Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial

Introduction

Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study.

Methods

In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO₂) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination.

Results

Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05).

Conclusions

TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.     

Prognostic factors of severe pneumonia in patients treated with rituximab in the intensive care unit

ObjectiveThe aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the intensive care unit (ICU).MethodsWe systematically reviewed the medical records of 40 patients who received RTX and developed severe pneumonia in the ICU at our hospital from January 2009 to January 2019 to evaluate the underlying conditions, clinical course, and possible prognostic factors.ResultsMost patients had underlying hematologic malignancies (n = 21, 52.5%), followed by rheumatologic diseases (n = 17, 42.5%). The most frequent causative pathogens were fungi (n = 11, 27.5%), followed by bacteria (n = 9, 22.5%) and Pneumocystis jirovecii pneumonia (n = 8, 20%). Thirty patients (75%) died, and the other 10 patients (25%) survived. Compared with survivors, patients who died were significantly older (60.6 ± 10.6 vs 44.4 ± 18.3 years) and had chronic lung disease (40% vs 0%).ConclusionOlder age and chronic lung disease were significantly associated with mortality in patients treated with RTX.     

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

BackgroundTo compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.MethodsWe performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression.ResultsThe questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression.Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p <  0.001; cluster headache 5.62 ± 0.99, p <  0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p <  0.001; cluster headache: − 5.25 ± 0.56, p <  0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).ConclusionMen with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.     

Hypoperfusion in nucleus accumbens in chronic migraine using 3D pseudo-continuous arterial spin labeling imaging MRI

BackgroundNucleus accumbens (NAcc) played an important role in pain mediation, and presents changes of neuronal plasticity and functional connectivity. However, less is known about altered perfusion of NAcc in chronic migraine (CM). The aim of this study is to investigate the altered perfusion of the NAcc in CM using a MR three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) imaging.MethodsThirteen CM patients and 15 normal controls (NC) were enrolled and underwent 3D PCASL and brain structural imaging. The cerebral blood flow (CBF) images were co-registered with the brain structural images, and the volume and CBF value of NAcc were extracted from the raw brain structural images and co-registered CBF images using an individual NAcc mask, which was obtained from the AAL3 template under transformation by the inverse deformation field generated from the segmentation of the brain structural images. The independent sample t test and receiver operating characteristic (ROC) curve was used to investigate the altered volume and perfusion of the NAcc in CM patients.ResultsThere was no significant difference for the volume of bilateral NAccs between CM and NC (p > 0.05). CM presented a lower CBF value (49.34 ± 6.09 ml/100 mg/min) compared with that of NC (55.83 ± 6.55 ml/100 mg/min) in left NAcc (p = 0.01), while right NAcc showed no significant difference between CM and NC (p = 0.11). ROC analysis identified that the area under the curve was 0.73 (95CI% 0.53–0.88) with cut-off value 48.63 ml/100 mg/min with sensitivity 50.00% and specificity 93.33%. The correlation analysis found a negative correlation between the CBF value of the left NAcc and VAS score (r = -0.61, p = 0.04).ConclusionHypoperfusion of the left NAcc was observed in CM, which could be considered as a potential diagnostic imaging biomarker in CM.     

Circulating long non‐coding RNA Coromarker expression correlated with inflammation,coronary artery stenosis,and plaque vulnerability in patients with coronary artery disease

