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.

Persisting Type 2 Endoleaks Following EVAR for AAA Are Associated With AAA Expansion.

PURPOSE: To determine the evolution of abdominal aortic aneurysm (AAA) diameter in the presence of persisting type 2 endoleaks (pEL2) following endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: This is a retrospective, single-center, case-control study. All patients with pEL2 (pEL2 group, persisting for > 12 months) between 2004 and 2018 were identified and compared with a 1:1 age- and gender-matched control with no endoleak (control group). Primary outcome measures were freedom from AAA expansion and freedom from AAA shrinkage over time. AAA diameter measurements were performed on computed tomography angiography (CTA). Secondary outcome measures were survival, AAA-related mortality, reinterventions for pEL2, incidence of secondary type 1 endoleaks (EL1), and infrarenal aortic branch vessel anatomy. RESULTS: A total of 773 patients were treated with EVAR for AAA between 2004 and 2018. Of them, 286 patients demonstrated type 2 endoleaks (EL2) in postoperative CTA or intraoperative angiography (37%). Forty-five of 286 EL2 (15.7%) were pEL2 (pEL2 group). Freedom from AAA expansion in the pEL2 group was 100%, 96.7%, 85.2%, and 54.3% after 1, 2, 3, and 4 years, respectively, compared with 100% after 1, 2, 3, and 4 years in the control group (p<0.01). Freedom from AAA shrinkage in the pEL2 group after 1, 2, 3, and 4 years was 95.5%, 90.4%, 90.4%, and 79.1%, respectively, compared with 86.7%, 34.8%, 19.3%, and 19.3% in the control group (p<0.01). Overall survival at 1, 2, 3, and 4 years was 100%, 97.6%, 95.0% and 95.0% in the pEL2 group and 100% at 1, 2, 3, and 4 years in the control group (p=0.17). There were no AAA-related deaths in either group. Patients with pEL2 had a significantly increased number of infrarenal aortic branches (p<0.05, respectively). Eighteen patients (40.0%) in the pEL2 group underwent 34 reinterventions for pEL2, with a median follow-up (FU) of 925 days (0-4173). Clinical success was achieved in 9 patients (50.0%). Four patients (8.9%) with pEL2 developed secondary EL1 after a median FU of 1278 days (662-2121). CONCLUSION: pEL2 are associated with AAA expansion during midterm FU. Further studies are warranted to evaluate the association of AAA expansion due to pEL2 with clinical outcomes to allow recommendations with regard to treatment indications.

Effect of Clomethiazole Vs. Clorazepate on Hepatic Fat and Serum Transaminase Activities in Alcohol-Associated Liver Disease: Results from a Randomized, Controlled Phase II Clinical Trial.

AIMS: Alcohol-associated liver disease (ALD) is a global health problem caused, among other factors, by oxidative stress from the formation of reactive oxygen species (ROS). One important source of ROS is microsomal ethanol metabolism catalyzed by cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption. Inhibition of CYP2E1 by clomethiazole (CMZ) decreases oxidative stress in cell cultures and improves ALD in animal studies. Our study aimed to assess the benefits of a CYP2E1 inhibitor (clomethiazole) in detoxification of patients with ALD. METHODS: Open label, randomized controlled clinical trial to study whether CYP2E1 inhibition improves ALD in the patients with alcohol use disorders admitted for alcohol detoxification therapy (ADT). Patients had to have a serum aspartate aminotransferase (AST) activity exceeding twice the upper normal limit at time of admission and be non-cirrhotic defined by fibroscan value <12 kPa. Sixty patients were randomly assigned to ADT with either CMZ or clorazepate (CZP) for 7-10 days in a 1:1 ratio. The chlorzoxazone test of CYP2E1 activity was performed at enrolment and at 2 points during the study. RESULTS: ADT improved hepatic steatosis (controlled attenuation parameter) in both groups significantly. A trend towards a greater improvement in hepatic fat content during ADT (-21.5%) was observed in the CMZ group (252 ± 48 dB/m vs. 321 ± 38 dB/m; P < 0.0001) compared with the CZP group (-13.9%; 273 ± 38 dB/m vs. 317 ± 39 dB/m; P < 0.0001). As already reported, serum AST (P < 0.004) and alanine aminotransferase (ALT) activities (P < 0.0006) significantly decreased in CMZ patients as compared with patients on CZP by the end of hospitalization. A significant correlation was found between AST (P = 0.023), ALT (P = 0.009), GGT (P = 0.039) and CAP. CONCLUSION: This study demonstrates that CMZ improves clinical biomarkers for ALD in humans most likely due to its inhibitory effect on CYP2E1. Because of its addictive potential, CMZ can only be given for a short period of time and therefore other CYP2E1 inhibitors to treat ALD are needed.

