NYU Langone Medical Center

Purpose Genomic alterations of BRAF and NRAS are oncogenic drivers in malignant melanoma and other solid tumors. Tovorafenib is an investigational, oral, selective, CNS-penetrant, small molecule, type II pan‑RAF inhibitor. This first-in-human phase 1 study explored the safety and antitumor activity of tovorafenib. Methods This two-part study in adult patients with relapsed or refractory advanced solid tumors included a dose escalation phase and a dose expansion phase including molecularly defined cohorts of patients with melanoma. Primary objectives were to evaluate the safety of tovorafenib administered once every other day (Q2D) or once weekly (QW), and to determine the maximum-tolerated and recommended phase 2 dose (RP2D) on these schedules. Secondary objectives included evaluation of antitumor activity and tovorafenib pharmacokinetics. Results Tovorafenib was administered to 149 patients (Q2D n = 110, QW n = 39). The RP2D of tovorafenib was defined as 200 mg Q2D or 600 mg QW. In the dose expansion phase, 58 (73%) of 80 patients in Q2D cohorts and 9 (47%) of 19 in the QW cohort had grade ≥ 3 adverse events. The most common of these overall were anemia (14 patients, 14%) and maculo-papular rash (8 patients, 8%). Responses were seen in 10 (15%) of 68 evaluable patients in the Q2D expansion phase, including in 8 of 16 (50%) patients with BRAF mutation-positive melanoma naïve to RAF and MEK inhibitors. In the QW dose expansion phase, there were no responses in 17 evaluable patients with NRAS mutation-positive melanoma naïve to RAF and MEK inhibitors; 9 patients (53%) had a best response of stable disease. QW dose administration was associated with minimal accumulation of tovorafenib in systemic circulation in the dose range of 400–800 mg. Conclusions The safety profile of both schedules was acceptable, with QW dosing at the RP2D of 600 mg QW preferred for future clinical studies. Antitumor activity of tovorafenib in BRAF-mutated melanoma was promising and justifies continued clinical development across multiple settings. ClinicalTrials.gov identifier NCT01425008.

Purpose To determine the factors associated with discharge location in patients with hip fractures and whether home discharge was associated with a lower readmission and complication rate. Methods Hip fracture patients who presented to our academic medical center for operative management of a hip fracture were enrolled into an IRB-approved hip fracture database. Radiographs, demographics, and injury details were recorded at the time of presentation. Patients were grouped based upon discharge disposition: home (with or without home services), acute rehabilitation facility (ARF), or sub-acute rehabilitation facility (SAR). Results The cohorts differed in marital status, with a greater proportion of patients discharged to home being married (51.7% vs. 43.8% vs. 34.1%) (P < 0.05). Patients discharged to home were less likely to require an assistive device (P < 0.05). Patients discharged to home experienced fewer post-operative complications (P < 0.05) and had lower readmission rates (P < 0.05). Being married was associated with an increased likelihood of discharge to home (OR = 1.679, CI = 1.391–2.028, P < 0.001). Being enrolled in Medicare/Medicaid was associated with decreased odds of discharge to home (OR = 0.563, CI = 0.457–0.693, P < 0.001). Use of an assistive device was associated with decreased odds of discharge to home (OR = 0.398, CI = 0.326–0.468, P < 0.001). Increases in CCI (OR = 0.903, CI = 0.846–0.964, P = 0.002) and number of inpatient complications (OR = 0.708, CI = 0.532–0.943, P = 0.018) were associated with decreased odds of home discharge. Conclusion Hip fracture patients discharged to home were healthier and more functional at baseline, and also less likely to have had a complicated hospital course. Those discharged to home also had lower rates of readmission and post-operative complications. Level of Evidence III.

