Continuous Glucose Monitoring Using the Dexcom G6 in Cardiac Surgery during the Postoperative Period.

Cardiac surgery is associated with hyperglycemia, which in turn is associated with adverse post-surgical outcomes such as wound infections, acute renal failure, and mortality. This pilot study seeks to determine if Dexcom G6Pro continuous glucose monitor (Dexcom G6Pro CGM) is accurate during the postoperative cardiac surgery period when fluid shifts, systemic inflammatory response syndrome (SIRS), and vasoactive medications are frequently encountered, compared to standard glucose monitoring techniques. METHODS: This study received IRB approval. In this prospective study, correlation between clinical and Dexcom glucose readings was evaluated. Clinical glucose (blood gas, metabolic panel, and point of care [POC]) dataset included 1428 readings from 29 patients, while the Dexcom G6Pro CGM data included 45,645 data points following placement to upper arm. Additionally, average clinical measurements of day and overnight temperatures and hemodynamics were evaluated. Clinical and Dexcom data were restricted to being at least 1 hour after prior clinical reading Matching Dexcom G6Pro CGM data were required within 5 minutes of clinical measure. Data included only if taken at least 2 hours after Dexcom G6Pro CGM insertion (warm-up time) and and analyzed only following ICU admission. Finally, a dataset excluding the first 24 hours after ICU admission was created to explore stability of the device. Patients remained on Dexcom G6Pro CGM until discharge or 10 days postoperatively. RESULTS: The population was 71% male, 14% with known diabetes; 66% required IV insulin infusion. The Clarke error grid plot of all measures post-ICU admission showed 53.5% in Zone A, 45.9% in Zone B, and 0.6% (n=5) in Zones D or E. The restricted dataset that excluded the first 24 hours post-ICU admission showed 55.9% in Zone A, 43.9% in Zone B, and 0.2% in Zone D. Mean absolute relative difference (MARD) between clinical and Dexcom G6Pro CGM measures was 20.6% and 21.6% in the entire post-ICU admission dataset, and the dataset excluding the first 24 hours after ICU admission, respectively. In the sub-analysis of the 12 patients who did not have more than a 5-minute tap in the operating room, a Consensus error grid, demonstrated that after ICU admission, percentage in zone A was 53.9%, zone B 45.4%, and zone C 0.7%. Similar percentages were obtained removing the first 24 hours post-ICU admission. These numbers are very similar to the entire cohort. A consensus error grid created post-ICU admission demonstrated: (Zone A) 54%, (Zone B) 45%, (Zone C) 0.9%, and the following for the dataset created excluding the first 24 hours: (Zone A) 56%, (Zone B) 44%, (Zone C) 0.4%, which demonstrated very close agreement with the original Clarke error grid. No adverse events were reported. CONCLUSIONS: Almost 100% of Dexcom G6Pro CGM and clinical data matching points fell within areas considered as giving clinically correct decisions (Zone A) and clinically uncritical decisions (Zone B). However, the relatively high MARD precludes its use for both monitoring and treatment in the clinical context. As technology evolves, interstitial glucose monitoring may become an important tool to limit iatrogenic anemia and mitigate glycemic fluctuations.

Decisional regret and impacts on quality of life following genitourinary reconstruction for neurogenic bladder: A comparison between acquired and congenital spinal cord injury.

