Notes

Cubic spline-based depth-dependent localization involving mitochondria-endoplasmic reticulum contact lenses through three-dimensional light-sheet super-resolution microscopy.
thing compared to PSV in tracheostomized subjects, but HFT via tracheostomy provided no measurable additional physiologic benefit compared to O
therapy via T-tube.
Inspiratory effort and breathing frequency increased significantly during unassisted breathing compared to PSV in tracheostomized subjects, but HFT via tracheostomy provided no measurable additional physiologic benefit compared to O2 therapy via T-tube.
Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO).

This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation).

A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7ion and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.
To investigate the association between enlarged perivascular spaces (PVS) in the basal ganglia (BG-PVS) and long-term motor outcomes in Parkinson disease (PD).

We reviewed the medical records of 248 patients with drug-naive early-stage PD (follow-up >3 years, mean age 67.44 ± 8.46 years, 130 female) who underwent brain MRI and dopamine transporter (DAT) scans at initial assessment. The number of baseline enlarged BG-PVS was counted on axial T2-weighted images. Then, patients were divided into 2 groups a PD group with a low number (0-10) of enlarged PVS (PD-EPVS-; n = 156) and a PD group with a high number (>10) of enlarged PVS (PD-EPVS+; n = 92). We used Cox regression models to compare the levodopa-induced dyskinesia (LID)-, wearing-off-, and freezing of gait (FOG)-free times between groups. We also compared longitudinal increases in levodopa-equivalent dose per body weight between groups using a linear mixed model.

Patients in the PD-EPVS+ group were older (72.28 ± 6.07 years) and had greater small vessel disease burden than those in the PD-EPVS- group (64.58 ± 8.38 years). The PD-EPVS+ group exhibited more severely decreased DAT availability in all striatal subregions except the ventral striatum. The risk of FOG was higher in the PD-EPVS+ group, but the risk of LID or wearing-off was comparable between groups. The PD-EPVS+ group required higher doses of dopaminergic medications for effective symptom control compared to the PD-EPVS- group.

This study suggests that baseline enlarged BG-PVS can be an indicator of the progression of motor disability in PD.
This study suggests that baseline enlarged BG-PVS can be an indicator of the progression of motor disability in PD.
Sensory loss with normal nerve conduction studies (NCS) from focal sensory root inflammatory demyelination is characteristic of chronic immune sensory polyradiculopathy (CISP). However, nonpure cases involving motor and distal sensory nerves exist (CISP-plus). We hypothesize that CISP-plus and CISP are fundamentally part of the same syndrome through comparison of clinical, neurophysiologic, and pathologic features.

CISP-plus (primary dorsal root with lesser motor and sensory nerve involvement) and CISP cases were retrospectively analyzed (1986-2019).

We identified 44 CISP-plus and 28 CISP cases (n = 72) with 86% (38/44) of patients with CISP-plus and 79% (22/28) of patients with CISP experiencing imbalance. On examination, large fiber sensory loss was present in 98% (43/44) of patients with CISP-plus and 96% (27/28) of patients with CISP. Gait ataxia was evident in 93% (41/44) of patients with CISP-plus and 79% (22/28) of patients with CISP. Mild distal weakness was common in CISP-plus (75%, 33/44). NCSocal sensory polyradiculopathy) together as proximal sensory CIDP.
To evaluate whether a retinal spectral-domain optical coherence tomography (SD-OCT) assessment at baseline is associated with long-term disability worsening in people with multiple sclerosis (PwMS), we performed SD-OCT and Expanded Disability Status Scale (EDSS) assessments among 132 PwMS at baseline and at a median of 10 years later.

In this prospective, longitudinal study, participants underwent SD-OCT, EDSS, and visual acuity (VA) assessments at baseline and at follow-up. Statistical analyses were performed using generalized linear regression models, adjusted for age, sex, race, multiple sclerosis (MS) subtype, and baseline disability. We defined clinically meaningful EDSS worsening as an increase of ≥2.0 if baseline EDSS score was <6.0 or an increase of ≥1.0 if baseline EDSS score was ≥6.0.

