Keith Sacco - Academia.edu (original) (raw)

Papers by Keith Sacco

Medical reports, Jun 1, 2024

The journal of allergy and clinical immunology/Journal of allergy and clinical immunology/The journal of allergy and clinical immunology, Feb 1, 2024

The Journal of Allergy and Clinical Immunology, Feb 1, 2023

Research Square (Research Square), Mar 22, 2021

Importance The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, developmen... more Importance The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). Objective To evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes. Evidence Review We searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded. Findings One hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom’s macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and Relevance BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.

Pediatric Dermatology, Jul 19, 2023

Clinical Microbiology and Infection, Apr 1, 2023

Annals of Allergy Asthma & Immunology, Nov 1, 2018

Allergy, Apr 26, 2017

Background: A documented penicillin allergy is associated with increased morbidity including leng... more Background: A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization. Methods: We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included. Results: Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P<.01). An increased prescription of penicillin (range 9.9%-49%) and cephalosporin (range 10.7%-48%) antibiotics was reported. Vancomycin and fluoroquinolone use was decreased. Inpatient penicillin allergy testing was associated with decreased healthcare cost in four studies. Conclusions: Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship.

Vaccine, May 1, 2021

Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic... more Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses. The magnitude of the antibody response to each of the 23 serotypes in Pneumovax®, and serotype-specific cut-offs in healthy pneumococcal vaccine-naïve adults has not been previously characterized. IgG antibody concentrations were measured prospectively for 23 pneumococcal serotypes pre and 4-6 weeks post-Pneumovax® vaccination in 100 healthy adults, using a multiplex bead-based assay. Antibodies to 19 of 23 serotypes were informative for distinguishing subjects who responded to vaccination, and the serotype threshold was determined to be 9 of 19 serotypes, which characterized an antibody response to pneumococcal vaccination. While this study may facilitate classification of IgG serotype-specific antibody responses post-pneumococcal vaccination in adult patients undergoing diagnostic immunological evaluation for antibody immunodeficiencies or other relevant contexts, additional studies in healthy children and S. pneumoniae protein-conjugate-vaccinated healthy adults will need to be undertaken in the future.

The Journal of Allergy and Clinical Immunology, Feb 1, 2022

The Journal of Allergy and Clinical Immunology, Feb 1, 2018

RATIONALE: To indicate and report the frequency of myelosuppression effect seen with prophylactic... more RATIONALE: To indicate and report the frequency of myelosuppression effect seen with prophylactic dose of Trimethoprim-Sulfamethoxazole (TMP-SMX) in two groups: innate immune defect patients without bone marrow suppression, and immune competent patients for urinary tract infection (UTI) METHODS: A retrospective, two groups' comparative study, of existing data for innate immune defect (i.e. Griscelli syndrome, Chronic granulomatous disease) and UTI patients who received TMP-SMX prophylaxis in Qatar. Data were collected regarding the CBC results (WBC, neutrophils, lymphocytes, and RBC, and platelet counts) at baseline and at maximum myelosuppression seen during the period of TMP-SMX administration. RESULTS: Total of 44 patients were involved in this study (18 innate immune defect and 26 UTI patients). None of the patients in both groups were received folic acid during the period of TMP-SMX administration. Clinical myelosuppression (i.e. less than normal value for age) was observed at higher rate in innate immune defect patients as compared to UTI patients among different cell lines including: neutrophil count (50% vs. 19.2%), lymphocytes count (33.3% vs. 11.5%), and platelets count (16.7% vs. 7.7%) respectively. Only suppression in neutrophils count was found to be statistically significant between the two groups (p-value 0.031). As most innate immune defect disorder does not associated with myelosuppression, the suppressions observed in this group were most likely due to TMP-SMX effect rather than disease itself. CONCLUSIONS: Innate immune defect patients on TMP-SMX prophylaxis are at higher risk of developing myelosuppression compared to other immune competent patients.

Pancreatology, 2018

characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the models. Po... more characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the models. Potential heterogeneity between centers was also estimated. Results 1349 cases of MAP from 24 tertiary hospitals were included. Mean age was 64.4 (19.4-97.6) and 50.5% were women. Gallstone-associated MAP was found in 61.1% cases. Mean Charlson Comorbidity Index was 0.85 (0-14). Median fasting length was 1 (IQR: 2) day and median length of hospital stay was 5 (IQR: 3) days (group A included 718 cases and group B 631). Univariate analysis showed that hospital stay was related with an older age (OR

Frontiers in Pediatrics

Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and... more Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are assoc...

Zenodo (CERN European Organization for Nuclear Research), Sep 23, 2021

Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected childr... more Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, a multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in children with COVID-19 (n=105) and MIS-C (n=76). pCOVID-19 was characterized by enhanced type I IFN responses, and MIS-C by type II IFN- and NF-κB dependent responses, matrisome activation, and increased levels of Spike protein. Reduced levels of IL-33 in pCOVID-19, and of CCL22 in MIS-C suggested suppression of Th2 responses. Expansion of TRBV11-2 T-cell clonotypes in MIS-C was associated with inflammation and signatures of T-cell activation, and was reversed by glucocorticoids. The association of MIS-C with the combination of HLA A*02, B*35, C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load. Use of IVIG was identified as a confounding factor in the interpretation of autoantibody levels.

Annals of Allergy Asthma & Immunology, Nov 1, 2016

Oncology Letters, Jun 16, 2016

Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is ... more Leptomeningeal metastasis (LM) is an uncommon presentation of relapse in breast cancer, which is associated with poor clinical outcomes and poor prognosis. Notably, LM most commonly occurs in breast cancer. The aim of the present review was to investigate the occurrence of LM as the primary presentation of relapse following remission in breast cancer patients and to determine whether specific histological subtypes are predisposed to meningeal metastases. In addition, the present review evaluated whether patients presenting with LM as the primary site of relapse exhibit differences in survival when compared with patients exhibiting metastasis to other sites. Cross-sectional studies have demonstrated that LM is commonly associated with other sites of distant metastasis including lung, liver and bone metastases. The histological breast cancer subtype most commonly associated with LM was invasive lobular carcinoma, while triple-negative breast cancer patients appear to be predisposed to the development of LM when considering the overall prevalence of histological breast cancer subtypes. At present, data regarding LM as the primary site of relapse are limited due to its rarity as the first site of metastasis in breast cancer. Case-controlled studies are required to investigate the incidence of LM as the primary site of recurrence in breast cancer patients as this would enable treatment standardization and identification of prognostic factors for improved survival.

Shock

The pathophysiology of pediatric sepsis is characterized by increased innate immune activation ea... more The pathophysiology of pediatric sepsis is characterized by increased innate immune activation earlier in life. Interleukin-1 is a pro-inflammatory cytokine implicated in the pathophysiology of sepsis and ferritin is a stable surrogate biomarker for elevated IL-1 levels. Data in adult sepsis has shown that use of anakinra, an anti-IL-1 receptor antagonist led to improved clinical outcomes in patients with features of macrophage activation and hyperferritinemia. However, data in pediatric sepsis is lack. Our narrative review sought to highlight the current understanding of using IL-1 inhibitors in pediatric sepsis. We identified 5 studies including 1 case report and 4 retrospective case series that described clinical outcomes in relation to use of anakinra for secondary hemophagocytic lymphohistiocytosis (HLH). A few patients in this pooled heterogenous cohort of 72 patients had concomitant infection meeting criteria for sepsis. All studies measured ferritin levels and reported a dec...