Role of mechanoregulation in mast cell-mediated immune inflammation of the smooth muscle in the pathophysiology of esophageal motility disorders.

Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that smooth muscle hypertrophy occurs above the obstruction and is due to mechanical stress on the smooth muscles. The mechanostressed smooth muscles release cytokines and other molecules that may recruit and microlocalize mast cells to smooth muscle bundles, so that their products may have a close bidirectional effect on each other. Acting in a paracrine fashion, the inflammatory cytokines induce genetic and epigenetic changes in the smooth muscles, leading to smooth muscle hypercontractility, hypertrophy, and impaired relaxation. These changes may worsen difficulty in the esophageal transport. Immune processes differ in the first phase of obstructive bolus transport, and the second phase of muscle hypertrophy and hypercontractility. Moreover, changes in the type of mechanical stress may change immune response and effect on smooth muscles. Understanding immune signaling in causes of obstructive bolus transport, type of mechanical stress, and associated smooth muscle changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders.NEW & NOTEWORTHY Esophageal disorders such as esophageal stricture or achalasia, and diffuse esophageal spasm are associated with smooth muscle hypertrophy and hypercontractility, above the obstruction, yet the cause of such changes is unknown. This review suggests that smooth muscle obstructive disorders may cause mechanical stress on smooth muscle, which then secretes chemicals that recruit, microlocalize, and activate mast cells to initiate immune inflammation, producing functional and structural changes in smooth muscles. Understanding the immune signaling in these changes may help pathophysiology-based prevention and targeted treatment of esophageal motility disorders.

Evaluating cerebrovascular reactivity measured by velocity selective inversion arterial spin labeling with different post-labeling delays: The effect of fast flow.

PURPOSE: Velocity selective arterial spin labeling (VSASL) quantification assumes that the labeled bolus continuously moves into the imaging voxel during the post-labeling delay (PLD). Faster blood flow could lead to a bolus duration shorter than the applied PLD of VSASL and cause underestimation of cerebral blood flow (CBF). This study aims to evaluate the performance of velocity-selective inversion (VSI) prepared arterial spin labeling (ASL) with different PLDs and pseudo-continuous ASL (PCASL) for quantification of hypercapnia-induced cerebrovascular reactivity (CVR), using phase-contrast (PC) MRI as a global reference. METHODS: We compared CVR obtained by VSI-ASL with PLD of 1520 ms (VSASL-1520), 1000 ms (VSASL-1000), and 500 ms (VSASL-500), PCASL with PLD of 1800 ms (PCASL-1800), and PC MRI on eight healthy volunteers at two sessions. RESULTS: Compared with PC MRI, VSASL-1520 produced significantly lower global CVR values, while PCASL-1800, VSASL-1000, and VSASL-500 yielded more consistent results. The reduced CVR in VSASL-1520 was more pronounced in carotid territories including frontal and temporal lobes than in vertebral territories such as the occipital lobe. This is largely caused by the underestimated perfusion during hypercapnia due to the reduced bolus duration being less than the PLD. CONCLUSION: Although VSASL offers certain advantages over spatially selective ASL due to its reduced susceptibility to delayed ATT, this technique is prone to biases when the ATT is excessively short. Therefore, a short PLD should be employed for reliable perfusion and CVR quantification in populations or conditions with fast flow.

Impact of vessel volume on thermodilution measurements in patients with coronary microvascular dysfunction.

