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1.
PLoS One ; 19(6): e0301223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837964

RESUMO

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries-two synthetic and two immunized-against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.


Assuntos
Antagonistas do Receptor A2 de Adenosina , Receptor A2A de Adenosina , Humanos , Animais , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/imunologia , Células HEK293 , Camundongos , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacologia , Macaca fascicularis , Biblioteca de Peptídeos
2.
World J Urol ; 42(1): 125, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38460045

RESUMO

PURPOSE: To review our 10-year experience with laser excision for urethral mesh erosion (UME) of mid-urethral slings (MUS). METHODS: Following Institutional Review Board approval, the charts of female patients with endoscopic laser excision of UME were retrospectively reviewed. Demographics, clinical presentation, surgical history, pre- and post-operative Urinary Distress Inventory-6 scores and quality of life ratings, operative reports, and outcomes were obtained from electronic medical records. UME cure was defined as no residual mesh on office cystourethroscopy 5-6 months after the final laser excision procedure. RESULTS: From 2011 to 2021, 23 patients met study criteria; median age was 56 (range 44-79) years. Twenty (87%) had multiple prior urogynecologic procedures. Median time from MUS placement to presentation with UME-related complaints was 5.3 [interquartile range (IQR) 2.3-7.6] years. The most common presenting symptom was recurrent urinary tract infection (rUTI) (n = 10). Median operating time was 49 (IQR 37-80) minutes. Median duration of follow-up was 24 (IQR 12-84) months. Fourteen (61%) required more than 1 laser excision procedure for UME. Although 5 were asymptomatic (22%), new (n = 5) or persistent (n = 8) urinary incontinence was the most common symptom on follow-up (57%). CONCLUSION: UME presenting symptoms are highly variable, necessitating a high index of suspicion in patients with a history of MUS, especially in the case of rUTI. Endoscopic laser excision is a minimally invasive, brief, safe, outpatient procedure with a high UME cure rate.


Assuntos
Lasers de Estado Sólido , Slings Suburetrais , Incontinência Urinária por Estresse , Infecções Urinárias , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Telas Cirúrgicas , Qualidade de Vida , Cistoscopia , Slings Suburetrais/efeitos adversos , Incontinência Urinária por Estresse/cirurgia
3.
J Endourol ; 38(3): 234-239, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185830

RESUMO

Introduction: To review the postrobotic-assisted sacrocolpopexy (RASC) course of women admitted for 23 hours post-RASC and identify events requiring intensive medical care or potentially leading to deleterious outcome or urgent readmission if that patient had same-day discharge (SDD) instead of observed overnight. Methods: Patients undergoing RASC from January to December 2020 at one institution were identified and relevant data were obtained via retrospective chart review. Patient exclusions: RASC start time after 12:00 PM, concurrent posterior colporrhaphy, rectopexy, or hysterectomy, or conversion to open. Results: Sixty-nine patients (median age 71 years old) met study criteria with majority American Society of Anesthesiologists class 2 (n = 46, 67%) or 3 (n = 22, 32%). Patient characteristics included prior abdominal surgeries (n = 58, 84%), prior hysterectomy/prolapse repair (n = 25, 37%), known allergy to pain medication (n = 25, 36%), and administration of a postoperative antiemetic (n = 37, 54%) or intra-/postoperative keterolac (n = 36, 52%). Median surgery length was 269 minutes. Postoperative events that may have resulted in urgent readmissions if they had SDD were observed in 6% of patients. In the 1st week post-RASC, there were no readmissions. Conclusions: In this limited quality assurance study, patients undergoing RASC experienced no major complications requiring intensive care. Postoperative events were almost entirely nausea and pain, with no readmissions within the 1st week.


