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Article ; Online: Operative trends for pancreatic and hepatic malignancies during the COVID-19 pandemic.

Manzella, Alexander / Ecker, Brett L / Eskander, Mariam F / Grandhi, Miral S / In, Haejin / Kravchenko, Timothy / Langan, Russell C / Kennedy, Timothy / Alexander, H Richard / Beninato, Toni / Pitt, Henry A

Surgery

2024

Abstract: Background: The COVID-19 pandemic disrupted routine health care, including many elective and non-cancer operations in the United States. Most hepato-pancreato-biliary malignancy patients require outpatient imaging, tissue sampling, and staging, and many ...

Abstract	Background: The COVID-19 pandemic disrupted routine health care, including many elective and non-cancer operations in the United States. Most hepato-pancreato-biliary malignancy patients require outpatient imaging, tissue sampling, and staging, and many undergo neoadjuvant therapy before operative intervention. The aims of this study were to evaluate the effect of the COVID-19 pandemic on hepato-pancreato-biliary oncologic operations and to determine whether trends in neoadjuvant therapy were altered by the pandemic. Methods: Adult patients in the United States undergoing oncologic operations for pancreatic, primary and secondary hepatic malignancies, with or without neoadjuvant therapy, were extracted from the Vizient Clinical Data Base. Control chart analysis was used to plot trends over time and to determine whether changes were statistically significant. Wilcoxon rank-sum tests also compared monthly operative volume from pre-pandemic (12 month) and pandemic (28 months) periods. Results: A total of 36,553 patients were identified over 40 months. Mean monthly pancreatic oncologic operations were unaffected by the pandemic (P = .257). Operations for pancreatic oncologic operations with prior neoadjuvant therapy increased throughout the pandemic (P = .002). Oncologic operations for primary and secondary hepatic malignancies were significantly reduced for 4 and 2 months, respectively, at the beginning of the pandemic but returned to their pre-pandemic baseline within 4 months (P = .169 and P = .598). Conclusion: Pancreatic operation volumes for cancer did not change, but pancreatic operations after neoadjuvant therapy continued to increase during the pandemic. Operations for hepatic malignancy were transiently disrupted but quickly normalized. These observations suggest that surgery for hepato-pancreato-biliary malignancies was prioritized during the pandemic.
Language	English
Publishing date	2024-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2024.02.023
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Article ; Online: ASO Visual Abstract: Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: A SEER Database Analysis of Mucinous and Non-mucinous Histologies.

Tsagkalidis, Vasileios / Choe, Jennie K / Beninato, Toni / Eskander, Mariam F / Grandhi, Miral S / In, Haejin / Kennedy, Timothy J / Langan, Russell C / Maggi, Jason C / Pitt, Henry A / Alexander, H Richard / Ecker, Brett L

Annals of surgical oncology

2024

Language	English
Publishing date	2024-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-15346-1
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Article: The Predictive Value of A, B, and C-Type Natriuretic Peptides in People at Risk of Heart Disease: Protocol for a Longitudinal Observational Study.

Prickett, Timothy C R / Pearson, John F / Troughton, Richard W / Kennedy, Martin A / Espiner, Eric A

JMIR research protocols

2023 Volume 12, Page(s) e37011

Abstract: ... to higher BNP levels. A closely related vascular hormone (C-type natriuretic peptide [CNP]) showed opposite ...

