Rejected

: To determine if thoracic spine manipulation (TSM) improves pain and disability in individuals with cervicogenic headache (CeH). A randomized controlled crossover trial was conducted on 48 participants (mean age: 34.4 years) with CeH symptoms. Participants were randomized to 6 sessions of TSM or no treatment (Hold) and after 4-weeks, groups crossed over. Outcomes were collected at 4, 8 and 12 weeks and included: headache disability inventory (HDI), neck disability index (NDI), and the global rating of change (GRC). Outcomes were analyzed using a linear mixed-effects model with Bonferroni correction. Odds of achieving the minimal clinically important difference (MCID) on the GRC of +4 or greater were also calculated. Scores at 4 weeks represent the only timepoint where 1 group is fully treated and other group has not received any treatment. Comparing hold to active treatment, HDI were not significantly different between groups (mean difference = 7.39, 95 CI: -4.39 to 19.18; P = 0.214) at any timepoint; the NDI was significant (mean difference = 6.90, 95 CI: 0.05 to 13.75; P = 0.048) at 4 weeks. Odds of achieving the +4 MCID on the GRC (OR = 38.0, 95 CI: 6.6 to 220.0; p < 0.001) favored TSM at 4 weeks. TSM had no effect on headache-related disability but resulted in significant improvements in neck-related disability and participant reported perceived improvement. Future studies are needed to examine the long-term impact of TSM in this population.

Triple-negative breast cancer (TNBC) cells are sensitive to PARP1 inhibitors in vitro. The combination of Olaparib and radiotherapy for TNBC is currently evaluated in the phase I RADIOPARP trial. RADIOPARP is a monocentric prospective open-label phase I dose-escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. Twenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without dose-limiting toxicities. At one-year follow-up, no treatment-related grade ≥3 toxicity was observed. One patient (4.2%) had persistent grade 2 adverse events (breast pain, fibrosis and deformity). There was no cardiac, pulmonary or digestive toxicity related to treatment. The one-year follow-up report of the RADIOPARP phase I trial, evaluating Olaparib associated with breast radiotherapy in TNBC patients, consequently demonstrated an excellent toxicity profile of this combination with few low-grade adverse events. This article is protected by copyright. All rights reserved.

Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain-containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB in the plasma membrane.

Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1,250 µmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 minutes after breathing 790 ppm of H2S followed by another 30 minutes of H2S inhalation. Effects of SS20 on survival was assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 minute of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 µmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-hour survival (6/6 [100%] in SS20 versus 1/6 [17%] in vehicle; P = 0.0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 versus 0/10 [0%] in vehicle; P = 0.0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. The current results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.

Surgical rib fixation in the general population can decrease morbidity, including length of stay and ventilator days. Elderly rib fractures convey high rates of morbidity and mortality, and it is unclear whether this population benefits from operative management.

Acute kidney injury (AKI) is defined by a sudden loss of excretory kidney function. AKI is part of a range of conditions summarized as acute kidney diseases and disorders (AKD), in which slow deterioration of kidney function or persistent kidney dysfunction is associated with an irreversible loss of kidney cells and nephrons, which can lead to chronic kidney disease (CKD). New biomarkers to identify injury before function loss await clinical implementation. AKI and AKD are a global concern. In low-income and middle-income countries, infections and hypovolaemic shock are the predominant causes of AKI. In high-income countries, AKI mostly occurs in elderly patients who are in hospital, and is related to sepsis, drugs or invasive procedures. Infection and trauma-related AKI and AKD are frequent in all regions. The large spectrum of AKI implies diverse pathophysiological mechanisms. AKI management in critical care settings is challenging, including appropriate volume control, nephrotoxic drug management, and the timing and type of kidney support. Fluid and electrolyte management are essential. As AKI can be lethal, kidney replacement therapy is frequently required. AKI has a poor prognosis in critically ill patients. Long-term consequences of AKI and AKD include CKD and cardiovascular morbidity. Thus, prevention and early detection of AKI are essential.

To estimate the prevalence of atypical anatomical morphologies at the sacroiliac joints (SIJ) in young adults by CT and analyze the diagnostic ability of MRI to detect the variations in addition to concomitant MRI findings that could be misdiagnosed as inflammatory changes.

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.

Neurovascular compression (NVC) in patients with trigeminal neuralgia (TN) can be a factor of treatment outcome especially in microvascular decompression and stereotactic radiosurgery. No such effect has been reported in percutaneous radiofrequency rhizotomy (RF). This study is to investigate if NVC affects the efficacy of RF in patients with TN.

Hospital mortality for critically ill patients has decreased significantly throughout the developed world over the past two decades, attributable to improvements in the quality of intensive care, advances in critical care medicine and technologies that provide long-term multiorgan support. However, the long-term outcomes of intensive care unit (ICU) survivors is emerging as a real issue. Cognitive and physical impairments suffered by ICU survivors are common including profound weakness, pain and delirium which are inextricably linked. This study aims to determine the effectiveness of the Assess, prevent and manage pain; Both spontaneous awakening and spontaneous breathing trials; Choice of sedation and analgesia; Delirium: assess, prevent and manage; Early mobility and exercise; Family engagement and empowerment (ABCDEF) bundle in reducing ICU-related short-term and long-term consequences of critical illness through a randomised controlled trial (RCT).