Perioperative chemotherapy with 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) for esophagogastric adenocarcinoma: ten years real-life experience from a surgical perspective.

PURPOSE: According to the results of FLOT4 trial, perioperative FLOT chemotherapy improved overall survival (OS) in locally advanced, resectable esophagogastric adenocarcinoma (EGA) compared to perioperative ECF/ECX. We report real-life data 10 years after introduction of perioperative FLOT at our institution. METHODS: Survival of 356 consecutive EGA patients (cT3/4 and/or cN + and/or cM1) who underwent curative surgical resection was retrospectively analysed from a prospective database. A total of 263 patients received preoperative chemotherapy according to FLOT protocol and 93 patients received an epirubicin/platinum/5FU-based regimen (EPF). Propensity score matching (PSM) according to pretretment characteristics was performed to compensate for heterogeneity between groups. RESULTS: Median OS did not differ between groups (FLOT/EPF 52.1/46.4 months, p = 0.577). After PSM, survival was non-significantly improved after FLOT compared to EPF (median OS not reached/46.4 months, p = 0.156). Perioperative morbidity and mortality did not differ between groups. Histopathologic response rate was 35% after FLOT and 26% after EPF (p = 0.169). R0 resection could be achieved more frequently after FLOT than after EPF (93%/79%, p = 0.023). CONCLUSION: Overall survival after perioperative FLOT followed by surgery is comparable to clinical trials. However, collective real-life application of FLOT failed to provide a significant survival benefit compared to EPF. In clinical reality, patient selection is triggered by age, comorbidity, tumor localization, and clinical tumor stage. Yet matched analyses support FLOT4 trial findings.

How is hip anatomy reconstruction and inlay wear associated up to 10 years after primary THA using ceramic on highly crosslinked polyethylene bearings?

INTRODUCTION: Conventional polyethylene (PE) wear has been reported to be associated with femoral offset reconstruction and cup orientation after THA. Thus, the present study aimed (1) to determine the polyethylene wear rate of 32 mm ceramic heads with highly cross-linked polyethylene (HXLPE) inlays up to 10 years postoperatively and (2) to identify patient and surgery-related factors affecting the wear rate. METHODS: A prospective cohort study was performed, investigating 101 patients with 101 cementless THAs and ceramic (32 mm) on HXLPE bearings after 6-24 months, 2-5 years and 5-10 years postoperatively. The linear wear rate was determined using a validated software (PolyWare®, Rev 8, Draftware Inc, North Webster, IN, USA) by two reviewers, blinded to each other. A linear regression model was used to identify patient and surgery-related factors on HXLPE -wear. RESULTS: After an initial bedding-in phase of 1 year after surgery, the mean linear wear rate was 0.059 ± 0.031 mm/y at ten years (mean 7.7 years; SD 0.6 years, range 6-10), being below the osteolysis relevant threshold of 0.1 mm/year. The regression analysis demonstrated that age at surgery, BMI, cup inclination or anteversion and the UCLA score were not associated with the linear HXLPE-wear rate. Only increased femoral offset showed a significant correlation with an increased HXLPE-wear rate (correlation coefficient of 0.303; p = 0.003) with a moderate clinical effect size (Cohen's f²=0.11). CONCLUSION: In contrast to conventional PE inlays, hip arthroplasty surgeons may be less concerned about osteolysis-related wear of the HXLPE if the femoral offset is slightly increased. This allows focusing on joint anatomy reconstruction, hip stability and leg length.

