Long-term outcome of operated Chiari I patients between 2005 and 2020 in Eastern Finland.

PURPOSE: The purpose of our study was to examine the long-term outcomes of operated Chiari malformation type 1 (CM1) patients and evaluate whether different duraplasty techniques affected outcome after surgery in Kuopio University Hospital catchment area. METHODS: In this retrospective study, a total of 93 patients were diagnosed with CM1 and underwent posterior fossa decompression surgery with or without duraplasty between 2005 and 2020. All patients' medical records were examined for baseline characteristics, surgical details, and long-term follow-up data after operation. RESULTS: The mean age of CM1 patients was 25.9 years (SD 19.2 years), with female preponderance 69/93 (73.4%). The mean clinical follow-up time was 26.5 months (SD 33.5 months). The most common presenting symptoms were headache, symptoms of extremities, and paresthesia. Posterior fossa decompression with duraplasty was performed in 87 (93.5%) patients and bony decompression in 6 (6.5%) patients. After surgery, preoperative symptoms alleviated in 84.9% (79/93) and the postoperative syringomyelia regression rate was 89.2% (33/37) of all patients. The postoperative complication rate was 34.4% (32/93), with aseptic meningitis being the most common, 25.8% (24/93). Revision surgery was required in 14% (13/93) of patients. No significant correlation between postoperative outcome and extent of dural decompression, or type of duraplasty performed was found. CONCLUSION: This is the largest reported series of surgically treated CM1 patients in Finland. Posterior fossa decompression is an effective procedure for CM1 symptomology. Duraplasty technique had no significant difference in complication rate or long-term outcomes.

Real-World Clinical Outcomes in Biological Subgroups of Breast Cancer in the Hospital District of Southwest Finland.

BACKGROUND: Comparing breast cancer survival trends globally, Finland is among the top three countries in Europe. However, outcome data on breast cancer subgroups in the Finnish population are limited. This retrospective, registry-based study aimed to assess patient characteristics and clinical outcomes of different breast cancer subgroups in early (EBC) and metastatic breast cancer (MBC) in a real-life clinical setting. MATERIALS AND METHODS: The study consisted of 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Patients were divided into four mutually exclusive groups: human epidermal growth factor receptor 2 positive (HER2+), triple negative, HER2-/hormone receptor positive (HR+), and HER2 and/or HR status unknown, and further into patients with EBC and MBC. Overall survival (OS) was assessed as a clinical outcome, as well as the following real-world (rw) clinical outcomes: disease-free survival (rwDFS), progression-free survival (rwPFS), and distant recurrence-free interval (rwDRFI). RESULTS: Within EBC, 5-year survival was the highest (88%) in HER2-/HR+, followed by 85% in HER2+, and 75% in triple negative. The rwDFS varied significantly in EBC (5-year rwDFS HER2 -/HR+, HER2+, triple negative: 87%, 80%, 71% respectively). In MBC, median survival was 2 years for both HER2-/HR+ and HER2+ and markedly shorter for triple negative (0.8 years). Independent predictors of mortality were age (hazard ratio [HR], 1.1), other subgroups than HER2-/HR+ (HR, 1.2-1.9), metastatic disease (HR, 9.8), and other malignancies (HR, 2.7). CONCLUSION: This registry-based study demonstrates significant differences in breast cancer outcomes on the subgroup level, as well as poorer outcomes compared with clinical trials, giving complementary insight on clinical characteristics in an unselected patient population. IMPLICATIONS FOR PRACTICE: This retrospective, registry-based study assessed the clinical outcomes of different breast cancer subgroups in 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Results demonstrated significant variation in the survival between subgroups in both early breast cancer and metastatic breast cancer, as well as differences between unselected patients representing the standard of care and randomized clinical trials. Although, according to the global comparison of survival trends, the net survival of patients with breast cancer in Finland is generally high, there is great variation between subgroups. These real-life breast cancer data provide tools to further evaluate medical need in different breast cancer subgroups.

