Recovery Of Symptoms Research Articles

548. Combined Results of the Phase 2a/2b/3 Randomized Controlled Trials of Ensitrelvir for the Treatment of COVID-19 Infection

Abstract Background Ensitrelvir is a selective SARS-CoV-2 3CL protease inhibitor developed as an oral therapy for the treatment of COVID-19 infection. We report the combined results for ensitrelvir 125 mg and 250 mg treatment from the Phase 2a, 2b, 3 parts of the Phase 2/3 study conducted in patients with COVID-19 with or without SARS-CoV-2 vaccination and risk factors for severe disease. Methods The multicenter, randomized, double-blind, placebo-controlled studies were conducted between September 2021 and August 2022 in Japan, South Korea and Vietnam. SARS-CoV-2-positive patients, aged 12–70 years old, were treated with ensitrelvir 125 mg PO (after a loading dose of 375 mg PO on Day 1 only), 250 mg PO (after a loading dose of 750 mg on Day 1only) or placebo, once daily for 5 days, and followed up for 28 days from the start of treatment. Time to resolution of 5 symptoms of COVID-19 (runny or stuffy nose, sore throat, cough, feeling hot or fever, low energy or tiredness) primarily among patients who were randomized within less than 72 hours of symptom onset and safety were assessed. Results In this post-hoc analysis, among patients who were randomized within less than 72 hours of symptom onset, 56.0% of patients were male in the ensitrelvir 125 mg group (N=407), 54.3% in the 250 mg group (N=398) and 52.5% in the placebo group (N=402). The mean (standard deviation) age was 35.8 (12.7) years in the 125 mg group, 35.1 (12.3) in the 250 mg group and 34.9 (12.3) years in the placebo group. The time to resolution of the 5 symptoms was significantly shorter in the 125 mg group (P=0.0120) compared with the placebo group (median: 167.9 hours in the 125 mg group [N=391], 167.8 hours in the 250 mg group [N=385], and 204.4 hours in the placebo group [N=377]). For patients who were randomized from onset within 120 hours, the median time to resolution was 183.2 hours in the 125 mg group (N=702), 168.9 in the 250 mg group (N=697) and 206.3 hours in the placebo group (N=692) (P=0.1235). One (0.1%) patient in the 125 mg group and 3 (0.4%) patients in the placebo group had serious adverse events; none resulted in death. No serious adverse events were observed in the 250 mg group. Conclusion Treatment of patients with COVID-19 with ensitrelvir significantly shortened the time to symptom recovery. Ensitrelvir was well tolerated. Disclosures Yuko Tsuge, MSc, SHIONOGI & CO., LTD.: Stocks/Bonds Hiroshi Yotsuyanagi, MD PhD, Shionogi: Advisor/Consultant|Shionogi: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Masaya Yamato, MD, PhD, Shionogi: Advisor/Consultant Takuhiro Sonoyama, MD, SHIONOGI & CO., LTD.: I am an employee of SHIONOGI & CO., LTD.|SHIONOGI & CO., LTD.: Stocks/Bonds

Cariprazine augmentation in patients with treatment resistant unipolar depression who failed to respond to previous atypical antipsychotic add-on. A case-series.

Among individuals receiving an adequate pharmacological treatment for Major Depressive Disorder (MDD), only 30% reach a full symptom recovery; the remaining 70% will experience either a pharmacological response without remission or no response at all thus configuring treatment resistant depression (TRD). After an inadequate response to an antidepressant, possible next step options include optimizing the dose of the current antidepressant, switching to a different antidepressant, combining antidepressants, or augmenting with a non-antidepressant medication. Augmentation strategies with the most evidence-based support include atypical antipsychotics (AAs). Few data are available in literature about switching to another antipsychotic when a first augmentation trial has failed. We present a case-series of patients with unipolar treatment resistant depression who were treated with a combination of antidepressant and low dose of cariprazine after failing to respond to a first augmentation with another AA. We report data about ten patients affected by unipolar depression, visited at the outpatients unit of Mental Health Department of ASL CN2 of Bra and NA1 of Napoli (Italy). All patients failed to respond to conventional antidepressant therapy. A low dose of AA (aripiprazole, risperidone or brexpiprazole) was added for one month to the ongoing antidepressant treatment without clinical improvement. A second augmentation trial was then made with cariprazine. Seven out of ten patients were responders at the end of period, of them 1 patient reached responder status by week 2. HAM-D mean scores decreased from 23.9 ± 3.9 (baseline) to 14.8 ± 5.3 (4 weeks). Cariprazine was well tolerated, no severe side effect was observed during the trial. Our sample of treatment resistant unipolar patients showed good response to augmentation with cariprazine. Failure to a first AA-augmentation trial does not preclude response to a second one. This preliminary result requires confirmation through more rigorous studies conducted over greater samples.

