Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.

INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis. RESULTS: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC. CONCLUSIONS: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.

Language Access and Orofacial Pain.

Clear and effective communication is vital to quality patient care. More than 66 million Americans (21.5%) speak a language other than English at home, with more than 25 million (8.2%) speaking English "less than very well." Addressing language differences in the orofacial pain setting is of utmost importance to care quality, treatment outcomes, and overall health equity. In the case presented, language-related communication challenges affect the diagnosis and management of a patient with orofacial pain. This case highlights the significance of language discordance in the clinical setting and demonstrates the need for greater language access in the orofacial pain field.

Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders.

BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes.

BACKGROUND: Treatment of hypereosinophilic syndrome (HES) often requires the use of immunomodulators with substantial side effect profiles. The emergence of biologics offers an alternative treatment modality. OBJECTIVE: To examine real-world practice data to describe the safety and consequences of various biologics suspected to directly or indirectly affect eosinophilic inflammation for the treatment of HES. METHODS: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater without a secondary cause; (2) clinical manifestations attributable to the eosinophilia; and (3) having received mepolizumab (anti-IL-5), benralizumab (afucosylated anti-IL-5 receptor α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside a placebo-controlled clinical trial. RESULTS: Of the 151 courses of biologics prescribed for 121 patients with HES, 59% resulted in improved HES symptoms and 77% enabled tapering of other HES medications. Overall, 105 patients were receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the glucocorticoid dose by a median reduction of 10 mg of daily prednisone equivalents. Biologics were generally safe and well-tolerated other than infusion reactions with alemtuzumab. Thirteen of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. CONCLUSIONS: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

Pain Management for Dental Medicine in 2021: Opioids, Coronavirus and Beyond.

Over the past year our attention has inevitably been on the coronavirus pandemic, the health and welfare of our families, patients, and office staffs as well as the re-opening of our dental practices. In addition, the opioid crisis continues, is very likely to worsen as a result of the pandemic and continues to be a challenge to Dentistry. National public health issues and healthcare disparities continue and have created a global concern for providing evidence-based, adequate pain management in the dental setting. We have brought together a group of national thought leaders and experts in this field who will share their insights on the current state of opioid prescribing in Dentistry and describe some of the exciting work being done in advancing pain management. The learning objectives for this conference proceedings were: Describing the implications of current public health concerns for safe and effective pain management in dental medicine.Identifying risk factors and understanding the current guidelines for the use of opioid and non-opioid medications in dental medicine.Analyzing the interprofessional collaborations necessary for effective pain management in dental medicine.Recognizing the challenges and opportunities brought about by the COVID-19 pandemic for the dental profession.Applying evidence-based strategies for managing the complex pain patient in the dental setting.Appraising new and future modalities for the assessment and management of orofacial pain.

Whole Person, Whole Journey: Developing a Person-Centred Regional Dementia Strategy.

We present the development of a regional dementia strategy in Southwestern Ontario, Canada. We worked with stakeholders in a regional health authority to develop a dementia strategy. We conducted interviews with persons with dementia and their care partners (n = 26) and health care administrators and policy makers (n = 33); and administered a priority-setting survey (n = 64). Both participant groups identified provider compassion, professionalism, and care in the early stages of dementia as system strengths. Both groups also highlighted a need for more integration and coordination, a need for more person-centred care, support for care partners, and more flexibility in the provision and receipt of services. The highest-ranked priorities were improving care partner support, improving access to care, and improving system-wide quality. We integrate these strengths, needs, and priorities in a strategic framework, "Whole Person, Whole Journey". Organizations developing a dementia strategy may use this framework as a springboard for their own work.

Effectiveness, Safety, and Predictors of Response to Botulinum Toxin Type A in Refractory Masticatory Myalgia: A Retrospective Study.

