While many risk indexes for predicting morbidity following urological surgery have been reported, determining the best ones for clinical use is challenging. A new frailty index (mFI-5) has emerged for endoscopic treatment of benign prostatic hyperplasia (BPH), but its effectiveness for predicting postoperative complications has not been investigated. We compared mFI-5 with the two most commonly used indexes, the American Society of Anesthesiologists (ASA) physical classification and the modified Charlson Comorbidity Index (mCCI), and the total number of comorbidities using the National Surgical Quality Improvement Program (NSQIP) database. We retrospectively queried the 2015-2020 NSQIP datasets for patients who underwent endoscopic treatment for BPH using Current Procedural Terminology and International Classification of Diseases codes. Patients were stratified by procedure type (transurethral resection of prostate [TURP], laser vaporization of prostate [LVP], laser enucleation of prostate [LEP]). Risk indexes were calculated and compared as predictors of postoperative using logistic regression and C-statistics. 38,128 patients were included with a mean age of 71. The overall complication rate was 10.6%. When stratifying based on surgery type, the complication rates were 11.0% for TURP, 10.3% for LVP, and 7.6% for LEP. Discriminatory ability of risk indexes was mostly comparable between risk indexes but differed based on procedure type and postoperative outcome. mCCI was found to be superior in predicting surgical complications for TURP and in predicting unplanned reoperation and increased length of stay for LVP. ASA Class was found to be superior in predicting all-cause complication, unplanned reoperation, and complication for LEP. mFI-5 was not superior to any index in predicting any postoperative outcome. mCCI and ASA Class have utility in predicting postoperative outcomes for LVP and LEP, respectively. Most risk indexes are comparable and therefore can be utilized at the ease of the provider.
Titanium-45 (45Ti) is a radionuclide with excellent physical characteristics for use in positron emission tomography (PET) imaging, including a moderate half-life (3.08 h), decay by positron emission (85%), and a low mean positron energy of 0.439 MeV. However, challenges associated with titanium chemistry have led to the underdevelopment of this radionuclide for incorporation into radiopharmaceuticals. Expanding on our recent studies, which showed promising results for the complexation of 45Ti with the tris hydroxypyridinone (THPMe) chelator, the current work aimed to optimize the chemistry and imaging attributes of [45Ti]Ti-THP-PSMA as a new PET radiopharmaceutical. Methods. Radiolabeling of THP-PSMA was optimized with [45Ti]Ti-citrate at varying pHs and masses of the precursor. The stability of the radiolabeled complex was assessed in mouse serum for up to 6 h. The affinity of [45Ti]Ti-THP-PSMA for prostate-specific membrane antigen (PSMA) was assessed using LNCaP (PSMA +) and PC3 (PSMA -) cell lines. In vivo imaging and biodistribution analysis were performed in tumor-bearing xenograft mouse models to confirm the specificity of the tumor uptake. Results. > 95% of radiolabeling was achieved with a high specific activity of 5.6 MBq/nmol under mild conditions. In vitro cell binding studies showed significant binding of the radiolabeled complex with the PSMA-expressing LNCaP cell line (11.9 ± 1.5%/mg protein-bound activity) compared to that with the nonexpressing PC3 cells (1.9 ± 0.4%/mg protein-bound activity). In vivo imaging and biodistribution studies confirmed specific uptake in LNCaP tumors (1.6 ± 0.27% ID/g) compared to that in PC3 tumors (0.39 ± 0.2% ID/g). Conclusion. This study showed a simple one-step radiolabeling method for 45Ti with THP-PSMA under mild conditions (pH 8 and 37 °C). In vitro cell studies showed promise, but in vivo tumor xenograft studies indicated low tumor uptake. Overall, this study shows the need for more chelators for 45Ti for the development of a PET radiopharmaceutical for cancer imaging.