Ultrasound guided platelet rich plasma or corticosteroid for supraspinatus tendonosis or partial tear: an observational study of clinical outcome

Background: The clinical application of platelet rich plasma (PRP) in rotator cuff tears has increased recently. Many studies have found no difference between placebo controls and PRP and corticosteroids (CS) and some have found more rapid benefits with PRP injections. The present study was undertaken with the objectives to observe and assess efficacies of the two different treatment modalities in terms of symptomatic relief and recovery of ROM and to ascertain the duration of symptom free period and functional improvement on follow up. Methods: Observational clinical outcome study, conducted at a tertiary care hospital between September 2020 and March 2022 after institute ethical committee clearance. A total of 100 patients, with a positive clinical test for supraspinatus and magnetic resonance imaging (MRI) suggestive of supraspinatus tendinitis were divided to 2 groups and based on whether they received either intra-articular CS or PRP injection under ultrasonography (USG) guidance All patients were followed up at for assessing the outcomes at 6 weeks, 3 months and 6 months from intervention Results: The clinical outcome of the group receiving the PRP was better than group receiving CS intervention. Conclusions: PRP should therefore be considered as a viable option to treat supraspinatus tendinopathy/partial tear as it is cheap, readily available modality using patients own blood which is more acceptable to patient and also safe to individual where complications related to corticosteroids anticipated. Ultrasound guided procedure were found to enhance the accuracy of injection.

Acute necrotizing encephalopathy of childhood secondary to parainfluenza infection: A review of two cases

IntroductionAcute necrotizing encephalopathy (ANE) of childhood is a rare inflammatory syndrome, classically associated with preceding febrile illness and followed by fulminant neurological deterioration including encephalopathy, seizures, and focal neurological deficits with multifocal lesions of the thalami, rostral brainstem, and cerebral and cerebellar gray and white matter. ANE is distinctly associated with significant rates of neurological sequelae and death. Multiple infectious and parainfectious etiologies have been associated with ANE, notably influenza A. Case ReportWe report two cases of ANE associated with parainfluenza infection. Both children were treated with high-dose methylprednisolone and intravenous immunoglobulin, and one treated with tocilizumab. However, both patients suffered rapid neurological deterioration and death despite aggressive intervention. ConclusionWe present two cases of ANE with rapid neurological deterioration and death despite aggressive medical therapy. Rapid treatment with immunomodulatory treatments can lead to symptomatic recovery of variable degree in some patients. While high-dose steroids, intravenous immunoglobulin, and plasma exchange are common therapies for ANE, some case reports have suggested interleukin-6 (IL-6) blockade with tocilizumab can be beneficial. We report the nineteenth documented child in pediatric literature treated for ANE with tocilizumab, who did not respond to treatment, suggesting the response is heterogeneous and warrants additional investigation.

Association of obesity with mild traumatic brain injury symptoms, inflammatory profile, quality of life and functional outcomes: a TRACK-TBI Study

ObjectivesObesity is associated with chronic inflammation, which may impact recovery from mild traumatic brain injury (mTBI). The objective was to assess the role of obesity in recovery of symptoms, functional...

Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation.

