New York Medical College
  • Valhalla, United States
Recent publications
AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology. In preclinical models, small-molecule kinase inhibitors targeting AXL have shown promising anti-tumorigenic potential. This review primarily focuses on the induction, regulation and biological functions of AXL in mediating these tumor-promoting pathways. We discuss a range of therapeutic strategies, including recently developed small-molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and antibody-drug conjugates (ADCs), anti-AXL-CAR, and combination therapies. These interventions are being examined in both preclinical and clinical studies, offering the potential for improved drug sensitivity and therapeutic efficacy. We further discuss the mechanisms of acquired therapeutic resistance, particularly the crosstalk between AXL and other critical receptor tyrosine kinases (RTKs) such as c-MET, EGFR, HER2/HER3, VEGFR, PDGFR, and FLT3. Finally, we highlight key research areas that require further exploration to enhance AXL-mediated therapeutic approaches for improved clinical outcomes. Signal Transduction and Targeted Therapy (2025) 10:37 ; https://doi.
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterised by IgG4-positive plasma cell infiltration into different tissues and organs. Among the heterogeneous clinical features of IgG4-RD, serositis, including pleural and pericardial effusions, is a rare and poorly understood presentation. We described a woman in her late 70s who developed recurrent chylothorax and failed to respond to corticosteroids, immunosuppressives and intrapleural octreotide injection while being treated for newly diagnosed IgG4-RD with serositis as the only manifestation. Her chylothorax was thought to be due to fibroinflammatory damage of the lymphatic duct system from her IgG4-RD, as other differential diagnoses have been largely excluded. We demonstrate the difficulty in establishing the diagnosis of IgG4-RD when only serositis is present, the importance of meticulous workup ruling out other causes and clinical judgement in identifying disease complications versus evaluating alternative diagnoses.
Introduction Prior to the permanent implant of a spinal cord stimulator, patients typically undergo a screening trial using a percutaneously placed lead to ensure adequate response. However, due to several factors, patients may not be candidates for this screening trial and therefore instead undergo a “permanent trial” where either a percutaneous lead or paddle lead is placed using a tunneled extension for the trial, with the intent of conversion to a permanent system. If these patients proceed with an implant, the epidural space is not re‐accessed and only an impulse generator (IPG) is needed. Although this technique is commonly employed, there is a paucity of literature describing outcomes with the “permanent trial” methodology. We present here our clinical experience with this technique. Methods Participants who underwent permanent trials at a single institution between 2014 and 2020 were identified. Charts were reviewed to collect demographic information, numerical rating score (NRS) data, length of follow‐up, revisions, complications, and removals. Results A total of 27 patients who underwent permanent trial placement were identified from a database of 762 patients who underwent SCS placement (3.54%). The permanent placement group included 7 paddle trials, 14 percutaneous trials, and 6 dorsal root ganglion (DRG) trials. The reasons for pursuing a permanent trial included previously aborted percutaneous trial ( n = 8), inability to hold anticoagulation for a prolonged period ( n = 4), previous thoracic spine surgery or presence of thoracic stenosis on MRI ( n = 4), and significant medical comorbidities precluding typical percutaneous trial lead placement at a surgery center ( n = 3). 24/27 (88.8%) proceeded to permanent implant, and 16/24 (66.7%) were considered responders (greater than 50% reduction in pain) after 3 months. Over an average follow‐up of 28.7 months, complications included 1 peri‐operative intracranial hemorrhage delaying IPG placement, 2 lead fractures, 1 lead migration, and 1 CSF leak. Three patients required revision surgery for lead migration, lead fracture, and CSF leak, respectively. One patient had his system explanted 25.9 months after initial placement due to increased pain from stimulation. Conclusion This study aims to characterize our experience with permanent trials for SCS. Here we demonstrate a higher rate of trial‐to‐implant conversion than previously documented for traditional percutaneous trials. We show similar rates of revisions and complications, elucidating the important role of permanent SCS trials in high‐risk patients.
BACKGROUND Increased specialty competitiveness, alongside the inception of virtual interviews, has increased the number of applications submitted to the Electronic Residency Application Service (ERAS) in anesthesiology. ERAS introduced signals to provide applicants with a means to demonstrate interest in a select group of residency programs. In the 2023 to 2024 application cycle, anesthesiology applicants had the opportunity to send 5 gold and 10 silver signals in a tiered system. METHODS This multicenter, cross-sectional (exempt) research survey was created by members of the executive council of the Association of Anesthesiology Core Program Directors (AACPD) and housed and distributed through REDCap and the University of Nebraska Medical Center. Publicly available contact information of anesthesiology core program directors was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website and membership roster of the AACPD. In total, 174 anesthesiology programs were identified. A survey invitation was distributed on March 12, 2024, to all programs via e-mail with reminders. The survey closed on April 30, 2024. Survey responses were collected anonymously, with instructions to provide 1 response per program. All statistical summaries and analyses were performed using SAS 9.3 (SAS Institute). RESULTS The survey was sent to all 174 identified programs, with a response rate of 48.9%. Small programs were defined as having <44 residents, medium 44 to 62 residents, and large >62 residents. Small programs received significantly fewer applications (median 1255) than medium (1420) and large (1558) programs ( P = .0005). There was a statistically significant difference in the number of gold signals received based on program size, with large programs receiving significantly more than medium (169 vs 116, P = .0238) or small programs (168 vs 71, P < .0001). Applicants sending gold signals were more likely to receive an interview compared to those who sent silver signals (56.7% vs 31%, P ≤ .0001). Of the those interviewed, applicants who sent gold signals comprised 42% (28.7%–52.6%), whereas applicants who sent silver signals comprised 45.5% (33%–54.7%). Applicants who did not send a program signal but signaled geographically made up a smaller portion of the interview group at 3% (0%–15.4%). The percentage of matched residents sending gold signals made up 66.7% (47.1%–82.4%) of a program’s match list, whereas those sending silver signals were 25% (11.1%–33.3%) of the matched cohort. CONCLUSIONS Anesthesiology applicants who sent program signals were selected for a large majority of available interview positions, and interviewed applicants who submitted gold and silver signals comprised the vast majority of matched resident cohorts.
Neuraxial anesthesia is an effective method of pain control for various procedures in obstetrics and gynecology, pain medicine, and orthopedic surgery. Spinals and epidurals can greatly enhance a patient’s quality of life but there often exists a limited understanding of the mechanics of performing such procedures, thus hindering the troubleshooting of non-functional or partially functional epidurals. Understanding how mechanical factors like patient anatomy, clinical history, anesthetic injection rate, pressure gradients between the epidural and intrathecal spaces, and medication infusion are crucial for preventing complications like false analgesic levels, failed epidurals, or total/high spinal. In addition to reviewing knowledge available in anesthesia textbooks, the present article introduces a simplified model for understanding neuraxial anesthesia and postulates a mechanism of action for epidurals. Additionally, this article aims to identify high-risk situations that could lead to a total spinal, while considering the unique anatomical changes experienced during pregnancy.
Trimetazidine is an antianginal medication approved in numerous countries for use in the symptomatic treatment of stable coronary artery disease and angina pectoris. Its main mechanism of action revolves around the inhibition of β-oxidation of free fatty acids in the myocardium, in addition to its antioxidant properties and inhibition of cardiac fibrosis. Based on current evidence, trimetazidine is classified by European guidelines as a second-line antianginal agent and as an add-on for the symptomatic treatment of stable angina in patients not adequately controlled with first-line antianginal therapies such as beta-blockers. However, its role in the treatment of cardiovascular disease extends past coronary artery disease, as numerous studies have demonstrated its potential benefit in heart failure patients as well. Unfortunately, trimetazidine’s role in the treatment of heart failure is still not clearly identified, since most studies on this topic were underpowered and unable to reach a decisive conclusion regarding any potential mortality benefits in heart failure. Current European guidelines have categorized trimetazidine as a class IIb recommendation in patients with heart failure with reduced ejection fraction and angina because of its additive effects of improved left ventricular function and anginal symptom relief in patients already on beta-blockers. Additionally, trimetazidine’s use in coronary interventions (ie, percutaneous coronary intervention and coronary artery bypass grafting) showed a reduction in the frequency of anginal attacks and myocardial damage, but the studies were also underpowered and therefore unable to conclusively determine whether trimetazidine should be incorporated in guideline-directed therapy for coronary interventions.
Background Patients with cryptogenic stroke or embolic stroke of undetermined source (ESUS) face a high risk of recurrent ischaemic stroke, but the optimal antithrombotic strategy remains unclear. This systematic review and meta-analysis compared the effectiveness and safety of oral anticoagulants (OACs) versus antiplatelets in these populations, with a focus on subgroup effects by key clinical characteristics. Methods Six databases were searched through March 2024 to identify randomised controlled trials (RCTs) comparing OACs and antiplatelets in patients with cryptogenic stroke or ESUS. The primary outcome was recurrent ischaemic stroke. Subgroup analyses evaluated treatment effects based on supracardiac atherosclerosis risk, presence of patent foramen ovale (PFO) and signs or risk factors for atrial cardiopathy. Meta-regression with interaction p values was employed to assess differences in treatment effects between subgroups. Results Nine RCTs comprising 15 451 participants were included. In the overall population, there was no significant difference in recurrent ischaemic stroke risk between OACs and antiplatelets (relative risk (RR) 0.90, 95% CI 0.79 to 1.02; I ² =0%). Subgroup analyses showed that OACs reduced ischaemic stroke risk in patients with low-risk supracardiac atherosclerosis (RR 0.53, 95% CI 0.35 to 0.80; I ² =0%) compared with those with high-risk supracardiac atherosclerosis (RR 0.91, 95% CI 0.78 to 1.06; I ² =0%) and evidence of supracardiac atherosclerosis (RR 1.13, 95% CI 0.84 to 1.53; I ² =0%) (p interaction=0.0002). Similarly, OACs were more effective in patients with signs or risk factors for atrial cardiopathy (RR 0.84, 95% CI 0.70 to 0.99; I ² =0%) than in those without atrial cardiopathy (RR 1.05, 95% CI 0.85 to 1.30; I ² =0%) (p interaction=0.02). There was no significant interaction by PFO status (p interaction=0.28). While the risk of major bleeding risk was comparable between groups (RR 1.34, 95% CI 0.73 to 2.44; I ² =65%), a significantly higher risk of major bleeding other than intracerebral haemorrhage was observed in patients taking OACs compared with antiplatelets (RR 1.69, 95% CI 1.18 to 2.43; I ² =0%). Conclusions OACs are more effective than antiplatelets for preventing ischaemic stroke in patients who had a cryptogenic stroke or ESUS with low-risk supracardiac atherosclerosis or atrial cardiopathy. The findings highlight the need for personalised treatment strategies and further trials in these subgroups. PROSPERO registration number CRD42024518903.
Background Insufficient nutrition during pregnancy can lead to negative health outcomes for both mother and foetus. Maternal undernourishment (MUN) can be due to many factors like hyperemesis gravidarum or poor access to nutrition. Just as MUN can affect the mother and foetus, it can adversely affect the vital placental interface between the two. We suspect an observed increase in fetuin-B and oxidative stress in MUN placentas could be major players responsible for the placental insufficiency often seen with MUN. Methods To establish a model of MUN during pregnancy, a reduced protein chow was fed to pregnant dams at a caloric deficit. We examined the MUN placentas and the downstream effects of fetuin-B and oxidative stress at the whole organ and trophoblast levels. We examined fetuin-B’s role in trophoblast pathology by measuring apoptosis, proliferation, TLR4 activation, expression of NF-ΚB p65, oxidative stress, and mitochondrial superoxide production. The effects of MUN and fetuin-B on mitochondrial superoxide production, antioxidant levels, metabolism, and electron transport chain complex activity were compared directly. Pharmaceutical interventions were utilised to narrow down specific pathways involved. Results Studies indicated that MUN and oxidative stress upregulated fetuin-B in the placenta. This relationship displayed a positive feedback loop as fetuin-B, in turn, promoted oxidative stress through activation of TLR4. Consequently, MUN, fetuin-B, and oxidative stress promoted apoptosis and reduced proliferative expansion of trophoblast, thereby reducing their quantity. MUN and fetuin-B reduced mitochondrial metabolism and function, promoting mitochondrial dysregulation and superoxide generation in MUN trophoblasts. Conclusions Our study sheds light on the mechanisms responsible for MUN-induced placental insufficiency while identifying therapeutic agents as possible add-on interventions.
Background Cerebral venous thrombosis (CVT) is a rare condition that presents with significant treatment challenges and has traditionally been managed with anticoagulation. However, for patients who fail anticoagulation or present with severe symptoms, endovascular thrombectomy (EVT) has emerged as a favorable treatment modality. This study examines the outcomes, complications, and comorbidities associated with EVT in patients with CVT. Methods A query of the 2015-2019 National (Nationwide) Inpatient Sample was performed for patients admitted to hospitals with ICD-10 diagnosis codes for CVT and ICD-10 procedure codes for usage of EVT. Demographic information, baseline comorbidities, complications, and discharge dispositions were compared between patients who underwent EVT and those who were managed medically. Results A total of 36,005 patients diagnosed with CVT were identified from 2015(Q4) to 2019. Of these patients, 325 (0.9%) received EVT. Patients who underwent EVT were older (<0.001), more likely to be female (p = 0.016), and had higher rates of diabetes mellitus (p = 0.012), hypertension (p < 0.001), and obesity (p < 0.001). These patients also presented with more severe neurological symptoms, including higher National Institutes of Health Stroke Scale scores (p < 0.001), coma (p < 0.001), and cerebral edema (p < 0.001). Patients undergoing EVT had a higher incidence of in-hospital mortality (p = 0.007) and were less likely to be discharged routinely (p < 0.001). Conclusions This study found that patients with CVT who underwent EVT were older, more likely to be female, and presented with more severe neurological conditions. After controlling for severity, EVT in patients with CVT was associated with significant risks, including higher rates of complications and inpatient mortality. Although EVT is associated with significant risks, the findings of this study suggest that its outcomes may reflect the severity of the underlying condition rather than the procedure itself. Careful patient selection and individualized management strategies are essential for optimizing outcomes in this high-risk population.
Purpose To assess the validity of a novel, low-cost glaucoma screening calculator in determining glaucoma risk in high-risk New York communities. Patients and Methods This prognostic community-based study was conducted in New York City neighborhoods from 2022 to 2024 among participants aged 40 years and older. Glaucoma screenings were held at community gatherings including local fairs, senior citizen homes, places of worship, and in the lobby of medical offices. The screenings were conducted by trained non-physician medical personnel comprised medical students and medical assistants working under physician supervision. Participants’ intraocular pressure (IOP) and central corneal thickness (CCT) were measured in both eyes with a handheld tonometer and pachymeter, respectively. Participants then completed a comprehensive eye exam by an ophthalmologist to confirm glaucoma status. Statistical analysis was completed using MedCalc version 22.023 (MedCalc Software Ltd. Ostend, Belgium) with 95% confidence intervals. Results Of the 823 study participants, 716 (mean age 62.9 ± 11.9 years) were eligible to participate and completed the comprehensive follow-up exam. 68% identified as Black, 6.7% identified as Hispanic/Latino, and 52.5% identified as female. The Laroche glaucoma calculator had a sensitivity of 93.5% (CI 89.1–96.5%), specificity of 91.3% (CI 88.5–93.6%), positive predictive value of 80.5% (CI 75.7–84.6%), negative predictive value of 97.3% (CI 95.5–98.4%) and accuracy of 91.9% (CI 89.6–93.8%). Conclusion The Laroche glaucoma calculator shows high sensitivity, specificity, positive predictive value, negative predictive value, and accuracy using affordable screening methods to determine glaucoma risk.
Non-typhoidal Salmonella (NTS) infections, though commonly associated with gastroenteritis, can demonstrate focal non-gastrointestinal organ involvement. We present the case of a mid-30s woman who presented with long-standing left flank pain and was subsequently diagnosed with refractory Salmonella pyelonephritis in the setting of nephrolithiasis, severe hydronephrosis and parenchymal thinning suggestive of renal atrophy despite normal serum creatinine and a normal appearing contralateral kidney. Despite several guideline-based antibiotic courses, we failed to clear her multidrug-resistant Salmonella species bacteriuria. We then established percutaneous nephrostomy (PCN) drainage but still were unable to clear her infection, and it was noted PCN output dropped below 30 cc per day suggesting a non-functional renal unit. This patient was successfully managed with minimally invasive laparoscopic robotic-assisted left nephrectomy which finally cleared her bacteriuria. This case illustrates challenges in the management of refractory atypical Salmonella infections and highlights the rare indication of nephrectomy in such cases.