BACKGROUND: Two invasive methods are available to estimate microvascular resistance: bolus and continuous thermodilution. Comparative studies have revealed a lack of concordance between measurements of microvascular resistance obtained through these techniques. AIMS: This study aimed to examine the influence of vessel volume on bolus thermodilution measurements. METHODS: We prospectively included patients with angina with non-obstructive coronary arteries (ANOCA) undergoing bolus and continuous thermodilution assessments. All patients underwent coronary CT angiography to extract vessel volume. Coronary microvascular dysfunction was defined as coronary flow reserve (CFR) < 2.0. Measurements of absolute microvascular resistance (in Woods units) and index of microvascular resistance (IMR) were compared before and after volumetric adjustment. RESULTS: Overall, 94 patients with ANOCA were included in this study. The mean age was 64.7 ± 10.8 years, 48% were female, and 19% had diabetes. The prevalence of CMD was 16% based on bolus thermodilution, while continuous thermodilution yielded a prevalence of 27% (Cohen's Kappa 0.44, 95% CI 0.23-0.65). There was no correlation in microvascular resistance between techniques (r = 0.17, 95% CI -0.04 to 0.36, p = 0.104). The adjustment of IMR by vessel volume significantly increased the agreement with absolute microvascular resistance derived from continuous thermodilution (r = 0.48, 95% CI 0.31-0.63, p < 0.001). CONCLUSIONS: In patients with ANOCA, invasive methods based on coronary thermodilution yielded conflicting results for the assessment of CMD. Adjusting IMR with vessel volume improved the agreement with continuous thermodilution for the assessment of microvascular resistance. These findings strongly suggest the importance of considering vessel volume when interpreting bolus thermodilution assessment.

Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer.

Transient permeation enhancers (PEs) have been widely used to improve the oral absorption of macromolecules. During pharmaceutical development, the correct selection of the macromolecule, PE, and the combination needs to be made to maximize oral bioavailability and ensure successful clinical development. Various in vitro and in vivo methods have been investigated to optimize this selection. In vitro methods are generally preferred by the pharmaceutical industry to reduce the use of animals according to the "replacement, reduction, and refinement" principle commonly termed "3Rs," and in vitro methods typically have a higher throughput. This paper compares two in vitro methods that are commonly used within the pharmaceutical industry, being Caco-2 and an Ussing chamber, to two in vivo models, being in situ intestinal instillation to rats and in vivo administration via an endoscope to pigs. All studies use solution formulation of sodium caprate, which has been widely used as a PE, and two macromolecules, being FITC-dextran 4000 Da and MEDI7219, a GLP-1 receptor agonist peptide. The paper shares our experiences of using these models and the challenges with the in vitro models in mimicking the processes occurring in vivo. The paper highlights the need to consider these differences when translating data generated using these in vitro models for evaluating macromolecules, PE, and combinations thereof for enabling oral delivery.

Omission of 5-Fluorouracil Bolus From Multidrug Regimens for Advanced Gastrointestinal Cancers: A Multicenter Cohort Study.

BACKGROUND: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus. The purpose of this study was to determine whether omission of the 5-FU bolus was associated with a difference in survival and toxicity. METHODS: A real-world database from Flatiron Health was queried for patients with advanced colorectal, gastroesophageal, and pancreatic cancers who received first-line FOLFOX, FOLFIRI, and FOLFIRINOX regimens. Cox proportional hazards and Kaplan-Meier analyses were performed to compare survival outcomes between patients who received the 5-FU bolus and those who did not. Inverse probability of treatment weighted (IPTW) analysis was performed to adjust for treatment selection bias. RESULTS: This study included 11,765 patients with advanced colorectal (n=8,670), gastroesophageal (n=1,481), and pancreatic (n=1,614) cancers. Among all first-line 5-FU multidrug regimens, 10,148 (86.3%) patients received a 5-FU bolus and 1,617 (13.7%) did not. After IPTW analysis, we found that omitting the bolus was not associated with a decrease in overall survival (hazard ratio, 0.99; 95% CI, 0.91-1.07; P=.74). However, omitting the bolus was associated with reductions in neutropenia (10.7% vs 22.7%; P<.01), thrombocytopenia (11.2% vs 16.1%; P<.01), and use of granulocyte colony-stimulating factors after treatment (19.6% vs 29.1%; P<.01). CONCLUSIONS: After adjusting for baseline clinical factors, we found that omission of the 5-FU bolus from FOLFOX, FOLFIRI, and FOLFIRINOX regimens was not associated with decreased survival, but resulted in decreased toxicity and possible health care savings.

The effect of bolus advisors on glycaemic parameters in adults with diabetes on intensive insulin therapy: A systematic review with meta-analysis.

AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.

Feasibility of a single-phase portal venous CT protocol using bolus tracking technique and lean body weight-based contrast media dose.