Aspirates of mediastinal neoplasms pose a unique diagnostic challenge due to the overlapping histologic characteristics of mediastinal lesions and the morphologic similarities between mediastinal neoplasms and those originating at other sites. Presented here is the first reported description of the cytomorphologic features of adenocarcinoma NOS of the thymus in aspirate and pleural effusion specimens. The morphologic similarities between thymic and metastatic adenocarcinomas and variable immunohistochemical staining patterns of thymic epithelial neoplasms underscore the importance of pathology-radiology correlation and the careful consideration of the clinical context in the interpretation of cytology specimens.

Introduction Many transmen chose to pursue penile prosthesis (PP) implantation as a stage of genital gender affirming surgery. The prosthesis facilitates penetrative intercourse, as the neophallus lacks rigid erectile tissue. While PP placement is a well-established and relatively low-risk surgical treatment option for erectile dysfunction is the cis-male population, published series of post-phalloplasty prosthesis placement have demonstrated a higher rate of complications and subsequent explant. Objective To demonstrate that an integrated surgical team that participates in all stages of phalloplasty creation can improve penile prosthesis outcomes in transmen. Methods We performed a retrospective review of all transmen who underwent PP implantation at our institution from January 2015 through October 2021, yielding a cohort of 44 men. Men who underwent phalloplasty for another reason (trauma, infection, priapism) were excluded. Both malleable (MPP) and inflatable (IPP) prostheses were included in the cohort. Home phalloplasty refers to phalloplasty performed at our institution, and outside phalloplasty at another institution. The surgical technique emphasizes exclusion of urinary flora from the operative field and avoiding excess anchor material to minimize niduses for infection. We analyzed preoperative, operative, and post-operative characteristics, stratified by whether the phalloplasty was performed at our institution. We also performed logistic regression for predictors of explant in the cohort. Results Cohort characteristics and outcomes are represented in Table 1. 44 PPs were implanted 28 at our institution, 16 at an outside institution. Average age was 32 and 33 in the cohorts, respectively. IPPs were more commonly implanted than MPP. Notably, operative time was significantly lower if the phalloplasty had been constructed at our institution (p=0.014). 16 men total required explant, 7/28 (25%) in the home phalloplasty group and 9/16 (56.3%) in the outside phalloplasty group. Predictors of explantation are shown in Table 2. Significant predictors included age (p=0.013), smoking (p=0.030), operative time (p=0.007), whether the phalloplasty was performed at our institution (p=0.043), and the number of pre-PP revision surgeries (p=0.047). On multivariate logistic regression including all variables significant on univariate analysis, only age (p=0.032) and operative time (p=0.010) remained significant predictors. Conclusions We present a large post-phalloplasty penile prosthesis cohort, demonstrating exceedingly low infection rate and improved explant rate in a cohort of men who all underwent both phalloplasty and prosthesis placement with the same surgical team. Our analysis suggests that phalloplasty characteristics, patient characteristics, and operative time can influence penile prosthesis outcomes. Disclosure No

Introduction Patients are increasingly looking to social media platforms for sources of medical information. TikTok is one of the newest social media platforms primarily geared towards younger audiences. Objective This study aimed to evaluate the quality of information regarding premature ejaculation (PE) on TikTok. Methods The term “premature ejaculation” was searched on TikTok in May 2022. The first 40 top videos that met inclusion criteria were included. Videos were sorted as reliable or unreliable based on accuracy of video content by three reviewers. Relevant user metrics were collected for each video, including: number of likes, shares, followers of user, video length, source of upload and speaker type. Quality of information was numerically evaluated using Patient Education Materials Assessment Tool (PEMAT) and 5-point modified DISCERN validated tools with mean scores obtained from the three reviewers. Results Eight videos were categorized as reliable and 32 videos were categorized as unreliable. Mean number of “likes” per video was higher in the reliable versus unreliable group (1,238 vs. 126, p < 0.018). Accounts posting reliable videos had higher mean number of followers versus unreliable (55,050 vs. 12,042, p = 0.025). The majority of unreliable videos (75%) were posted by self-identified patients or individual users versus 12.5% of reliable videos. 62.5% of reliable videos were posted by individual physicians or physician groups, versus 6.3% of unreliable videos. Few overall videos mentioned indications for PE treatment, types of treatment, or value of psychological intervention (12.5%, 15%, 22.5% and 5.0% respectively.) Video length and number of shares did not differ between groups. Reliable videos had a higher DISCERN (2.7 vs. 0, p < 0.001) and PEMAT (73.0 v. 45.1, p < 0.001). Conclusions Quality of information regarding premature ejaculation on TikTok is low with a significant percentage of videos on this topic fraught with inaccurate information. Given TikTok’s prominence as a social media platform primarily geared towards younger audiences, we emphasize a need for improvement in the quality of information available regarding premature ejaculation and its management. Disclosure No

Introduction There are various analgesic regimens for post-operative pain control following inflatable penile prosthesis (IPP) implantation. Specifically, post-operative pain control with opioids is a common practice, but efforts to minimize narcotic usage are vital given the current opioid epidemic in the United States. Pudendal nerve block (PNB) provides regional perineal and penile anesthesia and represents an attractive option to maximize pain control while minimizing post-operative narcotic use. However, there is a paucity of studies describing whether utilization of PNBs decreases intra- and post-operative narcotic requirements following IPP implantation. Objective To determine whether PNB utilization in a multiethnic population undergoing primary IPP implantation can decrease rates of post-operative opiate usage. Secondary objectives were to assess PNB utilization on intra-operative and 30-day safety outcomes. Methods A single institution retrospective study was conducted of patients who underwent primary IPP implantation between December 2015 and February 2022. Demographic data, intra-operative characteristics, and outcome measures were extracted from electronic medical records. Baseline characteristics of PNB (yes or no) were summarized and analyzed using a Student’s t-test, Chi-square test, or Mann-Whitney U for non-normally distributed variables. PNB usage and PACU opioid administration (yes or no) were analyzed using binary logistic regression for univariate and multivariate analysis. Results A total of 363 patients were included, 294 (81.0%) in the PNB group and 69 (19.0%) in the non-PNB group. The majority of patients were of Hispanic race (62.3%). History of chronic pain (17.7% vs. 7.2%, p=0.03) and hyperlipidemia (52.0% vs. 34.8%, p=0.01) were more prevalent in the PNB group. Significantly more IPPs in the PNB group had cylinders measuring 20 centimeters or greater (57.1% vs 41.2, p=0.017). Estimated blood loss of 50ml or greater (43.1% vs. 20.0%, p<0.001), PACU narcotic usage (61.6% vs. 75.4%, p=0.040) and time (minutes) spent in the PACU (144 [111-185] vs. 238 [162-307], p<0.001) were all significantly lower in the PNB group. There were no significant differences in postoperative and 30-day safety outcomes. On univariate analysis, both PNB (OR=0.52, p=0.043) and age above 65 (OR=0.53, p=0.004) were associated with a lower likelihood of receiving opiates in the PACU, while only age remained significant (OR=0.53, p=0.006) on multivariate analysis. Conclusions Pre-operative PNB decreases intra-operative estimated blood loss, post-operative opioid analgesic requirements and time spent in PACU in patients undergoing a primary IPP implantation. Thus, PBN represents a potentially attractive, non-opioid means of analgesia in patients undergoing primary IPP surgery. Disclosure No