There has been ongoing debate about whether to continue or withhold angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in patients undergoing noncardiac surgery. With over 200 million surgeries performed annually worldwide and millions of patients on ACE inhibitors and ARBs, it is crucial to elucidate the best management strategy for patients undergoing noncardiac surgery while on these medications. Several large randomized controlled trials, the Stop-or-Not and the Perioperative Ischemic Evaluation-3 trials, were conducted to investigate this important issue. Both clinical trials demonstrated no difference in cardiovascular adverse events, including vascular death, myocardial injury, stroke, and cardiac arrest, with continuation versus discontinuation of ACE inhibitors or ARBs in patients undergoing noncardiac surgery. However, these clinical trials showed a higher incidence of intraoperative hypotension in patients who continued taking their ACE inhibitor or ARB through the surgery. Based on this evidence, the American College of Cardiology 2024 Perioperative Guidelines recommend that patients undergoing elevated-risk surgery should have their ACE inhibitor or ARB withheld 24 hours before the surgery; however, patients with heart failure with reduced ejection fraction undergoing noncardiac surgery should continue their regimen. Currently, while the evidence indicates no difference in adverse outcomes between continuing and discontinuing ACE inhibitors and ARBs in patients undergoing noncardiac surgery, the decision to continue or withhold these medications remains individualized. Clinicians must consider various patient and clinical factors when making this decision, including the type of surgery, the risk for intraoperative blood loss and hypotension, and the specific indication of the ACE inhibitor or ARB.
Sodium–glucose cotransporter-2 (SGLT2) inhibitors were originally approved for use in type 2 diabetes, but in recent years, these medications were found to also have significant cardiovascular benefits in patients with heart failure with reduced and preserved ejection fraction and chronic kidney disease. Part of the cardiovascular benefits of SGLT2 inhibitors likely comes from their antihypertensive effect in addition to other unknown effects, but the mechanism by which these medications reduce blood pressure has not been identified yet. Multiple mechanisms have been proposed to describe SGLT2 inhibitors’ antihypertensive effect, including their associated weight loss and diuretic effect. However, studies have shown that these indirect mechanisms alone do not account for the antihypertensive effect seen with this medication, with more recent studies identifying a new potential mechanism by which SGLT2 inhibitors may derive their direct antihypertensive and cardiovascular benefits. In animal models, SGLT2 receptors were identified in parts of the brain responsible for regulating the sympathetic nervous system and adjusting blood pressure. In these studies, SGLT2 inhibitors suppressed the neuronal activity in these brain regions, reducing the sympathetic nervous system activity and blood pressure of the animals. Further investigation is needed to identify whether there are SGLT2 receptors in the central nervous system of humans and whether SGLT2 inhibitors can suppress neuronal activity in these brain regions. This information could be significant in learning more about the susceptibility and severity of primary hypertension in certain patient populations, as well as identifying whether SGLT2 inhibitors can be considered as a primary antihypertensive agent.
Syphilis is a disease caused by the spirochete bacterium Treponema pallidum , progressing in 4 stages: primary, secondary, latent, and tertiary syphilis. In the tertiary stage, patients may develop cardiovascular syphilis, which includes syphilitic aortitis, aortic aneurysm, aortic regurgitation, and coronary artery involvement. These cardiovascular manifestations increase morbidity and mortality during this late stage of syphilis. A recent large-scale, population-wide study has built on our knowledge of cardiovascular syphilis by identifying an increased risk for the development of acute myocardial infarction, heart failure, atrial fibrillation, ischemic stroke, hemorrhagic stroke, venous thromboembolism, and cardiovascular death in syphilis patients. This review discusses the incidence and pathophysiology of these various manifestations of cardiovascular syphilis, while also detailing the latest treatment options and the prognosis of these conditions. The clinical significance of this topic stems from the fact that the incidence of syphilis has spiked in recent years after previously reaching an all-time low in 1999. According to the Centers for Disease Control in the United States, from 2018 to 2022, the reported cases of syphilis increased by 80%. However, the incidence of cardiovascular syphilis has remained the same during this period, likely due to the efficacy of penicillin use early in the infection, preventing the progression of the disease to the tertiary stage. As a result, cardiovascular syphilis mostly remains a disease of the past, with only a few sporadic cases being reported in the literature in recent years.
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1,556 members
Brahmaraju Mopidevi
  • Department of Pathology
Fawaz Almufti
  • Department of Neurology Neurosurgery and Radiology
Gavin W Hougham
  • School of Medicine
Felipe Cabello
  • Department of Microbiology and Immunology
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Valhalla, United States
Head of institution
Edward C. Halperin, M.D., M.A.