The origins of allergy from a systems approach.

OBJECTIVE: The origins of allergic diseases have traditionally been explained by immunoglobulin E-mediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support a broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases, such as (1) inherent epithelial barrier dysfunction; (2) loss of immune tolerance; (3) disturbances in the gut; and (4) organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease. DATA SOURCES: We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in the specific microbiome, and inherent genetic predisposition. STUDY SELECTIONS: We performed a literature search targeting primary and review articles. RESULTS: We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders and evaluated immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior. CONCLUSION: Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a randomised controlled trial.

STUDY DESIGN: Randomised double-blind factorial-design placebo-controlled trial. OBJECTIVE: Urinary tract infections (UTIs) are common in people with spinal cord injury (SCI). UTIs are increasingly difficult to treat due to emergence of multi-resistant organisms. Probiotics are efficacious in preventing UTIs in post-menopausal women. We aimed to determine whether probiotic therapy with Lactobacillus reuteri RC-14+Lactobacillus GR-1 (RC14-GR1) and/or Lactobacillus rhamnosus GG+Bifidobacterium BB-12 (LGG-BB12) are effective in preventing UTI in people with SCI. SETTING: Spinal units in New South Wales, Australia with their rural affiliations. METHODS: We recruited 207 eligible participants with SCI and stable neurogenic bladder management. They were randomised to one of four arms: RC14-GR1+LGG-BB12, RC14-GR1+placebo, LGG-BB12+ placebo or double placebos for 6 months. Randomisation was stratified by bladder management type and inpatient or outpatient status. The primary outcome was time to occurrence of symptomatic UTI. RESULTS: Analysis was based on intention to treat. Participants randomised to RC14-GR1 had a similar risk of UTI as those not on RC14-GR1 (HR 0.67; 95% CI: 0.39-1.18; P = 0.17) after allowing for pre-specified covariates. Participants randomised to LGG-BB12 also had a similar risk of UTI as those not on LGG-BB12 (HR 1.29; 95% CI: 0.74-2.25; P = 0.37). Multivariable post hoc survival analysis for RC14-GR1 only vs. the other three groups showed a potential protective effect (HR 0.46; 95% CI: 0.21-0.99; P = 0.03), but this result would need to be confirmed before clinical application. CONCLUSION: In this RCT, there was no effect of RC14-GR1 or LGG-BB12 in preventing UTI in people with SCI.

Twenty-Year Comparative Analysis of Patients With Autoimmune Liver Diseases on Transplant Waitlists.

BACKGROUND & AIMS: The rarity of autoimmune liver disease poses challenges to epidemiology studies. However, waitlists for liver transplantation can be used to study patients with end-stage liver diseases. We used these waitlists to assess trends in numbers and demographics of patients awaiting liver transplant for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH). METHODS: We collected data from UK and US national registries for all adults on liver transplant waitlists, from January 1, 1995, through December 31, 2014. We analyzed data from patients with PBC (n = 1434 in the United Kingdom and n = 5598 in the United States), PSC (n = 1093 in the United Kingdom and n = 6820 in the United States), and AIH (n = 538 in the United Kingdom and n = 4949 in the United States). Numbers of listings per year were adjusted to the estimated populations during each year. Regression analyses were used to examine trends and comparative statistics were used to evaluate differences in individual characteristics among groups. RESULTS: Over the total study period, listings for PBC were 1.2 and 1.0 per million population per year in the United Kingdom and United States, respectively; for PSC, 0.9 and 1.2 per million population per year; and for AIH, 0.5 and 0.8 per million population per year. Over the period studied, numbers of listings for PBC decreased by 50% in both countries; changes in numbers of listings for PSC and AIH were smaller and not consistent between countries. By 2014, PSC had become the leading indication for liver transplantation among patients with autoimmune liver diseases in both countries. Median patient ages at time of listing were lower than those reported as median age of diagnosis for AIH and PBC. The ratio of women:men with PBC decreased by almost 50% from 1995 through 2014. Men with PSC were placed on the waitlist with higher disease severity scores than women in both countries. Among patients with PBC, those of black race were under-represented on waitlists from both countries. Among patients with PSC, Hispanics were under-represented on waitlists in the United States. Patients of non-white races were placed on waitlists at younger ages for all diseases; age differences in waitlist placement varied by up to 10 years, depending on race, among patients with PBC. CONCLUSIONS: In an analysis of data collected from UK and US national liver transplant registries over 20 years, we found that PSC has become the leading indication for liver transplantation among patients with autoimmune liver diseases. Numbers of patients with PBC placed on waitlists, and the ratio of women:men with PBC, each decreased by almost 50%, possibly due to increased treatment with ursodeoxycholic acid. Within groups of patients on the transplant waitlist for PBC, PSC, or AIH, we found differences in age, sex, disease severity scores, and ethnicity between diseases and countries that require further study.