BackgroundThe aim of the study was to assess the correlation between circulating long non‐coding RNA (lncRNA) OTTHUMT00000387022 (named Coromarker) expression and disease severity, inflammatory cytokine levels, and plaque vulnerability in patients with coronary artery disease (CAD).MethodsA total of 134 participants who received coronary angiography were enrolled and classified them as CAD patients (N = 89) and controls (N = 45). Blood samples were obtained from all subjects. Quantitative polymerase chain reaction was used to evaluate Coromarker expression. The enzyme‐linked immunosorbent test was used to measure inflammatory cytokines including high sensitivity C reactive protein (hsCRP), interleukin (IL)‐1β (IL‐1β), IL‐6, NOD‐like receptor protein 3 (NLRP3), and markers of coronary plaque stability including matrix metallopeptidase 9 (MMP‐9) and soluble CD40 ligand (sCD40L). The severity of coronary stenosis was determined from the Gensini Score.ResultsLncRNA Coromarker expression was elevated to a greater extent in CAD patients than in control subjects before and after adjustments for age/gender (both p < 0.001); it was an independent predictor of CAD risk (area under curve: 0.824, 95% CI: 0.732–0.915). Additionally, Coromarker expression was significantly associated with Gensini Score (r = 0.574, p < 0.001), hsCRP (r = 0.221, p = 0.015), IL‐1β (r = 0.351, p < 0.001), IL‐6 (r = 0.286, p < 0.01), and NLRP3 levels (r = 0.312, p < 0.001). Coromarker expression was found to be linked with MMP‐9 (r = 0.260, p < 0.01) and sCD40L (r = 0.441, p < 0.001).ConclusionCirculating lncRNA Coromarker expression correlates with increased disease severity and inflammation as well as plaque vulnerability in patients with CAD.     

Single breath-hold 3D measurement of left atrial volume using compressed sensing cardiovascular magnetic resonance and a non-model-based reconstruction approach

Background

Left atrial (LA) dilatation is associated with a large variety of cardiac diseases. Current cardiovascular magnetic resonance (CMR) strategies to measure LA volumes are based on multi-breath-hold multi-slice acquisitions, which are time-consuming and susceptible to misregistration.

Aim

To develop a time-efficient single breath-hold 3D CMR acquisition and reconstruction method to precisely measure LA volumes and function.

Methods

A highly accelerated compressed-sensing multi-slice cine sequence (CS-cineCMR) was combined with a non-model-based 3D reconstruction method to measure LA volumes with high temporal and spatial resolution during a single breath-hold. This approach was validated in LA phantoms of different shapes and applied in 3 patients. In addition, the influence of slice orientations on accuracy was evaluated in the LA phantoms for the new approach in comparison with a conventional model-based biplane area-length reconstruction. As a reference in patients, a self-navigated high-resolution whole-heart 3D dataset (3D-HR-CMR) was acquired during mid-diastole to yield accurate LA volumes.

Results

Phantom studies. LA volumes were accurately measured by CS-cineCMR with a mean difference of −4.73 ± 1.75 ml (−8.67 ± 3.54 %, r² = 0.94). For the new method the calculated volumes were not significantly different when different orientations of the CS-cineCMR slices were applied to cover the LA phantoms. Long-axis “aligned” vs “not aligned” with the phantom long-axis yielded similar differences vs the reference volume (−4.87 ± 1.73 ml vs −4.45 ± 1.97 ml, p = 0.67) and short-axis “perpendicular” vs “not-perpendicular” with the LA long-axis (−4.72 ± 1.66 ml vs −4.75 ± 2.13 ml; p = 0.98). The conventional bi-plane area-length method was susceptible for slice orientations (p = 0.0085 for the interaction of “slice orientation” and “reconstruction technique”, 2-way ANOVA for repeated measures). To use the 3D-HR-CMR as the reference for LA volumes in patients, it was validated in the LA phantoms (mean difference: −1.37 ± 1.35 ml, −2.38 ± 2.44 %, r² = 0.97). Patient study: The CS-cineCMR LA volumes of the mid-diastolic frame matched closely with the reference LA volume (measured by 3D-HR-CMR) with a difference of −2.66 ± 6.5 ml (3.0 % underestimation; true LA volumes: 63 ml, 62 ml, and 395 ml). Finally, a high intra- and inter-observer agreement for maximal and minimal LA volume measurement is also shown.

Conclusions

The proposed method combines a highly accelerated single-breathhold compressed-sensing multi-slice CMR technique with a non-model-based 3D reconstruction to accurately and reproducibly measure LA volumes and function.     