A total of 132 PwMS (mean age 43 years; 106 patients with relapsing-remitting MS) were included in analyses. Median duration of follow-up was 10.4 years. In multivariable models excluding eyes with prior optic neuritis, relative to patients with an average baseline ganglion cell + inner plexiform layer (GCIPL) thickness ≥70 µm (the mean GCIPL thickness of all eyes at baseline), an average baseline GCIPL thickness <70 µm was associated with a 4-fold increased odds of meaningful EDSS worsening (adjusted odds ratio [OR] 3.97, 95% confidence interval [CI] 1.24-12.70;
= 0.02) and an almost 3-fold increased odds of low-contrast VA worsening (adjusted OR 2.93, 95% CI 1.40-6.13;
= 0.04).

Lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS. Accordingly, SD-OCT at a single time point may help guide therapeutic decision-making among individual PwMS.

This study provides Class I evidence that lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS.
This study provides Class I evidence that lower baseline GCIPL thickness on SD-OCT is independently associated with long-term disability worsening in MS.
To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs).

Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.
To evaluate the validity of the 2016 clinical diagnostic criteria proposed for probable anti-NMDA receptor (NMDAR) encephalitis in children, we tested the criteria in a Japanese pediatric cohort.

We retrospectively reviewed clinical information of patients with neurologic symptoms whose CSF was analyzed for NMDAR antibodies (NMDAR-Abs) in our laboratory from January 1, 2015, to March 31, 2019.

Overall, 137 cases were included. Of the 41 cases diagnosed as probable anti-NMDAR encephalitis (criteria-positive) according to the 2016 criteria, 13 were positive and 28 were negative for anti-NMDAR-Abs. Of the 96 criteria-negative cases, 3 were positive and 93 were negative for anti-NMDAR-Abs. MLN2480 manufacturer The sensitivity of the criteria was 81.2%, specificity was 76.9%, positive predictive value (PPV) was 31.7%, and negative predictive value was 96.9%. Compared with the true-positive group, the false-positive group contained more male than female patients (malefemale, 49 in the true-positive vs 199 in the false-positive group,
= 0.0425). The majority of the cases with false-positive diagnoses were associated with neurologic autoimmunity.

The clinical diagnostic criteria are reliable for deciding to start immunomodulatory therapy in the criteria-positive cases. Low PPV may be caused by a lower prevalence of NMDAR encephalitis or lower level of suspicion for encephalitis in the pediatric population. Physicians should therefore continue differential diagnosis, focusing especially on other forms of encephalitis.

This study provides Class IV evidence that the proposed diagnostic criteria for anti-NMDAR encephalitis in children has a sensitivity of 81.2% and a specificity of 76.9%.
This study provides Class IV evidence that the proposed diagnostic criteria for anti-NMDAR encephalitis in children has a sensitivity of 81.2% and a specificity of 76.9%.
To determine whether patients in the community with lumbosacral radiculoplexus neuropathy (LRPN) have milder neuropathy than referral patients, we characterized the outcomes and survival of population-based compared to referral-based LRPN cohorts.

Previously, we found that the incidence of LRPN is 4.16/100,000/y, a frequency greater than other inflammatory neuropathies. The survival of patients with LRPN is uncharacterized.

Sixty-two episodes in 59 patients with LRPN were identified over 16 years (2000-2015). Clinical findings were compared to previous referral-based LRPN cohorts. Survival data were compared to those of age- and sex-matched controls.

At LRPN diagnosis, median age was 70 years, median Neuropathy Impairment Score (NIS) 22 points, 92% had pain, 95% had weakness, 23% were wheelchair-bound, and median modified Rankin Scale score (mRS) was 3 (range 1-4). At last follow-up, median NIS improved to 17 points (
< 0.001) with 56% having ≥4 points improvement, 16% were wheelchair-bound, and median mRS was 2.
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