Incidence and outcomes of AKI in postoperative patients admitted to ICU using full KDIGO criteria - a cohort study.

STUDY OBJECTIVE: Acute kidney injury (AKI) is a serious complication in postoperative ICU patients. The incidence of AKI varies substantially based on the type of surgery and definition used. This study focuses on the incidence of AKI in postoperative ICU patients using full KDIGO criteria and related outcomes regarding to different types of surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary level university hospital, eight anaesthesiological/surgical ICUs, between 2016 and 2018. PATIENTS: 6261 adult patients. MEASUREMENTS: Primary outcome was 28-day all-cause mortality in different stages of AKI according to complete KDIGO criteria. MAIN RESULTS: We found 3497 (55.9%) postoperative ICU patients with AKI. The severity distribution of AKI stage 1 to 3 was 19.7%, 28.4% and 7.8%, respectively, and 235 (4%) patients received RRT. The 28-day mortality was 3% (n = 205). Increasing AKI severity was associated with increased 28-day mortality when adjusted for other variables (AKI 2°: OR 2.81; 95% CI 1.55 to 5.24; p < 0.001 and AKI 3°: OR 11.37.; 95% CI 5.91 to 22.55; p < 0.001). Besides AKI stages 2 and 3, age (OR 1.02; 95% CI 1.01 to 1.04, p < 0.001), NYHA IV (OR 2.23; 95% CI 1.03 to 4.43, p = 0.042), need for surgical reintervention within 48 h (OR 2.92; 95% CI 1.76 to 4.72, p = 0.001), urgent surgery (OR 1.78; 95% CI 1.15 to 2.71, p = 0.01), emergency surgery (OR 2.63; 95% CI 1.58 to 4.31, p = 0.001), vascular surgery (OR 2.01; 95% CI 1.06 to 3.98, p = 0.033), and orthopedic and trauma surgery (OR 3.79; 95% CI 1.98 to 7.09, p < 0.001) versus cardiac surgery was significantly associated with increased risk for 28-days mortality in multivariate analysis. CONCLUSION: AKI based on full KDIGO criteria is very common in postoperative ICU patients and it is associated with stepwise increase in 28-days mortality.

Risk Factors for Local Failure Following Chemoradiation and Magnetic Resonance Image-Guided Brachytherapy in Locally Advanced Cervical Cancer: Results From the EMBRACE-I Study.

PURPOSE: To report clinical and treatment characteristics, remission and failure patterns, and risk factors for local failure (LF) from the EMBRACE-I study. MATERIALS AND METHODS: EMBRACE-I was a prospective, observational, multicenter cohort study on magnetic resonance imaging-based image-guided adaptive brachytherapy (MR-IGABT) in locally advanced cervical cancer. Treatment consisted of external beam radiotherapy, concurrent chemotherapy, and MR-IGABT. LF was defined as progressive or recurrent disease in the cervix, uterus, parametria, pelvic wall, or vagina. Competing risk analysis was used to estimate local tumor control (LC) and Cox proportional regression models for multivariable analysis and dose-response analysis. RESULTS: One thousand three hundred eighteen patients with a median follow-up of 52 months were available for this analysis. Eighty-one patients had persistent disease 3 months after end of treatment. Of those, 60 patients achieved LC at 6-9 months without further treatment, whereas 21 patients had progressive disease. In addition, 77 patients developed a local recurrence after complete remission comprising a total number of 98 LFs. LFs were located inside the MR-IGABT target volumes in 90% of patients with LF. In multivariable analysis, histology, minimal dose to 90% of high-risk clinical target volume (CTVHR), maximum tumor dimension, CTVHR > 45 cm3, overall treatment time, tumor necrosis on magnetic resonance imaging at diagnosis, uterine corpus infiltration at diagnosis and at MR-IGABT, and mesorectal infiltration at MR-IGABT had significant impact on LF. Dose-response analysis showed that a minimal dose to 90% of 85 Gy to the CTVHR led to 95% (95% CI, 94 to 97) LC 3 years postintervention for squamous cell in comparison to 86% (95% CI, 81 to 90) for adeno/adenosquamous carcinoma histology. CONCLUSION: The present study demonstrates the safety and validity of the GYN GEC-ESTRO/ICRU-89 target concept and provides large-scale evidence for dose prescription and new risk factors for LF in MR-IGABT in locally advanced cervical cancer.

Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD). METHODS: Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed in 215 prospectively recruited patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein catheterization. Patients with non-elective hospitalization or bacterial infection were excluded. Histological alpha-smooth muscle actin (α-SMA) area was quantified on full biopsy scans by automated morphometric quantification in a subset of 34 patients who underwent concomitant transjugular liver biopsy. RESULTS: Histological α-SMA proportionate area correlated with enhanced liver fibrosis (ELF) score (Spearman's ρ = 0.660, p < .001), markers of collagen formation (PRO-C3, ρ = 0.717, p < .001; PRO-C6, ρ = 0.526, p = .002) and tissue inhibitor of metalloproteinases-1 (TIMP1; ρ = 0.547, p < .001), indicating that these blood biomarkers are capable of reflecting the dynamic process of ECM turnover. CRP, IL-6 and PCT levels correlated with ELF, biomarkers of collagen synthesis/degradation and TIMP1, both in compensated and decompensated patients. Multivariate linear regression models (adjusted for HVPG) confirmed that CRP, IL-6 and PCT were independently linked to markers of liver fibrogenesis and ECM turnover. CONCLUSION: Systemic inflammation is linked to both liver fibrogenesis and ECM turnover in ACLD and this association is not confounded by the severity of liver disease, as evaluated by HVPG. Our study confirms experimental data on the detrimental impact of SI on ECM deposition and fibrosis progression in a thoroughly characterized cohort of patients with ACLD.

Omalizumab-Induced Aspirin Tolerance in Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease Patients Is Independent of Atopic Sensitization.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 enzyme. The impact of omalizumab on prevention of aspirin-induced hypersensitivity in N-ERD patients with and without atopic sensitization has not been thoroughly addressed. OBJECTIVE: To investigate the effect of omalizumab treatment on aspirin tolerance in atopic and nonatopic N-ERD patients. METHODS: This single-center, prospective trial evaluated overall omalizumab-induced aspirin tolerability in N-ERD patients by performing aspirin challenge testing before and after 6 months of anti-immunoglobulin E (IgE) therapy. The impact of omalizumab on CRSwNP asthma as well as serum and tissue biomarkers in patients with and without comorbid atopic sensitizations was further analyzed. RESULTS: Out of 33 patients included in the study, 56% developed complete aspirin tolerance and 18% tolerated higher dosages after 24 weeks. Polyp size and disease-specific symptoms (nasal polyp score [NPS] -1.9 ± 0.3, P < .001; Sino-Nasal Outcome Test [SNOT]-20 -16.7 ± 3.7, P < .001; Asthma Control Test [ACT] 3.2 ± 0.7, P < .001) improved in all patients irrespective of atopic sensitization. Effectiveness of omalizumab was accompanied by an increase in mean total serum IgE (307.8 ± 42 kU/L; P < .001) and a decrease in eosinophilic cationic protein (-10.6 ± 6.7 µg/L) and in relative eosinophilia (-2.5 ± 0.7%; P < .01). Whereas there was a significant reduction of tissue IgE (P < .05) in all patients after 4 weeks, the number of local eosinophils decreased only in atopic individuals (P < .05). CONCLUSIONS: Omalizumab induced complete aspirin tolerance in the majority of patients (56%) independent of atopic sensitization and demonstrated clinical efficacy in the treatment of CRSwNP and asthma. Inhibition of IgE can therefore be a promising treatment option in preventing NSAID hypersensitivity reactions in N-ERD patients.

Expression of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) in adenocarcinomas of the gastroesophageal junction change significantly after neoadjuvant treatment.

BACKGROUND: The effects of cytotoxic chemotherapy on the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in cancer cells and peritumoral cells are unclear. The aim of this study was to investigate the impact of neoadjuvant chemotherapy on PD-1 and PD-L1 expression in adenocarcinomas of the gastroesophageal junction. METHODS: PD-1 and PD-L1 expression in cancer cells and tumor-infiltrating lymphocytes in paired diagnostic biopsies and surgical specimens from patients with pretreated and curatively resected adenocarcinomas of the gastroesophageal junction were evaluated by immunohistochemistry. RESULTS: Paired tumor samples were available from 40 patients. PD-1 expression in cancer cells (p < 0.001; Exact Symmetry Test) and tumor-infiltrating lymphocytes (p < 0.001; Exact Symmetry Test) increased significantly after neoadjuvant therapy. Furthermore, we observed a significant decrease in PD-L1 expression in cancer cells (p = 0.003) after neoadjuvant therapy was observed. CONCLUSION: In this study we could show that tumor-cell expression of PD-1 and PD-L1 was significantly altered in patients with adenocarcinomas of the gastroesophageal junction after receiving neoadjuvant chemotherapy. Based on these observations, patients might profit from the combined use of cytotoxic chemotherapy and the blockade of the PD-1 axis.

