5 was 23.3% ± 17.8%, respectively. A decrease in R5 of 25.7% (AUC 0.77, p = .03) and an increase in X5 of 25.7% (AUC 0.75, p = .04) showed the best combination of sensitivity and specificity to detect an increase of FEV1 ≥ 12% and/or ≥200 mL. CONCLUSION: The IOS represents a valid alternative to spirometry to measure BDR in preschool children and should be the gold standard in this age group. We are considering a decrease of 26% in R5 and an increase of 26% in X5 as diagnostic threshold for BDR.

Differences in the Outcome of Colonic Atresia with and without Abdominal Wall Defects.

INTRODUCTION: Colonic atresia (CA) is a very rare disease. Two entities of CA can be differentiated: primary CA and CA with abdominal wall defects (AWD). This study aimed to investigate the differences between these two entities, especially for long-term outcomes. MATERIALS AND METHODS: Data from the major health insurance company (AOK) were analyzed. Sixty-two patients with ICD-10 codes Q42.1-2 and Q42.8-9 (atresia of the colon and rectum) who underwent surgery within 10 days after their first admission between 2007 and 2016 were obtained. RESULTS: Twenty-nine patients had an AWD, and 33 patients had primary colonic atresia (PCA). Significant differences between patients with PCA and AWD were found regarding prematurity but not for other concomitant malformations. Ostomy was the initial therapy of choice for 87.9% (29/33) of patients with PCA and 65.5% (19/29) with AWD. Central venous access was significantly more often in patients with AWD. Overall, patients with CA have an excellent short-term outcome. The 1-year mortality was 3% (1/33) in PCA and 6.9% (2/29) in AWD. Delayed management did not lead to higher mortality. Higher number of admission days and higher hospital costs were related to gastrostomy and short bowel in the long term. CONCLUSION: The long-term outcome of CA is related to short bowel and need for initial gastrostomy but not related to AWD, prematurity, or associated anomalies.

CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany.

Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.

Exhaled Aerosols in SARS-CoV-2 Polymerase Chain Reaction-Positive Children and Age-Matched-Negative Controls.

Background: Children and adolescents seem to be less affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease in terms of severity, especially until the increasing spread of the omicron variant in December 2021. Anatomical structures and lower number of exhaled aerosols may in part explain this phenomenon. In a cohort of healthy and SARS-CoV-2 infected children, we compared exhaled particle counts to gain further insights about the spreading of SARS-CoV-2. Materials and Methods: In this single-center prospective observational trial, a total of 162 children and adolescents (age 6-17 years), of whom 39 were polymerase chain reaction (PCR)-positive for SARS-CoV-2 and 123 PCR-negative, were included. The 39 PCR-positive children were compared to 39 PCR-negative age-matched controls. The data of all PCR-negative children were analyzed to determine baseline exhaled particle counts in children. In addition, medical and clinical history was obtained and spirometry was measured. Results: Baseline exhaled particle counts were low in healthy children. Exhaled particle counts were significantly increased in SARS-CoV-2 PCR-positive children (median 355.0/L; range 81-6955/L), compared to age-matched -negative children (median 157.0/L; range 1-533/L; p < 0.001). Conclusion: SARS-CoV-2 PCR-positive children exhaled significantly higher levels of aerosols than healthy children. Overall children had low levels of exhaled particle counts, possibly indicating that children are not the major driver of the SARS-CoV-2 pandemic. Trial Registration: [ClinicalTrials.gov], Identifier [NCT04739020].

Jejunoileal Atresia: A National Cohort Study.