Interstitial cystitis/bladder pain syndrome (IC/BPS) seriously reduces the patient's quality of life, yet current therapies only provide partial relief. In the spinal dorsal horn (SDH), neuroinflammation plays a pivotal role in the development of IC. Injection of human umbilical cord mesenchymal stem cells (hUMSCs) to reduce inflammation is an effective strategy, and heme oxygenase-1 (HO-1) exhibits anti-nociceptive effect in neuroinflammatory pain. This study aimed to test the therapeutic effects of hUMSCs overexpressing HO-1 on cyclophosphamide-induced cystitis rat model. Cystitis rats were transplanted with altered cells and then assessed for 3 weeks. A series of behavioral measurements would be trial including suprapubic mechanical allodynia, depressive-like behaviors, micturition frequency, and short-term memory function. Additionally, western blot, immunofluorescence staining, and ELISA kit test for anti-inflammation effect. HUMSCs were capable of being transduced to overexpress HO-1. Injection of hUMSCs overexpressing HO-1 was more effective than hUMSCs alone in alleviating behavioral symptoms in rats. Furthermore, hUMSCs overexpressing HO-1 inhibited the activation of glial and TLR4/p65/NLRP3 pathway, decreased the levels of pro-inflammatory cytokines in the SDH region. Surprisingly, it markedly increased anti-inflammatory cytokine IL-10, reduced MDA content, and protected GSH concentrations in local environment. Our results suggest that injecting hUMSCs overexpressing HO-1 intrathecally can significantly promote functional outcomes in cystitis rats by reducing neuroinflammation, at least, partly through downregulating TLR4/p65/NLRP3 signaling pathway in the SDH region. This cell therapy affords a new strategy for IC/BPS treatment.

Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

Some individuals with mild traumatic brain injury (mTBI), also known as concussion, have neuropsychiatric and physical problems that last longer than a few months. Symptoms following mTBI are not only impacted by the kind and severity of the injury but also by the post-injury experience and the individual's responses to it, making the persistence of mTBI particularly difficult to predict. We aimed to identify prognostic blood-based protein biomarkers predicting 6-month outcomes, in light of the clinical course after the injury, in a longitudinal mTBI cohort (N = 42). Among 420 target proteins quantified by multiple-reaction monitoring-mass spectrometry assays of blood samples, 31, 43, and 15 proteins were significantly associated with the poor recovery of neuropsychological symptoms at < 72h, 1week, and 1month after the injury, respectively. Sequential associations among clinical assessments (depressive symptoms and cognitive function) affecting the 6-month outcomes were evaluated. Then, candidate biomarker proteins indirectly affecting the outcome via neuropsychological symptoms were identified. Using the identified proteins, prognostic models that can predict the 6-month outcome of mTBI were developed. These protein biomarkers established in the context of the clinical course of mTBI may have potential for clinical application.

Stroke as initial manifestation of non-small cell lung cancer with Trousseau syndrome

ObjectiveStroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction.MethodsThe clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented.ResultsAll 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038).ConclusionTrousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.

Abstract 11763: A Unique Presentation of Heart Failure With Severe Pulmonary Hypertension and Pericardial Effusion in a Young Patient With a Ruptured Sinus of Valsalva Aneurysm

Case: 26 y/o female immigrant from a developing nation presented with shortness of breath at rest. On physical exam, she desaturated to 75% with minimal movement, had an audible pansystolic murmur, and 2+ pitting edema. Initial presentation was indicative of decompensated Heart Failure (HF). 2D Echocardiogram (Echo) showed a right sinus of Valsalva aneurysm (SOV) with a left to right shunt to the pulmonary artery, as well as, severe pulmonary hypertension (PHTN) and moderate pericardial effusion. CT Scan of the chest showed a right Ruptured SOV (RSOV) with a dissection flap extending into the aorta. Transesophageal Echocardiogram confirmed the diagnosis; noted a right RSOV extending into the pulmonary artery causing severe pulmonary HTN leading to HF and pericardial effusion. The patient underwent surgical correction with full recovery and resolution of symptoms. Conclusions: SOV is a rare cardiac complication with variable etiology. Congenital causes are often found early in age and resolved surgically. Cases regarding the management of adults, especially in the critical care setting, are not well described. Here we report a 26-year-old female who rapidly developed HF with PHTN and pericardial effusion secondary to an RSOV. This case shows the importance of Echo in managing HF and determining its etiology. Using Echo we saw a dilated Inferior Vena Cava of 2.7 cm characteristic of HF. Next, we were able to visualize a dilated RSOV with a shunt to the right, subsequent turbulent flow through the Aortic valve, and severe tricuspid regurgitation. Lastly, we were able to see elevated pulmonary artery systolic pressure secondary to the shunt, and subsequent pericardial effusion (fig 1). The patient's symptoms were initially managed with IV diuretics and resolved with surgery. This is a rare case of right-sided RSOV extending into the pulmonary artery, its successful treatment, and the important role of Echo in treating HF and PHTN.