Epidemiology of preoperative hematologic assessment of children cared for in a pediatric emergency department.

OBJECTIVE: To assess frequency of preoperative hematologic testing in a tertiary care pediatric emergency department (PED) and how often these values predict clinical outcome or change management decisions. METHODS: Single-center retrospective cohort study in a tertiary-care children's hospital PED. Patients 0-18years old, presenting between July 1, 2009-July 1, 2011, ultimately undergoing a surgical procedure within 48h of presentation were included. Patients were defined as having "preoperative" hematologic assessment if these studies were performed solely because the child was going to the operative suite. Patients who met trauma team activation criteria, underwent neurosurgical procedures, or had laboratory studies performed prior to PED arrival were excluded. The primary outcome was the prevalence of preoperative laboratory assessment. RESULTS: 528 children were included, of whom 301 (57%) underwent preoperative hematologic laboratory evaluations. Of these 301 patients, 115 (38%) had abnormal hematologic parameters, and only 3 (1%) of these patients had their perioperative management changed. One additional child had intraoperative bleeding that required blood products but did not undergo preoperative hematologic assessment. All four children had medical histories that would have identified their risk for perioperative bleeding events. CONCLUSION: Preoperative hematologic laboratory assessment occurs frequently in children initially cared for in a tertiary care pediatric emergency department who subsequently undergo operative interventions. Although age-based abnormal hematologic values are often found, rarely are these abnormalities clinically significant. This study suggests that children cared for in a PED without a history concerning for an increased risk of perioperative bleeding does not require preoperative hematologic assessment.

The Minnesota Medical Operations Coordination Center: A COVID-19 Statewide Response to Ensure Access to Critical Care and Medical-Surgical Beds.

BACKGROUND: COVID-19 led to unprecedented inpatient capacity challenges, particularly in ICUs, which spurred development of statewide or regional placement centers for coordinating transfer (load-balancing) of adult patients needing intensive care to hospitals with remaining capacity. RESEARCH QUESTION: Do Medical Operations Coordination Centers (MOCC) augment patient placement during times of severe capacity challenges? STUDY DESIGN AND METHODS: The Minnesota MOCC was established with a focus on transfer of adult ICU and medical-surgical patients; trauma, cardiac, stroke, burn, and extracorporeal membrane oxygenation cases were excluded. The center operated within one health care system's bed management center, using a dedicated 24/7 telephone number. Major health care systems statewide and two tertiary centers in a neighboring state participated, sharing information on system status, challenges, and strategies. Patient volumes and transfer data were tracked; client satisfaction was evaluated through an anonymous survey. RESULTS: From August 1, 2020, through March 31, 2022, a total of 5,307 requests were made, 2,008 beds identified, 1,316 requests canceled, and 1,981 requests were unable to be fulfilled. A total of 1,715 patients had COVID-19 (32.3%), and 2,473 were negative or low risk for COVID-19 (46.6%). COVID-19 status was unknown in 1,119 (21.1%). Overall, 760 were patients on ventilators (49.1% COVID-19 positive). The Minnesota Critical Care Coordination Center placed most patients during the fall 2020 surge with the Minnesota Governor's stay-at-home order during the peak. However, during the fall 2021 surge, only 30% of ICU patients and 39% of medical-surgical patients were placed. Indicators characterizing severe surge include the number of Critical Care Coordination Center requests, decreasing placements, longer placement times, and time series analysis showing significant request-acceptance differences. INTERPRETATION: Implementation of a large-scale Minnesota MOCC program was effective at placing patients during the first COVID-19 pandemic fall 2020 surge and was well regarded by hospitals and health systems. However, under worsening duress of limited resources during the fall 2021 surge, placement of ICU and medical-surgical patients was greatly decreased.

Clinical Utility of Patient-Reported Outcome Measures Used for Tendon and Nerve Transfers for Tetraplegia in New Zealand.

Purpose: This study determines the clinical utility of patient-reported outcome measures used to measure outcomes of upper extremity (UE) reconstructive procedures in individuals with tetraplegia. The patient-reported outcome measures are the Canadian Occupational Performance Measure, the Capabilities of Upper Extremity Questionnaire (CUE-Q), and the Personal Wellbeing Index. Methods: Retrospective data of 43 individuals with spinal cord injury (SCI) levels C4-C7 tetraplegia, and American Spinal Injury Association Impairment Scale grades A-D who had upper limb reconstructive surgery were reviewed. Participants were grouped according to their SCI level and resultant surgical procedures into higher SCI severity and lower SCI severity groups. Results: The mean age of participants was 26.3 years (SD 13.4; range 13-64 years). The higher-severity SCI group required elbow and hand reconstruction surgery, whereas the lower-severity group only required hand reconstruction surgery. Important differences in Canadian Occupational Performance Measure priorities were identified between the higher and lower SCI severity groups. Question redundancy was evident with the CUE-Q. The self-report Personal Wellbeing Index captures the possible impacts of improved UE function on an individual's perceived sense of personal wellbeing. Conclusions: In this patient-reported outcome measure analysis, we found that the level of impairment influences patient priorities. Functional measures ought to consider UE impairment and personal wellbeing as a construct in this population, given the demands of surgery. Type of Study/Level of Evidence: Prognostic II.

