Publications by authors named "Jeffrey Clark"

276 Publications

Case Report: Anterior Spinal Cord Ischemia Following Embolization of Cerebellar Arteriovenous Malformation: An Illustrative Case and Review of Spinal Cord Vascular Anatomy.

Front Neurol 2021 7;12:725065. Epub 2021 Sep 7.

Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.

Spinal cord ischemia (SCI) is a rare entity with high mortality and morbidity which can arise from causes such as atherosclerosis, aortic dissection or aneurysm, thromboembolic events or systemic hypotension, and is a potential complication of spinal surgery. Published literature contains very few reports of SCI as a complication of intracranial interventions, highlighting the uncommon nature of SCI in these circumstances. We report the occurrence of anterior SCI in a 69-year-old patient following successful embolization of a cerebellar arteriovenous malformation (AVM), marked by upper extremity weakness, lower extremity paraplegia, loss of bladder and bowel control, and hypercapnic respiratory failure requiring mechanical ventilation. Magnetic resonance imaging (MRI) demonstrated upper cervical diffusion restriction and T2/STIR hyperintensity. Unusually, SCI occurred in this case without intraprocedural catheter wedging or obvious flow limitation, prolonged procedure time, hypercoagulable state, or general hypotension. We review previous cases in the literature as well as spinal cord vascular anatomy, and discuss the possible etiologies of this complication. Spinal cord ischemia could be a very rare complication of neuroendovascular procedures even in the absence of warning signs and should be carefully evaluated in patients with suspected neurologic symptoms after such procedures.
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http://dx.doi.org/10.3389/fneur.2021.725065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452862PMC
September 2021

High resolution three-dimensional strain measurements in human articular cartilage.

J Mech Behav Biomed Mater 2021 Sep 1;124:104806. Epub 2021 Sep 1.

Department of Mechanical Engineering, Imperial College London, London, UK.

An unresolved challenge in osteoarthritis research is characterising the localised intra-tissue mechanical response of articular cartilage. The aim of this study was to explore whether laboratory micro-computed tomography (micro-CT) and digital volume correlation (DVC) permit non-destructive quantification of three-dimensional (3D) strain fields in human articular cartilage. Human articular cartilage specimens were harvested from the knee, mounted into a loading device and imaged in the unloaded and loaded states using a micro-CT scanner. Strain was measured throughout the cartilage volume using the micro-CT image data and DVC analysis. The volumetric DVC-measured strain was within 5% of the known applied strain. Variation in strain distribution between the superficial, middle and deep zones was observed, consistent with the different architecture of the material in these locations. These results indicate DVC method may be suitable for calculating strain in human articular cartilage.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104806DOI Listing
September 2021

Neoadjuvant versus Postoperative Chemoradiotherapy is Associated with Improved Survival for Patients with Resectable Gastric and Gastroesophageal Cancer.

Ann Surg Oncol 2021 Sep 3. Epub 2021 Sep 3.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.

Background: The optimal timing of chemoradiotherapy (CRT) for patients with localized gastric cancer remains unclear. This study aimed to compare the survival outcomes between neoadjuvant and postoperative CRT for patients with gastric and gastroesophageal junction (GEJ) cancer.

Methods: This retrospective study analyzed 152 patients with gastric (42%) or GEJ (58%) adenocarcinoma who underwent definitive surgical resection and received either neoadjuvant or postoperative CRT between 2005 and 2017 at the authors' institution. The primary end point of the study was overall survival (OS).

Results: The median follow-up period was 37.5 months. Neoadjuvant CRT was performed for 102 patients (67%) and postoperative CRT for 50 patients (33%). The patients who received neoadjuvant CRT were more likely to be male and to have a GEJ tumor, positive lymph nodes, and a higher clinical stage. The median radiotherapy (RT) dose was 50.4 Gy for neoadjuvant RT and 45.0 Gy for postoperative RT (p < 0.001). The neoadjuvant CRT group had a pathologic complete response (pCR) rate of 26% and a greater rate of R0 resection than the postoperative CRT group (95% vs. 76%; p = 0.002). Neoadjuvant versus postoperative CRT was associated with a lower rate of any grade 3+ toxicity (10% vs. 54%; p < 0.001). The multivariable analysis of OS showed lower hazards of death to be independently associated neoadjuvant versus postoperative CRT (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.36-0.91; p = 0.020) and R0 resection (HR 0.50; 95% CI 0.27-0.90; p = 0.021).

Conclusions: Neoadjuvant CRT was associated with a longer OS, a higher rate of R0 resection, and a lower treatment-related toxicity than postoperative CRT. The findings suggest that neoadjuvant CRT is superior to postoperative CRT in the treatment of gastric and GEJ cancer.
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http://dx.doi.org/10.1245/s10434-021-10666-yDOI Listing
September 2021

Results and molecular correlates from a pilot study of neoadjuvant induction FOLFIRINOX followed by chemoradiation and surgery for gastroesophageal adenocarcinomas.

Clin Cancer Res 2021 Jul 30. Epub 2021 Jul 30.

Department of Radiation Oncology, Massachusetts General Hospital.

Purpose: We performed a NCI-sponsored, prospective study of neoadjuvant FOLFIRINOX followed by chemoradiation (CRT) with carboplatin/paclitaxel followed by surgery in patients with locally advanced gastric or gastroesophageal (GEA) cancer.