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.

Patient- and cycle-specific factors affecting the outcome of frozen-thawed embryo transfers.

PURPOSE: This study attempted at identifying the main parameters influencing the outcome of frozen embryo transfers. METHODS: This is a single-center retrospective cohort study of 830 frozen-embryo-transfer cycles performed at a German university hospital from January 2012 to December 2016. Main outcome parameters were the clinical pregnancy and live birth rate. Twelve patient- and cycle-dependent factors were analyzed in terms of their influence on the outcome of frozen embryo transfers. Multivariate logistic regression analysis was used for the modelling of the dependency of the different parameters on outcomes. RESULTS: The clinical pregnancy rate in our study was 25.5%, the live birth rate was 16.1% with an average maternal age of 34.2 years at the time of the oocyte retrieval. In the univariate analysis age, number of transferred embryos, blastocyst versus cleavage stage transfer, embryo quality and mode of endometrial preparation affected the birth rate significantly. The birth rate after artificial endometrial preparation was significantly lower than the birth rate after transfers in modified natural cycles (12.8 versus 20.6% with p = 0.031). The multivariate logistic regression analysis showed a significant independent influence of age, number of transferred embryos, culture duration and mode of endometrial preparation on the frozen embryo transfer success rates. Body mass index, nicotine abuse, a history of PCO syndrome or endometriosis and the co-transfer of a second poor-quality embryo to a good-quality embryo appeared to be irrelevant for the outcome in our collective. CONCLUSION: Age, number of transferred embryos, embryo culture duration and the mode of endometrial preparation are independent predictive factors of frozen embryo transfer outcomes.

The Potential of Shear Wave Elastography to Reduce Unnecessary Biopsies in Breast Cancer Diagnosis: An International, Diagnostic, Multicenter Trial.

PURPOSE: In this prospective, multicenter trial we evaluated whether additional shear wave elastography (SWE) for patients with BI-RADS 3 or 4 lesions on breast ultrasound could further refine the assessment with B-mode breast ultrasound for breast cancer diagnosis. MATERIALS AND METHODS: We analyzed prospective, multicenter, international data from 1288 women with breast lesions rated by conventional 2 D B-mode ultrasound as BI-RADS 3 to 4c and undergoing 2D-SWE. After reclassification with SWE the proportion of undetected malignancies should be < 2 %. All patients underwent histopathologic evaluation (reference standard). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 lesions (28.6 %). The assessment with B-mode breast ultrasound resulted in 1.39 % (6 of 431) undetected malignancies (malignant lesions in BI-RADS 3) and 53.80 % (495 of 920) unnecessary biopsies (biopsies in benign lesions). Re-classifying BI-RADS 4a patients with a SWE cutoff of 2.55 m/s resulted in 1.98 % (11 of 556) undetected malignancies and a reduction of 24.24 % (375 vs. 495) of unnecessary biopsies. CONCLUSION: A SWE value below 2.55 m/s for BI-RADS 4a lesions could be used to downstage these lesions to follow-up, and therefore reduce the number of unnecessary biopsies by 24.24 %. However, this would come at the expense of some additionally missed cancers compared to B-mode breast ultrasound (rate of undetected malignancies 1.98 %, 11 of 556, versus 1.39 %, 6 of 431) which would, however, still be in line with the ACR BI-RADS 3 definition (< 2 % of undetected malignancies).

Complications and revisions in anatomic and reverse short stem shoulder arthroplasty.

