Publications by authors named "Michael Goldberg"

414 Publications

Home epinephrine-treated reactions in food allergy oral immunotherapy: Lessons from the coronavirus disease 2019 lockdown.

Ann Allergy Asthma Immunol 2021 May 16. Epub 2021 May 16.

Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir Medical Center, Zerifin, Israel; Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Oral immunotherapy (OIT) is effective in desensitizing patients with food allergy but adverse reactions limit its use.

Objective: To study the effect of the coronavirus disease 2019 lockdown in Israel between March 15, 2020, and April 30, 2020, on the incidence of home epinephrine-treated reactions.

Methods: All patients who were in the up-dosing phase of OIT for greater than or equal to 1 month during the lockdown, or a respective period in years 2015 to 2019, were studied. The incidence of home-epinephrine treated reactions during the 2020 lockdown was compared with that in the respective period in 2015 to 2019 and to periods before and after the lockdown.

Results: A total of 1163 OIT treatments were analyzed. Two epinephrine injections occurred during 2020 (0.7%) compared with 29 injections (3.28%) during 2015 to 2019 (P = .03). Patients treated in 2020 were older (8.1 vs 7 years, P < .01) and had a significantly lower single highest tolerated dose (12 vs 20 mg protein, P < .01). The rate of milk-OIT was lower (P = .01), but the total number of milk treatments was higher (99 vs 71 to 82) in 2020 compared with 2015 to 2019. On multivariate analysis, treatments during the 2020 lockdown were performed in older patients (P = .001), primarily for nonmilk (P = .03), began with a lower single highest tolerated dose (P = .006), and were associated with significantly less home epinephrine-treated reactions (P = .05) compared with those in 2015 to 2019. Patients treated in 2020 experienced more epinephrine-treated reactions in adjacent periods before (n = 8) and after (n = 6) the lockdown.

Conclusion: The lower rate of home epinephrine-treated reactions during the coronavirus disease 2019 lockdown in Israel suggests that potentially avoidable triggers contribute significantly to the rate of adverse reactions during OIT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2021.05.008DOI Listing
May 2021

Mutational signatures of replication timing and epigenetic modification persist through the global divergence of mutation spectra across the great ape phylogeny.

Genome Biol Evol 2021 May 13. Epub 2021 May 13.

University of Washington Department of Genome Sciences, 3720 15th Ave NE, Seattle WA 98105, United States of America.

Great ape clades exhibit variation in the relative mutation rates of different three-base-pair genomic motifs, with closely related species having more similar mutation spectra than distantly related species. This pattern cannot be explained by classical demographic or selective forces, but imply that DNA replication fidelity has been perturbed in different ways on each branch of the great ape phylogeny. Here, we use whole-genome variation from 88 great apes to investigate whether these species' mutation spectra are broadly differentiated across the entire genome, or whether mutation spectrum differences are driven by DNA compartments that have particular functional features or chromatin states. We perform principal component analysis and mutational signature deconvolution on mutation spectra ascertained from compartments defined by features including replication timing and ancient repeat content, finding evidence for consistent species-specific mutational signatures that do not depend on which functional compartments the spectra are ascertained from. At the same time, we find that many compartments have their own characteristic mutational signatures that appear stable across the great ape phylogeny. For example, in a mutation spectrum PCA compartmentalized by replication timing, the second PC explaining 21.2% of variation separates all species' late-replicating regions from their early-replicating regions. Our results suggest that great ape mutation spectrum evolution is not driven by epigenetic changes that modify mutation rates in specific genomic regions, but instead by trans-acting mutational modifiers that affect mutagenesis across the whole genome fairly uniformly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gbe/evab104DOI Listing
May 2021

Combinatorial advantage of Ses i 1-specific IgE and basophil activation for diagnosis of sesame food allergy.

Pediatr Allergy Immunol 2021 May 5. Epub 2021 May 5.

Yitzhak Shamir Medical Center, Institute of Allergy, Immunology and Pediatric Pulmonology, Zerifin, Israel.

Background: The prevalence of sesame food allergy (SFA) is increasing worldwide with the potential of anaphylactic reactions upon exposure. Utility of specific component IgE testing as an alternative to the oral food challenge (OFC), the diagnostic standard, is being investigated.

Methods: Patients (n = 42) with suspected SFA completed an open OFC to sesame. Diagnostic testing included serum levels of Ses i 1-specific IgE, skin prick test with high-protein extract, and basophil reactivity (% induced CD63 expression) for each patient. The diagnostic utility of these tests was evaluated at a 95% sensitivity, with the outcome measure being the number of OFCs required.