Some characteristics of hyperglycaemic crisis differ between patients with and without COVID-19 at a safety-net hospital in a cross-sectional study

ObjectiveTo compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (−) [COVID (−)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area.MethodsA cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis.ResultsA total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (−)]. A majority were either Black or Hispanic. Compared with COVID (−) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p < .01). COVID(+) patients had a higher mean pH (7.25 ± 0.10 vs 7.16 ± 0.16, p < .01) and lower anion gap (18.7 ± 5.7 vs 22.7 ± 6.9, p = .01) than COVID (−) patients. COVID (+) patients were given less intravenous fluids in the first 24 h (2.8 ± 1.9 vs 4.2 ± 2.4 L, p = .01) and were more likely to receive glucocorticoids (95% vs. 11%, p < .01). COVID (+) patients may have taken longer to resolve their hyperglycaemic crisis (53.3 ± 64.8 vs 28.8 ± 27.5 h, p = .09) and may have experienced more hypoglycaemia <3.9 mmol/L (35% vs 19%, p = .09). COVID (+) patients had a higher length of hospital stay (LOS, 14.8 ± 14.9 vs 6.5 ± 6.0 days, p = .01) and in-hospital mortality (27% vs 7%, p = .02).DiscussionCompared with COVID (−) patients, COVID (+) patients with DKA/HHS are more likely to have T2D. Despite less severe metabolic acidosis, COVID (+) patients may require more time to resolve the hyperglycaemic crisis and experience more hypoglycaemia while suffering greater LOS and risk of mortality. Larger studies are needed to examine whether differences in management between COVID (+) and (−) patients affect outcomes with DKA/HHS.     

Doubling survival and improving clinical outcomes using a left ventricular assist device instead of chest compressions for resuscitation after prolonged cardiac arrest: a large animal study

IntroductionDespite improvements in pre-hospital and post-arrest critical care, sudden cardiac arrest (CA) remains one of the leading causes of death. Improving circulation during cardiopulmonary resuscitation (CPR) may improve survival rates and long-term clinical outcomes after CA.MethodsIn a porcine model, we compared standard CPR (sCPR; n =10) with CPR using an intravascular cardiac assist device without additional chest compressions (iCPR; n =10) following 10 minutes of electrically induced ventricular fibrillation (VF). In a separate crossover experiment, 10 additional pigs were subjected to 10 minutes of VF and 6 minutes of sCPR; the iCPR device was then implanted if a return of spontaneous circulation (ROSC) was not achieved using sCPR. Animals were evaluated in respect to intra- and post-arrest hemodynamics, survival, functional outcome and cerebral and myocardial lesions following CPR. We hypothesized that iCPR would result in more frequent ROSC and better functional recovery than sCPR.ResultsiCPR produced a mean flow of 1.36 ± 0.02 L/min, leading to significantly higher coronary perfusion pressure (CPP) values during the early period of CPR (22 ± 10 mmHg vs. 9 ± 5 mmHg, P ≤0.01, 1 minute after start of CPR; 20 ± 11 mmHg vs. 10 ± 7 mmHg, P =0.03, 2 minutes after start of CPR), resulting in high ROSC rates (100% in iCPR vs. 50% in sCPR animals; P =0.03). iCPR animals showed significantly lower serum S100 levels at 10 and 30 minutes following ROSC (3.5 ± 0.6 ng/ml vs. 7.4 ± 3.0 ng/ml 30 minutes after ROSC; P ≤0.01), as well as superior clinical outcomes based on overall performance categories (2.9 ± 1.0 vs. 4.6 ± 0.8 on day 1; P ≤0.01). In crossover experiments, 80% of animals required treatment with iCPR after failed sCPR. Notably, ROSC was still achieved in six of the remaining eight animals (75%) after a total of 22.8 ± 5.1 minutes of ischemia.ConclusionsIn a model of prolonged cardiac arrest, the use of iCPR instead of sCPR improved CPP and doubled ROSC rates, translating into improved clinical outcomes.     