Experimental Design: The primary objective was to determine completion rate of neoadjuvant FOLFIRINOX x 8 followed by CRT. Secondary endpoints were toxicity and pathologic complete response (pCR) rate. Exploratory analysis was performed of ctDNA to treatment response.

Results: From Oct 2017 to June 2018, 25 patients were enrolled. All patients started FOLFIRINOX, 92% completed all 8 planned cycles, and 88% completed CRT. Twenty (80%) patients underwent surgical resection, and 7 had a pCR (35% in resected cohort, 28% ITT ). Tumor-specific mutations were identified in 21 (84%) patients, of whom 4 and 17 patients had undetectable and detectable ctDNA at baseline, respectively. Presence of detectable post-CRT ctDNA (p=0.004) and/or postoperative ctDNA (p=0.045) were associated with disease recurrence.

Conclusions: Here we show neoadjuvant FOLFIRINOX followed by CRT for locally advanced GEA is feasible and yields a high rate of pCR. ctDNA appears to be a promising predictor of postoperative recurrence.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0331DOI Listing
July 2021

Clinical impact of PET/MRI in oligometastatic colorectal cancer.

Br J Cancer 2021 Jul 19. Epub 2021 Jul 19.

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies.

Methods: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020.

Results: Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49-65 years). PET/MR and SCI results were divergent in 19% (95% CI 9-37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412).

Conclusions: These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC.
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http://dx.doi.org/10.1038/s41416-021-01494-8DOI Listing
July 2021

Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer.

JCO Precis Oncol 2021 12;5. Epub 2021 Jan 12.

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.

Purpose: This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) to predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC).

Materials And Methods: Twenty-nine patients with newly diagnosed LARC treated between January 2014 and February 2018 were enrolled. Patients received long-course neoadjuvant chemoradiation prior to surgery. Plasma ctDNA was collected at baseline, preoperatively, and postoperatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital polymerase chain reaction was used to assess mutation fraction in ctDNA.

Results: The median age was 54 years. The overall margin-negative, node-negative resection rate was 73% and was significantly higher among patients with undetectable preoperative ctDNA (n = 17, 88%) versus patients with detectable preoperative ctDNA (n = 9, 44%; = .028). Undetectable ctDNA was also associated with more favorable neoadjuvant rectal scores (univariate linear regression, = .029). Recurrence-free survival (RFS) was calculated for the subset (n = 19) who both underwent surgery and had postoperative ctDNA available. At a median follow-up of 20 months, patients with detectable postoperative ctDNA experienced poorer RFS (hazard ratio, 11.56; = .007). All patients (4 of 4) with detectable postoperative ctDNA recurred (positive predictive value = 100%), whereas only 2 of 15 patients with undetectable ctDNA recurred (negative predictive value = 87%).

Conclusion: Among patients treated with neoadjuvant chemoradiation for LARC, patients with undetectable preoperative ctDNA were more likely to have a favorable surgical outcome as measured by the rate of margin-negative, node-negative resections and neoadjuvant rectal score. Furthermore, we have confirmed prior reports indicating that detectable postoperative ctDNA is associated with worse RFS. Future prospective study is needed to assess the potential for ctDNA to assist with personalizing treatment for LARC.
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http://dx.doi.org/10.1200/PO.20.00220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232395PMC
January 2021

Clinical Usefulness of Genetic Testing For Patients with Moyamoya Disease: A Systematic Review.

World Neurosurg 2021 08 16;152:198-205.e1. Epub 2021 Jun 16.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Division of Pediatric Neurosurgery, Lurie Children's Hospital, Chicago, Illinois, USA. Electronic address:

Background: The effect of genetic factors on presentation and outcomes of moyamoya disease (MMD) is unclear. We aimed to examine differences in presentation of MMD by genetic variant, delineate the influence of genetic factors on outcomes, and characterize the applicability of genetic testing to management.

Methods: A systematic review was conducted using the PubMed, Embase, and Scopus databases. Title/abstract screening, full-text screening, and data extraction were conducted.

Results: Of 1329 articles, 12 were included. Genes included RNF213 (ring finger protein 213), VEGF (vascular endothelial growth factor), and soluble VEGR receptor (sVEGFR) 1 and 2. Patients heterozygous and homozygous for the p.R1480K variant of RNF213 had younger age of onset; were more frequently familial, had posterior cerebral artery involvement, had bilateral lesions; and were more likely to present with cerebral infarction or transient ischemic attack. The heterozygous p.4810K variant is associated with improved postoperative collateral formation. Stroke recurrence, stroke-free survival, neurologic status, and functional condition after surgery are not associated with the p.4180K genotype. Patients homozygous for p.4180K more frequently experience long-term cognitive impairment. Patients with the C/C genotype of VEGF 2634 or decreased sVEGFR-1 and sVEGFR levels postoperatively had greater postoperative collateral formation.

Conclusions: Genetic factors correlate with MMD presentation including age of onset, severity, and symptoms, and angiographic and clinical outcomes after surgery. Incorporation of genetic testing panels into practice may allow for risk stratification, management, and follow-up of children and adults with MMD. However, future studies are necessary to validate the usefulness of genetic testing for MMD before this situation occurs.
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http://dx.doi.org/10.1016/j.wneu.2021.05.130DOI Listing
August 2021

Care Patterns and Overall Survival in Patients With Early-Onset Metastatic Colorectal Cancer.

JCO Oncol Pract 2021 May 27:OP2001010. Epub 2021 May 27.

