Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-ß Signaling.

Mesenchymal stromal cells (MSCs) grown in high-density monolayers (sheets) are promising vehicles for numerous bioengineering applications. When MSC sheets are maintained in prolonged cultures, they undergo rapid senescence, limiting their downstream efficacy. Although rapamycin is a potential agent that can inhibit senescence in cell cultures, no study has investigated rapamycin's effect on MSCs grown in high-density culture and its effect on downstream target gene expression. In this study, placental-derived MSCs (PMSCs) were seeded at high density to generate PMSC sheets in 24 hours and were then treated with rapamycin or vehicle for up to 7 days. Autophagy activity, cell senescence and apoptosis, cell size and granularity, and senescence-associated cytokines (IL-6 and IL-8) were analyzed. Differential response in gene expression were assessed via microarray analysis. Rapamycin significantly increased PMSC sheet autophagy activity, inhibited cellular senescence, decreased cell size and granularity at all timepoints. Rapamycin also significantly decreased the number of cells in late apoptosis at day 7 of sheet culture, as well as caspase 3/7 activity at all timepoints. Notably, while rapamycin decreased IL-6 secretion, increased IL-8 levels were observed at all timepoints. Microarray analysis further confirmed the upregulation of IL-8 transcription, as well as provided a list of 396 genes with 2-fold differential expression, where transforming growth factor-ß (TGF-ß) signaling were identified as important upregulated pathways. Rapamycin both decreased senescence and has an immunomodulatory action of PMSCs grown in sheet culture, which will likely improve the chemotaxis of pro-healing cells to sites of tissue repair in future bioengineering applications.

COVID-19 Physician Burnout: Louisiana's Workforce Vulnerability and Strategies for Mitigation.

Background: Louisiana is historically one of the lowest-performing states in terms of health outcomes in the United States. Hurricane Katrina led to a decrease in available health care resources, with a larger impact on resources for those living below the poverty line. Subsequently, the coronavirus disease 2019 (COVID-19) pandemic has been shown to have had disproportionately large impacts on minority communities, uninsured populations, and rural communities-all of which are found in Louisiana. Methods: This review focuses on the unique challenges of health care in Louisiana, the influence of COVID-19 on physician burnout, and methods of reducing work exhaustion for those in the health care field. Results: A national survey showed that physician satisfaction decreased from June 29, 2021, through September 26, 2021, compared to before the pandemic. A critical component in the provision of the essential services of public health is the ability to build and sustain a clinically skilled and diverse physician workforce. Maintaining well-being and retaining the physician workforce are prerequisites to the equitable provision of access to health care services. Conclusion: Maintaining one's own wellness is critical to occupational sustainability, particularly when unique stressors such as those encountered during the COVID-19 pandemic are present. The future of a vital health care system depends on physicians maintaining healthy habits and seeking help when burnout symptoms are recognized, both at the individual and institutional level.

Compressibility of Osteochondral Autograft Transfer Donor Grafts: A Comparison of Different Donor Regions and How Much Shortening Occurs of Plugs After Impaction.

Background: Osteochondral autograft transfer (OAT) is a useful technique for full-thickness cartilage lesions of the distal femur. Various techniques recommend harvesting a plug 2 mm longer than the recipient hole to allow for graft impaction. Grafts with limited compressibility may not sit flush when impacted. Purpose: To compare the compressibility/shortening of OAT donor plug regions from the distal femur of human cadaveric knees after impaction. Study Design: Controlled laboratory study. Methods: A total of 20 cadaveric knees (mean age, 70.3 ± 8.4 years) were divided into 4 donor regions: medial intercondylar (IC) notch, lateral IC notch, medial trochlea, and lateral trochlea. Each region was subdivided into 4 zones: far superior (FSZ), middle superior (MSZ), middle inferior (MIZ), and far inferior (FIZ). A total of 320 grafts (6-mm diameter, 15-mm depth) were extracted, and a custom-built machine was used to strike the graft 5 times using a predetermined energy of 0.11 J. The graft length was measured initially and after each impact. Statistical analysis of the compressibility for each of the 4 regions and all 16 zones was performed utilizing analysis of variance, with post hoc testing using the Fisher's least significant difference. Results: Compression in the lateral IC notch, medial IC notch, medial trochlea, and lateral trochlea was 2.4 ± 1.5, 2.1 ± 0.7, 3.1 ± 2.2, and 2.1 ± 0.6 mm, respectively, with significant differences between the 4 regions (P < .01) and the most compression in the medial trochlea (P < .01). Subgroup analysis showed that the lateral trochlea had higher compressibility for FIZ versus MIZ (P = .02) and the lateral IC notch had higher compressibility for FSZ versus FIZ and MIZ (P < .05 for both). Conclusion: Compressibility varied between OAT donor sites in the distal femur. OAT donor grafts showed the highest compressibility in the medial trochlea (3.1 mm) and lateral IC notch FSZ (3.0 mm). Clinical Relevance: The lateral trochlea, medial IC notch, and the lower zones of the lateral IC notch grafts should not be oversized more than 2 mm in length, as these grafts may not compress adequately.