Programmed death ligand 2 expression plays a limited role in adenocarcinomas of the gastroesophageal junction after preoperative chemotherapy.

BACKGROUND: The effects of cytotoxic chemotherapy on the expression of programmed death ligand 2 (PD-L2) are unknown and little is known about how the tumor microenvironment changes following neoadjuvant chemotherapy in locally advanced gastroesophageal adenocarcinomas (AEG). Recently, a number of studies reported that cytotoxic chemotherapy affects the expression levels of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1). Regarding PD-L2, the second known ligand of PD­1, no data on potential changes in expression patterns in patients with preoperatively treated AEG are available. The aim of this study was to investigate the impact of cytotoxic chemotherapy on PD-L2 expression in patients with resectable AEG. METHODS: Consecutive patients with locally advanced AEG treated with preoperative cytotoxic chemotherapy were included. PD-L2 expression by cancer cells (CCs) and tumor-infiltrating lymphocytes (TILs) was investigated in samples of paired diagnostic biopsies and resected tumor specimens by immunohistochemistry using two different anti-PD-L2 antibodies. RESULTS: Included were 40 patients with AEG and available paired tumor tissue samples. PD-L2 expression was observed in one diagnostic biopsy sample by CCs and in one diagnostic biopsy sample by TILs. There was no difference concerning the expression levels measured by the two antibodies. CONCLUSION: In contrast to previously published studies reporting PD-L2 expression rates of up to 50% in AEGs, in our cohort, PD-L2 expression seems to play no significant role in AEG.

High-intensity interval training in the prehabilitation of cancer patients-a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of high-intensity interval training (HIIT) on health-related outcome parameters in the prehabilitation of patients diagnosed with cancer. METHODS: A systematic review and meta-analysis of comparative studies on HIIT in cancer prehabilitation conducted by screening standard databases from their inception to March 30, 2020. Outcomes of interest included cardiorespiratory fitness, feasibility, safety, clinical, and patient-reported outcomes. RESULTS: Of the 855 identified studies, 8 articles met the inclusion criteria (7 randomized, 1 non-randomized controlled trial) with a total of 896 patients. The study protocols were heterogeneous, but the methodological quality ranged from good to high according to PEDro scale. Meta-analysis revealed a significant improvement of peak oxygen consumption (VO2peak) achieved with HIIT compared to usual care. Furthermore, HIIT was feasible and safe, showing low risk of adverse events and positive effects on health-related outcomes in prehabilitative settings. CONCLUSION: In the phase of prehabilitation, HIIT has potential health benefits in patients diagnosed with cancer and is feasible and safe to perform. Nonetheless, larger randomized controlled trials focusing on long-term effects (such as cancer recurrence or survival rates) are missing, to underline the potential relevance of HIIT for cancer patients.

Resistance exercise and breast cancer-related lymphedema-a systematic review update and meta-analysis.

BACKGROUND: The purpose of this systematic review update and meta-analysis was to analyze resistance exercise (RE) intervention trials in breast cancer survivors (BCS) regarding their effect on breast cancer-related lymphedema (BCRL) status and upper and lower extremity strength. METHODS: Systematic literature search was conducted utilizing PubMed, MEDLINE, and Embase databases. Any exercise intervention studies-both randomized controlled and uncontrolled-which assessed the effects of RE on BCRL in BCS in at least one intervention group published between 1966 and 31st January 2020 were included. Included articles were analyzed regarding their level of evidence and their methodological quality using respective tools for randomized and nonrandomized trials of the Cochrane collaboration. Meta-analysis for bioimpedance spectroscopy (BIS) values as well as upper and lower extremity strength was conducted. RESULTS: Altogether, 29 studies were included in the systematic review. Results of six studies with altogether twelve RE intervention groups could be pooled for meta-analysis of the BCRL. A significant reduction of BCRL after RE was seen in BIS values (95% CI - 1.10 [- 2.19, - 0.01] L-Dex score). Furthermore, strength results of six studies could be pooled and meta-analysis showed significant improvements of muscular strength in the upper and lower extremities (95% CI 8.96 [3.42, 14.51] kg and 95% CI 23.42 [11.95, 34.88] kg, respectively). CONCLUSION: RE does not have a systematic negative effect on BCRL and, on the contrary, potentially decreases it.