Higher hydroxyurea adherence among young adults with sickle cell disease compared to children and adolescents

BackgroundSickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low.ObjectiveTo assess the relationship of HU adherence to health care utilization and patients’ characteristics.MethodsThis is a 5-year retrospective chart review. Patients’ demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin “HbF%”, mean corpuscular volume “MCV”, and absolute neutrophil count “ANC”. Age groups included children (<12 years), adolescents (12–17 years), and young adults (≥18 years).ResultsA total of 113 SCD patients on HU were included (median age 14 years, IQR 10–20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p = .003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p = .01) and lower ANC (10³/ml) (3.25 vs. 4.9 vs. 4.2, p = .01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p = .04; ANC 3.6 vs. 6.3, p = .002; MCV 102.3 vs. 93.1, p = .1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (r_s=–0.26, p = .01; r_s=–0.23, p = .01; r_s=0.24, p = .01) and hospitalizations (r_s=–0.27, p = .01; r_s=–0.31, p = .01; r_s=0.21, p = .02) as well as shorter length of stays (r_s=–0.27, p = .0045; r_s=–.34, p = 0.004; r_s=0.23, p = .02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients’ sex, socio-economic status, distance from hospital, and HU duration.ConclusionsYoung adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.

KEY MESSAGES

1. Young adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.
2. Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.
3. No significant association of HU adherence to patients’ sex, socio-economic status and distance from hospital.

     

Blood Th17 cells and IL‐17A as candidate biomarkers estimating the progression of cognitive impairment in stroke patients

BackgroundT helper (Th) cells regulate immunity and inflammation to engage in cognitive impairment in several neurological diseases, while their clinical relevance in stroke patients is not clear. The current study intended to assess the relationship of Th1 cells, Th17 cells, interferon‐gamma (IFN‐γ), and interleukin (IL)‐17A with cognitive function in stroke patients.MethodsOne hundred twenty stroke patients and 40 controls were enrolled in this muticenter study. Th1 and Th17 cells in peripheral blood were assessed by flow cytometry; meanwhile, IFN‐γ and IL‐17A in serum were detected by enzyme‐linked immunosorbent assay. Cognitive function of stroke patients was evaluated by Mini‐Mental State Examination (MMSE) score at enrollment (baseline), year 1, year 2, and year 3.ResultsTh1 cells (p = 0.037) and IFN‐γ (p = 0.048) were slightly increased, while Th17 cells (p < 0.001) and IL‐17A (p < 0.001) were greatly elevated in stroke patients compared with controls. Th17 cells (r _s = −0.374, p < 0.001) and IL‐17A (r _s = −0.267, p = 0.003) were negatively correlated with MMSE score at baseline, but Th1 cells and IFN‐γ were not. Meanwhile, Th17 cells (p = 0.001) and IL‐17A (p = 0.024) were increased in patients with cognitive impairment compared to those without cognitive impairment. Notably, Th17 cells were positively associated with 1‐year (r _s = 0.331, p < 0.001), 2‐year (r _s = 0.261, p = 0.006), and 3‐year (r _s = 0.256, p = 0.011) MMSE decline; IL‐17A was positively correlated with 1‐year (r _s = 0.262, p = 0.005), 2‐year (r _s = 0.193, p = 0.045), but not 3‐year MMSE decline. However, both Th1 cells and IFN‐γ were not linked with MMSE decline.ConclusionTh17 cells and IL‐17A estimate the progression of cognitive impairment in stroke patients.     

Aberrant blood MALT1 and its relevance with multiple organic dysfunctions,T helper cells,inflammation, and mortality risk of sepsis patients