Donor Side Preference in Maxillary Reconstruction With the Free Fibula Flap.

BACKGROUND: The implications on the choice of donor side when using the free fibula flap for reconstruction of unilateral maxillectomy defects has not been discussed in the literature so far. METHODS: A unilateral maxillectomy reconstruction was replicated using a 3D-printed skull model and fresh cadaveric dissections of left and right osteomyocutaneous fibula flaps for comparison. Detailed photo documentation was conducted to analyze and illustrate the anatomical differences of performing a reconstruction using the ipsilateral or contralateral sides and their relative benefits and risks. RESULTS: A more favorable lie of the septum and skin paddle and flexor hallucis longus muscle is attainable depending on which donor side is used and the planned direction of the pedicle. CONCLUSION: This study demonstrates why it is preferable to use the ipsilateral fibula if anastomosis is to the ipsilateral facial or neck recipient vessels, or the contralateral fibula where the contralateral recipient vessels are preferred.

Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment.

Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug-resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus isolates from across the UK and Ireland (comprising 153 clinical isolates from 143 patients and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (A and B) with little interclade recombination and the majority of environmental azole resistance found within clade A. Second, we show occurrences where azole-resistant isolates of near-identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-wide scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, while other regions under selection have no defined function. Lastly, pan-genome analysis identified genes linked to azole resistance and previously unknown resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.

ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids.

OBJECTIVE: Metabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progression METHODS: Through integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (NAFLD) and obesity-related hepatocellular carcinoma were analyzed to dissect the causal role of ITCH in steatosis RESULTS: We show that ITCH regulation of branched-chain amino acids (BCAAs) degradation enzymes is impaired in obese women with grade 3 compared with grade 0 steatosis, and that ITCH acts as a gatekeeper whose loss results in elevation of circulating BCAAs associated with hepatic steatosis. When ITCH expression was specifically restored in the liver of ITCH knockout mice, ACADSB mRNA and protein are restored, and BCAA levels are normalized both in liver and plasma CONCLUSIONS: Our data support a novel functional role for ITCH in the hepatic regulation of BCAA metabolism and suggest that targeting ITCH in a liver-specific manner might help delay the progression of metabolic hepatic diseases and insulin resistance.

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome.

BACKGROUND: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. RESULTS: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient's mice. In line with the results in humans, transplantation from 'high ferritin donors' resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient's mice. CONCLUSIONS: Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. Video abstract.

Nitinol Memory Rods Versus Titanium Rods: A Biomechanical Comparison of Posterior Spinal Instrumentation in a Synthetic Corpectomy Model.

