Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract.

ABSTRACT: Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577.

Developing a granular scale environmental burden index (EBI) for diverse land cover types across the contiguous United States.

Critical to identifying the risk of environmentally driven disease is an understanding of the cumulative impact of environmental conditions on human health. Here we describe the methodology used to develop an environmental burden index (EBI). The EBI is calculated at U.S. census tract level, a finer scale than many similar national-level tools. EBI scores are also stratified by tract land cover type as per the National Land Cover Database (NLCD), controlling for urbanicity. The EBI was developed over the course of four stages: 1) literature review to identify potential indicators, 2) data source acquisition and indicator variable construction, 3) index creation, and 4) stratification by land cover type. For each potential indicator, data sources were assessed for completeness, update frequency, and availability. These indicators were: (1) particulate matter (PM2.5), (2) ozone, (3) Superfund National Priority List (NPL) locations, (4) Toxics Release Inventory (TRI) facilities, (5) Treatment, Storage, and Disposal (TSD) facilities, (6) recreational parks, (7) railways, (8) highways, (9) airports, and (10) impaired water sources. Indicators were statistically normalized and checked for collinearity. For each indicator, we computed and summed percentile ranking scores to create an overall ranking for each tract. Tracts having the same plurality of land cover type form a 'peer' group. We re-ranked the tracts into percentiles within each peer group for each indicator. The percentile scores were combined for each tract to obtain a stratified EBI. A higher score reveals a tract with increased environmental burden relative to other tracts of the same peer group. We compared our results to those of related indices, finding good convergent validity between the overall EBI and CalEnviroScreen 4.0. The EBI has many potential applications for research and use as a tool to develop public health interventions at a granular scale.

Standard rectal swabs as a surrogate sample for gut microbiome monitoring in intensive care.

BACKGROUND: The purpose of this study was to investigate the use of routinely available rectal swabs as a surrogate sample type for testing the gut microbiome and monitoring antibiotic effects on key gut microorganisms, of patients hospitalised in an intensive care unit. A metagenomic whole genome sequencing approach was undertaken to determine the diversity of organisms as well as resistance genes and to compare findings between the two sampling techniques. RESULTS: No significant difference was observed in overall diversity between the faeces and rectal swabs and sampling technique was not demonstrated to predict microbial community variation. More human DNA was present in the swabs and some differences were observed only for a select few anaerobes and bacteria also associated with skin and/or the female genitourinary system, possibly reflecting sampling site or technique. Antibiotics and collections at different times of admission were both considered significant influences on microbial community composition alteration. Detection of antibiotic resistance genes between rectal swabs and faeces were overall not significantly different, although some variations were detected with a potential association with the number of human sequence reads in a sample. CONCLUSION: Testing the gut microbiome using standard rectal swab collection techniques currently used for multi-resistant organism screening has been demonstrated to have utility in gut microbiome monitoring in intensive care. The use of information from this article, in terms of methodology as well as near equivalence demonstrated between rectal swabs and faeces will be able to support and potentially facilitate the introduction into clinical practice.

Extracorporeal Membrane Oxygenation for COVID-19-Associated Multisystem Inflammatory Syndrome in a 5-year-old.

Severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is associated with multisystem inflammatory syndrome in children (MIS-C) that ranges from mild symptoms to cardiopulmonary collapse. A 5-year-old girl presented with shock and a rapid decline in left ventricular function requiring intubation. SARS-CoV-2 was diagnosed by viral Polymerase Chain Reaction (PCR), and she received remdesivir and COVID-19 convalescent plasma. Initial echocardiogram (ECHO) demonstrated low normal left ventricular function and mild left anterior descending coronary artery dilation. She remained hypotensive, despite high-dose epinephrine and norepinephrine infusions as well as stress-dose hydrocortisone. Admission SARS-CoV-2 IgG assay was positive, meeting the criteria for MIS-C. An ECHO 9 hours after admission demonstrated a severe decline in left ventricular function. Due to severe cardiogenic shock, she was cannulated for venoarterial extracorporeal support (ECMO). During her ECMO course, she was treated with remdesivir, intravenous methylprednisolone, intravenous immunoglobulin, and anakinra. She was decannulated on ECMO day 7, extubated the following day, and discharged home 2 weeks later without respiratory or cardiac support. The use of ECMO for cardiopulmonary support for pediatric patients with MIS-C is feasible and should be considered early as part of the treatment algorithm for patients with severe cardiopulmonary dysfunction.

Implementing and Sustaining Bedside Shift Report for Quality Patient-Centered Care.