INTRODUCTION: One current trend in the field of shoulder arthroplasty is a design shift to shorter and metaphyseal fixed humeral stem components. The aim of this investigation is to analyze complications resulting in revision surgery after anatomic (ASA) and reverse (RSA) short stem arthroplasty. We hypothesize that complications are influenced by the type of prosthesis and indication for arthroplasty. MATERIALS AND METHODS: A total of 279 short stem shoulder prostheses were implanted by the same surgeon (162 ASA; 117 RSA), and 223 of these prostheses were implanted as primary procedures; in 54 cases, arthroplasty was performed secondary to prior open surgery. Main indications were osteoarthritis (OA) (n = 134), cuff tear arthropathy (CTA) (n = 74) and posttraumatic deformities (PTr) (n = 59). Patients were evaluated at 6 weeks (follow-up 1; FU1), 2 years (FU2) and the time span of the last follow-up defined as FU3 with a minimum FU of 2 years. Complications were categorized into early complications (within FU1), intermediate complications (within FU2) and late complications (> 2 years; FU3). RESULTS: In total, 268 prostheses (96.1%) were available for FU1; 267 prostheses (95.7%) were available for FU2 and 218 prostheses (77.8%) were available for FU3. The average time for FU3 was 53.0 months (range 24-95). A complication leading to revision occurred in 21 prostheses (7.8%), 6 (3.7%) in the ASA group and 15 (12.7%) in the RSA group (p < 0.005). The most frequent cause for revision was infection (n = 9; 42.9%). After primary implantation, 3 complications (2.2%) occurred in the ASA and 10 complications (11.0%) in the RSA group (p < 0.005). The complication rate was 2.2% in patients with OA, 13.5% in CTA and 11.9% in PTr. CONCLUSIONS: Primary reverse shoulder arthroplasty had a significantly higher rate of complications and revisions than primary and secondary anatomic shoulder arthroplasty, respectively. Therefore, indications for reverse shoulder arthroplasty should be critically questioned in each individual case.

Does conventional specimen radiography after neoadjuvant chemotherapy of breast cancer help to reduce the rate of second surgeries?

PURPOSE: This is the first study to systematically evaluate the diagnostic accuracy of intraoperative specimen radiography on margin level and its potential to reduce second surgeries in patients treated with neoadjuvant chemotherapy. METHODS: This retrospective study included 174 cases receiving breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. Conventional specimen radiography (CSR) was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 1044 margins were assessed. Of 47 (4.5%) histopathological positive margins, CSR identified 9 correctly (true positive). 38 infiltrated margins were missed (false negative). This resulted in a sensitivity of 19.2%, a specificity of 89.2%, a positive predictive value (PPV) of 7.7%, and a negative predictive value (NPV) of 95.9%. The rate of secondary procedures was reduced from 23 to 16 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 25. In the subgroup of patients with cCR, the prevalence of positive margins was 10/510 (2.0%), PPV was 1.9%, and the NNT was 85. CONCLUSION: Positive margins after NACT are rare and CSR has only a low sensitivity to detect them. Thus, the rate of secondary surgeries cannot be significantly reduced by recommending targeted re-excisions, especially in cases with cCR. In summary, CSR after NACT is inadequate for intraoperative margin assessment but remains useful to document removal of the biopsy site clip.

Changes in serum omega fatty acids on a Mediterranean diet intervention in patients with gingivitis: An exploratory study.

BACKGROUND: Omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) are precursors of pro- and anti-inflammatory lipid mediators. Serum PUFA levels could influence the severity of inflammatory oral diseases, such as gingivitis. OBJECTIVE: The study analyzed serum PUFA levels in a six-week randomized controlled trial in individuals on the Mediterranean diet (MedD), associations with the intake of specific foods, and possible correlations with oral inflammatory parameters. METHODS: Data from 37 study participants on either a MedD (MedDG; n = 18) or a "Western diet" in the control group (CG, n = 19) were analyzed. Dental examinations and serum analyses were performed at two time points, T1 (baseline) and T2 (week 6). Serum PUFA status, adherence to the MedD, and data from a Food Frequency Questionnaire were analyzed. RESULTS: Within the MedDG omega-6 fatty acid levels decreased significantly. In the overall sample, the proportional decrease in sites with bleeding on probing correlated weakly to moderately with the decrease in total omega-6 fatty acid level (Spearman's ρ = 0.274) and the decrease in gingival index correlated moderately with the decrease in linoleic acid level (Spearman's ρ = 0.351). Meat and fast-food consumption correlated positively with levels of various omega-6 fatty acids, whereas nut, fish, and dairy product consumption correlated positively with omega-3 levels. CONCLUSION: Adherence to a MedD was associated with a decrease in serum omega-6 levels, which positively affected the omega-6/omega-3 ratio. The MedD associated reduction in serum omega-6 levels may be a mechanism that favorably affects gingival inflammatory parameters.