PURPOSE: To evaluate the impact of the use of lean body weight (LBW)-based contrast material (CM) dose and bolus tracking technique on portal venous phase abdominal CT image quality. MATERIALS AND METHODS: IRB-approved prospective study; informed consent was acquired. In the period July-November 2023, we randomly selected 105 oncologic patients scheduled for a portal venous phase abdominal CT to undergo our experimental protocol (i.e., 0.7 gI/Kg of LBW CM administration and bolus tracking on the liver). Included patients had performed a "standard" portal venous phase abdominal CT (i.e., 0.6 gI/Kg of total body weight (TBW) contrast material administration and 70 s fixed delay) on the same scanner within the previous 12 months. One reader evaluated CT images measuring liver, portal vein, kidney cortex, and spleen attenuation; values were normalized to paraspinal muscles. RESULTS: Median administered contrast dose (350 mgI/mL CM) was 99 mL (IQR: 81-115 mL) using the experimental protocol and 110 mL (IQR: 100-120 mL) using the standard one (p < 0.0001). Median acquisition delay using the experimental protocol was 65" (IQR 59-73"). Median normalized hepatic enhancement was significantly higher using the experimental protocol (1.97, IQR: 1.83-2.47 vs. 1.86, IQR: 1.58-2.11; p < 0.0001). Median normalized portal vein enhancement was significantly higher using the experimental protocol (3.43, IQR: 2.73-4.04 vs. 2.91, IQR: 2.58-3.41; p < 0.0001). No statistically significant differences were found in the kidneys' cortex and aorta normalized enhancement (p > 0.05). CONCLUSION: The combination of LBW-based CM dose administration and bolus tracking allows a significant CM dose reduction and a significant liver and portal vein enhancement increase. CLINICAL RELEVANCE STATEMENT: Lean body weight-based contrast material (CM) dose administration and bolus tracking technique in portal venous phase CT scans overcome differences in body composition and hemodynamics, improving reproducibility. It allows a significant CM dose reduction with increased liver and portal vein enhancement. KEY POINTS: Lean body weight (LBW)-based contrast material (CM) dosing could be superior to total body weight dosing. Portal venous phase CT with a liver bolus tracking technique improved liver and spleen enhancement with a reduced contrast dose. The combination of LBW-based CM dosing and liver bolus tracking technique enables more "customized" CT examinations.

Associations of bolus insulin injection frequency and smart pen engagement with glycaemic control in people living with type 1 diabetes.

AIM: To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). MATERIALS AND METHODS: Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. RESULTS: Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. CONCLUSIONS: Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.

Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium.

BACKGROUND: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR. METHODS: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. RESULTS: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively. CONCLUSION: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods.

A retrospective cohort study on oesophageal food bolus obstruction in the North Denmark region in 2021-two thirds were never diagnosed with a cause.

BACKGROUND: Food bolus obstruction (FBO) leading to hospital treatment is often associated with eosinophilic oesophagitis (EoE), stenosis, or oesophageal cancer (1). Danish national guidelines recommend that patients with FBO undergo a diagnostic upper endoscopy within two weeks of presentation to exclude possible malignancy, and histological evaluation of eight biopsies (2, 3). AIMS: The aims of this study were to (1) report the incidence and describe the causes and treatment of FBO in the North Denmark Region (NDR), (2) determine the proportion of patients who underwent upper endoscopy and biopsy according to regional and national guidelines, and (3) identify International Classification of Diseases 10th Revision (ICD-10) diagnosis and procedure codes applied to the hospital visits due to FBO in the NDR. METHODS: Among all acute hospital visits in the NDR in 2021, all visits with ICD-10 codes possibly reflecting FBO, as well as a random sample of 14,400 visits with unspecific ICD-10 codes (R and Z codes), were screened manually for possible FBO. Diagnosis, follow-up, and treatment of all patients with FBO were recorded. RESULTS: The median patient age was 66.0 (Q1-Q3: 49.8-81.0) years, and half of the patients had experienced FBO before. Two thirds of patients (66.0%) were never diagnosed with a cause of FBO, followed by 17.3% with EoE. 30% of patients did not undergo upper endoscopy within two weeks of the hospital visit, and 50.7% were never biopsied in the oesophagus. Of 1886 hospital visits with registry ICD-10 codes that possibly reflected FBO, 8.4% were due to FBO, while FBO was present in 0.028% of the random sample of unspecific ICD-10 codes. CONCLUSIONS: Most hospitalized FBO patients in the NDR in 2021 were never diagnosed with a cause. In these patients there is a high risk of overlooked EoE or upper gastrointestinal cancers. The area needs immediate focus and changed routines to improve treatment and prevent new FBO.

