Subacute Phase Research Articles

Micro- and Macrostructural Language Features in Vertebrobasilar or Carotid System Stroke Without Diagnosis of Aphasia.

This study aimed to investigate the macro- and microstructural features of language in patients with ischemic stroke without aphasia. Participants were grouped according to arterial system damage and given the Aphasia Language Assessment Test (ADD) to detect aphasia. A narrative sample was obtained and analyzed for macrostructural and microstructural features of the language. The study sample consisted of 31 participants with ischemic stroke (15 vertebrobasilar system [VBS] involvement and 16 carotid system [CS] involvement) and 31 healthy participants, totaling 62 individuals. The healthy control group scored higher than the stroke group on the microstructural feature type-token ratio and mean length of utterance in the narrative analysis and on the auditory comprehension, repetition, naming, grammar, speech act, and writing subtests in ADD. Effort behavior, errors, edits, repetitions, and pauses among microstructural features and uncertainty, filler expression, and anomia among macrostructural features were significantly higher in the vertebrobasilar and CS groups than in the healthy control group. The total ADD score and speech fluency and reading subtest scores were significantly higher in individuals with VBS damage than in individuals with CS lesions (p < .05). Language components may be impaired differently in patients with carotid and vertebrobasilar lesions. Speech and language disorders in individuals who have experienced cerebrovascular accidents should be evaluated in the subacute and chronic phases, and the therapeutic needs of patients with ischemic stroke should be determined, regardless of the presence of a clinical aphasia diagnosis.

Positive effects of lower extremity constraint-induced movement therapy on balance, leg strength and dual-task ability in stroke patients: a longitudinal cohort study.

To investigate whether high-intensity lower extremity constraint-induced movement therapy can improve balance, leg strength, and dual-task ability. A longitudinal cohort study in a real-world outpatient clinic. 147 community-dwelling participants in the subacute and chronic poststroke phases. Participants received lower extremity constraint-induced movement therapy for 6 hours/day during 2 consecutive weeks, including balance, strength, and functional training. The Berg Balance Scale (BBS), Single-Leg-Stance (SLS) bilaterally, one Repetition Maximum (1RM) in a leg press, symmetry of leg strength (Diff-1RM), Timed Up and Go (TUG), and the TUG Manual test were assessed before, after, and 3 months after lower extremity constraint-induced movement therapy. Compared with preintervention data, statistically significant improvements after lower extremity constraint-induced movement therapy (p < 0.001) were demonstrated for balance with an absolute value in BBS at 1.9 points (effect size 0.38) and SLS at 2.4 s (effect size 0.24), and for leg strength at 10.2 kg (effect size 0.54) for the affected leg. Diff 1RM decreased significantly at 5.8 kg (effect size 0.39) and improvements on dual-task ability at 2.7 s were significant (effect size 0.14). The effects persisted at the 3-month follow-up. High-intensity lower extremity constraint-induced movement therapy may be a feasible treatment option for middle-aged stroke patients to affect balance, leg strength, and dual-task ability positively in an out-patient clinical setting.

No impact of anti-inflammatory medication on inflammation-driven recovery following cervical spinal cord injury in rats

Following spinal cord injury (SCI), inflammation is associated with the exacerbation of damage to spinal tissue. Consequently, managing inflammation during the acute and subacute phases is a common target in SCI treatment. However, inflammation may also induce potential benefits, including the stimulation of neuroplasticity and repair. This positive role of inflammation in spinal cord healing and functional recovery is not fully understood. To address this knowledge gap, we examined the effects of two common anti-inflammatory medications, Diphenhydramine and Methylprednisolone, on the efficacy of rehabilitative motor training on recovery from subacute cervical SCI in adult rats. Training depends critically on neuroplasticity thus if inflammation is a key regulator, we propose that anti-inflammatory drugs will reduce subsequent recovery. Both drugs were administered orally over one month, alongside task-specific reaching and grasping training.After treatment, no substantial changes in motor recovery or lesion size between the treated and control groups were observed. Treated animals also did not show any discernible changes in sensory function or anxiety-like behavior. Taken together, our data indicate that the prolonged use of these anti-inflammatory agents at commonly used doses did not profoundly impact recovery following an SCI. Therefore, considering earlier reports of the benefits of pro-inflammatory stimuli on plasticity, further studies in this area are imperative to elucidate the true impact of treating inflammation and its implications for recovery after spinal cord injuries.

