Publications by authors named "Sadiq Rehmani"

23 Publications

  • Page 1 of 1

Optimal treatment strategies for stage I non-small cell lung cancer in veterans with pulmonary and cardiac comorbidities.

PLoS One 2021 18;16(3):e0248067. Epub 2021 Mar 18.

Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

Background: Veterans are at increased risk of lung cancer and many have comorbidities such as chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). We used simulation modeling to assess projected outcomes associated with different management strategies of Veterans with stage I non-small cell lung cancer (NSCLC) with COPD and/or CAD.

Patients And Methods: Using data from a cohort of 14,029 Veterans (years 2000-2015) with NSCLC we extended a well-validated mathematical model of lung cancer to represent the management and outcomes of Veterans with stage I NSCLC with COPD, with or without comorbid CAD. We simulated multiple randomized trials to compare treatment with lobectomy, limited resection, or stereotactic body radiation therapy (SBRT). Model output estimated expected quality adjusted life years (QALY) of Veterans with stage I NSCLC according to age, tumor size, histologic subtype, COPD severity and CAD diagnosis.

Results: For Veterans <70 years old lobectomy was associated with greater projected quality-adjusted life expectancy regardless of comorbidity status. For most combinations of tumors and comorbidity profiles there was no dominant treatment for Veterans ≥80 years of age, but less invasive treatments were often superior to lobectomy. Dominant treatment choices differed by CAD status for older patients in a third of scenarios, but not for patients <70 years old.

Conclusions: The harm/benefit ratio of treatments for stage I NSCLC among Veterans may vary according to COPD severity and the presence of CAD. This information can be used to direct future research study design for Veterans with stage I lung cancer and COPD and/or CAD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248067PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971489PMC
March 2021

Successes and Failures in Tracheal Bioengineering: Lessons Learned.

Ann Thorac Surg 2021 10 10;112(4):1089-1094. Epub 2020 Nov 10.

Department of Surgical Oncology, Nuvance Health, Vassar Brother's Medical Center, Poughkeepsie, New York. Electronic address:

Background: Controversy in tracheal reconstruction using grafts and bioengineered constructs highlights the importance of animal studies before human application. Small animal models help to refine designs but do not adequately model sizes relevant to human anatomy. We have conducted extensive large animal studies and summarize our findings in 26 consecutive transplants.

Methods: We pooled 26 large animal studies together to investigate common elements related to successes and failures. In general the engineered tracheal graft consisted of a decellularized extracellular matrix surgical patch supported by a 3-dimensional-printed plastic polymer scaffold. Circumferential graft coverage ranged from 50% to 100%, spanning the length of 4 to 6 tracheal rings. Some grafts included embedded stem cells. Control grafts were fabricated without the support scaffold. At death grafts were harvested and examined grossly and through histology.

Results: The support scaffold prevented graft malacia and collapse. Luminal epithelialization was most extensive in grafts with smaller circumferential coverage. Smaller circumferential coverage was also associated with longest animal survival. Chondrogenesis was only observed in grafts with embedded stem cells. Survival time was shortest in 100% circumferential grafts. Granulation tissue was an issue for all graft designs.

Conclusions: Large animal models capture challenges and complexities relevant to human anatomy. Development of granulation tissue remains a challenge, especially in circumferential grafts. Significant additional research is needed to investigate granulation tissue formation and to provide actionable insight into its management.
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http://dx.doi.org/10.1016/j.athoracsur.2020.10.021DOI Listing
October 2021

Lung Cancer Screening Uptake in the United States.

Chest 2020 01;157(1):236-238

Division of Pulmonary and Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

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http://dx.doi.org/10.1016/j.chest.2019.08.2176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609956PMC
January 2020

Adjuvant Radiation Therapy for Thoracic Soft Tissue Sarcomas: A Population-Based Analysis.

Ann Thorac Surg 2020 01 11;109(1):203-210. Epub 2019 Sep 11.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York; Department of Thoracic Surgery, Health Quest, Poughkeepsie, New York. Electronic address:

Background: The role of adjuvant radiation therapy (RT) in the management of thoracic soft tissue sarcomas (STSs) remains unclear. We aimed to study the characteristics of patients with thoracic STS who received RT after surgical resection and investigate the impact of RT on survival outcomes.

Methods: We queried National Cancer Database to identify patients with surgically resected thoracic STS from 2004 to 2012. Factors associated with receiving adjuvant RT were identified. Analyses were performed to identify prognostic factors and compare overall survival (OS) in both unmatched and propensity score-matched cohorts.