STUDY DESIGN: Biomechanical investigation. OBJECTIVE: To compare the biomechanical performance of nitinol memory metal rods and titanium rods when used as posterior spinal instrumentation in a synthetic model. METHODS: Biomechanical testing was performed using ultra-high-molecular-weight polyethylene blocks. Nineteen spinal constructs were created to allow comparison of 5.5-mm nitinol rods with 5.5-mm titanium rods. Static compression and rotational testing were performed on an Instron 8874 and Instron 4202 at 37°C to simulate body temperature. RESULTS: The average titanium construct stiffness under static compression or bending was 47.2 ± 9.1 N/mm while nitinol's stiffness averaged 48.9 ± 12.4 N/mm (P = .83). During axial rotation testing, the nitinol rod system showed no torsional stiffness difference from the titanium system: 0.95 ± 0.03 Nm/deg versus 0.96 ± 0.17 Nm/deg, respectively (P = 0.91). There was a statistically significant difference between the average torsional yield point for the titanium constructs (14.4 ± 1.6 Nm/deg) and nitinol constructs (21.3 ± 0.8 Nm/deg) (P = .004). The torsional toughness of the nitinol constructs was also statistically greater than the titanium rods: 473 GN/m3 versus 784 GN/m3 (P = .0006). There was no statistically significant difference between the nitinol group sustaining a higher number of fatigue cycles until failure and the titanium group (181 660 cycles vs 64 104 cycles, respectively, P = .22). CONCLUSIONS: This study provides biomechanical evidence that nitinol rods used in a posterior construct are comparable to titanium rods with regard to compression and have increased torsional failure load and torsional toughness. While nitinol trended toward superior fatigue resistance, there was no significant difference in nitinol versus titanium construct fatigue resistance.

Rebar Repair of Radial Meniscus Tears: A Reinforced Suture Technique.

The purpose of this paper is to describe the rebar repair as a technique for repair of radial meniscus tears and compare the rebar technique with current techniques used for meniscus repairs. This technique consists of 4 sutures placed with the inside-out technique. First, the vertical mattress reinforcement sutures are placed anteriorly and posteriorly to the tear. Then, 2 parallel horizontal sutures are placed directly in juxtaposition to the vertical sutures, ensuring the needles pass on the side of the reinforcing stitch away from the tear. This technique is less technically challenging than other meniscus repair techniques that require drilling of a transtibial tunnel. Overall, the rebar technique offers a more optimal way for stabilizing the meniscus by using 2 reinforcement sutures that run with the circumferential fibers to help restore the natural hoop stress of the meniscus. Also, the placement of the vertical mattress sutures in the rebar technique offers more direct reinforcement to the horizontal mattress sutures as compared with other techniques, which reduces the risk of pull-out tears.

The APOA1bp-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients.

BACKGROUND & AIMS: Atherosclerosis is characterized by an inflammatory disease linked to excessive lipid accumulation in the artery wall. The Notch signalling pathway has been shown to play a key regulatory role in the regulation of inflammation. Recently, in vitro and pre-clinical studies have shown that apolipoprotein A-I binding protein (AIBP) regulates cholesterol metabolism (SREBP) and NOTCH signalling (haematopoiesis) and may be protective against atherosclerosis, but the evidence in humans is scarce. METHODS: We evaluated the APOA1bp-SREBF-NOTCH axis in association with atherosclerosis in two well-characterized cohorts of morbidly obese patients (n = 78) within the FLORINASH study, including liver transcriptomics, 1H NMR plasma metabolomics, high-resolution ultrasonography evaluating carotid intima-media thickness (cIMT), and haematological parameters. RESULTS: The liver expression levels of APOA1bp were associated with lower cIMT and leukocyte counts, a better plasma lipid profile and higher circulating levels of metabolites associated with lower risk of atherosclerosis (glycine, histidine and asparagine). Conversely, liver SREBF and NOTCH mRNAs were positively associated with atherosclerosis, liver steatosis, an unfavourable lipid profile, higher leukocytes and increased levels of metabolites linked to inflammation and CVD such as branched-chain amino acids and glycoproteins. APOA1bp and NOTCH signalling also had a strong association, as revealed by the negative correlations among APOA1bp expression levels and those of all NOTCH receptors and jagged ligands. CONCLUSIONS: We here provide the first evidence in human liver of the putative APOA1bp-SREBF-NOTCH axis signalling pathway and its association with atherosclerosis and inflammation.

Prolonged survival after disseminated Rhinocladiella infection treated with surgical excision and posaconazole.