PURPOSE: Masticatory muscle pain disorders respond well to conservative therapy; however, in some patients the pain becomes refractory. Botulinum toxin type A (BoT-A) therapy has been shown to be an effective modality in the management of refractory headache disorders. Conversely, there are conflicting reports in the literature regarding the efficacy, safety, and predictors of therapeutic response to BoT-A therapy for management of refractory masticatory muscle pain. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent at least 2 injection cycles of 100 U of BoT-A for refractory masticatory myalgia in the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, between May 2012 and June 2016. Information regarding demographic, diagnostic, and therapeutic characteristics was extracted and analyzed. The χ2 test was used for analysis between independent and dependent variables. Forward step-wise-type logistic regression analysis was conducted to determine the predictors of outcome. RESULTS: Among 116 participants, 30.6% reported significant relief in pain for a mean period of 10.1 weeks. A total of 16.4% of participants reported at least 1 adverse effect. The effectiveness of the BoT-A therapy was found to be statistically associated with the presence of muscle hypertrophy (P = .004), range of motion (P = .02), concurrent use of opioid analgesics (P = .003), and local anesthetic trigger-point injections (P = .003). Logistic regression analyses suggested that the presence of muscle hypertrophy and occurrence of adverse effects were predictors of positive outcome. On the contrary, concurrent use of opioid analgesics was found to be a predictor for no or minimal relief. CONCLUSIONS: BoT-A therapy provides significant relief for approximately one third of patients with refractory masticatory muscle pain. Therapy is associated with a mild risk of adverse effects. The presence of muscle hypertrophy, occurrence of an adverse effect, and concurrent use of opioid analgesics were found to be predictors of outcome response.

A review of Canadian and international dementia strategies.

To inform future strategy development in Canada and other jurisdictions, we undertook an Internet search to identify existing national and Canadian provincial dementia strategies and their major themes. Twenty-two dementia strategies were identified through an Internet search, supplemented by hand searches of reference lists of retrieved documents. Thematic analysis identified 17 strategic themes; common themes included improved diagnoses and assessments, increased access to care, and improved education of the healthcare workforce. This review reinforces the importance of a multi-faceted response to dementia and illustrates that, despite variation in needs across populations and geographies, there are many common priorities. The strategic themes identified in this review may provide a useful starting point for the development of new national strategies or, alternatively, as a check to determine if important priority areas have been missed in strategy development.

Using a dual-task protocol to investigate motor and cognitive performance in healthy children and youth.

OBJECTIVES: Mild traumatic brain injury (or concussion) is a prevalent yet understudied health concern in children and youth. This injury can cause dysfunction in both motor and cognitive domains; however, most literature focuses on single-task neuropsychological tests which only assess cognition. Although dual-task research on concussed children and youth is needed as many daily activities require both motor and cognitive domains, we must first investigate whether performing simultaneous motor and cognitive tasks of varied complexity impact these domains in healthy children and youth. PARTICIPANTS AND DESIGN: Data collected from 106 healthy children and youth (5-18 years) created a normative dataset. Participants performed motor (postural stability) and cognitive (visual attention) tasks under single- and dual-task conditions. The cognitive task difficulty remained constant while the motor task had four conditions of increasing difficulty. The relationship between the number of correct responses (cognitive performance) and sway index (motor performance) was determined using two repeated measures ANOVAs (p<0.05). RESULTS: Dual-task conditions resulted in reduced postural stability, with greater differences on the foam surface (F2,206=16.070, p<0.0005). No statistically significant differences were observed in attention (F4,101=0.713, p=0.584). CONCLUSIONS: Postural stability decreased under dual-task conditions, but attention was maintained or improved. Consequently, attention took precedence over postural control when performing tasks concurrently, demonstrating the ability for dual-task methodology to isolate specific processes. This study provides a normative dataset to be used during clinical management to identify functional deficits following concussion and acts as a starting point to explore dual-task protocols in children and youth following concussion.

Successful Doxycycline Therapy in a Patient With Escherichia coli and Multidrug-Resistant Klebsiella pneumoniae Urinary Tract Infection.

