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Objectives The aim of this study was to assess the texture of repair tissue and tissue adjacent to the repair site after matrix-associated chondrocyte transplantation (MACT) of the knee using gray-level co-occurrence matrix (GLCM) texture analysis of T 2 quantitative maps. Methods Twenty patients derived from the MRI sub-study of multicenter, single-arm phase III study underwent examination on a 3 T MR scanner, including a T 2 mapping sequence 12 and 24 months after MACT. Changes between the time points in mean T 2 values and 20 GLCM features were assessed for repair tissue, adjacent tissue, and reference cartilage. Differences in T 2 values and selected GLCM features between the three cartilage sites at two time points were analyzed using linear mixed-effect models. Results A significant decrease in T 2 values after MACT, between time points, was observed only in repair cartilage ( p < 0.001). Models showed significant differences in GLCM features between repair tissue and reference cartilage, namely, autocorrelation ( p < 0.001), correlation ( p = 0.015), homogeneity ( p = 0.002), contrast ( p < 0.001), and difference entropy ( p = 0.047). The effect of time was significant in a majority of models with regard to GLCM features (except autocorrelation) ( p ≤ 0.001). Values in repair and adjacent tissue became similar to reference tissue over time. Conclusions GLCM is a useful add-on to T 2 mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant. Key Points • GLCM is a useful add-on to T 2 mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. • Repair and adjacent tissue became similar to reference tissue over time. • The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant.

In a phase 2 study in patients with metastatic renal cell carcinoma, overall survival was associated with T-cell responses against IMA901, a vaccine consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to determine the clinical effect of adding IMA901 to sunitinib, the standard first-line treatment in metastatic renal cell carcinoma with postulated favourable immunomodulatory effects. The IMPRINT study is an open-label, randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries. HLA-A*02-positive patients (aged ≥18 years) with treatment-naive, histologically confirmed metastatic or locally advanced (or both) clear-cell renal cell carcinoma were randomly assigned (3:2) to receive sunitinib plus up to ten intradermal vaccinations of IMA901 (4·13 mg) and granulocyte macrophage colony-stimulating factor (75 μg), with one dose of cyclophosphamide (300 mg/m2) 3 days before the first vaccination, or to receive sunitinib alone. Sunitinib (50 mg) was given orally once daily, with each cycle defined as 4 weeks on treatment followed by 2 weeks off treatment, until progression of disease as determined by the investigator, death, or withdrawal of consent. Block randomisation (block size five) was done centrally using an interactive web response system, stratified by prognostic risk, geographical region, and previous nephrectomy. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival from randomisation until death of any cause as determined by the investigator, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01265901. Between Dec 22, 2010, and Dec 15, 2012, we screened 1171 patients, of whom 339 were randomly assigned to receive sunitinib plus IMA901 (n=204) or sunitinib monotherapy (n=135). Patients had a median follow-up of 33·27 months (IQR 29·92–35·64). Median overall survival did not differ significantly between the groups (33·17 months [95% CI 27·81–41·36] in the sunitinib plus IMA901 group vs not reached [33·67–not reached] in the sunitinib monotherapy group; hazard ratio 1·34 [0·96–1·86]; p=0·087). 116 (57%) of 202 patients in the sunitinib plus IMA901 group and 62 (47%) of 132 in the sunitinib group had grade 3 or worse adverse events, the most common of which were hypertension, neutropenia, and anaemia in both groups, and mild-to-moderate transient injection-site reactions (eg, erythema, pruritus) were the most frequent IMA901-related side-effect in the sunitinib plus IMA901 group. Serious adverse events leading to death occurred in four (2%) patients (one respiratory failure and circulatory collapse [possibly related to sunitinib], one oesophageal varices haemorrhage [possibly related to sunitinib], one cardiac arrest [possibly related to sunitinib], and one myocardial infarction) and eight (6%) patients in the sunitinib group (one case each of renal failure, oesophageal varices haemorrhage, circulatory collapse, wound infection, ileus, cerebrovascular accident [possibly treatment related], and sepsis). IMA901 did not improve overall survival when added to sunitinib as first-line treatment in patients with metastatic renal cell carcinoma. The magnitude of immune responses needs to be improved before further development of IMA901 in this disease is indicated. Immatics Biotechnologies.

Background: Few studies exist for large defects comparing matrix-associated autologous chondrocyte implantation (M-ACI) with other cartilage repair methods due to the limited availability of suitable comparator treatments. Purpose: To compare the clinical efficacy of a novel hydrogel-based M-ACI method (NOVOCART Inject plus) versus microfracture (MFx) in patients with knee cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: Propensity score matched-pair analysis was used to compare the 24-month outcomes between the M-ACI treatment group from a previous single-arm phase 3 study and the MFx control group from another phase 3 study. Patients were matched based on preoperative Knee injury and Osteoarthritis Outcomes Score (KOOS), symptom duration, previous knee surgeries, age, and sex, resulting in 144 patients in the matched-pair set (72 patients per group). The primary endpoint was the change in least-squares means (ΔLSmeans) for the KOOS from baseline to the 24-month assessment. Results: Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 versus 3.7 cm2). Other differences included defect location (no patellar or tibial defects in the MFx group), number of defects (33.3% with 2 defects in the M-ACI group versus 9.7% in the MFx group), and defect cause (more patients with degenerative lesions in the M-ACI group). The M-ACI group had higher posttreatment KOOS (M-ACI versus MFX: 81.8 ± 16.8 versus 73.0 ± 20.6 points) and KOOS ΔLSmeans from baseline to 24 months posttreatment (M-ACI versus MFX: 36.9 versus 26.9 points). Treatment contrasts in KOOS ΔLSmeans from baseline indicated statistical significance in favor of M-ACI from 3 to 24 months posttreatment (P = .0026). Significant and clinically meaningful differences in favor of M-ACI at 24 months were also found regarding International Knee Documentation Committee (IKDC) score ΔLSmeans from baseline (37.8 versus 30.4 points; P = .0334), KOOS responder rates at 24 months (≥10-point improvement from baseline; 94.4% versus 65.3%; P < .0001), IKDC responder rates at 24 months (>20.5-point improvement from baseline; 83.3% versus 61.1%, P = .0126) and MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in a subgroup of patients (LS means, 86.9 versus 69.1; P = .0096). Conclusion: In this exploratory analysis, M-ACI using an in situ crosslinked hydrogel demonstrated superior clinical and structural (MOCART) 24-month outcomes compared with MFx in patients with knee cartilage defects.

