Severe Combined Immunodeficiency (SCID) Screening in Arizona: Lessons Learned from the First 2 Years.

PURPOSE: The incidence of severe combined immunodeficiency (SCID) in the USA was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of Native American and Hispanic populations compared to national percentages. The true incidence of SCID and non-SCID T cell lymphopenia has not previously been reported in Arizona. METHODS: A retrospective chart review was performed on all abnormal SCID newborn screening (NBS) tests in Arizona from January 1, 2018, to December 31, 2019, using data from the Arizona Department of Health Services and the Phoenix Children's Hospital's electronic medical record [IRB# 20-025]. RESULTS: Seven infants were diagnosed with SCID, yielding an incidence of 1 in 22,819 live births. Four of these infants had Artemis-type SCID. Thirteen infants were identified with an abnormal initial NBS which ultimately did not lead to a diagnosis of SCID. Four of these infants were diagnosed with congenital syndromes associated with T cell lymphopenia. Infants of Hispanic ethnicity were over-represented in this cohort. CONCLUSION: Over 2 years, NBS in Arizona confirmed an incidence more than 2.5 times that reported nationally. This increased incidence is likely reflective of Arizona's unique population profile, with a higher percentage of Native American population. The findings in our non-SCID cohort are in alignment with previously published data, except for an increased percentage of infants of Hispanic/Latino ethnicity, possibly reflecting Arizona's increased percentage of Hispanic/Latino population compared to the general US population.

Increased Likelihood of Detecting Ebola Virus RNA in Semen by Using Sample Pelleting.

Ebola virus RNA can reside for months or years in semen of survivors of Ebola virus disease and is probably associated with increased risk for cryptic sexual transmission of the virus. A modified protocol resulted in increased detection of Ebola virus RNA in semen and improved disease surveillance.

Lingual Tonsillectomy: Successful Treatment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome.

BACKGROUND: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is diagnosed clinically. Adult-onset PFAPA syndrome is rare and often has a more diverse clinical presentation that its childhood counterpart. This is the first reported case of adult-onset PFAPA syndrome with complete response to lingual tonsillectomy. CASE SUMMARY: A 41-year-old man was evaluated for periodic fevers associated with uvulitis, cervical lymphadenitis, pharyngitis, and lower extremity rash. He had a variable response to steroids and was intolerant of colchicine. Laboratory workup revealed intermittent elevation of erythrocyte sedimentation rate and C-reactive protein level. Computed tomography neck and laryngoscopy confirmed adenoidal and lingual tonsillar hypertrophy. He underwent adenoidectomy and lingual tonsillectomy with resolution of symptoms. CONCLUSIONS: Hypertrophy of the remaining lymphoid structures within Waldeyer's ring may be associated with remote recurrence of PFAPA syndrome after tonsillectomy. Lingual tonsillectomy may be an alternative treatment strategy in select patients with PFAPA, prominent lingual hypertrophy, and incomplete response to steroids.

IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation to MM has recently started to show promising clinical outcomes. However, IgG-RT initiation, dosing, route, timing, monitoring, and management in MM has not been standardized in the setting of TCE. Progress in MM treatment will involve greater recognition and screening of underlying secondary immunodeficiency, identification of risk-stratification markers, optimizing IgG-RT management, and implementing other approaches to decrease the risk of infection. In this review, we summarize infection risk, risk of HG, and management strategies for IgG-RT in patients with relapsed MM after TCE.

Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.

Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester. In our cohort of 95 CAR-T recipients, almost one-half had low CD4 T and B cell counts prior to CAR-T that remained persistently low post-CAR-T. Prior to CAR-T, the seronegative rate was lowest for tetanus and highest for pneumococcus irrespective of prior transplantation status (within 2 years of CAR-T). At 3 months post-CAR-T, overall seronegativity rates were similar to pre-CAR-T rates for the prior transplantation and no prior transplantation groups. For patients who received IVIG, loss of seropositivity was seen for hepatitis A (1 of 7; 14%). No seroconversion was noted for pneumococcus. For patients who did not receive IVIG, loss of seropositivity was seen for pneumococcus (2 of 5; 40%) and hepatitis A (1 of 4; 25%). CAR-T recipients commonly experience T cell and B cell lymphopenia and might not have adequate antibody titers against vaccine-preventable diseases despite IVIG supplementation. Loss of antibody titers post-CAR-T is possible, highlighting the need for revaccination. Additional studies with long-term follow-up are needed to inform the optimal timing of immunization post-CAR-T.