BACKGROUND: Two evidence-based practice projects and an innovative model provided best evidence and a framework for the implementation and sustainment of a bedside shift report (BSR) quality improvement project. PROBLEM: Without a standardized BSR process, there was a lack of Veteran involvement in care planning decisions and nurse dissatisfaction related to missed communication of pertinent patient information. APPROACH: Facilitators and barriers were identified and addressed during planning. Key elements of BSR were incorporated. After approval by shared governance, unit-based champions and leaders supported the change. Implementation began every 2 weeks on a different unit. OUTCOMES: Implementation was completed in 4 months for 11 units. After 15 months, there was consistent BSR on 82% of the units and improved patient satisfaction with nurses taking time to listen. CONCLUSIONS: Best evidence, unit-based champions, leadership support, project coordinators, and persistence are critical to implementing and sustaining practice change.

Non-invasive detection of high gamma band activity during motor imagery.

High gamma oscillations (70-150 Hz; HG) are rapidly evolving, spatially localized neurophysiological signals that are believed to be the best representative signature of engaged neural populations. The HG band has been best characterized from invasive electrophysiological approaches such as electrocorticography because of the increased signal-to-noise ratio that results when by-passing the scalp and skull. Despite the recent observation that HG activity can be detected non-invasively by electroencephalography (EEG), it is unclear to what extent EEG can accurately resolve the spatial distribution of HG signals during active task engagement. We have overcome some of the limitations inherent to acquiring HG signals across the scalp by utilizing individual head anatomy in combination with an inverse modeling method. We applied a linearly constrained minimum variance (LCMV) beamformer method on EEG data during a motor imagery paradigm to extract a time-frequency spectrogram at every voxel location on the cortex. To confirm spatially distributed patterns of HG responses, we contrasted overlapping maps of the EEG HG signal with blood oxygen level dependence (BOLD) functional magnetic resonance imaging (fMRI) data acquired from the same set of neurologically normal subjects during a separate session. We show that scalp-based HG band activity detected by EEG during motor imagery spatially co-localizes with BOLD fMRI data. Taken together, these results suggest that EEG can accurately resolve spatially specific estimates of local cortical high frequency signals, potentially opening an avenue for non-invasive measurement of HG potentials from diverse sets of neurologically impaired populations for diagnostic and therapeutic purposes.

The relationship between quality of life and coping strategies of adults with celiac disease adhering to a gluten-free diet.

In the United States, the prevalence of celiac disease has increased from 1 in 4,600 persons to 1 in 133 persons during the past 10 years. Although celiac disease can be managed by strict adherence to a gluten-free diet, dietary management can be challenging. A descriptive, correlational design was used to examine factors and perceived causes that interfere with adherence to a gluten-free diet, identify coping strategies, and examine the relationship between coping strategies and quality of life in 156 adults with a diagnosis of celiac disease. The Psychological General Well-Being Index and the Brief COPE were used to measure the major variables. Results indicated that problems outside the home interfere with dietary adherence. A moderate negative significant relationship (r [154] = -.46, p < .01) was found between quality of life and stress, with 54% of participants reporting a minimal amount of stress. Emotion-focused coping was found to have a significant negative effect on quality of life (H[18] = 56.67, p < .001). Implications for future research should include investigation of cognitive behavioral interventions to decrease the negative effects of stress on quality of life for adults with celiac disease adhering to a gluten-free diet.

Emergency: Variceal hemorrhage from esophageal varices associated with alcoholic liver disease.

Esophageal varices occur in about half of all people with alcoholic cirrhosis. About one-third of these will experience variceal hemorrhage, a life-threatening event. This article describes alcoholic cirrhosis and its complications, discusses the etiology of esophageal varices and the risk factors for hemorrhage, and addresses emergent treatment. Further treatment options, including endoscopic variceal ligation, endoscopic injection sclerotherapy, balloon tamponade, and transjugular intrahepatic portosystemic shunt placement, are also discussed.

Infection risk from the use of continuous local-anesthetic infusion pain pumps in aesthetic and reconstructive abdominal procedures.

