United States

Background
Lung nodules identified by Low-Dose Computed Tomography (LDCT) are classified radiologically in the Lung Reporting and Data System (LungRADS). Herein, we elucidate clinical and radiomic factors associated with follow-up LungRADS 4 categorization and lung cancer diagnosis in patients with initial LungRADS 2-3 nodules.

Methods
We reviewed 2847 patients’ charts with LDCT screening between 2015 and 2019, identifying 2174 (76.7%) with LungRADS 2-3 baseline nodules, of which 908 had follow-up screening available (41.8%). We abstracted gender, race, smoking history, body mass index (BMI), history of chronic obstructive pulmonary disease (COPD), emphysema, pneumonia, cancer, and family history of lung cancer. Association with subsequent LungRADS 4 nodules and lung cancer was assessed via Cox proportional hazards regression. Among a subset of 132 patients, we performed radiomic analysis by annotating the largest nodule of each baseline scan and training machine learning models using 86 textural features. Clinical, radiomic and combined models were developed via Lasso regression and random forest analyses using five-fold cross-validation to predict a subsequent LungRADS 4 result or lung cancer diagnosis.

Results
Among patients with baseline LungRADS 2-3 nodules, 23 (1.1%) developed lung cancer. Age(p=0.04), pack-years (p&lt;0.005), family history of lung cancer (p&lt;0.005), COPD (p=0.02) and emphysema (p&lt;0.005) were associated with lung cancer. 39 patients with follow-up screening (4.3%) progressed to LungRADS 4. Emphysema (p&lt;0.005) was associated with this finding. Machine learning models trained with clinical variables yielded an average area-under-receiver operating characteristic curve (AUC) of 0.543 (random forest) and 0.799 (Lasso regression) for subsequent findings of LungRADS 4 and lung cancer. Radiomic analysis of the largest baseline nodule found an AUC of 0.574 (random forest) and 0.728 (Lasso regression) for findings of LungRADS 4 and lung cancer. Fusion of clinical and radiomic features yielded AUCs of 0.591 (random forest) and 0.718 (Lasso regression) for findings of LungRADS 4 and lung cancer. 


Conclusion
Clinical and radiomic factors showed association with lung cancer diagnosis and LungRADS 4 categorization on follow-up screening in patients with baseline LungRADS 2-3 nodules. Assessment of these features may aid to predict which patients with likely benign screening findings may progress to a higher LungRADS category or develop lung cancer.


2022 AMA Research Challenge

Analysis of Clinical and Radiologic factors associated with follow up Lung RADS score and lung cancer diagnosis in a low-intermediate risk lung cancer screening population

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Ricardo Correa, MD, EdD
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Stephanie Strohbeen, MD
 
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Background
Lung nodules identified by Low-Dose Computed Tomography (LDCT) are classified radiologically in the Lung Reporting and Data System (LungRADS). Herein, we elucidate clinical and radiomic factors associated with follow-up LungRADS 4 categorization and lung cancer diagnosis in patients with initial LungRADS 2-3 nodules.

Methods
We reviewed 2847 patients’ charts with LDCT screening between 2015 and 2019, identifying 2174 (76.7%) with LungRADS 2-3 baseline nodules, of which 908 had follow-up screening available (41.8%). We abstracted gender, race, smoking history, body mass index (BMI), history of chronic obstructive pulmonary disease (COPD), emphysema, pneumonia, cancer, and family history of lung cancer. Association with subsequent LungRADS 4 nodules and lung cancer was assessed via Cox proportional hazards regression. Among a subset of 132 patients, we performed radiomic analysis by annotating the largest nodule of each baseline scan and training machine learning models using 86 textural features. Clinical, radiomic and combined models were developed via Lasso regression and random forest analyses using five-fold cross-validation to predict a subsequent LungRADS 4 result or lung cancer diagnosis.

Results
Among patients with baseline LungRADS 2-3 nodules, 23 (1.1%) developed lung cancer. Age(p=0.04), pack-years (p<0.005), family history of lung cancer (p<0.005), COPD (p=0.02) and emphysema (p<0.005) were associated with lung cancer. 39 patients with follow-up screening (4.3%) progressed to LungRADS 4. Emphysema (p<0.005) was associated with this finding. Machine learning models trained with clinical variables yielded an average area-under-receiver operating characteristic curve (AUC) of 0.543 (random forest) and 0.799 (Lasso regression) for subsequent findings of LungRADS 4 and lung cancer. Radiomic analysis of the largest baseline nodule found an AUC of 0.574 (random forest) and 0.728 (Lasso regression) for findings of LungRADS 4 and lung cancer. Fusion of clinical and radiomic features yielded AUCs of 0.591 (random forest) and 0.718 (Lasso regression) for findings of LungRADS 4 and lung cancer. 


Conclusion
Clinical and radiomic factors showed association with lung cancer diagnosis and LungRADS 4 categorization on follow-up screening in patients with baseline LungRADS 2-3 nodules. Assessment of these features may aid to predict which patients with likely benign screening findings may progress to a higher LungRADS category or develop lung cancer.

poster

Background: The development of tricuspid valve regurgitation (TVR) is a common complication of mitral valve disease. Although severe TVR is usually operated on at the same time as left-sided surgery, there is no clear consensus concerning treatment of mild-moderate TVR.

Methods: We searched electronic databases such as PubMed, Cochrane Library, Scopus, and Web of science to identify studies comparing concomitant tricuspid valve repair at the time of mitral valve surgery to mitral valve surgery alone in patients with mild to moderate TVR. Heterogeneity was measured via the I2 statistic. The Mantel-Haenszel method was used to pool study estimates and the restricted maximum-likelihood estimator was used to estimate between- study heterogeneity. Effect sizes are provided in the form of odds ratios (OR) with 95% confidence intervals (CI).

Results: Our analysis included a total of 25 studies (N = 8,980). The concomitant tricuspid repair group had significantly lower all-cause mortality (OR: 0.57; 95% CI: 0.44 to 0.74) and cardiovascular mortality (OR: 0.49; 95% CI: 0.29 to 0.84). However, the concomitant repair group also had higher odds of permanent pacemaker implantation (OR: 2.09; 95% CI: 1.45 to 3.00). Additionally, while there was no significant difference between the two groups in terms of tricuspid valve reinterventions, stroke, acute kidney injury, concomitant tricuspid valve repair showed statistically significant lower odds for hospitalization due to heart failure (OR: 0.55; 95% CI: 0.22 to 0.58).

Conclusion: Concomitant repair of the tricuspid valve in mild to moderate TVR is a promising intervention to reduce both all-cause and cardiovascular mortality in patients undergoing mitral valve surgeries; however, this risk needs to be weighed against the significantly increased risk of pacemaker implantation.

Concomitant tricuspid valve repair for mild or moderate tricuspid regurgitation for patients undergoing mitral valve surgery? A systematic review and meta-analysis for efficacy and safety

Background: Malperfusion syndrome (MPS) presents a great challenge in treating acute type A aortic dissection (ATAAD) and has a high mortality despite a technically successful operation. We aimed to evaluate the long-term outcomes and progression of the distal aorta in acute type A aortic dissection patients with MPS treated with endovascular fenestration/stenting (F/S) followed by open aortic repair.

Methods: From January 1996-March 2021, 927 patients presented with ATAAD. Five-hundred-and-thirty-four patients had DeBakey I dissection with no-MPS and underwent immediate open repair (no-MPS group), while 97 patients with MPS underwent F/S and delayed open aortic repair (MPS group). Data were collected from the STS database, medical record review, survey, and the national death index (Dec 12, 2021). 