OBJECTIVE: To report on a patient with a symptomatic, polymicrobial Escherichia coli and multidrug-resistant (MDR), extended-spectrum ß-lactamase (ESBL)-positive Klebsiella pneumoniae urinary tract infection (UTI) who was successfully treated with oral doxycycline hyclate. CASE SUMMARY: A 70-year-old white male inpatient with a history of recurrent UTI, type 2 diabetes, hypertension, obesity, and diverticular disease was diagnosed with UTI and empirically treated with oral ciprofloxacin. Symptoms persisted 2 days later, and the patient was transitioned to amoxicillin/clavulanate by a different provider. The next day, upon receipt of the urine culture and susceptibility panel revealing E coli and MDR, ESBL-positive K pneumoniae infection, treatment was switched to doxycycline hyclate, which resulted in clinical improvement. DISCUSSION: Complicated UTI involving multiple pathogens requires careful clinical judgment to select the appropriate antimicrobial agent, improve clinical outcomes, and prevent resistance. Treatment with doxycycline was based on the susceptibility panel and local resistance patterns. Advantages of doxycycline for UTI include its oral formulation, wide spectrum of activity, ability to achieve high concentration in the urine, and low toxicity. CONCLUSION: Doxycycline hyclate may be an effective treatment option for patients with susceptible MDR UTI.

Haemophagocytic lymphohistiocytosis: A fulminant syndrome associated with multiorgan failure and high mortality that frequently masquerades as sepsis and shock.

Acquired haemophagocytic lymphohistiocytosis (HLH) is a condition involving cytokine overproduction by defective cytotoxic T lymphocytes and natural killer cells, resulting in life-threatening cytopenias and multiorgan infiltration and dysfunction. Triggers for acquired HLH vary and include viruses, malignancies and autoimmune conditions. Recent reports suggest that HLH may be underdiagnosed owing to variable clinical presentations, diagnostic criteria and a low level of awareness on the part of medical personnel, thus delaying prompt treatment and contributing to high mortality rates. Five patients in whom acquired HLH was diagnosed, following bone marrow investigations, for the period of May - September 2013 are presented. All were at an advanced stage of their disease at time of diagnosis. The three patients who were HIV-positive had a coexisting malignancy at the time of HLH diagnosis, which may have triggered HLH. A definite trigger was not identified in the remaining two HIV-negative patients despite early concerns regarding autoimmune disease. Two patients received timeous diagnosis, started chemotherapy and are currently improving. The remaining three succumbed to their illness. Adult acquired HLH may be more common in the acute care setting than currently appreciated. As awareness of this condition and its treatment is currently low, it may remain undiagnosed until the disease has evolved into multiorgan failure. Fever in the absence of infectious agents, marked hyperferritinaemia, unexplained cytopenias, organomegaly or liver dysfunction should raise the suspicion of HLH. Timeous introduction of therapy will improve outcomes.

Pain and temporomandibular disorders: a pharmaco-gender dilemma.

Gender is the biggest risk factor in the development of temporomandibular disorders (TMD) and orofacial pain. Gender differences in pain thresholds, temporal summation, pain expectations, and somatic awareness exist in patients with chronic TMD or orofacial pain. There are gender differences in pharmacokenetics and pharmacodynamics of medications used to treat pain. A better understanding of the mechanisms that contribute to the increased incidence and persistence of chronic pain in females is needed. Future research will elucidate the sex effects on factors that protect against developing pain or prevent debilitating pain. Gender-based treatments for TMD and orofacial pain treatment will evolve from the translational research stimulated by this knowledge.

Zinc supplementation does not alter sensitive biomarkers of copper status in healthy boys.

