Töölö Hospital

BackgroundProstate Cancer (PCa) represents the second leading cause of cancer-related death in men. Prostate-specific antigen (PSA) serum testing, currently used for PCa screening, lacks the necessary sensitivity and specificity. New non-invasive diagnostic tools able to discriminate tumoral from benign conditions and aggressive (AG-PCa) from indolent forms of PCa (NAG-PCa) are required to avoid unnecessary biopsies.MethodsIn this work, 32 formerly N-glycosylated peptides were quantified by PRM (parallel reaction monitoring) in 163 serum samples (79 from PCa patients and 84 from individuals affected by benign prostatic hyperplasia (BPH)) in two technical replicates. These potential biomarker candidates were prioritized through a multi-stage biomarker discovery pipeline articulated in: discovery, LC-PRM assay development and verification phases. Because of the well-established involvement of glycoproteins in cancer development and progression, the proteomic analysis was focused on glycoproteins enriched by TiO2 (titanium dioxide) strategy.ResultsMachine learning algorithms have been applied to the combined matrix comprising proteomic and clinical variables, resulting in a predictive model based on six proteomic variables (RNASE1, LAMP2, LUM, MASP1, NCAM1, GPLD1) and five clinical variables (prostate dimension, proPSA, free-PSA, total-PSA, free/total-PSA) able to distinguish PCa from BPH with an area under the Receiver Operating Characteristic (ROC) curve of 0.93. This model outperformed PSA alone which, on the same sample set, was able to discriminate PCa from BPH with an AUC of 0.79.To improve the clinical managing of PCa patients, an explorative small-scale analysis (79 samples) aimed at distinguishing AG-PCa from NAG-PCa was conducted. A predictor of PCa aggressiveness based on the combination of 7 proteomic variables (FCN3, LGALS3BP, AZU1, C6, LAMB1, CHL1, POSTN) and proPSA was developed (AUC of 0.69).ConclusionsTo address the impelling need of more sensitive and specific serum diagnostic tests, a predictive model combining proteomic and clinical variables was developed. A preliminary evaluation to build a new tool able to discriminate aggressive presentations of PCa from tumors with benign behavior was exploited. This predictor displayed moderate performances, but no conclusions can be drawn due to the limited number of the sample cohort.Data are available via ProteomeXchange with identifier PXD035935.

There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.

Abstract IntroductionThis study comprises all hospitalized work related burn injuries in one country during 2011-2015. The purpose was to describe demographics, causes and risk factors of occupational burn injuries with special focus on the outcome of return to work. Material and methodsThis is a retrospective study on two data sources of which Finnish Workers’ Compensation Center´s (FWCC) register includes all work-related burn cases at a given time. Additional data has been obtained from those patients, who were referred to the National Burn Centre (NBC) during the same time according to the Emergency Management of Severe Burns (EMSB) criteria. We compare demographics, injury mechanisms and general burn data of these two patient groups. ResultsBased on FWCC register, in 2011-2015 occurred 11623 work related burn cases of whom 54% were men. During the study period NBC admitted 26 patients fulfilling EMSB criteria. The most severe patients treated in NBC had injuries affecting multiple body parts. In FWCC data hand was most injured body part. Kitchen/bakery work was the most common profession in FWCC register but in NBC material industrial and transport professions dominated. In FWCC register patients had lower mean age (37 years vs. 43 years). Most severe injuries occurred among older patients: in NBC data those with total body surface area 40% or over had mean age 53 years. Majority of patients returned to work. ConclusionSafety at work in Finland is good and the vast majority of work-related burn injuries are minor. Young adults working in kitchen and bakery work are susceptible to minor burn injuries whereas, unexpectedly, elderly men working in transports and industry sustain most severe burn accidents. Retirement after work related injury becomes very expensive for all parties and this data can be used in preventing those cases as well as the minor accidents.

BackgroundSpinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.MethodsWe randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.ResultsOf the 100 patients analyzed, patients receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml-1 (74.7 mg) or 0.25 mg ml-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013–0.32, P = 0.033). The occurrence of adverse events was similar among the groups.ConclusionsOxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.

BackgroundDespite the well described heterogeneity in glioblastoma (GBM), treatment is standardized, and clinical trials investigate treatment effects at population level. Genomics-driven oncology for stratified treatments allow clinical decision making in only a small minority of screened patients. Addressing tumor heterogeneity, we aimed to establish a clinical translational protocol in recurrent GBM (recGBM) utilizing autologous glioblastoma stem cell (GSC) cultures and automated high-throughput drug sensitivity and resistance testing (DSRT) for individualized treatment within the time available for clinical application.ResultsFrom ten patients undergoing surgery for recGBM, we established individual cell cultures and characterized the GSCs by functional assays. 7/10 GSC cultures could be serially expanded. The individual GSCs displayed intertumoral differences in their proliferative capacity, expression of stem cell markers and variation in their in vitro and in vivo morphology. We defined a time frame of 10 weeks from surgery to complete the entire pre-clinical work-up; establish individualized GSC cultures, evaluate drug sensitivity patterns of 525 anticancer drugs, and identify options for individualized treatment. Within the time frame for clinical translation 5/7 cultures reached sufficient cell yield for complete drug screening. The DSRT revealed significant intertumoral heterogeneity to anticancer drugs (p < 0.0001). Using curated reference databases of drug sensitivity in GBM and healthy bone marrow cells, we identified individualized treatment options in all patients. Individualized treatment options could be selected from FDA-approved drugs from a variety of different drug classes in all cases.ConclusionsIn recGBM, GSC cultures could successfully be established in the majority of patients. The individual cultures displayed intertumoral heterogeneity in their in vitro and in vivo behavior. Within a time frame for clinical application, we could perform DSRT in 50% of recGBM patients. The DSRT revealed a remarkable intertumoral heterogeneity in sensitivity to anticancer drugs in recGBM that could allow tailored therapeutic options for functional precision medicine.

