Prognosis Outcome Research Articles

Neuronal plasma biomarkers in acute ischemic stroke.

Early imaging-based detection of acute ischemic stroke (AIS) has improved in the era of reperfusion therapy. Despite of this, prognosis of outcome after AIS remains a challenge. Therefore, parameters that support clinical decision making are sought. Blood-based biomarkers have the potential to provide valuable information in addition to the established prognostic factors. Neuronal biomarkers of acute or degenerative neuronal injury have shown to be reliably detected in plasma. These biomarkers are well-established in neurodegenerative pathology, such as Alzheimer's disease. In this study, we explored the association between stroke diameter and plasma biomarkers for neuronal injury and tau pathophysiology (brain-derived tau [BD-tau], phosphorylated-tau-217 [p-tau21] and neurofilament light [NfL]) in patients (n = 193) admitted to the acute ward, Akershus University Hospital. All patients received a final diagnosis of AIS, transient ischemic attack or stroke mimics. Blood samples were obtained the day after admission. We find that levels of BD-tau (p = .004) and NfL (p = .011) were higher after AIS than in patients with stroke mimics. The cortical stroke diameter correlated with BD-tau (tau-b = 0.64, p < .001) and p-tau217 (tau-b = 0.36, p = .003). Linear regression confirmed BD-tau to be the strongest variable associated with stroke diameter, pointing to the potential clinical value of plasma BD-tau in outcome prediction after AIS.

A-313 Use of the Preeclampsia Ratio in the Prognosis of Preterm Delivery and Adverse Outcomes

Abstract Background Preeclampsia (PE) is a hypertensive disorder of pregnancy that is characterized by high blood pressure and end-organ dysfunction with or without proteinuria after 20 weeks gestation. PE occurs in 6-8% of pregnancies and contributes to significant fetal, neonatal, and maternal morbidity and mortality. The ratio of two angiogenic placental proteins, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), are used in the management of PE. The purpose of this study was to evaluate use of the sFlt-1/PlGF ratio (PE ratio) generated using the ADVIA Centaur® and Atellica® IM sFlt-1 assay and the ADVIA Centaur and Atellica IM PlGF assays in the prognosis of preterm delivery and adverse outcomes in women presenting with signs and symptoms of PE. Methods A total of 654 females with singleton pregnancies between gestational weeks 20+0 days and 35+6 days and who had signs and symptoms of PE, but without severe features of PE were enrolled at 24 collection sites and followed prospectively for two weeks. Serum samples were collected at enrollment and adverse outcomes that included preterm delivery were prospectively collected within the two weeks after enrollment. Serum samples from approximately half of the population (n=316) were tested in singlicate using the sFlt-1 and PlGF assays on the ADVIA Centaur system in a derivation study that determined the optimal cutoff of the PE ratio in relation to adverse outcome. The remaining serum samples (n=338) were subsequently tested on the ADVIA Centaur system in a cut-off validation study that evaluated the clinical performance (sensitivity [SE], specificity [SP], positive predictive value [PPV], negative predictive value [NPV]) of the PE ratio at the derived cutoff in relation to adverse outcome. Method comparison studies were performed between the ADVIA Centaur versus the Roche Elecsys sFlt-1 and PlGF assays (n=255) and the ADVIA Centaur versus the Atellica IM sFlt-1 and PlGF assays (n=316). Results The rate of maternal adverse outcomes within two weeks was similar in the derivation study (32.3%) and validation study (28.1%). Using a receiver operating characteristic (ROC) curve analysis with the derivation cohort, a derived cutoff of 38 showed optimal clinical performance of the PE ratio in relation to adverse outcome (SE=72.5%, SP=94.7%, PPV=84.6%, NPV=89.5%). Similar clinical performance results of the PE ratio at the cutoff of 38 in relation to adverse outcome were found with the verification cohort (SE=88.42%, SP=87.65%, PPV=73.68%, NPV=95.09%). Weighted Deming regression analysis demonstrated equivalency between the Centaur, Roche, and Atellica PE ratios with correlation coefficients (r) of 0.9242 (Centaur vs Roche) and 0.995 (Centaur vs Atellica). Conclusions Measurement of sFlt-1 and PlGF to determine PE ratio can be performed on either the ADVIA Centaur or Atellica Analyzer and can be used to identify women presenting with PE or signs and symptoms of PE who are at high risk of experiencing an adverse event in the subsequent two weeks. Not available for sale in the U.S.A. The products/features mentioned herein are not commercially available in all countries. Their future availability cannot be guaranteed.