Division of Hematology & Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, MA.

Purpose: Colorectal cancer (CRC) incidence in patients younger than 50 years of age, commonly defined as early-onset (EO-CRC), is rising. EO-CRC often presents with distinct clinicopathologic features. However, data on prognosis are conflicting and outcomes with modern treatment approaches for metastatic disease are still limited.

Materials And Methods: We prospectively enrolled patients with metastatic CRC (mCRC) to a biobanking and clinical data collection protocol from 2014 to 2018. We grouped the cohort based on age at initial diagnosis: < 40 years, 40-49 years, and ≥ 50 years. We used regression models to examine associations among age at initial diagnosis, treatments, clinicopathologic features, and survival.

Results: We identified 466 patients with mCRC (45 [10%] age < 40 years, 109 [23%] age 40-49 years, and 312 [67%] age ≥ 50 years). Patients < 40 years of age were more likely to have received multiple metastatic resections (odds ratio [OR], 3.533; = .0066) than their older counterparts. Patients with EO-CRC were more likely to receive triplet therapy than patients > 50 years of age (age < 40 years: OR, 6.738; = .0002; age 40-49 years: OR, 2.949; = .0166). Patients 40-49 years of age were more likely to have received anti-EGFR therapy (OR, 2.633; = .0016). Despite differences in care patterns, age did not predict overall survival.

Conclusion: Despite patients with EO-CRC receiving more intensive treatments, survival was similar to the older counterpart. However, EO-CRC had clinical and molecular features associated with worse prognoses. Improved biologic understanding is needed to optimize clinical management of EO-CRC. The cost-benefit ratio of exposing patients with EO-CRC to more intensive treatments has to be carefully evaluated.
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http://dx.doi.org/10.1200/OP.20.01010DOI Listing
May 2021

Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.

Pancreatology 2021 May 15. Epub 2021 May 15.

Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA. Electronic address:

Background: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series.

Methods: This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test.

Results: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006).

Conclusion: Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
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http://dx.doi.org/10.1016/j.pan.2021.05.011DOI Listing
May 2021

TIPS for Adults Without Cirrhosis With Chronic Mesenteric Venous Thrombosis and EHPVO Refractory to Standard-of-Care Therapy.

Hepatology 2021 May 21. Epub 2021 May 21.

Department of Radiology, Section of Vascular and Interventional Radiology, Northwestern University, Chicago, IL, USA.

Background And Aims: Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy.

Approach And Results: Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%.

Conclusions: TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.
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http://dx.doi.org/10.1002/hep.31915DOI Listing
May 2021

Acute-care hospital reencounters in COVID-19 patients.

Geroscience 2021 May 21. Epub 2021 May 21.

Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, 625 N. Michigan Ave, Suite 1150, Chicago IL, 60630, USA.

Acute-care hospital reencounters (ACHEs)-encompassing emergency department visits, observation stays, and hospital readmissions-following COVID-19 hospitalization may exacerbate health care system strain and impair recovery from illness. We sought to characterize these reencounters and factors associated with reencounters. We identified the first consecutive 509 patients hospitalized for COVID-19 within an IL hospital network, and examined ACHEs, experienced within 30 days and 4 months of index hospitalization. We identified independent predictors of reencounter using binary logistic regression. Of 509 patients, 466 (91.6%) were discharged alive from index COVID-19 hospitalization. Within 30 days and 4 months, 12.4% and 21.5% of patients, respectively, experienced ACHEs. The median time to first ACHE was 24.2 (IQR 6.5, 55) days. COVID-19 symptom exacerbation was the leading reason for early ACHE (44.8%). Reencounters, both within 30 days and 4 months, were associated with a history of a neurological disorder before COVID-19 (OR 2.78 [95% CI 1.53, 5.03] and OR 2.75 [95% CI 1.67, 4.53], respectively). Older patients and those with diabetes mellitus, chronic obstructive pulmonary disease, or organ transplantation tended towards more frequent ACHEs. Steroid treatment during COVID-19 hospitalization demonstrated reduced odds of 30-day reencounter (OR 0.31 [95% CI 0.091, 0.79]). Forty-nine patients had repeat SARS-CoV-2 nasopharyngeal testing during a reencounter; twelve (24.5%) patients had positive reencounter tests and experienced more frequent reencounters than those testing negative. COVID-19 symptom exacerbation is a leading cause of early ACHE after COVID-19 hospitalization, and steroid use during index hospitalization may reduce early reencounters. Neurologic illness before COVID-19 predicts ACHEs.
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http://dx.doi.org/10.1007/s11357-021-00378-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138514PMC
May 2021

Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer.

Clin Cancer Res 2021 Apr 29. Epub 2021 Apr 29.

Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts.

Purpose: Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. We evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection.

Experimental Design: A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence.

Results: Of 103 patients, 84 [stage I (9.5%), II (23.8%), III (47.6%), IV (19%)] had evaluable plasma drawn after completion of definitive therapy, defined as surgery only ( = 39) or completion of adjuvant therapy ( = 45). In "landmark" plasma drawn 1-month (median, 31.5 days) after definitive therapy and >1 year follow-up, 15 patients had detectable ctDNA, and all 15 recurred [positive predictive value (PPV), 100%; HR, 11.28 ( < 0.0001)]. Of 49 patients without detectable ctDNA at the landmark timepoint, 12 (24.5%) recurred. Landmark recurrence sensitivity and specificity were 55.6% and 100%. Incorporating serial longitudinal and surveillance (drawn within 4 months of recurrence) samples, sensitivity improved to 69% and 91%. Integrating epigenomic signatures increased sensitivity by 25%-36% versus genomic alterations alone. Notably, standard serum carcinoembryonic antigen levels did not predict recurrence [HR, 1.84 ( = 0.18); PPV = 53.9%].