Results: Overall, 1215 patients were identified, of whom 557 (45.8%) received adjuvant RT. Tumor grade (odds ratio [OR], 2.87; 95% confidence interval [CI], 2.18-3.77), tumor size (OR, 1.82; 95% CI, 1.36-2.42), and tumor margins (OR, 1.97; 95% CI, 1.43-2.72) were found to be significant predictors of receiving RT. Mean OS of patients receiving RT in the unmatched cohort was 91 months vs 88 months for patients who did not (P = .556). When adjusted for all variables, adjuvant RT was found to be associated with improved survival (hazard ratio, 0.79; 95% CI, 0.61-0.96). Survival analysis of the matched cohort also demonstrated improved survival with adjuvant RT (120 months vs 100 months; P = .02). Subgroup analysis in both the unmatched and matched cohorts showed patients with high-grade tumors more likely to benefit from adjuvant RT.

Conclusions: This population-based analysis is the largest dataset of primary thoracic STSs to date and suggests significant survival benefit associated with adjuvant RT. The improvement in OS was more notable in patients with high-grade tumors. Randomized prospective studies are warranted to further understand the benefit of RT in this group.
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http://dx.doi.org/10.1016/j.athoracsur.2019.07.075DOI Listing
January 2020

Association of tumor location with economic outcomes and air leak complications in thoracic lobectomies: results from a national hospital billing dataset.

Clinicoecon Outcomes Res 2019 6;11:373-383. Epub 2019 Jun 6.

Medical Devices - Epidemiology, Johnson and Johnson, New Brunswick, NJ, USA.

To assess whether tumor location during thoracic lobectomies affects economic outcomes or air leak complications. Retrospective, observational study using Premier Healthcare Database. The study included patients aged ≥18 years who underwent elective inpatient thoracic lobectomy for lung cancer between 2012 and 2014 (first qualifying=index admission). Three mutually exclusive tumor location groups were formed: upper lobe, middle lobe, and lower lobe. Primary outcomes were index admission's length of stay (LOS), total hospital costs, and operating room time; in-hospital air leak complications (composite of air leak/pneumothorax) served as an exploratory outcome. Multivariable models were used to examine the association between tumor location and the study outcomes, accounting for covariates and hospital-level clustering. 8,750 thoracic lobectomies were identified: upper lobe (n=5,284), middle lobe (n=512), and lower lobe (n=2,954). Compared with the upper lobe, the middle and lower lobe groups had statistically significant (<0.05): shorter adjusted LOS (7.0 days upper vs 5.8 days middle, 6.6 days lower), lower adjusted mean total hospital costs ($26,177 upper vs $23,109 middle, $24,557 lower), and lower adjusted odds of air leak complications (odds ratio middle vs upper=0.81, 95% CI=0.74-0.89; odds ratio lower vs upper=0.60, 95% CI=0.46-0.78). Findings were similar but varied in statistical significance when stratified by open and video-assisted thoracoscopic surgery approach. Among patients undergoing elective thoracic lobectomy for lung cancer in real-world clinical practice, upper lobe tumors were significantly associated with increased in-hospital resource use and air leak complications as compared with lower or middle lobe tumors.
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http://dx.doi.org/10.2147/CEOR.S190644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559234PMC
June 2019

Mutational landscape of head and neck squamous cell carcinomas in a South Asian population.

Genet Mol Biol 2019 Jul-Sep;4242(3):526-542. Epub 2019 Nov 14.

Surgical Specialty Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is among the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA analysis (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel recurrent mutations in ASNS (asparagine synthetase) that may affect substrate binding, and variants in driver genes including TP53, PIK3CA, FGFR2, ARID2, MLL3, MYC and ALK. Using the IntOGen platform, we identified MAP kinase, cell cycle, actin cytoskeleton regulation, PI3K-Akt signaling and other pathways in cancer as affected in the samples. This data is the first of its kind from the Pakistani population. The results of this study can guide a better mechanistic understanding of HNSCC in the population, ultimately contributing new, rational therapeutic targets for the treatment of the disease.
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http://dx.doi.org/10.1590/1678-4685-GMB-2018-0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905448PMC
November 2019

Robotic Thoracic Surgery Training for Residency Programs: A Position Paper for an Educational Curriculum.

Innovations (Phila) 2018 Nov/Dec;13(6):417-422

Department of General Surgery, Brookdale University Hospital and Medical Center, Brooklyn, NY USA.