Physical status, symptoms and health-related quality of life during a severe exacerbation of COPD: Recovery and discriminative capacity for future events

ObjectiveSevere acute exacerbations of chronic obstructive pulmonary disease (AECOPD) can have a negative impact on functional capacity, symptoms and health-related quality of life (HRQOL). This study aimed to i) investigate the recovery of muscle strength, functional capacity, symptoms, and HRQOL in patients after a severe AECOPD; ii) compare with matched patients with stable COPD (SCOPD); and iii) assess whether these assessments at hospital discharge could discriminate patients’ risk for future events. MethodsThis observational study assessed patients with AECOPD during hospital discharge (T1) and one month after discharge (T2). Patients with SCOPD were assessed once. Quadriceps force, handgrip strength, short physical performance battery (SPPB), 6-min walk distance (6 MWD), COPD assessment test (CAT), London chest activity of daily living (LCADL), modified medical research council, checklist individual strength-fatigue, patient health questionnaire, and physical activity (Actigraph) were measured. Exacerbation-related readmission and mortality within six months and 1-year were collected. ResultsForty-four patients with AECOPD were matched with 44 patients with SCOPD. At T2, a significant improvement was found for the SPPB total score, 6 MWD, CAT score, and LCADL score. Compared to patients with SCOPD, a worse LCADL score was found at T2 in patients with AECOPD. Patients with AECOPD that were readmitted or died had a worse SPPB classification and five-repetition sit-to-stand test at T1. ConclusionPatients after severe AECOPD improved in functional capacity and HRQOL one month after hospital discharge, but ADL performance was still worse compared to SCOPD. Patients who were readmitted or died had significantly worse scores on functional tests at hospital discharge.

4 Extending the 5P Clinical Decision Rule Predicting Concussion Recovery Using an Evidence-Based Assessment Model

Objective:Construction of predictive algorithms of concussion symptom recovery at 4 and 12 weeks post-injury using an evidence-based assessment (EBA) model to guide clinical decision-making, extending the 2016 5P decision rule.Participants and Methods:Children and adolescents, ages 8-18 (n=1,551; mean age=12.78; 62% male), followed over 12 weeks in the prospective multicenter cohort study (Predicting Persistent Post-Concussive Problems in Pediatrics, 5P; Zemek et al., 2016). The age-specific PostConcussion Symptom Inventory (PCSI) (8-12, 17 items; 1318 years, 20 items) was completed at six timepoints from the ED and at 1, 2, 4, 8, and 12-weeks post-injury. Logistic regression analysis was applied to the set of key variables including the PCSI Total Retrospective-Adjusted PostInjury Difference (RAPID) scores, patient demographics and pre-injury history, and injury characteristics to predict participant recovery status (Recovered, Not Recovered) at the 4- and 12-week endpoints. The resulting recovery-predictive equations identified the significant sets of variables with symptom scores at four successive post-injury timepoints (ED, 1, 2, 4 weeks). Logistic Regression Threshold values were established at the 90th CI against which individual patient data was applied to determine recovery status. Participants with sub-threshold sums were deemed recovered at the target endpoint (4- or 12-weeks post-injury).Results:A total of 19 predictive equations were generated for the two age groups across the recovery timeline. Four sets of equations were developed to predict symptom recovery status at 4-weeks post-injury for the two age groups (8-12 AUC=0.679-0.884; 13-18 AUC=0.752-0.909). Prediction of symptom recovery status at 12-weeks post-injury yielded six equations for the 8-12 age group (AUC=0.723-0.825), and five equations for the 13-18 age group (AUC=0.724-0.887). Total PCSI RAPID score was identified as a significant variable in each of these 19 equations. Participant sex was identified as significant in 18 of the 19 constructed equations. Other variables that were identified as significant at varying timepoints included age, pre-injury history of learning disability and migraines, and an early post-injury sign in the ED (answering questions more slowly than usual). Examples of the equations include: Week 1 predicting symptom recovery status at 4-weeks: 8-12 yr group-(Sex*.802)+(week 1 Total RAPID Score*.142)+(Age2* .053)+(-3.851) with AUC=0.808; 13-18 yr group-(Sex*.980)+(Week 1 Total RAPID Score*.071)+(-3.261) with AUC=0.861.Conclusions:Clinicians’ management of the concussion recovery of children and adolescents can benefit from EBA guidance. The 5P dataset (Zemek et al., 2016) provides an important window into “typical” and “atypical” recovery trajectories, establishing an initial predictive decision rule for a 4-week recovery endpoint, at the ED timepoint only, reporting AUC=0.69. The current study extends the prediction modeling using successive post-injury timepoints reflecting a typical management timeline. Symptom reports from both 1- and 2-weeks post injury with patient demographics/ history predicted symptom recovery status at 4- and 12-weeks post-injury, significantly improve predictive accuracy over the ED timepoint alone. These predictive equations, when applied to the individual patient, can serve to assist the clinician’s understanding of the patients’ recovery trajectory, i.e., on track for a typical or atypical recovery, further informing the intervention strategy.

Hyperosmolar hyperglycemic state presenting as transient global aphasia

Hyperosmolar hyperglycemic state (HHS) is an emergency condition characterized by severe dehydration secondary to uncontrolled hyperglycemic state in the absence of ketoacidosis. HHS can present with a variety of neurological symptoms including encephalopathy and seizures. In this report, we present a case of acute-onset transient global aphasia in a 65-year-old male with chronic poor glycemic control. Post-evaluation, we establish the etiology of transient global aphasia as HHS in which patient had complete recovery of symptoms following normalization of blood glucose levels.

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Evidence of Ongoing Cerebral Microstructural Reorganization in Children With Persisting Symptoms Following Mild Traumatic Brain Injury: A NODDI DTI Analysis.

Approximately 300-550 children per 100,000 sustain a mild traumatic brain injury (mTBI) each year, of whom ∼25-30% have long-term cognitive problems. Following mTBI, free water (FW) accumulation occurs in white matter (WM) tracts. Diffusion tensor imaging (DTI) can be used to investigate structural integrity following mTBI. Compared with conventional DTI, neurite orientation dispersion and density imaging (NODDI) orientation dispersion index (ODI) and fraction of isolated free water (FISO) metrics may allow a more advanced insight into microstructural damage following pediatric mTBI. In this longitudinal study, we used NODDI to explore whole-brain and tract-specific differences in ODI and FISO in children with persistent symptoms after mTBI (n = 80) and in children displaying clinical recovery (n = 32) at 1 and 2-3 months post-mTBI compared with healthy controls (HCs) (n = 21). Two-way repeated measures analysis of variance (ANOVA) and voxelwise two-sample t tests were conducted to compare whole-brain and tract-specific diffusion across groups. All results were corrected at positive false discovery rate (pFDR) <0.05. We also examined the association between NODDI metrics and clinical outcomes, using logistical regression to investigate the value of NODDI metrics in predicting future recovery from mTBI. Whole-brain ODI was significantly increased in symptomatic participants compared with HCs at both 1 and 2 months post-injury, where the uncinate fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF) were particularly implicated. Using region of interest (ROI) analysis in significant WM, bilateral IFOF and UF voxels, symptomatic participants had the highest ODI in all ROIs. ODI was lower in asymptomatic participants, and HCs had the lowest ODI in all ROIs. No changes in FISO were found across groups or over time. WM ODI was moderately correlated with a higher youth-reported post-concussion symptom inventory (PCSI) score. With 87% predictive power, ODI (1 month post-injury) and clinical predictors (age, sex, PCSI score, attention scores) were a more sensitive predictor of recovery at 2-3 months post-injury than fractional anisotropy (FA) and clinical predictors, or clinical predictors alone. FISO could not predict recovery at 2-3 months post-injury. Therefore, we found that ODI was significantly increased in symptomatic children following mTBI compared with HCs at 1 month post-injury, and progressively decreased over time alongside clinical recovery. We found no significant differences in FISO between groups or over time. WM ODI at 1 month was a more sensitive predictor of clinical recovery at 2-3 months post-injury than FA, FISO, or clinical measures alone. Our results show evidence of ongoing microstructural reorganization or neuroinflammation between 1 and 2-3 months post-injury, further supporting delayed return to play in children who remain symptomatic. We recommend future research examining the clinical utility of NODDI following mTBI to predict recovery or persistence of post-concussion symptoms and thereby inform management of mTBI.