Self-Crosslinking AuNPs Composite Hydrogel Bolus for Radiophotothermal Therapy.

Radiophotothermal therapy is a promising treatment for superficial tumors. Traditional radiotherapy requires tissue boluses on the patient's skin to increase therapeutic effectiveness due to the dose-buildup effect of high-energy radiation. However, combining radiotherapy with photothermal therapy leads to uncertainties as the low-penetration near-infrared light dose is reduced after penetrating the bolus. To enhance precision and effectiveness, this study introduces a novel bolus made of AuNPs@poly(AM-THMA-DMAEMA) composite hydrogel. This hydrogel is prepared through a one-pot method involving the reduction of trihydrate chloroauric acid (HAuCl4·3H2O) and copolymerization of acrylamide (AM) and N-[Tris(hydroxymethyl)methyl]acrylamide (THMA) in a redox system with dimethylaminoethyl methacrylate (DMAEMA) and potassium persulfate (KPS). The gold nanoparticles (AuNPs) improve the mechanical strength (tensile strength of 320.84 kPa, elongation at break of 830%) and antibacterial properties (>99% against Staphylococcus aureus). The local surface plasmon resonance (LSPR) effect of AuNPs enables the hydrogel to absorb near-infrared light for precise monitoring of the infrared radiation dose. The hydrogel's biocompatibility is enhanced by the absence of additional crosslinking agents, and its excellent surface adhesion strength is due to numerous hydrogen bonds and electrostatic interactions. This study offers new possibilities for nanoparticle composite hydrogels as tissue boluses, achieving high precision and efficiency in radiophotothermal therapy.

Programmed intermittent bolus versus continuous infusion for catheter-based erector spinae plane block on quality of recovery in thoracoscopic surgery: a single-centre randomised controlled trial.

BACKGROUND: Regional anaesthesia techniques, including the erector spinae fascial plane (ESP) block, reduce postoperative pain after video-assisted thoracoscopic surgery (VATS). Fascial plane blocks rely on spread of local anaesthetic between muscle layers, and thus, intermittent boluses might increase their clinical effectiveness. We tested the hypothesis that postoperative ESP analgesia with a programmed intermittent bolus (PIB) regimen is better than a continuous infusion (CI) regimen in terms of quality of recovery after VATS. METHODS: We undertook a prospective, double-blinded, randomised, controlled trial involving 60 patients undergoing VATS. All participants received ESP block catheters and were randomly assigned to CI or PIB of local anaesthetic regimen for postoperative analgesia. The primary outcome was Quality of Recovery-15 (QoR-15) score 24 h after surgery. Secondary outcomes included postoperative respiratory function, opioid consumption, verbal rating pain score, time to first mobilisation, nausea, vomiting, and length of hospital stay. RESULTS: Overall QoR-15 scores at 24 h after VATS were similar (PIB 115.5 [interquartile range 107-125] vs CI 110 [93-128]; Δ<6, P=0.29). The only quality of recovery descriptor showing a significant difference was nausea and vomiting, which was favourable in the PIB group (10 [10-10] vs 10 [7-10]; P=0.03). Requirement for rescue antiemetics up to 24 h after surgery was lower in the PIB group (4 [14%] vs 11 [41%]; P=0.04). There were no differences in other secondary outcomes between groups. CONCLUSIONS: Delivering ESP block analgesia after VATS via a PIB regimen resulted in similar QoR-15 at 24 h compared with a CI regimen.

sEMG-based automatic characterization of swallowed materials.