Results: Compared to the no-MPS group, the MPS group had more patients with hypertension (89% vs. 73%, p<0.001), and acute renal failure (60% vs. 4.3%, p<0.001. Both groups had similar aortic root and arch procedures. Postoperatively, the MPS group had similar operative mortality (5.2% vs. 7.9%, p=0.35), more new-onset dialysis (22% vs. 7.7%, p<0.001), similar permanent dialysis (4.7% vs. 2.9%, p=0.50), and prolonged ventilation (72% vs. 49%, p<0.001). The growth rate of the aortic arch (0.38 vs 0.35 mm/year, p=0.81) was similar between the MPS and no-MPS groups. The descending thoracic aorta (1.03 vs. 0.68 mm/year) and abdominal aorta growth rate (0.76 vs. 0.59 mm/year) were significantly higher in the MPS group. The cumulative incidence of reoperation over 10 years (16.2% vs. 17.7%, p=0.91) and 15-year survival outcome (50.4% vs 48.4%, p=0.43) were similar between MPS and no-MPS groups.

Conclusions: Endovascular fenestration/stenting followed by open aortic repair was a valid approach for patients with MPS.

Progression of Distal Aorta after Endovascular Fenestration/Stenting in Acute Type A Aortic Dissection

Background: Azadirachta indica, or neem, is a medicinal plant used commonly throughout South Asia. Neem has demonstrated a wide range of biological activities. This project focuses on the anti-cancer abilities of neem. Our laboratory observations support the anti-cancer effects of neem as a single agent and suggests the ability of neem to improve the efficacy of existing anti-cancer drugs in combination therapies.
Methods: Two different prostate cancer cell lines were used to test the anti-cancer effects of neem. PC3 an androgen receptor negative cell line and C4-2B an androgen independent cell line both have high metastatic potential. Each cell was treated with several different conditions including neem alone, enzalutamide alone, abiraterone alone, and docetaxel alone. Each cell line was also administered combination treatments including neem with enzalutamide, neem with abiraterone and neem with docetaxel. For each of the treatments, a clonogenic assay was used to determine ability of single cell to grow into a colony. Comparisons were analyzed between each of the treatments. 
Results: For both PC3 and C4-2B, enzalutamide alone, abiraterone alone, and docetaxel alone resulted in a lesser number of colonies as compared to the no treatment condition. Treatment conditions involving docetaxel consistently resulted in less than 0-5 colonies per quantification of clonogenic assay. Abiraterone only treatment resulted in less cells compared to no treatment. Neem only and enzalutamide only also resulted in lesser number of colonies though not to the extent of abiraterone and docetaxel. Adjunctive conditions including neem with enzalutamide, neem with abiraterone, and neem with docetaxel produced even less colonies than when the prostate cancer cell lines were treated with their preexisting cancer drug component alone.
Conclusion: As expected, the preexisting prostate cancer drugs (enzalutamide, abiraterone, docetaxel) decreased the ability of single PC3 and C4-2B cells to grow into colonies. Neem alone treatment also appeared to decrease the ability of the prostate cancer cells to grow, although, to a lesser extent than some of the preexisting prostate cancer drugs. Neem as an adjunct to the preexisting cancer drugs appeared to improve the efficacy of the drugs’ ability to decrease cell proliferation.

Anticancer Effect of Azadirachta Indica Products on Prostate Cancer

Background
Patients undergoing radical cystectomy are frequently prescribed prolonged courses of opioids for pain management and have high rates of readmission postoperatively. We aim to determine the association between opioid use and complication rate or length of hospital stay.
Methods
185 total patients who underwent radical cystectomy between 2016 and 2021 were identified in IRB-approved retrospective and prospective databases. data was analyzed using the Wilcoxon-Rank-Sums tests, Chi Squared and Fisher's Exact Tests where appropriate. Multivariate logistic regressions were performed to analyze independent factors associated with postop outcomes. 
Results
This study included 185 patients of median age and BMI of 71.0 and 27.0, respectively. There was no statistically significant difference found in age, BMI, prior tobacco use, or incidence of comorbidities between patients who did and did not require readmission. 21.62% were readmitted within 90 days of surgery. Patients who were readmitted were significantly more likely to have received a longer course of opiates than those who did not undergo readmission. When adjusting for independent demographic variables, multivariate regression analysis demonstrated that each individual day of postoperative opioid use was associated with an increase in the odds of major postoperative complication by 26.84% and an increase in the odds of readmission by 22.23%.
Conclusion
Opioid use represents a possible risk factor for postoperative complications and readmission following radical cystectomy. Further studies are needed to demonstrate if certain classifications of complications are avoidable with conservative administration of opiates in the postoperative period. 