Results: Twenty-seven patients (64%) were diagnosed with SFA. Ses i 1 IgE differed significantly between allergic and tolerant patients (p = .0001). ROC curve analysis for Ses i 1 IgE yielded an AUC of 0.88 ± 0.05. Levels of Ses i 1 IgE correlated to induced CD63+ expression on basophils (p = .0001). Ses i 1 IgE was not sufficiently robust as a single step for diagnosis. Used concurrently, BAT and Ses i 1 IgE yielded correct positive classifications for 25 of 27 sesame-allergic patients with two false positives (93% PPV). Both tests were negative in 5 non-allergic patients. Patients with divergent Ses i 1 IgE and BAT results required OFC (n = 10, 24% of patients). Alternatively, sequential use of BAT, ruling in SFA followed by Ses i 1 IgE diagnosing non-allergic patients, yielded a 89% PPV, with 19% requiring OFC.

Conclusion: Ses i 1 IgE and BAT used together can decrease the need for OFC in most SFA patients. A prospective cohort trial is necessary to validate these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13533DOI Listing
May 2021

Positive predictive value and stroke workflow outcomes using automated vessel density (RAPID-CTA) in stroke patients: One year experience.

Neuroradiol J 2021 Apr 28:19714009211012353. Epub 2021 Apr 28.

Department of Radiology, Allegheny Health Network, USA.

Purpose: Several new techniques have emerged for detecting anterior circulation large vessel occlusion by quantifying relative vessel density including RAPID-CTA, potentially allowing for faster triage and decreased time to mechanical thrombectomy. We present our one-year experience on positive predictive value of RAPID-CTA for the detection of large vessel occlusion in patients presenting with stroke symptoms and its effect on treatment time and clinical outcomes.

Materials And Methods: Three hundred and ten patients presenting with stroke symptoms with relative vessel density <60% on RAPID-CTA were included (average age 70 years, 145 male, 165 female). Examinations were considered positive if there was evidence of large vessel occlusion or high grade stenosis. Computed tomography angiography to groin puncture time was calculated during one-year time intervals before and after RAPID-CTA installation. Ninety-day Modified Rankin Scale scores were obtained for patients in each cohort.

Results: Of the 310 patients, 270 had large vessel occlusion or high grade stenosis (87% positive predictive value), with 161 having large vessel occlusion. Using 45% relative vessel density threshold, 129/161 large vessel occlusion were detected (80% sensitivity) and 163/172 examinations were positive (95% positive predictive value). Computed tomography angiography to groin puncture time was significantly lower after deployment of RAPID-CTA (93 min vs 68 min, <0.05). Average 90 day modified Rankin Scale score was lower in the RAPID-CTA group with a higher percentage of patients with functional independence, although the data was not statistically significant.

Conclusion: RAPID-CTA had high positive predictive value for large vessel occlusion with a 45% relative vessel density threshold, which could facilitate active worklist reprioritization. Time to treatment was significantly lower and clinical outcomes were improved after deployment of RAPID-CTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19714009211012353DOI Listing
April 2021

Two sequential activation modules control the differentiation of protective T helper-1 (Th1) cells.

Immunity 2021 Apr 26;54(4):687-701.e4. Epub 2021 Mar 26.

Center for Immunology, Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455 USA. Electronic address:

Interferon-γ (IFN-γ)-producing CD4 T helper-1 (Th1) cells are critical for protection from microbes that infect the phagosomes of myeloid cells. Current understanding of Th1 cell differentiation is based largely on reductionist cell culture experiments. We assessed Th1 cell generation in vivo by studying antigen-specific CD4 T cells during infection with the phagosomal pathogen Salmonella enterica (Se), or influenza A virus (IAV), for which CD4 T cells are less important. Both microbes induced T follicular helper (Tfh) and interleukin-12 (IL-12)-independent Th1 cells. During Se infection, however, the Th1 cells subsequently outgrew the Tfh cells via an IL-12-dependent process and formed subsets with increased IFN-γ production, ZEB2-transcription factor-dependent cytotoxicity, and capacity to control Se infection. Our results indicate that many infections induce a module that generates Tfh and poorly differentiated Th1 cells, which is followed in phagosomal infections by an IL-12-dependent Th1 cell amplification module that is critical for pathogen control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2021.03.006DOI Listing
April 2021

Characteristics and associated morbidities of young adults with misconceived food allergy: A cross-sectional study.

EClinicalMedicine 2021 Mar 26;33:100766. Epub 2021 Feb 26.

Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir Medical Center, Zerifin, Israel.

