United States

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.

AMA Research Challenge 2022

Anticancer Effect of Azadirachta Indica Products on Prostate Cancer

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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.

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

Background: The Achilles Tendon is difficult to visualize because it yields a low signal-to-noise ratio that precludes MRI visualization. While ultrasound yields competent qualitative images, it provides limited quantitative measures. Recent studies, however, have shown aligning the Achilles at a 55-degree angle to the MRI’s primary axis, denoted “the magic angle,” boosts signal-to-noise ratio. Wengler et al., applied diffusion tensor imaging (DTI), an MRI measure that creates images by leveraging the movement of water, to visualize and quantify diffusivity within the Achilles tendons of participants. This paper promoted DTI as a visualization tool for Achilles pathologies, and we further built upon its findings by studying whether DTI yields reproducible results.

Methods: Participants (n=10) with healthy Achilles were included. The right Achilles was imaged in an MRI with the ankle placed at a 55-degree angle relative to the magnet in a 3T MRI. 6-mm transverse slice images were obtained with the following parameters: 1 mm2 isotropic resolution, 2 signal averaging, 5000/58 ms repetition/echo times, 500s/mm2 diffusion strength, 30 gradient directions, and 5 mins scan time. Participants were then given a 5–10-minute break and had the same Achilles re-imaged, following the same steps as before. The MRI images were post-processed with DSI Studio, an open-source diffusion analysis software (http://dsi-studio.labsolver.org). Fractional anisotropy (FA) along with mean (MD), radial (RD), and axial diffusivity (AD) were measured, and reliability was assessed by visualizing Bland-Altman plots. Scan and rescan values were averaged within-participant and mean (SD) were reported for the group. Average differences between scan and rescan values are also reported descriptively.

Results: Average diffusivity of scan and rescan images were, FA: (mean (SD)) 0.419(0.092); RD: 0.893(0.304) mm2/s; AD: 1.663(0.545) mm2/s; and MD: 1.150 (0.371) mm2/s. Average difference between scan and rescan were, FA: 0.008(0.072); RD: 0.075(0.267) mm2/s; AD: 0.114(0.455) mm2/s; and MD: 0.088 (0.323) mm2/s. Bland-Altman plots showed the difference between each scan and rescan was within 95% confidence interval for all four diffusivity measures.

Conclusion: Our preliminary study demonstrates that DTI of the AT produces results that are unbiased (bias less than 10% for all metrics), however, consistency between values suggests the need for further optimization (30% inconsistency between scans).

Preliminary Reproducibility Analysis of Diffusion Tensor Imaging of the Achilles Tendon

Abstract Title: Qualitative Interviews with Primary Care and Gynecological Providers about Obesity Treatment 

Matta K, McCabe C, Bailey-Davis L

Background

To reduce the rates of obesity, the United States Preventive Services Task Force (USPSTF) guidelines recommend that clinicians offer/refer any patient with a BMI of 30 kg/m2 or higher to an intensive, multicomponent behavioral intervention. Despite this recommendation, obesity remains a pervasive concern. The purpose of this study was to evaluate the perceived use of USPSTF guidelines in treating obesity by community medicine physicians (CMPs) and gynecologists. The 5 A’s model (e.g., assess, advice, agree, assist, and arrange) was used to organize the process of obesity treatment.

Methods

Semi-structured interviews of CMPs and gynecologists at Geisinger Health were conducted in March-May 2022. Telephone interviews were completed by trained interviewers using an internal service that transcribed the data verbatim. The study team reviewed the transcripts independently in their entirety to identify initial codes using an open coding approach. These preliminary codes were then organized using the 5 A’s model for obesity treatment as themes. Data were further divided into the subthemes of “facilitators,” “barriers,” or “existing” practice within each 5 A theme.

Results

Recruitment response was 36%; 22 physicians contacted, 4 gynecologists and 4 CMPs were interviewed. Overall, physicians indicated that assessment and advice were routinely practiced and aligned with guidelines but agree, assist, and arrange were areas of weakness. By each A, the facilitators include: Assess: medical jargon in conversation Advice: personalizing advice; Agree: shared-decision making about referrals; Assist: none; and Arrange: specialty referrals. Conversely, barriers include: Assess: patient discomfort; Advice: lacking education; Agree: none; Assist: anti-obesity medications; Arrange: referrals out of Geisinger/referral results.


Conclusion

Physicians are adopting practices to advance Agreement, perceive barriers to Assisting and Arranging, and although Assessment and Advice were commonly practiced, there is discomfort with starting conversations and management strategies. These findings are mixed relevant to prior 5 As research. Our finding that Assess and Advice are practiced and that physicians struggle with the Assist and Arrange is consistent, however greater facilitation of Agreement is novel. These findings are useful for understanding why obesity treatment practices are not aligned with the guidelines, and where improvements could be made to support physicians and patients.

Qualitative Interviews with Primary Care and Gynecological Providers about Obesity Treatment

Background
The literature finds that 70% of transgender people report healthcare discrimination, along with radically increased rates of MDD, AUD, SI, SA, and mental illness. 41% self-reported a history of SA, with nonaccess to gender-affirming surgery equating a 71% higher odds.

Case Presentation
Joshua, a 16 year-old transgender male, using he/him/his pronouns, with no known psychiatric history, was admitted to the children's hospital for intentional Tylenol overdose, presenting with severe abdominal pain, somnolence, and nonbilious emesis, with elevated LFTs and INR, but metabolic panel and CBC otherwise within normal limits. The patient was promptly treated with N-acetylcysteine, showing improved alertness the next day, along with quiet but appropriate affect and mood. The patient admitted to two years of depression and two suicide attempts. Inpatient PHQ-9 was 29. Joshua reported a supportive household, but consistent bullying and misgendering at school, with peers and teachers refusing to use his chosen name and continuing to refer to him as “a girl”, harassing him any time that he uses male restrooms. Joshua has never followed with a psychiatrist or received gender-affirming treatment, but desires hormone therapy. While inpatient, Joshua's senior resident was adamant that she and her team use Joshua's chosen name and consistently use male pronouns, presenting Joshua as a "16 year-old male". 

Discussion
The hospital used a standard EMR, allowing for SOGIE data to be put into charts, but not allowing names or genders to be changed. The team was intentional about using accurate pronouns and Joshua's chosen name in documentation, and on a virtual "post-it". However, when running the list at the end of the day, the senior resident incorrectly named Joshua as "Allison", misgendering him. Despite the team's efforts, this was the name and sex printed from the EMR.

A survey of 204 transgender children found an overwhelming preference to use their chosen names in documentation, even when considering safety concerns. Even when SOGIE data is available, it is rarely automated into documentation. This case study presents a common barrier to affirmative care for transgender patients through limits in the EMR, necessitating a conscious effort by providers and recognition of their shortcomings.

Next from AMA Research Challenge 2022

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