Need for nursing care after laparoscopic and open colorectal cancer surgery: a claims data analysis in German primary care.

PURPOSE: Our study analyzes the influence of minimally invasive vs. open surgery on the postoperative need for nursing care in patients with colorectal carcinoma. Colorectal cancer is an age-related disease, and oncologic surgery is increasingly performed in elderly patients. Long-term effects of the procedural choice on patients' self-sufficiency and autonomy have not been scientifically addressed so far. METHODS: Multivariable logistic regression models based on claims data from a statutory health insurer (AOK, Baden-Württemberg, Germany) were applied to assess potential risk factors for assignment patients to a nursing care level, a German scale to categorize individual need for nursing care, at 12 and 36 months after colorectal cancer surgery. RESULTS: A total of 3996 patients were eligible to be included in the analysis. At 36 months postoperatively, 44 of 427 (10.3%) patients after minimally invasive colon cancer surgery and 231 of 1287 (17.9%) patients after open procedure were newly graded into a nursing care level (OR = 0.62, 95%CI = 0.44-0.90, p = 0.010). Thirty-four of 251 (13.5%) patients receiving minimally invasive rectal cancer surgery compared to 142 of 602 (23.6%) patients after open approach were newly assigned to a nursing care level (OR = 0.53, 95%CI = 0.34-0.81, p = 0.003). CONCLUSIONS: Laparoscopically assisted resection of colorectal cancer seems to be superior in preserving physical autonomy of elderly patients with colorectal cancer.

A New Practical Decision Rule to Better Differentiate BI-RADS 3 or 4 Breast Masses on Breast Ultrasound.

OBJECTIVES: The BI-RADS classification provides a standardized way to describe ultrasound findings in breast cancer diagnostics. However, there is little information regarding which BI-RADS descriptors are most strongly associated with malignancy, to better distinguish BI-RADS 3 (follow-up imaging) and 4 (diagnostic biopsy) breast masses. METHODS: Patients were recruited as part of an international, multicenter trial (NCT02638935). The trial enrolled 1294 women (6 excluded) categorized as BI-RADS 3 or 4 upon routine B-mode ultrasound examination. Ultrasound images were evaluated by three expert physicians according to BI-RADS. All patients underwent histopathological confirmation (reference standard). We performed univariate and multivariate analyses (chi-square test, logistic regression, and Krippendorff's alpha). RESULTS: Histopathologic evaluation showed malignancy in 368 of 1288 masses (28.6%). Upon performing multivariate analysis, the following descriptors were significantly associated with malignancy (P < .05): age ≥50 years (OR 8.99), non-circumscribed indistinct (OR 4.05) and microlobulated margin (OR 2.95), nonparallel orientation (OR 2.69), and calcification (OR 2.64). A clinical decision rule informed by these results demonstrated a 97% sensitivity and missed fewer cancers compared to three physician experts (range of sensitivity 79-95%) and a previous decision rule (sensitivity 59%). Specificity was 44% versus 22-83%, respectively. The inter-reader reliability of the BI-RADS descriptors and of the final BI-RADS score was fair-moderate. CONCLUSIONS: A patient should undergo a diagnostic biopsy (BI-RADS 4) instead of follow-up imaging (BI-RADS 3) if the patient is 50 years or older or exhibits at least one of the following features: calcification, nonparallel orientation of mass, non-circumscribed margin, or posterior shadowing.