Assuntos
Prolapso de Órgão Pélvico , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Idoso , Alta do Paciente , Estudos Retrospectivos , Prolapso de Órgão Pélvico/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Dor , Complicações Pós-Operatórias , Procedimentos Cirúrgicos em Ginecologia/métodos
4.
Cell Rep ; 42(12): 113503, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38019654

RESUMO

CD276/B7-H3 represents a promising target for cancer therapy based on widespread overexpression in both cancer cells and tumor-associated stroma. In previous preclinical studies, CD276 antibody-drug conjugates (ADCs) exploiting a talirine-type pyrrolobenzodiazepine (PBD) payload showed potent activity against various solid tumors but with a narrow therapeutic index and dosing regimen higher than that tolerated in clinical trials using other antibody-talirine conjugates. Here, we describe the development of a modified talirine PBD-based fully human CD276 ADC, called m276-SL-PBD, that is cross-species (human/mouse) reactive and can eradicate large 500-1,000-mm3 triple-negative breast cancer xenografts at doses 10- to 40-fold lower than the maximum tolerated dose. By combining CD276 targeting with judicious genetic and chemical ADC engineering, improved ADC purification, and payload sensitivity screening, these studies demonstrate that the therapeutic index of ADCs can be substantially increased, providing an advanced ADC development platform for potent and selective targeting of multiple solid tumor types.


Assuntos
Imunoconjugados , Neoplasias , Humanos , Camundongos , Animais , Imunoconjugados/farmacologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Anticorpos Monoclonais Humanizados , Fatores de Transcrição , Neoplasias/tratamento farmacológico , Antígenos B7
5.
Antib Ther ; 6(3): 211-223, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37680350

RESUMO

In vivo VHH discovery approaches have been limited by the lack of methodologies for camelid B cell interrogation. Here, we report a novel application of the Beacon® optofluidic platform to the discovery of heavy-chain-only antibodies by screening alpaca B cells. Methods for alpaca B cell enrichment, culture, IgG2/3 detection, and sequencing were developed and used to discover target-specific VHH from an alpaca immunized with prostate-specific membrane antigen (PSMA) or a second target. PSMA-specific hits were expressed as VHH-Fc and characterized using label-free techniques. Anti-PSMA IgG2/3 titer plateaued on day 153, when on-Beacon IgG2/3 secretion and target binding rates peaked. Of 13 recombinantly expressed VHH-Fc, all but one bound with nanomolar affinity, and five were successfully humanized. Repertoire sequencing uncovered additional variants within the clonal lineages of the validated hits. The establishment of this workflow extends the powerful Beacon technology to enable rapid VHH discovery directly from natural camelid immune repertoires.

6.
Neurourol Urodyn ; 42(8): 1655-1667, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37497812

RESUMO

INTRODUCTION: Over 350 000 sacral neuromodulation (SNM) devices have been implanted since approval by the Food and Drug Administration (FDA) in 1998. SNM technology and clinical applications have evolved, with minimal safety updates after initial trials. We aim to provide an updated overview of real-world SNM safety. These insights will guide informed consent, preoperative counseling, and patient expectation-setting. MATERIALS AND METHODS: The FDA Manufacturer and User Facility Device Experience (MAUDE) database is a repository for medical device safety reports. We performed MAUDE categorical (1/1/98-12/31/10) and keyword (1/1/11-9/30/21) searches for "Interstim." A random sample of 1000 reports was reviewed and categorized by theme. To corroborate our MAUDE database analysis, a legal librarian searched the Public Access to Court Electronic Records (PACER) database, as well as Bloomberg Law's dockets database for all lawsuits related to SNM devices. RESULTS: Our search of the MAUDE database returned 44 122 SNM-related adverse events (AEs). The figure illustrates the prevalence of event categories in the random sample. The largest proportion of reports (25.6%) related to a patient's need for assistance with device use, followed by loss/change of efficacy (19.0%). Interestingly, a fall preceded issue onset in 32% of non-shock pain, 30% of lead/device migration, and 27% of painful shock reports. Our legal search revealed only four lawsuits: one for patient complications after an SNM device was used off-label, one case of transverse myelitis after implant, one for device migration or poor placement, and the fourth claimed the device malfunctioned requiring removal and causing permanent injury. CONCLUSIONS: This review confirms the real-world safety of SNM devices and very low complication rates as seen in the original clinical trials. Our findings indicate that 43.2% (95% confidence interval 40.1%-46.3%) of SNM "complications" are not AEs, per se, but rather reflect a need for improved technical support or more comprehensive informed consent to convey known device limitations to the patient, such as battery life. Similarly, the number of lawsuits is shockingly low for a device that has been in the market for 24 years, reinforcing the safety of the device. Legal cases involving SNM devices seem to relate to inappropriate patient selection-including at least one case in which SNM was used for a non-FDA approved indication-lack of appropriate follow-up, and/or provider inability to assist the patient with utilizing the device after implantation.


Assuntos
Terapia por Estimulação Elétrica , Estados Unidos , Humanos , United States Food and Drug Administration , Terapia por Estimulação Elétrica/efeitos adversos , Bases de Dados Factuais
7.
Urology ; 169: 70-75, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35970359

RESUMO

OBJECTIVE: To assess the long-term patient outcomes, including the resolution of symptoms and need for subsequent procedures, after vaginal mesh removals (VMR) we evaluate our 14-year experience with VMR from a tertiary center with three FPMRS-trained surgeons. Although the use of transvaginal mesh (TVM) had decreased significantly before its ban in 2019, surgeons are still treating TVM complications and performing vaginal or open/robotic VMR for mesh-related complications. METHODS: A retrospective review of women undergoing VMR with 6 months minimum follow-up was undertaken. The data abstracted included demographics, provider notes, operative reports, pathology findings, outside medical records, peri-operative information, and reoperations. RESULTS: From 2006 to 2020, 133 patients were identified, and 113 patients met study criteria with at least 6 months follow-up. The most common presenting symptoms were dyspareunia (77%) and pain (71%). The majority of VMR were performed vaginally (84.5%). Vaginal mesh was removed from anterior (60%), posterior (11%), and anterior and posterior (10%) compartments. Two ureteral injuries and one rectal injury were repaired intraoperatively. VMR resulted in resolution of pain in 50% of patients. Some patients had persistent pain (21%) and a few developed de novo pain (4%). More than half of the patients had dyspareunia resolution (52%), but 12% had persistent dyspareunia and 2% developed de novo dyspareunia. CONCLUSION: VMR complexity requires advanced surgical expertise. Most patients undergoing VMR had resolution of their presenting symptoms. However, outcomes for pain, sexual function, continence, and/or prolapse can be unpredictable, resulting in multiple surgeries.


Assuntos
Dispareunia , Prolapso de Órgão Pélvico , Slings Suburetrais , Humanos , Feminino , Prolapso de Órgão Pélvico/cirurgia , Prolapso de Órgão Pélvico/complicações , Telas Cirúrgicas/efeitos adversos , Dispareunia/epidemiologia , Dispareunia/etiologia , Slings Suburetrais/efeitos adversos , Dor , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
8.
J Urol ; 208(3): 666-667, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35942794
9.
Female Pelvic Med Reconstr Surg ; 28(5): 332-335, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35421039

RESUMO

OBJECTIVE: The aim of this study was to examine potential bias in reports to the Manufacturer and User Facility Device Experience (MAUDE) database involving vaginal mesh by identifying the party submitting the report, the nature of the complaints, and whether the reports were edited. METHODS: All reports submitted to the MAUDE database involving synthetic transvaginal mesh from January 2000 through December 2017 (40,266 safety reports) were identified. A random 2% sample (900) of these reports was reviewed in depth to determine the specific relevant details, including reporter type (patient, manufacturer, lawyer) and details of the complaint/injury. RESULTS: Of the 40,226 reports to MAUDE identified, 28,473 (70.7%) were sling reports, and 11,793 (29.3%) described mesh products augmenting pelvic organ prolapse repair. Of the 900 reports reviewed in depth, 46%, 41%, 10%, and 2% of entries were reported by the manufacturer, attorney, health care provider, and patients, respectively. In the 4 years after submission, 18.6% of reports were modified at least once. CONCLUSIONS: The MAUDE database allows physicians, manufacturers, and patients to immediately report adverse events experienced due to medical devices. While this database is an important means to identify potential danger to patients, any individual can file a report and, thus, it should not be the sole source of evidence to consider when assessing device safety. Further, the MAUDE database provides no information into the total number of cases performed without complication.


Assuntos
Prolapso de Órgão Pélvico , Telas Cirúrgicas , Bases de Dados Factuais , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Próteses e Implantes , Telas Cirúrgicas/efeitos adversos , Estados Unidos , United States Food and Drug Administration
10.
Female Pelvic Med Reconstr Surg ; 28(3): e108-e114, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35272343

RESUMO

IMPORTANCE: A better understanding of the effect of elective cesarean delivery (CD) on the development of pelvic floor disorders can help obstetricians counsel pregnant women. OBJECTIVE: This study aimed to perform a systematic review and meta-analysis evaluating whether primary elective CD is protective against pelvic floor disorders. STUDY DESIGN: Using the MOOSE criteria, electronic databases were searched for studies that compared the prevalence of pelvic floor disorders among primiparous women. Outcomes of interest were urinary incontinence (UI), fecal incontinence (FI), anal incontinence (AI), and pelvic organ prolapse (POP). Comparisons were made between CD before the onset of labor ("Elective CD"), CD after trial of labor ("Labor CD"), and vaginal delivery (VD). Risk ratios (RRs) were computed using STATA. Between-study heterogeneity was assessed via Cochrane's homogeneity test and review of the I2 statistic. RESULTS: Nineteen studies were included. The overall prevalence of UI for Elective CD was estimated at 7% (95% confidence interval [CI], 3%-13%), Labor CD at 14% (95% CI, 8%-21%), and VD at 26% (95% CI, 20%-32%). Meta-analysis demonstrated a decreased risk of UI after Elective CD compared with Labor CD (RR, 0.75; P = 0.011) or VD (RR, 0.43; P < 0.001). There was a decreased risk of FI or AI after Elective CD compared with VD, but not when compared with Labor CD. Only 2 studies examined POP, precluding meta-analysis. CONCLUSIONS: Among primiparous women, Elective CD may be protective against UI when compared with Labor CD. There was not a protective effect of Elective CD against FI and AI when compared with Labor CD. More data on the effect of elective CD on POP are needed.


Assuntos
Incontinência Fecal , Distúrbios do Assoalho Pélvico , Incontinência Urinária , Cesárea/efeitos adversos , Parto Obstétrico/efeitos adversos , Incontinência Fecal/epidemiologia , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Distúrbios do Assoalho Pélvico/epidemiologia , Distúrbios do Assoalho Pélvico/etiologia , Gravidez , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia
11.
J Minim Invasive Gynecol ; 29(5): 626-632, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986410

RESUMO

STUDY OBJECTIVE: This study aimed to apply a structured human factors analysis to understand conditions contributing to vaginal retained foreign objects (RFOs). DESIGN: All potential vaginal RFO events from January 1, 2000, to May 21, 2019, were analyzed by trained human factors researchers. Each narrative was reviewed to identify contributing factors, classified using the Human Factors Analysis and Classification System for Healthcare. SETTING: An 890-bed, academic medical center in Southern California. PATIENTS: Patients who underwent a vaginal procedure in which a vaginal RFO-related event occurred were included in this study. However, no patient information was included, and only the relevant details from their procedures were included. INTERVENTIONS: No interventions were developed or implemented. MEASUREMENTS AND MAIN RESULTS: Over the 19-year period, 45 events were reported. The most common items were vaginal packing and vaginal sponges (53.33%). Less frequently retained items involved broken instruments (20.20%). Most cases were laparoscopic hysterectomies or vaginal deliveries. Based on the Human Factors Analysis and Classification System, 75 contributing factors were identified, consisting primarily of preconditions for unsafe acts (communication challenges, coordination breakdowns and issues with the design of tools/technology) and unsafe acts (errors). CONCLUSION: Although rare, vaginal RFOs do occur. The top 2 contributing factors were skill-based errors and communication breakdowns. Both types of errors can be addressed and improved with human factors interventions, including simulation, teamwork training, and streamlining workflow to reduce the opportunity for errors.


Assuntos
Corpos Estranhos , Feminino , Corpos Estranhos/etiologia , Corpos Estranhos/cirurgia , Humanos , Erros Médicos , Vagina/cirurgia
12.
J Urol ; 207(2): 415-416, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34781694
13.
Antib Ther ; 4(3): 185-196, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34541454

RESUMO

BACKGROUND: Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in aggressive timelines. METHODS: In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the severe acute respiratory syndrome coronavirus-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb™ mouse model for increased diversity. RESULTS: The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. CONCLUSIONS: By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.

14.
World J Urol ; 39(12): 4499-4503, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34383134

RESUMO

OBJECT: To use a contemporary population-based cohort to investigate temporal trends in the national incidence of pelvic fracture urethral injuries (PFUIs) in the United States. METHODS: Using the NIS (National Inpatient Sample), we identified patients with a severe PFUI by a combination of an ICD-9 diagnosis code for pelvic fracture (808.xx) and ICD-9 procedure code for suprapubic tube (57.17 or 57.18) from 1998 to 2014. We compared the annual rates of PFUIs and the annual rates of pelvic fractures alone. RESULTS: An estimated total of 6052 ± 347 males with PFUIs were identified. The average age was 38.4 ± 0.5 years. 9.1% ± 0.8% of patients died while hospitalized. In the time frame studied, the rate of PFUI significantly decreased during from 532 patients in 1998 to 255 patients in 2014. Sensitivity analysis excluding patients with bladder repairs identified a similar trend. The annual rate of PFUI per 1000 pelvic fractures has also decreased from 14.6 ± 1.6 in 1998 to 6.5 ± 0.9 in 2014 (p = 0.001). CONCLUSIONS: In this population level study, the number of severe PFUIs has decreased in the United States from 1998 to 2014, which coincides with the implementation and enforcement of seat belt and air bag regulations. Given the rarity of these cases, there is a strong need for collaborative efforts in research and teaching at tertiary care centers for reconstructive urology.


Assuntos
Fraturas Ósseas/complicações , Uretra/lesões , Adulto , Humanos , Incidência , Escala de Gravidade do Ferimento , Masculino , Fatores de Tempo , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologia
15.
Int Neurourol J ; 25(2): 172-176, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33957719

RESUMO

PURPOSE: We sought to describe and analyze the adverse events associated with synthetic male slings reported to the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: We queried the MAUDE database for all entries including the terms "Male Sling," "InVance," "Virtue," or "Advance" from January 1st, 2009 to December 31st, 2018. We collected and analyzed information about the event type, date received, report source, source type, and manufacturer. We reviewed and categorized the event description text for each medical device report (MDR). RESULTS: A total of 497 adverse events related to the male sling were identified. The adverse events were classified as injury (95.4%), malfunction (4.2%), and other (0.4%). There were no deaths described. The slings involved were the Advance or Advance XP sling (69.8%), InVance (15.5%), Virtue Quadratic (12.3%), or unknown (2.4%). The 4 most common adverse events described were urinary incontinence (46.7%), sling erosion (9.1%), mechanical malfunction (8.2%), and pain/numbness (8.2%). There was no increase in the number of reports in the years following the FDA warnings for urogynecologic mesh. CONCLUSION: There was an overall modest number of MDRs related to male slings and the majority of them were reported by the manufacturer. The reporting of adverse events for male slings does not seem to be affected by the controversy and scrutiny towards transvaginal mesh and midurethral slings. Further clinical studies and more objective and detailed databases are needed to investigate the safety of these synthetic slings.

16.
Urology ; 156: 85-89, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34010679

RESUMO

OBJECTIVES: To compare continence outcomes and health-related quality of life (HRQOL) among women with limited activity restrictions vs traditional restrictions following mid-urethral sling (MUS) surgery. METHODS: Thirty-six women who underwent MUS surgery were randomized: (1) the Restrictions group was given traditional postoperative restrictions for 6 weeks while (2) the Limited Restrictions group was instructed to resume normal activities other than pelvic rest. Patients undergoing concomitant surgery for Stage III and IV prolapse were excluded. Participants completed questionnaires related to urinary symptoms (UDI-6, IIQ-7) for continence outcomes and HRQOL (SF-12) at baseline, 1 to 6 weeks, 3 months, 6 months, and at least 1 year after surgery. RESULTS: There was no difference in mean scores on the UDI-6 or IIQ-7 between groups at baseline or any time after surgery. The Limited Restrictions group reported better scores than the Restrictions group on the SF-12 mental health component at 1 week (56.7 vs 50.2, P = .01) and 4 weeks (58.4 vs 53.3, P = .04). The Restrictions group reported better SF-12 physical health scores at 5 weeks (55.7 vs 53.0, P = .02) but there was no difference in HRQOL scores between the two groups at any other time. CONCLUSION: In this pilot study, there was no difference in continence outcomes for women with traditional vs limited activity restrictions following MUS surgery. There were differences in HRQOL in the early post-operative period, but these differences were not sustained. Larger prospective studies are needed, but it appears that activity restrictions after MUS surgery may not be necessary.


Assuntos
Convalescença , Exercício Físico , Qualidade de Vida , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Projetos Piloto , Período Pós-Operatório , Autorrelato , Slings Suburetrais/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
17.
Urology ; 153: 11-13, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33864857

RESUMO

OBJECTIVE: To quantify and describe urologic adverse events and symptoms after vaccination with the Pfizer-BioNTech and Moderna COVID-19 vaccines. METHODS AND MATERIALS: We queried the FDA Vaccine Adverse Event Reporting System (VAERS) for all reported symptoms following the Pfizer-BioNTech and Moderna vaccines as of February 12th, 2021. All urologic symptoms were isolated and the reported adverse events associated with each symptom were reviewed. RESULTS: Out of 15,785 adverse event reports, only 0.7% (113) described urologic symptoms. A total of 156 urologic symptoms were described amongst the 113 adverse event reports. The Pfizer-BioNTech vaccine was responsible for 61% of these reports and the Moderna vaccine was responsible for 39%. These symptoms were grouped into five different categories: Lower Urinary Tract Symptoms (n = 34, 22%), Hematuria (n = 22, 14%), Urinary Infection (n = 41, 26%), Skin and/or Soft Tissue (n = 16, 10%), and Other (n = 43, 28%). The median age of the patients reporting urologic symptoms was 63 years (IQR 44-79, Range: 19-96) and 54% of the patients were female. CONCLUSION: Urologic symptoms reported after COVID-19 vaccination are extremely rare. Given the common prevalence of many of these reported symptoms in the general population, there does not appear to be a correlation between vaccination and urologic symptoms, but as the vaccination criteria expands, further monitoring of the Vaccine Adverse Event Reporting System is needed.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Doenças Urológicas/induzido quimicamente , Vacina de mRNA-1273 contra 2019-nCoV , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Vacina BNT162 , Feminino , Hematúria/induzido quimicamente , Humanos , Sintomas do Trato Urinário Inferior/induzido quimicamente , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Estados Unidos , United States Food and Drug Administration , Infecções Urinárias/induzido quimicamente , Adulto Jovem
18.
J Clin Invest ; 131(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33914704

RESUMO

Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B. burgdorferi from infected ticks in animal models. Maintenance of a protective plasma concentration of a human mAb for tick season presents a significant challenge for a preexposure prophylaxis strategy. Here, we describe the optimization of mAb 2217 by amino acid substitutions (2217LS: M428L and N434S) in the Fc domain. The LS mutation led to a 2-fold increase in half-life in cynomolgus monkeys. In a rhesus macaque model, 2217LS protected animals from tick transmission of spirochetes at a dose of 3 mg/kg. Crystallographic analysis of Fab in complex with OspA revealed that 2217 bound an epitope that was highly conserved among the B. burgdorferi, B. garinii, and B. afzelii species. Unlike most vaccines that may require boosters to achieve protection, our work supports the development of 2217LS as an effective preexposure prophylaxis in Lyme-endemic regions, with a single dose at the beginning of tick season offering immediate protection that remains for the duration of exposure risk.


Assuntos
Anticorpos Antibacterianos , Anticorpos Monoclonais/farmacologia , Borrelia burgdorferi , Doença de Lyme , Substituição de Aminoácidos , Animais , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/farmacologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Antígenos de Superfície/genética , Antígenos de Superfície/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Borrelia burgdorferi/genética , Borrelia burgdorferi/imunologia , Modelos Animais de Doenças , Humanos , Lipoproteínas/genética , Lipoproteínas/imunologia , Doença de Lyme/tratamento farmacológico , Doença de Lyme/genética , Doença de Lyme/imunologia , Doença de Lyme/transmissão , Macaca fascicularis , Macaca mulatta , Masculino , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Carrapatos/imunologia , Carrapatos/microbiologia
19.
J Urol ; 206(2): 390-398, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33780281

RESUMO

PURPOSE: For patients with persistent irritative lower urinary tract symptoms, such as dysuria and urinary frequency, evaluation for the atypical organisms Ureaplasma and Mycoplasma has been a common part of care. However, these species are genitourinary colonizers and have not been established as causative pathogens in chronic lower urinary tract symptoms. We therefore sought to evaluate diagnostic testing patterns for Ureaplasma and Mycoplasma and characterize the associations of these bacteria with irritative lower urinary tract symptoms using molecular detection techniques. MATERIALS AND METHODS: Ureaplasma/Mycoplasma testing patterns for 2019 were assessed using an anonymized data repository. Clean catch urine specimens (179) were collected prospectively from female and male patients with and without irritative lower urinary tract symptoms. Quantitative polymerase chain reaction evaluated urinary Ureaplasma and Mycoplasma DNA concentrations, while next-generation sequencing assessed the relative abundance of Ureaplasma and Mycoplasma within the urinary bacterial population. RESULTS: Ureaplasma/Mycoplasma testing was common, with 575 tests performed in 2019 in our community hospital system. In our cohort, Ureaplasma and Mycoplasma were identified in similar proportions in symptomatic and asymptomatic subjects: 25% of female controls and 27% of females with lower urinary tract symptoms and 9.5% of asymptomatic males and 3.3% of men with symptoms (p=0.87 and p=0.91 for females and males, respectively). Regression analysis revealed that both abundance and concentrations of Mycoplasmataceae correlated negatively with a range of irritative lower urinary tract symptoms, including dysuria and urethral pain. CONCLUSIONS: A statistically significant negative correlation of Ureaplasma/Mycoplasma levels with a variety of lower urinary tract symptoms suggests that polymerase chain reaction-based Mycoplasmataceae detection has little diagnostic benefit in assessment of chronic irritative urinary symptoms.


Assuntos
Sintomas do Trato Urinário Inferior/complicações , Mycoplasma/isolamento & purificação , Ureaplasma/isolamento & purificação , Sistema Urinário/microbiologia , Adolescente , Adulto , Criança , DNA Bacteriano/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Mycoplasma/genética , Reação em Cadeia da Polimerase , Estudos Prospectivos , Análise de Sequência de DNA , Ureaplasma/genética , Adulto Jovem
20.
J Surg Educ ; 78(5): 1655-1659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33558192

RESUMO

INTRODUCTION: To assess the impact of resident participation on patient satisfaction by comparing post-discharge satisfaction scores between academic faculty, private urologists who work with residents, and private urologists with no involvement in resident education. METHODS: Post-discharge Hospital Consumer Assessment of Healthcare Providers and Systems surveys from academic and private urologists at a single institution with an accredited Urology residency program from January 1, 2014 to December 31, 2016 (n = 530) were reviewed. The surveys were de-identified and categorized based on 3 subgroups of providers: academic faculty, private with residents, and private without residents. Overall rating, physician (MD) communication, nursing (RN) communication, discharge information, and overall management during their hospitalization were assessed. RESULTS: The faculty group received an overall patient satisfaction score of 88.3% (percentage of 9 or 10). The private with resident group had an overall satisfaction score of 92.0% and the private without resident group had an overall satisfaction score of 96.7%. There was no statistical difference in patient satisfaction scores between groups across all categories with the exception of MD and RN communication. Private urologists with residents had better MD and RN communication scores than the 2 other groups (p < 0.001, p = 0.013, respectively). CONCLUSIONS: Resident involvement in patient care with faculty or private attendings did not have a negative effect on patient satisfaction scores of any factor measured. Patients were more satisfied with MD and RN communication when residents worked with private attendings.


Assuntos
Internato e Residência , Urologia , Assistência ao Convalescente , Humanos , Alta do Paciente , Satisfação do Paciente , Urologia/educação
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