Conclusions: Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable with tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0410DOI Listing
April 2021

The Incidence, Risk Factors, and Outcomes With 5-Fluorouracil-Associated Coronary Vasospasm.

JACC CardioOncol 2021 Mar 16;3(1):101-109. Epub 2021 Mar 16.

Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Coronary vasospasm is a recognized side effect of 5-FU (fluorouracil). There are limited and conflicting data on the incidence, risk factors and prognostic effect of 5-FU associated vasospasm.

Objectives: To assess the incidence, risk factors and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center.

Methods: We conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram (ECG) changes and/or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared to patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review.

Results: From approximately 4019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (58±13 vs. 64±13 years, P = 0.001), and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%, P = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not.

Conclusion: In a large, single-center report of 5-FU associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors and had no significant difference in progression-free or overall survival compared to those who did not develop vasospasm.
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http://dx.doi.org/10.1016/j.jaccao.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018593PMC
March 2021

Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers".

Ann Clin Transl Neurol 2021 05 30;8(5):1073-1085. Epub 2021 Mar 30.

Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Objective: Most SARS-CoV-2-infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non-hospitalized Covid-19 "long haulers".

Methods: This is a prospective study of the first 100 consecutive patients (50 SARS-CoV-2 laboratory-positive (SARS-CoV-2 ) and 50 laboratory-negative (SARS-CoV-2 ) individuals) presenting to our Neuro-Covid-19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid-19, were never hospitalized for pneumonia or hypoxemia, and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient-reported quality of life measures and standardized cognitive assessments.

Results: Mean age was 43.2 ± 11.3 years, 70% were female, and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: "brain fog" (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), and myalgias (55%), with only anosmia being more frequent in SARS-CoV-2 than SARS-CoV-2 patients (37/50 [74%] vs. 18/50 [36%]; p < 0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS-CoV-2 patients performed worse in attention and working memory cognitive tasks compared to a demographic-matched US population (T-score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p < 0.01).

Interpretation: Non-hospitalized Covid-19 "long haulers" experience prominent and persistent "brain fog" and fatigue that affect their cognition and quality of life.
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http://dx.doi.org/10.1002/acn3.51350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108421PMC
May 2021

Abnormal movements in hospitalized COVID-19 patients: A case series.

J Neurol Sci 2021 04 26;423:117377. Epub 2021 Feb 26.

Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America. Electronic address:

Background: Abnormal movements in Covid-19 patients have been reported with varying degree of frequency, prompting neurologic consultation and additional diagnostic evaluation. We sought to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation.

Methods: We retrospectively analyzed the first 50 consecutive patients with confirmed Covid-19 hospitalized at our tertiary medical care center who underwent acute inpatient neurology consultation from March 2020 through May 2020. Indication for neurologic consultation and diagnostic studies performed were identified by electronic medical record review.

Results: Of the 50 initial consultation requests, 11 (22.0%) patients were evaluated for abnormal movements (nine male and two female). Myoclonus was diagnosed in 6/11 (54.5%) patients. Additionally, two patients were diagnosed with seizures (confirmed on EEG in one), while two additional patients were diagnosed with tremor (physiologic and probable functional). A single case of serotonin syndrome was also identified.

Conclusion: Abnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent type of abnormal movement observed. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.
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http://dx.doi.org/10.1016/j.jns.2021.117377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908881PMC
April 2021

Crizotinib in Patients With MET-Amplified NSCLC.

J Thorac Oncol 2021 06 4;16(6):1017-1029. Epub 2021 Mar 4.

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, Pennsylvania.

Introduction: MET amplification is a rare, potentially actionable, primary oncogenic driver in patients with NSCLC.

Methods: The influence of MET amplification on the clinical activity of the ALK, ROS1, and MET inhibitor, crizotinib (250 mg twice daily), was examined in patients with NSCLC (NCT00585195) who were enrolled into high (≥4 MET-to-CEP7 ratio), medium (>2.2 to <4 MET-to-CEP7 ratio), or low (≥1.8 to ≤2.2 MET-to-CEP7 ratio) amplification categories. Retrospective next-generation sequencing profiling was performed on archival tumor tissue. End points included objective response rate (ORR), duration of response, and progression-free survival.

Results: A total of 38 patients with a MET-to-CEP7 ratio greater than or equal to 1.8 by local fluorescence in situ hybridization testing received crizotinib. All patients were response-assessable, among whom 21, 14, and 3 had high, medium, and low MET amplification, respectively. ORRs of 8 of 21 (38.1%), 2 of 14 (14.3%), and 1 of 3 (33.3%), median duration of response of 5.2, 3.8, and 12.2 months, and median progression-free survival values of 6.7, 1.9, and 1.8 months were observed for those with high, medium, and low MET amplification, respectively. MET amplification gene copy number greater than or equal to 6 was detected by next-generation sequencing in 15 of 19 (78.9%) analyzable patients. Of these 15 patients, objective responses were observed in six (40%), two of whom had concurrent MET exon 14 alterations. No responses were observed among five patients with concurrent KRAS, BRAF, or EGFR mutations.

