Giovanni Michele Perottino, MD

All Publications

• Preoperative Hemoglobin A1C, Glycemic Status, and Postoperative Outcomes in General Surgery. JAMA surgery Schaschinger, T., Niederegger, T., Brandt, J., Knoedler, S., Knoedler, L., Matar, D. Y., Alobuia, W., Perottino, G. M., Poultsides, G. A., Sabagh, M., Orgill, D. P., Pratschke, J., Panayi, A. C., Hundeshagen, G. 2025

  Abstract

  Dysglycemia is increasingly recognized as a major contributor to adverse surgical outcomes. However, the clinical utility of preoperative hemoglobin A1C (HbA1c) screening in general surgery remains unclear.To determine whether elevated HbA1c is associated with increased 30-day postoperative complications, readmissions, and mortality in patients undergoing general surgery procedures.This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program database from 2021 to 2023. Multivariable logistic regression was used to evaluate associations between glycemic status and complications within 30 days after surgery. The multicenter database comprised more than 700 participating institutions worldwide, predominantly in the US. Participants included adult patients (18 years or older) undergoing general surgery procedures with available HbA1c data.Glycemic status categorized by documented diabetes diagnosis and HbA1c levels, ranging from normoglycemia to very poor glycemic control. Patients without a diagnosis but HbA1c levels higher than 6.4% (to convert to proportion of total hemoglobin, multiply by 0.01) were considered to have undiagnosed diabetes.Main outcomes included occurrence of any, surgical, and medical complications, as well as readmissions, reoperations, and mortality within 30 days after surgery.Among 282 131 patients (mean [SD] age, 60 [15] years), 36% had diagnosed diabetes, whereas 6.4% had HbA1c values in the diabetes range but no diagnosis. In those patients with diabetes, risk of any complication increased progressively from near normal (HbA1c level <6.0%; odds ratio [OR], 1.06; 95% CI, 1.00-1.11) to very poor glycemic control (HbA1c level >9.0%; OR, 1.32; 95% CI, 1.25-1.39). Undiagnosed diabetes was also associated with higher risks of medical complications (OR, 1.11; 95% CI, 1.04-1.18) and mortality (OR, 1.24; 95% CI, 1.07-1.42).Dysglycemia-both diagnosed and undiagnosed-is highly prevalent among general surgery patients and independently associated with increased risks of complications, readmissions, or mortality. A significant proportion of patients had HbA1c levels in the diabetes range, despite lacking a diabetes diagnosis. These findings support routine preoperative HbA1c screening and the adoption of individualized glycemic management strategies to optimize surgical risk assessment, reduce complications, and improve perioperative outcomes.

  View details for DOI 10.1001/jamasurg.2025.4706

  View details for PubMedID 41191374

• Biomarkers of rejection in liver transplantation. Current opinion in organ transplantation Perottino, G., Harrington, C., Levitsky, J. 2022; 27 (2): 154-158

  Abstract

  Liver transplantation is a lifesaving therapy for thousands of individuals with end-stage liver disease across the world. Allograft rejection, which is traditionally detected through an invasive graft biopsy, is a major complication for liver transplant recipients in the postoperative period. Biomarkers represent a relatively newer and safer means of detecting and predicting transplant rejection when compared with the current standard of care: liver biopsy. This review serves to compile recent progress in the field of biomarker discovery in liver allograft rejection.Several promising biomarkers exist in the field of liver transplant rejection. Recent developments include blood genomic assays measuring miRNA, mRNA and donor-derived cell-free DNA. Additionally, serum levels of cytokines, proteoforms, donor-specific antibodies and immunophenotyping have shown promising results in predicting rejection pre and/or posttransplant.Biomarkers represent a novel method of predicting the risk of developing allograft rejection. The findings discussed in the studies outlined in this review are promising in the potential to improve patient management, reduce complications from over- or under-immunosuppression, and ultimately enhance outcomes.