Postoperative pain control after abdominal procedures can be an area of significant concern. Continuous local-anesthetic infusion pain pumps have been clearly documented in recent literature to provide effective early postoperative pain control, in addition to other benefits. Our goal was to evaluate any increase in the risk of infection with the use of pain pumps with aesthetic and reconstructive abdominal procedures. A retrospective chart review evaluated 159 patients who underwent abdominoplasty (with or without suction-assisted lipectomy), panniculectomy, or a transverse rectus abdominis myocutaneous (TRAM) flap for breast reconstruction. Information was collected on descriptive and demographic information, and the incidence of postoperative infection. Of the 159 patients who underwent abdominal procedures, 100 (62.9%) received the pain pump for postoperative pain control. None of those 100 patients developed an infection. Fifty-nine patients did not receive a pain pump, and 2 of those patients (3.3%) developed an infection. Overall, 1.3% (2 of 159) of patients in our study developed a postoperative infection. There is no increase in the risk of postoperative infection with the use of continuous local-anesthetic infusion pain pumps used after aesthetic and reconstructive abdominal procedures.

Postoperative seroma formation after abdominoplasty with placement of continuous infusion local anesthetic pain pump.

The most common complication after abdominoplasty is seroma formation. The incidence of seroma formation in abdominal procedures as a whole, including abdominoplasty, panniculectomy and transverse rectus abdominis myocutaneous flap abdominal donor sites, ranges from 1% to 38%. A recent concern among surgeons is the possibility of a causal relationship between the use of continuous infusion devices such as local anesthetic pain pumps and the development of seromas. A case of postoperative, persistent, recurrent seroma formation after abdominoplasty with the use of continuous infusion local anesthetic pain pump is presented. After several attempts at aspiration and drain catheter placement, only open surgical excision of the seroma cavity was found to be definitively effective in treating the development of seroma.

Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells.

The cellular source(s) and the clinical significance of persistent low-level viremia, below 50 HIV RNA copies per ml of plasma, achieved in many patients with high adherence to highly active antiretroviral therapy (HAART) remain unclear. Also, it is not clear if residual plasma HIVs during HAART can become predominant populations in the rebounding plasma viral loads after therapy interruption. Since, different HIV quasispecies tend to compartmentalize in various cell types and tissue locations in patients during chronic infection, the phylogenetic relationships between HIV sequences amplified from residual plasma viruses and CD4 T cells of five patients on long-term suppressive therapy were examined. Three of these patients stopped therapy voluntarily for 3 weeks, but only one of them demonstrated viral load rebound in plasma. In phylogenetic analyses, the residual plasma viruses were found to be distinct genetically from the majority of CD4 T cell-associated virus populations in four of five patients. The compartmental analyses revealed that in all patients, plasma- and CD4 T cell-derived viral sequences were compartmentalized separately. Interestingly, the plasma sequences obtained before and after HAART-off in two patients were produced apparently from the same compartment, which was different from the circulating CD4 T cell-compartment. These results suggest the possibility that residual plasma viruses in patients on long-term suppressive HAART may be produced persistently from a cellular source yet to be identified, and are capable of spreading quickly in vivo, accounting for the rapid rebound of viral loads in plasma after therapy interruption.

Continuous-infusion local anesthetic pain pump use and seroma formation with abdominal procedures: is there a correlation?

BACKGROUND: Seroma formation is the most commonly occurring complication in plastic surgery abdominal procedures. Continuous local anesthetic pain pump delivery systems are often used to decrease postoperative pain. An unreported concern with use of these devices in abdominal procedures is the effect of continuous fluid infiltration of the surgical site and a possible increase in the incidence of seroma formation. METHODS: The authors performed a retrospective chart review to evaluate all patients (n = 159) who underwent abdominal procedures (abdominoplasty, panniculectomy, and transverse rectus abdominis myocutaneous flap harvest) over a 3-year period. Patient charts were evaluated for sex, age, body mass index, procedure performed, surgeon, operation length, pain pump use, postoperative seroma formation, and any complications. In cases with pain pump use, catheter placement location, anesthetic medication and strength, continuous-infusion rate, and duration of pain pump use were also reviewed. If a postoperative seroma formation was identified, treatment and outcomes were also recorded. RESULTS: The overall seroma formation rate was 11.3 percent (18 of 159 patients). Other complications occurred at a rate of 2.5 percent (four of 159). The incidence of seroma was 11.0 percent (11 of 100) in patients with pain pump use versus 11.9 percent (7 of 59) in those who did not use a pain pump. There was no statistically significant difference (p = 0.9) in the incidence of seroma formation between those who did and did not use a pain pump device. CONCLUSION: There was no correlation between increased rate of seroma formation and use of a continuous-infusion local anesthetic pain pump system in our patient population.

Exposures to air pollutants during pregnancy and preterm delivery.