Background: Many patients with self-reported food allergy are not allergic but suffer from similar burdens. We aimed to characterize young adults with misconceived food allergy.

Methods: A cross-sectional study of individuals ( = 12,592) aged 17-18 years, recruited to the Israel Defense Forces (IDF) at a single urban-area recruitment center over a six month-period. All participants underwent a comprehensive medical and psychological evaluation. Cognitive tests were performed and a Combined Intellectual-Education score assigned. Participants who reported food elimination due to allergy were skin-tested and underwent oral food challenges, when indicated. The characteristics, psychological evaluation and cognitive tests of individuals with no reported food allergy ( = 12,444), misconceived food allergy ( = 64) and true food allergy ( = 84) were compared.

Findings: The prevalence of atopic co-morbidities was higher in recruits reporting compared to those not reporting food allergy while the rate of other co-morbidities was comparable. Anxiety disorder was diagnosed significantly more in individuals who reported food allergy (4·1%) compared to those who did not (1·7%) ( = 0·04). Further analysis revealed that this diagnosis was concentrated in individuals with misconceived (8/64, 12·5%) compared to true food allergy (2/84, 2·4%), ( = 0·02). Patients with misconceived food allergy were mostly of female sex, had lower Combined Intellectual-Education scores compared to patients with true ( = 0·001) and no reported food allergy ( = 0·01), and required the longest mean evaluation time (147·6 ± 109·4 days).

Interpretation: Patients with misconceived food allergy have higher rates of anxiety disorder and are often from a lower educational level and of female sex. Medical and educational attention is required to improve care of this specific population.

Funding: The research reported in this publication was supported by the Israel Defense Forces (IDF) Medical Corps and Directorate of Defense Research & Development, Israeli Ministry of Defense (IMOD DDR&D).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933257PMC
March 2021

Complex Primary Total Knee Arthroplasty in a Patient with Achondroplasia, Osteoarthritis, and Severe Coronal Instability.

Arthroplast Today 2021 Apr 24;8:24-28. Epub 2021 Feb 24.

Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, CA, USA.

Genu varum in patients with achondroplasia is common and is often exacerbated by the associated generalized ligamentous laxity. Despite this, development of knee osteoarthritis is rare. There are only a few previously published case reports of total knee arthroplasty in this population. We present 2-year follow-up of a patient with achondroplasia who underwent staged bilateral primary total knee arthroplasties using hinged components. Technical considerations and careful preoperative planning are required in patients with achondroplasia given their small skeletal stature, metaphyseal deformities, and ligamentous laxity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.artd.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917396PMC
April 2021

Incidence of postural headache after lumbar puncture requiring epidural blood patch: Effects of needle caliber; 2-year experience.

Neuroradiol J 2021 Mar 8:19714009211000630. Epub 2021 Mar 8.

Department of Radiology, Allegheny Health Network, USA.

Purpose: A common complication of lumbar puncture (LP) is postural headaches. Epidural blood patches are recommended if patients fail conservative management. Owing to a perceived increase in the number of post-lumbar puncture headaches (PLPHs) requiring epidural blood patches at a regional hospital in our network, the decision was made to switch from 20 to 22 gauge needles for routine diagnostic LPs.

Materials And Methods: Patients presenting for LP and myelography at one network regional hospital were included in the study. The patients were contacted by nursing staff 3 days post-procedure; those patients who still had postural headaches after conservative management and received epidural blood patches were considered positive cases. In total, 292 patients were included; 134 underwent LP with 20-gauge needles (53 male, 81 female, average age 57.7) and 158 underwent LP with 22-gauge needles (79 male, 79 female, average age 54.6).

Results: Of 134 patients undergoing LP with 20-gauge needles, 15 (11%) had PLPH requiring epidural blood patch (11 female, 3 male, average age 38). Of 158 patients undergoing LP with 22-gauge needles, only 5 (3%) required epidural blood patches (all female, average age 43). The difference was statistically significant ( < 0.01). Risk factors for PLPH included female gender, younger age, lower body mass index, history of prior PLPH and history of headaches.

Conclusion: Switching from 20-gauge to 22-gauge needles significantly decreased the incidence of PLPH requiring epidural blood patch. Narrower gauge or non-cutting needles should be considered in patients with risk factors for PLPH, allowing for CSF requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/19714009211000630DOI Listing
March 2021

Neural correlates of goal-directed and non-goal-directed movements.

Proc Natl Acad Sci U S A 2021 02;118(6)

Center for Neuroscience, Indian Institute of Science, Bangalore 560012, India.