Targeting the central nervous system: The future of therapeutic strategies for MS

Targeting the central nervous system: The future of therapeutic strategies for MS Tara M. DeSilva from the Department of Neurosciences, Cleveland Clinic, looks at the future of therapeutic strategies for MS, focusing on targeting the central nervous system. Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease initially characterized by white matter lesions in the central nervous system (i.e., brain, spinal cord, and optic nerve) detected by magnetic resonance imaging (MRI). Lesions are caused by the infiltration of immune cells, resulting in loss of the insulation (myelin) around nerve fibers (neuronal axons). Early in the MS disease course, myelin regenerates; however, over time, sustained demyelination results in axonal injury and permanent disability. (1) The location of a lesion in the brain, spinal cord, or optic nerve determines the type of deficit a patient with MS will experience. Most patients with MS initially present with a relapsing-remitting disease course. During this phase, manifestations of clinical deficits indicate a relapse followed by a recovery or remittance of symptoms. Eventually, MS patients enter into a progressive disease course. During the progressive phase, there is no remittance, and symptoms gradually worsen, leading to permanent disability (Fig. 1).

Early life threatening constrictive pericarditis following off-pump CABG

Abstract We present a unique case of aggressive symptomatic constrictive pericarditis within one month following off pump coronary artery bypass grafting surgery. The patient had a medical history of Hodgkin’s lymphoma treated with radiotherapy and chemotherapy 20 years ago. Investigations confirmed constrictive pericardium with patent grafts and good biventricular function. Pericardiectomy was successful with remarkable recovery of symptoms.

Symptom burden, sleep disturbance and recovery following concussion in female children and adolescents

Symptom burden, sleep disturbance and recovery following concussion in female children and adolescents

A retrospective review of divers treated for inner ear decompression sickness at Fiona Stanley Hospital hyperbaric medicine unit 2014-2020.

Inner ear decompression sickness (IEDCS) is increasingly recognised in recreational diving, with the inner ear particularly vulnerable to decompression sickness in divers with a right-to-left shunt, such as is possible through a persistent (patent) foramen ovale (PFO). A review of patients treated for IEDCS at Fiona Stanley Hospital Hyperbaric Medicine Unit (FSH HMU) in Western Australia was performed to examine the epidemiology, risk factors for developing this condition, the treatment administered and the outcomes of this patient population. A retrospective review of all divers treated for IEDCS from the opening of the FSH HMU on 17 November 2014 to 31 December 2020 was performed. Patients were included if presenting with vestibular or cochlear dysfunction within 24 hours of surfacing from a dive, and excluded if demonstrating features of inner ear barotrauma. There were a total of 23 IEDCS patients and 24 cases of IEDCS included for analysis, with 88% experiencing vestibular manifestations and 38% cochlear. Median dive time was 40 minutes and median maximum depth was 24.5 metres. The median time from surfacing to hyperbaric oxygen treatment (HBOT) was 22 hours. Vestibulocochlear symptoms fully resolved in 67% and complete symptom recovery was achieved in 58%. A PFO was found in 6 of 10 patients who subsequently underwent investigation with bubble contrast echocardiography upon follow-up. IEDCS occurred predominantly after non-technical repetitive air dives and ongoing symptoms and signs were often observed after HBOT. Appropriate follow-up is required given the high prevalence of PFO in these patients.

Efficacy of Pentosan Polysulfate Treatment in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization. Self-evaluation scales can provide more objective results on pre- and post-treatment satisfaction. The aim of this study was to investigate the effect of pentosan polysulfate treatment on symptoms in IC-BPS patients. This study included 37 adult male and female patients with IC-BPS who reported pain, urinary urgency, polyurea, and nocturia without urinary tract infection for a minimum of six months prior to the study and were taking 300 mg/day oral pentosan polysulfate. Pre- and post-treatment symptoms, Interstitial Cystitis Symptom Index (ICSI) Scores, quality of life (QoL) scores (1-4), and satisfaction conditions were examined. Following the application of inclusion and exclusion criteria, mean age of 37 suitable patients was 46.0±11.9 years and 27% (10 individuals) of the patients were male. Pre-treatment, ICSI scores, and measures of satisfaction degree and QoL increased significantly after the treatment (p<0.001). Adverse reaction was detected in two patients (5.4%) among the patients treated with pentosan polysulfate. Oral pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome treatment could achieve recovery in symptoms, increase Interstitial Cystitis Symptom Index score and improve quality of life and patient satisfaction.

Fermentation of Ganoderma lucidum and Raphani Semen with a probiotic mixture attenuates cyclophosphamide-induced immunosuppression through microbiota-dependent or -independent regulation of intestinal mucosal barrier and immune responses

BackgroundProbiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PurposeWe established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. MethodsFirst, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. ResultsProbiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. ConclusionThis is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.