Notes

Chitosan self-assembled polymeric nanoparticles with regard to percutaneous supply of betamethasone connected eczema.
PI3K activation enables tumor immune evasion by promoting an inhibitory myeloid microenvironment. Activating mutations in PI3K may be useful as a biomarker of poor response to immunotherapy. Our data suggest that some oncogenes promote tumorigenesis by enabling tumor cells to avoid clearance by the immune system. Identification of those mechanisms can advance rational combination strategies to increase the efficacy of immunotherapy.
PI3K activation enables tumor immune evasion by promoting an inhibitory myeloid microenvironment. Activating mutations in PI3K may be useful as a biomarker of poor response to immunotherapy. Our data suggest that some oncogenes promote tumorigenesis by enabling tumor cells to avoid clearance by the immune system. Identification of those mechanisms can advance rational combination strategies to increase the efficacy of immunotherapy.
This post hoc analysis assessed speed, magnitude and maintenance of pain improvement in patients with early rheumatoid arthritis (RA) receiving baricitinib, baricitinib and methotrexate (MTX), or MTX over 1 year. Cumulative pain and quality of life benefits were also assessed.

Randomised, double-blind, phase 3 study RA-BEGIN (NCT01711359) compared baricitinib 4 mg (N=159), baricitinib 4 mg +MTX (N=215) and MTX (N=210) in patients with RA who had no or limited prior disease-modifying antirheumatic drug treatment. Pain was assessed on a 0-100 mm Visual Analogue Scale (VAS). Proportion of patients with ≥30%, ≥50% and ≥70% pain improvement from baseline; ≤20 mm and ≤10 mm on the pain VAS; and time to achieve pain improvement thresholds were assessed over 52 weeks, as were Patient Global Assessment (PtGA) and 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS) outcomes.

Baricitinib monotherapy or combination with MTX provides greater (least square mean changes (LSM) from baseline -40 mm and -43 mm, respectively) and more rapid (median 12 and 8 weeks to ≥70% improvement, respectively) pain relief than MTX alone (LSM -31 mm, median 20 weeks to ≥70% improvement) over 52 weeks. Baricitinib, alone or combination, provides 9-10 additional weeks of limited to no pain, similar gain in achievable wellness measured through PtGA, and 5-7 additional weeks with change in SF-36 PCS ≥5 vs MTX over 1 year.

Patients treated with baricitinib reported significantly greater and more rapid pain relief, more weeks with limited to no pain, and clinically meaningful improvements in physical health than patients treated with MTX alone over 1 year.
Patients treated with baricitinib reported significantly greater and more rapid pain relief, more weeks with limited to no pain, and clinically meaningful improvements in physical health than patients treated with MTX alone over 1 year.
Effective analgesia is an important element of enhanced recovery after surgery (ERAS), but the clinical impact of regional anesthesia and analgesia for colorectal surgery remains unclear.

We aimed to determine the impact of regional anesthesia following colorectal surgery in the setting of ERAS.

We performed a systematic review of nine databases up to June 2020, seeking randomized controlled trials comparing regional anesthesia versus control in an ERAS pathway for colorectal surgery. We analyzed the studies with successful ERAS implementation, defined as ERAS protocols with a hospital length of stay of ≤5 days. Data were qualitatively synthesized. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool.

Of the 29 studies reporting ERAS pathways, only 13 comprising 1170 patients were included, with modest methodological quality and poor reporting of adherence to ERAS pathways. Epidural analgesia had limited evidence of outcome benefits in open surgery, while spinal analgesia with intrathecal opioids may potentially be associated with improved outcomes with no impact on length of stay in laparoscopic surgery, though dosing must be further investigated. There was limited evidence for fascial plane blocks or other regional anesthetic techniques.

Although there was variable methodological quality and reporting of ERAS, we found little evidence demonstrating the clinical benefits of regional anesthetic techniques in the setting of successful ERAS implementation, and future studies must report adherence to ERAS in order for their interventions to be generalizable to modern clinical practice.

CRD42020161200.
CRD42020161200.
Peripheral nerve impairments and dementia are common among older adults and share risk factors. However, few studies have examined whether peripheral nerve function and dementia are associated. We evaluated whether lower extremity peripheral nerve impairments were associated with higher incidence of dementia and whether associations differed by comorbidity subgroups (diabetes, low vitamin B
, and
ε4 allele carriers).