Conclusions: Patients with high-level, MET-amplified NSCLC responded to crizotinib with the highest ORR. Use of combined diagnostics for MET and other oncogenes may potentially identify patients most likely to respond to crizotinib.
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http://dx.doi.org/10.1016/j.jtho.2021.02.010DOI Listing
June 2021

Social Media in Neurosurgery: A Systematic Review.

World Neurosurg 2021 05 5;149:38-50. Epub 2021 Feb 5.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address:

Objective: Social media has been used increasingly in neurosurgery by individuals. We aimed to identify demographics and preferences of social media use, describe the scope of social media use, and characterize its utility.

Methods: A systematic review was conducted using PubMed, Embase, and Scopus databases. Titles and abstracts from articles identified in the search were read and selected for full-text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for relevant data.

Results: Of 431 resultant articles, 29 were included. Patients and caregivers most commonly used Facebook and Twitter, whereas nearly 50% of neurosurgeons used LinkedIn and Doximity. Patient and caregiver users of social media tended to be <35 years old. Content of posts varied from requesting/providing information (∼40%) to seeking emotional support/forming connections (∼30%). A total of 20.6% of videos were irrelevant to clinical neurosurgery. Factual accuracy of most videos was poor to inadequate. Social media use was associated with greater academic impact for neurosurgical departments and journals. Posts with photos and videos and weekend posts generated 1.2-2 times greater engagement.

Conclusions: Patients and caregivers who use social media are typically younger than 35 years old and commonly use Facebook or Twitter. Neurosurgeons prefer Doximity and LinkedIn. Social media yields information regarding common symptoms and uncovers novel symptoms. Videos are poor-to-inadequate quality and often irrelevant to clinical neurosurgery. Optimizing social media use will augment the exchange of ideas regarding clinical practice and research and empower patients and caregivers.
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http://dx.doi.org/10.1016/j.wneu.2021.01.135DOI Listing
May 2021

Incidence of catheter-associated right atrial thrombus detected by transthoracic echocardiogram.

Echocardiography 2021 03 1;38(3):435-439. Epub 2021 Feb 1.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Introduction: The development of right atrial (RA) thrombus (RAT) is a known complication of central venous catheter insertion (CVC). Deeper insertion of CVC within the RA may increase the risk for RAT development versus those placed at the superior vena cava (SVC)-RA junction. We sought to evaluate the incidence of catheter-associated RAT as detected by transthoracic echocardiograms (TTEs), characterize thrombi though multimodal imaging, and evaluate thrombi management with follow-up imaging.

Methods: A retrospective analysis was conducted of consecutive TTEs from our institution between October 1, 2018, and January 1, 2020, in which a venous catheter was visualized in the RA. Studies were reviewed in detail to determine the presence of suspected RAT. Demographic data, comorbidities, laboratory values, characteristics of the catheter and the thrombus, subsequent imaging and management, and outcomes were collected.

Results: A total of 364 TTEs were performed in 290 patients with a venous catheter visualized in the RA. Of these 290 patients, 15 had an imaging suspicion for RAT yielding an incidence of 5.2%. Management strategies included anticoagulation in 13 (86.7%) patients and catheter removal in 11 (73.3%) patients. At eight months of follow-up, 11 (73.3%) patients had resolution of RAT based on subsequent imaging.

Conclusion: In patients with deeply placed CVC catheters, the incidental detection of RAT by TTE was not trivial. Anticoagulation and catheter removal and replacement, if deemed safe, were effective methods of thrombus management. RAT as a complication of CVCs must be accounted for when addressing factors that influence depth of CVC insertion.
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http://dx.doi.org/10.1111/echo.14987DOI Listing
March 2021

Conditional Survival in Resected Pancreatic Ductal Adenocarcinoma Patients Treated with Total Neoadjuvant Therapy.

J Gastrointest Surg 2021 Jan 26. Epub 2021 Jan 26.

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA, 02114-3117, USA.

Background: Dynamic survival data based on time already survived are lacking for resected borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC) patients who received total neoadjuvant therapy (TNT) with FOLFIRINOX followed by chemoradiation. Conditional survival, i.e., the probability of surviving an additional length of time after having already survived an amount of time, offers such information. We aimed to determine actuarial and conditional overall (OS, COS) and disease-free survival (DFS, CDFS) among this cohort.

Methods: Clinicopathologic data were retrospectively collected for resected BR/LA PDAC patients who received TNT (2011-2019). COS and CDFS rates were calculated for patients being event (death/recurrence)-free at multiple intervals and by recurrence status.

Results: After a median follow-up of 32.1 months, the 183 patients had a median OS and DFS of 39.1 months and 16.8 months, respectively. COS and CDFS increased as a function of time already survived. The probability of surviving an additional 24 months if a patient survived 2 years post-operatively was 70%, whereas the 4-year actuarial OS was 47%. Similarly, the probability of surviving disease-free an additional 24 months after 2 years was 66%, while actuarial 48-month DFS was 27%. COS for disease-free patients increased further over time. For patients remaining disease-free 12 months post-operatively, BR vs. LA status at diagnosis, tumor ≤ 4 cm at diagnosis, and R0 resection were independent predictors of favorable additional OS and DFS.