Influence on the patient's oral hygiene depending on the treatment performed by either one or different pre-graduate practitioners - a randomized, controlled, clinical short-term trial.

OBJECTIVES: Plaque control by improved domestic oral hygiene is essential in periodontal treatment. However, changing treatment providers may interfere with building a dentist-patient relationship and in turn affect treatment success. The aim of this randomized, controlled, prospective short-term study was to determine the influence of either one or four different pre-graduate practitioners on patients' oral hygiene parameters during active periodontal therapy. MATERIAL AND METHODS: A total of 55 patients with periodontitis were allocated to two groups. Within the group "continuous treatment" (CT, n = 27), each patient was treated by one individual practitioner over the treatment period. For patients of the group "discontinuous treatment" (DT, n = 28), treatment in each session was performed by a different practitioner. Periodontal parameters (BOP, PBI, and PCR) were assessed at two timepoints: T1 (baseline) and T2 (end of active therapy). RESULTS: With CT, the PBI improved in 93% of the patients, compared to 71% with DT (p = 0.048). T1-T2 intragroup analysis showed a statistically significant improvement of all observed clinical parameters with no differences in ∆PBI, ∆BOP, and ∆PCR. Spearman's correlation analysis revealed a weak correlation between PCR and BOP of CT only. CONCLUSIONS: In the present study, improvement of all parameters was comparable between the groups. PBI, as a parameter displaying patient's domestic plaque control compliance, improved in more patients from CT than DT. This is possibly indicating an advantage of continuous treatment by one single practitioner. CLINICAL RELEVANCE: Treatment by either a single practitioner or by multiple, constantly changing practitioners might influence patients' compliance to modify their behaviour when medically necessary.

The anesthetist's choice of inhalational vs. intravenous anesthetics has no impact on survival of glioblastoma patients.

Recent data suggest that the type of anesthesia used during the resection of solid tumors impacts the long-term survival of patients favoring total-intravenous-anesthesia (TIVA) over inhalative-anesthesia (INHA). Here we sought to query this impact on survival in patients undergoing resection of glioblastoma (GBM). All patients receiving elective resection of a newly diagnosed, isocitrate-dehydrogenase-1-(IDH1)-wildtype GBM under general anesthesia between January 2010 and June 2017 in the Department of Neurosurgery, Heidelberg University Hospital, were included. Patients were grouped according to the applied anesthetic technique. To adjust for potential prognostic confounders, patients were matched in a 1:2 ratio (TIVA vs. INHA), taking into account the known prognostic factors: age, extent of resection, O-6-methylguanine-DNA-methyltransferase-(MGMT)-promoter-methylation-status, pre-operative Karnofsky-performance-index and adjuvant radio- and chemotherapy. The primary endpoint was progression-free-survival (PFS) and the secondary endpoint was overall-survival (OS). In the study period, 576 patients underwent resection of a newly diagnosed, IDH-wildtype GBM. Patients with incomplete follow-up-data, on palliative treatment, having emergency or awake surgery; 54 patients remained in the TIVA-group and 417 in the INHA-group. After matching, 52 patients remained in the TIVA-group and 92 in the INHA-group. Median PFS was 6 months in both groups. The median OS was 13.5 months in the TIVA-group and 13.0 months in the INHA-group. No significant survival differences associated with the type of anesthesia were found either before or after adjustment for known prognostic factors. This retrospective study supports the notion that the current anesthetic approaches employed during the resection of IDH-wildtype GBM do not impact patient survival.

Cryostorage to What End? - Autologous Stem Cell Products in Burkitt Lymphoma, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, and Myeloproliferative Neoplasm Patients.

INTRODUCTION: Recently, we identified a huge discrepancy between the collection practice and the actual utilization of cryopreserved peripheral blood stem cells (PBSCs) for high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ABSCT). Specifically, patients with Burkitt lymphoma, acute leukemia, and myeloproliferative neoplasms (MPN) were frequently not referred for ABSCT after successful PBSC collection. OBJECTIVE: The aim of this study was to identify variables that are associated with the non-utilization of PBSC grafts. METHODS: We retrospectively analyzed the collection, storage, and disposal of PBSC grafts in Burkitt lymphoma (n = 18), acute lymphoblastic leukemia (ALL, n = 22), MPN (n = 18), and acute myeloid leukemia (AML, n = 71) patients. Patients who underwent autologous PBSC collection at 2 collection and transplantation centers between 2001 and 2012 were included and followed up until 2016. RESULTS: None of the Burkitt lymphoma patients were referred for ABSCT. Only in 1 (6%) patient, the graft was discarded after the patient's death. In all other patients (n = 17, 94%), the grafts were stored independently of the patient's status (death, n = 4, 22%; no follow-up, n = 6, 33%; no indication for ABSCT given, n = 7, 39%). In ALL patients, 4 (18%) patients underwent ABSCT after a median follow-up of 74 (1-182) months. In the remaining patients, PBSC grafts were either discarded (8 patients, 36%) or stored until the reference date (10 patients, 45%). Seven of 18 MPN patients (39%) underwent ABSCT. ABSCT was performed in 24 (34%) AML patients. In 20 (28%) patients who were not referred to ABSCT, an allogeneic transplantation (TPL) was performed. Fifteen (21%) patients received palliative care or deceased, and their grafts were discarded in all but 1 patient. Additional grafts were discarded in 21 (31%) patients and stored in 9 (13%) patients who underwent ABSCT or allogeneic TPL (n = 44). CONCLUSIONS: As the role and efficacy of autologous HDCT/ABSCT are not established in the analyzed entities, the indication for PBSC collection should be reanalyzed in regular intervals. Moreover, PBSC grafts from patients who have deceased, have insufficient grafts, or have already undergone an allogeneic TPL should be considered for disposal or (if applicable) for research use, to economize storage costs on a rational basis.

Low-dose peripheral blood stem cell graft after high-dose chemotherapy - an evaluation of hematopoietic reconstitution.

BACKGROUND: High-dose (HD) chemotherapy followed by autologous blood stem-cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) patients. However, the collection of sufficient peripheral blood stem cell (PBSC) grafts can be challenging, and the question arises whether reinfusion of low-dose grafts will lead to a hematopoietic recovery. METHODS: The hematopoietic recovery of 148 MM patients who underwent HD melphalan chemotherapy and received PBSC transplants with varying CD34+ cells doses (3-4 × 106 [n = 86], 2-2.5 × 106 [n = 53], < 2 × 106 [n = 9] per kg body weight [bw]) was analyzed in this retrospective single-center study. RESULTS: All patients reached hematopoietic reconstitution, even those who received < 2 × 106 CD34+ cells/kg bw. 62 (42%) patients received granulocyte-colony-stimulating factor (G-CSF). The median duration to leukocyte recovery ≥1.0 × 109/L was 12 days in every group. The median duration to platelet recovery ≥20 × 109/L was 11, 13 and 13 days, respectively. In the multivariate analysis, a low number of reinfused CD34+ cells was associated with prolonged time until leukocyte reconstitution (p = 0.010, HR 0.607) and platelet recovery (p < 0.001, HR 0.438). G-CSF support significantly accelerated leukocyte (p < 0.001, HR 16.742) but not platelet reconstitution. CONCLUSION: In conclusion, reinfusion of low- and even very-low-dose PBSC grafts leads to sufficient hematopoietic reconstitution. No severe adverse events were observed during or after HD chemotherapy and ASCT in the analyzed cohort. While the impact of CD34+ cell dose is marginal, G-CSF significantly accelerates the leukocyte recovery.

Soluble intercellular adhesion molecule (ICAM)-1 detects invasive fungal infections in patients following liver transplantation.