INTRODUCTION: Patient expectations and baseline health are important drivers of outcomes following major genitourinary reconstructive surgery for neurogenic bladder (NGB). Differences in expectations and quality of life (QoL) improvements among different populations with NGB remain insufficiently explored in the literature. OBJECTIVE: To compare decisional regret (DR) and urinary-related QoL (UrQoL) in patients undergoing urinary diversion for NGB arising from spinal cord injury of acquired (A-SCI) and congenital (C-SCI) etiologies. We hypothesize that patients with A-SCI have higher expectations of improvement in QoL following surgery when compared with C-SCI, which may lead to higher DR and decreased UrQoL, postoperatively. DESIGN: In this cross-sectional survey study, we compared A-SCI to C-SCI in terms of DR, UrQoL, and postoperative changes in self-reported physical health, mental health, and pain using validated patient-reported outcome measures. SETTING: Participants were enrolled from a quaternary care institution via mail and MyChart. PARTICIPANTS: The A-SCI group consistied of 17 patients with traumatic spinal cord injury the C-SCI group was composed of 20 patients with spina bifida. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Decisional Regret Scale, Short form- Qualiveen (SF-Qualiveen), and Patient-reported outcomes measurement Information system-10 (PROMIS-10) Global Health surveys. RESULTS: The A-SCI group displayed poorer preoperative physical health than the C-SCI cohort, but absolute postoperative changes in this score, along with mental health score and pain level, were not significant after adjusting for baseline scores and follow-up time. SF-Qualiveen scores revealed significantly worse impact of NGB in UrQoL for A-SCI than for C-SCI when adjusted for other factors. No differences in DR were seen between the groups. CONCLUSIONS: Patients with A-SCI demonstrate lower self-reported baseline physical health compared with patients with C-SCI, which may have implications in setting patient expectations when undergoing urinary diversion. In this small cohort, we found a milder self-reported postoperative impact of NGB in UrQoL in patients with C-SCI.

Practice Trends among US Gastroenterologists following the 2020 American Gastroenterological Association Guidelines on Gastric Intestinal Metaplasia: Data from a Tertiary Care Center.

BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.

Are there specific cytologic features that can predict BRAFV600E mutational status of papillary thyroid carcinoma in fine-needle aspiration specimens?

BACKGROUND: BRAFV600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features. METHODS: A computerized search for diagnosed PTC surgical pathology cases tested for BRAFV600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAFV600E mutational status and histologic subtypes. RESULTS: Study cohort consisted of 113 cases (74 BRAFV600E mutated, 39 BRAFV600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status. CONCLUSION: CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

Can Nonalcoholic Steatohepatitis Be Surgically Cured?: Liver Histologic Comparison After Metabolic Surgery Versus Usual Care.

OBJECTIVE: To compare histologic outcomes in patients with fibrotic nonalcoholic steatohepatitis (NASH) and obesity after metabolic surgery versus nonsurgical care. BACKGROUND: There are no published data comparing the effects of metabolic surgery versus nonsurgical care on histologic progression of NASH. METHODS: Repeat liver biopsies were performed in patients with body mass index >30 kg/m 2 at a US health system whose baseline liver biopsy between 2004 and 2016 confirmed a histologic diagnosis of NASH including the presence of liver fibrosis, but without cirrhosis. Baseline characteristics of liver histology for patients who underwent simultaneous liver biopsy at the time of metabolic surgery were balanced with a nonsurgical control group using overlap weighting methods. The primary composite endpoint required both resolution of NASH and improvement of at least 1 fibrosis stage in the repeat liver biopsy. RESULTS: A total of 133 patients (42 metabolic surgery and 91 nonsurgical controls) had a repeat liver biopsy with a median interval of 2 years. Overlap weighting provided balance for baseline histologic disease activity, fibrosis stage, and time interval between liver biopsies. In overlap-weighted patients, 50.1% in the surgical and 12.1% in the nonsurgical group met the primary endpoint (odds ratio=7.3; 95% CI, 2.8-19.2, P <0.001). NASH resolution and fibrosis improvement occurred in 68.5% and 64.1% of surgical patients, respectively. Surgical and nonsurgical patients who met the primary endpoint lost more weight than their counterparts who did not meet the primary endpoint [mean weight loss difference in the surgical group: 12.2% (95% CI, 7.3%-17.2%) and in the nonsurgical group: 11.6% (95% CI, 6.2%-16.9%)]. CONCLUSIONS: Among patients with fibrotic noncirrhotic NASH, metabolic surgery resulted in simultaneous NASH resolution and fibrosis improvement in half of patients.

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax. REVIEW METHODS: Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis. RESULTS: Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36). CONCLUSION: Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.