Objective: Robotic-assisted surgery is increasingly being used in thoracic surgery. Currently, the Integrated Thoracic Surgery Residency Program lacks a standardized curriculum or requirement for training residents in robotic-assisted thoracic surgery. In most circumstances, because of the lack of formal residency training in robotic surgery, hospitals are requiring additional training, mentorship, and formal proctoring of cases before granting credentials to perform robotic-assisted surgery. Therefore, there is necessity for residents in Integrated Thoracic Surgery Residency Program to have early exposure and formal training on the robotic platform. We propose a curriculum that can be incorporated into such programs that would satisfy both training needs and hospital credential requirements.

Methods: We surveyed all 26 Integrated Thoracic Surgery Residency Program Directors in the United States. We also performed a PubMed literature search using the key word "robotic surgery training curriculum." We reviewed various robotic surgery training curricula and evaluation tools used by urology, obstetrics gynecology, and general surgery training programs. We then designed a proposed curriculum geared toward thoracic Integrated Thoracic Surgery Residency Program adopted from our credentialing experience, literature review, and survey consensus.

Results: Of the 26 programs surveyed, we received 17 responses. Most Integrated Thoracic Surgery Residency Program directors believe that it is important to introduce robotic surgery training during residency. Our proposed curriculum is integrated during postgraduate years 2 to 6. In the preclinical stage postgraduate years 2 to 3, residents are required to complete introductory online modules, virtual reality simulator training, and in-house workshops. During clinical stage (postgraduate years 4-6), the resident will serve as a supervised bedside assistant and progress to a console surgeon. Each case will have defined steps that the resident must demonstrate competency. Evaluation will be based on standardized guidelines.

Conclusions: Expansion and utilization of robotic assistance in thoracic surgery have increased. Our proposed curriculum aims to enable Integrated Thoracic Surgery Residency Program residents to achieve competency in robotic-assisted thoracic surgery and to facilitate the acquirement of hospital privileges when they enter practice.
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http://dx.doi.org/10.1097/IMI.0000000000000573DOI Listing
April 2019

Radiation therapy improves survival for unresectable postpneumonectomy lung tumors.

J Surg Res 2018 07 12;227:60-66. Epub 2018 Mar 12.

Department of Thoracic Surgery, Icahn School of Medicine, Mount Sinai Health System, New York, New York.

Background: Additional resection for cancer in the single lung is often considered a prohibitive risk. The role of radiation therapy (RT) in this patient population is less clear with very limited available data. In this study, we sought to examine patients with postpneumonectomy lung cancer not amenable to surgery, identify factors associated with receiving RT, and determine the impact of RT on survival outcomes.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2013) was queried for patients with inoperable contralateral lung cancer after pneumonectomy. Univariate and multivariate analyses were performed to identify factors associated with the receipt of RT. Survival outcomes were examined using the Kaplan-Meier method.

Results: In total, 191 patients with inoperable postpneumonectomy lung cancer were included. RT was delivered to 122 (63.9%) patients; 69 (36.1%) patients did not receive RT. On multivariate analysis, disease stage was identified as the only predictor associated with receipt of RT (P < 0.001). The median overall survival (OS) and disease-specific survival (DSS) for patients receiving RT were higher than those for patients who did not receive RT (25 versus 8 mo and 29 versus 10 mo, respectively; P < 0.001). Similarly, patients who received RT had a higher 3-y OS (34% versus 14%, P < 0.001) than those who did not receive RT. On subset analysis, survival benefit with RT was observed in patients with all tumor size groups, and there was a trend toward superior survival in patients with stage I/II disease, who received RT compared with those who did not. On multivariate Cox regression analysis, RT use was independently associated with decreased hazards of death after adjusting for other factors (HR, 0.539; P < 0.001).

Conclusions: Based on our analysis of the Surveillance, Epidemiology, and End Results (SEER) database, RT is associated with improved outcomes in inoperable patients with a contralateral lung cancer after pneumonectomy compared with observation alone.
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http://dx.doi.org/10.1016/j.jss.2018.02.015DOI Listing
July 2018

Racial Disparity in Utilization of High-Volume Hospitals for Surgical Treatment of Esophageal Cancer.

Ann Thorac Surg 2018 08 21;106(2):346-353. Epub 2018 Apr 21.

Institute for Translational Epidemiology, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Utilization of high-volume hospitals (HVH) for esophagectomy has been associated with improved perioperative outcomes and reduced mortality. We aimed to test the hypothesis that black-white racial disparities exist in HVH utilization and identify predictors of in-hospital surgical outcomes of esophageal cancer while adjusting for HVH utilization patterns.

Methods: We queried the New York Statewide Planning and Research Cooperative System database (1995 to 2012) for esophageal cancer patients who underwent surgical resection exclusively. Only records for patients with self-reported white or black race and a valid New York State ZIP code were included (n = 2,895). Analysis was performed to identify factors associated with HVH hospital (≥20 esophagectomies/year) utilization and determine predictors of complications and in-hospital mortality.

Results: Black patients (361 [12.5%]) were significantly different (p < 0.001) than their white counterparts in the proportion of women, Medicaid, income distribution, and privately insured individuals. Although 55% patients overall utilized an HVH, blacks were significantly less likely to utilize an HVH than whites (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.14 to 0.24), even though 74.5% resided within 8.9 miles of one. Operations performed at HVHs were associated with lower in-hospital mortality (OR, 0.48; 95% CI, 0.35 to 0.65); however, mortality remained higher for blacks (OR, 2.04; 95% CI, 1.65 to 3.30; propensity matched OR, 2.45; 95% CI, 1.5 to 4.03).

Conclusions: Black patients were less likely to undergo esophagectomy at an HVH and experienced higher mortality. Efforts should be made to understand factors influencing patients' decision process and improve referral practices to ensure optimal care is provided across all segments of the population, irrespective of race, insurance, or income status.
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http://dx.doi.org/10.1016/j.athoracsur.2018.03.042DOI Listing
August 2018

Pulmonary Resection for Second Lung Cancer After Pneumonectomy: A Population-Based Study.

Ann Thorac Surg 2017 Oct 12;104(4):1131-1137. Epub 2017 Jul 12.

Department of Thoracic Surgery, Icahn School of Medicine, Mount Sinai Health System, New York, New York. Electronic address:

Background: Pulmonary resection for a second lung cancer after pneumonectomy is generally considered to be at prohibitive risk. Using a population-based database, we examined treatment patterns and survival in patients who underwent pulmonary resection after pneumonectomy for lung cancer.

Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) to identify patients who underwent pneumonectomy and subsequently experienced contralateral non-small cell lung cancer (NSCLC). Multivariate logistic regression was performed to identify the factors associated with the receipt of surgical resection. Survival was estimated with the Kaplan-Meier method.

Results: Of 13,370 patients who underwent pneumonectomy, 402 (3.0%) experienced subsequent contralateral NSCLC, and 170 (42%) met the selection criteria. Surgical resection was performed in 63 (37.1%) cases (sublobar n = 56, lobectomy, n = 7). Patients with stage I/II disease and tumor size 2 cm or smaller were more likely to undergo surgical procedures. The 1-month and 3-month mortality after resection was 11.1% (sublobar resection 10.7%, lobectomy 14.3%) and 12.7% (sublobar 12.5%, lobectomy 14.3%), respectively. The overall 1-year and 3-year survival after surgical resection was 79% and 54%, respectively. The patients who underwent sublobar resection had higher median overall survival than did those who underwent lobectomy (42 vs 18 months). Similarly, median survival after resection for metachronous tumors was higher than after resection for metastatic cancers (40 vs 28 months).

Conclusions: On the basis of our analysis of the SEER database, sublobar resection can be performed in selected patients with small tumors (≤2 cm) and early-stage disease (stage I/II). Although perioperative mortality is significant, the favorable 1-year and 3-year survival may justify the role of an additional procedure on the single lung.
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http://dx.doi.org/10.1016/j.athoracsur.2017.04.043DOI Listing
October 2017

Circumferential Three-Dimensional-Printed Tracheal Grafts: Research Model Feasibility and Early Results.

Ann Thorac Surg 2017 Sep 13;104(3):958-963. Epub 2017 Jun 13.

Department of Otolaryngology, Mount Sinai West, Mount Sinai Health System, New York, New York.

Background: Methods for tracheal graft research have presented persistent challenges to investigators, and three-dimensional (3D)-printed biosynthetic grafts offer one potential development platform. We aimed to develop an efficient research platform for customizable circumferential 3D-printed tracheal grafts and evaluate feasibility and early structural integrity with a large-animal model.

Methods: Virtual 3D models of porcine subject tracheas were generated using preoperative computed tomography scans. Two designs were used to test graft customizability and the limits of the construction process. Designs I and II used 270-degree and 360-degree external polycaprolactone scaffolds, respectively, both encompassing a circumferential extracellular matrix collagen layer. The polycaprolactone scaffolds were made in a fused-deposition modeling 3D printer and customized to the recipient's anatomy. Design I was implanted in 3 pigs and design II in 2 pigs, replacing 4-ring tracheal segments. Data collected included details of graft construction, clinical outcomes, bronchoscopy, and gross and histologic examination.

Results: The 3D-printed biosynthetic grafts were produced with high fidelity to the native organ. The fabrication process took 36 hours. Grafts were implanted without immediate complication. Bronchoscopy immediately postoperatively and at 1 week demonstrated patent grafts and appropriate healing. All animals lived beyond a predetermined 1-week survival period. Bronchoscopy at 2 weeks showed significant paraanastomotic granulation tissue, which, along with partial paraanastomotic epithelialization, was confirmed on pathology. Overall survival was 17 to 34 days.

Conclusions: We propose a rapid, reproducible, resource efficient method to develop various anatomically precise grafts. Further graft refinement and strategies for granulation tissue management are needed to improve outcomes.
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http://dx.doi.org/10.1016/j.athoracsur.2017.03.064DOI Listing
September 2017

Three-Dimensional-Printed Bioengineered Tracheal Grafts: Preclinical Results and Potential for Human Use.

Ann Thorac Surg 2017 Sep 11;104(3):998-1004. Epub 2017 Jun 11.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York. Electronic address:

Background: We aimed to develop a process using three-dimensional (3D) printing to create bioengineered tracheal grafts (BETGs) for reconstruction of anterior tracheal defects in a large-animal model (porcine) that would have translational relevance for potential human use.

Methods: Preoperative computed tomographic scans were used to create virtual 3D models of the animal airways. Anatomically scaled tracheal grafts were subsequently developed using 3D-printed polycaprolactone and extracellular matrix. A 4-cm anterior tracheal defect (about 50% of the length of the subject trachea) was surgically created in 4-week-old female Yorkshire pigs and reconstructed using the customized grafts. Gross and microscopic analyses of the grafts were performed.

Results: The BETGs were implanted in 7 animals. There was adequate graft-native trachea size match at the operation. The trachea was successfully reconstructed in all cases. Gross examination at autopsy showed a structurally intact, well-incorporated graft. Histologic evaluation showed respiratory mucosal coverage and vascularity of the graft. Five of 7 animals outlived the 3-month study period. The animals had approximately 100% growth during the study period.

Conclusions: We report of a 3D-printed BETG to repair long-segment anterior tracheal defects in a large-animal model. Although the study duration is short, this work presents an efficient strategy for tracheal graft bioengineering with potential translational relevance for human use.
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http://dx.doi.org/10.1016/j.athoracsur.2017.03.051DOI Listing
September 2017

Primary Non-Hodgkin's Lymphoma of the Gallbladder: A Population-based Analysis.

Anticancer Res 2017 05;37(5):2581-2586

Department of Surgery, Icahn School of Medicine, Mount Sinai Health System, New York, NY, U.S.A.

Background/aim: Primary Non-Hodgkin's lymphoma of the gallbladder (PNHL-GB) is extremely rare and data on clinical characteristics, optimal management and outcomes of these patients are limited to anecdotal reporting. We, therefore, sought to examine these patients using a population-based database.

Materials And Methods: Surveillance, epidemiology, and end results (SEER) database was queried between 1973 and 2013.

Results: One hundred and six cases with PNHL-GB were identified (mean age=70.5 ±15 years, whites 92%, male: female 1.03:1). The majority of patients had loco-regional disease (61%) and DLBCL histology (33%). Ninenty cases (85%) had undergone surgical resection, 6 (5.6%) received radiotherapy. Median overall survival (OS) of the entire cohort was 41 months with a 5-year survival rate of 40%. Patients receiving adjuvant RT had superior OS compared to surgery alone (140 ±27 vs. 86 ±16 months, respectively) and patients with DLBCL demonstrated lower survival compared to other histologies (13 vs. 53 months, respectively, p=0.034).

Conclusion: Our study presents the largest dataset of PNHL-GB describing clinical features and outcomes of these patients in addition to summarizing the literature.
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http://dx.doi.org/10.21873/anticanres.11602DOI Listing
May 2017

Pneumopericardium Leading to Cardiac Tamponade in a Patient with Lung Cancer.

Thorac Cardiovasc Surg Rep 2016 Dec 29;5(1):13-15. Epub 2016 Jan 29.

Department of Thoracic Surgery, Mount Sinai St. Luke's and Mount Sinai West, New York, United States.