Cognitive Reserve and Its Association with Cognitive and Mental Health Status following an Acute Spinal Cord Injury.

BACKGROUND: Mild cognitive impairment (MCI) is a common secondary condition associated with spinal cord injury (SCI). Cognitive reserve (CR) is believed to protect against cognitive decline and can be assessed by premorbid intelligence (pmIQ). Despite the potential utility of pmIQ as a complementary metric in the evaluation of MCI in SCI, this approach has been infrequently employed. The purpose of this study was to examine the association between MCI and pmIQ in adults with SCI with the aim of exploring the potential value of pmIQ as a marker of CR in this population. METHODS: Cognitive function was assessed on three occasions in adults with SCI over a 12-month period post-injury, and pmIQ was assessed once at baseline. Demographic and mental health measures were also collected, and logistic regression was conducted to determine the strength of association between pmIQ and MCI while adjusting for factors such as mental health and age. RESULTS: The regression analysis revealed that at the time of admission to SCI rehabilitation, the MCI assessed by a valid neurocognitive screen was strongly associated with pmIQ. That is, if a person has MCI, there was 5.4 greater odds (p < 0.01) that they will have poor pmIQ compared to a person without MCI after adjustment for age and mental health. CONCLUSIONS: The assessment of CR is an important area that should be considered to improve the process of diagnosing MCI in adults with an acute SCI and potentially facilitate earlier intervention to slow or prevent cognitive decline.

The Hairline Brow Lift.

Effective rejuvenation of the upper face results when effective brow repositioning is combined with maintenance or improvement of brow shape. Endoscopic brow lift techniques have increased in popularity as surgeons have investigated less invasive surgical procedures. This article provides a comparison of hairline brow lift with other open and endoscopic techniques used for improving brow position. It includes a detailed description of hairline brow lift with videos illustrating the authors' preferred technique. It also provides a description of ideal candidates including indications and contraindications to procedure, and common modifications to technique used in select patient populations.

Improving screening systems of autism using data sampling.

OBJECTIVES: Autism Spectrum Disorder (ASD) is a complex range of neurodegenerative conditions that impact individuals' social behaviour and communication skills. However, ASD data often contains far more controls than cases. This poses a serious challenge when creating classification models due to deriving models that favour controls during the classification of individuals. This problem is known as class imbalance, and it may reduce the performance in classification models derived by machine learning (ML) techniques due to individuals may remain undetected. METHODS: ML appears to help in the distressing disorder by improving outcome quality besides speeding up the access to early diagnosis and consequential treatment. A screening dataset that consists of over 1100 instances was used to perform extensive quantitative analysis using different data resampling techniques and according to specific evaluation metrics. We measure the effect of class imbalance on autism screening performance using different data resampling techniques with a ML classifier and with respect to sensitivity, specificity, and F1-measure. We would like to know which resampling methods work well in balancing autism screening data. RESULTS: The results reveal that data resampling, and especially oversampling, improve results derived by the considered ML classifier. More importantly, there was superiority in terms of sensitivity and specificity for models derived by Naive Bayes classifier when oversampling methods have been used for data pre-processing on the autism data considered. CONCLUSION: The results reported encourages further improvement of the design and implementation of ASD screening systems using intelligent technology.

Food Allergies: An Example of Translational Research.

Food allergies have been rising in prevalence since the 1990s, imposing substantial physical, psychosocial, and economic burdens on affected patients and their families. Until recently, the only therapy for food allergy was strict avoidance of the allergenic food. Recent advances in translational studies, however, have led to insights into allergic sensitization and tolerance. This article provides an overview of cutting-edge research into food allergy and immune tolerance mechanisms utilizing mouse models, human studies, and systems biology approaches. This research is being translated and implemented in the clinical setting to improve diagnosis and reduce food allergy's public health burden.

Identifying Predictors of Higher Acute Care Costs for Patients With Traumatic Spinal Cord Injury and Modeling Acute Care Pathway Redesign: A Record Linkage Study.