You have accessJournal of UrologyStone Disease: Surgical Therapy (Including ESWL) V (MP78)1 May 2024MP78-05 STEERABLE URETEROSCOPIC RENAL EVACUATION DEVICE, A SINGLE CENTER EXPERIENCE Andrea J. Moyer, Luke Griffiths, Gregory Mullen, Leah Beland, Matthew Mikula, Tareq Aro, Jared Winoker, David Hoenig, Zeph Okeke, and Arun Rai Andrea J. MoyerAndrea J. Moyer , Luke GriffithsLuke Griffiths , Gregory MullenGregory Mullen , Leah BelandLeah Beland , Matthew MikulaMatthew Mikula , Tareq AroTareq Aro , Jared WinokerJared Winoker , David HoenigDavid Hoenig , Zeph OkekeZeph Okeke , and Arun RaiArun Rai View All Author Informationhttps://doi.org/10.1097/01.JU.0001008856.05210.73.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the past decades, the prevalence of nephrolithiasis has increased globally. The goal of surgical treatment of kidney stones is to maximize stone free rate (SFR) while minimizing morbidity. Kim et al. recently reported SFR after ureteroscopy (URS) of 49.6% in renal stones. Residual fragments can lead to significant stone events such as stone growth, pain, infection, or additional procedures. For large stone burdens, percutaneous nephrolithotomy (PCNL) is preferred to achieve this goal. PCNL is invasive and those with contraindications have limited treatment options. The CVAC™ calculus vacuum aspiration catheter is a steerable ureteroscopic renal evacuation (SURE) device used to remove small stone fragments after laser lithotripsy designed to improve stone free outcomes.We sought to report our experience using a novel SURE device in the management of nephrolithiasis and describe its efficacy and safety. METHODS: A retrospective chart review of all patients at our institution undergoing SURE from January 2022 through August 2023 was performed. Use of SURE was at the discretion of the surgeon. For all patients, URS with laser lithotripsy was performed until stone fragments were less than 2mm in size. Stone volumes were calculated for spheroids using formulas based on maximum stone diameter. Postoperative imaging was performed with either CT or ultrasound (US) with the majority performed at two months. SFR was defined as <2mm of residual stone. RESULTS: SURE was performed 104 times on a total of 91 patients. Average stone burden was 931mm3. Post-operative imaging was performed in 62 patients. 51.6% of these patients achieved SFR of <2mm of residual stone on US or CT. 11.3% had residual stone of 2-4mm and 37.1% of >4mm (Table 1). Only two intraoperative complications of minor ureteral tears managed with stents were reported. Overall, there were eight postoperative complications. Five patients (5.5%) developed postoperative sepsis, two patients developed urinary tract infections, and one patient had stent migration requiring return to the operating room for replacement. Eleven patients (12%) had second stage procedures to treat their stone disease. CONCLUSIONS: SURE is a safe and effective treatment option for patients undergoing URS with high SFR comparable to URS alone. SURE was also associated with low morbidity, even when treating large volume stone disease. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1264 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Andrea J. Moyer More articles by this author Luke Griffiths More articles by this author Gregory Mullen More articles by this author Leah Beland More articles by this author Matthew Mikula More articles by this author Tareq Aro More articles by this author Jared Winoker More articles by this author David Hoenig More articles by this author Zeph Okeke More articles by this author Arun Rai More articles by this author Expand All Advertisement PDF downloadLoading ...