  View details for DOI 10.1097/MOT.0000000000000959

  View details for PubMedID 35232928

• Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach. Frontiers in immunology Tran, S. D., Lin, J., Galvez, C., Rasmussen, L. V., Pacheco, J., Perottino, G. M., Rahbari, K. J., Miller, C. D., John, J. D., Theros, J., Vogel, K., Dinh, P. V., Malik, S., Ramzan, U., Tegtmeyer, K., Mohindra, N., Johnson, J. L., Luo, Y., Kho, A., Sosman, J., Walunas, T. L. 2024; 15: 1331959

  Abstract

  Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors.We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs.Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43).Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

  View details for DOI 10.3389/fimmu.2024.1331959

  View details for PubMedID 38558818

  View details for PubMedCentralID PMC10978703

• 1262 Immune checkpoint inhibitor-induced inflammatory arthritis is associated with cutaneous, endocrine, and gastrointestinal immune-related adverse events: a machine learning approach Journal for Immunotherapy of Cancer Tran, S., Lin, J., Galvez, C., Rasmussen, L., Pacheco, J., Perottino, G., rahbari, K., Miller, C., John, J., Theros, J., Vogel, K., Dinh, P., Malik, S., Razman, U., Luo, Y., Kho, A., Sosman, J., Walnuas, T. 2023; 11

  View details for DOI 10.1136/jitc-2023-SITC2023.1262

• Malnutrition in Lung Transplant Recipients: Weighing the Outcomes The Journal of Heart and Lung Transplantation Collins, M., Tomic, R., Myers, C., O'Boye, A., Brakman, E., Perottino, G. M. 2022; 41 (4)

  View details for DOI 10.1016/j.healun.2022.01.1578

• BMI Change and Outcomes in Lung Transplant Recipients The Journal of Heart and Lung Transplantation Collins, M., O'Boye, A., Arunachalam, A., Myers, C., Perottino, G., Tomic, R. 2022; 41 (4): S406

  View details for DOI 10.1016/j.healun.2022.01.1021

• Neutropenia and outcomes in lung transplant recipients Authors The Journal of Heart and Lung Transplantation Perottino, G., Patel, P., Pesce, L., Arunachalam, A., Tomic, R. 2022; 41 (4): S313

  View details for DOI 10.1016/j.healun.2022.01.776

• Frailty Measurements are Poor Predictor of Lung Transplantation Outcomes Tomic, R., Perottino, G. M., Collins, M., Oboye, A., Amblavanan, A., Sala, M. ELSEVIER SCIENCE INC. 2021: S361-S362

  View details for Web of Science ID 000631254401143

• Weight Change and Outcomes in Lung Transplant Recipients Collins, M., O'Boye, A., Perottino, G., Pesce, L., Tomic, R. ELSEVIER SCIENCE INC. 2021: S359

  View details for Web of Science ID 000631254401136

• Frailty Measurements are Poor Predictor of Lung Transplantation Outcomes The Journal of Heart and Lung Transplantation Tomic, R., Perottino, G. M., Collins, M., O'Boye, A., Amblavanan, A., Sala, M. 2021; 40 (4): S361-S362

  View details for DOI 10.1016/j.healun.2021.01.1018

• Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes Treg development. Clinical and experimental immunology Aqel, S. I., Kraus, E. E., Jena, N., Kumari, V., Granitto, M. C., Mao, L., Farinas, M. F., Zhao, E. Y., Perottino, G., Pei, W., Lovett-Racke, A. E., Racke, M. K., Fuchs, J. R., Li, C., Yang, Y. 2019; 196 (2): 215-225

  Abstract

  Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (Teff ) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (Treg ) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and Treg cells by promoting Th17 development and suppressing Treg development. Here we show that three novel small molecule IL-6 inhibitors, madindoline-5 (MDL-5), MDL-16 and MDL-101, significantly suppress IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner in vitro. MDL-101 showed superior potency in suppressing IL-17 production compared to MDL-5 and MDL-16. Treatment of myelin-specific CD4 T cells with MDL-101 in vitro reduced their encephalitogenic potential following their subsequent adoptive transfer. Furthermore, MDL-101 significantly suppressed proliferation and IL-17 production of anti-CD3-activated effector/memory CD45RO+ CD4+ human CD4 T cells and promoted human Treg development. Together, these data demonstrate that these novel small molecule IL-6 inhibitors have the potential to shift the Teff  : Treg balance, which may provide a novel therapeutic strategy for ameliorating disease progression in MS.

  View details for DOI 10.1111/cei.13258

  View details for PubMedID 30615197

  View details for PubMedCentralID PMC6468176