Conclusions: For resected TNT-treated BR/LA PDAC patients, the probability of surviving an additional length of time increases as a function of survival already accrued. Dynamic survival estimates may allow personalized follow-up and counseling.
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http://dx.doi.org/10.1007/s11605-020-04897-9DOI Listing
January 2021

Impact of PET/MRI in the Treatment of Pancreatic Adenocarcinoma: a Retrospective Cohort Study.

Mol Imaging Biol 2021 06 7;23(3):456-466. Epub 2021 Jan 7.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.

Purpose: Imaging is central to the diagnosis and management of Pancreatic Ductal Adenocarcinoma (PDAC). This study evaluated if positron emission tomography (PET)/magnetic resonance imaging (MRI) elicited treatment modifications in PDAC when compared to standard of care imaging (SCI).

Procedures: This retrospective study included consecutive patients with PDAC who underwent 2-deoxy-2-[F]fluoro-D-glucose ([F]F-FDG) PET/MRI and SCI from May 2017 to January 2019. SCI included abdominal computed tomography (CT), MRI, and/or PET/CT. For patients who had more than one pair of PET/MRI and SCI, each management decision was independently evaluated. Treatment strategies based on each modality were extracted from electronic medical records. Follow-up was evaluated until January 2020.

Results: Twenty-five patients underwent 37 PET/MRI's, mean age was 65 ± 9 years and 13 (13/25, 52 %) were men. 49 % (18/37, 95 % CI 33-64 %) of the PET/MRI scans changed clinical management. Whether the SCI included a PET/CT or not did not significantly modify the probability of management change (OR = 0.9, 95 % CI 0.2-4, p = 1). One hundred percent (33/33) of the available follow-up data confirmed PET/MRI findings.

Conclusions: PET/MRI significantly changed PDAC management, consistently across the different SCI modalities it was compared to. These findings suggest a role for PET/MRI in the management of PDAC.
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http://dx.doi.org/10.1007/s11307-020-01569-7DOI Listing
June 2021

Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions.

Clin Cancer Res 2021 Mar 7;27(6):1695-1705. Epub 2021 Jan 7.

Division of Gastrointestinal Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

Purpose: Receptor tyrosine kinase fusions in colorectal cancers are rare, but potentially therapeutically relevant. We describe clinical, molecular, and pathologic attributes of RTK fusion-associated colorectal cancer.

Experimental Design: We identified all cases with RTK fusions in patients with colorectal cancer seen at Dana-Farber Cancer Institute (Boston, MA) who underwent OncoPanel testing between 2013 and 2018. Clinical, histologic, and molecular features were extracted from the patient charts and molecular testing results.

Results: We identified 12 driver oncogenic fusions in various RTKs. These fusions occurred exclusively in and wild-type tumors and were enriched in right-sided and mismatch repair-deficient (MMR-D) colorectal cancers. All of the MMR-D colorectal cancers with RTK fusions were found in tumors with acquired MMR-D due to promoter hypermethylation and one was associated with a sessile serrated polyp. Molecular profiles of MMR-D colorectal cancer with RTK fusions largely resembled V600E-mutated MMR-D colorectal cancer, rather than those secondary to Lynch syndrome. We describe two patients with fusion-associated microsatellite stable (MSS) colorectal cancer who derived clinical benefit from therapeutic targeting of their translocation. The first harbored an fusion and received sequential crizotinib and alectinib therapy for a total of 7.5 months until developing an L1196Q gatekeeper mutation. The second patient, whose tumor contained an fusion, continues to benefit from entrectinib after 9 months of therapy.

Conclusions: RTK fusions in colorectal cancer are a rare, but important disease subgroup that occurs in and wild-type tumors. Despite enrichment in acquired MMR-D tumors, RTK fusions also occur in MSS colorectal cancer and provide an important therapeutic target.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4073DOI Listing
March 2021

Impact of Treatment Sequencing on Survival for Patients with Locally Advanced Gastric Cancer.

Ann Surg Oncol 2021 May 3;28(5):2856-2865. Epub 2021 Jan 3.

Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.

Background: Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered.

Methods: Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S).

Results: One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p < 0.001). At a median follow-up of 37 months, survival rates on an intention-to-treat basis with TNT + S, Periop, and S + Adj were 52.6%, 59.4%, and 45.3%, respectively. Regimen and completion of MMT significantly affected overall mortality risk. Compared with Periop, TNT + S had similar mortality risk (hazard ratio [HR] 1.28, p = 0.421), whereas S + Adj had increased mortality risk (HR 1.64, p = 0.027).

Conclusions: The choice of treatment sequencing has a major impact on completion rates of multimodal therapy in patients with locally advanced gastric cancer. Less than 50% of patients treated with upfront surgery or perioperative chemotherapy receive all intended therapies. TNT has higher intended therapy completion rates and comparable survival compared with perioperative therapy in our data. Further prospective investigations of TNT are warranted.
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http://dx.doi.org/10.1245/s10434-020-09248-1DOI Listing
May 2021

Transcranial Doppler Ultrasound Evidence of Active Cerebral Embolization in COVID-19.

J Stroke Cerebrovasc Dis 2021 Mar 9;30(3):105542. Epub 2020 Dec 9.

Northwestern University, Feinberg School of Medicine, Ken and Ruth Davee Department of Neurology. Electronic address:

Objective: To report six consecutive patients with confirmed coronavirus disease-2019 (COVID-19) who underwent Transcranial Doppler (TCD) ultrasonography evaluation for cerebral microemboli in the setting of suspected or confirmed acute ischemic stroke.