Association between Postoperative Opioid Administration and Surgical Outcomes in Patients Undergoing Radical Cystectomy

Introduction: The gold standard treatment for muscle invasive bladder cancer is radical cystectomy (RC). Robotic assisted radical cystectomy (RARC) has the benefits of decreased blood loss, lower transfusion rates, and shorter length of stay (LOS) when compared to open radical cystectomy (ORC). However, both RARC and ORC are complicated by a high rate of perioperative morbidity with a surgical site complications (SSC) rate ranging from 13-23%. In this study, we sought to determine whether the smaller incisions made during the minimally invasive RARC with intracorporeal urinary diversion (ICUD) resulted in a decreased rate of wound related complications when compared to ORC with extracorporeal urinary diversions (ECUD). 
Methods: We retrospectively reviewed our institutional bladder cancer database for patients undergoing a RC and urinary diversion from 2013 to 2020. Patients were stratified by surgical technique as ORC with ECUD vs. RARC with robotic ICUD. SSC was defined as wound infection, dehiscence, and evisceration and categorized by time of occurrence within 30 days and 31-90 days. Perioperative complications were graded by the Clavien-Dindo classification. Chi-squared analysis was performed to compare the correlation between patient demographics, operative approach, and perioperative characteristics with the presence of SSC.
Results: Of the 273 patients, 128 (46.8%) had ORC with ECUD and 145 (53.1%) had RARC with ICUD. Wound complication rates were significantly lower in patients undergoing the robotic vs. open approach for both 30 day (0.7% vs. 25.0%, p<0.001) and 90 day timeframes (1.4% vs. 28.9%, p<0.001) (Table). Robotic approach led to significantly lower rates of dehiscence vs. open approach in both 30 (0.7% vs. 14.8%, p<0.001) and 90 day totals (1.4% vs. 18.0%, p<0.001). The majority (40.3%) of open and robotic groups were 70-79 years of age (37.5% and 42.8%, p=0.189). 83.5% of patients in both arms had an ileal conduit with the remainder being continent diversions (p=0.02). 
Conclusion: Overall, the SSC rate was significantly lower across all wound complication subcategories (wound infection, dehiscence, and evisceration) in RARC with ICUD which may translate to better perioperative outcomes (shorter LOS and lower readmission rate) and improved patient quality of life. Further studies with larger sample sizes are needed to reinforce the findings.

Evaluation in the Differences of Surgical Site Infection Rates in Robotically Assisted vs. Open Radical Cystectomy

Nationwide Priapism Emergency Department Encounters in the United States

Bladder cancer (BC) accounts for over 500,000 cases diagnosed yearly worldwide and about 83,700 new cases diagnosed in USA in 2021. It is estimated that 17,200 patients will die each year in the USA, due to high rates of tumor recurrence and cancer progression. In early stages, (noninvasive), BC is associated with a favorable course, but 20% of the cases are aggressive and have dismal prognosis[1]. The purpose of our study is to identify biomarkers that
will help in the diagnosis of the disease in early stages to improve survival.
Exosomes are extracellular vesicles that bud off the cell membrane that can be secreted in most body fluids including blood, urine and CSF. Exosomes carry markers of the secretory cells of origin, including those of endosome origin, those involved in intracellular transport, those of cell membrane origin as well as RNA and double stranded DNAs. MicroRNA contained within the exosome has been implicated in modulating recipient cell functions. Tumor cells release exosomes into the extracellular space which has led to increased use of liquid biopsy to identify biomarkers that can aid in early detection of cancer[2]. We studied exosomal miRNA expression from urine samples in patients with BC to evaluate their possible role as tumor markers.
Urine samples were collected from 14 patients with BC at different stages seen in a protocol approved, at the UOB in the NIH. Exosomal RNAs isolated from urine samples were extracted and quantified. RNA was amplified for miRNA expression profile using 384-SeraMir profile qPCR array.
Significant and highly expressed microRNAs were selected for analysis. MicroRNAs commonly dysregulated in urine BC samples were: has-125b-5p, hsa-Let-7b, hsa-148a-5p, hsa- 30da-5p, hsa-423-5p, hsa-16-5p and hsa-191-5p. MicroRNA profiles from the urine samples will
be matched with the tumor tissues in each case. From the total of MicroRNAs obtained, 274 were known microRNAs and 334 were novel predicted microRNAs.
Our study demonstrates the potential of exosomal microRNAs as a useful biomarker to detect non- and invasive bladder cancer. The biomarkers have great potential not only for diagnosis, but also for early detection, detection of tumor recurrence and progression, and treatment response.