Endothelial pyroptosis-driven microglial activation in choroid plexus mediates neuronal apoptosis in hemorrhagic stroke rats

BackgroundSpontaneous intracerebral hemorrhage (ICH) is associated with alarmingly high rates of disability and mortality, and current therapeutic options are suboptimal. A critical component of ICH pathology is the initiation of a robust inflammatory response, often termed “cytokine storm,” which amplifies the secondary brain injury following the initial hemorrhagic insult. The precise sources and consequences of this cytokine-driven inflammation are not fully elucidated, necessitating further investigation. MethodsTo address this knowledge gap, our study conducted a comprehensive cytokine profiling using Luminex® assays, assessing 23 key cytokines. We then employed single-cell RNA sequencing and spatial transcriptomics at three critical time points post-ICH: the hyperacute, acute, and subacute phases. Integrating these multimodal analyses allowed us to identify the cellular origins of cytokines and elucidate their mechanisms of action. ResultsLuminex® cytokine assays revealed a significant upregulation of IL-6 and IL-1β levels at the 24-h post-ICH time point. Through the integration of scRNA-seq and spatial transcriptomics in the hemorrhagic hemisphere of rats, we observed a pronounced activation of cytokine-related signaling pathways within the choroid plexus. Initially, immune cell presence was sparse, but it surged 24 h post-ICH, particularly in the choroid plexus, indicating a substantial shift in the immune microenvironment. We traced the source of IL-1β and IL-6 to endothelial cells, establishing a link to pyroptosis. Endothelial pyroptosis post-ICH induced the production of IL-1β and IL-6, which activated microglial polarization characterized by elevated expression of Msr1, Lcn2, and Spp1 via the NF-κB pathway in the choroid plexus. Furthermore, we identified neuronal populations undergoing apoptosis, mediated by the Lcn2-SLC22A17 pathway in response to IL-1β and IL-6 signaling. Notably, the inhibition of pyroptosis using VX-765 significantly mitigated neurological impairments. ConclusionsOur study provides evidence that endothelial pyroptosis, characterized by the release of IL-1β and IL-6, triggers microglial polarization through NF-κB pathway activation, ultimately leading to microglia-mediated neuronal apoptosis in the choroid plexus post-ICH. These findings suggest that targeted therapeutic strategies aimed at mitigating endothelial cell pyroptosis and neutralizing inflammatory cytokines may offer neuroprotection for both microglia and neurons, presenting a promising avenue for ICH treatment.

EEG Provides Insights Into Motor Control and Neuroplasticity During Stroke Recovery.

In many branches of medicine, treatment is guided by measuring its effects on underlying physiology. In this regard, the efficacy of rehabilitation/recovery therapies could be enhanced if their administration was guided by measurements that directly capture treatment effects on neural function. Measures of brain function via EEG may be useful toward this goal and have advantages such as ease of bedside acquisition, safety, and low cost. This review synthetizes EEG studies during the subacute phase poststroke, when spontaneous recovery is maximal, and focuses on movement. Event-related measures reflect cortical activation and inhibition, while connectivity measures capture the function of cortical networks. Several EEG-based measures are related to motor outcomes poststroke and warrant further evaluation. Ultimately, they may be useful for clinical decision-making and clinical trial design in stroke neurorehabilitation.

Effects of anodal transcranial direct current stimulation on intracranial compliance in the subacute phase of stroke

ObjectivesTranscranial direct current stimulation (tDCS) increases cerebral blood flow. This study evaluated the effects of anodal tDCS (A-tDCS) on intracranial compliance (ICC) in patients with subacute stroke using a non-invasive method. MethodsThis was a randomized, proof-of-concept, double-blind, pilot study. Patients with ischemic stroke of the middle cerebral artery (MCA) were divided into the following two groups: 1) A-tDCS in the motor cortex on the affected side for 30min at 2mA, and 2) sham tDCS in the motor cortex on the affected side. The primary outcomes were intracranial compliance (P2/P1 ratio and time-to-peak [TTP]) and ICC normalization after the intervention (P2/P1 ratio <1). Secondary outcomes were systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation. ResultsNo significant differences were observed in the P2/P1 ratio (P = 0.509) and TTP (P = 0.480) between the groups. However, the A-tDCS group was significantly associated with a normal P2/P1 ratio after intervention (B = 2.583; standard error [SE]: 1.277; P = 0.043; corrected for age and stroke severity). No significant associations were observed between the groups and systolic blood pressure (F = 0.16; P = 0.902), diastolic blood pressure (F = 0.18; P = 0.892), heart rate (F = 0.11; P = 0.950), or peripheral oxygen saturation (F = 0.21; P = 0.750). ConclusionICC morphology normalization was observed in the A-tDCS group. However, no differences were observed in the P2/P1 ratio, TTP, or hemodynamic variables between the groups. A sample size of 66 patients with ischemic stroke of the MCA can be estimated using the observed effect size and standard α = 5% and β = 20% for future trials. Furthermore, this will aid in conducting the necessary randomized trials targeting these populations.

Self-management support program delivered in the sub-acute phase after traumatic injury—study protocol for a pragmatic randomized controlled trial

BackgroundTraumatic injuries, defined as physical injuries with sudden onset, are a major cause of distress and disability, with far-reaching societal consequences. A significant proportion of trauma survivors report persistent symptoms and difficulties after the injury, and studies show unmet health care needs. Self-management programs delivered in the sub-acute phase after traumatic injuries are scarcely evaluated. The aim of the present study is to evaluate the effectiveness of a self-management program (SEMPO), delivered 3–4 months after moderate-to-severe traumatic injury.MethodsThis study protocol describes a pragmatic randomized controlled trial (RCT) with two classical RCT arms (intervention and control) and an explorative self-selection arm. 220 patients will be recruited from Oslo University Hospital, the largest Trauma Referral Centre in Norway. Patients aged 18–72 years residing in the south-east region of Norway, admitted to the Trauma Centre directly or within 72 h after having sustained a moderate to severe traumatic injury, defined as a New Injury Severity Score > 9, having at least 2 days hospital stay, and reporting injury-related symptoms and impairment at discharge from the acute hospital will be included. Patients will be randomly assigned to either a classical RCT randomization arm (intervention or control arm) or to a self-selection arm. In the randomization arm, participants are further randomized into intervention or control group. Participants allocated to the self-selection arm will choose to partake either in the intervention or control arm. The primary outcome is the level of self-efficacy in trauma coping assessed 6 months after completion of the intervention, with a similar time point for the control group. Secondary outcomes include symptom burden, physical functioning and disability, return to work and health care utilization, health-related quality of life, and communication competency. In addition, patients will be asked to nominate one domain-related measurement as their preferred outcome measure.DiscussionThis RCT will determine the effect of a self-management program tailored to patients with moderate to severe physical trauma, and the self-selection arm incorporates the potential influence of patient treatment preferences on intervention results. If the intervention proves effective, cost-effectiveness and cost-utility analyses will be performed and thereby provide important information for clinicians and policy makers.Trial registrationThe study is registered in Clinical Trials with the identifier: NCT06305819. Registered on March 05, 2004.

Cardiac rehabilitation and secondary prevention of CVD: time to think about cardiovascular health rather than rehabilitation

AbstractDuring the past century, there have been major developments in the medical and surgical treatment of cardiovascular disease (CVD). These advancements have resulted in more people surviving initial events and having reduced length of stay in hospital; consequently, there is an increasing number of people in need of ongoing and lifelong cardiovascular risk management. The physical and emotional effects of living with CVD are ongoing with broad challenges ranging from the individual to system level. However, post-discharge care of people with coronary disease continues to follow a 50-year-old cardiac rehabilitation model which focuses on the sub-acute phase and is of a finite in duration. The aim of this paper is to consider the concept of supporting survivors to live well with CVD rather than ‘rehabilitating’ them and propose factors for consideration in reframing secondary prevention towards optimizing cardiovascular health. We discuss deeply-held potential considerations and challenges associated with the concept of supporting survivors achieve optimal cardiovascular health and live well with CVD rather than ‘rehabilitating’ them. We propose the concept of 5 x P’s for reframing traditional cardiac rehabilitation towards the concept of cardiovascular health for survivors beyond ‘rehabilitation’. These include the need for personalization, processes, patient-centered care, parlance, and partnership. Taken together, consideration of challenges at the systems and population level will ultimately improve engagement with secondary prevention as well as outcomes for all people who need it.

Investigating the effects of excitatory and inhibitory somatosensory rTMS on somatosensory functioning in the acute and subacute phases of stroke: a preliminary double-blind and randomized trial.

Repetitive transcranial magnetic stimulation (rTMS) targeting the primary somatosensory cortex (S1) has a potential effect on somatosensory functioning following a stroke. However, S1-rTMS was combined with peripheral therapies in previous trials. Moreover, these studies have commonly targeted the ipsilesional S1 with excitatory rTMS paradigms. This double-blind, randomized trial (registration number: ChiCTR2200059098) investigated two forms of paradigms, that is ipsilesional excitatory and contralesional inhibitory rTMS, as a stand-alone treatment in post-stroke somatosensation. Patients in the acute and subacute phases of stroke were randomly assigned to either contralesional 1-Hz or ipsilesional 10-Hz rTMS group and received 10 daily sessions of treatment in two consecutive weeks. Results indicate that the contralesional inhibitory and ipsilesional excitatory stimulation were equally effective in improving somatosensory functioning. Moreover, this effect was most prominent in deep sensations and subjective sensations. Using single-pulse EMG recordings, our data also revealed an increased MEP amplitude in the ipsilesional motor cortex following ipsilesional excitatory treatment. This preliminary study demonstrates the primary somatosensory cortex as an effective rTMS target in somatosensory recovery following stroke. https://www.chictr.org.cn/showproj.html?proj=166474, ChiCTR2200059098.

Unusual patterns of codeswitching in an unbalanced bilingual person with aphasia: effects of language and executive functions impairment

ABSTRACT Background Bilingual individuals with aphasia may exhibit unique patterns of language impairment and recovery. While code-switching (CS) is a common feature of bilingual speech, pathological CS following brain damage can provide insights into the neural mechanisms controlling bilingual language processing. Aims This study aimed to examine language impairment and recovery patterns in IZ, an unbalanced Hebrew-English bilingual with non-fluent aphasia, focusing on the unusual CS behavior observed during his subacute phase of recovery. Methods and procedures IZ underwent language and narrative assessments in both languages during the subacute and chronic phases of recovery. Ten cognitive tests were administered to assess various domains of cognitive function. Language performance was evaluated through naming and syntactic processing tasks in L1-Hebrew and L2-English. The frequency and type of CS were analyzed using the matrix language frame model. Outcomes and results During the subacute phase, IZ displayed significant language deficits in both L1-Hebrew and L2-English, with more severe impairment in L1-Hebrew naming and L2-English syntactic processing. He exhibited frequent involuntary CS, primarily using L1-Hebrew as the matrix language while embedding L2-English content words. Cognitive testing revealed reduced performance across multiple domains. In the chronic phase, IZ showed parallel improvements in both languages, particularly in L1-Hebrew naming and L2-English syntactic processing, along with a marked reduction in CS frequency. Conclusions IZ’s case demonstrates a double dissociation between lexical and syntactic processing across L1 and L2. The results suggest that matrix language selection in bilinguals may be governed by distinct neural mechanisms for each language, with specific brain regions responsible for activating lexical representations. Damage to these regions may lead to pathological CS, as observed in this case. This study underscores the importance of understanding bilingual language control mechanisms in aphasia rehabilitation.

Protective potential of Bacillus subtilis (NMCC-path-14) against extraarticular manifestations during acute and sub-acute phase of arthritis using mice model

Extra-articular manifestations (EAM), which are associated with rheumatoid arthritis (RA), affect the quality of life of patients and are one of the critical causes of early mortality. This study was aimed at investigating whether Bacillus subtilis NMCC-path-14 (1 × 108 CFU/animal/day) could serve as a valuable therapeutic agent in managing EAM using complete Freund's adjuvant (CFA) induced arthritis during acute and sub-acute phases. Arthritis was induced using intra-dermal administration of CFA in the right hind paw of mice on day 1. Dexamethasone (Dexa) (5 mg/kg/day/animal) was used as a standard treatment. Animals in Dexa and Bacillus subtilis concurrent treatment (BS-CT) received treatments on day 1. The Bacillus subtilis pre-treatment (BS-PT) group received a probiotic dose 7 days before arthritis induction. Parameters like body weight, relative organ weight, colon length, hematology, serum biochemistry, antioxidant capacity, and histopathology of liver, kidney, spleen, colon, stress-related behavioral changes, and cortisol levels were evaluated on days 7 (acute) and 14 (sub-acute). Dexa failed to manage the EAM in arthritic mice and instead exacerbated them. On the other hand, B. subtilis NMCC-path-14 significantly declined EAM with no notable side effects, highlighting its safety and effectiveness. The current data show that B. subtilis NMCC-path-14 may be an alternative option for arthritis treatment that can reduce systemic symptoms associated with arthritis. More studies are required to comprehend the underlying mechanisms of mitigating the EAM by B. subtilis NMCC-path-14.

Sensory Stimulation and Robot-Assisted Arm Training After Stroke: A Randomized Controlled Trial.

Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a promising add-on therapy that is thought to directly drive plasticity processes. First positive effects on sensorimotor function have been shown. However, clinical studies are scarce, and the effect of RSS combined with robot-assisted training has not been evaluated yet. Therefore, our objective was to investigate the feasibility and sensorimotor effects of RSS (compared to a control group receiving sham stimulation) followed by robot-assisted arm therapy. Forty participants in the subacute phase (4.4-23.9weeks) after stroke with a moderate to severe arm paresis were randomized to RSS or control group. Participants received 12 sessions of (sham-) stimulation within 3weeks. Stimulation of the fingertips and the robot-assisted therapy were each applied in 45-min sessions. Motor and sensory outcome assessments (e.g. Fugl-Meyer-Assessment, grip strength) were measured at baseline, post intervention and at a 3-week follow-up. Participants in both groups improved their sensorimotor function from baseline to post and follow-up measurements, as illustrated by most motor and sensory outcome assessments. However, no significant group effects were found for any measures at any time ( P >0.058). Stimulations were well accepted, no safety issues arose. Feasibility of robot-assisted therapy with preceding RSS in persons with moderate to severe paresis was demonstrated. However, RSS preceding robot-assisted training failed to show a preliminary effect compared to the control intervention. Participants might have been too severely affected to identify changes driven by the RSS, or these might have been diluted or more difficult to identify because of the additional robotic training and neurorehabilitation. for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A478 ).