PURPOSE: Despite antifungal prophylaxis, liver transplanted patients are endangered by invasive fungal infections (IFI). Routinely used microbiological procedures are hallmarked by significant weaknesses, which may lead to a delay in antifungal treatment. METHODS: Culture-based fungal findings, routinely used biomarkers of infection/inflammation (e.g., procalcitonin or C-reactive protein), as well as corresponding plasma concentrations of soluble Intercellular Adhesion Molecule (ICAM)-1 were analysed in 93 patients during a period of 28 days following liver transplantation (LTX). RESULTS: Plasmatic sICAM-1 was significantly elevated in patients affected by an IFI within the first 28 days in comparison to fungally colonised or unobtrusive LTX patients. sICAM-1 might therefore be helpful for the identification of IFI patients after LTX (e.g., Receiver Operating Characteristic (ROC)-Area Under the Curve (AUC): 0.714 at 14d after LTX). The diagnostic performance of sICAM-1 was further improved by its combined use with different other IFI biomarkers (e.g., midregional proadrenomedullin). CONCLUSION: The diagnostic deficiencies of routinely used microbiological procedures for IFI detection in patients after LTX may be reduced by plasmatic sICAM-1 measurements. Clinical Trial Notation. German Clinical Trials Register: DRKS00005480.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma.

Background: Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities. The association of PD-1/PD-L1 expression and its impact on patient prognosis with SBA is unclear. Material and methods: Seventy-five consecutive patients who underwent surgery for SBA were retrospectively analyzed and stained for PD-L1 expression in the tumour or the stroma. Analysis of mismatch repair genes was performed to determine microsatellite status. Kaplan-Meier estimate was used to analyze patient survival. Univariate and multivariable Cox regression-analyses were used to assess the impact of PD-L1 expression and microsatellite status on patient survival.Results: PD-L1 was weakly upregulated within the tumour or the stroma and associated with prolonged survival (p = .0071 and p = .0472, respectively). Fifty-one tumours (68%) revealed microsatellite stability (MSS) and 24 tumours (32%) were microsatellite instable (MSI) without correlating with patient survival (p = .611). Neither PD-L1 expression in the tumour nor in the stroma was identified as an independent risk factor influencing survival (p = .572 and p = .3055).Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival.

Diltiazem Prophylaxis for the Prevention of Atrial Fibrillation in Patients Undergoing Thoracoabdominal Esophagectomy: A Retrospective Cohort Study.

BACKGROUND: Atrial fibrillation (AF) represents the most frequent arrhythmic disorder after thoracoabdominal esophageal resection and is associated with a significant increase in perioperative morbidity and mortality. METHODS: In this retrospective cohort study, 167 patients who underwent thoracoabdominal esophagectomy at a large university hospital were assessed. We compared patients who received a 14-day postoperative course of diltiazem with a control group of patients who did not undergo diltiazem prophylaxis. Diltiazem therapy started immediately upon admission to the intensive care unit (ICU) with a loading dose of 0.25 mg/kg bodyweight (i.v.) followed by continuous infusion (0.1 mg/kg bodyweight/h) for 40-48 h. Oral administration (Dilzem® 180 mg uno retard, once a day) was started on postoperative day 3. RESULTS: A total of 117 patients were assessed. Twelve (10.3%) of all patients developed postoperative new-onset atrial fibrillation in the first 30 days after surgical intervention. Prevalence of new-onset AF showed no significant differences between the diltiazem group and control group (p = 0.74). The prevalence of bradycardia (14.7% vs. 3.6%; p = 0.03) and dose of norepinephrine required (0.09 vs. 0.04 µg/kg bodyweight/min; p = 0.04) were higher in the diltiazem group. There were no significant differences between the groups for the median postoperative duration of hospital/ICU stay or mortality. CONCLUSIONS: A prophylactic 14-day postoperative course of diltiazem was not associated with a reduction in new-onset AF or 30-day mortality following thoracoabdominal esophagectomy. Prophylactic diltiazem therapy was associated with drug-related adverse effects such as bradycardia and increased requirement of norepinephrine. German Clinical Trial Registration Number: DKRS00016631.