Västmanlands sjukhus Västerås

Cenobamate was approved in 2020 by the EMA for the adjunctive treatment of focal-onset seizures in adults. Based on data from clinical trials and early experience in adult patients, we used cenobamate in children whose seizures were not controlled with available options. We prospectively collected clinical data in patients who started treatment with cenobamate and report dosage, efficacy, retention rate, and adverse effects. Overall, 50 patients (median age 12.2 years, range 3.1-18.5, 19 patients below age 10 years; 44% female, median concomitant antiseizure medications 2) were treated with cenobamate for a median duration of 16 months (range 3-28). After gradually increasing cenobamate to clinical effect at a reduced dosage schedule, 60% (29/48) of children were responders (≥50% reduction) and 12% were free of major motor seizures. Patients were treated with an average daily dose of 3.7mg/kg. During cenobamate treatment, 8 (16%) patients were able to discontinue at least one concomitant antiseizure medication. The retention rate at 12 months was 82%. The most common adverse events were somnolence (42%), nausea/vomiting (4%), and ataxia (4%). The findings of this single-center real-world study are in line with prior controlled studies and real-world experience in adult patients, as well as with the limited published experience in children. The efficacy and lack of serious side effects found in this study supports the use of cenobamate as a treatment for epilepsy also in children and infants.

Risk factors for dementia include cardiovascular disease, smoking, and diabetes, which also are linked to compromised oral health and periodontal disease. Tooth loss, the hallmark of compromised oral health, is of interest for its systemic effects, including potential impacts on cognitive function. To evaluate tooth loss as a prognostic indicator in dementia, we conducted a register-based cohort study to assess associations of compromised oral health, defined by tooth loss, with mortality risk and progression of cognitive decline. The study population, obtained from linked Swedish nationwide health and quality assurance registries, comprised 3,361 individuals diagnosed with dementia from 2010 to 2013, with follow-up until 2018. Participants were categorized by tooth count: severe tooth loss (<10 remaining teeth), moderate tooth loss (10 to 19 remaining teeth), and a reference group with ≥20 remaining teeth. Mortality rate was analysed by Cox and Poisson regression models, and cognitive decline was assessed by longitudinal analyses of Mini Mental State Examination scores. Analyses were adjusted for demographic and health variables. Tooth loss at the time of dementia diagnosis was not independently associated with increased mortality after covariate adjustment (hazard ratio, 1.12 [95% CI, 0.97 to 1.28] for severe tooth loss vs reference). Annual Mini Mental State Examination scores declined across all groups, with no statistically significant differences among groups. After robust covariate control, no association was observed between tooth loss and increased mortality or cognitive decline in individuals newly diagnosed with dementia. Further studies are needed to determine whether tooth loss is an independent risk factor or a contributing marker in dementia prognosis.

Onset of depression and anxiety can occur before, during, or after pregnancy, and ongoing conditions can either improve or deteriorate at all stages. National and international guidelines recommend that maternal health care should contribute to improving pregnant women's mental health by consistently asking pertinent questions during pregnancy and offering necessary support and care. The implementation of a program for psychosocial assessment has been carried out in a region in Sweden. The program includes the identification of risk factors and ongoing mental ill-health, consultation with psychologists within maternal and child health care, and care pathways to other health care providers. The general aim of this research project is to investigate the effects of a program for psychosocial assessment during pregnancy on patients, as well as to evaluate the experiences of midwives and psychologists when working with the program. A multimethod study design will be used to evaluate possible effects of a program for psychosocial assessment during pregnancy, including a pre- and postimplementation comparison, alongside a qualitative study of the professionals' perspectives. Data sources for the research project include patient data from the Swedish Pregnancy Register, medical records, questionnaire responses, and interviews with midwives and psychologists. The recruitment process is completed, and data collection and analysis are ongoing. The dissemination plan includes several publications of original research and two doctoral theses. This study's results are expected to be relevant for maternal health care, both nationally and internationally, as scientific evaluations of the effects of implementing a program for psychosocial assessment during pregnancy are scarce. The implementation and evaluation of the program may hopefully, in the future, serve as a model for more standardized and effective care. It may influence national policies and attract attention as a model for improving perinatal mental health and maternity care. DERR1-10.2196/67179.

The aim of this study was to evaluate the early experiences of prostate artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH). This retrospective study included all patients treated for BPH who were referred to the radiology department for PAE in Västmanland between 2018 and 2021. Data were collected on patient demographics, International Prostate Symptom Score (IPSS), prostate-specific antigen level, and peri- and post-procedure outcomes. Clinical success was defined as a decrease in the IPSS by ≤3 points or catheter freedom. A total of 96 patients (median age 74 years) underwent PAE. Before PAE, 65% of the patients were treated with α-blockers and 83% with 5α-reductase inhibitors. Clinical success was achieved in 60 patients (63%). Among catheterized patients, 33 (53%) achieved catheter freedom. In the non-catheterized group, 27 (79%) experienced clinical success. No significant differences in outcomes were observed based on the presence of a median lobe. PAE appears to be a viable treatment option for BPH and may provide substantial symptom relief and catheter freedom for most patients. These findings suggest that PAE may be an effective alternative to more invasive procedures. Further research is needed to refine the patient selection criteria.