The proteomic signature of circulating extracellular vesicles following intracerebral hemorrhage: Novel insights into mechanisms underlying recovery

Circulating extracellular vesicles (EVs) can participate in innate repair processes triggered after intracerebral hemorrhage (ICH). We aimed to describe changes in the proteomic profile of circulating EVs between the acute and subacute phases of ICH and to compare the findings depending on outcomes, as an approach to unraveling such repair mechanisms.This was a prospective observational study including patients with non-traumatic supratentorial ICH. Exclusion criteria were previous disability, signs of herniation on baseline computed tomography, or limited life expectancy. EVs were isolated from blood samples at 24 h and 7 days after symptom onset. After 6-months' follow-up, patients were dichotomized into poor and good outcomes, defining good as an improvement of >10 points or > 50 % on the National Institutes of Health Stroke Scale and a modified Rankin Scale of 0–2. The protein cargo was analyzed by quantitative mass spectrometry and compared according to outcomes.Forty-four patients completed follow-up, 16 (35.5 %) having good outcomes. We identified 1321 proteins in EVs, 37 with differential abundance. In patients with good outcomes, proteins related to stress response (DERA, VNN2, TOMM34) and angiogenesis (RHG01) had increased abundance at 7 days. EVs from patients with poor outcomes showed higher levels of acute-phase reactants (CRP, SAA2) at 7 days compared with 24 h.In conclusion, the protein content of circulating EVs in patients with ICH changes over time, the changes varying depending on the clinical outcome, with greater abundance of proteins potentially involved in the repair processes of patients with good outcomes.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report

BackgroundCoronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment.Case presentationIn this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child’s thrombus has dissolved, and the myocardial ischemia has resolved.ConclusionsThis case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Genetic deletion of the apoptosis associated speck like protein containing a card in LysM+ macrophages attenuates spinal cord injury by regulating M1/M2 polarization through ASC-dependent inflammasome signaling axis

Apoptosis associated speck like protein containing a card (ASC), the key adaptor protein of the assembly and activation of canonical inflammasomes, has been found to play a significant role in neuroinflammation after spinal cord injury (SCI). The previous studies indicated that widely block or knockout ASC can ameliorate SCI. However, ASC is ubiquitously expressed in infiltrated macrophages and local microglia, so further exploration is needed on which type of cell playing the key role. In this study, using the LysMcre;Ascflox/flox mice with macrophage-specifc ASC conditional knockout (CKO) and contusive SCI model, we focus on evaluating the specific role of ASC in lysozyme 2 (LysM)+ myeloid cells (mainly infiltrated macrophages) in this pathology. The results revealed that macrophage-specifc Asc CKO exhibited the follow effects: (1) A significant reduction in the numbers of infiltrated macrophages in the all phases of SCI, and activated microglia in the acute and subacute phases. (2) A significant reduction in ASC, caspase-1, interleukin (IL)-1β, and IL-18 compared to control mice. (3) In the acute and subacute phases of SCI, M1 subset differentiation was inhibited, and M2 differentiation was increased. (4) Histology and hindlimb motor recoveries were improved. In conclusion, this study elucidates that macrophage-specific ASC CKO can improve nerve function recovery after SCI by regulating M1/M2 polarization through inhibiting ASC-dependent inflammasome signaling axis. This indicates that ASC in peripheral infiltrated macrophages may play an important role in SCI pathology, at least in mice, could be a potential target for treatment.

Acute Multiple Cranial Neuropathies in Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report and Scoping Review of the Literature.