The association between preterm delivery (PTD) and exposure to air pollutants has recently become a major concern. We investigated this relationship in Incheon, Republic of Korea, using spatial and temporal modeling to better infer individual exposures. The birth cohort consisted of 52,113 singleton births in 2001-2002, and data included residential address, gestational age, sex, birth date and order, and parental age and education. We used a geographic information system and kriging methods to construct spatial and temporal exposure models. Associations between exposure and PTD were evaluated using univariate and multivariate log-binomial regressions. Given the gestational age, birth date, and the mother's residential address, we estimated each mother's potential exposure to air pollutants during critical periods of the pregnancy. The adjusted risk ratios for PTD in the highest quartiles of the first trimester exposure were 1.26 [95% confidence interval (CI), 1.11-1.44] for carbon monoxide, 1.27 (95% CI, 1.04-1.56) for particulate matter with aerodynamic diameter < or = 10 microm, 1.24 (95% CI, 1.09-1.41) for nitrogen dioxide, and 1.21 (95% CI, 1.04-1.42) for sulfur dioxide. The relationships between PTD and exposures to CO, NO2, and SO2 were dose dependent (p < 0.001, p < 0.02, p < 0.02, respectively) . In addition, the results of our study indicated a significant association between air pollution and PTD during the third trimester of pregnancy. In conclusion, our study showed that relatively low concentrations of air pollution under current air quality standards during pregnancy may contribute to an increased risk of PTD. A biologic mechanism through increased prostaglandin levels that are triggered by inflammatory mediators during exposure periods is discussed.

Sexual dysfunction in men after open or endovascular repair of abdominal aortic aneurysms.

Few studies have thoroughly investigated the incidence and detailed the degree of sexual disability after aortic aneurysm surgery. Reports prior to 1990 vary greatly in the incidence of postoperative dysfunction mostly because of nonstandardized methods of assessment. In this article, we compare the incidence of reported sexual dysfunction after aortic reconstruction, open and endovascular abdominal aortic aneurysm repair. Pertinent studies on sexual dysfunction following open and endovascular aortic aneurysm repair were identified from a MEDLINE search of English-language publications since 1966. Newer standardized methods of assessment have identified relatively high rates of sexual dysfunction prior to and after intervention. Aortic aneurysm patients have a baseline incidence of sexual dysfunction of approximately 30%, which doubles over the next 7 years. Patients who had open aortic operations reported significantly increased sexual dysfunction during the first postoperative year. Endovascular repair with unilateral internal iliac occlusion results in new sexual dysfunction in approximately 10% of patients, but this increases significantly with bilateral internal iliac occlusion. When compared with open operation, the incidence of sexual dysfunction is lower overall in patients with endovascular aortic aneurysm repairs, which includes those who have internal iliac artery occlusion, but it is increased with bilateral iliac occlusion. Surgeons should be aware of the preoperative prevalence of sexual dysfunction in patients undergoing aortic procedures.

Mind-body and mind-gut connection in inflammatory bowel disease.

A bidirectional pathway between the brain and immune system known as psychoneuroimmunology has been the basis of much research and discussion within this interdisciplinary field over the past 25 years. An overly aggressive immune response in inflammatory bowel disease makes the psychoneuroimmunology framework applicable in establishing evidence-based outcomes. Mind-body and mind-gut connections and behavioral interventions can influence outcomes for patients with inflammatory bowel disease. Professional nurses can help develop behavioral interventions to improve quality of life with symptom management for this patient population. Healthcare providers and patients through partnerships should consider the effects of psychosocial factors in manifestations of health and illness.

Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells.

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing drug cytotoxicity. In this study, curcumin was tested for its potential ability to modulate the expression and function of Pgp in the multidrug-resistant human cervical carcinoma cell line KB-V1. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) showed that treatment with 1, 5, and 10 microM curcumin for up to 72hr was able to significantly lower Pgp expression in KB-V1 cells. Curcumin (1-10 microM) decreased Pgp expression in a concentration-dependent manner and was also found to have the same effect on MDR1 mRNA levels. The effect of curcumin on Pgp function was demonstrated by rhodamine 123 (Rh123) accumulation and efflux in Pgp-expressing KB-V1 cells. Curcumin increased Rh123 accumulation in a concentration-dependent manner (1-55 microM) and inhibited the efflux of Rh123 from these cells, but did not affect the efflux of Rh123 from the wild-type drug-sensitive KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with an increased intracellular accumulation of Rh123. In addition, curcumin inhibited verapamil-stimulated ATPase activity and the photoaffinity labeling of Pgp with the prazosin analog [125I]iodoarylazidoprazosin in a concentration-dependent manner, demonstrating that curcumin interacts directly with the transporter. Thus, curcumin seems to be able to modulate the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells. In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells.