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Article ; Online: Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration.

Tyagi, Pradeep / Hafron, Jason / Kaufman, Jonathan / Chancellor, Michael

International journal of molecular sciences

2024 Volume 25, Issue 9

Abstract: Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. ... ...

Abstract	Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette-Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy's role in BC management, ultimately improving patient outcomes.
MeSH term(s)	Humans ; Urinary Bladder Neoplasms/drug therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/adverse effects ; Administration, Intravesical ; Immunotherapy/methods ; Treatment Outcome
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2024-05-01
Publishing country	Switzerland
Document type	Journal Article ; Review ; Comparative Study
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25094945
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: How to… collect urine samples from young children.

Kaufman, Jonathan

Archives of disease in childhood. Education and practice edition

2019 Volume 105, Issue 3, Page(s) 164–171

Abstract: Urine samples are commonly collected from young children to diagnose or exclude urinary tract infections, but collection from precontinent children is challenging. Each collection method has advantages and limitations. Non-invasive methods (urine pads, ... ...

Abstract	Urine samples are commonly collected from young children to diagnose or exclude urinary tract infections, but collection from precontinent children is challenging. Each collection method has advantages and limitations. Non-invasive methods (urine pads, bags, clean catch) are convenient but can be time-consuming and are limited by sample contamination. Voiding stimulation methods (bladder-lumbar stimulation, Quick-Wee) can expedite clean catch collection. Invasive methods (catheter, suprapubic aspiration) can be more reliable, but require expertise to perform and cause pain for the child. This article reviews each collection method, and describes collection procedures, indications and strategies to optimise success and reduce contamination.
MeSH term(s)	Child, Preschool ; Female ; Humans ; Infant ; Male ; Pediatrics/standards ; Practice Guidelines as Topic ; Urinary Tract Infections/diagnosis ; Urinary Tract Infections/urine ; Urine Specimen Collection/methods ; Urine Specimen Collection/standards
Language	English
Publishing date	2019-08-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2148818-6
ISSN	1743-0593 ; 1743-0585
ISSN (online)	1743-0593
ISSN	1743-0585
DOI	10.1136/archdischild-2019-317237
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Article ; Online: Obituary: A Remembrance of Robert S. Siffert MD (1918-2015).

Kaufman, Jonathan J

Clinical orthopaedics and related research

2016 Volume 474, Issue 5, Page(s) 1348–1351

MeSH term(s)	Biomedical Research/history ; Education, Medical/history ; History, 20th Century ; History, 21st Century ; Humans ; Orthopedic Procedures/education ; Orthopedic Procedures/history ; Orthopedics/education ; Orthopedics/history ; United States
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article ; Portraits
ZDB-ID	80301-7
ISSN	1528-1132 ; 0009-921X
ISSN (online)	1528-1132
ISSN	0009-921X
DOI	10.1007/s11999-016-4772-9
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Article ; Online: Colleges and Crime-Comparing Homicide and Suicide Rates Among College Towns and Their Counterparts.

Prentice, Carter M / Song, Jamie / Degli Esposti, Michelle / Jay, Jonathan / Wiebe, Douglas J / Jacovides, Christina L / Seamon, Mark J / Kaufman, Elinore J

The Journal of surgical research

2023 Volume 293, Page(s) 490–496

Abstract: Introduction: To investigate differences in homicide and suicide rates across college town status and determine whether college towns were predisposed to changes in rates over time.: Methods: We analyzed county-level homicide and suicide rates (total ...

Abstract	Introduction: To investigate differences in homicide and suicide rates across college town status and determine whether college towns were predisposed to changes in rates over time. Methods: We analyzed county-level homicide and suicide rates (total and by firearm) across college town status using 2015-2019 CDC death certificate data and data from the American Communities Project. Results: Population-level homicide rates were similar across college town status, but younger age groups were at increased risk for firearm homicide and total homicide in college towns. College town status was associated with lower population-level firearm suicide rates, but individuals aged less than 18 y were at increased risk for total and firearm suicide. Finally, college towns were not classified as outliers for changes in either firearm homicide or suicide rates over time. Conclusions: College towns had similar homicide rates and significantly lower firearm suicide rates than other counties; however, individuals aged less than 18 y were at increased risk for both outcomes. The distinctive demographic, social, economic, and cultural features of college towns may contribute to differing risk profiles among certain age groups, thus may also be amenable to focused prevention efforts.
MeSH term(s)	Humans ; United States/epidemiology ; Homicide ; Cities ; Suicide ; Firearms ; Population Surveillance ; Wounds, Gunshot/epidemiology
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	80170-7
ISSN	1095-8673 ; 0022-4804
ISSN (online)	1095-8673
ISSN	0022-4804
DOI	10.1016/j.jss.2023.09.020
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Article ; Online: Cargo selective vesicle tethering: The structural basis for binding of specific cargo proteins by the Golgi tether component TBC1D23.

Cattin-Ortolá, Jérôme / Kaufman, Jonathan G G / Gillingham, Alison K / Wagstaff, Jane L / Peak-Chew, Sew-Yeu / Stevens, Tim J / Boulanger, Jérôme / Owen, David J / Munro, Sean

Science advances

2024 Volume 10, Issue 13, Page(s) eadl0608

Abstract: The Golgi-localized golgins golgin-97 and golgin-245 capture transport vesicles arriving from endosomes via the protein TBC1D23. The amino-terminal domain of TBC1D23 binds to the golgins, and the carboxyl-terminal domain of TBC1D23 captures the vesicles, ...

Abstract	The Golgi-localized golgins golgin-97 and golgin-245 capture transport vesicles arriving from endosomes via the protein TBC1D23. The amino-terminal domain of TBC1D23 binds to the golgins, and the carboxyl-terminal domain of TBC1D23 captures the vesicles, but how it recognizes specific vesicles was unclear. A search for binding partners of the carboxyl-terminal domain unexpectedly revealed direct binding to carboxypeptidase D and syntaxin-16, known cargo proteins of the captured vesicles. Binding is via a threonine-leucine-tyrosine (TLY) sequence present in both proteins next to an acidic cluster. A crystal structure reveals how this acidic TLY motif binds to TBC1D23. An acidic TLY motif is also present in the tails of other endosome-to-Golgi cargo, and these also bind TBC1D23. Structure-guided mutations in the carboxyl-terminal domain that disrupt motif binding in vitro also block vesicle capture in vivo. Thus, TBC1D23 attached to golgin-97 and golgin-245 captures vesicles by a previously undescribed mechanism: the recognition of a motif shared by cargo proteins carried by the vesicle.
MeSH term(s)	Golgi Matrix Proteins/metabolism ; Membrane Proteins/metabolism ; Golgi Apparatus/metabolism ; Biological Transport ; Endosomes/metabolism ; Protein Binding
Chemical Substances	Golgi Matrix Proteins ; Membrane Proteins
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adl0608
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Article ; Online: Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

Ackerman, A Lenore / Jackson, Nicholas J / Caron, Ashley T / Kaufman, Melissa R / Routh, Jonathan C / Lowder, Jerry L

Scientific reports

2023 Volume 13, Issue 1, Page(s) 18412

Abstract: This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation ... ...

Abstract	This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of "persistency" in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex.
MeSH term(s)	Humans ; Pelvic Floor ; Trigger Points ; Lower Urinary Tract Symptoms/diagnosis ; Muscle Hypertonia
Language	English
Publishing date	2023-10-27
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-44862-5
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Article: Myofascial Frequency Syndrome: A novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

Ackerman, A Lenore / Jackson, Nicholas J / Caron, Ashley T / Kaufman, Melissa R / Routh, Jonathan C / Lowder, Jerry L

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Patients presenting with lower urinary tract symptoms (LUTS) are historically classified to several symptom clusters, primarily overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Accurate diagnosis, however, ... ...

Abstract	Background: Patients presenting with lower urinary tract symptoms (LUTS) are historically classified to several symptom clusters, primarily overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Accurate diagnosis, however, is challenging due to overlapping symptomatic features, and many patients do not readily fit into these categories. To enhance diagnostic accuracy, we previously described an algorithm differentiating OAB from IC/BPS. Herein, we sought to validate the utility of this algorithm for identifying and classifying a real-world population of individuals presenting with OAB and IC/BPS and characterize patient subgroups outside the traditional LUTS diagnostic paradigm. Methods: An Findings: Application of a diagnostic algorithm to an unselected group of 551subjects presenting for urologic care identified OAB and IC/BPS in 137 and 96 subjects, respectively. An additional 110 patients (20%) with bothersome urinary symptoms lacked either bladder pain or urgency characteristic of IC/BPS and OAB, respectively. In addition to urinary frequency, this population exhibited a distinctive symptom constellation suggestive of myofascial dysfunction characterized as "persistency": bothersome urinary frequency resulting from bladder discomfort/pelvic pressure conveying a sensation of bladder fullness and a desire to urinate. On examination, 97% of persistency patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. We therefore classified this symptom complex "myofascial frequency syndrome". To confirm this symptom pattern was attributable to the pelvic floor, we confirmed the presence of "persistency" in 68 patients established to have pelvic floor myofascial dysfunction through comprehensive evaluation corroborated by symptom improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming that myofascial frequency syndrome is a distinct LUTS symptom complex. Interpretation: This study describes a novel, distinct phenotype of LUTS we classified as Funding: This work was supported by the AUGS/Duke UrogynCREST Program (R25HD094667 (NICHD)) and by NIDDK K08 DK118176 and Department of Defense PRMRP PR200027, and NIA R03 AG067993.
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.14.23288590
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Article ; Online: Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction

A. Lenore Ackerman / Nicholas J. Jackson / Ashley T. Caron / Melissa R. Kaufman / Jonathan C. Routh / Jerry L. Lowder

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract This study describes a novel, distinct phenotype of urinary symptoms named “myofascial urinary frequency syndrome” (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom ... ...