BackgroundMALT1 is linked with multiple organic dysfunctions, inflammatory storm, and T helper (Th) cell differentiation. Herein, the current study aimed to investigate the correlation of peripheral blood mononuclear cell (PBMC) MALT1 with Th1 cells, Th17 cells, and prognosis of sepsis patients.MethodsIn general, 78 sepsis patients and 40 health controls (HCs) were enrolled. MALT1 expression was detected in PBMCs from all subjects by RT‐qPCR. Besides, Th1 and Th17 cells were measured in PBMCs from sepsis patients by flow cytometry; interleukin 17A (IL‐17A) and interferon gamma (IFN‐γ) were determined in serum from sepsis patients by ELISA.ResultsMALT1 expression was higher in sepsis patients than HCs (p < 0.001). MALT1 expression was positively correlated with Th17 cells (r _s = 0.291, p = 0.038) and IL‐17A (r _s = 0.383, p = 0.001), but not with Th1 cells (r _s = 0.204, p = 0.151) or IFN‐γ (r _s = 0.175, p = 0.125) in sepsis patients. MALT1 expression was positively correlated with APACHE II score (r _s = 0.275, p = 0.015), C‐reactive protein (CRP) (r _s = 0.257, p = 0.023), and sequential organ failure assessment (SOFA) score (r _s = 0.306, p = 0.006) (MALT1 expression was positively correlated with SOFA respiratory system score (r _s = 0.348, p = 0.002), and SOFA liver score (r _s = 0.260, p = 0.021), but not with SOFA scores in nervous system, cardio vascular system, coagulation, and renal system (all p > 0.05)). MALT1 expression (p = 0.010), Th1 cells (p = 0.010), Th17 cells (p = 0.038), and IL‐17A (p = 0.012), except for IFN‐γ (p = 0.102), elevated in sepsis deaths compared with sepsis survivors.ConclusionPBMC MALT1 is highly expressed in sepsis patients with its overexpression associated with multiple organic dysfunctions, elevated Th17 cells, and increased mortality risk.     

Cranial autonomic symptoms: prevalence,phenotype and laterality in migraine and two potentially new symptoms

BackgroundWhilst cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalalgias (TAC’s), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management.MethodsMigraineurs seen in a tertiary headache service between 2014 and 2018 (n = 340): cohort one, and a separate cohort of headache patients seen between 2014-May 2021 reporting voice change, or throat swelling, or both, as CAS were selected (n = 64): cohort two. We performed a service evaluation of our records regarding age, sex, diagnosis, headache and CAS frequency and laterality as acquired from the first consultation, during which a detailed headache history is taken by a headache trained physician.ResultsCohort 1: Mean age 43 (range 14–94, SD 15). The most common diagnosis was chronic migraine (78%). Median monthly headache frequency was 26 days (IQR 15–75). At least one CAS was reported in 74%, with a median of two (IQR 0–3). The most common were nasal congestion (32%), lacrimation (31%) and aural fullness (25%). Most patients reported their most common headache as unilateral (80%) and with it strictly unilateral CAS (64%). There was a positive association between headache and CAS laterality (χ²₁ = 20.7, P < 0.001), with a positive correlation between baseline headache frequency and number of CAS reported (r = 0.11, P = 0.047). Cohort two: mean age 49 (range 23–83, SD 14). Diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described trigeminal distribution pain; 25% involving all three divisions. Throat swelling was reported by 54, voice change by 17, and both by 7. The most common CAS reported were lacrimation (n = 47), facial swelling (n = 45) and rhinorrhoea (n = 37). There was significant agreement between the co-reporting of throat swelling (χ²₁ = 7.59, P = 0.013) and voice change (χ²₁ = 6.49, P = 0.02) with aural fullness.ConclusionsCAS are common in migraine, are associated with increasing headache frequency and tend to lateralise with headache. Voice change and throat swelling should be recognized as possible parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic endophenotype.     

超声诊断产伤性肛门括约肌损伤的研究进展

产伤性肛门括约肌损伤（OASIS）是分娩的并发症之一,如临床处理不当,可能发展为肛门失禁。本文主要针对 OASIS的超声研究进展进行综述。     

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study

BackgroundThe pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects.MethodsUsing the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine (n = 25), those with chronic migraine (n = 24), and age-matched and sex-matched healthy subjects (n = 16). Patients with chronic migraine were further divided into those with (n = 12) and without (n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University.ResultsWe found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability (r = -0.425, p = 0.055, n = 20), and lower GABA/water (r = -0.424, p = 0.062, n = 20) and Glx/Water (r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality.ConclusionsNeurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01452-6.     

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.     