You have accessJournal of UrologyCME1 Apr 2023MP13-02 COMPARING MFI-5, ASA CLASS, AND MCCI AS PREDICTORS OF POSTOPERATIVE OUTCOMES FOLLOWING ENDOSCOPIC TREATMENT OF BPH Justin James, Grace Jun, Jacob Gaines, Zeph Okeke, Gregory Mullen, and Arun Rai Justin JamesJustin James More articles by this author , Grace JunGrace Jun More articles by this author , Jacob GainesJacob Gaines More articles by this author , Zeph OkekeZeph Okeke More articles by this author , Gregory MullenGregory Mullen More articles by this author , and Arun RaiArun Rai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003233.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While frailty has emerged as a predictor of morbidity following urological surgery, it remains difficult to measure. A new frailty index (modified Frailty Index-5(mFI-5)) has emerged for endoscopic treatment of benign prostatic hyperplasia (BPH); however, its discriminatory abilities for postoperative complications has not been investigated. Therefore, we compared mFI-5 to two most commonly used indexes, the American Society of Anesthesiologists physical classification (ASA) and modified Charlson Comorbidity Index (mCCI) using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: We retrospectively queried the 2015-2020 NSQIP datasets for patients who underwent endoscopic treatment for BPH using CPT and ICD codes. Patients were stratified by procedure type (transurethral resection of the prostate (TURP), laser vaporization (LVP) and enucleation (LEP) of the prostate). Risk indexes were calculated and compared as predictors of postoperative outcomes using C-statistics (AUC). RESULTS: 38,128 patients were included with a mean age of 71. The overall complication rate was 10.6%, but upon stratifying by procedure, the complication rates were 11.0%, 10.3%, and 7.6% for TURP, LVP, and LEP, respectively. In aggregate, ASA Class, mFI-5, and mCCI were fair models of mortality (AUC>0.7) and not superior to the other (p>0.05). ASA Class and mCCI were poor models (AUC: 0.6-0.7) for 30-day readmission and surgical complications; however, mFI-5 failed to model either postoperative outcome. All indexes failed to model any other postoperative outcomes (any complication, medical complications, reoperation, disease severity, length of stay ≥2 days) (AUC<0.6). Upon stratifying by endoscopic procedure, all three indexes remained fair models of mortality (AUC>0.7) and not superior to the other (p>0.05). Likewise, when stratifying by endoscopic procedure, all three indexes remained poor models for any readmissions and surgical complications (AUC>0.6). CONCLUSIONS: All three indexes are fair models of mortality for endoscopic treatment of BPH. However, these indexes were inadequate models for all other postoperative outcomes, despite previous studies demonstrating an association. Endoscopic treatment of BPH needs better risk indexes to predict post-operative complications. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e173 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin James More articles by this author Grace Jun More articles by this author Jacob Gaines More articles by this author Zeph Okeke More articles by this author Gregory Mullen More articles by this author Arun Rai More articles by this author Expand All Advertisement PDF downloadLoading ...
Cell labelling agents that enable longitudinal in vivo tracking of administered cells will support the clinical development of cell-based therapies. Radionuclide imaging with gamma and positron-emitting radioisotopes can provide quantitative and longitudinal mapping of cells in vivo. To make this widely accessible and adaptable to a range of cell types, new, versatile and simple methods for directly radiolabelling cells are required. We have developed [111In]In-DTPA-CTP, the first example of a radiolabelled peptide that binds to the extracellular membrane of cells, for tracking cell distribution in vivo using Single Photon Emission Computed Tomography (SPECT). [111In]In-DTPA-CTP consists of (i) myristoyl groups for insertion into the phospholipid bilayer, (ii) positively charged lysine residues for electrostatic association with negatively charged phospholipid groups at the cell surface and (iii) a diethylenetriamine pentaacetate derivative that coordinates the γ-emitting radiometal, [111In]In3+. [111In]In-DTPA-CTP binds to 5T33 murine myeloma cells, enabling qualitative SPECT tracking of myeloma cells' accumulation in lungs immediately after intravenous administration. This is the first report of a radiolabelled cell-membrane binding peptide for use in cell tracking.
You have accessJournal of UrologyCME1 Apr 2023MP25-06 DEVELOPMENT OF A MULTI-INSTITUTIONAL, SIMULATION-BASED SURGICAL SKILLS BOOTCAMP FOR JUNIOR UROLOGY RESIDENTS Justin Lee, Miyad Movassaghi, Nitya Abraham, William Atallah, Jamie Kanofsky, Evan Kovac, Michael Maren, Gregory Mullen, Allison Polland, Courtney Phillips, John Phillips, Rollin Say, Michael Smigelski, Jeffrey Weiss, Andrew Winer, Alexander Small, Christopher Anderson, and Gina Badalato Justin LeeJustin Lee More articles by this author , Miyad MovassaghiMiyad Movassaghi More articles by this author , Nitya AbrahamNitya Abraham More articles by this author , William AtallahWilliam Atallah More articles by this author , Jamie KanofskyJamie Kanofsky More articles by this author , Evan KovacEvan Kovac More articles by this author , Michael MarenMichael Maren More articles by this author , Gregory MullenGregory Mullen More articles by this author , Allison PollandAllison Polland More articles by this author , Courtney PhillipsCourtney Phillips More articles by this author , John PhillipsJohn Phillips More articles by this author , Rollin SayRollin Say More articles by this author , Michael SmigelskiMichael Smigelski More articles by this author , Jeffrey WeissJeffrey Weiss More articles by this author , Andrew WinerAndrew Winer More articles by this author , Alexander SmallAlexander Small More articles by this author , Christopher AndersonChristopher Anderson More articles by this author , and Gina BadalatoGina Badalato More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003253.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In order to increase junior resident proficiency and improve patient safety, simulation-based procedural trainings, or bootcamps, have become an emerging educational tool. Our goal was to assess the viability and efficacy of a multi-institutional, predominantly skills-based bootcamp for junior urology residents. METHODS: First and second year urology residents from the New York Section of the American Urologic Association (AUA) attended a live, procedurally-focused EMPIRE (Educational Multi-Institutional Program for Instructing REsidents) Boot Camp. The curriculum included simulation-based trainings including urethral catheterization, cystoscopy, renal and bladder ultrasound, and robotic simulation (Figure 1). Faculty from 10 institutions helped lead the various exercises. The seminar also included a didactic on urologic emergencies. A questionnaire assessing the experience was distributed to all faculty and resident participants immediately following the course. RESULTS: Twenty-nine junior residents and 16 faculty members participated in this course. Following completion, 11 faculty (69%; 11/16) and 23 trainees (79%; 23/29) submitted an evaluation. On a 5-point Likert scale of relative efficacy, with a higher number being more favorable, the score for each activity ranged from a mean of 4.39 ± 0.64 for the renal bladder ultrasound station to 4.83 ± 0.38 for the urethral catheterization workshop. The majority of trainees “strongly agreed” the event was fun and engaging (20/23; 4.83 ± 0.48) and felt better prepared for upcoming residency rotations (20/23; 4.78 ± 0.59) after the boot camp. Over 90% (21/23; mean 4.91 ± 0.28) strongly agreed the course provided a high-yield overview of urologic emergencies. 73% (8/11) of faculty rated the event as “excellent” for skills training. When asked about skills sessions for interns at their institutions in prior years, 45% (5/11) faculty noted no prior advanced skills sessions were offered. CONCLUSIONS: A skills-based collaborative urology boot camp is feasible and is perceived to be effective in preparing junior trainees for residency in a multi-institutional environment. Multi-institutional efforts such as these can help ensure trainees have equitable access to fundamental training experiences. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e344 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Lee More articles by this author Miyad Movassaghi More articles by this author Nitya Abraham More articles by this author William Atallah More articles by this author Jamie Kanofsky More articles by this author Evan Kovac More articles by this author Michael Maren More articles by this author Gregory Mullen More articles by this author Allison Polland More articles by this author Courtney Phillips More articles by this author John Phillips More articles by this author Rollin Say More articles by this author Michael Smigelski More articles by this author Jeffrey Weiss More articles by this author Andrew Winer More articles by this author Alexander Small More articles by this author Christopher Anderson More articles by this author Gina Badalato More articles by this author Expand All Advertisement PDF downloadLoading ...
Supplementary Figure from HER2 Mediates PSMA/mGluR1-Driven Resistance to the DS-7423 Dual PI3K/mTOR Inhibitor in PTEN Wild-type Prostate Cancer Models
Introduction and Objective: Postoperative infection and sepsis account for the most common complications following percutaneous nephrolithotomy (PCNL), as high as 14% in low-risk patients. Although the American Urological Association (AUA) recommends perioperative antibiotics for 24 hours or less for PCNL, practice patterns vary regarding duration of antibiotic therapy. We aimed to compare the efficacy of 24-hour antibiotic coverage vs short-course protocol of antibiotic prophylaxis for PCNL. Materials and Methods: Low-risk patients with a sterile preoperative urine culture undergoing PCNL were prospectively randomized to antibiotics for up to 24 hours after procedure (24Hr) or continued until external urinary catheters were removed (CR) study groups. Patients were given a first generation cephalosporin, or ciprofloxacin in patients with penicillin allergy. Exclusion criteria included age <18 years, receiving antibiotics immediately before the procedure, history of urosepsis, presence of indwelling catheter >1 week, multistage procedure, immunosuppression, pregnancy, multiple antibiotic allergies, and patients who are breastfeeding. Results: Ninety-eight patients were randomized to either 24Hr (n = 49) or CR (n = 49). Mean duration of antibiotic administration was 20.6 and 34.0 hours in the 24Hr and CR groups (p = 0.04), respectively. Age, comorbidities, stone size, operative time, number of punctures, dilations, and proportion of "tubeless" procedures were similar between groups. There were no differences in febrile episodes, rates of systemic inflammatory response syndrome, bacteremia, or culture-proven postoperative urinary tract infection between the 24Hr and CR groups. Overall complication rates were similar between groups. In a subgroup analysis which excluded "tubeless" patients (24 and 29 patients in 24Hr and CR groups, respectively), no differences were seen in postoperative outcomes. Conclusions: In a randomized, prospective study, we found that a 24-hour protocol for antibiotic prophylaxis is not associated with increased risk of infection-related events compared to giving antibiotics until external catheters are removed in patients with low infectious risk undergoing PCNL. Clinicaltrials.gov: NCT02579161
Abstract Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase receptor HER2, while PTEN-mutant LNCaP cells upregulate androgen receptor and HER3. PSMA, mGluR1, and HER2 exert control over one another in a positive feedback loop that allows cells to overcome treatment with DS-7423. Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for patients with PTEN wild-type PI3K/AKT-mutant prostate cancer based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors.