Abstract	Abstract This study describes a novel, distinct phenotype of urinary symptoms named “myofascial urinary frequency syndrome” (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit “persistency”: a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of “persistency” in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reply to Comment on Di Marco, N., Kaufman, J., Rodda, C.P. Shedding Light on Vitamin D Status and Its Complexities during Pregnancy, Infancy and Childhood: An Australian Perspective.

Di Marco, Nelfio / Kaufman, Jonathan / Rodda, Christine P

International journal of environmental research and public health

2019 Volume 16, Issue 9

Abstract: We thank the author(s) for their most informative letter in response to our article [ ... ]. ...

Abstract	We thank the author(s) for their most informative letter in response to our article [...].
MeSH term(s)	Australia ; Child ; Continental Population Groups ; Female ; Humans ; Infant ; Pregnancy ; Public Health ; Vitamin D ; Vitamins
Chemical Substances	Vitamins ; Vitamin D (1406-16-2)
Language	English
Publishing date	2019-05-06
Publishing country	Switzerland
Document type	Journal Article ; Comment
ISSN	1660-4601
ISSN (online)	1660-4601
DOI	10.3390/ijerph16091576
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Article ; Online: Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA.

Khan, Mohammad K / Nasti, Tahseen H / Qian, Joshua Y / Kleber, Troy J / Switchenko, Jeffrey M / Kaufman, Jonathan L / Nooka, Ajay J / Dhodapkar, Madhav V / Buchwald, Zachary S / Obiekwe, Daby / Lonial, Sagar / Ahmed, Rafi

The Lancet. Haematology

2024

Abstract: Background: Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. Single immune-checkpoint inhibitors, such as anti-programmed death-1 (anti- ... ...

Abstract	Background: Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. Single immune-checkpoint inhibitors, such as anti-programmed death-1 (anti-PD1), have not been successful. We aimed to evaluate the activity and safety of the combination of pembrolizumab and low-dose, single-fraction, hypofractionated radiotherapy to treat patients with relapsed or refractory multiple myeloma. Methods: For this prospective, single-centre, single-group, open-label, phase 2 trial, we recruited patients with relapsed or refractory multiple myeloma from the Winship Cancer Institute (Emory University, Atlanta, GA, USA). Key inclusion criteria were aged 18 years or older, Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, relapsed or refractory multiple myeloma as indicated by progression under International Myeloma Working Group (IMWG) criteria, and adequate candidacy for both pembrolizumab and radiotherapy. Baseline and post-treatment assessments were serial bone-marrow biopsy, peripheral blood collections, staging, serial serum and urine paraprotein analysis, serial PET-CT imaging, and a physical examination. On day 1, patients received hypofractionated 8 gray in 1 fraction (8 Gy/1 fx) radiotherapy to either symptomatic or progressing extra-osseous or osseous myeloma sites. Patients also received pembrolizumab (200 mg/kg intravenously) on day 2 or 3, then once every 3 weeks (±7 days) for 2 years or until progressive disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or death. Dose reduction and interruptions were not allowed. The primary outcome was acute toxicity defined as grade 3 or worse toxicity at 3 months within the radiated site when used in combination with pembrolizumab. All patients were analysed per protocol and included in safety analyses. This trial is registered on ClinicalTrials.gov (NCT03267888); it is completed and closed to accrual. Findings: 32 patients were screened between June 1, 2018, and Sept 2, 2022, and 25 were enrolled in the trial and treated on protocol. Of the 25 treated patients, 11 (44%) were female and 14 (56%) were male. 19 (76%) patients were White and six (24%) were Black or African American. Toxicity, as the primary outcome, was deemed to be acceptable as no grade 4 or 5 adverse events were observed. At 3-month follow-up, eight (32%) of 25 patients had treatment benefit (one had stable disease, three had partial response, two had very good partial response, and two had complete response). There was no grade 3 or worse radiation-related toxicity within irradiated volumes. One (4%) patient of the 25 who received combination treatment had a grade 3 pembrolizumab-related adverse event. There were no treatment-related deaths. Interpretation: Combination treatment of low-dose, single-fraction radiotherapy with pembrolizumab was safe, with early promise of response activity. Our approach could be an option for patients with relapsed or refractory multiple myeloma who have not responded to previous treatment. Larger trials to substantiate our findings are needed. Funding: Merck Sharp & Dohme.
Language	English
Publishing date	2024-05-23
Publishing country	England
Document type	Journal Article
ISSN	2352-3026
ISSN (online)	2352-3026
DOI	10.1016/S2352-3026(24)00105-4
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