Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome.

BACKGROUND: Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). METHODS: We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. RESULTS: Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. CONCLUSIONS: Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

Positive donor blood cultures are not associated with worse heart transplant survival.

BACKGROUND: Recent evidence has demonstrated that transplantation of hearts with blood culture positive donors (BCPDs) to pediatric recipients is safe and effective. Few studies have analyzed the effect of BCPD on adult heart transplant recipients. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from September, 1987 to March, 2021. Exclusion criteria included pediatric donors/recipients, donor ejection fraction <10% or >85%, inactive listed recipients, donors missing blood cultures, and recipients missing follow-up time. Outcomes were compared with fully adjusted logistic models. To account for discrepancies in BCPD and non-BCPD covariates, an inverse proportionally weighted model with regression adjustment (IPWRA) was used. RESULTS: A total of 60 592 donors were non-BCPD, while 4009 were BCPD. 7% of hearts not transplanted were BCPD, while 6% of hearts transplanted were BCPD (p = .001). These rates have been nearly constant since 2005. There were no differences in short term survival between the two groups in the adjusted or IPWRA models (p = .103 and .277, respectively). Additionally, the BCPD group had longer ischemic time (3.24 vs. 3.06 h, p < .001), older donor age (32.73 vs. 31.65 years, p < .001), and older recipient age (52.76 vs. 52.09 years, p = .001). The IPWRA revealed an average additional 3.4 years of overall survival and 2.25 years of graft function for BCPD versus non-BCPD recipients, although these results failed to reach statistical significance (p = .387 and .527, respectively). CONCLUSIONS: Given the need for more donor hearts, donors with positive blood cultures should be considered. Great care in evaluating such patients is advised to eliminate donors with untreated infections, while carefully selected donors can be considered and used.

Nighttime sleep and daytime sleepiness patterns among left ventricular assist device patients.

Despite the high prevalence of sleep disturbance in the heart failure population, information about its consequence on daytime function in patients with left-ventricular assist devices (LVADs) is limited. This study examined the nighttime and daytime sleep patterns and changes from pre-implant to 6 months post-implant. This study included 32 LVAD patients. Demographics, nighttime and daytime sleep variables were collected pre-implant and at 1, 3, and 6 months post-implant. Wrist actigraphy and self-report questionnaires measured objective and subjective sleep, respectively. Objective nighttime sleep data were sleep efficiency (SE), sleep latency (SL), total sleep time (TST), wake after sleep onset (WASO), and sleep fragmentation (SF). Objective daytime sleep data were nap times. Self-reported Subjective Sleep Quality Scale (SSQS) and Stanford Sleepiness Scale (SSS) were subjective measures. Increased SF and WASO scores and decreased TST and SE scores were found pre-LVAD implant, indicative of poor sleep quality. TST, SE, naptime and SSQS scores were higher at 3 and 6 months post-implant compared to baseline. Decreases in TST and SF scores were observed at 3 and 6 months post-implant along with increases in SSS scores. Increasing SSS scores and decreasing overall scores from pre- and up to 6 months post-implant suggest improvement in daytime function. This study provides information on sleep-daytime function in the LVAD patient population. Improvements in daytime sleepiness do not imply "good" sleep quality, consistent with the extant knowledge in LVAD literature. Future investigations should elucidate the mechanism by which sleep-daytime function influences quality of life.

Effects of Ionic Liquids on Metalloproteins.

In the past decade, innovative protein therapies and bio-similar industries have grown rapidly. Additionally, ionic liquids (ILs) have been an area of great interest and rapid development in industrial processes over a similar timeline. Therefore, there is a pressing need to understand the structure and function of proteins in novel environments with ILs. Understanding the short-term and long-term stability of protein molecules in IL formulations will be key to using ILs for protein technologies. Similarly, ILs have been investigated as part of therapeutic delivery systems and implicated in numerous studies in which ILs impact the activity and/or stability of protein molecules. Notably, many of the proteins used in industrial applications are involved in redox chemistry, and thus often contain metal ions or metal-associated cofactors. In this review article, we focus on the current understanding of protein structure-function relationship in the presence of ILs, specifically focusing on the effect of ILs on metal containing proteins.

Reduction of microglial progranulin does not exacerbate pathology or behavioral deficits in neuronal progranulin-insufficient mice.