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. METHOD: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman's criteria, hence referred to as symptomatic controls. RESULTS: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). CONCLUSIONS: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

Engineering chimeric thermostable GH7 cellobiohydrolases in Saccharomyces cerevisiae.

We report here the effect of adding different types of carbohydrate-binding modules (CBM) to a single-module GH7 family cellobiohydrolase Cel7A from a thermophilic fungus Talaromyces emersonii (TeCel7A). Both bacterial and fungal CBMs derived from families 1, 2 and 3, all reported to bind to crystalline cellulose, were used. Chimeric cellobiohydrolases with an additional S-S bridge in the catalytic module of TeCel7A were also made. All the fusion proteins were secreted in active form and in good yields by Saccharomyces cerevisiae. The purified chimeric enzymes bound to cellulose clearly better than the catalytic module alone and demonstrated high thermal stability, having unfolding temperatures (T m) ranging from 72 °C to 77 °C. The highest activity enhancement on microcrystalline cellulose could be gained by a fusion with a bacterial CBM3 derived from Clostridium thermocellum cellulosomal-scaffolding protein CipA. The two CBM3 fusion enzymes tested were more active than the reference enzyme Trichoderma reesei Cel7A both at moderate (45 °C and 55 °C) and at high temperatures (60 °C and 65 °C), the hydrolysis yields being two- to three-fold better at 60 °C, and six- to seven-fold better at 65 °C. The best enzyme variant was also tested on a lignocellulosic feedstock hydrolysis, which demonstrated its potency in biomass hydrolysis even at 70 °C.

Hyperspectral Imaging in Brain Tumor Surgery-Evidence of Machine Learning-Based Performance.

BACKGROUND: Hyperspectral imaging (HSI) has the potential to enhance surgical tissue detection and diagnostics. Definite utilization of intraoperative HSI guidance demands validated machine learning and public datasets that currently do not exist. Moreover, current imaging conventions are dispersed, and evidence-based paradigms for neurosurgical HSI have not been declared. METHODS: We presented the rationale and a detailed clinical paradigm for establishing microneurosurgical HSI guidance. In addition, a systematic literature review was conducted to summarize the current indications and performance of neurosurgical HSI systems, with an emphasis on machine learning-based methods. RESULTS: The published data comprised a few case series or case reports aiming to classify tissues during glioma operations. For a multitissue classification problem, the highest overall accuracy of 80% was obtained using deep learning. Our HSI system was capable of intraoperative data acquisition and visualization with minimal disturbance to glioma surgery. CONCLUSIONS: In a limited number of publications, neurosurgical HSI has demonstrated unique capabilities in contrast to the established imaging techniques. Multidisciplinary work is required to establish communicable HSI standards and clinical impact. Our HSI paradigm endorses systematic intraoperative HSI data collection, which aims to facilitate the related standards, medical device regulations, and value-based medical imaging systems.

Effect of temperature on lignin-derived inhibition studied with three structurally different cellobiohydrolases.

Non-productive enzyme adsorption onto lignin inhibits enzymatic hydrolysis of lignocellulosic biomass. Three cellobiohydrolases, Trichoderma reesei Cel7A (TrCel7A) and two engineered fusion enzymes, with distinctive modular structures and temperature stabilities were employed to study the effect of temperature on inhibition arising from non-productive cellulase adsorption. The fusion enzymes, TeCel7A-CBM1 and TeCel7A-CBM3, were composed of a thermostable Talaromyces emersonii Cel7A (TeCel7A) catalytic domain fused to a carbohydrate-binding module (CBM) either from family 1 or from family 3. With all studied enzymes, increase in temperature was found to increase the inhibitory effect of supplemented lignin in the enzymatic hydrolysis of microcrystalline cellulose. However, for the different enzymes, lignin-derived inhibition emerged at different temperatures. Low binding onto lignin and thermostable structure were characteristic for the most lignin-tolerant enzyme, TeCel7A-CBM1, whereas TrCel7A was most susceptible to lignin especially at elevated temperature (55 °C).