Are 99mTC-Sestamibi Single Photon Emission Computed Tomography Scan Results Associated to the Parathyroid Cell Type in Primary Hyperparathyroidism?

INTRODUCTION: 99mTC-sestamibi scintigraphy (SPECT-CT) is a common imaging modality for parathyroid localization in primary hyperparathyroidism (PHPT). Prior studies have suggested that the cellular composition of parathyroid adenomas influences SPECT-CT imaging results. Other biochemical and anatomical factors may also play a role in false negative results. Therefore, after controlling for confounding variables, we sought to determine whether the histologic composition of parathyroid adenomas is associated to SPECT-CT results in patients with single gland disease causing PHPT. METHODS: A retrospective review of patients with PHPT due to confirmed single gland disease was performed over a 2-y period. A 1:1 propensity score matching was done between patients with positive and negative SPECT-CT results with regard to demographical, biochemical, and anatomical characteristics followed by blinded pathologic examination of cell composition in the matched pairs. RESULTS: Five hundred forty two patients underwent routine four gland exploration and 287 (53%) patients were found to have a single adenoma. Of those, 26% had a negative SPECT-CT result. There were significant differences between groups with regards to biochemical profile, gland location, and gland size. All of which became nonsignificant after propensity score matching. Adenomas were primarily composed of chief cells, with no difference between groups (95% versus 97%, P = 0.30). In the positive SPECT-CT group, chief cells were the dominant cell type in 68% of the cases, followed by mixed type (13%), oxyphil cells (12%), and clear cells (7%). This was similar to the negative SPECT-CT group (P = 0.22). CONCLUSIONS: While certain patient's clinical characteristics are associated with SPECT-CT imaging results, histologic cell type is not significantly associated.

Late Referral and Patient Transfer is Associated with Worse Outcomes for Patients Presenting with Initially Uncomplicated Type B Aortic Dissections.

BACKGROUND: Acute type B aortic dissections (TBADs) can become complicated at any time point, necessitating surgical repair. We sought to investigate the effect of interhospital transfer on the development of delayed complications in acute type B aortic dissection (dcTBAD). METHODS: All patients who presented with acute TBAD to a tertiary aortic center from 2015 to 2019 were analyzed. Patients were divided into initially complicated type B aortic dissection (icTBAD) (0-24 hours from symptom onset), dcTBAD (25 hours to 14 days), and uncomplicated type B aortic dissection (ucTBAD) groups. Criteria for complicated dissection were aortic rupture, malperfusion, or rapid aortic growth. Demographics, patient history, the timing of presentation, imaging findings, and clinical outcomes were compared between groups. RESULTS: Of 120 acute TBADs included, 27 (22%) were initially complicated (aortic rupture, n = 9; malperfusion, n = 18). Twenty-one (18%) developed delayed complications (aortic rupture, n = 3; malperfusion, n = 14; rapid growth, n = 4) at a median of 7.0 [4.0, 9.0] days from symptom onset. Seventy-two (60%) remained uncomplicated. Overall, 111 (93%) presented as transfers from outside hospitals (icTBAD, n = 25; dcTBAD, n = 21; ucTBAD, n = 65). Of those, dcTBADs were more likely to have a prolonged delay between presentation to the outside hospital and referral to the tertiary center compared to ucTBADs (median = 1.00 [0.0, 5.0] days delayed vs. 0.00 [0.0, 0.0] days delayed; P < 0.001). Initially uncomplicated patients referred for transfer ≥24 hours from presentation went on to develop dcTBAD more often than those transferred in <24 hours (73% vs 13%; P < 0.001). Of dcTBADs, 38% had no high-risk features on initial imaging. Patients with dcTBAD had significantly longer length of stay (median = 12 vs 7 days; P = 0.006). In-hospital mortality was significantly higher in dcTBADs than ucTBADs (9.5% vs 0%; P = 0.047). In-hospital mortality was not significantly different between dcTBADs and icTBADs (9.5% vs. 11%; P > 0.05). CONCLUSIONS: The incidence and consequence of dcTBADsare not insignificant. Late referral and transfer to a tertiary aortic center (≥24 hours from initial presentation) was associated with dcTBADsrequiring surgical intervention. The development of dcTBADwas associated with increased length of stay and increased in-hospital mortality.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases.