What are the cortical neural correlates that distinguish goal-directed and non-goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non-goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity: First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2006372118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017686PMC
February 2021

Medical clown support is associated with better quality of life of children with food allergy starting oral immunotherapy.

Pediatr Allergy Immunol 2021 Jan 16. Epub 2021 Jan 16.

Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir (Former Assaf Harofeh) Medical Center, Zerifin, Israel.

Background: The start of oral immunotherapy (OIT) for food allergy is a critical period in the treatment process, with a potential to influence patient quality of life (QOL) and subsequently treatment outcome. The association of medical clowning with QOL at OIT initiation was examined.

Methods: Children aged 4-12 years supported by a medical clown (MC) during the induction week of OIT for food allergy were studied. Children in the same age range starting OIT without the support of a MC served as controls. Parents of all children completed the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF), and children aged 8-12 years completed the Food Allergy Quality of Life Questionnaire-Child Form (FAQLQ-CF). QOL scores of parents and children with and without a MC support were compared.

Results: Children with (n = 88) and without (n = 212) the support of a MC were comparable in demographics and clinical characteristics. The study group had a significantly lower single highest tolerated dose compared to controls (57 ± 83 vs 162 ± 274 mg protein, respectively, P < .001). Parental perception of the QOL of children was not associated with a MC support (P = .81) but rather with previous reaction severity (P < .01). In contrast, the QOL of children aged 8-12 years (n = 119) was positively associated primarily with a MC support, total score 3.7 ± 1.1 vs 4.6 ± 1.3 (P < .001).

Conclusions: While the perception of QOL of parents of children with food allergy at OIT initiation is mainly associated with previous reaction severity, the QOL of the children themselves is primarily positively associated with MC support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13445DOI Listing
January 2021

Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia.

Orphanet J Rare Dis 2021 01 14;16(1):31. Epub 2021 Jan 14.

Department of Orthopedics and Sports Medicine, Seattle Children's Hospital, Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, USA.

Background: Recognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making.

Methods: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients.

Results: After a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting.

Conclusions: The guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-021-01678-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809733PMC
January 2021

Medullary Thyroid Cancer in Patients Older than 45-Epidemiologic Trends and Predictors of Survival.

Cancers (Basel) 2020 Oct 26;12(11). Epub 2020 Oct 26.

Section of Surgical Oncology, Department of Surgery, Westchester Medical Center/New York Medical College, Valhalla, NY 10595, USA.

Sporadic medullary thyroid cancer (MTC) can occur anytime in life although they tend to present at a later age (≥45 years old) when the tumors are more easily discernible or become symptomatic. We aimed to identify the factors affecting the survival in patients ≥45 years of age diagnosed with MTC. We analyzed the Surveillance, Epidemiology, and End Results (SEER) registry from 1973-2016 focusing on patients ≥45 years of age with MTC as an isolated primary. A total of 2533 patients aged ≥45 years with MTC were identified. There has been a statistically significant increase of 1.19% per year in the incidence of MTC for this group of patients. The disease was more common in females and the Caucasian population. Most patients had localized disease on presentation (47.6%). Increasing age and advanced stage of presentation were associated with worse survival with HR 1.05 ( < 0.001) and HR 3.68 ( < 0.001), respectively. Female sex and surgical resection were associated with improved survival with HR 0.74 ( < 0.001) and 0.36 ( < 0.001), respectively. In conclusion, the incidence of MTC in patients ≥45 years of age is increasing. Patients should be offered surgical resection at an early stage to improve their outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692716PMC
October 2020

Microbial signature in IgE-mediated food allergies.

Genome Med 2020 10 27;12(1):92. Epub 2020 Oct 27.

The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.

Background: Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state.

Methods: To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31).

Results: The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs.

Conclusions: Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-020-00789-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592384PMC
October 2020

Subjective oral symptoms are insufficient predictors of a positive oral food challenge.

Pediatr Allergy Immunol 2021 Feb 9;32(2):342-348. Epub 2020 Nov 9.

Shamir Medical Center, Institute of Allergy, Immunology and Pediatric Pulmonology, Zerifin, Israel.

Background: Subjective oral symptoms, especially if recurrent, might lead to termination of an oral food challenge (OFC) for fear of a subsequent severe reaction.

Methods: In a single-center retrospective cohort study, oral food challenges to milk, egg, peanut, sesame, or tree nuts performed between January 2016 and January 2018 in patients aged ≥3 years, at the Institute of Allergy, Immunology and Pediatric Pulmonology in Shamir Medical Center, were analyzed. Subjective oral symptoms during the challenge were documented, and their association with the challenge outcome was examined.