Anti-phospholipid antibodies nephropathy is associated with an increased risk of kidney failure: a systematic literature review and meta-analysis.

Anti-phospholipid antibodies nephropathy (aPL-N) is a complex feature of anti-phospholipid syndrome due to microvascular lesions. Renal prognosis and predictors of outcome are not yet known. We performed a systematic review of the literature (February 2006-January 2024) using the PubMed, Scopus, Cochrane Library and EMBASE databases. Two reviewers independently conducted literature screening and data extraction in a blinded, standardized manner. A random effects model was used to pool odds ratios (ORs) [with 95% confidence interval (CI)] for the primary analysis, the risk of kidney failure. Subgroup analyses were performed for clinical and laboratory features that predicted renal outcomes. Heterogeneity was assessed by I2. Six records involving 709 patients were included in the meta-analysis. Biopsy-proven aPL-N was found in 238/832 (28.6%) patients. Acute kidney injury (AKI) was present at diagnosis in 20/65 (30.8%), while 73/233 (31.3%) patients with aPL-N developed chronic kidney disease (CKD)/end-stage kidney disease (ESKD) at follow-up. aPL-N was associated with an increased risk of CKD/ESKD [OR 6.89 (95% CI 2.42-19.58)] and AKI [OR 2.97 (95% CI 1-4-6.29)]. Arterial hypertension and positivity for lupus anticoagulant, anti-cardiolipin antibodies and anti-β2 glycoprotein I antibodies were associated with an increased risk of developing aPL-N [OR 3.7 (95% CI 1.9-7.23), OR 4.01 (95% CI 1.88-8.53), OR 2.35 (95% CI 1.31-4.21) and OR 19.2 (95% CI 2.91-125.75), respectively]. aPL-N is associated with poor renal outcomes. High blood pressure and aPL positivity have been identified as predictors of adverse renal outcomes. This up-to-date knowledge on renal outcomes and predictors of renal outcomes in aPL-N enables a personalized follow-up and therapeutic approach.

Efficacy and safety of ketogenic diet in infants with epilepsy: KIWE RCT

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with &gt; 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Analysis of Fetal Growth and Pregnancy Outcome in Pregnant Women Infected with Novel Coronavirus in Mid-Pregnancy.

To investigate whether fetal prenatal ultrasound, fetal growth rate, and pregnancy outcome statistically differ between women infected with novel coronavirus (COVID-19) in mid-pregnancy and an uninfected control group. A retrospective analysis of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), and z-scores for each among 46 pregnant women diagnosed with COVID-19 in mid-pregnancy between December 01, 2022 and June 31, 2023 was conducted. A control group included 92 pregnant women negative for COVID-19 during the same period and was also analyzed. To examine fetal growth, rate of increase in BPD, HC, AC, FL, and estimated fetal weight (EFW) between second and third trimester scans were analyzed. In addition, pregnancy outcome, maternal comorbidities, and neonatal prognosis were assessed. The occurrence of gestational diabetes differed significantly between groups, but the fetal growth rate and EFW did not. Similarly, pregnancy outcomes and neonatal prognoses did not differ significantly between groups. Gestational diabetes was a complication that differed between patients with and without COVID-19 in this study. COVID-19 in pregnant women did not affect fetal development. Therefore, these preliminary data suggest that increased fetal monitoring is not necessary for women infected with COVID-19 during the second trimester, and these women should be reassured of the low risk of adverse fetal outcomes.

Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

The role of epigenetics in the diagnosis, treatment and rehabilitation of patients with malignant neoplasms

Background. Epigenetics is a branch of genetics that studies the influence of external factors on gene expression. Many studies have shown the role of epigenetic regulation mechanisms in gene expression, including patients with cancer. Despite the clear prospects of using the principles and methods of epigenetics in the diagnosis, treatment and recovery, the implementation of this new technology remains at a relatively low level.Objective: to determine the importance of epigenetic mechanisms in the diagnosis, outcome prognosis and rehabilitation of patients with oncological diseases.Material and methods. The search for publications was performed in scientific databases and electronic libraries: PubMed/ MEDLINE, ScienceDirect, Google Schoolar, eLibrary. The review included 79 articles on the role of epigenetic mechanisms in the diagnosis, treatment and rehabilitation of cancer patients.Results. DNA methylation, covalent histone modifications, and microRNA regulation are the most studied epigenetic changes (EGC) in cancer patients. Liquid biopsy is alternative approach to the detection of epigenetic biomarkers. A number of biomarkers were identified that make it possible to diagnose oncological diseases, e.g. lung cancer and breast cancer, and predict their course. Some EGC were assosiated with the implementation of rehabilitation measures, such as nutritional support, physical activity, maintaining circadian rhythms and acupuncture.Conslusion. The analysis of publications confirmed the significant importance of EGC on the development of malignant neoplasms. The results indicated a sufficient number of studies dedicated to EGC biomarkers as new diagnostic tools and predicting the oncological disease outcome. But there is an insufficient number of studies on EGC mechanisms in rehabilitation. Further investigation on epigenetic mechanisms of variability will allow making significant progress in the development of targeted drugs and personalized rehabilitation of patients with malignant neoplasms.

Distal Radius Fracture Rehabilitation.

Distal radius fracture (DRF) is arguably the most common upper extremity fracture resulting from a fall accident. These clinical practice guidelines (CPG) were developed to guide all aspects of the management of DRF by physical therapists and other rehabilitation practitioners, such as certified hand therapists. This CPG employed a systematic review methodology to locate, appraise, and synthesize contemporary evidence while developing practice recommendations for determining the prognosis of outcomes, examination, and interventions while managing individuals with DRF. The quality of the primary studies found in the literature search was appraised using standardized tools. The strength of the available evidence for a particular practice domain (e.g., prognosis or intervention) was graded as strong, moderate, weak, or conflicting, where such gradings guided the level of obligation for each practice recommendation. Lastly, the CPG also provided the gaps in the evidence pool for the rehabilitation of DRF that future research efforts can address. J Orthop Sports Phys Ther 2024;54(9):CPG1-CPG78. doi:10.2519/jospt.2024.0301.

Physical Therapists' Prognosis of Outcomes After a Hip or Quadriceps Exercise Intervention in Patients With Patellofemoral Pain: A Secondary Analysis of a Randomized Trial.

OBJECTIVE: Can physical therapists who are treating patients with patellofemoral pain (PFP) predict the outcome of a 12-week exercise intervention based on initial assessment, and what are the physical therapists' reasons for prediction? DESIGN: Secondary analysis of a randomized trial. METHODS: After the initial assessment, physical therapists were asked to predict the prognosis of 200 patients with PFP who were allocated to 12 weeks of quadriceps exercises (QEs) or hip exercises (HEs) on a 1-to-10 Likert scale, and to describe their reasoning for the prediction score. OUTCOMES: measures were changes from baseline to weeks 12 and 26 on the Anterior Knee Pain Scale (range 0-100) and a transition questionnaire (TransQ). Linear mixed-effects models were used to assess the prediction. Secondly, we used a qualitative approach to summarize the physical therapists' reasoning (written notes) when predicting the outcome. RESULTS: There was no association between physical therapists' prognosis and changes in Anterior Knee Pain Scale for QE or HE at weeks 12 and 26 (slopes: -0.14 to -0.51 with wide 95% confidence intervals). There was no association between physical therapists' assessment of prognosis using TransQ for QE or HE at weeks 12 and 26 (odds ratio: 0.99 to 1.17 with wide 95% confidence intervals). CONCLUSION: Physical therapists' prognosis based on initial assessment was not associated with outcomes after 12 weeks of either quadriceps or hip exercise therapy among patients with PFP. Physical therapists' prognoses were not useful as a source of information and to identify PFP patients with poor or good projected outcomes. J Orthop Sports Phys Ther 2024;54(8):541-550. Epub 6 June 2024. doi:10.2519/jospt.2024.12258.

Impact of seizure onset zone and intracranial electroencephalography ictal characteristics on epilepsy surgery outcomes in tuberous sclerosis complex

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1–3 was defined as good and 4–6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.