Purpose: The pO(2) threshold of an ideal PET hypoxia tracer for radiotherapy planning in cancer would match those observed in clinically and biologically relevant processes such as radioresistance and HIF1 alpha expression. To iden-tify such tracers, we directly compared uptake in vitro of hypoxia PET tracers ([F-18]FMISO, [Cu-64]CuATSM, and an-alogues [Cu-64]CuATS, [Cu-64]CuATSE, [Cu-64]CuCTS, [Cu-64]CuDTS, [Cu-64]CuDTSE, [Cu-64]CuDTSM) with levels of radioresistance and HIF1 alpha expression in cultured cancer cells under identical hypoxic conditions ranging from extreme hypoxia to normoxia. Pimonidazole uptake was also compared as a marker of hypoxia. Methods: A custom-built hypoxia apparatus enabled all experiments to be performed under identical hypoxic conditions with constant measurement of pO(2) in media using an OxyLab pO2TM probe. HCT116 human colonic carcinoma and MCF-7 human Caucasian breast adenocarcinoma cells were irradiated using a cobalt teletherapy unit. Clonogenic assays were used to assess survival. HIF1 alpha expression was determined by western blotting, tracer uptake by gamma counting and pimonidazole binding by flow cytometry. Results: Radioresistance, pimonidazole binding and HIF1 alpha expression increased gradually as pO2 decreased between 25 mmHg and 0 mmHg. In contrast, all the PET hypoxia tracers showed a sharp increase in uptake only when pO2 levels fell below 1 mmHg. Above this threshold, tracer uptake was not elevated above that in normoxic cells. Conclusion: This study highlights an important mismatch in pO2 thresholds between these PET tracers and other markers of hypoxia: tracer uptake only occurred at oxygen levels that were well below levels that induced radioresistance, pimonidazole uptake and HIF1 alpha expression. Although their pO2 thresholds do not match the threshold for resistance to conventionally fractionated radiotherapy (pO2 2.5-10 mmHg), their specificity for extreme hypoxia (pO2 MUCH LESS-THAN 1 mmHg) suggests these PET tracers may be of particular use to predict outcomes in ste-reotactic radiation therapy where these maximally resistant cells play a key role in determining the biological effect. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Our objectives were to assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-tris(hydroxypyridinone) (68Ga-THP) prostate-specific membrane antigen (PSMA) for PET/CT in guiding the management of patients with prostate cancer. Methods: Patients were prospectively recruited to group A (high-risk untreated prostate cancer; Gleason score ≥ 4 + 3, or prostate-specific antigen (PSA) level > 20 ng/mL or clinical stage > T2c), group B (biochemical recurrence and eligible for salvage treatment after radical prostatectomy with 2 consecutive rises in PSA with a 3-mo interval between reads and a final PSA level > 0.1 ng/mL or a PSA level ≥ 0.5 ng/mL), or group C (biochemical recurrence with radical curative radiotherapy or brachytherapy at least 3 mo before enrollment, and an increase in PSA level > 2.0 ng/mL above the nadir level after radiotherapy or brachytherapy). Patients underwent evaluation with PET/CT 60 min after intravenous administration of 160 ± 30 MBq of 68Ga-THP PSMA. Safety was assessed through vital signs, cardiovascular profile, serum hematology, biochemistry, urinalysis, PSA, and adverse events (AEs). A change in management was reported when the predefined clinical management of the patient was altered as a result of the 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT: 20 in group A, 21 in group B, and 8 in group C. No patients experienced serious AEs, discontinued the study because of AEs, or died during the study. Two patients had treatment-emergent AEs attributed to 68Ga-THP PSMA (pruritus in one patient and a rash at the intravenous catheter site in another). A management change secondary to the PET/CT findings occurred in 42.9% of all patients: 30% in group A, 42.9% in group B, and 75% in group C. Conclusion: 68Ga-THP PSMA was safe to use, with no serious AEs and no AEs resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned phase III study of 68Ga-THP PSMA in patients with prostate cancer.