Results: A total of 323 patients underwent 652 oral food challenges to the investigated foods (milk, 71; egg, 22; peanut, 48; sesame, 24; and tree nuts, 487). Subjective oral symptoms were experienced in 237 (36.3%) of all OFCs performed, and their rate was comparable across most foods tested. The rate of positive challenges was significantly higher when subjective oral symptoms were experienced during the challenge than when they were not (69.6% vs 30.4%, respectively, P < .001). However, the false-positive rate of such symptoms in predicting a positive food challenge was 30.3% for all foods; peanut, 40%; sesame, 27.3%; milk, 35.5%; egg, 33%; and tree nuts, 28.4%. Overall, subjective oral symptoms (SOS) provided sensitivity of 56.7, specificity 80.4, PPV 69.6, and NPV 69.0 for predicting OFC outcome. Importantly, reactions during positive challenges with and without subjective oral symptoms were comparable to severity.

Conclusions: Continuing OFCs with subjective oral symptoms is recommended for it will prevent false-positive results in a third of cases without increasing patients' risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13392DOI Listing
February 2021

A Prospective Validation of the NUT CRACKER Diagnostic Algorithm for Walnut and Pecan Allergy with Prediction of Severity.

J Allergy Clin Immunol Pract 2021 01 8;9(1):265-274.e6. Epub 2020 Oct 8.

Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel; Department of Pediatrics, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: We previously devised an algorithm using skin prick tests (SPT), basophil activation tests (BAT), and co-allergy status to reduce the need for oral food challenges (OFCs) in 63 patients with suspected walnut/pecan allergies.

Objective: To validate prospectively the NUT CRACKER (Nut Co-Reactivity-Acquiring Knowledge for Elimination Recommendations) diagnostic algorithm in a new cohort of patients (n = 120) and to study the utility of SPT and BAT in predicting walnut-pecan allergy severity in both groups (n = 183).

Methods: Patients (n = 183) aged 8 (6-11) years, median (interquartile range), with suspected tree nut allergy were studied. SPT used ground nut extract (10 mg/mL), and BAT assessed allergen-induced basophil CD63 expression. Allergy was determined based on a recent reaction or a positive OFC, and tolerance was defined by regular consumption or a negative OFC.

Results: Walnut BAT was significantly higher in walnut/pecan dual compared with single walnut allergy (P = .003) and predicted the need for epinephrine during positive walnut OFCs (P = .009). Results of walnut and pecan BAT correlated with the corresponding nut eliciting dose (P = .014 and P < .001, respectively). Receiver operating curves for walnut and pecan allergy in the prospective cohort yielded area under the curves ranging from 0.87 to 0.93 for SPT and BAT. Concordant with the original study, pecan-allergic patients were all co-allergic for walnut. The algorithm decreased the need for OFCs by 78.8 % with 6 of 240 (2.5%) falsely positives and no false negatives.

Conclusion: The algorithm was validated prospectively and awaits broader testing across other populations. The use of BAT further associates with severity in walnut/pecan allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.09.041DOI Listing
January 2021

Data File Standard for Flow Cytometry, Version FCS 3.2.

Cytometry A 2021 Jan 16;99(1):100-102. Epub 2020 Sep 16.

Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada.

FCS 3.2 is a revision of the flow cytometry data standard based on a decade of suggested improvements from the community as well as industry needs to capture instrument conditions and measurement features more precisely. The unchanged goal of the standard is to provide a uniform file format that allows files created by one type of acquisition hardware and software to be analyzed by any other type. The standard retains the overall FCS file structure and most features of previous versions, but also contains a few changes that were required to support new types of data and use cases efficiently. These changes are incompatible with existing FCS file readers. Notably, FCS 3.2 supports mixed data types to, for example, allow FCS measurements that are intrinsically integers (e.g., indices or class assignments) or measurements that are commonly captured as integers (e.g., time ticks) to be more represented as integer values, while capturing other measurements as floating-point values in the same FCS data set. In addition, keywords explicitly specifying dyes, detectors, and analytes were added to avoid having to extract those heuristically and unreliably from measurement names. Types of measurements were formalized, several keywords added, others removed, or deprecated, and various aspects of the specification were clarified. A reference implementation of the cyclic redundancy check (CRC) calculation is provided in two programming languages since a correct CRC implementation was problematic for many vendors. © 2020 International Society for Advancement of Cytometry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cyto.a.24225DOI Listing
January 2021

ISAC Probe Tag Dictionary: Standardized Nomenclature for Detection and Visualization Labels Used in Cytometry and Microscopy Imaging.