We studied Black and White Health, Aging, and Body Composition Study participants 70 to 79 years of age and without dementia at enrollment. Lower extremity sensory and motor peripheral nerve function was measured at year 4 (the analytic baseline of this study). Sensory nerve impairments were measured with monofilament (1.4 g, 10 g) and vibration threshold of the toe. Monofilament insensitivity was defined as unable to detect monofilament (3 of 4 touches), and vibration detection impairment was defined as >130 μm. Fibular motor impairments were defined as <1 mV compound motor action n; for ≥3 impairments, the HR was 2.37 (95% CI 1.29-4.38). In subgroup analyses, effect estimates were generally higher among those with diabetes, low vitamin B
, and
ε4 allele except for vibration detection.

Peripheral nerve impairments, especially sensory, were associated with a higher risk of dementia even after adjustment for age and other health factors. These associations may represent a shared susceptibility to nervous system degeneration.
Peripheral nerve impairments, especially sensory, were associated with a higher risk of dementia even after adjustment for age and other health factors. These associations may represent a shared susceptibility to nervous system degeneration.
Prolonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence.

We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT).

We included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54-6.03; RR 2.16, 95% CI 1.66-2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57-2.70; RR 2.01, 95% CI 1.43-2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15-0.59), but not in RCTs (RR 0.72, 95% CI 0.49-1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders.

PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.
PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.
Neurofilament light (NfL) appears to be a promising fluid biomarker in repeat-expansion spinocerebellar ataxias (SCAs), with piloting studies in mixed SCA cohorts suggesting that NfL might be increased at the ataxic stage of SCA type 1 (SCA1). We here hypothesized that NfL is increased not only at the ataxic stage of SCA1, but also at its (likely most treatment-relevant) preataxic stage.

We assessed serum NfL (sNfL) and CSF NfL (cNfL) levels in both preataxic and ataxic SCA1, leveraging a multicentric cohort recruited at 6 European university centers, and clinical follow-up data, including actually observed (rather than only predicted) conversion to the ataxic stage. Levels of sNfL and cNfL were assessed by single-molecule array and ELISA technique, respectively.

Forty individuals with SCA1 (23 preataxic, 17 ataxic) and 89 controls were enrolled, including 11 preataxic individuals converting to the ataxic stage. Mycro 3 sNfL levels were increased at the preataxic (median 15.5 pg/mL [interquartile range 10.5-21.wing stratification of preataxic individuals regarding proximity to onset, early detection of neurodegeneration even before volumetric MRI alterations, and potentially capture of treatment response in clinical trials.

ClinicalTrials.gov Identifier NCT01037777.

This study provides Class III evidence that NfL levels are increased in both ataxic and preataxic SCA1 and are associated with ataxia onset.
This study provides Class III evidence that NfL levels are increased in both ataxic and preataxic SCA1 and are associated with ataxia onset.
Both genetic and environmental factors contribute to stroke risk. We sought to identify novel metabolites associated with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort and determine whether they reflected genetic or environmental variation.

This was a stroke case-cohort observational study nested in REGARDS. Cases were defined as incident stroke and metabolomic profiles were compared to a randomly selected control cohort. In baseline plasma samples, 162 metabolites were measured using liquid chromatography-tandem mass spectrometry. Cox proportional hazards models were adjusted for age, sex, race, and age by race in the base model. Fully adjusted models included traditional stroke risk factors. Mediation analyses conducted for these stroke risk factors used the metabolite as mediator. Genome-wide associations with the leading candidate metabolites were calculated using array data. Replication analyses in the Jackson Heart Study (JHS) were conducted using raation analyses suggest that environmental exposures rather than genetic variation link nucleoside levels to stroke risk.

This study provides Class II evidence that guanosine and pseudouridine are associated with incident stroke.
This study provides Class II evidence that guanosine and pseudouridine are associated with incident stroke.A 73-year-old woman presented with transient episodes of dysarthria and horizontal diplopia. She had stereotactic radiosurgery 18 years prior for a retroclival meningioma. Neurologic examination was notable for right-sided tongue deviation, tongue fasciculations, and intermittent impaired abduction of the right eye. MRI ruled out recurrence or progression of the retroclival meningioma. EEG failed to reveal electrographic seizures. EMG showed spontaneous depolarizations in bursts that sounded like "marching soldiers" in the right hemitongue, consistent with myokymia. Focal myokymia is an unusual EMG finding that is usually seen in demyelinating disorders, after radiation, or in neoplastic/inflammatory conditions. The clinical presentation and EMG findings were most consistent with delayed radiation-induced myokymia. Similar cases of transient dysarthria and tongue myokymia from radiation have been infrequently reported in the literature; however, this case uniquely exhibited additional episodes of transient horizontal diplopia, which was possibly from ocular myokymia or neuromyotonia.
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