Cerebral abscess due to pigmented molds is a rare but usually fatal infection occasionally seen in transplant recipients. A 67-year-old man of Iraqi origin underwent a deceased donation renal transplant for renal failure and 2 months later was diagnosed with an abscess in the left posterior frontal lobe of his brain. Subsequent biopsy proved this to be due to the mold Rhinocladiella mackenziei. Further interventions included two operations to aspirate the lesion, voriconazole, then liposomal amphotericin B, then a combination of posaconazole and flucytosine which he continued for over 4 years. He also suffered from right ankle pain and was diagnosed with septic arthritis; R mackenziei was isolated from pus aspirated from the ankle joint. He responded well to the treatment and has had little loss of function, and on CT, the cerebral lesion has stabilized. Beta-D-glucan, initially at very high levels proved useful to monitor response over the 5 years and the latest sample was negative (38 pg/mL). This case is notable for the first disseminated case of this infection, its favorable outcome on a novel antifungal combination and a new approach to monitoring the course of disease.

Serum IgE and IgG reactivity to Aspergillus recombinant antigens in patients with cystic fibrosis.

PURPOSE: The diagnosis of aspergillosis in cystic fibrosis (CF) patients remains a challenge due to overlapping features of both diseases. This is further complicated by inconsistent antibody reactivity to the currently used crude antigen, which has led a more focused evaluation of the efficacy of IgE response to a number of pure Aspergillus fumigatus recombinant proteins in patients with CF and asthma. In this study, we dissected the IgE and IgG responses to multiple A. fumigatus recombinant antigens in CF patients with different Aspergillus diseases. METHODOLOGY: Serum IgE and IgG antibodies were measured in 12 CF patients with allergic bronchopulmonary aspergillosis (ABPA), 12 with Aspergillus sensitization (AS) and 12 with Aspergillus bronchitis (AB) against recombinant antigens Asp f1, f2, f3, f4 and f6. RESULTS: The ABPA group showed significantly greater IgE reactivity to Asp f1, f2, f3 and f4 compared to patients with AS. Patients with AB expressed higher IgG positivity to Asp f1 and Asp f2 compared with those with ABPA. There were very low IgE antibody levels against all recombinant antigens in patients with AS. Aspf1 IgG reactivity in ABPA patients correlated with positive culture. CONCLUSION: The use of multiple recombinant antigens may improve the diagnostic accuracy in CF complicated with ABPA or AB. Asp f1 reactivity may relate to the presence of actively growing Aspergillus spp., which might be a useful marker for guiding antifungal therapy in ABPA.

Proximity of the Neurovascular Bundle During Posterior-Lateral Meniscal Repair: A Comparison of the Transpatellar, Anteromedial, and Anterolateral Portals.

PURPOSE: To compare the neurovascular proximity of the transpatellar portal with that of the medial and lateral portals and to determine the safe penetration depth for an all-inside device for use on the posterior horn lateral meniscus. METHODS: Dissection of the popliteal fossa was performed in 10 cadaveric knees to identify all structures. Arthroscopy was performed using penetration depths of 10, 12, 14, and 16 mm with the all-inside system through the anteromedial, anterolateral, and transpatellar portals. Penetrations were made 5 and 10 mm lateral to the posterior horn root at the meniscocapsular junction. Needle-tip distances were measured from the popliteal artery and vein, tibial nerve, and common peroneal nerve. RESULTS: Among 240 trials, the average distance to the popliteal neurovascular bundle using the medial, transpatellar, and lateral approaches was 6.9 mm, 6.5 mm, and 3.1 mm, respectively. The transpatellar-portal needle had a larger distance from the neurovascular bundle than the lateral portal (P = .001), with no statistical difference compared with the medial portal (P = .58). Compared with the position at a 10-mm distance from the root, the position at a 5-mm distance from the root was closer to the neurovascular bundle in all approaches (P = .001). The transpatellar approach set to 14 mm had a 5% rate of capsular underpenetration and 10% rate of gastrocnemius penetration. The transpatellar and medial portals had no neurovascular penetrations, whereas the lateral approach had a 14% rate of penetration (P < .05). CONCLUSIONS: The transpatellar portal and anteromedial portal are in less proximity to the neurovascular bundle compared with the anterolateral portal for all-inside meniscal repair of the posterior horn lateral meniscus. Low rates of neurovascular penetration, gastrocnemius muscle penetration, and capsular underpenetration occurred with a depth setting of 14 mm. CLINICAL RELEVANCE: This study shows the utility of medial and transpatellar portals when using all-inside devices to repair posterior horn lateral meniscal tears and neurovascular proximity based on penetration depth.