Cytometry A 2021 Jan 16;99(1):103-106. Epub 2020 Sep 16.

Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada.

Since the advent of microscopy imaging and flow cytometry, there has been an explosion in the number of probes, consisting of a component binding to an analyte and a detectable tag, to mark areas of interest in or on cells and tissue. Probe tags have been created to detect and/or visualize probes. Over time, these probe tags have increased in number. The expansion has resulted in arbitrarily created synonyms of probe tags used in publications and software. The synonyms are problematic for readability of publications, accuracy of text/data mining, and bridging data from multiple platforms, protocols, and databases for Big Data analysis. Development and implementation of a universal language for probe tags will ensure equivalent quality and level of data being reported or extracted for clinical/scientific evaluation as well as help connect data from many platforms. The International Society for Advancement of Cytometry Data Standards Task Force composed of academic scientists and industry hardware/software/reagent manufactures have developed recommendations for a standardized nomenclature for probe tags used in cytometry and microscopy imaging. These recommendations are shared in this technical note in the form of a Probe Tag Dictionary. © 2020 International Society for Advancement of Cytometry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cyto.a.24224DOI Listing
January 2021

Do Physicians Have Collective, Not Just Individual, Obligations to Respond to the Opioid Crisis?

AMA J Ethics 2020 08 1;22(1):E668-674. Epub 2020 Aug 1.

Pediatric orthopedic surgeon at Seattle Children's Hospital and a clinical professor of orthopedics at the University of Washington in Seattle.

Evidence-based clinical guidelines could mitigate variations in care for some patients. However, patient and clinician distress can arise when guidelines are misapplied or mandated by processes that are not evidence based, fail to integrate physician expertise and patient preference, or fail to motivate informed, shared decision making. Physicians can choose to collectively advocate at national, state, and local levels for policy changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/amajethics.2020.668DOI Listing
August 2020

NSQIP versus institutional morbidity and mortality conference: complementary complication reporting in pediatric spine fusion.

Spine Deform 2021 Jan 2;9(1):113-118. Epub 2020 Sep 2.

Department of Orthopaedic Surgery, Department of Orthopaedics and Sports Medicine, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.

Purpose: Other fields of medicine have demonstrated underreported surgical complication rates by institutional M&M compared to NSQIP. However, a study comparing surgical complication rates in the pediatric spine population, using an identical set of patients rather than nationally extrapolated, has not been performed.

Methods: A single institution's ASC-NSQIP Pediatric spine fusion cases and its departmental team-reported M&M database for the same were reviewed for January 1, 2012 to December 31, 2018. Differences in surgical complication reporting between the two databases for the identical patient cohort were recorded.

Results: NSQIP identified 50 pediatric spine fusion patients with complications out of 386 NSQIP-algorithm-sampled cases (13%). Of these complications, 23 were not reported in the M&M conference database (6% of NSQIP-sampled cases, 2.5% of all M&M cases). The most common under-reported complication categories include pneumonia (100% under-reported), clostridium difficile (100%), urinary tract infection (83%), and superficial wound disruption (67%). During the same 7 years, M&M covered 924 spine fusions and identified 162 complications. Of these 162 patients, 22 were included in the NSQIP sampling and were not reported as complications (6% of NSQIP sampled patients).

Conclusion: Recognizing complication rates is central to implement strategies for delivering better quality care. NSQIP data may serve as an important quality check for pediatric spine institutional M&M data, but both may not include all complications even within its sampled patients. In general, NSQIP's protocols identified more medical complications, while M&M has a surgical focus, benefits from the limitless follow-up, and involves timely departmental awareness of complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43390-020-00197-zDOI Listing
January 2021

Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way.

Periodontol 2000 2020 10;84(1):45-68

Department of Dentistry, Mount Sinai Hospital, Thodupuzha, India.