Utilizing a Quality Improvement Approach to improve Positioning of Acute Burn Patients.

Patient positioning, using "anti-deformity positioning," is a standard practice in burn rehabilitation to assist with edema management, scar contracture prevention, and wound healing. Consistently providing proper positioning requires the combined effort of the multidisciplinary burn team. Our primary goal was to increase the frequency that patients were correctly positioned to over 90%. At a medium-sized, academic burn unit, random audits were conducted by burn lead therapists on the compliance of proper patient positioning over six months. Using this data as a trigger, a quality improvement project was designed using the PDSA (Plan-Do-Study-Act) cycle. Surveys were distributed to therapy and nursing staff to identify barriers to proper positioning. Effects on positioning compliance post-intervention were monitored. In the six months prior to intervention, average correct positioning was 76%. Surveys identified the following barriers to care: nursing needed more education and the approach was too heavily reliant on nursing efforts alone. To address this, therapists provided education to all nurses, communicated daily about positioning expectations, shifted the project to a multidisciplinary approach, and made changes in therapy workflow. The median compliance improved from 79% to 91% (p < 0.05). Coordinating efforts of the entire burn team improves consistency for positioning in burn patients. Utilizing the PDSA cycle allowed us to identify areas for improvement and develop appropriate interventions to increase education for nursing staff and workflow improvements for therapists. Following the completion of our interventions we were able to obtain an immediate improvement in our patient positioning compliance.

Recent guidelines addressing chronic rhinosinusitis with nasal polyps: practical aspects.

Chronic rhinosinusitis (CRS) is common in adults. It is diagnosed based on a high index of suspicion alongside objective means of assessing sinus inflammation. Determining the impact of CRS on patient quality of life is an important starting point for discussions regarding treatment, and is critical for longitudinal assessment of response to specific treatments. CRS can be further categorized by the presence or absence of nasal polyps. Recent Joint Task Force on Practice Parameters Grading of Recommendations Assessment, Development, and Evaluation guidelines for the management of CRS with nasal polyps (CRSwNP) focused on 3 treatment options: intranasal corticosteroids with multiple delivery methods, biologics (monoclonal antibodies targeting type 2 inflammation), and aspirin therapy after desensitization, which only applies to the subset of patients with CRSwNP who experience acute respiratory reactions following nonsteroidal anti­inflammatory drug ingestion. The authors of the guidelines made conditional recommendations in favor of each of these 3 treatment options, highlighting the importance of shared decision­making when choosing appropriate therapy for individuals with CRSwNP.

Safety and tolerability of Evusheld in patients with CVID: The Mayo Clinic experience.

Background: The past 2 years of the COVID-19 pandemic brought with it many unknowns for patients with immunodeficiency. Because of the concern for severe infection in those with immunocompromise, patients have been eager for effective prevention, vaccination, and treatment strategies. Preexposure prophylaxis provides another means of prevention in those with immunocompromise. A combination of tixagevimab and cilgavimab (Evusheld [AstraZeneca Cambridge, United Kingdom]) was granted emergency use authorization for preexposure prophylaxis at the end of 2021, but questions remained regarding how this would be tolerated and the side effects associated with its use. Objectives: Our aim was to evaluate the safety and tolerability of Evusheld in patients with CVID from our tri-site institution. Methods: We performed an institutional review board-approved, retrospective chart review of patients with common variable immunodeficiency (CVID) who received Evusheld before March 26, 2022. Results: Of the 45 patients with CVID who received Evusheld, 41 (91%) received the recommended full dose of 600 mg. The majority of patients (39 of 45 [87%]) tolerated Evusheld without adverse events. The adverse events reported included immediate injection site pain, fatigue and cough, an episode of shingles, and chest pain. Conclusions: This is an initial report on the safety and tolerability of Evusheld injections in patients with CVID. The majority of patients tolerated the injections without adverse events. For patients with reported chest pain, the results of a subsequent cardiac workup were negative. The efficacy of Evusheld could not be evaluated owing to the short median follow-up of this study (19 days).