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcoma and myxoid malignant fibrous histiocytoma arising in patients aged ≤40 years with clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34 cm (median 4.1 cm). Anatomic sites included proximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P = .025, P = .005), while tumor depth was also associated with worse EFS (P = <.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis.

Efficacy of One Dose of Laxative on Postoperative Constipation Following Total Knee Arthroplasty.

Postoperative constipation is a common problem among orthopaedic surgical patients leading to discomfort, increased length of stay, and other complications. The primary purpose of this study was to determine the effectiveness of polyethylene glycol compared with docusate sodium for the prevention of constipation, after total knee arthroplasty. The secondary purpose was to examine the effectiveness of polyethylene glycol on pain and strain with bowel movement. A two-group nonequivalent cohort design was used to evaluate the effect of one 17-g dose of polyethylene glycol by mouth on postoperative day 1 compared with usual care with docusate sodium 100 mg starting the day of surgery and continued twice daily at home. There was no significant difference in the rate of constipation between the two cohorts in the 3 days after surgery. There was no difference in reported pain and strain. Future research should focus on the use of pharmacologic and nursing interventions together for prevention of postoperative constipation in patients with arthroplasty surgery.

Impact of Clinical and Endoscopic Features on the Development of Metachronous Colorectal Advanced Serrated Lesions.

BACKGROUND AND AIMS: High-risk adenomas predict metachronous advanced adenomatous neoplasia. Limited data exist on predictors of metachronous advanced serrated lesions (mASLs). We analyzed clinical and endoscopic predictors of mASLs. METHODS: In this retrospective cohort study, adults with >1 outpatient colonoscopy between 2008 and 2019 at a tertiary center were included. Serrated lesions (SLs) included sessile SLs (SSLs), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). Patient and endoscopic characteristics were obtained using electronic medical records. Five-year cumulative incidence of mASL (HP ≥10 mm, SSL ≥10 mm or with dysplasia, any TSA) and factors associated with mASL were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 4990 patients were included and 45.4% were women. Mean age was 60.9 ± 9.2 years and median follow-up time was 3.7 years. Female sex and active smoking were associated with mASL. Endoscopically, any SSL and TSA were associated with mASL. The 5-year cumulative incidence for mASL was 26% (95% confidence interval [CI], 18%-32%) for SSL ≥10 mm, 17% (95% CI, 3.5%-29%) for HP ≥10 mm, 21% (95% CI, 0%-42%) for 3-4 SSLs <10 mm, 18% (95% CI, 0%-38%) for TSA, and 27% (95% CI, 3.6%-45%) for SSL with low-grade dysplasia. Baseline synchronous nonadvanced SL and nonadvanced adenoma were not associated with mASL. CONCLUSIONS: Our data support current recommendations for a 3-year surveillance interval in patients with baseline SSL ≥10 mm, SSL with dysplasia, and TSA. A 3-year interval may be more appropriate than 3-5 years for patients with baseline HP ≥10 mm or 3-4 SSLs <10 mm. Patients with synchronous nonadvanced SLs and adenomas do not appear to be at increased risk of mASL.

Clustering of uveal melanoma: County wide analysis within Ohio.