Computer-aided prognosis of tuberculous meningitis combining imaging and non-imaging data

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. Clinical features, such as coma, can predict death, but they are insufficient for the accurate prognosis of other outcomes, especially when impacted by co-morbidities such as HIV infection. Brain magnetic resonance imaging (MRI) characterises the extent and severity of disease and may enable more accurate prediction of complications and poor outcomes. We analysed clinical and brain MRI data from a prospective longitudinal study of 216 adults with TBM; 73 (34%) were HIV-positive, a factor highly correlated with mortality. We implemented an end-to-end framework to model clinical and imaging features to predict disease progression. Our model used state-of-the-art machine learning models for automatic imaging feature encoding, and time-series models for forecasting, to predict TBM progression. The proposed approach is designed to be robust to missing data via a novel tailored model optimisation framework. Our model achieved a 60% balanced accuracy in predicting the prognosis of TBM patients over the six different classes. HIV status did not alter the performance of the models. Furthermore, our approach identified brain morphological lesions caused by TBM in both HIV and non-HIV-infected, associating lesions to the disease staging with an overall accuracy of 96%. These results suggest that the lesions caused by TBM are analogous in both populations, regardless of the severity of the disease. Lastly, our models correctly identified changes in disease symptomatology and severity in 80% of the cases. Our approach is the first attempt at predicting the prognosis of TBM by combining imaging and clinical data, via a machine learning model. The approach has the potential to accurately predict disease progression and enable timely clinical intervention.

Intranuclear Irradiation Inhibits Solid Tumor Growth by Upregulating Caspase8 and Activating Apoptosis.

Radioimmunotherapy (RIT) is a novel and promising cancer treatment method, with ongoing research focusing on RIT antibody selection, radionuclides, treatment options, and benefited patient groups. As we dive into the mechanisms of tumor biology, a deeper exploration of how RIT affects tumor tissue is needed to provide new ways to improve clinical treatment outcome and patient prognosis. We labeled the anti-PD-L1 monoclonal antibody atezolizumab with iodine-131 (131I), separated and purified the labeled mAb with Sephadex G-25 medium gel filtration resin, and tested product stability. We detected the in vivo activity of 131I-PD-L1 mAb by analyzing its in vivo biodistribution and performing SPECT imaging and then set different treatment groups to study the effect of 131I-atezolizumab on the survival of tumor-bearing mice. Western blot, real-time quantitative PCR, and immunohistochemistry were used to detect the expression level of Caspase8 and Nlrp3 in tumor. TUNEL fluorescence staining was used to detect the apoptosis in the tumor. The radiopharmaceutical molecular probe 131I-atezolizumab showed high stability and in vivo biological activity. The treatment regimen adopted had a positive effect on the survival of tumor-bearing mice. 131I internal irradiation upregulated Caspase8 in tumor and ultimately inhibited solid tumor growth by activating apoptosis pathways. We also found a significant increase in the expression of NLRP3, which plays an important role in the pyroptosis pathway, in tumor. In summary, our data demonstrated that radiopharmaceuticals combined with immunotherapy affected tumor tissue by modulating relevant biological pathways, thereby achieving better antitumor effects compared with single therapy and providing new insights for promoting better patient prognosis and combination treatment strategies.

Speech recognition and speech audiometry parameters in evaluation of aural rehabilitation progress in cochlear implant patients. Review paper.

&lt;b&gt;Introduction:&lt;/b&gt; Speech audiometry is well established and frequently used test in audiology as well as in cochlear implant recipient's performance evaluation. Expanding indications for cochlear implantation forces use of more refined methods of both assessment and prognosis of outcome of aural rehabilitation. Variability of speech intelligibility tests and materials require standardized protocol facilitating outcome comparison.&lt;b&gt;Aim:&lt;/b&gt; Aim of this review paper is analysis of usage of speech audiometry and other speech intelligibility tests and its results reporting in patients with cochlear implant in Poland and in the World.&lt;b&gt;Materials and methods:&lt;/b&gt; Protocols of many different domestic and foreign health centers where compared, showing many methodological differences. Selection of literature for analysis was made according to PRISMA algorithm recommendations. Twenty research papers were chosen for review process.&lt;b&gt;Discussion:&lt;/b&gt; In many papers we found lack of data regarding methodology of performed tests. Many authors indicate difficulties in comparing results, especially if publication lacks basic technical information. Despite that if right method is applied, results can be compared. In literature only one level of material presentation in test is prevalent. Speech audiometry is significant in exploring connections between multiple pre-op and post-op prognostic aspects of cochlear implantation.&lt;b&gt;Conclusions:&lt;/b&gt; Because of variability in presentation and reporting of CI patients outcomes, consensus is needed in area of system facilitating comparison of research results. This may provide simple solution for accurate analysis and choosing right set of data. Schematic of presentation of audiological data in authors health center was proposed as example.