Pneumopericardium resulting in cardiac tamponade in patients with lung cancer is not documented. We report a case of squamous cell carcinoma of the lung complicated by pneumopericardium and subsequent cardiac tamponade. The patient underwent an urgent pericardial window with rapid improvement in symptoms. We discuss the possible pathogenesis and treatment options for this rare condition.
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http://dx.doi.org/10.1055/s-0036-1571360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177421PMC
December 2016

Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model.

Ann Thorac Surg 2017 Feb 27;103(2):381-389. Epub 2016 Oct 27.

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York. Electronic address:

Background: Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model.

Methods: hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors. An anterior 4 cm × 3 cm defect was surgically created in the trachea of 4-week-old female Yorkshire pigs. The defect was reconstructed using the bioengineered graft (n = 7) or control (n = 3, ECM only). The study duration was 3 months.

Results: Survival ranged from 7 days (n = 3) to 3 months (n = 7). Early death was due to graft malacia (n = 1, control), graft infection (n = 1, bioengineered), and pneumonia (n = 1, bioengineered). There was substantial animal growth at 3 months (>200% weight). Surveillance bronchoscopy showed patent airway, mild stenosis, and integration of the graft with the native trachea. On histology, luminal epithelialization and neovascularization with scant submucosa were observed in both the bioengineered graft and control groups. Chondrogenesis was seen only in the bioengineered graft. The neocartilage was less mature and organized compared to native cartilage. SRY immunostain was positive in the neocartilage but not control or native trachea.

Conclusions: We demonstrate the feasibility of the bioengineered graft for reconstruction of long anterior tracheal defects with favorable short-term outcomes. Furthermore, we show its ability to facilitate chondrogenesis, neovascularization, and epithelialization. Importantly, it supported rapid animal growth offering potential solutions for both pediatric and adult applications.
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http://dx.doi.org/10.1016/j.athoracsur.2016.10.034DOI Listing
February 2017

Robotically Assisted Thoracic Surgery: Proposed Guidelines for Privileging and Credentialing.

Innovations (Phila) 2016 Nov/Dec;11(6):386-389

From the Departments of *Thoracic Surgery and †Surgery, Icahn School of Medicine, Mount Sinai Health System, New York, NY USA.

Objective: Increased use of robotically assisted thoracic surgery (RATS) necessitates effective credentialing guidelines to ensure safe outcomes. We provide a stepwise algorithm for granting privileges and credentials in RATS. This algorithm reflects graduated responsibility and complexity of the surgical procedures performed. Furthermore, it takes into account volume, outcomes, surgeon's competency, and appropriateness of robot usage.

Methods: We performed a literature review for available strategies to grant privileges and credentials for implementing robotic surgery. The following terms were queried: robot, robotic, surgery, and credentialing. We provide this algorithm on the basis of review of the literature, our institutional experience, and the experience of other medical centers around the United States.

Results: Currently, two pathways for robotic training exist: residency and nonresidency-trained. In the United Sates, Joint Commission: Accreditation, Health Care, Certification requires hospitals to credential and privilege physicians on their medical staff. In the proposed algorithm, a credentialing designee oversees and reviews all requests. Residency-trained surgeons must fulfill 20 cases with program directors' attestation to obtain full privileges. Nonresidency-trained surgeons are required to fulfill simulation, didactics including online modules, wet laboratories (cadaver or animal), and observation of at least two cases before provisional privileges can be granted. A minimum number of cases (10 per year) are required to maintain privileges. All procedures are monitored via departmental QA/QI committee review. Investigational uses of the robot require institutional review board approval, and complex operations may require additional proctoring and QA/QI review.

Conclusions: Safety concerns with the introduction of novel and complex technologies such as RATS must be paramount. Our algorithm takes into consideration appropriate use and serves as a basic guideline for institutions that wish to implement a RATS program.
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http://dx.doi.org/10.1097/IMI.0000000000000320DOI Listing
May 2017

Robotic Lung Cancer Surgery: A Missed Opportunity and a Faulty Conclusion.

Ann Surg 2018 02;267(2):e34

Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY.

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http://dx.doi.org/10.1097/SLA.0000000000001996DOI Listing
February 2018

Treatment of Benign Tracheal Stenosis Using Endoluminal Spray Cryotherapy.

JAMA Otolaryngol Head Neck Surg 2016 11;142(11):1082-1087

Department of Otolaryngology-Head and Neck Surgery, Mount Sinai West, Mount Sinai Health System, New York, New York.