Methods: Patient data were obtained from medical records from Northwestern Memorial Hospital, Chicago, IL between May and June 2020. All patients with confirmed COVID-19 who underwent clinical TCD ultrasonography for microemboli detection were included.

Results: A total of eight TCD studies were performed in six patients with COVID-19 (4 men and 2 women, median age 65±5), four with confirmed ischemic stroke and two with refractory encephalopathy. Microemboli were detected in three male patients, two patients had suffered a confirmed ischemic stroke and one who developed prolonged encephalopathy. Microemboli of varying intensity were identified in multiple vascular territories in two patients, and microemboli persisted despite therapeutic anticoagulation in a third patient. Of the three patients without evidence of microemboli on TCD ultrasonography, two patients had suffered a confirmed ischemic stroke, while one remained with refractory encephalopathy.

Conclusions: TCD ultrasonography for microemboli detection identified three patients with confirmed COVID-19 with evidence of cerebral arterial microemboli, including one who was therapeutically anticoagulated. TCD ultrasonography provides a non-invasive method for evaluating cerebral microemboli in patients with COVID-19 and may be useful in assessing response to treatment in cases with suspected or confirmed disorders of hypercoagulability. Further studies investigating the prevalence of cerebral microemboli and associated risk factors are needed to characterize their pathogenic mechanism and guide therapeutic interventions in hospitalized COVID-19 patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837312PMC
March 2021

Patient Education in Neurosurgery: Part 2 of a Systematic Review.

World Neurosurg 2021 03 8;147:190-201.e1. Epub 2020 Dec 8.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address:

Background: Increasing focus has been placed on patient education to optimize care. In the second part of a 2-part systematic review, we characterize the scope of interventions specifically created to improve neurosurgery patient education, assess the effectiveness of these interventions, and extract features of existing interventions that may be incorporated into future patient education interventions. Our findings may help promote the creation of effective, patient-centered educational interventions.

Methods: A 2-part systematic review was conducted using the PubMed, Embase, and Scopus databases. Titles and abstracts were read and selected for full text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes.

Results: Of 1617 resultant articles, 33 were included. Print materials, electronic materials, models, and interventions using multiple modalities improved patient knowledge, decreased anxiety, and increased satisfaction. Electronic materials were preferred. Interventions using multiple modalities engaging multiple sensory systems were reported most beneficial. Video was rated the most effective medium for reinforcing spoken conversation between neurosurgeons and patients. Three-dimensional models decreased the time required for preoperative patient conversation but could be perceived as emotionally confronting. Virtual reality was preferred to patient models.

Conclusions: Electronic interventions using multiple modalities in concert with each other may be most effective. Interventions should incorporate baseline knowledge and health literacy and address patient concerns and needs in a manner that is valid cross-contextually, uses clear communication, and is continuous. These interventions will improve the patient-friendliness of discussions with patients.
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http://dx.doi.org/10.1016/j.wneu.2020.11.169DOI Listing
March 2021

Patient Education in Neurosurgery: Part 1 of a Systematic Review.

World Neurosurg 2021 03 8;147:202-214.e1. Epub 2020 Dec 8.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address:

Background: Patient education has become increasingly important in neurosurgery. However, little is known regarding how to comprehensively educate neurosurgical patients. In the first part of a 2-part systematic review, we identify baseline patient understanding and educational needs, examine existing patient education materials, and characterize shortcomings in neurosurgical patient education practices. Our findings may guide neurosurgeons, departments, and professional associations in improving communication with patients.

Methods: A 2-part systematic review was conducted using the PubMed, Embase, and Scopus databases. Titles and abstracts were read and selected for full text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes.

Results: Of 1617 resultant articles, 41 were included. Patient comprehension was low. Patient informational needs differed across patients and between patients and neurosurgeons. Patient informational needs were often unmet, promoting dissatisfaction. Written educational materials from government agencies, professional associations, neurosurgery departments, neurosurgeons, or widely read Web sites were written at a reading level above the recommended reading level, with complex topics written at a higher level. Information found on hospital and university Web sites was poor quality because of self-marketing and lack of reference to peer-reviewed literature. Educational videos created by universities and hospitals were poor quality.

Conclusions: Current in-clinic discussions and education materials show shortcomings, promoting poor comprehension. Neurosurgeons, departments, and professional organizations can act to improve the effectiveness of patient education initiatives. This policy will better inform patients, increase rapport between neurosurgeons and patients, and improve patient decision making and satisfaction.
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http://dx.doi.org/10.1016/j.wneu.2020.11.168DOI Listing
March 2021

Associations of baseline patient-reported outcomes with treatment outcomes in advanced gastrointestinal cancer.

Cancer 2021 02 10;127(4):619-627. Epub 2020 Nov 10.

Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.

Background: Patient-reported outcomes (PROs) assessing quality of life (QOL) and symptom burden correlate with clinical outcomes in patients with cancer. However, to the authors' knowledge, data regarding associations between PROs and treatment response are lacking.

Methods: The authors prospectively approached consecutive patients with advanced gastrointestinal cancer who were initiating a new treatment. Prior to treatment, patients reported their QOL (Functional Assessment of Cancer Therapy-General [FACT-G], 4 subscales: Functional, Physical, Emotional, Social; higher scores indicate better QOL) and symptom burden (Edmonton Symptom Assessment System [ESAS], Patient Health Questionnaire-4 [PHQ-4]; higher scores represent greater symptoms). Regression models were used to examine associations of baseline PROs with treatment response (clinical benefit or progressive disease [PD] at time of first scan), healthcare utilization, and survival.