Short-Term Clinical and Quality Outcomes Have Inconsistent Changes From a Quality Improvement Initiative to Increase Access to Physical Therapy in the Cardiovascular and Surgical ICU.

Studies of mobility during critical illness have mostly examined transitions from immobility (passive activities) or limited mobility to active "early mobility." DESIGN: Observational analysis of a quality improvement initiative. SETTING: Two ICUs (surgical ICU, cardiovascular ICU) at a tertiary academic medical center. PATIENTS: Critically ill surgical and cardiovascular patients. INTERVENTIONS: Doubling available physical therapy. MEASUREMENTS AND MAIN RESULTS: We examined the outcomes of therapy time/patient/day, ICU and hospital length of stay, disposition location, and change in functional status. We adjusted for age, sex, illness severity, and number of surgeries. Among 1,515 patients (703 baseline, 812 quality improvement), total therapy time increased from 71,994 to 115,389 minutes and from 42,985 to 93,015 minutes, respectively, in each ICU. In the cardiovascular ICU per patient therapy increased 17% (95% CI, -4.9 to 43.9; p = 0.13), and in the surgical ICU, 26% (95% CI, -1 to 59.4; p = 0.06). In the cardiovascular ICU, there was a 27.4% decrease (95% CI, -52.5 to 10.3; p = 0.13) in ICU length of stay, and a 12.4% decrease (95% CI, -37.9 to 23.3; p = 0.45) in total length of stay, whereas in the surgical ICU, the adjusted ICU length of stay increased 19.9% (95% CI, -31.6 to 108.6; p = 0.52) and total length of stay increased 52.8% (95% CI, 1.0-130.2; p = 0.04). The odds of a lower level of care discharge did not change in either ICU (cardiovascular ICU: 2.6 [95% CI, 0.6-12.2; p = 0.22]); surgical ICU: 3.6 [95% CI, 0.9-15.4; p = 0.08]). CONCLUSIONS: Among diverse cardiothoracic and surgical patients, a quality improvement initiative doubling physical therapy shifts is associated with increased total administered therapy time, but when distributed among a greater number of patients during the quality improvement period, the increase is tempered. This was not associated with consistent changes in ICU length of stay or changes in disposition location.

Predicting ICU readmission among surgical ICU patients: Development and validation of a clinical nomogram.

BACKGROUND: Unplanned intensive care unit readmission within 72 hours is an established metric of hospital care quality. However, it is unclear what factors commonly increase the risk of intensive care unit readmission in surgical patients. The objective of this study was to evaluate predictors of readmission among a diverse sample of surgical patients and develop an accurate and clinically applicable nomogram for prospective risk prediction. METHODS: We retrospectively evaluated patient demographic characteristics, comorbidities, and physiologic variables collected within 48 hours before discharge from a surgical intensive care unit at an academic center between April 2010 and July 2015. Multivariable regression models were used to assess the association between risk factors and unplanned readmission back to the intensive care unit within 72 hours. Model selection was performed using lasso methods and validated using an independent data set by receiver operating characteristic area under the curve analysis. The derived nomogram was then prospectively assessed between June and August 2017 to evaluate the correlation between perceived and calculated risk for intensive care unit readmission. RESULTS: Among 3,109 patients admitted to the intensive care unit by general surgery (34%), transplant (9%), trauma (43%), and vascular surgery (14%) services, there were 141 (5%) unplanned readmissions within 72 hours. Among 179 candidate predictor variables, a reduced model was derived that included age, blood urea nitrogen, serum chloride, serum glucose, atrial fibrillation, renal insufficiency, and respiratory rate. These variables were used to develop a clinical nomogram, which was validated using 617 independent admissions, and indicated moderate performance (area under the curve: 0.71). When prospectively assessed, intensive care unit providers' perception of respiratory risk was moderately correlated with calculated risk using the nomogram (ρ: 0.44; P < .001), although perception of electrolyte abnormalities, hyperglycemia, renal insufficiency, and risk for arrhythmias were not correlated with measured values. CONCLUSION: Intensive care unit readmission risk for surgical patients can be predicted using a simple clinical nomogram based on 7 common demographic and physiologic variables. These data underscore the potential of risk calculators to combine multiple risk factors and enable a more accurate risk assessment beyond perception alone.