Abstract	Background: Heart disease and stroke are major and often unheralded causes of serious morbidity and premature death in middle age. Early detection of those most at risk is an urgent unmet need for instituting preventative measures. In an earlier community study (Canterbury Health, Ageing and Life Course [CHALICE]) of healthy people aged 50 years, contrary to previous reports, low levels of the heart hormone B-type natriuretic peptide (BNP) were associated with reduced measures of heart function and higher markers of vascular risk. A specific gene variant (rs198358) was found to be an independent contributor to higher BNP levels. A closely related vascular hormone (C-type natriuretic peptide [CNP]) showed opposite associations-higher levels were correlated with higher vascular risk and reduced cardiac function. To determine whether these novel findings predict serious heart or vascular disease in later life, this proposal re-examines the same CHALICE participants 15 years later. Objective: The primary objective is to determine the predictive value of (1) low plasma concentrations of the circulating cardiac hormones (atrial natriuretic peptide [ANP] and BNP) and (2) high levels of the vascular hormone CNP at age 50 years in detecting impaired cardiac and vascular function 15 years later. Secondary objectives are to determine specific associations of individual analytes (ANP, BNP, CNP, cyclic guanosine monophosphate [cGMP]) with echo-derived changes in cardiac performance at ages 50 years and 65 years. Methods: All of the 348 participants (205/348, 58.9% female; 53/348, 15.2% Māori or Pacifica ethnicity) participating in the original CHALICE study-free of history of heart or renal disease at age 50 years and who consented to further study-will be contacted, recruited, and restudied as previously described. Data will include intervening health history, physical examination, heart function (speckle-tracking echocardiography), vascular status (carotid intimal thickness), and genetic status (genome-wide genotyping). Laboratory measures will include fasting blood sampling and routine biochemistry, ANP, BNP, CNP, their downstream effector (cGMP), and their bio-inactive products. Humoral metabolic-cardiovascular risk factors will be measured after an overnight fast. Primary outcomes will be analyzed using multiple linear regression. Results: The study will commence in 2022 and be completed in 2024. Conclusions: Proving our hypothesis-that low BNP and high CNP at any age in healthy people predict premature aging of heart and blood vessels, respectively-opens the way to early detection and improved outcomes for those most at risk. Confirmation of our hypotheses would improve current methods of screening and, in appropriate cases, enable interventions aimed at increasing natriuretic hormones and reducing risk of serious cardiovascular complications using drugs already available. Such advances in detection, and from interventional corrections, have the potential to not only improve health in the community but also reduce the high costs inevitably associated with heart failure. International registered report identifier (irrid): PRR1-10.2196/37011.
Language	English
Publishing date	2023-01-11
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2719222-2
ISSN	1929-0748
ISSN	1929-0748
DOI	10.2196/37011
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Article: A Report of a Rare Case of Rapidly Progressing Immature Teratoma With Associated Splenic Metastasis and Gliomatosis Peritonei.

Adkoli, Anusha / Smith, Colton / Kennedy, Timothy / Aikins, James / Girda, Eugenia

Cureus

2024 Volume 16, Issue 2, Page(s) e54080

Abstract: Gliomatosis peritonei (GP) is a rare condition of mature glial tissue within the peritoneum often associated with immature teratomas. This was a case of rapid progression of immature teratoma with splenic lesions and associated GP. The patient was a 21- ... ...

Abstract	Gliomatosis peritonei (GP) is a rare condition of mature glial tissue within the peritoneum often associated with immature teratomas. This was a case of rapid progression of immature teratoma with splenic lesions and associated GP. The patient was a 21-year-old female who presented with abdominal pain and CT imaging showing suspected malignant teratoma. The patient underwent exploratory laparotomy with fertility-sparing debulking surgery and was diagnosed with stage IIIC grade 3 immature teratoma. She then received adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. Surveillance imaging demonstrated a non-avid splenic lesion. The tumor markers remained normal. She underwent robotic splenectomy and partial peritonectomy with intra-operative findings revealing numerous peritoneal nodules. Follow-up surveillance imaging showed no further lesions. The final histopathology examination demonstrated mature and mesenchymal neural tissue consistent with residual teratoma and no immature elements. The specimens were largely composed of nodules of mature glial tissue and focal areas of mature neuronal tissue. Immunohistochemistry demonstrated glial fibrillary acidic protein (GFAP) and S100 expression, confirming neural origin tissue. Octamer-binding transcription factor 4 (OCT-4) immunostain was negative which confirmed the absence of immature neural tissue. We report a rare case of rapid progression of immature teratoma with splenic metastasis and peritoneal nodules found ultimately to be mature teratoma and associated GP. Recognition of rapidly growing teratoma with new lesions as potential GP is imperative to prevent misdiagnosis as recurrence or progression of disease. This case was treated with secondary debulking surgery which should be a consideration of management if surgically feasible.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.54080
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Article ; Online: Extent of Resection and Long-Term Outcomes for Appendiceal Adenocarcinoma: a SEER Database Analysis of Mucinous and non-Mucinous Histologies.

Annals of surgical oncology

2024

Abstract: Background: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy ... ...