ObjectiveTo assess if arthroscopic partial meniscectomy (APM) is superior to placebo surgery in the treatment of patients with degenerative tear of the medial meniscus.MethodsIn this multicentre, randomised, participant-blinded and outcome assessor-blinded, placebo-surgery controlled trial, 146 adults, aged 35–65 years, with knee symptoms consistent with degenerative medial meniscus tear and no knee osteoarthritis were randomised to APM or placebo surgery. The primary outcome was the between-group difference in the change from baseline in the Western Ontario Meniscal Evaluation Tool (WOMET) and Lysholm knee scores and knee pain after exercise at 24 months after surgery. Secondary outcomes included the frequency of unblinding of the treatment-group allocation, participants' satisfaction, impression of change, return to normal activities, the incidence of serious adverse events and the presence of meniscal symptoms in clinical examination. Two subgroup analyses, assessing the outcome on those with mechanical symptoms and those with unstable meniscus tears, were also carried out.ResultsIn the intention-to-treat analysis, there were no significant between-group differences in the mean changes from baseline to 24 months in WOMET score: 27.3 in the APM group as compared with 31.6 in the placebo-surgery group (between-group difference, −4.3; 95% CI, −11.3 to 2.6); Lysholm knee score: 23.1 and 26.3, respectively (−3.2; −8.9 to 2.4) or knee pain after exercise, 3.5 and 3.9, respectively (−0.4; −1.3 to 0.5). There were no statistically significant differences between the two groups in any of the secondary outcomes or within the analysed subgroups.ConclusionsIn this 2-year follow-up of patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after APM were no better than those after placebo surgery. No evidence could be found to support the prevailing ideas that patients with presence of mechanical symptoms or certain meniscus tear characteristics or those who have failed initial conservative treatment are more likely to benefit from APM.

The latissimus dorsi (LD) muscle flap is frequently used for free tissue transfer to reconstruct large defects of the extremities. As a free flap, the LD also can be harvested as a muscle-sparing flap (MS-LD), preserving the innervation and insertion of the remaining muscle. Conventional harvesting of the LD flap, however, results in a long scar on the lateral back. Harvesting using an endoscopic approach minimizes donor site morbidity. We present our modified endoscopic technique with CO2 insufflation and standard endoscopic instruments for harvesting the LD or MS-LD muscle flap. Ten patients (mean age 43 years, range 22-66) underwent endoscopically harvested LD or MS-LD free-flap reconstruction for upper and lower extremity defects. Harvesting required only a short (3-5 cm) incision in the axilla for dissection of the vascular pedicle and the motor nerve, and the remainder of the dissection was performed endoscopically with CO2 insufflation. Dissection was achieved through three of four 5-mm ports and 30° view angle optics. Six of the flaps were MS-LD flaps. The largest flap size was 18 × 16 cm. Mean flap harvest time was 164 min (range 105-270 min). One total flap was lost 3 days postoperatively due to anastomotic thrombosis in a trauma patient who was later diagnosed with hypercoagulopathy. No donor site scar or wound complications were observed during the follow-up (20.1 months). Endoscopic harvesting of an LD muscle free flap with CO2 insufflation and standard laparoscopic equipment is a feasible option for free-flap reconstruction. © 2016 Wiley Periodicals, Inc. Microsurgery 37:383-387, 2017.

Background The development of modern medicine has resulted in changes in the predisposing conditions, clinical picture, treatment and results of treatment of intracranial abscesses. This study sought to evaluate these changes in a hospital district. Methods A retrospective analysis of the clinical data of all patients treated due to intracranial abscesses at a tertiary referral centre, between 1970–2012. Results The total number of intracranial abscesses was 166. The incidence of intracranial abscesses was 0.33/100 000/year (2000–2012). The most common predisposing conditions were infection of the ear-, nose- and throat region (22%), odontogenic infection (15%) and cardiac anomaly (13%). Lately (2000–2012), infections of the ear-, nose- and throat region (15%) and cardiac anomalies (5%) have become less common, whereas odontogenic infections (32%) have become more common. The most common pathogens belong to Streptococcus spp (42%), Fusobacteriae (14%), Actinomycetales (8%) and Staphylococcus spp (8%). Most patients (66%) experienced a favourable recovery; the proportion of patients with favourable outcome enabling return to prior occupation rose over time, from 12% in 1970–1989 to 24% in 1990–2012. Conclusions The predisposing conditions for intracranial abscesses have changed markedly within the study period. Odontogenic infections have become a common predisposing condition, whereas infections of the ear-, nose- and throat region and cardiac malformations are nowadays less common as predisposing conditions compared to at the beginning of the study period. The proportion of patients with favourable outcome enabling return to prior occupation seems to have increased with time.

We herein present a technique of using the umbilical stalk for reconstruction of the external auditory meatus. A 49-year-old female presented with locally aggressive melanoma affecting her mastoid region. She underwent radical excision including the skin and soft tissues around the external ear with simultaneous lymph node clearance. The resultant defect measured 15 cm × 8 cm in diameter and was 2.5 cm deep. This was reconstructed with a similarly sized microvascular paraumbilical perforator flap that included the umbilical stalk. In the post-operative course there was complete flap survival but a prolonged wound dehiscence near the auditory meatus that required revision surgery. At 15-months follow-up, the patient was melanoma-free and the auditory meatus was patent. Hearing was also preserved. The umbilical stalk is one of the few skin covered tubed structures in the human body that may be used without major donor morbidity to "replace like with like," the auditory channel.