The Benefit of Thrombectomy in Patients With Low ASPECTS Is a Matter of Shades of Gray—What Current Trials May Have Missed

Randomized trials supporting the benefit of endovascular treatment in acute ischemic stroke patients with a large early infarction are not yet available. Few retrospective studies exist that suggest a potential positive treatment effect on functional outcome, as well as procedural safety. However, potential benefit or harm of MT in patients with low initial ASPECTS is still a subject of current debate, and in particular, how to select these patients for treatment. The purpose of this pilot study was to evaluate how early tissue water uptake in acute ischemic brain might determine lesion fate and functional outcome in low ASPECTS patients undergoing MT. We observed that the degree of early water uptake measured by quantitative NWU was significantly associated with functional outcome in low ASPECTS patients, yielding a higher diagnostic power compared to other parameters such as ASPECTS, age, or NIHSS. No conclusive evidence of a beneficial effect of successful reperfusion was observed in patients with low ASPECTS and high NWU, which highlights the potential of NWU as a tool to specify patient selection.

Bias for Treatment Effect by Measurement Error in Pretest in ANCOVA Analysis

This paper investigated consequences of measurement error in the pretest on the estimate of the treatment effect in a pretest–posttest design with the analysis of covariance (ANCOVA) model, focusing on both the direction and magnitude of its bias. Some prior studies have examined the magnitude of the bias due to measurement error and suggested ways to correct it. However, none of them clarified how the direction of bias is affected by measurement error. This study analytically derived a formula for the asymptotic bias for the treatment effect. The derived formula is a function of the reliability of the pretest, the standardized population group mean difference for the pretest, and the correlation between pretest and posttest true scores. It revealed a concerning consequence of ignoring measurement errors in pretest scores: treatment effects could be overestimated or underestimated, and positive treatment effects can be estimated as negative effects in certain conditions. A simulation study was also conducted to verify the derived bias formula.

Attachment and mentalization as predictors of outcome in family therapy for adolescent anorexia nervosa

Anorexia nervosa-focussed family therapy (FT-AN) is the first-line treatment for adolescent anorexia nervosa (AN), but the predictors of poor treatment response are not well understood. The main aim of this study was to investigate the role of attachment and mentalization in predicting treatment outcome. The secondary aims of the study were to investigate therapeutic alliance at 1 month as a predictor of outcome, and to test the associations between alliance and baseline attachment and mentalization. 192 adolescents with AN and their parents were recruited as they began family therapy in out-patient specialist eating disorder services. Self-report measures of attachment, mentalization, and emotion regulation were completed at the start of treatment by adolescent patients and one of their parents. Self-reported alliance scores were collected at one month. Higher scores on the Certainty Scale of the Reflective Functioning Questionnaire, completed by parents, which indicate over-certainty about mental states, were the strongest predictor of poor outcome (Odds Ratio: 0.42, CI: 0.20–0.87). Similarly, for adolescents, higher Lack of Clarity scores on the Difficulties in Emotion Regulation Scale, representing being unclear about one’s feelings, were predictive of positive treatment outcome (OR: 1.10, CI: 1.00–1.21). Higher alliance scores at 1 month predicted positive outcome, and were associated with attachment security and mentalization. These novel findings suggest that, particularly in parents, a tendency towards excessive certainty about mental states in others may predict poor outcome in FT-AN. Further research is warranted to replicate the finding and characterise families at risk of poor outcome.

The Effectiveness of FFC-AL-EIT on Psychosocial Outcomes and Care Interactions

This study included a subset of 59 communities and 550 residents from the full FFC-AL-EIT study. Participants were mostly white (98%), female (69%) and had a mean age of 89.30 (SD=7.63). Sites were randomized to the four step FFC-AL-EIT intervention implemented by a function focused care nurse facilitator working with a facility champion over 12 months versus education only. Resident measures included depression, agitation, resistiveness to care and the quality of care interactions and were obtained at baseline, 4 and 12 months. There was a significant positive treatment effect related to depression, agitation, resistiveness to care and quality of care interactions with either less decline or some improvement in these behaviors and symptoms and improvement in the quality of care provided between the treatment versus control group. The study suggests there is some benefit to implementing FFC-AL-EIT for psychosocial outcomes and care interactions among residents in assisted living communities.

CSNK2 in cancer: pathophysiology and translational applications

Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.

Aktivitas Anti Inflamasi Ekstrak Biji Litsea Garciae Vidal Pada Odema Telapak Kaki Dan Gambaran Histologis Kaki Mencit

Litsea garciae or malek is a native species from Borneo and belongs to the Lauraceae family. Scientifically, the use of these plants is not widely known. The purpose of this study was to determine the anti-inflammatory activity of Litsea garciae seeds against edema in mice feet and to determine the histology of the carrageenan-induced integument thickness of mice. The study used a completely randomized design with 5 treatment groups. The treatment group consisted of a negative treatment group (K1), a positive treatment group (K2) with 3 different dosages of Malek seed extract groups. The treatment doses used were Malek seed extract at a dose of 0.625 mg/g BW (P1), 1.25 mg/g BW (2), and 2.50 mg/g BW (P3). Edema percentage and integument thickness were analyzed by the One-Way ANOVA test with (α = 0.05). The results showed that the Malek seed extract dose of 0.625 mg/g BW had anti-inflammatory activity against edema of the mice's feet. The percentage of inflammation with doses of 0.625 mg/g BW, 1.25 mg/g BW and 2.5 mg/g BW was 31.10%, 22.58%, and 25.83%. The percentage of reduction in inflammation in the positive control treatment of Na-diclofenac (42.70%) was significantly differ-ent from the treatment of Malek seed extract at a dose of 0.0625–2.5 mg/g BW. The percentage of reduction in inflammation in the group treated with 1.25 mg/g BW (P2) Malek seed extract was not significantly different from the 2.5 mg/g BW (P3) treatment of Malek seed extract. The results of histological observations of mice's feet showed that the extract of Malek seeds did not have a significant effect on the thickness of the carrageenan-induced mice leg integument.