Immunoglobulin treatment for B-cell immunodeficiencies.

This article aims to describe the rationale and utility of immunoglobulin therapies in patients with B-cell immunodeficiency states. We describe the historical perspective, mechanism of actions, and indications for use in this population. We then focus upon management pearls and special considerations for its utility. Finally, we elaborate upon the important economic implications for these patients and the need to develop individualized management strategies in this vulnerable population.

Optimal use of intranasal corticosteroids and intranasal saline, is there a clear answer?

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a prevalent condition that poses a significant burden on both quality of life and healthcare utilization. Notwithstanding the heterogenous nature of CRS endotypes and phenotypes, isotonic saline and corticosteroids are recommended as first line medical therapy by recent clinical guidelines. We provide an overview of recent studies of topical saline and corticosteroids for people with CRS and emphasize areas of unmet needs. RECENT FINDINGS: Recent trials suggest exhalation delivery systems of corticosteroid are effective and well tolerated but did not involve comparison with another active treatment. Recent comparative efficacy studies show no clear differences in doses of topical corticosteroid, method of topical corticosteroid delivery, advantage over macrolide antibiotic, or method or type of saline irrigation. SUMMARY: The preeminent formulation, dosage, and delivery of topical corticosteroid and saline for people with CRS represents an area of ongoing research need.

Effectiveness of Physical Distancing: Staying 6 Feet Over to Put Respiratory Viruses 6 Feet Under.

Community transmission of severe acute respiratory illness Coronavirus-2 (SARS-CoV-2) in Arizona was noted in March 2020. It was our hypothesis that the associated implementation of physical distancing and masking led to a decline in circulation and detection of common respiratory viruses. Nasopharyngeal swabs processed with the Biofire, Film Array respiratory panel at Mayo Clinic Arizona were reviewed from January 1, 2017, to July 31, 2020. A total of 13,324 nasopharyngeal swabs were analyzed. Between April and July 2017- 2019 (Period A) a mean of 262 tests were performed monthly, falling to 128 for the corresponding months of 2020 (Period B). A reduction in the monthly mean number of positive tests (Period A 71.5; Period B 2.8) and mean positivity rate (Period A 25.04%; Period B 2.07%) was observed. Rhinovirus/enterovirus was the most prevalent virus, with a monthly mean of 21.6 cases (30.2% of positives) for Period A and 2 cases (72.7% of positives) for Period B. Positivity for a second virus occurred in a mean of 2.1 positive tests (3.3%) in Period A but was absent in Period B. Implementation of distancing and masking coincides with a marked reduction in respiratory virus detection and likely circulation. Data from the fall/winter of 2020 will help clarify the potential role for distancing and masking as a mitigation strategy, not only for SARS-CoV-2 but also in the seasonal battle against common respiratory viruses.

Learning early about peanut-triggered food protein-induced enterocolitis syndrome.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food allergy that typically presents with repetitive emesis and may be associated with lethargy, marked pallor, hypotension, hypothermia, and/or diarrhea. Although many foods are known to cause FPIES, peanut-triggered FPIES is emerging due to changes in the feeding practice guidelines, which recommends early peanut introduction in infants. Objective: We aimed to characterize peanut-triggered acute FPIES cases in our pediatric population and to describe their attributes, treatment, and outcomes. We hypothesized that increases in the incidence of peanut-triggered FPIES coincided with implementation of the guidelines for early peanut introduction. Methods: A retrospective chart review was conducted of pediatric patients who presented to Phoenix Children's Hospital Emergency Department and subspecialty clinics during a 6-year period (January 2013 to September 2019). Results: Thirty-three cases of patients with acute FPIES were identified, five of which were peanut triggered. In those patients with peanut-triggered FPIES, the median age for peanut introduction was 7 months (range, 5-24 months). Two patients had positive peanut skin-prick test results. All five cases were identified in the past 2 years (2018 to 2019). No peanut-triggered reactions were documented in the preceding 4-year period (2013 to 2017). Conclusion: Peanut may be an emerging trigger of acute FPIES, coinciding with an earlier introduction of peanut in the infant diet after implementation of the new addendum guidelines for the prevention of peanut allergy. Oats and rice were the most common triggers of acute FPIES in our cohort. Further study will help clarify the significance and reproducibility of these findings.