Loss-of-function mutations in progranulin (GRN), most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Individuals with loss-of-function mutations on both GRN alleles develop neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disorder. Progranulin is a secreted glycoprotein expressed by a variety of cell types throughout the body, including neurons and microglia in the brain. Understanding the relative importance of neuronal and microglial progranulin insufficiency in FTD pathogenesis may guide development of therapies. In this study, we used mouse models to investigate the role of neuronal and microglial progranulin insufficiency in the development of FTD-like pathology and behavioral deficits. Grn-/- mice model aspects of FTD and NCL, developing lipofuscinosis and gliosis throughout the brain, as well as deficits in social behavior. We have previously shown that selective depletion of neuronal progranulin disrupts social behavior, but does not produce lipofuscinosis or gliosis. We hypothesized that reduction of microglial progranulin would induce lipofuscinosis and gliosis, and exacerbate behavioral deficits, in neuronal progranulin-deficient mice. To test this hypothesis, we crossed Grnfl/fl mice with mice expressing Cre transgenes targeting neurons (CaMKII-Cre) and myeloid cells/microglia (LysM-Cre). CaMKII-Cre, which is expressed in forebrain excitatory neurons, reduced cortical progranulin protein levels by around 50%. LysM-Cre strongly reduced progranulin immunolabeling in many microglia, but did not reduce total brain progranulin levels, suggesting that, at least under resting conditions, microglia contribute less than neurons to overall brain progranulin levels. Mice with depletion of both neuronal and microglial progranulin failed to develop lipofuscinosis or gliosis, suggesting that progranulin from extracellular sources prevented pathology in cells targeted by the Cre transgenes. Reduction of microglial progranulin also did not exacerbate the social deficits of neuronal progranulin-insufficient mice. These results do not support the hypothesis of synergistic effects between progranulin-deficient neurons and microglia. Nearly complete progranulin deficiency appears to be required to induce lipofuscinosis and gliosis in mice, while partial progranulin insufficiency is sufficient to produce behavioral deficits.

Erratum to: Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers.

In the article entitled: "Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers" published in the January 2016 issue of theJournal, Can J Anesth 2016; 63: 24-30, in the second column of page 29, the second to last sentence of the first paragraph should read: "Another study by Sorenson et al. examined 15 healthy males under different physiologic conditions". The publisher apologizes most sincerely for this error.

Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers.

PURPOSE: Previous studies have found that most cerebral oximeters are subject to inaccuracies secondary to extracranial contamination of the cerebral oximetric signals. We hypothesized that the more advanced second-generation FORE-SIGHT ELITE cerebral oximeter would be significantly less affected by extracranial tissue hypoxemia than the more widely used first-generation INVOS™ 5100C monitor. METHODS: Twenty healthy volunteers aged 18-45 yr had the INVOS and FORE-SIGHT probes placed on their forehead in a random sequence while in the supine position. A pneumatic head cuff was then placed around each volunteer's head just below both the oximeter and a concomitantly placed scalp forehead pulse oximeter probe. The subjects' scalp cerebral oxygen saturation (SctO2) values were measured and compared using the two different devices in sequence, both before and after scalp tissue ischemia was induced by the pneumatic cuff. RESULTS: Extracranial ischemia resulted in a significant reduction in SctO2 values from baseline in both devices. The INVOS 5100C recorded a median [interquartile range] decrease in SctO2 from baseline at five minutes of 15.1% [12.6 - 17.6], while that recorded by the FORESIGHT ELITE device was 8.6% [4.0 -12.3] at five minutes (median difference, 7.9%; 99% confidence interval, 1.9 to 16.5; P = 0.002). CONCLUSION: Updated technological algorithms employed in the FORE-SIGHT ELITE cerebral oximeter may be responsible for less extracranial contamination than was observed in the previous-generation INVOS 5100C device. The impact that this extracranial contamination may have on the clinical use of these devices remains to be determined.

Nitrosothiol formation and protection against Fenton chemistry by nitric oxide-induced dinitrosyliron complex formation from anoxia-initiated cellular chelatable iron increase.

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO.

Residual Neuromuscular Block in the Elderly: Incidence and Clinical Implications.

BACKGROUND: Elderly patients are at increased risk for anesthesia-related complications. Postoperative residual neuromuscular block (PRNB) in the elderly, defined as a train-of-four ratio less than 0.9, may exacerbate preexisting muscle weakness and respiratory dysfunction. In this investigation, the incidence of PRNB and associated adverse events were assessed in an elderly (70 to 90 yr) and younger cohort (18 to 50 yr). METHODS: Data were prospectively collected on 150 younger and 150 elderly patients. Train-of-four ratios were measured on arrival to the postanesthesia care unit (PACU). After tracheal extubation, patients were examined for adverse respiratory events during transport to the PACU, for 30 min after PACU admission, and during hospital admission. Postoperative muscle weakness was quantified using a standardized examination, and PACU and hospital lengths of stay were determined. RESULTS: The incidence of PRNB was 57.7% in elderly and 30.0% in younger patients (difference, -27.7%; 99% CI, -41.2 to -13.1%; P < 0.001). Airway obstruction, hypoxemic events, signs and symptoms of muscle weakness, postoperative pulmonary complications, and increased PACU and hospital lengths of stay were observed more frequently in the elderly (all P < 0.01). Within each cohort, most adverse events were observed in patients with PRNB. Younger patients with PRNB received larger total doses of rocuronium than did those without it (60 vs. 50 mg, P < 0.01), but there were no differences in rocuronium dose between elderly patients with PRNB and those without it (both 50 mg). CONCLUSION: The elderly are at increased risk for PRNB and associated adverse outcomes.

An Unusual Presentation of Pyloric Stenosis: A Case Report.

A full-term newborn female presented with non-bilious emesis immediately after feeding and abdominal distension on day one of life with neither palpable abdominal mass nor electrolyte derangements. The baby was initially admitted to rule out gastrointestinal obstruction versus sepsis as a cause of vomiting and abdominal distension. Initial imaging studies involving an upper gastrointestinal (GI) series showed obstruction at the level of the duodenum, but it was only during surgical exploration that the diagnosis of infantile hypertrophic pyloric stenosis was made. This case report highlights the atypical presentation of pyloric stenosis and the need to investigate cases of vomiting immediately after feeding in a newborn with ultrasonography at the least to minimize complications.

The Cause of Severe Metabolic Acidosis With Vomiting in a Neonate.

We present a 22-day-old male born full term who presented with worsening non-projectile, non-bilious vomiting and failure to thrive (FTT) and was admitted to the pediatric intensive care unit (PICU) for severe metabolic acidosis with an elevated anion gap. Despite changing the formula, the patient continued to have spit-ups after feeds since birth. Before this admission, his vomiting worsened with every feed, which was now forceful along with two days of loose stools. Obstructive causes of emesis were ruled out with an upper gastrointestinal series, and a decision was made to evaluate for organic causes of FTT. Transient resolution of symptoms was noticed when the patient was placed NPO (nothing by os/mouth) briefly. His symptoms returned on resuming cow milk-based formula feeds. At this time, a presumptive diagnosis of cow milk protein allergy (CMPA) was made. Positive fecal occult blood supported the diagnosis, and his formula was changed to an extensively hydrolyzed formula (eHF). This is a case of severe CMPA with prolonged vomiting and FTT presenting with severe metabolic acidosis with an elevated anion gap. This case report highlights how CMPA can lead to severe dehydration with metabolic acidosis and increased anion gap.

The Impact of Social Determinants of Health in Pediatric Shunted Hydrocephalus.

BACKGROUND: Social risk factors have been shown to negatively affect health outcomes in children. However, this has not been characterized regarding pediatric shunted hydrocephalus. OBJECTIVE: To explore the impact of social risk factors on outcomes in pediatric shunted hydrocephalus with the goal of identifying specific areas of intervention that might improve the outcomes of children undergoing cerebrospinal fluid (CSF) diversion. METHODS: In an all-payer administrative database, records between January 2010 and October 2020 were analyzed to identify children undergoing CSF shunting procedures. Children with social risk factors were compared with those without regarding rates of infection, shunt-related interventions, and mortality within 5 years of their shunting procedure. RESULTS: Among the 5420 children who underwent first-time shunting procedures, 263 (4.9%) were identified to have social risk factors. Children with identified social risk factors had increased odds of central nervous system infection (odds ratio [OR] 2.06, 95% CI 1.45-2.91), revision (OR 2.43, 95% I 1.89-3.12), and mortality (OR 2.86, 95% CI 1.23-5.72). The mean numbers of computed tomography studies (14.60 ± 17.78 vs 6.34 ± 6.10), MRI studies (18.76 ± 24.37 vs 7.88 ± 24.37), and shunt series X-rays (17.22 ± 19.04 vs 7.66 ± 8.54) were increased among children with social risk factors. CONCLUSION: Children with social risk factors had increased rates of central nervous system infection, shunt-related interventions, and mortality within 5 years of CSF shunting. We underscore the importance of characterizing the impact of social risk factors in specific conditions, such as pediatric shunted hydrocephalus, and look to future directions aimed to mitigate these risk factors with coordination and direction of individualized resources, encouragement of advocacy, and community partnership.

Sequence-specific destabilization of azurin by tetramethylguanidinium-dipeptide ionic liquids.

The thermal unfolding of the copper redox protein azurin was studied in the presence of four different dipeptide-based ionic liquids (ILs) utilizing tetramethylguanidinium as the cation. The four dipeptides have different sequences including the amino acids Ser and Asp: TMG-AspAsp, TMG-SerSer, TMG-SerAsp, and TMG-AspSer. Thermal unfolding curves generated from temperature-dependent fluorescence spectroscopy experiments showed that TMG-AspAsp and TMG-SerSer have minor destabilizing effects on the protein while TMG-AspSer and TMG-SerAsp strongly destabilize azurin. Red-shifted fluorescence signatures in the 25 °C correlate with the observed protein destabilization in the solutions with TMG-AspSer and TMG-SerAsp. These signals could correspond to interactions between the Asp residue in the dipeptide and the azurin Trp residue in the unfolded state. These results, supported by appropriate control experiments, suggest that dipeptide sequence-specific interactions lead to selective protein destabilization and motivate further studies of TMG-dipeptide ILs.

Disaster medicine and pandemic response: A novel curriculum to improve understanding of complex care delivery during the COVID-19 pandemic.

Background: Despite a 2009 recommendation from the AMA that disaster medicine and public health response training should be implemented in medical schools, anywhere from 31% to 47% of medical education programs lack a formalized disaster medicine curriculum. A need for disaster medicine response training for University of Alabama medical students in an appropriately socially distanced format was identified during the COVID-19 pandemic. Methods: Our emergency medicine faculty in collaboration with the Federal Emergency Management Agency Center for Disaster Preparedness (FEMA CDP) created and implemented a novel virtual disaster medicine and pandemic response course for third-year medical students at the University of Alabama at Birmingham (UAB). The course was administered via a teleconferencing platform (Zoom, Zoom Video Communications, Inc.) in spring 2020 to more than 130 medical students. Results: Using pre- and postcourse surveys, we assessed a change in student confidence levels for their ability to explain topics covered in the course and their understanding of a chosen disaster. The students reported an average increase of 2.183 on a 5-point scale, with a score of 5 representing "completely confident" and a score of 1 representing "not at all confident." This course established the feasibility of a virtual instructor-led training (VILT) format for disaster medicine education and provided a template for the delivery of over 300 courses to more than 4,000 first responders and medical professionals through the FEMA CDP. Conclusions: Through collaboration with the FEMA CDP, our UAB faculty were able to successfully deliver a novel virtual disaster-preparedness and response course. The course resulted in subjective improvement of students' content understanding while also establishing the feasibility and effectiveness of a VILT format that could be readily applied to future courses in undergraduate medical education and beyond.

Thermodynamic destabilization of azurin by four different tetramethylguanidinium amino acid ionic liquids.

The thermal unfolding of the copper redox protein azurin was studied in the presence of four different amino acid-based ionic liquids (ILs), all of which have tetramethylguanidium as cation. The anionic amino acid includes two with alcohol side chains, serine and threonine, and two with carboxylic acids, aspartate and glutamate. Control experiments showed that amino acids alone do not significantly change protein stability and pH changes anticipated by the amino acid nature have only minor effects on the protein. With the ILs, the protein is destabilized and the melting temperature is decreased. The two ILs with alcohol side chains strongly destabilize the protein while the two ILs with acid side chains have weaker effects. Unfolding enthalpy (ΔHunf°) and entropy (ΔSunf°) values, derived from fits of the unfolding data, show that some ILs increase ΔHunf°while others do not significantly change this value. All ILs, however, increase ΔSunf°. MD simulations of both the folded and unfolded protein conformations in the presence of the ILs provide insight into the different IL-protein interactions and how they affect the ΔHunf° values. The simulations also confirm that the ILs increase the unfolded state entropies which can explain the increased ΔSunf° values.

360° ab-interno trabeculotomy in refractory primary open-angle glaucoma.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of microinvasive glaucoma surgery (MIGS) with 360° ab-interno trabeculotomy using the TRAB360 device as a stand-alone procedure in patients with refractory primary open-angle glaucoma (POAG) and preoperative IOP ≥18 mmHg. SETTING: This study evaluated patients treated in a tertiary-referral clinical practice setting. DESIGN: This study is a retrospective analysis of 81 eyes. METHODS: Patients with refractory open-angle glaucoma underwent stand-alone 360° ab-interno trabeculotomy using the TRAB360 device. Effectiveness was determined by reduction in medicated IOP and the use of medications from baseline. Safety was determined by the rate of adverse events and secondary surgical interventions. The time points assessed were baseline and postoperative day 1, week 1, and months 1, 3, 6, and 12. A subgroup analysis was performed on eyes with medicated preoperative IOP values of ≥25 mmHg. RESULTS: The reductions in IOP from 1 day to 12 months postoperatively were statistically significant compared to baseline values. The mean reduction in IOP at 12 months was 7.3±6.7 mmHg from baseline. At 12 months, 59% eyes achieved ≥20% reduction in IOP and IOP <18 mmHg with the same or fewer numbers of IOP-lowering medications compared with those at baseline. The mean number of IOP-lowering medications was reduced from 1.7±1.3 at baseline to 1.1±1.0 at 12 months. At 12 months, 67% of eyes with preoperative IOP values of ≥25 mmHg achieved ≥20% reduction in IOP and IOP <18 mmHg with the same or fewer numbers of IOP-lowering medications compared with those at baseline. The most common adverse event for all eyes was mild, transient hyphema (57 eyes). During the first year after the procedure, 20 (25%) eyes were considered failures since they required reinterventions. CONCLUSION: Trabeculotomy using the TRAB360 device resulted in significant IOP reductions up to 1 year with a favorable safety profile. The device is an effective stand-alone MIGS procedure for patients with refractory POAG.

Utility of Longitudinal Measurement of the Liver With Ultrasound in Comparison to Computed Tomography Liver Volume in Assessing Hepatomegaly.

ABSTRACT: The purpose of the study is to retrospectively compare the longitudinal measurement of the liver on ultrasound (US) with liver volume as measured on computed tomography (CT). This institutional review board-approved retrospective study with prospective image analysis included adult patients with US examinations of the liver and CT examinations of the abdomen performed within 2 weeks of each other from January 1, 2010, to April 30, 2016. We recorded the dome-to-tip longitudinal length measurement of the right lobe of the liver on the US study. The liver volume was calculated using manual 3-dimensional segmentation of the CT data set. Additional linear liver measurements and qualitative assessments were retrospectively made on the US and CT images. Hepatomegaly was defined as a liver volume 2000 mL or greater. The sample had 302 patients including 140 males and 162 females. Liver length measured on US had a moderate positive correlation with liver volume measured on CT, with a Pearson correlation coefficient of 0.7078. The optimum cutoff of liver length (US) was found to be 17 cm by Youden index, with a sensitivity of 76.0% and specificity of 73.4% for hepatomegaly. Additional linear measurements and qualitative assessments of the liver did not significantly improve the diagnosis of hepatomegaly. In conclusion, liver length measured with US has only a moderate correlation with liver volume. Commonly used US liver length maximum values of 16 to 18 cm produce a significant number of false-negatives and false-positives for the diagnosis of hepatomegaly.

Procedural Timeout Compliance Is Improved With Real-Time Clinical Decision Support.

PURPOSE: The goal of this study was to assess compliance with a presurgical safety checklist before and after the institution of a surgical flight board displaying a surgical safety checklist with embedded real-time clinical decision support (CDS). We hypothesized that the institution of a surgical flight board with embedded real-time data support would improve compliance with the presurgical safety checklist. METHODS: In this prospective, observational trial, surgeon-led procedural timeout compliance for 300 procedures was studied. In phase I (PI), procedural timeouts were performed using a simple paper checklist. In phase II (PII), an electronic surgical flight board with an embedded safety checklist was installed in each operating room, but the timeout procedure consisted of the same paper process as in PI. In phase III (PIII), the flight board safety checklist was used. Ten procedures each from 10 surgeons were evaluated in each phase. Compliance was scored on a 12-point scale with each point representing a different item on the checklist. RESULTS: Timeout compliance in PI ranged from 4.5 to 8.6 and 8.75 to 12 in PIII. All 10 surgeons demonstrated statistically improved compliance from PI to PIII. Compliance was significantly improved in 8 of 12 safety check items. Decreased compliance was not seen with any checklist item. Of the items with CDS, compliance with procedure consent and special safety precautions improved from PI to PIII, as did compliance with display of essential imaging, critical events or concerns, and number of procedures (i.e., >1 surgeon performing procedures). CONCLUSIONS: Using the electronic medical record with real-time CDS improves compliance with presurgical safety checklists.

Postoperative Intravenous Acetaminophen for Craniotomy Patients: A Randomized Controlled Trial.

OBJECTIVE: To determine whether opioids during the first 24 postoperative hours were significantly altered when receiving intravenous (IV) acetaminophen during that time compared with those receiving placebo (normal saline). METHODS: One hundred forty patients undergoing any type of craniotomy were randomly assigned to receive either 1 g of IV acetaminophen or placebo upon surgical closure, and every 6 hours thereafter, up to 18 hours postoperatively. Analgesic requirements for the first 24 postoperative hours were recorded. Time to rescue medications in the postanesthesia care unit (PACU)/intensive care unit (ICU), amount of rescue medication, ICU and hospital lengths of stay, number of successful neurological examinations, sedation, delirium, satisfaction, and visual analog scale pain scores were also recorded. RESULTS: Compared with the placebo group, more patients in the IV acetaminophen group (10/66 [15.2%] vs. 4/65 [6.2%] in the placebo group) did not require opioids within the first 24 postoperative hours, but this did not reach significance (odds ratio, -9.0%, 95% confidence interval -20.5% to 1.8%; P = 0.166). Both groups had similar times to rescue medications, amounts of rescue medications, ICU and hospital lengths of stay, numbers of successful neurological examinations, sedation, delirium, satisfaction scores, visual analog scale pain scores, and temperatures within the first 24 postoperative hours. CONCLUSIONS: The opioid requirements within the first 24 postoperative hours were similar in the placebo and acetaminophen groups. This study is informative for the design and planning of future studies investigating the management of postoperative pain in patients undergoing craniotomies.

Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves mucosal lining in colitis associated cancer.

In colitis associated cancer (CAC), chronic inflammation exposes the epithelial mucosal defensive lining to inflammatory mediators such as cytokines and anti-microbial peptides (AMPs) causing the dysbiosis of microbiota population and the dysregulation of immune response. Matrix Metalloproteinases (MMPs) are zinc dependent endopeptidases which mediate inflammation, tissue remodeling, and carcinogenesis. MMP9 is undetectable in healthy tissue, although highly upregulated during inflammation and cancer. We have previously shown that MMP9 plays a protective role in CAC opposite to its conventional role of acute inflammation and cancer mediator. In this study, we investigated the mechanistic role of MMP9 in preserving the epithelial mucosal integrity to suppress the progression of tumor microenvironment in CAC. We used transgenic mice constitutively expressing MMP9 in colonic epithelium (TgM9) as an in vivo model and intestinal cell line CaCo2BBE as an in vitro model. We induced CAC with three cycles of dextran sodium sulfate (DSS). We observed that MMP9 expression in colonic epithelium maintains the microbiota. We also observed that MMP9 mediates pro-inflammatory cytokine levels and AMPs but suppresses IL-22 resulting in lower levels of REG3-g and S100A8 AMPs. We also found that MMP9 maintains an efficient barrier function and the integrity of tight junctions. We also observed increased levels of mucin and intestinal trefoil factor among TgM9 mice in CAC. We also found that MMP9 expressing CaCo2BBE cells had increased expressions of EGFR and nuclear transcription factor- specificity protein 1 (Sp1). These data imply that MMP9 acts as a tumor suppressor in CAC by sustaining the epithelial mucosal integrity due to the activation of EGFR-Sp1 signaling pathway.