Monitoring of ingestive activities is critically important for managing the health and wellness of individuals with various health conditions, including the elderly, diabetics, and individuals seeking better weight control. Monitoring swallowing events can be an ideal surrogate for developing streamlined methods for effective monitoring and quantification of eating or drinking events. Swallowing is an essential process for maintaining life. This seemingly simple process is the result of coordinated actions of several muscles and nerves in a complex fashion. In this study, we introduce automated methods for the detection and quantification of various eating and drinking activities. Wireless surface electromyography (sEMG) was used to detect chewing and swallowing from sEMG signals obtained from the sternocleidomastoid muscle, in addition to signals obtained from a wrist-mounted IMU sensor. A total of 4675 swallows were collected from 55 participants in the study. Multiple methods were employed to estimate bolus volumes in the case of fluid intake, including regression and classification models. Among the tested models, neural networks-based regression achieved an R2 of 0.88 and a root mean squared error of 0.2 (minimum bolus volume was 10 ml). Convolutional neural networks-based classification (when considering each bolus volume as a separate class) achieved an accuracy of over 99% using random cross-validation and around 66% using cross-subject validation. Multiple classification methods were also used for solid bolus type detection, including SVM and decision trees (DT), which achieved an accuracy above 99% with random validation and above 94% in cross-subject validation. Finally, regression models with both random and cross-subject validation were used for estimating the solid bolus volume with an R2 value that approached 1 and root mean squared error values as low as 0.00037 (minimum solid bolus weight was 3 gm). These reported results lay the foundation for a cost-effective and non-invasive method for monitoring swallowing activities which can be extremely beneficial in managing various chronic health conditions, such as diabetes and obesity.

Effect of different tube feeding methods on gastroesophageal reflux features in preterm infants: a pH-impedance monitoring study.

A stepwise approach is currently considered the best choice to manage gastroesophageal reflux (GER) in preterm infants. This study aimed to evaluate the effect of different tube feeding techniques on GER frequency and features in symptomatic tube-fed preterm neonates. Tube-fed infants < 34 weeks' gestation were eligible for this prospective, bicentric, cross-over study if, due to GER symptoms, they underwent a diagnostic 24-h combined pH and multiple intraluminal impedance (pH-MII) monitoring. During the monitoring period, each infant received the same feeding cycle, repeated twice: continuous tube feeding, bolus feeding followed by tube feeding permanence and by tube feeding removal. The impact of these three feeding modalities on pH-MII GER features was assessed. Thirty-one infants were enrolled. Despite a low number of reflux episodes, a significant decrease in total GERs (P < 0.001), in GERs detected by pH monitoring (P < 0.001), and in both acid and non-acid GERs detected by MII (P < 0.001 and P = 0.009, respectively) was observed in association with continuous feeding compared to bolus feeds, followed or not by tube feeding removal. Compared to continuous feeding, both bolus feeding modalities were associated with a significantly higher number of proximal GERs (P < 0.001). No difference in any pH-MII parameter was observed in relation to tube feeding persistence after bolus feeding administration. CONCLUSIONS: Continuous feeding and boluses may have a different impact on pH-MII GER features in symptomatic tube-fed preterm infants, whereas the permanence of the feeding tube across LES did not seem to worsen GER indexes. WHAT IS KNOWN: • Due to the functional and anatomical immaturity of the gastrointestinal tract, gastroesophageal reflux (GER) is common in preterm infants. • A stepwise therapeutical approach which firstly undertakes conservative strategies is the most advisable choice to avoid potentially harmful pharmacological overtreatments in the preterm population. WHAT IS NEW: • Continuous feeding and boluses may have a different impact on GER features assessed by pH-MII monitoring in tube-fed preterm infants. • The permanence of the feeding tube during or after the feeding period did not seem to worsen GER occurrence. • By reducing GER features, especially acid GER, continuous feeding may potentially contribute to limit the need for antiacid medications in this population.

Real-world community hospital hyperglycemia management in noncritically ill, type 2 diabetic patients: a comparison between basal-bolus insulin and correctional insulin.