Purpose: Jejunoileal atresia (JIA) is a rare disease. We aimed to determine the overall incidence of this malformation and associated malformations in a national cohort. Furthermore, we compared the treatment results of this cohort with the current literature. Methods: Data from the major health insurance company, which covers ~30% of the German population, were analyzed. All patients with ICD-10-Code Q41.1-9 (atresia of jejunum, ileum, other parts and not designated parts of the small bowel) who underwent any surgical procedure for small bowel were analyzed in a 10-year period between 2007 and 2016. Results: A total of 435 patients were included in the study. The incidence was 2.1 per 10,000 live births. The male:female ratio was 1:2. Sixty-four percent were premature, 21% had associated cardiac anomalies, 16% had abdominal wall defects, 7% had urogenital malformations, and 7% had cystic fibrosis. Sixty percent of all patients with jejunoileal atresia, 57% of patients with accompanying abdominal wall defects and 72% of patients with associated cystic fibrosis required ostomy as the initial procedure. In 25% of all patients, only one intestinal operation was coded. In 39% of patients, two operations were coded. Twelve percent of all patients required feeding gastrostomy or jejunostomy. Sixteen percent of all patients presented with liver-related complications, i.e., cholestasis or liver insufficiency. Six patients underwent an intestinal lengthening procedure (2 Bianchi, 4 STEP). In five patients, initial lengthening was performed within 1 year after the first intestinal operation. Mortality until 1 year after initial surgery was 5%. Of those who died, 88% were premature, 34% had cardiac anomalies and 16% had abdominal wall defects. None had cystic fibrosis. Patients with ostomy significantly more often needed operative central venous line or operative feeding tube. Short bowel was coded significantly more often in these patients. Conclusion: Patients with JIA present with low mortality. The rate of ostomies is higher than in literature. To give clinical recommendations for the initial surgical approach, further clinical research is needed.

Comparison of perioperative outcomes between laparoscopic and open partial splenectomy in children and adolescents.

BACKGROUND: In order to avoid consequences of total splenectomy, partial splenectomy (PS) is increasingly reported. The purpose of this study was to compare perioperative outcomes of laparoscopic PS (LPS) and open PS (OPS) in children and adolescents. AIM: To compare perioperative outcomes of patients with LPS and OPS. METHODS: After institutional review board approval, a total of 26 patients that underwent LPS or OPS between January 2008 and July 2018 were identified from the database of our tertiary referral center. In total, 10 patients had LPS, and 16 patients underwent OPS. Blood loss was calculated by Mercuriali's formula. Pain scores, analgesic requirements and complications were assessed. The Wilcoxon rank sum test was used for comparison. To compare categorical variables, Fisher's exact test was applied. RESULTS: LPS was performed in 10 patients; 16 patients had OPS. Demographics (except for body mass index and duration of follow-up), indicating primary disease, preoperative spleen size and postoperative spleen volume, perioperative hematological parameters, postoperative pain scores, analgesic requirements, adverse events according to the Clavien-Dindo classification and the comprehensive complication index, median time from operation to initiation of feeds, median time from operation to full feeds, median time from operation to mobilization and median length of hospital stay did not differ between LPS and OPS. Median (range) operative time (min) was longer in LPS compared to the OPS group [185 (135-298) vs 144 (112-270), respectively; P = 0.048]. Calculated perioperative blood loss (mL of red blood cell count) was higher in the LPS group compared to OPS [87 (-45-777) vs -37 (-114-553), respectively; P = 0.039]. CONCLUSION: This is the first study that compared outcomes of LPS and OPS. Both operative approaches had comparable perioperative outcomes. LPS appears to be a viable alternative to OPS.

AlloHSCT in paediatric ALL and AML in complete remission: improvement over time impacted by accreditation?

Allogeneic hematopoietic stem cell transplantation (alloHSCT) has become a well-established treatment option for many patients suffering from malignant and non-malignant diseases. In the past decade, high-resolution HLA-typing, remission surveillance, pre-emptive immune intervention, and standardisation in supportive care measures have substantially improved transplant outcomes. This retrospective study evaluated transplant procedures in 162 paediatric patients with acute lymphoblastic leukaemia (n = 124) or acute myeloid leukaemia (n = 38) who received their first alloHSCT in our institution over an 11-year period. We observed a significant reduction in risk of non-relapse mortality (NRM) over time (HR = 0.34, 95% CI 0.12-0.98; P = 0.05), the 4-year NRM estimate decreased from 20% in 2005-2008 to 7% in 2012-2016 (P = 0.02) and an increase in survival after relapse. There was no significant difference in patients who received a graft from a sibling, haplo, or an unrelated donor with regard to their overall survival (P = 0.45), event-free survival (P = 0.61), and non-relapse mortality (P = 0.19). Our data suggest that a specific transplant infrastructure with a highly experienced team in an accredited transplant centre likely contributes to better transplant outcomes for acute leukaemia patients in complete remission regardless of donor type.

Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation "MSC-FFM"-Outcome Report of 92 Patients.

(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.

Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM).

The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.

Procalcitonin ratio as a predictor of successful surgical treatment of severe necrotizing soft tissue infections.

BACKGROUND: Necrotizing soft tissue infections often are characterized by fulminant presentation and lethal outcomes. Besides critical care support and antibiotic therapy, aggressive surgical treatment is important for the therapy of necrotizing fasciitis. The aim of this study was to develop a procalcitonin (PCT) ratio indicating successful surgical intervention. METHODS: The study group consisted of 38 patients treated with clinical signs of sepsis caused by a necrotizing soft tissue infection. All patients received radical surgical treatment, and serum levels of PCT and C-reactive protein were monitored postoperatively. The ratio of day 1 to day 2 was calculated and correlated with the successful elimination of the infectious source and clinical recovery. RESULTS: An eradication of the infectious focus was successfully performed in 84% of patients, averaging 1.9 operations (range 1 to 6) to achieve an elimination of the infectious source. The PCT ratio was significantly higher in the group of patients with successful surgical intervention (1.665 vs .9, P < .001). A ratio higher than the calculated cutoff of 1.14 indicated successful surgical treatment with a sensitivity of 83.3% and a specificity of 71.4%. The positive predictive value was 75.8%, and the negative predictive value was 80.0%. CONCLUSIONS: The PCT ratio of postoperative day 1 to day 2 following major surgical procedures for necrotizing soft tissue infections represents a valuable clinical tool indicating successful surgical eradication of the infectious focus.

Association between a single-pass whole-body computed tomography policy and survival after blunt major trauma: a retrospective cohort study.

INTRODUCTION: Single-pass, whole-body computed tomography (pan-scan) remains a controversial intervention in the early assessment of patients with major trauma. We hypothesized that a liberal pan-scan policy is mainly an indicator of enhanced process quality of emergency care that may lead to improved survival regardless of the actual use of the method. METHODS: This retrospective cohort study included consecutive patients with blunt trauma referred to a trauma center prior to (2000 to 2002) and after (2002 to 2007) the introduction of a liberal single-pass pan-scan policy. The overall mortality between the two periods was compared and stratified according to the availability and actual use of the pan-scan. Logistic regression analysis was employed to adjust mortality estimates for demographic and injury-related independent variables. RESULTS: The study comprised 313 patients during the pre-pan-scan period, 223 patients after the introduction of the pan-scan policy but not undergoing a pan-scan and 608 patients undergoing a pan-scan. The overall mortality was 23.3, 14.8 and 7.9% (P < 0.001), respectively. By univariable logistic regression analysis, both the availability (odds ratio (OR) 0.57, 95% confidence interval (CI): 0.36 to 0.90) and the actual use of the pan-scan (OR 0.28, 95% CI: 0.19 to 0.42) were associated with a lower mortality. The final model contained the Injury Severity Score, the Glasgow Coma Scale, age, emergency department time and the use of the pan-scan. 2.7% of the explained variance in mortality was attributable to the use of the pan-scan. This contribution increased to 7.1% in the highest injury severity quartile. CONCLUSIONS: In this study, a liberal pan-scan policy was associated with lower trauma mortality. The causal role of the pan-scan itself must be interpreted in the context of improved structural and process quality, is apparently moderate and needs further investigation with regard to the diagnostic yield and changes in management decisions. (The Pan-Scan for Trauma Resuscitation [PATRES] Study Group, ISRCTN35424832 and ISRCTN41462125).