The tolerable upper intake levels (UL) for zinc for children were based on limited data and there is concern that the UL may be set too low. The first effect of excessive zinc intake is a reduction in copper status. The primary objective of this study was to examine the effect of zinc supplementation on copper status in children. Healthy, 6- to 8-y-old boys from Ontario, Canada were assigned to take a placebo (n = 10) or 5 mg (n = 10), 10 mg (n = 9), or 15 mg (n = 8) of zinc supplement daily for 4 mo in a double-blinded, placebo-controlled, randomized trial. Biochemical measures were evaluated at baseline and after 2 and 4 mo of supplementation. Food records were completed near the baseline and 4-mo visits. Age and anthropometric measurements did not differ (P > 0.05) between treatment groups at baseline. Mean zinc intakes from food alone (10.9-14.8 mg zinc/d) approached or exceeded the UL of 12 mg/d. Compared with the placebo group, the zinc groups had a greater change in the urine zinc:creatinine ratio at 4 mo (P = 0.02). Traditional (plasma copper and ceruloplasmin activity) and more sensitive biomarkers of copper status, including erythrocyte SOD1 activity and the erythrocyte CCS:SOD1 protein ratio, were unchanged in zinc-supplemented boys, demonstrating that copper status was not depressed. Serum lipid measures and hemoglobin concentrations were also unaffected and gastrointestinal symptoms were not reported. These data provide evidence in support of the need for reexamining the current UL for zinc for children.

Sexual issues in special populations: geriatric oncology - sexuality and older adults.

OBJECTIVE: To provide an overview of sexuality and sexual expression in older adult cancer survivors and to outline implications for nursing and interdisciplinary practice. DATA SOURCES: Research articles, abstracts, reviews, and clinical expertise. CONCLUSION: Unique features of sexuality in late life provide evidence to support clinical exploration of sexuality for older adult cancer survivors. Approaches to intervention with older adult cancer survivors are predicated on adaptation of best practices in sexuality and sexual health to create care that is sensitive to age and generation. Targeted research in sexuality for older adult cancer survivors includes intimacy, relationship, sexual experience, and imbedded sexual behavior. IMPLICATIONS FOR NURSING PRACTICE: Nurses can improve the care of older adults with cancer by careful consideration of intimacy and sexuality using standards of practice with younger adults integrated with understanding of issues unique to later life.

Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome.

CONTEXT: Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH). OBJECTIVE: The objective of the study was to determine the prevalence and characteristics of NASH and abnormal aminotransferase activity in women with PCOS. DESIGN: The study is a retrospective chart review. SETTING: The setting is an academic endocrinology clinic. PATIENTS: Patients were 200 women with PCOS, defined as irregular menses and hyperandrogenism. MAIN OUTCOME MEASURES: Biopsy-documented NASH and aminotransferase levels were the main outcome measures. RESULTS: Fifteen percent (29 of 200) had aspartate aminotransferase and/or alanine aminotransferase more than 60 U/liter. Women with aminotransferase elevations had lower high-density lipoprotein (HDL) (41 vs. 50 mg/dl, P = 0.006), higher triglycerides (174 vs. 129 mg/dl, P = 0.024), and higher fasting insulin (21 vs. 12 microIU/ml, P = 0.036) compared with women with normal aminotransferases. Six women (mean age 29 yr) with persistent aminotransferase elevations underwent liver biopsy. All six had NASH with fibrosis. Compared with the 194 of 200 PCOS women who did not undergo biopsy, women with biopsy-documented NASH had lower HDL (median 34 vs. 50 mg/dl, P < 0.001), and higher triglycerides (245 vs. 132 mg/dl, P = 0.025), fasting insulin (26 vs. 13 microIU/ml, P = 0.038), aspartate aminotransferase (144 vs. 22 U/liter, P < 0.001), and alanine aminotransferase (143 vs. 28 U/liter, P < 0.001). CONCLUSION: Abnormal aminotransferase activity is common in women with PCOS. Low HDL, high triglycerides, and high fasting insulin were associated with abnormal aminotransferase activity. Some women already had evidence of NASH with fibrosis. Further studies are needed to evaluate whether to screen PCOS women for liver disease at an earlier age than is currently recommended for the general population.