Periodontitis is a highly prevalent disease. As it progresses, it causes serious morbidity in the form of periodontal abscesses and tooth loss and, in the latter stages, pain. It is also now known that periodontitis is strongly associated with several nonoral diseases. Thus, patients with periodontitis are at greater risk for the development and/or exacerbation of diabetes, chronic obstructive pulmonary disease, and cardiovascular diseases, among other conditions. Although it is without question that specific groups of oral bacteria which populate dental plaque play a causative role in the development of periodontitis, it is now thought that once this disease has been triggered, other factors play an equal, and possibly more important, role in its progression, particularly in severe cases or in cases that prove difficult to treat. In this regard, we allude to the host response, specifically the notion that the host, once infected with oral periodontal pathogenic bacteria, will mount a defense response mediated largely through the innate immune system. The most abundant cell type of the innate immune system - polymorphonuclear neutrophils - can, when protecting the host from microbial invasion, mount a response that includes upregulation of proinflammatory cytokines, matrix metalloproteinases, and reactive oxygen species, all of which then contribute to the tissue damage and loss of teeth commonly associated with periodontitis. Of the mechanisms referred to here, we suggest that upregulation of reactive oxygen species might play one of the most important roles in the establishment and progression of periodontitis (as well as in other diseases of inflammation) through the development of oxidative stress. In this overview, we discuss both innate and epigenetic factors (eg, diabetes, smoking) that lead to the development of oxidative stress. This oxidative stress then provides an environment conducive to the destructive processes observed in periodontitis. Therefore, we shall describe some of the fundamental characteristics of oxidative stress and its effects on the periodontium, discuss the diseases and other factors that cause oxidative stress, and, finally, review potentially novel therapeutic approaches for the management (and possibly even the reversal) of periodontitis, which rely on the use of therapies, such as resveratrol and other antioxidants, that provide increased antioxidant activity in the host.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/prd.12342DOI Listing
October 2020

Neuroradiologic manifestations of COVID-19: what the emergency radiologist needs to know.

Emerg Radiol 2020 Dec 21;27(6):737-745. Epub 2020 Aug 21.

Department of Ophthalmology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global pandemic with a wide spectrum of clinical signs and symptoms. Neurologic manifestations are relatively common, with severe cases often demonstrating striking findings on neuroimaging. Because the neuroradiologic findings may be the first evidence of COVID-19, the emergency radiologist has a critical role to play in not only the detection and management of the disease but also in the safety of other patients and hospital staff. Therefore, radiologists, especially those who specialize in emergency radiology, need to be aware of the neuroradiologic manifestations of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10140-020-01840-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441306PMC
December 2020

Patient Characteristics and Risk Factors for Home Epinephrine-Treated Reactions During Oral Immunotherapy for Food Allergy.

J Allergy Clin Immunol Pract 2021 01 1;9(1):185-192.e3. Epub 2020 Aug 1.

Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir Medical Center, Zerifin, Israel; Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Oral immunotherapy (OIT) is effective in desensitizing food-allergic patients but adverse events limit its applicability.

Objective: To identify risk factors for home epinephrine-treated reactions during the build-up phase of OIT.

Methods: A retrospective cohort study of patients older than 3.7 years undergoing OIT for food allergy at Shamir Medical Center between April 2010 and March 2019. All patients with a final disposition of full desensitization, partial desensitization, or failure were analyzed. Risk factors and outcome of home epinephrine-treated reactions were examined.

Results: A total of 1037 patients (mean age, 8.4 years) who underwent 1100 OIT treatments (milk, n = 710; peanut, n = 213; egg, n = 50; sesame, n = 57; and tree nuts, n = 70) reached a final disposition and were analyzed. Full desensitization was achieved in 763 (69.4%) treatments, partial desensitization in 219 (19.9%), and 118 (10.7%) failed. Epinephrine was administered to 121 patients (11.7%) during 10.8% of treatments. Milk OIT was a significant risk factor both for epinephrine-treated reactions (odds ratio, 2.15; 95% CI, 1.25-3.68) and for low rate of full desensitization following such reactions compared with nonmilk OIT (18.2% vs 73.9%, respectively; P < .0001). Risk factors during milk OIT included asthma, pre-OIT reaction severity, lower tolerated dose, and epinephrine-treated reactions during clinic updosing, whereas risk factors during nonmilk OIT were male sex and lower tolerated dose.

Conclusions: Milk OIT poses a significant risk for home epinephrine-treated reactions during OIT and for poor outcome following such reactions. Together with the additional risk factors described for both milk and nonmilk OIT, this information may assist in patient selection for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.07.034DOI Listing
January 2021

Reply.

AJNR Am J Neuroradiol 2020 08 9;41(8):E64. Epub 2020 Jul 9.

Neuroscience InstituteCerebrovascular CenterAllegheny Health NetworkPittsburgh, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3174/ajnr.A6686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658895PMC
August 2020

Best practice guidelines for management of spinal disorders in skeletal dysplasia.

Orphanet J Rare Dis 2020 06 24;15(1):161. Epub 2020 Jun 24.

Victorian Clinical Genetics Services, Murdoch Children's Research Institute, University of Melbourne, Parkville, Victoria, Australia.