Successful Treatment of Steroid-Refractory Checkpoint Inhibitor Myocarditis with Globulin Derived-Therapy: A Case Report and Literature Review.

Immune checkpoint inhibitor (ICI) monoclonal antibody drugs are an important interface of immunology and cancer biology with the intended goal to create cancer specific treatments with less systemic toxicity. Recognition of immune-related adverse events is critical and these include significant cardiovascular toxicity and myocarditis. Compared with other immune-related events, ICI associated myocarditis is rare but is associated with high mortality. The majority of cases present early in the course of therapy and patients can rapidly progress to fulminant myocarditis. Initially, the mainstay of treatment in patients with ICI-associated myocarditis is immunosuppressive therapy with glucocorticoids. For those who do not respond to steroids, the optimal treatment is unclear. This review summarizes the potential adjunctive treatment options for patients with steroid-refractory myocarditis by illustrating a case of myocarditis that was treated with Thymoglobulin and immunoglobulin.

Investigation of the causes of non-tolerance to optometric prescriptions for spectacles.

OBJECTIVES: To study non-tolerance to spectacle prescriptions in a busy community optometric practice, with several practitioners. METHODS: A spectacle non-tolerance was defined in a pragmatic way, as a patient who had collected spectacles from the practice and subsequently returned because they were either having problems with, or were unable to wear, their new spectacles. Patients over 16 years of age, who met the above definition of non-tolerance were sequentially recruited over a 6 month period. Patients experiencing adaptation problems were first seen by a dispensing optician and any dispensing issues resolved. If the spectacle dispensing was felt to be correct, or if the non-tolerance persisted, then the patient was re-examined by an optometrist and the results analysed. RESULTS: Non-tolerance examinations accounted for 62 of the 3091 eye examinations during the study period. The average rate of non-tolerance, averaged across the practitioners, was 1.8%, varying from 1.3-3.3% for individual practitioners. Gender was not a factor in non-tolerance, however age was, with presbyopes accounting for 88.1%. The most common reasons for non-tolerance were, in order of decreasing frequency: prescription related (61.0%), dispensing related (22.0%), pathology (8.5%), data entry error (6.8%) and binocular vision anomalies (1.7%). Of prescription related errors, gauging the spherical element accounted for the majority of inaccuracies, followed by problems with the near/intermediate addition. In every case, the final prescription was within 1.00 D of the not tolerated, prescription; 84.4% were within +/-0.50 D. CONCLUSIONS: Spectacle prescription non-tolerance forms a small, but important, form of adverse reaction in optometric clinics. Most non-tolerances can be resolved by small changes, within 0.50 D, to the prescription.

Renal Trauma: The Rugby Factor.

INTRODUCTION: Renal trauma accounts for 5% of all trauma cases. Rare mechanisms of injuries including sports participation are increasingly common. Rugby-related trauma poses a conundrum for physicians and players due to the absence of clear guidelines and a paucity of evidence. Our series highlights traumatic rugby-related renal injuries in our institution, and emphasize the need for international guidelines on management. METHODS: A retrospective review of all abdominal traumas between January 2006 and April 2013, specifically assessing for renal related trauma that were secondary to rugby injuries was performed. All patients' demographics, computerized tomography results, hematological and biochemical results and subsequent management were recorded. RESULTS: Five male patients presented with rugby-related injuries. Mean age was 21 years old. All patients were hemodynamically stable and managed conservatively in acute setting. One patient was detected to have an unknown pre-existing atrophic kidney that had been subsequently injured, and was booked for an elective nephrectomy an 8-week interval. CONCLUSION: Rugby-related trauma has generated essential attention. This paper serves to highlight this type of injury and the need for defined guidelines on role of imaging and international consensus on timing of return to contact sport, in both professional and amateur settings.