PURPOSE: To determine if a greater than expected number of cases (clustering) of uveal melanoma occurred within Ohio for any specific region or time period as compared to others. DESIGN: Analysis of population database. METHODS: Ohio Cancer Incidence Surveillance System (OCISS) database (2000-2019) was accessed for the diagnosis of uveal melanoma using the International Classification of Disease for Oncology codes: C69.3 (choroid), C69.4 (ciliary body and iris). Counties within Ohio were grouped by geographic regions (7) and socioeconomic variables. Age- and race-standardized incidence ratios (SIR) were calculated to determine temporal or geographic clustering. RESULTS: Over the twenty-year period, the total number of uveal melanoma cases reported within Ohio were 1,617 with the overall age-adjusted annual incidence of 6.72 cases per million population (95% CI 6.30-7.16). There was an increase in the incidence of uveal melanoma over 20 years (p<0.001) across seven geographic regions, but no significant difference in incidence rates between the regions. There was no difference in incidence based on county classification by age composition (p = 0.14) or education level (p = 0.11). Counties with a low median household income (p<0.001), those classified as urban (p = 0.004), and those with a greater minority population (p = 0.004) had lower incidence. Less populated counties had a higher incidence of uveal melanoma (p<0.001). CONCLUSIONS: There is no evidence of geographic or temporal clustering of uveal melanoma within Ohio from 2000 to 2019.

Management of patients with chronic mesenteric ischemia across three consecutive eras.

BACKGROUND: Endovascular intervention (EI) is the most commonly used modality for chronic mesenteric ischemia (CMI). Since the inception of this technique, numerous publications have reported the associated clinical outcomes. However, no publication has reported the comparative outcomes over a period of time in which both the stent platform and adjunctive medical therapy have evolved. This study aims to assess the impact of the concomitant evolution of both the endovascular approach and optimal guideline-directed medical therapy (GDMT) on CMI outcomes over three consecutive time eras. METHODS: A retrospective review at a quaternary center from January 2003 to August 2020 was performed to identify patients who underwent EIs for CMI. The patients were divided into three groups based on the date of intervention: early (2003-2009), mid (2010-2014), and late (2015-2020). At least one angioplasty/stent was performed for the superior mesenteric artery (SMA) and/or celiac artery. The patients' short- and mid-term outcomes were compared between the groups. Univariable and multivariable Cox proportional hazard models were also conducted to evaluate the clinical predictors for primary patency loss in SMA only subgroup. RESULTS: A total of 278 patients were included (early, 74; mid, 95; late, 109). The overall mean age was 71 years, and 70% were females. High technical success (early, 98.6%; mid, 100%; late, 100%; P = .27) and immediate resolution of symptoms (early, 86.3%; mid, 93.7%; late, 90.8%; P = .27) were noted over the three eras. In both the celiac artery and SMA cohorts, the use of bare metal stents (BMS) declined over time (early, 99.0%; mid, 90.3%; late, 65.5%; P < .001) with a proportionate increase in covered stents (CS) (early, 0.99%; mid, 9.7%; late, 28.9%; P < .001). The use of postoperative antiplatelet and statins has increased over time (early, 89.2%; mid, 97.9%; late, 99.1%; P = .003) and (early, 47%; mid, 68%; late, 81%; P = .001), respectively. In the SMA stent-only cohort, no significant differences were noted in primary patency rates between BMS and CS (hazard ratio, 0.95; 95% confidence interval, 0.26-2.87; P = .94). High-intensity preoperative statins were associated with fewer primary patency loss events compared to none/low- or moderate-intensity statins (hazard ratio, 0.30; 95% confidence interval, 0.11-0.72; P = .014). CONCLUSIONS: Consistent outcomes were observed for CMI EIs across three consecutive eras. In the SMA stent-only cohort, no statistically significant difference in early primary patency was noted for CS and BMS, making the use of CS at additional cost controversial and possibly not cost effective. Notably, the preoperative high-intensity statins were associated with improved SMA primary patency. These findings demonstrate the importance of guideline-directed medical therapy as an essential adjunct to EI in the treatment of CMI.

Formalin Fixation Followed by Paraffin Embedding Allows Long-Term Storage of Proteins for Liquid Chromatography-Tandem Mass Spectrometry Analysis.

