Cancer-associated fibroblast activation predicts progression, metastasis, and prognosis of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and the metastatic disease is associated with poor prognosis. Cancer-associated fibroblasts (CAFs) promote progression of cancer, but their role in cSCC is largely unknown. We examined the potential of CAF markers in the assessment of metastasis risk and prognosis of primary cSCC. We utilized multiplexed fluorescence immunohistochemistry for profiling CAF landscape in metastatic and non-metastatic primary human cSCCs, in metastases, and in premalignant epidermal lesions. Quantitative high-resolution image analysis was performed with two separate panels of antibodies for CAF markers and results were correlated with clinical and histopathological parameters including disease-specific mortality. Increased stromal expression of fibroblast activation protein (FAP), α-smooth muscle actin, and secreted protein acidic and rich in cysteine (SPARC) were associated with progression to invasive cSCC. Elevation of FAP and platelet-derived growth factor receptor-ß (PDGFRß) expression was associated with metastasis risk of primary cSCCs. High expression of PDGFRß and periostin correlated with poor prognosis. Multimarker combination defined CAF subset, PDGFRα-/PDGFRß+/FAP+, was associated with invasion and metastasis, and independently predicted poor disease-specific survival. These results identify high PDGFRß expression alone and multimarker combination PDGFRα-/PDGFRß+/FAP+ by CAFs as potential biomarkers for risk of metastasis and poor prognosis.

Depression and Nigral Neuron Density in Lewy Body Spectrum Diseases.

Parkinson's disease and other Lewy body spectrum diseases (LBDs) are associated with a specific risk for clinical depression. In the present clinicopathological study with 73 patients with LBD, we observed that the substantia nigra pars compacta dopamine neuron density was markedly lower in patients who had comorbid depression antemortem than in nondepressed patients (1.52 vs 2.32 n/mm2 , p = 0.004). There were no differences in cognition, motor disease severity, antiparkinsonian medications, or disease duration between groups. The results implicate the substantia nigra as an important psychomotor modulatory area of mood in patients with Lewy body disorders. ANN NEUROL 2021;;89:1046-1050.

Both comorbidity and worse performance status are associated with poorer overall survival after external beam radiotherapy for prostate cancer.

BACKGROUND: In this retrospective study, we evaluated the biochemical recurrence rate, metastatic disease progression, and prostate cancer-specific and overall survival in patients curatively treated with external beam radiotherapy (EBRT) for early prostate cancer (PC). We also examined the prognostic effect of comorbidity by Charlson Comorbidity Index (CCI) and overall performance status by Eastern Clinical Oncology Group (ECOG) score. METHODS: A total of 665 men treated between 2008 and 2013 were enrolled from Tampere University Hospital, Finland. Prostate-specific antigen (PSA) tests and hospital records were used to determine the 5-year survival for each aforementioned endpoint using a Kaplan-Meyer estimate. To analyze the impact of the selected prognostic factor, we used a Cox regression model to calculate the corresponding hazard ratio (HR) and 95% confidence interval (CI). RESULTS: With a median follow-up-time of 7.12 years, the 5-year overall survival (OS) after EBRT was 88.9% [86.5 -91.3%], prostate cancer-specific survival (PCSS) was 97.9% [96.7 -99.1%], metastasis-free survival (MFS) 94.8% [93.0 -96.6%] and biochemical recurrence-free survival (BRFS) 88.7% [86.2 -91.2%]. Both CCI (HR = 1.38, [1.25-1.51]) and ECOG score (HR = 1.63, [1.29-2.05]) declined OS, as well as Gleason score and T score (P <  0.05). Gleason score and T grade also associated to worse PCSS, MFS and BRFS. CONCLUSIONS: CCI and ECOG score are useful tools in evaluating the overall life expectancy of the patient after EBRT for PC. T-stage and Gleason score remain still the major prognostic factors.

Diffusion parameters of the core of cingulum are associated with age-related ventricular enlargement: a diffusion tensor tractography study.

PURPOSE: To evaluate the influence of the size of lateral ventricles on diffusion parameters of the normal cingulate bundle. METHODS: Eighty normal subjects (17-55 years) underwent MRI at 3 T including diffusion tensor imaging. Superior (SC) and inferior (IC) cingulum were analyzed separately. Mean diffusivity (MD0.30) and fractional anisotropy (FA0.30) were measured by tractography at FA threshold 0.30; further diffusion parameters were analyzed by tractography-based core analysis in volumes of 3.0 cm3/1.5 cm3. The diffusion parameters were correlated with corresponding cross-sectional coronal areas of lateral ventricles. The analysis was performed also separately for young (17-34) and middle-aged (35-55) subjects. RESULTS: FA0.30 values did not correlate with ventricular size, but there was a weak negative correlation (r = - 0.225) between MD0.30 of SC and ventricular size. In all controls and in the older age group, ventricular size correlated positively with core FA of SC (r = 0.262/r = 0.391) and negatively with mean diffusivity (r = - 0.324/r = - 0.303) and radial diffusivity (λ2: r = - 0.238/r = - 0.277; λ3: r = - 0.353/r = - 0.424) of the core of SC. In the younger age group, only the mean diffusivity of SC correlated with ventricular size (r = - 0.273). Ventricular size was not associated with axial diffusivity. The core parameters of IC did not correlate with ventricular size. CONCLUSION: Radial diffusivity of the core of cingulum decreases in age-dependent ventricular enlargement, which can be related to tissue compaction with stretching of axons and diminution of extracellular spaces. The phenomenon, which is reverse to the assumed effect of age-related myelin loss, can influence on DTI parameters in middle-aged subjects.

Insect herbivory dampens Subarctic birch forest C sink response to warming.

Climate warming is anticipated to make high latitude ecosystems stronger C sinks through increasing plant production. This effect might, however, be dampened by insect herbivores whose damage to plants at their background, non-outbreak densities may more than double under climate warming. Here, using an open-air warming experiment among Subarctic birch forest field layer vegetation, supplemented with birch plantlets, we show that a 2.3 °C air and 1.2 °C soil temperature increase can advance the growing season by 1-4 days, enhance soil N availability, leaf chlorophyll concentrations and plant growth up to 400%, 160% and 50% respectively, and lead up to 122% greater ecosystem CO2 uptake potential. However, comparable positive effects are also found when insect herbivory is reduced, and the effect of warming on C sink potential is intensified under reduced herbivory. Our results confirm the expected warming-induced increase in high latitude plant growth and CO2 uptake, but also reveal that herbivorous insects may significantly dampen the strengthening of the CO2 sink under climate warming.

Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome.

BACKGROUND: In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known. OBJECTIVE: We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome. METHODS: A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions. RESULTS: Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% (p = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication (p = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications. CONCLUSION: A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.