Purpose: Ultrasound (US) is considered a first-line study for painless jaundice. However, in our hospital system, patients with new-onset painless jaundice often have a contrast-enhanced computed tomography (CECT) or magnetic resonance cholangiopancreatography (MRCP) regardless of the sonographic findings. Thus, we investigated the accuracy of US for detection of biliary dilatation in patients with new-onset painless jaundice. Methods: Our electronic medical record was searched from January 1, 2012, to January 1, 2020, for adult patients with new-onset painless jaundice. Presenting complaint/setting, laboratory values, imaging studies/findings, and final diagnoses were recorded. Patients with pain or known liver disease were excluded. A gastrointestinal physician reviewed the laboratory values/chart to classify the type of suspected obstruction. Two radiologists blindly re-reviewed the US scans, and κ between the radiologists was calculated. Fisher exact test and the 2-sample t test were used for statistical analysis. Results: Three hundred sixty patients presented with jaundice (>3 mg/dL), of whom 68 met the inclusion criteria (no pain and no known liver disease). Laboratory values had an overall accuracy of 54%, but were accurate in 87.5% and 85% for obstructing stones/pancreaticobiliary cancer. Ultrasound demonstrated overall accuracy of 78%, but only 69% for pancreaticobiliary cancer and 12.5% for common bile duct stone. Seventy-five percent of the patients underwent follow-up CECT or MRCP regardless of presenting setting. In the emergency department or inpatient setting, 92% of the patients underwent CECT or MRCP regardless of US, and 81% had follow-up CECT or MRCP within 24 hours. Conclusion: A US-first strategy in the setting of new-onset painless jaundice is accurate only 78% of the time. In practice, US was almost never a stand-alone imaging examination in patients presenting to the emergency department or inpatient setting with new-onset painless jaundice, no matter the suspected diagnosis based on clinical and laboratory grounds or on the US findings themselves. However, for milder elevations of unconjugated bilirubin (suspicious for Gilbert disease) in the outpatient setting, a US demonstrating lack of biliary dilatation was often a definitive study for exclusion of pathology.

Total hip arthroplasty (THA) has been referred to as the operation of the century given its success and predictable improvement in quality of life. With the increase in number of THAs performed every year, there is a concomitant rise in the incidence of revision and re-revision surgeries. Failure of THA and revision hip arthroplasty may occur due to a variety of reasons, often in older patients with multiple comorbidities. Revision procedures in this setting are associated with worse outcomes as they are often complicated by limited bone stock and poor soft tissue and bone quality, making reconstruction more challenging. The purpose of this review is to discuss modern techniques for limb salvage following failed THA in the setting of significant bone loss. These include proximal femur replacement, total femur replacement, hip resection arthroplasty, and hip disarticulation.

There is a need for the neuroscience community to advocate for uniformity in the determination of brain death/death by neurologic criteria (BD/DNC). Engagement with state medical societies is one example of this type of advocacy. After determining that her hospital policy on determination of BD/DNC was unclear and inconsistent with accepted standards, the principal author submitted a resolution to the Illinois State Medical Society (ISMS) in an attempt to encourage consistency in institutional policies on the determination of BD/DNC across the state. ISMS ultimately approved a resolution on this topic, but it has some shortcomings, so its impact is unclear. Nonetheless, other neuroscience clinicians are encouraged to engage with their state medical societies to advocate for uniformity in the determination of BD/DNC.

Introduction: Chronic discogenic low back pain (CD-LBP) is caused by degenerated disks marked by neural and vascular ingrowth. Spinal cord stimulation (SCS) has been shown to be effective for pain relief in patients who are not responsive to conventional treatments. Previously, the pain-relieving effect of two variations of SCS has been evaluated in CD-LBP: Burst SCS and L2 dorsal root ganglion stimulation (DRGS). The aim of this study is to compare the effectivity in pain relief and pain experience of Burst SCS with that of conventional L2 DRGS in patients with CD-LBP. Materials and methods: Subjects were implanted with either Burst SCS (n = 14) or L2 DRGS with conventional stimulation (n = 15). Patients completed the numeric pain rating score (NRS) for back pain and Oswestry disability index (ODI) and EuroQoL 5D (EQ-5D) questionnaires at baseline, and at three, six, and 12 months after implantation. Data were compared between time points and between groups. Results: Both Burst SCS and L2 DRGS significantly decreased NRS, ODI, and EQ-5D scores as compared with baseline. L2 DRGS resulted in significantly lower NRS scores at 12 months and significantly increased EQ-5D scores at six and 12 months. Conclusions: Both L2 DRGS and Burst SCS resulted in reduction of pain and disability, and increased quality of life in patients with CD-LBP. L2 DRGS provided significantly increased pain relief and improvement in quality of life when compared with Burst SCS. Clinical trial registration: The clinical trial registration numbers for the study are NCT03958604 and NL54405.091.15.