Bridging Histopathology and Radiomics Toward Prognosis of Metastasis in Early Breast Cancer.

Tumor histomorphology is crucial for the prognostication of breast cancer outcomes because it contains histological, cellular, and molecular tumor heterogeneity related to metastatic potential. To enhance breast cancer prognosis, we aimed to apply radiomics analysis-traditionally used in 3D scans-to 2D histopathology slides. This study tested radiomics analysis in a cohort of 92 breast tumor specimens for outcome prognosis, addressing -omics dimensionality by comparing models with moderate and high feature counts, using least absolute shrinkage and selection operator for feature selection and machine learning for prognostic modeling. In the test folds, models with radiomics features [area under the curves (AUCs) range 0.799-0.823] significantly outperformed the benchmark model, which only included clinicopathological (CP) parameters (AUC = 0.584). The moderate-dimensionality model with 11 CP + 93 radiomics features matched the performance of the highly dimensional models with 1,208 radiomics or 11 CP + 1,208 radiomics features, showing average AUCs of 0.823, 0.799, and 0.807 and accuracies of 79.8, 79.3, and 76.6%, respectively. In conclusion, our application of deep texture radiomics analysis to 2D histopathology showed strong prognostic performance with a moderate-dimensionality model, surpassing a benchmark based on standard CP parameters, indicating that this deep texture histomics approach could potentially become a valuable prognostic tool.

Multimodal Imaging of Bilateral Retinal Pigment Epithelial Immunoglobulin Light Chain Deposition in Patients with Systemic Immunoglobulin Light Chain Deposition

ObjectiveTo describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DesignA retrospective observational case series. ParticipantsWe examined six eyes in three patients (one with multiple myeloma, one with membranous nephropathy, and one with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch’s membrane complex and acquired serous retinal detachment. MethodsFundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain optical coherence tomography (OCT), swept-source OCT (SS-OCT), en-face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. Main Outcome MeasuresMultimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. ResultsBilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch’s membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and “angiographically silent” serous retinal detachment in patients with systemic immunoglobulin light chain deposition. ConclusionsWe have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality.

Hematological Malignancies in Older Patients: Focus on the Potential Role of a Geriatric Assessment Management.

Geriatric assessment management is a multidimensional tool used to evaluate prognosis for clinical outcomes and targets for interventions in older adults with cancer receiving chemotherapy. In this review, we evaluated the possible application of geriatric assessment management (GAM) in hematological malignancies. In older patients with Diffuse Large B Cell Lymphoma, GAM might be helpful in both predicting planned hospital admissions and improving quality of life. In chronic myeloid leukemia, the Charlson Comorbidity Index demonstrates how comorbidities could affect treatment compliance and overall outcomes. In multiple myeloma, the application of different scores such as the International Myeloma Working Group Frailty Index and the Revised Myeloma Comorbidity Index can identify frail patients who need suitable interventions in treatment plan (reducing drug dose or changing treatment). Therefore, including GAM in the management plan of older patients with hematological malignancies may direct and optimize cancer care.

Lack of mismatch repair enhances resistance to methylating agents for cells deficient in oxidative demethylation