Results: From May 2019 to April 2020, a total of 112 patients with advanced gastrointestinal cancer were enrolled. For treatment response, 64.3% had CB and 35.7% had PD. Higher baseline ESAS-Physical (odds ratio, 1.04; P = .027) and lower FACT-G Functional (odds ratio, 0.92; P = .038) scores were associated with PD. Higher ESAS-Physical (hazard ratio [HR], 1.03; P = .044) and lower FACT-G Total (HR, 0.96; P = .005), FACT-G Physical (HR, 0.89; P < .001), and FACT-G Functional (HR, 0.87; P < .001) scores were associated with a greater hospitalization risk. Lower FACT-G Total (HR, 0.96; P = .009) and FACT-G Emotional (HR, 0.86; P = .012) scores as well as higher ESAS-Total (HR, 1.03; P = .014) and ESAS-Physical (HR, 1.04; P = .032) scores were associated with worse survival.

Conclusions: Baseline PROs are associated with treatment response in patients with advanced gastrointestinal cancer, namely physical symptoms and functional QOL, in addition to health care use and survival. The findings of the current study support the association between PROs and important clinical outcomes, including the novel finding of treatment response.
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http://dx.doi.org/10.1002/cncr.33315DOI Listing
February 2021

Prospective Phase II Trials Validate the Effect of Neoadjuvant Chemotherapy on Pattern of Recurrence in Pancreatic Adenocarcinoma.

Ann Surg 2020 Oct 19. Epub 2020 Oct 19.

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Objective: The objective of this study was to characterize the patterns of first recurrence after curative-intent resection for pancreatic adenocarcinoma (PDAC).

Summary Background Data: We evaluated the first site of recurrence after neoadjuvant treatment as locoregional (LR) or distant metastasis (DM). To validate our findings, we evaluated the pattern from two phase II clinical trials evaluating neoadjuvant chemotherapy (NAC) in PDAC.

Methods: We identified site of first recurrence from a retrospective cohort of patients from 2011-2017 treated with neoadjuvant chemotherapy followed by chemoradiation and then an operation or an operation first followed by adjuvant therapy, as well as two separate prospective cohorts of patients derived from two phase II clinical trials evaluating patients treated with neoadjuvant chemotherapy in borderline-resectable and locally advanced PDAC RESULTS:: In the retrospective cohorts, 160 out of 285 patients (56.1%) recurred after a median disease-free survival (mDFS) of 17.2 months. The pattern of recurrence was DM in 81.9% of patients, versus LR in 11.1%. This pattern was consistent in patients treated with upfront resection and adjuvant chemotherapy (DM 83.0%, LR 16.9%) regardless of margin-involvement (DM 80.1%, LR 19.4%). The use of NAC did not alter pattern of recurrence; 81.7% had DM and 18.3% had LR. This pattern also remained consistent regardless of margin-involvement (DM 94.1%, LR 5.9%). In the Phase II borderline-resectable trial (NCI# 01591733) cohort of 32 patients, the mDFS was 34.2 months. Pattern of recurrence remained predominantly DM (88.9%) versus LR (11.1%). In the Phase II locally-advanced trial (NCI# 01821729) cohort of 34 patients, the mDFS was 30.7 months. Although there was a higher rate of local recurrence in this cohort, pattern of first recurrence remained predominantly DM (66.6%) versus LR (33.3%) and remained consistent independent of margin-status.

Conclusions: The pattern of recurrence in PDAC is predominantly DM rather than LR, and is consistent regardless of the use of NAC and margin involvement.
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http://dx.doi.org/10.1097/SLA.0000000000004585DOI Listing
October 2020

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

Eur J Nucl Med Mol Imaging 2021 04 9;48(4):1235-1245. Epub 2020 Oct 9.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, White Building Rm 250, 55 Fruit St, Boston, MA, 02114, USA.

Purpose: The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer.

Methods: This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage. Two readers reviewed T and N stage, mesorectal fascia involvement, tumor length, distance from the anal verge, sphincter involvement, and extramural vascular invasion (EMVI). Sigmoidoscopy, digital rectal examination, and follow-up imaging, along with surgery when available, served as the reference standard.

Results: PET/MR outperformed MR in evaluating tumor size (42.5 ± 21.03 mm per the reference standard, 54 ± 20.45 mm by stand-alone MR, and 44 ± 20 mm by PET/MR, P = 0.004), and in identifying N status (correct by MR in 36/62 patients [58%] and by PET/MR in 49/62 cases [79%]; P = 0.02) and external sphincter infiltration (correct by MR in 6/10 and by PET/MR in 9/10; P = 0.003). No statistically significant differences were observed in relation to any other features.

Conclusion: PET/MR provides a more precise assessment of the local extent of rectal cancers in evaluating cancer length, N status, and external sphincter involvement. PET/MR offers the opportunity to improve clinical decision-making, especially when evaluating low rectal tumors with possible external sphincter involvement.
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http://dx.doi.org/10.1007/s00259-020-05036-xDOI Listing
April 2021

Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients.

Ann Clin Transl Neurol 2020 11 5;7(11):2221-2230. Epub 2020 Oct 5.

Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Objective: Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19.

Methods: We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression.

Results: Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001).

Interpretation: Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.
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http://dx.doi.org/10.1002/acn3.51210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664279PMC
November 2020
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