BackgroundAdoptive T cell therapy utilizing high-precision neoantigen targeting is a promising concept for the treatment of solid tumors. Personalized tumor trained lymphocytes (pTTL) is an autologous T cell product originating from regional lymph nodes (RLN) and targeting patient-specific neoantigens. A phase I/II First in Human (FIH) clinical trial of pTTL in Stage IV colorectal cancer (CRC) patients is ongoing.Methods pTTL is produced through in vitro expansion of T cells derived from tumor-adjacent RLNs. The T cells are stimulated with a patient-specific array of neoantigens utilizing the proprietary EpiTCer® technology. Tumor specific mutations are identified from next generation sequencing data obtained from tumor and normal tissue samples, and personal neoantigen epitopes are selected and ranked using the bioinformatic software PIOR®. Neoantigen epitope containing proteins are produced and linked to EpiTCer® beads (paramagnetic micro-particles), used for tumor-selective T cell expansion in pTTL manufacturing. pTTL is characterized by FACS phenotyping of T cell differentiation and activation markers. Neoantigen specificity is assessed by FACS and/or Fluorospot analysis of IFNγ, TNFα, degranulation marker CD107a and co-expression of cell activation induced markers (CD25, OX40, 4-1BB, and CD40-L) after restimulation of pTTL with EpiTCer® beads. TCR-sequencing of RLN cells and corresponding pTTL measures clonality of starting material and T cell product.Results and ConclusionsCharacterization of pTTL reveals that the pTTL manufacturing process generates a T cell product with individually varying CD4/CD8 ratios and minor proportions of other cells, mainly NK-cells. It contains a significant proportion of memory T cells with limited percentages of terminally differentiated T cells, indicating functionality. Functionality is also supported by upregulation of IFN-γ and TNF-α production and increased surface expression of CD107a, i.e. markers of anti-tumor killing potential, in response to specific EpiTCer® beads restimulation. TCR sequencing shows that pTTL is oligoclonal, indicating antigen-specific expansion during manufacturing from polyclonal RLNs. Moreover, neoantigen-specificity is corroborated by the upregulation of T cell activation-induced marker coexpression of varying magnitude after stimulation with separate neoantigens on a subgroup of CD4+ and CD8+ T cells within pTTL.In the ongoing FIH trial, up to 16 patients with Stage IV CRC will be treated with a single-dose pTTL after chemotherapy-based preconditioning with cyclophosphamide and fludarabine. A dose-escalation design is applied. The primary endpoint is safety. Secondary outcomes include objective response, overall survival, and progression-free survival. Biomarkers for pTTL persistence, pTTL characteristics, and response will be evaluated.Trial RegistrationTrial Registration EUDRA CT #2022-000394-96. Clinicaltrials.gov Identifier #NCT05908643.Ethics ApprovalThe study was approved by Swedish Ethical Review Authority, approval number 2022-01842-01.

Background and purposeThere is conflicting evidence regarding treatment outcomes after minimally invasive sacroiliac joint fusion for long-lasting severe sacroiliac joint pain. The primary aim of our cohort study was to investigate change in patient-reported outcome measures (PROMs) after minimally invasive sacroiliac joint surgery in daily practice in the Swedish Spine Registry. Secondary aims were to explore the proportion of patients reaching a patient acceptable symptom score (PASS) and the minimal clinically important difference (MCID) for pain scores, physical function, and health-related quality of life outcomes; furthermore, to evaluate self-reported satisfaction, walking distance, and changes in proportions of patients on full sick leave/disability leave and report complications and reoperations.MethodsData from the Swedish Spine Registry was collected for patients with first-time sacroiliac joint fusion, aged 21 to 70 years, with PROMs available preoperatively, at 1 or 2 years after last surgery. PROMs included Oswestry Disability Index (ODI), Numeric Rating Scale (NRS) for low back pain (LBP) and leg pain, and EQ-VAS, in addition to demographic variables. We calculated mean change from pre- to postoperative and the proportion of patients achieving MCID and PASS.Results68 patients had available pre- and postoperative data, with a mean age of 45 years (range 25–70) and 59 (87%) were female. At follow-up the mean reduction was 2.3 NRS points (95% confidence interval [CI] 1.6–2.9; P < 0.001) for LBP and 14.8 points (CI 10.6–18.9; P < 0.001) for ODI. EQ-VAS improved by 22 points (CI 15.4–30.3, P < 0.001) at follow-up. Approximately half of the patients achieved MCID and PASS for pain (MCID NRS LBP: 38/65 [59%] and PASS NRS LBP: 32/66 [49%]) and physical function (MCID ODI: 27/67 [40%] and PASS ODI: 24/67 [36%]). The odds for increasing the patient’s walking distance to over 1 km at follow-up were 3.5 (CI 1.8–7.0; P < 0.0001), and of getting off full sick leave or full disability leave was 0.57 (CI 0.4–0.8; P = 0.001). In the first 3 months after surgery 3 complications were reported, and in the follow-up period 2 reoperations.ConclusionWe found moderate treatment outcomes after minimally invasive sacroiliac joint fusion when applied in daily practice with moderate pain relief and small improvements in physical function.