Importance: Tracheal stenosis is a debilitating disorder with heterogeneity in terms of disease characteristics and management. Repeated recurrences substantially alter patients' quality of life. There is limited evidence for the use of spray cryotherapy (SCT) in the management of benign airway disease.

Objective: To report our early results for the use of SCT in patients with benign tracheal stenosis.

Design, Setting, And Participants: Data were extracted from the medical records of a consecutive series of patients with benign airway stenosis secondary to granulomatosis with polyangiitis (GPA) (n = 13), prior tracheotomy or tracheal intubation (n = 8), and idiopathic strictures (n = 5) treated from September 1, 2013, to September 30, 2015, at a tertiary care hospital.

Main Outcomes And Measures: Airway narrowing was quantified on a standard quartile grading scale. Response to treatment was assessed by improvement in airway caliber and the time interval for reintervention.

Exposures: Delivery of 4 5-second SCT cycles and 2 balloon dilatations.

Results: Twenty-six patients (median [range] age, 53 [16-83] years; 20 [77%] female) underwent 48 SCT sessions. Spray cryotherapy was successfully used without any substantial intraoperative or postoperative complications in all patients. In a median (range) follow-up of 11 (1-26) months, all patients had improvement in symptoms. Before the institution of SCT, 23 patients (88%) had grade III or IV stenosis. At the last evaluation after induction of SCT, 4 (15%) had grade III or IV stenosis, with a mean (SD) change of 1.39 (0.51) (P < .001). Patients with GPA required significantly fewer SCT procedures (mean [SD], 1.38 [0.96] vs 2.31 [1.18]; P = .03) during the study period.

Conclusions And Relevance: Spray cryotherapy was a safe adjunct modality to accomplish airway patency in patients with benign tracheal stenosis. Although efficacy evidence is limited for SCT, it may be useful for patients who have experienced treatment failure with conventional modalities. Further analysis of this cohort will determine the physiologic durability of the reported short-term changes. Additional trials are warranted for further evaluation of this modality.
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http://dx.doi.org/10.1001/jamaoto.2016.2018DOI Listing
November 2016

Antitumor activity of paclitaxel is significantly enhanced by a novel proapoptotic agent in non-small cell lung cancer.

J Surg Res 2015 Apr 10;194(2):622-630. Epub 2014 Nov 10.

Division of Thoracic Surgery, Department of Surgery, Mount Sinai St. Luke's Hospital, Mount Sinai Health System, New York, NY, USA; Division of Thoracic Surgery, Department of Surgery, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, New York, NY, USA. Electronic address:

Background: Newer targeted agents are increasingly used in combination chemotherapy regimens with enhanced survival and improved toxicity profile. Taxols, such as paclitaxel, independently potentiate tumor destruction via apoptosis and are used as first line therapy in patients with advanced non-small cell lung cancer (NSCLC). Procaspase-3-activating compound-1 (PAC-1) is a novel proapoptotic agent that directly activates procaspase-3 (PC-3) to caspase-3, leading to apoptosis in human lung adenocarcinoma cells. Hence, we sought to evaluate the antitumor effects of paclitaxel in combination with PAC-1.

Methods: Human NSCLC cell lines (A-549 and H-322m) were incubated in the presence of PAC-1 and paclitaxel. Tumor cell viability was determined by a tetrazolium-based colorimetric assay (MTT assay). Western blot and flow cytometric analysis were performed to evaluate expression of PC-3 and the proportion of apoptotic cells, respectively. A xenograft murine model of NSCLC was used to study the in vivo antitumor effects of PAC-1.

Results: PAC-1 significantly reduced the inhibitory concentration 50% of paclitaxel from 35.3 to 0.33 nM in A-549 and 8.2 to 1.16 nM in H-322m cell lines. Similarly, the apoptotic activity significantly increased to 85.38% and 70.36% in A-549 and H322m, respectively. Significantly enhanced conversion of PC-3 to caspase-3 was observed with PAC-1 paclitaxel combination (P < 0.05). Mice treated with a drug combination demonstrated 60% reduced tumor growth rate compared with those of controls (P < 0.05).

Conclusions: PAC-1 significantly enhances the antitumor activity of paclitaxel against NSCLC. The activation of PC-3 and thus the apoptotic pathway is a potential strategy in the treatment of human lung cancer.
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http://dx.doi.org/10.1016/j.jss.2014.11.004DOI Listing
April 2015

The incidence of trocar-site hernia in minimally invasive bariatric surgery: a comparison of multi versus single-port laparoscopy.