Therapeutic Strategies for Dry Mouth Management with Emphasis on Electrostimulation as a Treatment Option

Objectives. Xerostomia is a subjective sensation of dry mouth. It is commonly associated with salivary gland hypofunction. Both changes in the composition of the saliva and a reduction in the quantity secreted may be an objective finding of dry mouth. Although there are no currently available cures for the conditions resulting in dry mouth, there are several treatment options that give hope for patients who suffer from xerostomia. Individuals with some residual salivary gland function, which are contraindicated to pharmacological therapies, would benefit the most from identifying novel, alternative effective methods for stimulating production of saliva. The aim of this study was to give an overview of the latest and most relevant data related to treatment modalities for the management of dry mouth conditions. Data Resources and Study Selection. The present review was prepared by searching the National Library of Medicine database using the relevant medical terms and their combinations. A total of thirty-three studies met the inclusion criteria. Data were extracted by one author and verified by another. Conclusion. A number of patients showed positive treatment outcomes, and the adverse effects of both electrical stimulation (ES) and acupuncture have been reported as mild and transient. In patients who have undergone radiotherapy, acupuncture is shown to increase salivation. However, in patients with Sjogren’s syndrome, the effects of ES devices seem to be elusive. Moreover, due to the instability of the findings in relation to longevity of clinical effect, patient satisfaction, quality of life, and clinical effectiveness of such treatments, the results remain vague.

Potential predictors of the immunotherapy effectiveness

The development of novel predictors of immunotherapy efficacy is a clinically important and rapidly developing area. The currently existing predictors (PD-L1, MSI tumor status) do not always guarantee a positive treatment result. In addition, performing these analyses is characterized by the complexity, high cost, and long execution period. Thus, identifying potential new biomarkers in peripheral blood, which would be more accurate and accessible from a technical and economic point of view, is of great interest and is the object of active research. The article is a literature review of the currently available studies written worldwide on the topic of potential markers of the immunotherapy effectiveness. The most interesting and promising studies with intermediate conclusions are presented. We highlighted a number of clinical studies on the use of various assays and platforms for monitoring peripheral immune status. These studies point to the usefulness of these biomarkers as potential prognostic indicators.

EXCITE: Experiences of Patients with Adjuvant and Metastatic Melanoma using Disease- Specific Social Media Communities in the Advent of Novel Therapies (Preprint)

BACKGROUND Immunotherapy and targeted therapy treatments are novel treatments available for patients with metastatic and adjuvant melanoma. As recently approved treatments, information surrounding the patients and caregiver’s experience with these therapies, perceptions of treatments, and the effect the treatments have on their day-to-day life are lacking. Such insights would be valuable for any future decision making with regards to treatment options. OBJECTIVE This study aimed to use health-related social media data to understand the experience of patients with adjuvant and metastatic melanoma who are receiving either immunotherapy or targeted therapies. This study also included caregivers’ perspectives. METHODS Publicly available social media posts by patients with self-reported adjuvant or metastatic melanoma (and their caregivers) between January 2014 to October 2019 were programmatically extracted, de-identified, cleaned and analysed using a combination of natural language processing and qualitative data analyses. This study identified spontaneously reported symptoms and their impacts, symptom duration, and the impact of treatment for both treatment groups. RESULTS Overall 1,037 users (9,023 posts) and 114 users (442 posts) were included in the metastatic group and adjuvant group, respectively. The most commonly identified symptoms in both groups were fatigue, pain or exanthema. Symptom impacts reported by both groups were physical impacts, impacts on family, and impacts on work. Positive treatment impacts were reported in both groups and covered the areas of work, social and family life, and general health and quality of life. CONCLUSIONS This study explored health-related social media to better understand the experience and perspectives of patients with melanoma receiving immunotherapy or targeted therapy treatments as well as the experience of their caregivers. This exploratory work uncovered the most commonly discussed concerns among patients and caregivers on the forums including symptoms and their impacts, thus contributing to a deeper understanding of the patient/caregiver experience. CLINICALTRIAL None

Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage

We previously reported that t(14;18)-negative follicular lymphomas (FL) show a clear reduction of newly acquired N-glycosylation sites (NANGS) in immunoglobulin genes. We therefore aimed to investigate in-depth the occurrence of NANGS in a larger cohort of t(14;18)-positive and t(14;18)-negative FL, including early (I/II) and advanced (III/IV) stage treatment naïve and relapsed tumors. We determined the clonotype using a next generation sequencing approach in a series of 68 FL with fresh frozen material (36 t(14;18)-positive and 32 t(14;18)-negative). The frequency of NANGS differed considerably between t(14;18)-positive and t(14;18)-negative FL III/IV, but no difference was observed among t(14;18)-positive and t(14;18)-negative FL I/II. The introduction of NANGS in all t(14;18)-negative clinical subgroups occurred significantly more often in the FR3 region. Moreover, t(14;18)-negative treatment naïve FL, specifically those with NANGS, showed a strong bias for IGHV4-34 usage compared to t(14;18)-positive treatment naïve cases with NANGS, while IGHV4-34 usage was never found in relapsed FL. In conclusion, subgroups of t(14;18)-negative FL might use different mechanisms of BCR stimulation compared to the lectin-mediated binding described in t(14;18)-positive FL, including responsiveness to autoantigens as indicated by biased IGHV4-34 usage and strong NANGS enrichment in FR3.