The potency of common proinflammatory cytokines measurement for revealing the risk and severity of anxiety and depression in psoriasis patients

ObjectiveProinflammatory cytokines mediate anxiety and depression in various ways, such as immunity, inflammation, and the hypothalamic–pituitary–adrenal axis. This study intended to further explore the linkage of common proinflammatory cytokine levels with anxiety and depression in psoriasis patients.MethodsTotally, 150 psoriasis patients and 50 healthy controls (HCs) were included; the serum samples were collected, then common proinflammatory cytokines were measured by ELISA. Hospital Anxiety and Depression Scale (HADS) was assessed.ResultsHADS‐anxiety (HADS‐A) score, HADS‐depression (HADS‐D) score, TNF‐α, IL‐1β, IL‐6, IL‐12, IL‐17A, and IL‐23 were all increased in psoriasis patients compared to HCs (all p < 0.05). In psoriasis patients, TNF‐α (p = 0.001), IL‐12 (p = 0.035), and IL‐17A (p < 0.001), but not IL‐1β (p = 0.255), IL‐6 (p = 0.248), and IL‐23 (p = 0.216), were positively linked to HADS‐A score. Meanwhile, TNF‐α (p = 0.007) and IL‐17A (p = 0.007) were enhanced in psoriasis patients with anxiety in contrast to those without anxiety; whereas IL‐1β (p = 0.178), IL‐6 (p = 0.360), IL‐12 (p = 0.239), and IL‐23 (p = 0.450) were not different. TNF‐α (p < 0.001), IL‐1β (p = 0.013), Il‐17A (p < 0.001), and IL‐23 (p = 0.023), but not IL‐6 (p = 0.143) and IL‐12 (p = 0.158), were positively linked to HADS‐D score. Concurrently, TNF‐α (p = 0.015), IL‐17A (p < 0.001), and IL‐23 (p = 0.017) were climbed in psoriasis patients with depression by comparison to those without depression; whereas IL‐1β (p = 0.113), IL‐6 (p = 0.237), IL‐12 (p = 0.660) did not differ.ConclusionTNF‐α, IL‐17A, and IL‐23 increments reflect anabatic anxiety and depression in psoriasis patients, uncovering the potency of proinflammatory cytokines measurement for monitoring or even preventing psoriasis patients'' anxiety and depression.     

A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study

IntroductionThe effect of mean arterial pressure titration to a higher level on microcirculation in septic shock patients with previous hypertension remains unknown. Our goal is to assess the effect of mean arterial pressure titration to a higher level on microcirculation in hypertensive septic shock patients.MethodsThis is a single-center, open-label study. Hypertensive patients with septic shock for less than 24 hours after adequate fluid resuscitation and requiring norepinephrine to maintain a mean arterial pressure of 65 mmHg were enrolled. Mean arterial pressure was then titrated by norepinephrine from 65 mmHg to the normal level of the patient. In addition to hemodynamic variables, sublingual microcirculation was evaluated by sidestream dark field imaging.ResultsNineteen patients were enrolled in the study. Increasing mean arterial pressure from 65 mmHg to normal levels was associated with increased central venous pressure (from 11 ± 4 to 13 ± 4 mmHg, P = 0.002), cardiac output (from 5.4 ± 1.4 to 6.4 ± 2.1 l/minute, P = 0.001), and central venous oxygen saturation (from 81 ± 7 to 83 ± 7%, P = 0.001). There were significant increases in small perfused vessel density (from 10.96 ± 2.98 to 11.99 ± 2.55 vessels/mm², P = 0.009), proportion of small perfused vessels (from 85 ± 18 to 92 ± 14%, P = 0.002), and small microvascular flow index (from 2.45 ± 0.61 to 2.80 ± 0.68, P = 0.009) when compared with a mean arterial pressure of 65 mmHg.ConclusionsIncreasing mean arterial pressure from 65 mmHg to normal levels is associated with improved microcirculation in hypertensive septic shock patients.

Trial registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01443494","term_id":"NCT01443494"}}NCT01443494; registered 28 September 2011.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0866-0) contains supplementary material, which is available to authorized users.     