Abstract	Background: Mucinous appendiceal adenocarcinomas (MAA) and non-mucinous appendiceal adenocarcinomas (NMAA) demonstrate differences in rates and patterns of recurrence, which may inform the appropriate extent of surgical resection (i.e., appendectomy versus colectomy). The impact of extent of resection on disease-specific survival (DSS) for each histologic subtype was assessed. Patients and methods: Patients with resected, non-metastatic MAA and NMAA were identified in the Surveillance, Epidemiology, and End Results database (2000-2020). Multivariable models were created to examine predictors of colectomy for each histologic subtype. DSS was calculated using Kaplan-Meier estimates and examined using Cox proportional hazards modeling. Results: Among 4674 patients (MAA: n = 1990, 42.6%; NMAA: n = 2684, 57.4%), the majority (67.8%) underwent colectomy. Among colectomy patients, the rate of nodal positivity increased with higher T-stage (MAA: T1: 4.6%, T2: 4.0%, T3: 17.1%, T4: 21.6%, p < 0.001; NMAA: T1: 6.8%, T2: 11.4%, T3: 25.6%, T4: 43.8%, p < 0.001) and higher tumor grade (MAA: well differentiated: 7.7%, moderately differentiated: 19.2%, and poorly differentiated: 31.3%; NMAA: well differentiated: 9.0%, moderately differentiated: 20.5%, and 44.4%; p < 0.001). Nodal positivity was more frequently observed in NMAA (27.6% versus 16.4%, p < 0.001). Utilization of colectomy was associated with improved DSS for NMAA patients with T2 (log rank p = 0.095) and T3 (log rank p = 0.018) tumors as well as moderately differentiated histology (log rank p = 0.006). Utilization of colectomy was not associated with improved DSS for MAA patients, which was confirmed in a multivariable model for T-stage, grade, and use of adjuvant chemotherapy [hazard ratio (HR) 1.00, 95% confidence interval (CI) 0.81-1.22]. Conclusions: Colectomy was associated with improved DSS for patients with NMAA but not MAA. Colectomy for MAA may not be required.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-15233-9
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Article ; Online: Pancreatectomy for intraductal papillary mucinous neoplasm: has anything changed in North America?

Davis, Catherine H / Choubey, Ankur P / Langan, Russell C / Grandhi, Miral S / Kennedy, Timothy J / August, David A / Alexander, H Richard / Pitt, Henry A

HPB : the official journal of the International Hepato Pancreato Biliary Association

2023 Volume 26, Issue 1, Page(s) 109–116

Abstract: Background: Multiple guidelines on the management of intraductal papillary mucinous neoplasm (IPMN) have been published over the past decade. However, practice data are lacking. This study aims to determine whether pancreatectomy procedures, IPMN ... ...

Abstract	Background: Multiple guidelines on the management of intraductal papillary mucinous neoplasm (IPMN) have been published over the past decade. However, practice data are lacking. This study aims to determine whether pancreatectomy procedures, IPMN pathology, or outcomes have changed. Methods: ACS-NSQIP Procedure Targeted Pancreatectomy database was queried for patients with IPMN from 2014 to 2019. Cases were stratified by pathology, tumor stage/cyst size and procedure. Pancreatectomies for IPMN by year, 30-day morbidity, and clinically relevant postoperative pancreatic fistula (CR-POPF) were quantified. Mann-Kendall trend tests were performed to assess surgical trends and associated outcomes over time. Results: 3912 patients underwent pancreatectomy for IPMN. 21% demonstrated malignancy and 79% were benign. Morbidity and mortality occurred in 29.7% and 1.5% of cases, respectively. Over time, no change was observed in use of pancreatectomy for IPMN (10%) or in benign/malignant pathology, or cyst size. Robotic approach increased from 9.1% to 16.5% with decreases in laparoscopic (19.5%-15.0%) and open interventions (71.5%-68.1%, p = 0.016). No change was observed over time in morbidity or mortality; however, rates of CR-POPF decreased (18.8%-13.8%, p < 0.001). Conclusions: Practice patterns in treatment of IPMN have not changed significantly in North America. More patients are undergoing robotic pancreatectomy, and postoperative pancreatic fistula rates are improving.
MeSH term(s)	Humans ; Pancreatectomy/adverse effects ; Pancreatectomy/methods ; Carcinoma, Pancreatic Ductal/pathology ; Pancreatic Intraductal Neoplasms/surgery ; Pancreatic Fistula/etiology ; Pancreatic Fistula/surgery ; Pancreatic Neoplasms/pathology ; Cysts/surgery ; Retrospective Studies
Language	English
Publishing date	2023-09-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2023.09.001
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Article: Association between

Greendyk, Joshua D / Allen, William E / Alexander, H Richard / Beninato, Toni / Eskander, Mariam F / Grandhi, Miral S / Kennedy, Timothy J / Langan, Russell C / Maggi, Jason C / De, Subhajyoti / Court, Colin M / Ecker, Brett L

Biomedicines

2023 Volume 11, Issue 11

Abstract: Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC). ...

Abstract	Several molecular biomarkers have been identified to guide induction treatment selection for localized pancreatic ductal adenocarcinoma (PDAC).
Language	English
Publishing date	2023-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11113058
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Article ; Online: Measuring Implicit Bias in ICU Notes Using Word-Embedding Neural Network Models.

Cobert, Julien / Mills, Hunter / Lee, Albert / Gologorskaya, Oksana / Espejo, Edie / Jeon, Sun Young / Boscardin, W John / Heintz, Timothy A / Kennedy, Christopher J / Ashana, Deepshikha C / Chapman, Allyson Cook / Raghunathan, Karthik / Smith, Alex K / Lee, Sei J

Chest

2024

Abstract: Background: Language in nonmedical data sets is known to transmit human-like biases when used in natural language processing (NLP) algorithms that can reinforce disparities. It is unclear if NLP algorithms of medical notes could lead to similar ... ...

