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Article ; Online: Characterization of a Diverse Set of Conditionally Reprogrammed Head and Neck Cancer Cell Cultures.

Ow, Thomas J / Mehta, Vikas / Li, Daniel / Thomas, Carlos / Shrivastava, Nitisha / Kawachi, Nicole / Gersten, Adam J / Zhu, Jing / Schiff, Bradley A / Smith, Richard V / Rosenblatt, Gregory / Augustine, Stelby / Prystowsky, Michael B / Yin, Shanye / Gavathiotis, Evripidis / Guha, Chandan

The Laryngoscope

2024 Volume 134, Issue 6, Page(s) 2748–2756

Abstract: Objective: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR).: Methods: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR ... ...

Abstract	Objective: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR). Methods: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded. Successful CR cultures were validated against banked reference tumors with short tandem repeat genotyping. Cell morphology was archived with photodocumentation. Clinical and demographic factors were evaluated for associations with successful establishment of CR culture. Human papilloma virus (HPV) genotyping, clonogenic survival, MTT assays, spheroid growth, and whole exome sequencing were carried out in selected cultures. Results: Forty four patients were enrolled, with 31 (70%) successful CR cultures, 32% derived from patients who identified as Black and 61% as Hispanic. All major head and neck disease sites were represented, including 15 (48%) oral cavity and 8 (26%) p16-positive oropharynx cancers. Hispanic ethnicity and first primary tumors (vs. second primary or recurrent tumors) were significantly associated with successful CR culture. HPV expression was conserved in CR cultures, including CR-024, which carried a novel HPV-69 serotype. CR cultures were used to test cisplatin responses using MTT assays. Previous work has also demonstrated these models can be used to assess response to radiation and can be engrafted in mouse models. Whole exome sequencing demonstrated that CR cultures preserved tumor mutation burden and driver mutations. Conclusion: CR culture is highly successful in propagating HNSCC cells. This study included a high proportion of patients from underrepresented minority groups. Level of evidence: Not Applicable Laryngoscope, 134:2748-2756, 2024.
MeSH term(s)	Humans ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/virology ; Head and Neck Neoplasms/genetics ; Female ; Male ; Squamous Cell Carcinoma of Head and Neck/virology ; Squamous Cell Carcinoma of Head and Neck/pathology ; Squamous Cell Carcinoma of Head and Neck/genetics ; Middle Aged ; Tumor Cells, Cultured ; Aged ; Exome Sequencing ; Cellular Reprogramming/genetics ; Adult ; Cellular Reprogramming Techniques
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.31236
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Article ; Online: Risk Estimation of Severe COVID-19 Based on Initial Biomarker Assessment Across Racial and Ethnic Groups.

Kroll, Martin H / Bi, Caixia / Salm, Ann E / Szymanski, James / Goldstein, D Yitzchak / Wolgast, Lucia R / Rosenblatt, Gregory / Fox, Amy S / Kapoor, Hema

Archives of pathology & laboratory medicine

2023 Volume 147, Issue 10, Page(s) 1109–1118

Abstract: Context.—: Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis.: Objective.—: To develop predictive models of COVID- ... ...

Abstract	Context.—: Disease courses in COVID-19 patients vary widely. Prediction of disease severity on initial diagnosis would aid appropriate therapy, but few studies include data from initial diagnosis. Objective.—: To develop predictive models of COVID-19 severity based on demographic, clinical, and laboratory data collected at initial patient contact after diagnosis of COVID-19. Design.—: We studied demographic data and clinical laboratory biomarkers at time of diagnosis, using backward logistic regression modeling to determine severe and mild outcomes. We used deidentified data from 14 147 patients who were diagnosed with COVID-19 by polymerase chain reaction SARS-CoV-2 testing at Montefiore Health System, from March 2020 to September 2021. We generated models predicting severe disease (death or more than 90 hospital days) versus mild disease (alive and fewer than 2 hospital days), starting with 58 variables, by backward stepwise logistic regression. Results.—: Of the 14 147 patients, including Whites, Blacks, and Hispanics, 2546 (18%) patients had severe outcomes and 3395 (24%) had mild outcomes. The final number of patients per model varied from 445 to 755 because not all patients had all available variables. Four models (inclusive, receiver operating characteristic, specific, and sensitive) were identified as proficient in predicting patient outcomes. The parameters that remained in all models were age, albumin, diastolic blood pressure, ferritin, lactic dehydrogenase, socioeconomic status, procalcitonin, B-type natriuretic peptide, and platelet count. Conclusions.—: These findings suggest that the biomarkers found within the specific and sensitive models would be most useful to health care providers on their initial severity evaluation of COVID-19.
MeSH term(s)	Humans ; COVID-19/diagnosis ; SARS-CoV-2 ; COVID-19 Testing/methods ; Ethnicity ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2023-0039-SA
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Article ; Online: The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren.