Background: Corticosteroid injection is the mainstay of nonoperative treatment for trigger finger (stenosing tenosynovitis), but despite substantial experience with this treatment, there is minimal available evidence as to the optimal corticosteroid dosing. The purpose of this study is to compare the efficacy of 3 different injection dosages of triamcinolone acetonide for the treatment of trigger finger. Methods: Patients diagnosed with a trigger finger were prospectively enrolled and treated with an initial triamcinolone acetonide (Kenalog) injection of 5 mg, 10 mg, or 20 mg. Patients were followed longitudinally over a 6-month period. Patients were assessed for duration of clinical response, clinical failure, Visual Analog Scale (VAS) pain scores, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. Results: A total of 146 patients (163 trigger fingers) were enrolled over a 26-month period. At 6-month follow-up, injections were still effective (without recurrence, secondary injection, or surgery) in 52% of the 5-mg group, 62% of the 10-mg group, and 79% of the 20-mg group. Visual Analog Scale at final follow-up improved by 2.2 in the 5-mg group, 2.7 in the 10-mg group, and 4.5 in the 20-mg group. The QuickDASH scores at final follow-up improved by 11.8 in the 5-mg group, 21.5 in the 10-mg group, and 28.9 in the 20-mg group. Conclusions: Minimal evidence exists to guide the optimal dosing of steroid injection in trigger digits. When compared with 5-mg and 10-mg doses, a 20-mg dose was found to have a significantly higher rate of clinical effectiveness at 6-month follow-up. The VAS and QuickDASH scores were not significantly different between the 3 groups.

The aim of this study was to evaluate the bone healing of tight‐fit implants placed in the maxilla and mandible of subjects compromised with metabolic syndrome (MS) and type‐2 Diabetes Mellitus (T2DM). Eighteen Göttingen minipigs were randomly distributed into three groups: (i) control (normal diet), (ii) MS (cafeteria diet for obesity induction), (iii) T2DM (cafeteria diet for obesity induction + Streptozotocin for T2DM induction). Maxillary and mandibular premolars and molar were extracted. After 8 weeks of healing, implants with progressive small buttress threads were placed, and allowed to integrate for 6 weeks after which the implant/bone blocks were retrieved for histological processing. Qualitative and quantitative histomorphometric analyses (percentage of bone‐to‐implant contact, %BIC, and bone area fraction occupancy within implant threads, %BAFO) were performed. The bone healing process around the implant occurred predominantly through interfacial remodeling with subsequent bone apposition. Data as a function of systemic condition yielded significantly higher %BIC and %BAFO values for healthy and MS relative to T2DM. Data as a function of maxilla and mandible did not yield significant differences for either %BIC and %BAFO. When considering both factors, healthy and MS subjects had %BIC and %BAFO trend towards higher values in the mandible relative to maxilla, whereas T2DM yielded higher %BIC and %BAFO in the maxilla relative to mandible. All systemic conditions presented comparable levels of %BIC and %BAFO in the maxilla; healthy and MS presented significantly higher %BIC and %BAFO relative to T2DM in the mandible. T2DM presented lower amounts of bone formation around implants relative to MS and healthy. Implants placed in the maxilla and in the mandible showed comparable amounts of bone in proximity to implants.