Neuromuscular sonography detects changes in muscle echotexture and nerve diameter in ICU patients within 24 h

PurposeDuring an ICU stay, changes in muscles and nerves occur that is accessible via neuromuscular sonography.Methods17 patients recruited from the neurological and neurosurgical ICU (six women; 66 ± 3 years) and 7 healthy controls (three women, 75 ± 3 years) were included. Muscle sonography (rectus abdominis, biceps, rectus femoris and tibialis anterior muscles) using gray-scale values (GSVs), and nerve ultrasound (peroneal, tibial and sural nerves) analyzing the cross-sectional area (CSA) were performed on days 1 (t1), 3 (t2), 5 (t3), 8 (t4), and 16 (t5) after admission.ResultsTime course analysis revealed that GSVs were significantly higher within the patient group for all of the investigated muscles (rectus abdominis: F = 7.536; p = 0.011; biceps: F = 14.761; p = 0.001; rectus femoris: F = 9.455; p = 0.005; tibialis anterior: F = 7.282; p = 0.012). The higher GSVs were already visible at t1 or, at the latest, at t2 (tibialis anterior muscles). CSA was enlarged in all of the investigated nerves in the patient group (peroneal nerve: F = 7.129; p = 0.014; tibial nerve: F = 28.976, p < 0.001; sural nerve: F = 13.051; p = 0.001). The changes were visible very early (tibial nerve: t1; peroneal nerve: t2). The CSA of the motor nerves showed an association with the ventilation time and days within the ICU (t1 through t4; p < 0.05).DiscussionWe detected very early changes in the muscles and nerves of ICU-patients. Nerve CSA might be a useful parameter to identify patients who are at risk for difficult weaning. Therefore our observations might be severity signs of neuromuscular suffering for the most severe patients.     

Comparison of outcomes from sepsis between patients with and without pre-existing left ventricular dysfunction: a case-control analysis

Introduction

The aim of this study was to determine if there are differences between patients with pre-existing left ventricular dysfunction and those with normal antecedent left ventricular function during a sepsis episode in terms of in-hospital mortality and mortality risk factors when treated in accordance with a sepsis treatment algorithm.

Methods

We performed a retrospective case-control analysis of patients selected from a quality improvement database of 1,717 patients hospitalized with sepsis between 1 January 2005 and 30 June 2010. In this study, 197 patients with pre-existing left ventricular systolic dysfunction and sepsis were compared to 197 case-matched patients with normal prior cardiac function and sepsis.

Results

In-hospital mortality rates (P = 0.117) and intubation rates at 24 hours (P = 0.687) were not significantly different between cases and controls. There was no correlation between the amount of intravenous fluid administered over the first 24 hours and the PaO₂/FiO₂ ratio at 24 hours in either cases or controls (r² = 0.019 and r² = 0.001, respectively). Mortality risk factors for cases included intubation status (P = 0.016, OR = 0.356 for no intubation), compliance with a sepsis bundle (P = 0.008, OR = 3.516 for failed compliance), a source of infection other than the lung (P = 0.019, OR = 2.782), and the initial mixed venous oxygen saturation (P = 0.004, OR = 0.997). Risk factors for controls were the initial platelet count (P = 0.028, OR = 0.997) and the serum lactate level (P = 0.048, OR = 1.104). Patients with pre-existing left ventricular dysfunction who died had a lower initial mean mixed venous oxygen saturation than those who survived (61 ± 18% versus 70 ± 16%, P = 0.002).

Conclusions

Clinical outcomes were not different between septic patients with pre-existing left ventricular dysfunction and those with no cardiac disease. There was no correlation between fluid administration and oxygenation at 24 hours in either cohort. The mortality risk factor profile of patients with pre-existing left ventricular dysfunction was different when compared with control patients, and may be related to oxygen delivery determinants.     

Increase in ACC GABA+ levels correlate with decrease in migraine frequency,intensity and disability over time

BackgroundAn imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.MethodsWe observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time.ResultsThe results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8).ConclusionThe correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01352-1.     