References
Key statistics for Bladder Cancer. American Cancer Society. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Accessed June 27, 2022.
Piao XM, Cha EJ, Yun SJ, Kim WJ. Role of Exosomal miRNA in Bladder Cancer: A Promising Liquid Biopsy Biomarker. Int J Mol Sci. 2021;22(4):1713. Published 2021 Feb 8. doi:10.3390/ijms22041713


Urinary Exosomal miRNAs Can Be Utilized as Biomarkers to Detect Early and Invasive Bladder Cancer

OBJECTIVE: Postoperative infection after surgical nephrolithiasis procedures is a significant morbidity concern. Preoperative antibiotics are recommended by multiple professional guidelines to prevent life-threatening infection. However, the efficacy of different antibiotic approaches continues to be poorly understood. The primary objective of this study was to investigate the relationship between perioperative antibiotic regimens and incidence of postoperative urinary tract infection (UTI), systemic inflammatory response syndrome (SIRS), and urosepsis.

METHODS: A retrospective analysis of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) was conducted in this case-cohort study of patients who underwent nephrolithiasis surgery. Subjects whose stone surgery occurred between 2015 and 2021, had a definitive preoperative urine culture, received perioperative antibiotics, and completed a postoperative follow-up visit were included. 25 subjects experienced postoperative UTI, SIRS, or sepsis. 240 did not have any infection-related postoperative issues. Chi-Square tests were performed to determine if there was a relationship between categorical variables of interest [sex, urine culture results, antibiotic regimen, and route of antibiotic administration (oral or intravenous)] and a postoperative infectious outcome.

RESULTS: Postoperative infection was found to be significantly associated with sex [χ2 (1, N=265) = 4.73, p=0.030] but not with urine culture results [χ2 (1, N=265) = 1.86, p=0.17], antibiotic regimen [χ2 (29, N=265) = 44.59, p=0.77], or route of antibiotic administration [χ2 (3, N=265) = 2.22, p=0.53]. A likelihood ratio of 6.9 was seen between positive urine culture and postoperative infection.

CONCLUSION: The risk for postoperative infection after stone surgery is higher among women compared to men. Our data demonstrate no basis for specificity of antibiotic regimen to prevent postoperative infections after surgical nephrolithiasis treatment. To reduce risk of postoperative infection, more important than type of antibiotic, route of administration, or urine culture is simply the importance of consistently giving preoperative antibiotics. These data support AUA and EUA guidelines on the importance of preoperative antibiotics to reduce infectious morbidity after surgery.

Urologic perioperative infection outcomes and prescribed antibiotics

Background
The Brain Injury Guidelines (BIG) provide an approach to stratify TBI patients into 3 categories of severity (BIG 1 to 3) by variables including anatomic size, location, and the use of antiplatelet agents (APA) and anticoagulants (AC). The BIG classify patients on APA or AC as BIG 3 regardless of injury severity, indicating a therapeutic plan involving hospitalization, neurosurgery consultation, and repeat head CT (RHCT). Current evidence is controversial when comparing hematoma progression rates in TBI patients on APA/AC therapies. We evaluated whether pre-injury antiplatelet or anticoagulant use in TBI patients alone should disqualify them from BIG 1 consideration, and if appropriate reclassification could help conserve hospital resources without compromising patient safety.