Purpose: This study evaluated the safety and efficacy of two insulin regimens for inpatient hyperglycemia management: combination short-plus long-acting insulin (basal-bolus insulin regimen, BBIR) vs. short-acting insulin only (correctional insulin only regimen, CIOR). Methods: Chart reviews identified noncritically ill patients with pre-existing type 2 diabetes mellitus receiving insulin injections. Study participants (N = 138) were divided into BBIR (N = 104) and CIOR (N = 34) groups. Data for the entire duration of each patient's stay were analyzed. Results: The primary outcome of percent hyperglycemic days was higher in BBIR vs. CIOR (3.97 ± 0.33% vs. 1.22 ± 0.38%). The safety outcome of percent hypoglycemic events was not different between BBIR and CIOR (0.78 ± 0.22% vs. 0.53 ± 0.37%). Regarding secondary outcomes, the percentage of euglycemic days was lower in BBIR vs. CIOR (26.74 ± 2.97% vs. 40.98 ± 5.91%). Overall blood glucose (BG) and daily insulin dose were higher in BBIR vs. CIOR (231.43 ± 5.37 vs. 195.55 ± 6.25 mg/dL and 41.36 ± 3.07 vs. 5.02 ± 0.68 units, respectively). Insulin regimen-associated differences in hyperglycemia and daily insulin dose persisted after adjusting for covariates. Conclusion: Our observations linking BBIR to worse glycemic outcomes differ from those reported in the randomized controlled Rabbit 2 and Rabbit 2 Surgery trials. This discrepancy can be partly explained by the fact that BBIR patients displayed worse glycemic baselines. Also, there was no diabetes stewardship team to monitor BG and modify insulin therapy, which is relevant since achieving euglycemia in BBIR patients requires more dose adjustments. This study highlights challenges with standard inpatient glycemic management and calls for further research assessing the benefits of pharmacist-led diabetes stewardship.

Eosinophilic oesophagitis: a common cause of food bolus obstruction.

BACKGROUND: Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence. AIMS: To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy. METHODS: Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented. RESULTS: One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7-year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow-up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE. CONCLUSION: EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment.

Effective bolus dose of remimazolam for i-gel® insertion in nonparalyzed patients: a dose-finding study.

PURPOSE: Remimazolam is a recently developed ultra-short-acting benzodiazepine used for anesthesia induction and maintenance. Nevertheless, the effective bolus dose of remimazolam for i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK) insertion without the use of neuromuscular blocking agents (NMBAs) has not been well established. METHODS: This study included 25 adult patients scheduled for surgery under general anesthesia who were eligible for i-gel use. Anesthesia was induced with predetermined bolus doses of remimazolam, starting at 0.3 mg·kg-1 for the first patient, without the use of NMBAs. All patients concurrently received remifentanil using target-controlled infusion (TCI) at a fixed effect-site concentration (Ce) of 3.0 ng·mL-1. Insertion of the i-gel was attempted 90 sec after remimazolam administration, and insertion conditions were assessed. Subsequent doses of remimazolam were decreased or increased by 0.05 mg·kg-1, depending on the success or failure of i-gel insertion. RESULTS: The mean (standard deviation) 50% effective dose (ED50) of a remimazolam bolus for successful i-gel insertion as determined by the modified Dixon's up-and-down method was 0.100 (0.027) mg·kg-1. The ED50 and ED95 estimated by isotonic regression were 0.111 (83% confidence interval [CI], 0.096 to 0.131) mg·kg-1 and 0.182 (95% CI, 0.144 to 0.195) mg·kg-1, respectively. None of the patients required treatment for hypotension or bradycardia during anesthesia induction. CONCLUSION: Based on the ED95 of remimazolam bolus dose determined in our study, we recommend using 0.182 mg·kg-1 of remimazolam in combination with remifentanil TCI at a Ce of 3.0 ng·mL-1 for successful i-gel insertion without NMBAs in adult patients. This regimen seems effective with a low risk of hemodynamic instability during anesthesia induction. STUDY REGISTRATION: ClinicalTrials.gov ( NCT05298228 ); first submitted 6 March 2022.