STUDY DESIGN: Record linkage study using healthcare utilization and costs data. OBJECTIVE: To identify predictors of higher acute-care treatment costs and length of stay for patients with traumatic spinal cord injury (TSCI). SUMMARY OF BACKGROUND DATA: There are few current or population-based estimates of acute hospitalization costs, length of stay, and other outcomes for people with TSCI, on which to base future planning for specialist SCI health care services. METHODS: Record linkage study using healthcare utilization and costs data; all patients aged more than or equal to 16 years with incident TSCI in the Australian state of New South Wales (June 2013-June 2016). Generalized Linear Model regression to identify predictors of higher acute care treatment costs for patients with TSCI. Scenario analysis quantified the proportionate cost impacts of patient pathway modification. RESULTS: Five hundred thirty-four incident cases of TSCI (74% male). Total cost of all acute index episodes approximately AUD$40.5 (95% confidence interval [CI] ±4.5) million; median cost per patient was AUD$45,473 (Interquartile Range: $15,535-$94,612). Patient pathways varied; acute care was less costly for patients admitted directly to a specialist spinal cord injury unit (SCIU) compared with indirect transfer within 24 hours. Over half (53%) of all patients experienced at least one complication during acute admission; their care was less costly if they had been admitted directly to SCIU. Scenario analysis demonstrated that a reduction of indirect transfers to SCIU by 10% yielded overall cost savings of AUD$3.1 million; an average per patient saving of AUD$5,861. CONCLUSION: Direct transfer to SCIU for patients with acute TSCI resulted in lower treatment costs, shorter length of stay, and less costly complications. Modeling showed that optimizing patient-care pathways can result in significant acute-care cost savings. Reducing potentially preventable complications would further reduce costs and improve longer-term patient outcomes. LEVEL OF EVIDENCE: 3.

Dietary flavonoids and colorectal adenoma recurrence in the Polyp Prevention Trial.

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non-steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; P(trend) = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence.

Clinical Features of Extrapulmonary Sarcoidosis Without Lung Involvement.

BACKGROUND: Compared with pulmonary sarcoidosis, sarcoidosis without lung involvement may involve other immunopathologic mechanisms and be associated with other demographic and clinical features. METHODS: This was a retrospective analysis of clinical data collected in real time on 1,686 patients with biopsy-proven sarcoidosis from two large university sarcoidosis outpatient clinics in the United States. We compared differences in demographics characteristics and clinical presentation between pulmonary and nonpulmonary sarcoidosis (NPS). Patients were considered to have NPS only if they had normal chest imaging and no features consistent with pulmonary involvement on the basis of currently accepted criteria. RESULTS: A total of 8.3% of this sarcoidosis cohort met criteria for NPS. NPS was significantly more common in white than black patients, and more common in women than men. The skin was the most common organ involved, and was observed in nearly one-half of patients with NPS. Isolated skin sarcoidosis was the overwhelmingly most common pattern of organ involvement seen in the NPS group (25%), and no other pattern of involvement was found in more than 5% of patients with NPS. CONCLUSIONS: Significant demographic and sex differences were observed between patients with pulmonary and nonpulmonary sarcoidosis. These differences reflect previous data concerning differences between patients with skin and lung sarcoidosis because the skin was the major organ involved with NPS. Although the lungs are likely the primary site of exposure in pulmonary sarcoidosis, the high prevalence of skin involvement in NPS suggests the skin is the most conducive site of antigen capture outside of the respiratory tract.

The Expanded Use of Autoaugmentation Techniques in Oncoplastic Breast Surgery.

BACKGROUND: Autoaugmentation techniques have been applied to oncoplastic reductions to assist with filling larger, more remote defects, and to women with smaller breasts. The purpose of this report is to describe the use of autoaugmentation techniques in oncoplastic reduction and compare the results with those of traditional oncoplastic reduction. METHODS: The authors queried a prospectively maintained database of all women who underwent partial mastectomy and oncoplastic reduction between 1994 and October of 2015. The autoaugmentation techniques were defined as (1) extended primary nipple autoaugmentation pedicle, and (2) primary nipple pedicle and secondary autoaugmentation pedicle. Comparisons were made to a control oncoplastic group. RESULTS: There were a total of 333 patients, 222 patients (67.7 percent) without autoaugmentation and 111 patients (33 percent) with autoaugmentation (51 patients with an extended autoaugmentation pedicle, and 60 patients with a secondary autoaugmentation pedicle). Biopsy weight was smallest in the extended pedicle group (136 g) and largest in the regular oncoplastic group (235 g; p = 0.017). Superomedial was the most common extended pedicle, and lateral was the most common location. Inferolateral was the most common secondary pedicle for lateral and upper outer defects. There were no significant differences in the overall complication rate: 15.5 percent in the regular oncoplastic group, 19.6 percent in the extended pedicle group, and 20 percent in the secondary pedicle group. CONCLUSIONS: Autoaugmentation techniques have evolved to manage complex defects not amenable to standard oncoplastic reduction methods. They are often required for lateral defects, especially in smaller breasts. Autoaugmentation can be performed safely without an increased risk of complications, broadening the indications for breast conservation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.