Background: Disorders of the spine present a common and difficult management concern in patients with skeletal dysplasia. Due to the rarity of these conditions however, the literature, largely consisting of small, single institution case series, is sparse in regard to well-designed studies to support clinical decision making in these situations.

Methods: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, "best practice" guidelines in the care of spinal disorders in patients with skeletal dysplasia.

Results: Starting with 33 statements, the group a developed a list of 31 "best practice" guidelines.

Conclusions: The guidelines are presented and discussed to provide context for clinicians in their decision making in this often-challenging realm of care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-020-01415-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313125PMC
June 2020

Compassionate Care: Making It a Priority and the Science Behind It.

J Pediatr Orthop 2020 Jul;40 Suppl 1:S4-S7

Seattle Children's Hospital and the University of Washington, Seattle, WA.

Background: Compassion is the deep feeling that arises when confronted with another's suffering coupled with a strong desire to alleviate that suffering. Until recently, evidence was lacking as to whether compassion was innate, acquired, or modifiable. Because patients who experience compassionate health care report better clinical outcomes, an understanding of the science behind it may give rise to methods of incorporating compassion into clinical care delivery.

Methods: A high-level summary of the social and neuroscience research was constructed.

Results: Functional neuroimaging of empathy and compassion demonstrates neural networks involving the insula, cingulate, and prefrontal cortices suggesting neurological hard wiring for these emotional and cognitive experiences. Neuroscience and social science research evidence supports the presence of cognitive and/or emotional empathy in all individuals studied; that empathy and compassion can be taught; and that both internal and external factors influence their expression.

Conclusions: Burnout may result when clinicians know what their patients need (thereby activating the empathy/pain neural pathways) but are unable to deliver that care (therefore inactivation of the compassion/reward neural pathways). Understanding the neuroscience underlying empathy and compassion informs practical programs that mitigate burnout and creates a more compassionate workplace.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001502DOI Listing
July 2020

Pediatric Orthopaedists Are Not Immune: Characterizing Self-reported Burnout Rates Among POSNA Members.

J Pediatr Orthop 2020 Jul;40(6):e527-e531

Seattle Children's Hospital, Seattle, WA.

Background: There are no published data characterizing burnout rates for pediatric orthopaedic surgeons. The primary purpose of this study was to identify the rates of self-reported personal and team burnout among members of the Pediatric Orthopaedic Society of North America (POSNA). A secondary aim was to determine whether specific demographic variables were more likely to be associated with self-reported burnout.

Methods: During its 2018 annual meeting, the POSNA Wellness Taskforce launched a web-based survey in which members were asked to respond to 2 previously validated questions related to personal and team burnout. The survey was distributed by a closed POSNA membership e-mail list and responses were analyzed anonymously. Descriptive statistics were calculated. Pearson χ testing was used to analyze differences in burnout rates as a function of age and sex.

Results: A total of 615 POSNA members completed the survey, a 47% response rate. Overall, 38% reported personal burnout and 46% reported team burnout. Women were more likely to report both personal (P<0.001) and team burnouts (P<0.005). Members aged 40 to 59 years were more likely to report personal burnout, irrespective of sex (P<0.001). Members aged 50 to 59 years were more likely than those in other age groups to report team burnout (P<0.001). There was no significant association found between the presence of burnout and either race, ethnicity, LGBTQ status, or educational background.

Conclusions: As a group, pediatric orthopaedists report moderately high rates of both personal and team member burnout. Individual-specific factors such as age and sex may play an important role in determining one's risk for experiencing burnout. Recognizing that burnout affects a significant minority of POSNA members is a crucial first step.

Level Of Evidence: Level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001440DOI Listing
July 2020

Cerebrovascular Disease in COVID-19.

AJNR Am J Neuroradiol 2020 07 14;41(7):1170-1172. Epub 2020 May 14.

Neuroscience Institute, Cerebrovascular Center (R.C., A.H.T.), Allegheny Health Network, Pittsburgh, Pennsylvania.

Coronavirus disease 19 (COVID-19) is a pandemic originating in Wuhan, China, in December 2019. Early reports suggest that there are neurologic manifestations of COVID-19, including acute cerebrovascular disease. We report a case of COVID-19 with acute ischemic stroke. To our knowledge, this is the first reported case of COVID-19-related cerebral infarcts that includes brain imaging at multiple time points and CT angiography. There is a growing body of published evidence that complications of COVID-19 are not limited to the pulmonary system. Neuroradiologists should be aware of a wide range of neurologic manifestations, including cerebrovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3174/ajnr.A6588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357639PMC
July 2020