Background Concomitant upper extremity and hip fractures present a challenge in postoperative mobilization in the geriatric population. Operative fixation of proximal humerus fractures allows for upper extremity weight bearing. This retrospective study compared outcomes between operative and non-operative proximal humerus fracture patients with concomitant hip fractures. Methods A trauma database of 13,396 patients age > 55 years old was queried for concomitant hip and proximal humerus fracture patients between 2014–2021. Medical records were reviewed for demographics, hospital quality measures, Neer classification, morphine milligram equivalents (MME), and outcomes. All hip fractures were treated operatively. Patients were grouped based on operative vs. non-operative treatment of their proximal humerus fracture. Primary outcomes included comparing postoperative ambulatory status, pain, length of stay (LOS), intensive care unit (ICU) need, discharge disposition, and readmission rates. Results Forty-eight patients (0.4%) met inclusion criteria. Twelve patients (25%) underwent operative treatment for their proximal humerus fracture and 36 (75%) received non-operative treatment. Patients with operative fixations were younger (p < 0.01), had more complex Neer classifications (p = 0.031), more likely to be community ambulators (p < 0.01), and required more inpatient MMEs (p < 0.01). There were no differences in LOS (p = 0.415), need for ICU (p = 0.718), discharge location (p = 0.497), 30-day readmission (p = 0.228), or 90-day readmission (p = 0.135) between cohorts. At 6 months postoperatively, among community or household ambulators, a higher percentage of operative patients returned to their baseline ambulatory functional status, however, this was not significant (70% vs. 52%, p = 0.342). There were three deaths in the non-operative cohort and no deaths in the operative cohort. Conclusion Patients with hip fractures and concomitant proximal humerus fractures treated operatively required more inpatient MMEs and trended toward maintaining baseline ambulatory function. There were no differences in inpatient LOS, ICU need, discharge location, or readmissions. Future larger, multicenter studies are needed to further delineate if operative repair of concomitant proximal humerus fractures provides a benefit in the geriatric population.

Introduction: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. Methods: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. Results: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. Discussion: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Background: Patients undergoing surgery for adult spinal deformity (ASD) are often elderly, frail, and at elevated risk of adverse events perioperatively, with proximal junctional failure (PJF) occurring relatively frequently. Currently, the specific role of frailty in potentiating this outcome is poorly defined. Purpose: To determine if the benefits of optimal realignment in ASD, with respect to the development of PJF, can be offset by increasing frailty. Study design: Retrospective cohort. Methods: Operative ASD patients (scoliosis >20°, SVA>5 cm, PT>25°, or TK>60°) fused to pelvis or below with available baseline (BL) and 2-year (2Y) radiographic and HRQL data were included. The Miller Frailty Index (FI) was used to stratify patients into 2 categories: Not Frail (FI <3) and Frail (>3). Proximal Junctional Failure (PJF) was defined using the Lafage criteria. "Matched" and "unmatched" refers to ideal age-adjusted alignment post-operatively. Multivariable regression determined impact of frailty on development of PJF. Results: 284 ASD patients met inclusion criteria (62.2yrs±9.9, 81%F, BMI: 27.5 kg/m2±5.3, ASD-FI: 3.4±1.5, CCI: 1.7±1.6). 43% of patients were characterized as Not Frail (NF) and 57% were characterized as Frail (F). PJF development was lower in the NF group compared to the F group, (7% vs. 18%; P=0.002). F patients had 3.2X higher risk of PJF development compared to NF patients (OR: 3.2, 95% CI: 1.3-7.3, P=0.009). Controlling for baseline factors, F unmatched patients had a higher degree of PJF (OR: 1.4, 95% CI:1.02-1.8, P=0.03), however, with prophylaxis there was no increased risk. Adjusted analysis shows F patients when matched post-operatively in PI-LL had no significantly higher risk of PJF. Conclusions: An increasingly frail state is significantly associated with the development of PJF after corrective surgery for ASD. Optimal realignment may mitigate the impact of frailty on eventual PJF. Prophylaxis should be considered in frail patients who do not reach ideal alignment goals.