Single-Pulse Transcranial Magnetic Stimulation for the preventive treatment of difficult-to-treat migraine: a 12-month prospective analysis

BackgroundInitial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine.MethodsThis is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a ≥ 4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders).ResultsOne hundred fifty-three patients were included in the analysis (F:M = 126:27, median age 43, IQR 32.3–56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0 days, from 18.0 (IQR: 12.0–26.0) to 13.0 days (IQR: 5.75–24.0) (P = 0.002, r = − 0.29) and the median reduction in monthly migraine days (MMD) was 4.0 days, from 13.0 (IQR: 8.75–22.0) to 9.0 (IQR: 4.0–15.25) (P = 0.002, r = − 0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N = 79/153) at baseline to 19% (N = 29/153) at month 3, to 8% (N = 7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64–69) at baseline to 62 at month 3 (IQR: 56–65) (P < 0.001, r = − 0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity.ConclusionsThis open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.     

Inter‐alpha‐trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk,activity, and treatment outcomes of rheumatoid arthritis

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (r_s  = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (r_s  = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (r_s  = −0.337, p = 0.001), IL‐6 (r_s  = −0.221, p = 0.033), and IL‐17A (r_s  = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (r_s  = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.     

Gastric tonometry guided therapy in critical care patients: a systematic review and meta-analysis

IntroductionThe value of gastric intramucosal pH (pHi) can be calculated from the tonometrically measured partial pressure of carbon dioxide (P_CO2) in the stomach and the arterial bicarbonate content. Low pHi and increase of the difference between gastric mucosal and arterial P_CO2 (P_CO2 gap) reflect splanchnic hypoperfusion and are good indicators of poor prognosis. Some randomized controlled trials (RCTs) were performed based on the theory that normalizing the low pHi or P_CO2 gap could improve the outcomes of critical care patients. However, the conclusions of these RCTs were divergent. Therefore, we performed a systematic review and meta-analysis to assess the effects of this goal directed therapy on patient outcome in Intensive Care Units (ICUs).MethodsWe searched PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials comparing gastric tonometry guided therapy with control groups. Baseline characteristics of each included RCT were extracted and displayed in a table. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes. Another measure of effect (risk difference, RD) was used to reassess the effects of gastric tonometry on total mortality. We performed sensitivity analysis for total mortality. Continuous outcomes were presented as standardised mean differences (SMDs) together with 95% CIs.ResultsThe gastric tonometry guided therapy significantly reduced total mortality (OR, 0.732; 95% CI, 0.536 to 0.999, P = 0.049; I² = 0%; RD, −0.056; 95% CI, −0.109 to −0.003, P = 0.038; I² = 0%) when compared with control groups. However, after excluding the patients with normal pHi on admission, the beneficial effects of this therapy did not exist (OR, 0.736; 95% CI 0.506 to 1.071, P = 0.109; I² = 0%). ICU length of stay, hospital length of stay and days intubated were not significantly improved by this therapy.ConclusionsIn critical care patients, gastric tonometry guided therapy can reduce total mortality. Patients with normal pHi on admission contributed to the ultimate result of this outcome; it may indicate that these patients may be more sensitive to this therapy.     

Comparison of pregnenolone sulfate,pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study

BackgroundNeurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age.MethodsThirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay.ResultsSerum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student’s t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R² = 0.1369; P = 0.0482) and age (R² = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R² = 0.04436, P = 0.4337, linear regression analysis).ConclusionLow levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01231-9.     

The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials

BackgroundMigraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies.MethodsMEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study.ResultsWe pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a significant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no significant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo.ConclusionsAtogepant has shown good efficacy and safety in the prophylactic treatment of migraine, and further studies are expected.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01391-2.     

The key role of pulse wave transit time to predict blood pressure variation during anaesthesia induction

ObjectiveTo establish the relationship between pulse wave transit time (PWTT) before anaesthesia induction and blood pressure variability (BPV) during anaesthesia induction.MethodsThis prospective observational cohort study enrolled consecutive patients that underwent elective surgery. Invasive arterial pressure, electrocardiography, pulse oximetry, heart rate and bispectral index were monitored. PWTT and BPV were measured with special software. Anaesthesia was induced with propofol, sufentanil and rocuronium.ResultsA total of 54 patients were included in this study. There was no correlation between BPV and the dose of propofol, sufentanil and rocuronium during anaesthesia induction. Bivariate linear regression analysis demonstrated that PWTT (r = –0.54), age (r = 0.34) and systolic blood pressure (r = 0.31) significantly correlated with systolic blood pressure variability (SBPV). Only PWTT (r = –0.38) was significantly correlated with diastolic blood pressure variability (DBPV). Patients were stratified into high PWTT and low PWTT groups according to the mean PWTT value (96.8 ± 17.2 ms). Compared with the high PWTT group, the SBPV of the low PWTT group increased significantly by 3.4%. The DBPV of the low PWTT group increased significantly by 2.1% compared with the high PWTT group.ConclusionsPWTT, assessed before anaesthesia induction, may be an effective predictor of haemodynamic fluctuations during anaesthesia induction.     

Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance

IntroductionThe stress index (SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw).MethodsLung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a ‘normal’ PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals.ResultsPaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg⁻¹, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (P_TP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat- and SI-groups respectively, without differences in overinflated lung areas at end- inspiration in both groups. Cytokines and histopathology showed no differences.ConclusionsSetting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0726-3) contains supplementary material, which is available to authorized users.     

经会阴三维超声评估妊娠及分娩对女性肛门括约肌复合体的影响

目的 采用经会阴三维超声成像技术分析妊娠及分娩对肛门括约肌复合体（ASC）的影响。方法 对131名妇女,包括15名未育女性（未育组）、31名中孕期孕妇（中孕组）、31名晚孕期孕妇（晚孕组）、24名剖宫产产妇（剖宫产组）及30名阴道分娩产妇（阴道分娩组,均为初产妇,产后42~60天）的ASC进行三维容积成像。于静息及缩肛状态下,分别在远端平面测量肛门外括约肌（EAS）3、6、9、12点方向厚度,近、中、远3个平面测量肛门内括约肌（IAS）相同4个位置的厚度,于中部平面测量耻骨直肠肌（PRM）4（左侧）、8（右侧）点方向厚度。对不同状态下、不同方位的各肌肉厚度进行统计学分析。结果 静息状态下,剖宫产组近端平面12点及9点方向、中部平面3点及9点方向IAS厚度均较未育组及阴道分娩组厚（P均<0.05）;剖宫产组及经阴道分娩组远端平面4个方位EAS厚度较晚孕组薄（P均<0.05）。缩肛状态下,晚孕组及剖宫产组近端平面12点及9点方向IAS及远端平面12点EAS的厚度较经阴道分娩组厚（P均<0.05）。静息及缩肛状态下,经阴道分娩组左右两侧PRM厚度较晚孕组及剖宫产组薄（P均<0.05）。未育组静息及缩肛状态下、中孕组缩肛状态下、晚孕组静息状态下PRM的厚度均为左侧大于右侧（P均<0.05）。结论 ASC于中孕期、晚孕期、剖宫产、经阴道分娩发生不同程度变化;ASC增厚是女性在妊娠过程中的自身保护机制。     

Validation of photoacoustic/ultrasound dual imaging in evaluating blood oxygen saturation

Photoacoustic imaging (PAI) was performed to evaluate oxygen saturation (sO₂) of blood-mimicking phantoms, femoral arteries in beagles, and radial arteries in humans at various sO₂ plateaus. The accuracy (root mean square error, RMSE) of PAI sO₂ compared with reference sO₂ was calculated. In blood-mimicking phantoms, PAI achieved an accuracy of 1.49% and a mean absolute error (MAE) of 1.09% within 25 mm depth, and good linearity (R = 0.968; p < 0.001) was obtained between PAI sO₂ and reference sO₂. In canine femoral arteries, PAI achieved an accuracy of 2.16% and an MAE of 1.58% within 8 mm depth (R = 0.965; p < 0.001). In human radial arteries, PAI achieved an accuracy of 3.97% and an MAE of 3.28% in depth from 4 to 14 mm (R = 0.892; p < 0.001). For PAI sO₂ evaluation at different depths in healthy volunteers, the RMSE accuracy of PAI sO₂ increased from 2.66% to 24.96% with depth increasing from 4 to 14 mm. Through the multiscale method, we confirmed the feasibility of the hand-held photoacoustic/ultrasound (PA/US) in evaluating sO₂. These results demonstrate the potential clinical value of PAI in evaluating blood sO₂. Consequently, protocols for verifying the feasibility of medical devices based on PAI may be established.