Foksinska, Aleksandra / Crowder, Camerron M / Crouse, Andrew B / Henrikson, Jeff / Byrd, William E / Rosenblatt, Gregory / Patton, Michael J / He, Kaiwen / Tran-Nguyen, Thi K / Zheng, Marissa / Ramsey, Stephen A / Amin, Nada / Osborne, John / Might, Matthew

Frontiers in artificial intelligence

2022 Volume 5, Page(s) 910216

Abstract: There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need ... ...

Abstract	There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments. A promising avenue for treatment is drug repurposing, where FDA-approved drugs are repositioned as novel treatments. However, linking disease mechanisms to drug action can be extraordinarily difficult and requires a depth of knowledge across multiple fields, which is complicated by the rapid pace of biomedical knowledge discovery. To address these challenges, The Hugh Kaul Precision Medicine Institute developed an artificial intelligence tool, mediKanren, that leverages the mechanistic insight of genetic disorders to identify therapeutic options. Using knowledge graphs, mediKanren enables an efficient way to link all relevant literature and databases. This tool has allowed for a scalable process that has been used to help over 500 rare disease families. Here, we provide a description of our process, the advantages of mediKanren, and its impact on rare disease patients.
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Journal Article
ISSN	2624-8212
ISSN (online)	2624-8212
DOI	10.3389/frai.2022.910216
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Article ; Online: A comparison of running suture versus figure-8 sutures as the initial step in achieving hemostasis during laparoscopic partial nephrectomy.

Rosenblatt, Gregory S / Fuchs, Gerhard J

Journal of endourology

2010 Volume 24, Issue 3, Page(s) 421–424

Abstract: Background and purpose: During laparoscopic partial nephrectomy, the importance of the initial suture placed under warm ischemic conditions cannot be underestimated. Inadequate hemostasis may lead to further surgical complications. Our goal was to ... ...

Abstract	Background and purpose: During laparoscopic partial nephrectomy, the importance of the initial suture placed under warm ischemic conditions cannot be underestimated. Inadequate hemostasis may lead to further surgical complications. Our goal was to determine which method of suture ligation (running vs figure-8 interrupted) provides better initial hemostasis when performing partial nephrectomy in an ex-vivo porcine model. Materials and methods: Deep partial nephrectomy defects were cut in the lateral aspect of six porcine kidneys. The renal artery was cannulated, and the kidneys were perfused from a water reservoir. The level (cm H(2)O) at which parenchymal leakage occurred was measured and recorded in three situations: No parenchymal suture; running suture along the base of the defect; and interrupted figure-8 sutures placed in parallel along the base of the defect. Results: Six kidneys were studied. Using interrupted figure-8 sutures, the mean leak pressure was 56.7 cm H(2)O (over baseline). Using a running suture, the mean leak pressure was 147.5 cm H(2)O (over baseline). Mean values were compared using two-tailed t test and found to be statistically significant (P = 0.05). Conclusion: In an ex-vivo porcine kidney model, use of a running suture along the base of a renal tumor defect (simulating that which is seen during partial nephrectomy) appears to allow for better initial hemostatic control, as compared with interrupted figure-8 sutures placed in parallel.
MeSH term(s)	Animals ; Blood Pressure/physiology ; Hemostasis, Surgical/methods ; Kidney/surgery ; Laparoscopy ; Nephrectomy/methods ; Sus scrofa/surgery ; Sutures
Language	English
Publishing date	2010-03
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	356931-7
ISSN	1557-900X ; 0892-7790
ISSN (online)	1557-900X
ISSN	0892-7790
DOI	10.1089/end.2009.0179
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Zs.A 2628: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of Nonadherence to NCCN Adjuvant Radiotherapy Initiation Guidelines in Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

Ponduri, Anusha / Liao, David Z / Schlecht, Nicolas F / Rosenblatt, Gregory / Prystowsky, Michael B / Kabarriti, Rafi / Garg, Madhur / Ow, Thomas J / Schiff, Bradley A / Smith, Richard V / Mehta, Vikas

Journal of the National Comprehensive Cancer Network : JNCCN

2021 , Page(s) 1–7

Abstract: Background: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban ... ...

Abstract	Background: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. Methods: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. Results: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). Conclusions: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.
Language	English
Publishing date	2021-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2021.7007
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Article ; Online: Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods.

Li, Daniel / Thomas, Carlos / Shrivastava, Nitisha / Gersten, Adam / Gadsden, Nicholas / Schlecht, Nicolas / Kawachi, Nicole / Schiff, Bradley A / Smith, Richard V / Rosenblatt, Gregory / Augustine, Stelby / Gavathiotis, Evripidis / Burk, Robert / Prystowsky, Michael B / Guha, Chandan / Mehta, Vikas / Ow, Thomas J

Journal of medical virology

2022 Volume 95, Issue 2, Page(s) e28388

Abstract: Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional ... ...