JNK pathway‐associated phosphatase in acute ischemic stroke patients: Its correlation with T helper cells,clinical properties,and recurrence risk

ObjectiveJKAP modifies T‐cell immune response and inflammation, also involves in cardia‐cerebrovascular disease etiology. This study intended to explore JKAP''s relation with T‐helper 1 (Th1), T‐helper 17 (Th17) cell levels, clinical properties, and recurrence‐free survival (RFS) in acute ischemic stroke (AIS) patients.MethodsA total of 155 AIS patients were analyzed. Serum JKAP, interferon‐gamma (IFN‐γ), and interleukin‐17A (IL‐17A) were detected by ELISA; then blood Th1 and Th17 cells were quantified by flow cytometry. Besides, 30 healthy subjects were enrolled as controls to detect JKAP, Th1, and Th17 cells.ResultsJKAP level was lower (p < 0.001), Th1 cells were not differed (p = 0.068), but Th17 cells were elevated in AIS patients versus controls (p < 0.001). Meanwhile, JKAP was negatively correlated with Th1 cells (p = 0.038), Th17 cells (P<0.001), IFN‐γ (p = 0.002), and IL‐17A (p < 0.001) in AIS patients. JKAP was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), but Th17 cells (p = 0.001), IFN‐γ (p = 0.035), and IL‐17A (p = 0.008) levels were positively associated with NIHSS score. Additionally, accumulating RFS was numerically longer in patients with JKAP Quantile (Q) 4 than patients with JKAP Q1–Q3 (p = 0.068), and numerically better in patients with JKAP Q3–Q4 than patients with JKAP Q1–Q2 (p = 0.069), but without statistical significance.ConclusionJKAP correlates with lower Th1 and Th17 cell percentages as well as milder disease severity.     

Comparative assessment of health-related quality of life with and without anticonvulsant therapy in patients with childhood epilepsy with centrotemporal spikes

ObjectiveTo estimate anti-seizure medication (ASM) treatment burden and its effects on health-related quality of life (HRQOL) in new-onset childhood epilepsy with centrotemporal spikes (CECTS) using different treatment approaches in Kazakhstan.MethodsForty-three patients were followed prospectively during 2015 to 2020 for at least 2 years. Patients were divided into three groups: (1) history of ≤3 seizures (n = 32); (2) ≥4 seizures (n = 6); (3) cerebral palsy coexisting with CECTS (n = 5). The first group was subdivided into treated (n = 8) and observed (n = 24) subgroups. The shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) was completed by parents after 6 months of follow-up.ResultsAt the end of the study, all children had a sustained remission from seizures for at least 2 years. Differences were identified in emotional, social, and physical subscales between patients in the low seizure frequency group. Signs of low self-esteem, anxiety, depression, limited social interaction owing to pharmacotherapy, painful medical procedures, and stigma were reasons for decreased HRQOL in the treated subgroup. Overall HRQOL in treated (89.2 ± 5.2) patients was significantly decreased compared with observed children with low seizure frequency (98.0 ± 3.0).ConclusionASM therapy does not necessarily improve and may decrease HRQOL in children with low seizure frequency CECTS.     

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

Background

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.

Methods

In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.

Results

Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m²; female > 78 g/m²). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).

Conclusion

In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.     

Galcanezumab in episodic migraine: the phase 3, randomized,double-blind,placebo-controlled PERSIST study

BackgroundGalcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia.MethodsThis phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score.ResultsIn total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo).ConclusionsGalcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia.Trial registrationClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT03963232","term_id":"NCT03963232"}}NCT03963232 (PERSIST), registered May 24, 2019.     

Eupalinilide B as a novel anti-cancer agent that inhibits proliferation and epithelial–mesenchymal transition in laryngeal cancer cells

ObjectiveTo investigate the anti-cancer effects and potential mechanisms of eupalinilide B in laryngeal cancer cells.MethodsLaryngeal cancer cell lines were selected to study the anti-tumor effects of eupalinilide B in vitro and in vivo. Lysine-specific demethylase 1 (LSD1) activity was assessed in vitro and dialysis experiments were performed to identify the anti-tumor target of the drug.ResultsEupalinilide B concentration-dependently inhibited the proliferation of laryngeal cancer cells, exhibiting potent inhibitory activity against TU686 (IC₅₀ = 6.73 µM), TU212 (IC₅₀ = 1.03 µM), M4e (IC₅₀ = 3.12 µM), AMC-HN-8 (IC₅₀ = 2.13 µM), Hep-2 (IC₅₀ = 9.07 µM), and LCC cells (IC₅₀ = 4.20 µM). Subsequent target verification experiments demonstrated that eupalinilide B selectively and reversibly inhibited LSD1. Furthermore, eupalinilide B, as a natural product, suppressed epithelial–mesenchymal transition in TU212 cells. An in vivo experiment further indicated that eupalinilide B could significantly reduce the growth of tumors in TU212 xenograft mouse models.ConclusionsEupalinilide B might be a novel LSD1 inhibitor for treating laryngeal cancer.     