The aim of this study was to assess the texture of repair tissue and tissue adjacent to the repair site after matrix-associated chondrocyte transplantation (MACT) of the knee using gray-level co-occurrence matrix (GLCM) texture analysis of T quantitative maps. Twenty patients derived from the MRI sub-study of multicenter, single-arm phase III study underwent examination on a 3 T MR scanner, including a T mapping sequence 12 and 24 months after MACT. Changes between the time points in mean T values and 20 GLCM features were assessed for repair tissue, adjacent tissue, and reference cartilage. Differences in T values and selected GLCM features between the three cartilage sites at two time points were analyzed using linear mixed-effect models. A significant decrease in T values after MACT, between time points, was observed only in repair cartilage (p < 0.001). Models showed significant differences in GLCM features between repair tissue and reference cartilage, namely, autocorrelation (p < 0.001), correlation (p = 0.015), homogeneity (p = 0.002), contrast (p < 0.001), and difference entropy (p = 0.047). The effect of time was significant in a majority of models with regard to GLCM features (except autocorrelation) (p ≤ 0.001). Values in repair and adjacent tissue became similar to reference tissue over time. GLCM is a useful add-on to T mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant. • GLCM is a useful add-on to T mapping in the evaluation of knee cartilage after MACT by increasing the sensitivity to changes in cartilage structure. • Repair and adjacent tissue became similar to reference tissue over time. • The results suggest that cartilage tissue adjacent to the repair site heals along with the cartilage implant.

Global distributions of chlorine monoxide (ClO) were retrieved from infrared limb emission spectra recorded with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS), covering the time period from July 2002 to April 2012. The retrieval was performed by constrained non-linear least squares fitting using spectral lines in the fundamental band of ClO around 844 cm−1. The vertical resolution of V8 ClO is 4 km at 18–20 km and 7.5–9.5 km at 40 km altitude. The considerable improvement at 40 km with respect to the previous V5 data version is achieved by extension of the spectral range for retrieval of upper stratospheric ClO. Errors are by far dominated by measurement noise and increase from 0.4–0.5 ppbv at 20 km to 0.8 ppbv at 50 km altitude. Thus, in general, individual ClO profiles are noisy, and profile averaging has to be performed for, e.g., analysis of the upper stratospheric maximum. However, strongly enhanced lower stratospheric ClO amounts of more than 1.5 ppbv during polar winter are well detected in single measurements. Along with the standard representation of the data, an alternative coarse grid representation that obviates the need to apply averaging kernels in certain situations is also provided. Due to improved modeling of the atmospheric continuum and the instrumental offset, the high bias in upper stratospheric ClO that had particularly affected the previous V5 data over the period 2005–2012 has been removed. A comparison with ClO measurements of the Microwave Limb Sounder (MLS) on the Aura satellite shows good agreement between the lower stratospheric enhancements observed by the two instruments in polar winter. There is also good agreement between the upper stratospheric ClO amounts observed in the northern hemisphere and at southern hemispheric low latitudes. With the support of simulations from the Earth system model ECHAM/MESSy Atmospheric Chemistry (EMAC), deviations between the ClO amounts of MIPAS and MLS in the Antarctic lower stratosphere during July and in the upper stratosphere, especially at southern mid- and high latitudes during winter, are attributed to the different local solar times of the measurements.

By means of a nationwide, prospective, multicenter, observational cohort registry collecting data on 7375 patients with laboratory-confirmed SARS-CoV-2 admitted to children's hospitals in Germany, March 2020–November 2022, our study assessed the clinical features of children and adolescents hospitalized due to SARS-CoV-2, evaluated which of these patients might be at highest risk for severe COVID-19, and identified underlying risk factors. Outcomes tracked included: symptomatic infection, case fatality, sequelae at discharge and severe disease. Among reported cases, median age was one year, with 42% being infants. Half were admitted for reasons other than SARS-CoV-2. In 27%, preexisting comorbidities were present, most frequently obesity, neurological/neuromuscular disorders, premature birth, and respiratory, cardiovascular or gastrointestinal diseases. 3.0% of cases were admitted to ICU, but ICU admission rates varied as different SARS-CoV-2 variants gained prevalence. Main risk factors linked to ICU admission due to COVID-19 were: patient age (> 12 and 1–4 years old), obesity, neurological/neuromuscular diseases, Trisomy 21 or other genetic syndromes, and coinfections at time of hospitalization. With Omicron, the group at highest risk shifted to 1–4-year-olds. For both health care providers and the general public, understanding risk factors for severe disease is critical to informing decisions about risk-reduction measures, including vaccination and masking guidelines.