The primary outcome was to compare overall postoperative surgical complications within 30 days after Hartmann's procedure (HP) compared with intersphincteric abdominoperineal excision (iAPE). The secondary outcome was major surgical complications (Clavien-Dindo ≥ III). There is uncertainty regarding the optimal surgical method in patients with rectal cancer when an anastomosis is unsuitable. Rectal cancer patients with a tumor height >5 cm, registered in the Swedish Colorectal Cancer Registry who received HP or iAPE electively in 2017-2020 were included, (HP, n = 696; iAPE, n = 314). Logistic regression analysis adjusting for body mass index, American Society of Anesthesiologists classification, sex, age, preoperative radiotherapy, tumor height, cancer stage, operating hospital, and type of operation was performed. Patients in the HP group were older and had higher American Society of Anesthesiologists scores. The mean operating time was less for HP (290 vs 377 min). Intraoperative bowel perforations were less frequent in the HP group, 3.6% versus 10.2%. Overall surgical complication rates were 20.3% after HP and 15.9% after iAPE (P = 0.118). Major surgical complications were 7.5% after HP and 5.7% and after iAPE (P = 0.351). Multiple regression analysis indicated a higher risk of overall surgical complications after HP (odds ratio: 1.63; 95% confidence interval = 1.09-2.45). HP was associated with a higher risk of surgical complications compared with iAPE. In patients unfit for anastomosis, iAPE may be preferable. However, the lack of statistical power regarding major surgical complications, prolonged operating time, increased risk of bowel perforation, and lack of long-term outcomes, raises uncertainty regarding recommending intersphincteric abdominoperineal excision as the preferred surgical approach.

I was deeply impressed by the recently published work “Deep Isoflurane Anesthesia Is Associated with Alterations in Ion Homeostasis and Specific Na+/K+-ATPase Impairment in the Rat Brain” by Reiffurth et al.1A long time ago, I was introduced by chance to Professor Gunnar Ronquist at Uppsala University, Sweden, and was introduced to his method of analyzing adenylate kinase in cerebrospinal fluid (CSF). This enzyme, which has a central role in energy metabolism—catalyzing the dismutation reaction 2 ADP ↔ AMP + ATP—is strictly intracellular. Its physicochemical properties of low molecular weight (about 22,000 Da) and high turnover rate in CSF explain its value as a damage marker. If found extracellularly, e.g., in CSF, it indicates disruption of cellular integrity. So, adenylate kinase leaked into the CSF signals neuronal damage. By then, CSF adenylate kinase had already been used to detect brain damage associated with brain tumors,2 in schizophrenia,3 in neurologic diseases,4 after open-heart surgery,5 in meningoencephalitis,6 after circulatory arrest,7 and in hypoxic newborns.8 I thought, it would be interesting to use this analysis to show that deep isoflurane anesthesia for induced hypotension for orthognathic surgery carries no risk to the brain.Unfortunately, the hypothesis was wrong. In a first pilot study, “nine out of ten patients showed a marked increase in CSF adenylate kinase postoperatively compared with preoperative values.”9 Our first guess was that hypotension explained the result. However, in a subsequent study, in which patients were randomly assigned to hypo- or normotension, we could not confirm the hypothesis.10 At this stage, we speculated on the role of ion pumps. A PhD student worked hard for several months trying to set up a mouse model to investigate this aspect, but he unfortunately failed. I guess the time was not right. Happily, technologic progress has come so far that Clemens Reiffurth et al. now have detailed insights into ion flows during isoflurane anesthesia.1I look forward to following the work of this group and congratulate them on their success so far.Support was provided solely from institutional and/or departmental sources.Dr. Enlund has received consulting fees from Nimbelle AB (Stockholm, Sweden) and honoraria for lectures from Mälardalen University (Västerås, Sweden) and is on the board of the ENCORE trial.