Prevalence and correlative factors of hyperhomocysteinemia in elderly patients with femoral neck fracture: A cross‐sectional study

AimsThe occurrence of hyperhomocysteinemia (HHcy) in elderly patients with femoral neck fracture (FNF) draws little attention from surgeons preoperatively. The aim of our study was to determine the prevalence and correlative factors of HHcy in elderly patients (≥65 years) with FNF prior to surgery.MethodsWe retrospectively investigated 286 elderly FNF patients aged 65–98 years admitted to our institution from September 2020 to September 2021. Categorical variables were compared using the Chi‐squared test, and continuous variables were compared using the Mann–Whitney U test. Univariable and multivariable logistic regression were used to determine the associations of variables with the odds of HHcy.ResultsAmong the 286 elderly FNF patients, the prevalence of HHcy was 30.77% and the mean Hcy level was 14.52 ± 10.49 μmol/L. The mean Hcy level and the prevalence of HHcy in male patients were significantly higher than that in female patients (16.41 ± 9.58 μmol/L vs. 14.00 ± 10.69 μmol/L, p = 0.002; 43.55% vs. 27.23%, p = 0.014). Multivariate analysis indicated that being male patient (OR 2.187, 95% CI 1.187–4.028, p = 0.012), hypertension (OR 1.993, 95% CI 1.141–3.479, p = 0.015), and low HDL‐C (OR 2.979, 95% CI 1.353–6.558, p = 0.007) were significant correlative factors of HHcy among elderly FNF patients.ConclusionsThis study found a high prevalence of HHcy in elderly FNF patients, with being male patient, hypertension, and low levels of HDL‐C as the significant correlative factors after adjusting for age and other covariables. However, further large‐scale studies in wider regions are warranted to confirm these findings.     

Clinical value of YKL‐40 in patients with polymyositis/dermatomyositis: A cross‐sectional study and a systematic review

IntroductionWe performed a cross‐sectional study to investigate the clinical usefulness of YKL‐40 in patients with dermatomyositis (DM) and conducted a systematic review to summarize the clinical value of YKL‐40 in patients with polymyositis (PM)/DM.Materials and methodsA cross‐sectional study and a systematic review were performed to study the clinical value of YKL‐40 in patients with PM/DM. Serum YKL‐40 level was detected using enzyme‐linked immunosorbent assay, and its association with clinical and laboratory parameters was analyzed. In the systematic review, electronic databases of OVID Embase, OVID Medline, and web of science were searched to collect studies that reported clinical use of YKL‐40 in patients with PM/DM.ResultsIn the cross‐sectional study, serum YKL‐40 level was higher in patients with DM than in healthy controls (median [interquartile range]: 84.09 [52.72–176.4] ng/ml versus 27.37 [12.30–53.58] ng/ml, p < 0.0001). Serum levels of YKL‐40 were associated with the course of DM (r = −0.469, p < 0.001), CRP (r = 0.303, p = 0.043), CK (r = 0.263, p = 0.037), and global disease activity (r = 0.628, p < 0.001). The area under the ROC curve was 0.835 (95% confidence interval 0.751–0.920). In the systematic review, a total of four studies were included with moderate to high quality. Serum level of YKL‐40 has the possibility for diagnosing PM/DM, identifying PM/DM patients with interstitial lung disease (ILD) or rapid progress ILD, and predicting death.ConclusionSerum YKL‐40 level is a possible useful biomarker for PM/DM diagnosis and may be used to predict prognosis.