Acid Suppression to Prevent Gastrointestinal Bleeding in Patients With Ventricular Assist Devices.

BACKGROUND: The high incidence of gastrointestinal bleeding (GIB) in patients with ventricular assist devices (VAD) is well known, but there is limited evidence to support the use of proton pump inhibitors (PPIs) or histamine receptor antagonists (H2RA) for preventing GIB in patients with VAD. MATERIALS AND METHODS: The surgical ICU and VAD databases within a large regional academic cardiac mechanical support and transplant center were queried for patients who underwent VAD implantation between 2010 and 2014. An observational cohort study was conducted to identify which acid suppressing drug regimen was associated with the fewest number of GIB events within 30 d after VAD implantation: PPI, H2RA, or neither. Secondary outcomes included timing, etiology, and location of GIB. Multivariable logistic regression was used to compare treatment cohorts to GIB. Odds ratios, 95% confidence intervals, and P-values were reported from the model. RESULTS: One hundred thirty-eight patients were included for final analysis, 19 of which had a GIB within 30 days of VAD implantation. Both H2RA and PPI use were associated with reduced GIB compared with the cohort with no acid suppressive therapy. In the multivariate analysis, the PPI cohort showed a statistically significant reduction in GIB (Odds ratio 0.18 [95% confidence interval 0.04-0.79] P = 0.026). CONCLUSIONS: Using PPI postoperatively in patients with new VAD was associated with a reduced incidence of GIB. Given that GIB is a known complication after VAD placement, clinicians should consider the use of acid suppressive therapy for primary prevention.

Publisher Correction: Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women.

In the version of this article originally published, the received date was missing. It should have been listed as 2 January 2018. The error has been corrected in the HTML and PDF versions of this article.

Outcomes When Using Adjunct Dexmedetomidine with Propofol Sedation in Mechanically Ventilated Surgical Intensive Care Patients.

Objective: Compare the duration of mechanical ventilation between patients receiving sedation with continuous infusions of propofol alone or combination with the use of dexmedetomidine and propofol. Design: Retrospective, propensity matched (1:1) cohort study, employing eight variables chosen a priori for matching. Timing of exposure to dexmedetomidine initiation was incorporated into a matching algorithm. Setting: Level 1, university-based, 32-bed, adult, mixed trauma and surgical intensive care unit (SICU). Continuous sedation was delivered according to a protocol methodology with daily sedation vacation and spontaneous breathing trials. Choice of sedation agent was physician directed. Patients: Between 2010 and 2014, 149 SICU patients receiving mechanical ventilation for >24 h received dexmedetomidine with propofol. Propensity matching resulted in 143 pair cohorts. Interventions: Dexmedetomidine with propofol or propofol alone. Measurements and Main Results: There was no statistical difference in SICU length of stay (LOS), with a median absolute difference of 5.3 h for propofol alone group (p = 0.43). The SICU mortality was not statistically different (RR = 1.002, p = 0.88). Examining a 14-day period post-treatment with dexmedetomidine, on any given day (excluding days 1 and 14), dexmedetomidine with propofol-treated patients had a 0.5% to 22.5% greater likelihood of being delirious (CAM-ICU positive). In addition, dexmedetomidine with propofol-treated patients had a 4.5% to 18.8% higher likelihood of being above the target sedation score (more agitated) compared to propofol-alone patients. Conclusions: In this propensity matched cohort study, adjunct use of dexmedetomidine to propofol did not show a statistically significant reduction with respect to mechanical ventilation (MV) duration, SICU LOS, or SICU mortality, despite a trend toward receiving fewer hours of propofol. There was no evidence that dexmedetomidine with propofol improved sedation scores or reduced delirium.