Abstract	Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.
MeSH term(s)	Animals ; Humans ; Mice ; Carcinoma, Squamous Cell/pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA, Viral/genetics ; Head and Neck Neoplasms ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Papillomavirus Infections ; Squamous Cell Carcinoma of Head and Neck ; Biological Specimen Banks
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; DNA, Viral
Language	English
Publishing date	2022-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28388
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Article ; Online: Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy.

Rosenblatt, Gregory S / Conlin, Michael J

BMC urology

2006 Volume 6, Page(s) 23

Abstract: Background: Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can ... ...

Abstract	Background: Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires. Methods: From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes. Results: The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up. Conclusion: Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy.
MeSH term(s)	Female ; Humans ; Intraoperative Care ; Laparoscopy/methods ; Male ; Middle Aged ; Nephrectomy/methods ; Renal Veins ; Tissue Donors
Language	English
Publishing date	2006-09-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2059857-9
ISSN	1471-2490 ; 1471-2490
ISSN (online)	1471-2490
ISSN	1471-2490
DOI	10.1186/1471-2490-6-23
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Article ; Online: Enlargement of accessory spleen after splenectomy can mimic a solitary adrenal tumor.

Rosenblatt, Gregory S / Luthringer, Daniel J / Fuchs, Gerhard J

Urology

2010 Volume 75, Issue 3, Page(s) 561–562

Abstract: We report on a 72-year-old woman who had previously undergone splenectomy and subsequently presented with an incidental 5-cm adrenal mass. Laparoscopic adrenalectomy was performed, and the mass was identified to be an accessory spleen. Remaining ... ...

Abstract	We report on a 72-year-old woman who had previously undergone splenectomy and subsequently presented with an incidental 5-cm adrenal mass. Laparoscopic adrenalectomy was performed, and the mass was identified to be an accessory spleen. Remaining accessory splenic tissue may undergo compensatory hypertrophy after splenectomy. When a biochemically inactive, well-marginated ovoid adrenal mass is identified in a postsplenectomy patient, consideration should be given to the presence of accessory spleen. In such cases, radionuclide imaging with technetium sulfur colloid may provide information that would confirm the presence of accessory normal tissue and would therefore support observation rather than surgical resection.
MeSH term(s)	Adrenal Gland Neoplasms/diagnosis ; Aged ; Diagnosis, Differential ; Female ; Humans ; Hypertrophy/complications ; Postoperative Complications/diagnosis ; Spleen/pathology ; Splenectomy
Language	English
Publishing date	2010-03
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	192062-5
ISSN	1527-9995 ; 0090-4295
ISSN (online)	1527-9995
ISSN	0090-4295
DOI	10.1016/j.urology.2009.05.070
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Article ; Online: Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy

Rosenblatt Gregory S / Conlin Michael J

BMC Urology, Vol 6, Iss 1, p

2006 Volume 23

Abstract: Abstract Background Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling ... ...

Abstract	Abstract Background Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires. Methods From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes. Results The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up. Conclusion Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy.
Keywords	Diseases of the genitourinary system. Urology ; RC870-923 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Urology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	621
Language	English
Publishing date	2006-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Urolithiasis in adults with congenital megaureter.

Rosenblatt, Gregory S / Takesita, Ken / Fuchs, Gerhard J

Canadian Urological Association journal = Journal de l'Association des urologues du Canada

2009 Volume 3, Issue 6, Page(s) E77–80

Abstract: The primary presentation of congenital megaureter in adults is rare. Development of urolithiasis may lead to this unusual underlying diagnosis. Urinary tract stones can form either within the dilated ureteral segment or in a part of the upper urinary ... ...

Abstract	The primary presentation of congenital megaureter in adults is rare. Development of urolithiasis may lead to this unusual underlying diagnosis. Urinary tract stones can form either within the dilated ureteral segment or in a part of the upper urinary tract proximal to the abnormal ureteral segment. We report two cases of nephrolithiasis that occurred in adults found to have segmental megaureter. The first case is that of a 58-year-old man who presented with left lower quadrant pain. Computed tomography scan revealed a 2-cm stone in the distal left ureter within an area of isolated segmental distal ureteral dilation. The second case is a 48-year-old man who developed recurrent renal urolithiasis associated with isolated distal megaureter.Although a rare condition in adults, congenital megaureter may present when kidney stones develop as a result of the ureteral abnormality. Typically, stones will develop within the dilated segment of ureter. Atypically, stones may develop away from the site of the underlying abnormality. Congenital megaureter is a diagnosis that urologists and radiologists need to consider in the setting of isolated distal ureteral dilation, as the diagnosis of adult megaureter may require more involved surgical measures to prevent recurrence of adverse symptoms.
Language	English
Publishing date	2009-06-09
Publishing country	Canada
Document type	Journal Article
ISSN	1920-1214
ISSN (online)	1920-1214
DOI	10.5489/cuaj.1185
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