Methods 
This retrospective study investigated TBI patients presenting to the ED of an urban Level I trauma center from January 2018 until March 2022. Patients categorized as BIG 3 due to prehospital APA/AC use but otherwise fitting all requirements of a BIG 1 injury classification (“Anatomical BIG 1”) were compared to patients with similar anatomic injuries (“True BIG 1”). Head CT progression rates between these two groups were compared.

Results
271 TBI patient records were examined. 27 patients were sorted as true BIG 1, 49 patients as BIG 2, and 195 patients as BIG 3. Thirty five “anatomic BIG 1” patients classified as BIG 3 due to APA/AC status were identified. 19 patients were on APA therapy, 5 were on a DOAC, 3 were on clopidogrel, 3 were on dual APA therapy, 2 were on warfarin, 2 were on dual APA/DOAC therapy, and 1 was on dual APA/AC therapy. All 35 patients showed no progression on RHCT.

Conclusion
Antithrombotic (AT) use in patients with anatomic BIG 1 brain injuries does not appear to increase risk of progression. Pre-hospital AT use consequently does not appear to warrant escalation of care to BIG 3 in patients with such injuries. This could increase patient savings on hospitalization costs as well as reduce exposure to radiation as current practice guidelines indicate that an RHCT not necessary for BIG 1 brain injuries.

Antithrombotic Use In Patients with Mild Brain Injury May Not Mandate Brain Injury Guidelines (BIG) Elevation

Abstract Title: Perceptions Toward Secure Text Messaging Immediately After Hospital Discharge: An Exploratory Study

Authors: Nicholas R. Piniella, OMS-III1,2, Michael Pardo, MD2, Theresa Fuller, MS2, Nathaniel Bessa, BS2, Anuj K Dalal, MD2,3

Institutional Affiliation: 1New York Institute of Technology College of Osteopathic Medicine; 2Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital; 3Harvard Medical School

Background: Patients remain uniquely vulnerable after hospital discharge. Readmissions within seven days may be preventable, especially if patient-reported concerns are quickly addressed by their inpatient physicians. However, few data exist regarding patient and physician attitudes toward post-discharge communication. This exploratory study aims to assess patients’ and physicians’ perceptions regarding direct, secure text messaging during the early discharge period.

Methods: This IRB-approved, prospective, observational study was conducted on patients hospitalized on the general medicine service at a large academic hospital in Boston, MA from 04/01/2018 through 10/31/2018. Subjects were recruited from a convenience sample of English-speaking adult patients who owned a smartphone and were willing to participate in secure text messaging. Subjects were administered a 15-item survey assessing attitudes toward post-discharge communication. The patients’ inpatient physician was instructed on using a HIPAA-compliant mobile messaging application upon discharge; the message thread would terminate after seven days. Physicians were administered surveys assessing post-discharge communication upon patient discharge and after seven days. Data were collected using REDCap. Descriptive statistics were used to analyze responses.

Results: Of 36 patients approached, 29 eligible subjects completed the survey (19 female, 51.8y ± 16.6). Twenty-eight respondents (97%) indicated they were likely to contact their hospital team post-discharge: 27 (96%) by secure text message; 20 (71%) by calling the provider, 18 (64%) by email, 16 (57%) via patient portal, and 15 (54%) by calling the hospital. Of the 29 physicians surveyed, 12 (41%) completed both surveys. Two of nine respondents to the question (22%) believed their patient would want to contact them. Six (50%) physicians were willing to initiate secure messaging. Three (25%) physicians initiated secure messaging; of these, 2 (67%) physicians reported that the time involved was less than 15 minutes. All three physicians reported a favorable experience.

Conclusion: This exploratory study found that patients have a strong desire to text their hospital physicians immediately after discharge, but physicians may underestimate this interest. While the few physicians who participated seemed to favorably rate their experience, larger studies are required to substantiate this finding and thoroughly understand the perceived barriers to adoption.

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Analysis of Clinical and Radiologic factors associated with follow up Lung RADS score and lung cancer diagnosis in a low-intermediate risk lung cancer screening population

Next from 2022 AMA Research Challenge

Concomitant tricuspid valve repair for mild or moderate tricuspid regurgitation for patients undergoing mitral valve surgery? A systematic review and meta-analysis for efficacy and safety

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