Abstract	Background: Language in nonmedical data sets is known to transmit human-like biases when used in natural language processing (NLP) algorithms that can reinforce disparities. It is unclear if NLP algorithms of medical notes could lead to similar transmissions of biases. Research question: Can we identify implicit bias in clinical notes, and are biases stable across time and geography? Study design and methods: To determine whether different racial and ethnic descriptors are similar contextually to stigmatizing language in ICU notes and whether these relationships are stable across time and geography, we identified notes on critically ill adults admitted to the University of California, San Francisco (UCSF), from 2012 through 2022 and to Beth Israel Deaconess Hospital (BIDMC) from 2001 through 2012. Because word meaning is derived largely from context, we trained unsupervised word-embedding algorithms to measure the similarity (cosine similarity) quantitatively of the context between a racial or ethnic descriptor (eg, African-American) and a stigmatizing target word (eg, nonco-operative) or group of words (violence, passivity, noncompliance, nonadherence). Results: In UCSF notes, Black descriptors were less likely to be similar contextually to violent words compared with White descriptors. Contrastingly, in BIDMC notes, Black descriptors were more likely to be similar contextually to violent words compared with White descriptors. The UCSF data set also showed that Black descriptors were more similar contextually to passivity and noncompliance words compared with Latinx descriptors. Interpretation: Implicit bias is identifiable in ICU notes. Racial and ethnic group descriptors carry different contextual relationships to stigmatizing words, depending on when and where notes were written. Because NLP models seem able to transmit implicit bias from training data, use of NLP algorithms in clinical prediction could reinforce disparities. Active debiasing strategies may be necessary to achieve algorithmic fairness when using language models in clinical research.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2023.12.031
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Article ; Online: Regulation of stress granule formation in human oligodendrocytes.

Pernin, Florian / Cui, Qiao-Ling / Mohammadnia, Abdulshakour / Fernandes, Milton G F / Hall, Jeffery A / Srour, Myriam / Dudley, Roy W R / Zandee, Stephanie E J / Klement, Wendy / Prat, Alexandre / Salapa, Hannah E / Levin, Michael C / Moore, G R Wayne / Kennedy, Timothy E / Vande Velde, Christine / Antel, Jack P

Nature communications

2024 Volume 15, Issue 1, Page(s) 1524

Abstract: Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to ... ...

Abstract	Oligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.
MeSH term(s)	Humans ; Cytoplasmic Granules/metabolism ; Stress Granules ; Oligodendroglia ; Cytokines/metabolism ; Stress, Physiological ; Multiple Sclerosis/metabolism
Chemical Substances	Cytokines
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45746-6
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Article ; Online: Adult Kawasaki disease: a rare and challenging diagnosis-a case report.

O' Connor, Timothy / McNally, Cora / Kennedy, Mark W

European heart journal. Case reports

2023 Volume 7, Issue 9, Page(s) ytad397

Abstract: Background: Kawasaki disease (KD) is an acute systemic vasculitis which predominantly occurs in childhood but rarely in adulthood. Diagnosis relies on the presence of typical clinical features; however, patients may present atypically, increasing the ... ...

Abstract	Background: Kawasaki disease (KD) is an acute systemic vasculitis which predominantly occurs in childhood but rarely in adulthood. Diagnosis relies on the presence of typical clinical features; however, patients may present atypically, increasing the challenge of timely diagnosis for physicians. Case summary: We report a case of a 40-year-old male presenting with persistent fever, rash, and unilateral neck swelling. Initial investigations were suggestive of necrotizing lymphadenitis, with a presumed infective aetiology. However, extensive microbiology and immunological investigations remained negative. Cardiac injury was evident with elevated troponin T and NT-proBNP; however, left ventricular systolic function was normal. After 4 days, clinical features consistent with KD were noted and the results of a lymph node biopsy supported this diagnosis. Despite timely treatment with intravenous immunoglobulins (IVIG) and high-dose aspirin, follow-up computed tomography (CT) coronary angiography demonstrated two sequential aneurysms (max 6 mm) in the right coronary artery, plus one small subtle aneurysm in the proximal left anterior descending artery (4 mm). Discussion: Diagnosis of adult KD remains challenging, as symptoms often present sequentially over time rather than simultaneously and many of the clinical features necessary for diagnosis share commonality with other infectious disease processes.
Language	English
Publishing date	2023-08-18
Publishing country	England
Document type	Case Reports
ISSN	2514-2119
ISSN (online)	2514-2119
DOI	10.1093/ehjcr/ytad397
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