RéSUMé: OBJECTIF: Le remimazolam est une benzodiazépine à action ultra-courte récemment mise au point et utilisée pour l'induction et le maintien de l'anesthésie. Toutefois, la dose efficace en bolus de remimazolam pour l'insertion de l'i-gel® (Intersurgical Ltd., Wokingham, Berkshire, Royaume-Uni) sans utiliser de bloqueurs neuromusculaires (BNM) n'a pas été bien établie. MéTHODE: Cette étude a inclus 25 adultes devant bénéficier d'une intervention chirurgicale sous anesthésie générale qui étaient éligibles à l'utilisation d'un i-gel. L'anesthésie a été induite avec des doses prédéterminées en bolus de remimazolam, à partir de 0,3 mg·kg−1 pour la première personne, sans utiliser de BNM. Toutes les personnes anesthésiées ont reçu en parallèle du rémifentanil en perfusion à objectif de concentration à une concentration au site effecteur (Ce) de 3,0 ng·mL−1. L'insertion de l'i-gel a été tentée 90 secondes après l'administration de remimazolam, et les conditions d'insertion ont été évaluées. Les doses subséquentes de remimazolam ont été diminuées ou augmentées de 0,05 mg·kg−1, en fonction du succès ou de l'échec de l'insertion de l'i-gel. RéSULTATS: La dose efficace moyenne (écart type) de 50 % (DE50) d'un bolus de remimazolam pour une insertion réussie de l'i-gel, telle que déterminée par la méthode « up-and-down ¼ de Dixon modifiée, était de 0,100 (0,027) mg·kg−1. Les DE50 et DE95 estimées par régression isotonique étaient de 0,111 (intervalle de confiance [IC] à 83 %, 0,096 à 0,131) mg·kg−1 et 0,182 (IC 95 %, 0,144 à 0,195) mg·kg−1, respectivement. Aucun·e patient·e n'a eu besoin de traitement pour une hypotension ou une bradycardie pendant l'induction de l'anesthésie. CONCLUSION: D'après la DE95 de la dose de remimazolam en bolus déterminée dans notre étude, nous recommandons d'utiliser 0,182 mg·kg−1 de remimazolam en association avec une perfusion à objectif de concentration de rémifentanil à une Ce de 3,0 ng·mL−1 pour réussir l'insertion de l'i-gel sans BNM chez la patientèle adulte. Ce schéma semble efficace avec un faible risque d'instabilité hémodynamique lors de l'induction de l'anesthésie. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05298228); première soumission le 6 mars 2022.

The association between prolonged capillary refill time and microcirculation changes in children with sepsis.

BACKGROUNDS: In children with sepsis, circulatory shock and multi-organ failure remain major contributors to mortality. Prolonged capillary refill time (PCRT) is a clinical tool associated with disease severity and tissue hypoperfusion. Microcirculation assessment with videomicroscopy represents a promising candidate for assessing and improving hemodynamic management strategies in children with sepsis. Particularly when there is loss of coherence between the macro and microcirculation (hemodynamic incoherence). We sought to evaluate the association between PCRT and microcirculation changes in sepsis. METHODS: This was a prospective cohort study in children hospitalized with sepsis. Microcirculation was measured using sublingual video microscopy (capillary density and flow and perfused boundary region [PBR]-a parameter inversely proportional to vascular endothelial glycocalyx thickness), phalangeal tissue perfusion, and endothelial activation and glycocalyx injury biomarkers. The primary outcome was the association between PCRT and microcirculation changes. RESULTS: A total of 132 children with sepsis were included, with a median age of two years (IQR 0.6-12.2). PCRT was associated with increased glycocalyx degradation (PBR 2.21 vs. 2.08 microns; aOR 2.65, 95% CI 1.09-6.34; p = 0.02) and fewer 4-6 micron capillaries recruited (p = 0.03), with no changes in the percentage of capillary blood volume (p = 0.13). Patients with hemodynamic incoherence had more PBR abnormalities (78.4% vs. 60.8%; aOR 2.58, 95% CI 1.06-6.29; p = 0.03) and the persistence of these abnormalities after six hours was associated with higher mortality (16.5% vs. 6.1%; p < 0.01). Children with an elevated arterio-venous CO2 difference (DCO2) had an abnormal PBR (aOR 1.13, 95% CI 1.01-1.26; p = 0.03) and a lower density of small capillaries (p < 0.05). Prolonged capillary refill time predicted an abnormal PBR (AUROC 0.81, 95% CI 0.64-0.98; p = 0.03) and relative percentage of blood in the capillaries (AUROC 0.82, 95% CI 0.58-1.00; p = 0.03) on admission. A normal CRT at 24 h predicted a shorter hospital stay (aOR 0.96, 95% CI 0.94-0.99; p < 0.05). CONCLUSIONS: We found an association between PCRT and microcirculation changes in children with sepsis. These patients had fewer small capillaries recruited and more endothelial glycocalyx degradation. This leads to nonperfused capillaries, affecting oxygen delivery to the tissues. These disorders were associated with hemodynamic incoherence and worse clinical outcomes when the CRT continued to be abnormal 24 h after admission.