The human alkylation B (AlkB) homologs, ALKBH2 and ALKBH3, respond to methylation damage to maintain genomic integrity and cellular viability. Both ALKBH2 and ALKBH3 are direct reversal repair enzymes that remove 1-methyladenine (1meA) and 3-methylcytosine (3meC) lesions commonly generated by alkylating chemotherapeutic agents. Thus, the existence of deficiencies in ALKBH proteins can be exploited in synergy with chemotherapy. In this study, we investigated possible interactions between ALKBH2 and ALKBH3 with other proteins that could alter damage response and discovered an interaction with the mismatch repair (MMR) system. To test whether the lack of active MMR impacts ALKBH2 and/or ALKBH3 response to methylating agents, we generated cells deficient in ALKBH2, ALKBH3, or both in addition to Mlh homolog 1 (MLH1), another MMR protein. We found that MLH1koALKBH3ko cells showed enhanced resistance toward SN1- and SN2-type methylating agents, whereas MLH1koALKBH2ko cells were only resistant to SN1-type methylating agents. Concomitant loss of ALKBH2 and ALKBH3 (ALKBH2ko3ko) rendered cells sensitive to SN1- and SN2-agents, but the additional loss of MLH1 enhanced resistance to both types of damage. We also showed that ALKBH2ko3ko cells have an ATR-dependent arrest at the G2/M checkpoint, increased apoptotic signaling, and replication fork stress in response to methylation. However, these responses were not observed with the loss of functional MLH1 in MLH1koALKBH2ko3ko cells. Finally, in MLH1koALKBH2ko3ko cells, we observed elevated mutant frequency in untreated and temozolomide treated cells. These results suggest that obtaining a more accurate prognosis of chemotherapeutic outcome requires information on the functionality of ALKBH2, ALKBH3, and MLH1.

A Multimodal Ensemble Deep Learning Model for Functional Outcome Prognosis of Stroke Patients.

The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3-6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3-6. Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3-6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

Rehabilitation potential in patients with prostate cancer: psychological aspect

Objective. To determine a list of psychological characteristics associated with the prognosis of prostate cancer outcome and rehabilitation potential in patients with cancer. Materials and methods. The study of psychological characteristics (subjective and personal characteristics of study participants (n = 148)) associated with rehabilitation potential was carried out using the following psychological methods: Methodology of Subjective Control Level (E.F. Bazhin, E.A. Golynkina, L.M. Etkind), Questionnaire of ways to cope (adapted by T.L. Kryukova, E.V. Kuftyak, M.S. Zamyshlyaeva), Questionnaire SF-36 “Assessment of the quality of life”, Test of vitality (adapted by D.A. Leontiev, E.I. Rasskazova), Basic Beliefs Scale (adapted by M.A. Padun, A.V. Kotelnikova). Results. A favorable prognosis for the outcome of prostate cancer is associated with the patient`s involvement in the events of his life and active participation in them, understanding of the significance of the problem, partial independence from others, slight limitation of role functioning due to the emotional state, optimal social functioning in combination with beliefs about the benevolence of the world around him and ability to control events. Conclusions. A list of psychological characteristics associated with the course of the disease in patients with prostate cancer was obtained. These psychological characteristics can define the rehabilitation potential, being associated with the possibilities of recovery after antitumor treatment.

Clinical significance of procollagen type III N-terminal peptide in patients with alcoholic liver disease

Background. Alcoholic liver disease (ALD) – is a disease that leads to the development of liver cirrhosis (LC) with a high mortality rate. N-terminal type lll procollagen peptide (PIIINP) is one of the optimal biomarkers for assessing fibrogenesis.Objective: to determine the clinical significance of PIIINP blood level in patients with ALD.Materials and methods. 97 patients with ALD were examined. The age of the patients was 48,5±9,9 years, there were 30 women, 67 men. Steatosis was diagnosed in 12 patients, 11 – alcoholic hepatitis (AH), 74 – LC. In group with LC, 16 patients was diagnosed AH against confirmed cirrhosis. PIIINP blood level determined by ELISA. Control group consisted of 22 healthy volunteers who have not consumed alcohol in hepatotoxic doses.Results. In all patients, PIIINP blood level was increased. In steatosis PIIINP slightly increased the norm, indicating the beginning of fibrogenesis. In LC, PIIINP blood level was higher than in patients with steatosis, which reflected increasing of fibrosis and progression of the disease. The highest levels of PIIINP were observed in cases with AH. Levels PIIINP in patients with AH but without LC and in patients with AH against the background of the formed LC did not differ. In Maddray index of more than 32 (9 patients), the PIIINP level was higher than in 18 patients with index values &lt;32, which confirmed the role of AH in development of fibrosis and decompensation of liver function.Conclusion. Determination of PIIINP blood level in patients with ALD will allow predict the activity of fibrogenesis and the severity of subsequent changes in liver tissue. In cases of severe AH, PIIINP may be an additional criterion determining the severity and prognosis of hepatitis outcomes.