Cranial nerve (CN) involvement is not a common feature of typical chronic inflammatory demyelinating polyneuropathy (CIDP). Patients with acute presentation of CN palsy in CIDP may be misdiagnosed and treated as other pathologies. We report a patient with multiple cranial neuropathies at the onset of CIDP in detail. In addition, we reviewed a large cohort of patients with CN involvement in CIDP and summarized their characteristics and clinical findings. We presented a 28-year-old woman who presented with progressive weakness and involvement of CN III, VII, X, XII in the subacute phase who was diagnosed as CIDP and was treated accordingly. A scoping review of the literature resulted in a total of 59 patients with available patient-level data [61.2% men, median age of 32 (Q1-Q3; 20-51.5) years]. CN impairment was present in the acute phase of the polyneuropathy in 10 out of 43 patients (23.3%), while it took a median of 7.7 [Q1-Q3; 3-13] years for other patients to present CN palsy. Sensitivity analysis did not reveal any difference among patients with acute-phase presentation of CN symptoms (N = 11) compared with those with delayed CN palsy (N = 33) in terms of demographics, patterns of CN involvement, associated diminished sensorimotor findings, or relapse. However, patients with acute presentation of CN palsy underwent plasmapheresis approximately 4 times more than those with delayed CN presentations (45.5% vs. 12.1%, P = 0.02). In this case presentation and review study, we observed that in one-fourth of patients with CIDP and CN neuropathy, CN involvement occurred in the acute phase. This finding indicates the necessity of considering CIDP among differential diagnoses of patients with CN involvement and polyneuropathies.

Expert Management of Type B Aortic Dissection From Onset With Thoracic Endovascular Aortic Repair

BackgroundThoracic endovascular aortic repair is a key treatment of acute type B aortic dissection. We recognized the importance of managing type B aortic dissections from their onset and established our strategy in 2013. Here, we report the early and late outcomes of our comprehensive strategy for the management of type B aortic dissections. MethodsThis was a single-institution, observational, retrospective study. Between April 2013 and March 2024, 227 consecutive patients with acute type B aortic dissection were admitted to our institute and treated by our strategy. Early and late outcomes were also assessed for all patients. ResultsThoracic endovascular aortic repair plus optimal medical treatment was performed to close the primary entry tear in 90 patients (40%) in the acute (12%), subacute (14%), and chronic (14%) phases. Optimal medical treatment alone was performed in 137 patients (60%). The early and late outcomes showed significant improvement. ConclusionsOur strategy provided excellent early and late outcomes of acute type B aortic dissection, avoided postoperative paraplegia, and completely prevented thoracoabdominal aortic replacement.

Serum Endocan Levels in Children with Acute Rheumatic Fever.

Acute rheumatic fever is an immunologically delayed autoimmune sequel of throat infection caused by group A streptococcus. The aim of this study was to evaluate endocan levels in patients with acute rheumatic fever and compare with the control group. The aim of this study was to evaluate endocan levels in patients with acute rheumatic fever and compare with the control group. Twenty-three children with acute rheumatic fever (11 men, 12 females; mean age 13 ± 2.7 years; range 5 to 15 years) and a healthy control group of 31 children (16 men, 15 females; mean age 13.8 ± 2.4 years; range 5 to 15 years) were recruited. The sedimentation rate, C-reactive protein, antistreptolysin-O titres, and endocan levels were examined in each group. Before anti-inflammatory therapy, endocan levels in the acute rheumatic fever group were not statistically significant to those in the control group, respectively (200.64 ng/L, 120.71 ng/L, P = 0.208). After anti-inflammatory therapy, endocan levels were significantly higher in the acute rheumatic fever group than in the control group, respectively (260.87 ng/L vs. 120.71 ng/L, P < 0.01). A significant difference was found in endocan levels before and after anti-inflammatory therapy in the group of acute rheumatic fever, respectively (200.64 ng/L vs. 260.87 ng/L, P = 0.033). Endocan levels after anti-inflammatory therapy were statistically higher in the severe carditis group compared to those of the mild carditis group, respectively (344.56 ng/L vs. 191.01 ng/L, P < 0.01). Our study showed that serum endocan levels increased during the subacute phase of acute rheumatic fever. We suggest that serum endocan level can be used as a new biomarker to identify the degree of cardiac involvement in acute rheumatic fever.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury.