Optimization of uniformity in coronary artery enhancement using a bolus tracking technique with a dual region of interest in coronary computed tomographic angiography.

BACKGROUND: Consistent coronary artery enhancement is essential to achieve accurate and reproducible quantification of coronary plaque composition. PURPOSE: To optimize coronary artery uniformity of enhancement using a bolus tracking technique with a dual region of interest (ROI) in coronary computed tomography angiography (CCTA) on a 320-detector CT scanner. MATERIAL AND METHODS: This prospective study recruited 100 consecutive patients who underwent CCTA and were randomly divided into two groups, namely, a manual trigger group (n = 50), in which a manual fast start technique was used to start the diagnostic scan with the visual evaluation of attenuation in the left atrium and left ventricle, and an automatic trigger group (n = 50), in which a bolus tracking technique was used to automatically start the breath-holding command and diagnostic scan with two ROIs placed in the right and left ventricles. Coronary artery image quality was assessed using quantitative and qualitative scores. The enhancement uniformity was characterized by attenuation variability of the ascending aorta (AAO) and coronary arteries. RESULTS: No statistically significant differences in the image quality of the coronary arteries were observed between the two groups (all P > 0.05). The coefficients of variation (COVs) of arterial attenuation in the automatic trigger group were significantly smaller than in the manual trigger group (AAO: 9.89% vs. 17.93%; LMA: 10.35% vs. 18.98%; LAD proximal: 12.09% vs. 20.84%; LCX proximal: 11.85% vs. 20.95%; RCA proximal: 12.13% vs. 20.84%; all P < 0.05). CONCLUSION: The automatic trigger technique accompanied with dual ROI provides consistent coronary artery enhancement and optimizes coronary artery enhancement uniformity in CCTA on a 320-detector CT scanner.

The influence of epidural analgesic techniques on obstetrical outcomes.

PURPOSE: The aim of this study is to compare and evaluate the obstetrical differences between three techniques, including the programmed intermittent epidural bolus (PIEB), the patient-controlled epidural analgesia (PCEA), and the continuous epidural analgesia (CEA). METHODS: This is a retrospective cohort study that investigates the obstetrical outcomes of 2240 patients who received EA during labor in a tertiary maternal unit over the course of 9 years (2011-2018). The only inclusion criterion was the use of epidural analgesia during childbirth and the only exclusion criteria were multiplets' gestation. Multivariate logistic regression, Kruskal-Wallis test, and the log-rank test were utilized to compare the differences between the three EA techniques in terms of cesarean section rate, the incidence of perineal tears, the use of Oxytocin, the duration of labor, and the incidence of paresthesia. RESULTS: Out of the 2240 included deliveries; 1084 utilized PIEB, 1086 PCEA, and 70 CEA techniques. The incidence of Cesarean section was the highest in the CEA group (45.7%) compared to PIEB (24.8%) and PCEA (24.4%) P < 0.001. A significantly shorter duration of labor (vaginal delivery) was observed in the PCEA group (n: 821, 336.7 min) compared to the PIEB group (n: 814, 368.8 min) P < 0.001. There were no statistically significant differences in the incidence of perineal tears, the need of uterotonics, and the incidence of paresthesia. CONCLUSION: The results of this study indicate that the PIEB and PCEA techniques are superior to the CEA technique when it comes to analgesia during childbirth. In this study, the PCEA technique seems to be the best-suited technique for childbirth, since it had a significantly shorter duration of labor than the PIEB technique.