Maurerwillumsen7150

197), whereas excellent agreement was achieved at cut-offs of 50% (κ=0.908) and 5% (κ=0.823). DIA on mIF showed that PD-L1 commonly colocalised with CD68

macrophages and CD8

cytotoxic cells were closer to PD-L1

/CK

tumour cells (TCs) than to PD-L1

/CK

TCs in spatial distribution.

A combination of mIF and DIA is useful for the quantification of PD-L1 expression and IC populations in NSCLC. Further validation of TPS at a cut-off of 1% and assay harmonisation is essential for translating this method in a diagnostic setting.

A combination of mIF and DIA is useful for the quantification of PD-L1 expression and IC populations in NSCLC. Further validation of TPS at a cut-off of 1% and assay harmonisation is essential for translating this method in a diagnostic setting.

Cribriform comedo-type adenocarcinoma was a colon cancer subtype recognised in the previous WHO classification of tumours that is no longer included in the recent edition. Previous reports have described colon cancers with cribriform growth as having worse overall survival and being associated with microsatellite stability. We sought to validate whether cribriform carcinoma (CC) is a distinct morphological subtype with clinical relevance in the context of modern colon cancer diagnosis.

Consecutive cases of non-neoadjuvantly treated colon cancer resections were identified (n=177) and reviewed to evaluate for CC and other histopathological and clinical features. CC was defined as solid nests of cancer with round, 'punched out' spaces and intraluminal bridges, reminiscent of ductal carcinoma in situ of the breast.

CC was present in 18.6% of the consecutive case cohort. Compared with all other cases, CC was associated with positive lymph nodes, increased depth of invasion, extramural venous involvement (EMVI), and microsatellite stability, and was less likely to have tumour infiltrating lymphocytes (p<0.05). In contrast to previous reports, we did not find significantly worse overall, disease-specific or recurrence-free survival for CC. Morphological features mimicking CC occurred in 33.3% of all other colon cancer cases.

Identifying CC may be useful due to its association with worse stage at presentation and EMVI, but given that cribriform-like appearance may be found in many colon cancer cases and that we did not find a survival difference for CC, CC may not necessitate its own subtype classification.

Identifying CC may be useful due to its association with worse stage at presentation and EMVI, but given that cribriform-like appearance may be found in many colon cancer cases and that we did not find a survival difference for CC, CC may not necessitate its own subtype classification.

To describe the identification of regulator of G-protein signaling 8 (RGS8) as an autoantibody target in patients with cerebellar syndrome associated with lymphoma.

Sera of 4 patients with a very similar unclassified reactivity against cerebellar Purkinje cells were used in antigen identification experiments. Immunoprecipitations with cerebellar lysates followed by mass spectrometry identified the autoantigen, which was verified by recombinant immunofluorescence assay, immunoblot, and ELISA with the recombinant protein.

The sera and CSF of 4 patients stained the Purkinje cells and molecular layer of the cerebellum. RGS8 was identified as the target antigen in all 4 sera. In a neutralization experiment, recombinant human RGS8 was able to neutralize the autoantibodies' tissue reaction. Patient sera and CSF showed a specific reactivity against recombinant RGS8 in ELISA and immunoblot, whereas no such reactivity was detectable in the controls. Clinical data were available for 2 of the 4 patients, remarkably both presented with cerebellar syndrome accompanied by B-cell lymphoma of the stomach (patient 1, 53 years) or Hodgkin lymphoma (patient 2, 74 years).

Our results indicate that autoantibodies against the intracellular Purkinje cell protein RGS8 represent new markers for paraneoplastic cerebellar syndrome associated with lymphoma.

This study provided Class IV evidence that autoantibodies against the intracellular Purkinje cell protein RGS8 are associated with paraneoplastic cerebellar syndrome in lymphoma.

This study provided Class IV evidence that autoantibodies against the intracellular Purkinje cell protein RGS8 are associated with paraneoplastic cerebellar syndrome in lymphoma.

To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS).

Sixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention.

Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Selleck Binimetinib Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT.

Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS.

This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS.

Clinical trial registration number NCT03652519.

Clinical trial registration number NCT03652519.

Gout is often not adequately treated, and we aimed to apply urate lowering treatment (ULT) combined with individual information to achieve target serum urate (sUA) in clinical practice, and to identify predictors of achievement of this sUA target.

Patients with a recent gout flare and sUA >360 µmol/L (>6 mg/dL) were consecutively included in a single-centre study and managed with a treat-to-target approach combining nurse-led information about gout with ULT. All patients were assessed with tight controls at baseline, 1, 2, 3, 6, 9 and 12 months including clinical examination, information on demographics, lifestyle, self-efficacy and beliefs about medicines. The treatment target was sUA <360 µmol/L and multivariable logistic regression was used to identify predictors of target attainment with ORs and 95% CIs.

Of 211 patients (mean age 56.4 years, disease duration 7.8 years, 95% males), 186 completed the 12-month study. Mean sUA levels decreased from baseline mean 500 to 311 µmol/L at 12 months with 85.