Surg Endosc 2013 Apr 12;27(4):1287-91. Epub 2012 Dec 12.

St. Luke's-Roosevelt Hospital Center, Institute for Bariatric and Minimally Invasive Surgery, 1111 Amsterdam Avenue, Babcock 4W, New York, NY 10025, USA.

Introduction: Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations.

Methods: There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture.

Results: Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1-18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias.

Conclusions: SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.
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http://dx.doi.org/10.1007/s00464-012-2597-5DOI Listing
April 2013

Surgical residents' perception of the 16-hour work day restriction: concern for negative impact on resident education and patient care.

J Am Coll Surg 2012 Dec 4;215(6):868-77. Epub 2012 Oct 4.

Department of Surgery, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA.

Background: Effective July 1, 2011, the Accreditation Council for Graduate Medical Education (ACGME) instituted a 16-hour duty period limitation for postgraduate year I (PGY I) residents. Our aim was to assess the attitudes and perception of general surgery residents regarding the new duty hour limitation as well as the transfer of care process under the new guidelines.

Study Design: An anonymous, web-based survey was conducted nationally 7 months after the institution of the 16-hour duty limitation.

Results: A total of 464 completed surveys were analyzed. Overall, 75% of residents expressed dissatisfaction with the new duty hour limitation. PGY II to V residents reported a higher level of dissatisfaction compared with PGY I residents (87% vs 54%, p < 0.01). Eighty-nine percent of PGY II to V residents responded that there has been a shift of responsibilities from the PGY I class to PGY II to V residents, with 73% reporting increased fatigue as a result. Seventy-five percent of PGY I and 94% of PGY II to V residents expressed concerns about the adverse impact of the restrictions on the education of PGY I residents (p < 0.01). Residents at all PGY training levels reported encountering problems due to inadequate sign-outs (PGY I, 59%; PGY II to V, 85%; p < 0.01). Sixty-two percent of PGY I residents and 54% of PGY II to V residents believed that the new 16-hour duty restriction contributes to inadequate sign-outs (p = NS). Most PGY II to V residents (86%) believe there is a decreased level of patient ownership due to the work hour restrictions.

Conclusions: The results of the survey suggest that the majority of general surgery residents are concerned over the potential negative impact of the duty limitation on resident education and patient care. Further research is needed to address these concerns.
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http://dx.doi.org/10.1016/j.jamcollsurg.2012.08.005DOI Listing
December 2012

Fluoroquinolones inhibit HCV by targeting its helicase.

Antivir Ther 2012 25;17(3):467-76. Epub 2011 Oct 25.

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

Background: HCV has infected >170 million individuals worldwide. Effective therapy against HCV is still lacking and there is a need to develop potent drugs against the virus. In the present study, we have employed two culture models to test the activity of fluoroquinolone drugs against HCV: a subgenomic replicon that is able to replicate independently in the cell line Huh-8 and the Huh-7 cell culture model that employs cells transfected with synthetic HCV RNA to produce the infectious HCV particles. Fluoroquinolones have also been shown to have inhibitory activity against certain viruses, possibly by targeting the viral helicase. To tease out the mechanism of the antiviral activity of fluoroquinolones, their effect on HCV NS3 helicase protein was also tested.

Methods: Huh-7 cells producing the HCV virion as well as Huh-8 cells were grown in the presence or absence of 12 different fluoroquinolones. Afterwards, Huh-7 and Huh-8 cells were lysed and viral RNA was extracted. The extracted RNA was reverse transcribed and quantified by real-time quantitative PCR. Fluoroquinolones were also tested on purified NS3 protein in a molecular-beacon-based in vitro helicase assay.

Results: To varying degrees, all of the tested fluoroquinolones effectively inhibited HCV replication in both Huh-7 and Huh-8 culture models. The inhibition of HCV NS3 helicase activity was also observed with all 12 of the fluoroquinolones.

Conclusions: Fluoroquinolones inhibit HCV replication possibly by targeting the HCV NS3 helicase. These drugs hold promise for the treatment of HCV infection.
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http://dx.doi.org/10.3851/IMP1937DOI Listing
August 2012

The spread of HIV in Pakistan: bridging of the epidemic between populations.

PLoS One 2011 25;6(7):e22449. Epub 2011 Jul 25.

Department of Microbiology, Dow University of Health Sciences, Karachi, Pakistan.

In the last two decades, 'concentrated epidemics' of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022449PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143131PMC
December 2011
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