In an anatomical pathology laboratory, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to characterize amyloid deposits identified in formalin-fixed paraffin-embedded tissue (FFPET). However, the development of additional tests is partially limited by the lack of information the passage of time has on the proteins in FFPET. To investigate the reliability of LC-MS/MS in the analysis of old FFPET specimens, 1 bone marrow aspirate clot was analyzed by LC-MS/MS yearly from 2014 to 2018, in 3 consecutive months. Peptide-spectrum match, number of peptides identified, and percentage of the proteins covered were the parameters collected for the hemoglobin subunits alpha (HbA), beta (HbB), delta (HbD), and gamma (HbG). These proteins are constant components of the peripheral blood and are present in high and low abundance, allowing the monitorization of the performance of the test across varying protein concentrations. The hemoglobin subunits were stable over the years studied; 71% to 74% of HbA, 77% to 80% of HbB, 69% to 77% of HbD, and 57% to 63% of HbG were covered, with no statistical difference between 2014 and 2018. The number of peptides identified was also constant, 11 to 13 for HbA, 13 to 15 for HbB, 11 to 14 for HbD, and 7 to 9 for HbG. Peptide spectrum match was only slightly more variable: 209 to 327 for HbA, 569 to 1052 for HbB, 286 to 533 HbD, and 142 to 292 for HbG. In conclusion, high abundance hemoglobins, HbA and HbB, and relatively low abundance ones, HbD and HbG, are preserved in FFPET and confidently identified by LC-MS/MS for at least 5 years.

Association of Metformin, Dipeptidyl Dipeptidase-4 Inhibitors, and Insulin with Coronavirus Disease 2019-Related Hospital Outcomes in Patients with Type 2 Diabetes.

OBJECTIVE: The effects of diabetes medications on COVID-19 hospitalization outcomes have not been consistent. We sought to determine the effect of metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and insulin on admission to the intensive care unit (ICU), need for assisted ventilation, development of renal insufficiency, and mortality in patients admitted with COVID-19 infection after controlling for clinical variables and other relevant diabetes-related medications in patients with type 2 diabetes mellitus (DM). METHODS: This was a retrospective study of patients hospitalized with COVID-19 from a single hospital system. Univariate and multivariate analyses were performed that included demographic data, glycated hemoglobin, kidney function, smoking status, insurance, Charlson comorbidity index, number of diabetes medications, and use of angiotensin-converting enzyme inhibitors and statin prior to admission and glucocorticoids during admission. RESULTS: A total of 529 patients with type 2 DM were included in our final analysis. Neither metformin nor DPP4i prescription was associated with ICU admission, need for assisted ventilation, or mortality. Insulin prescription was associated with increased ICU admission but not with need for assisted ventilation or mortality. There was no association of any of these medications with development of renal insufficiency. CONCLUSIONS: In this population, limited to type 2 DM and controlled for multiple variables that have not been consistently studied (such as a measure of general health, glycated hemoglobin, and insurance status), insulin prescription was associated with increased ICU admission. Metformin and DPP4i prescriptions did not have an association with the outcomes.

Neoplastic Progression of Barrett's Esophagus Among Organ Transplant Recipients: a Retrospective Cohort Study.

BACKGROUND: Several small studies reported high risk of progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) patients who undergo solid organ transplantation (SOT) and implied that this may be due to immunosuppressant use. However, the major shortcoming of these studies was the lack of a control population. Therefore, we aimed to determine the rates of neoplastic progression in BE patients who underwent SOT and compare to that in controls and identify the predictors of progression. METHODS: This was a retrospective cohort study of BE patients seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. Demographics, endoscopic and histological findings, history of SOT and fundoplication, immunosuppressant use, and follow-up were abstracted. RESULTS: The study population consisted of 3466 patients with BE, of which 115 had SOT (lung 35, liver 34, kidney 32, heart 14, and pancreas 2) and 704 patients on chronic immunosuppressants but no history of SOT. During a median follow-up of 5.1 years, there was no difference in the annual risk of progression between the three groups (SOT=0.61%, no SOT but on immunosuppressants= 0.82%, and no SOT/no immunosuppressants= 0.94%, p=0.72). On multivariate analysis, immunosuppressant use (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.04-1.82, p=0.025) but not SOT (OR 0.39, 95%CI 0.15-1.01, p=0.053) was associated with neoplastic progression in BE patients. CONCLUSION: Immunosuppression is a risk factor for progression of BE to HGD/EAC. Therefore, close surveillance of BE patients on chronic immunosuppressants needs to be considered.

Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality.

BACKGROUND AND PURPOSE: Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort. METHODS: Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models. RESULTS: Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare. CONCLUSIONS: Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.

Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Predictors for Distal Revascularization Following Femoral Endarterectomy in Chronic Limb-Threatening Ischemia Patients.

OBJECTIVE: This study aims to identify the clinical variables which are predictive for the benefit of concomitant distal revascularization (DR) to prevent Chronic limb-threatening ischemia (CLTI) progression and the need for major limb amputation. METHODS: This is a retrospective cohort study of patients who presented with lower limb ischemia and required at least femoral endarterectomy (FEA), recruited over a period of 15 years (2002-2016). The patient cohort was divided into three groups based on the type of intervention: A (FEA alone), B (FEA + catheter-based intervention/(CBI)), and C (FEA + surgical bypass (SB)). The primary endpoint was to identify independent predictors for the use of concomitant DR (CBI or SB). Secondary endpoints were amputation rate, length of stay, mortality rate, postoperative ankle-brachial index and complications, readmission rate, re-intervention rate, resolution of symptoms and wound status. RESULTS: A total of 400 patients were included, 68.0% were males. Most presenting limbs were at Rutherford class (RC) III and WIfI stage 2, with an ankle-brachial index (ABI) of .47 ± .21 and a TASC II class C lesion. No significant differences were found in the primary-assisted and secondary patency rates between the three groups (P > .05, in all). In the multivariate analyses, clinical variables associated with DR were hyperlipidemia (hazard ratio (HR) 2.1-2.2), TASC II D (HR 2.62), Rutherford class 4 (HR 2.3) and 5 (HR 3.7), as well as WIfI stage ≥3 (HR 1.48). CONCLUSIONS: Femoral endarterectomy is sufficient to treat intermittent claudication. However, patients in whom rest pain, tissue loss or TASC II D anatomic lesion severity are present may benefit from concomitant distal revascularization. Taking into consideration the overall assessment of operative risk factors for each individual patient, proceduralists should have a lower threshold for performing early or concomitant distal revascularization to reduce CLTI progression including additional tissue loss and/or major limb amputation.

Thrombotic outcomes in patients in a large clinical enterprise following COVID-19 vaccination.

Vaccination against COVID-19 reduces infection-related mortality. Unfortunately, reports of vaccine-induced immune thrombotic thrombocytopenia (VITT) in individuals administered adenovirus-vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S) have spurred side effect concerns. To address vaccine hesitancy related to this, it is essential to determine the incidence of VITT (defined by a 50% decrease in platelet count and positive anti-PF4 immunoassay within 4-28 days after vaccination) among patients administered two doses of an mRNA-based COVID-19 vaccination. We identified a retrospective cohort of 223,345 patients in the Cleveland Clinic Enterprise administered a COVID-19 vaccine at any location in Northeast Ohio and Florida from 12/4/2020 to 6/6/2021. 97.3% of these patients received an mRNA-based vaccination. Patients with: (1) a serial complete blood count both before and after vaccination and (2) a decrease in platelet count of ≥ 50% were selected for chart review. The primary outcome was the incidence of thrombotic events, including venous thromboembolism (VTE) and arterial thrombosis, 4-28 days post vaccination. Of 74 cohort patients with acute thrombosis, 72 (97.3%) demonstrated clear etiologies, such as active malignancy. Of two patients with unprovoked thrombosis, only one had findings concerning for VITT, with a strongly positive anti-PF4 antibody assay. In this large, multi-state, retrospective cohort, of 223,345 patients (97.2% of whom received the mRNA-based mRNA-1273 or BNT162b2 vaccines), we detected a single case that was concerning for VITT in a patient who received an mRNA vaccine. The overwhelming majority of patients with a thrombotic event 4-28 days following vaccination demonstrated clear etiologies.