Spinal cord injury (SCI) results in significant neurological deficits, and microglia play the critical role in regulating the immune microenvironment and neurological recovery. Protein lactylation has been found to modulate the function of immune cells. Therefore, this study aimed to elucidate the effects of glycolysis-derived lactate on microglial function and its potential neuroprotective mechanisms via lactylation after SCI. Single-cell RNA sequencing (scRNA-seq) data were obtained from figshare to analyze cellular and molecular alterations within the spinal cord post-SCI, further focusing on the expression of microglia-related genes for cell sub-clustering, trajectory analysis, and glycolysis function analysis. We also evaluated the expression of lactylation-related genes in microglia between day 7 after SCI and sham group. Additionally, we established the mice SCI model and performed the bulk RNA sequencing in a time-dependent manner. The expression of glycolysis- and lactylation-related genes was evaluated, as well as the immune infiltration analysis based on the lactylation-related genes. Then, we investigated the bio-effects of lactate on the inflammation and polarization phenotype of microglia. Finally, adult male C57BL/6 mice were subjected to exercise first to increase lactate level, before SCI surgery, aiming to evaluate the protective effects of lactate-mediated lactylation of microglia-related proteins on SCI. scRNA-seq identified a subcluster of microglia, recombinant chemokine C-X3-C-motif receptor 1+ (CX3CR1+) microglia, which is featured by M1-like phenotype and increased after SCI. KEGG analysis revealed the dysfunctional glycolysis in microglia after SCI surgery, and AUCell analysis suggested that the decreased glycolysis an increased oxidative phosphorylation in CX3CR1+ microglia. Differential gene analysis suggested that several lactylation-related genes (Fabp5, Lgals1, Vim, and Nefl) were downregulated in CX3CR1+ microglia at day 7 after SCI, further validated by the results from bulk RNA sequencing. Immunofluorescence staining indicated the expression of lactate dehydrogenase A (LDHA) in CX3CR1+ microglia also decreased at day 7 after SCI. Cellular experiments demonstrated that the administration of lactate could increase the lactylation level and inhibit the pro-inflammatory phenotype in microglia. Functionally, exercise-mediated lactate production resulted in improved locomotor recovery and decreased inflammatory markers in SCI mice compared to SCI alone. In the subacute phase of SCI, metabolic remodeling in microglia may be key therapeutic targets to promote nerve regeneration, and lactate contributed to neuroprotection after SCI by influencing microglial lactylation and inflammatory phenotype, which offered a novel approach for therapeutic intervention.

Long-term effect of corticosteroid treatment during acute COVID-19 infection on pulmonary function test results.

The outbreak of the novel coronavirus 19 has led to unprecedented clinical challenges globally. Various therapeutic and pharmacologic interventions have been proposed, yet evidence of their long-term efficacy remains limited. Corticosteroids (CS) have shown efficacy in the sub-acute phase of the pandemic. This study aims to evaluate the long-term effects on pulmonary function tests (PFTs) in patients treated with CS during acute coronavirus disease 2019 (COVID-19) infection. A retrospective study was conducted from February 2020 to March 2021. Clinical and demographic data were extracted from electronic medical records of patients attending the post-COVID outpatient clinic at the Pulmonary Institute of Soroka University Medical Center. A multivariate linear mixed effects model was employed to obtain adjusted estimates for the impact over time. The study included 405 patients, of whom 155 (38.3%) received CS treatment. Approximately 60% completed two or more follow-up visits. PFTs [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC)] returned to baseline more rapidly (0.9% and 0.85% per month, respectively) in patients treated with CS. This accelerated recovery was observed across all patients, including those with a body mass index (BMI) above 30 kg/m2 and those with known chronic lung disease. Systemic CS treatment during acute COVID-19 infection was associated with a faster recovery of PFTs during long-term follow-up, even among subgroups at higher risk of long-term pulmonary damage.