Introduction Withdrawal of NIV in COVID-19 patients at end of life presents several challenges. Patients are often more alert and have a higher symptom burden than in other end of life situations where NIV is withdrawn. The NIV withdrawal guideline, created by the centre, was updated to reflect the requirement for higher doses of anticipatory medications required for some patients in this cohort after learning from the first wave of COVID-19. The aim of this study was to review staff response to the guideline and its efficacy. Method A questionnaire was sent to physician associates, nursing staff and doctors of all grades who have worked on the Respiratory Support Unit during the COVID-19 pandemic. This collected several types of data on staff perception of NIV withdrawal in COVID-19 patients. Results The questionnaire generated 39 responses from the multidisciplinary team (MDT). 97% of respondents found the withdrawal of NIV in COVID-19 challenging, and 74% felt this was more difficult in patients with COVID-19 than with other pathologies. 87% were aware of the Trust guideline regarding NIV withdrawal and 82% used it in their practice. All respondents felt the guideline was useful. While the majority of healthcare workers felt that adequate symptom control was achieved, 20% of respondents did not. This unease was further evidenced as 64% of respondents had issues or concerns regarding the use of anticipatory medications. The predominant concerns were that medication doses were started too low (35%) or too late (46%). 71% of respondents found discussions with families regarding commencing palliation challenging. All members of the multidisciplinary team found an MDT approach, including the involvement of Palliative Care colleagues, a useful source of support. The team was united in finding debriefs useful. Conclusions Overall, this study identified that timing and dosage of anticipatory medications are a particular challenge in withdrawal of NIV in patients with COVID-19. There is scope for additional learning regarding symptom management during withdrawal of NIV. Maintaining a close relationship with the Palliative Care team provides benefit to patients, their families and staff. Further work will also focus on supporting staff in difficult conversations.
Hexahistidine tags (His-tags), incorporated into recombinant proteins to facilitate purification using metal-affinity chromatography, are useful binding sites for radiolabeling with [99mTc(CO)3]+ and [188Re(CO)3]+ for molecular imaging and radionuclide therapy. Labeling efficiencies vary unpredictably, and the method is therefore not universally useful. To overcome this, we have made quantitative comparisons of radiolabeling of a bespoke Celluspots array library of 382 His-tag-containing peptide sequences with [99mTc(CO)3]+ and [188Re(CO)3]+ to identify key features that enhance labeling. A selected sequence with 10-fold enhanced labeling efficiency compared to the most effective literature-reported sequences was incorporated into an exemplar protein and compared biologically with non-optimized analogues, in vitro and in vivo. Optimal labeling with either [99mTc(CO)3]+ or [188Re(CO)3]+ required six consecutive His residues in the protein sequence, surrounded by several positively charged residues (Arg or Lys), and the presence of phosphate in the buffer. Cys or Met residues in the sequence were beneficial, to a lesser extent. Negatively charged residues were deleterious to labeling. His-tags with adjacent positively charged residues could be labeled as much as 40 times more efficiently than those with adjacent negatively charged residues. 31P NMR of [Re(CO)3(H2O)3]+ and electrophoresis of solutions of [99mTc(CO)3(H2O)3]+ suggest that phosphate bridges form between cationic residues and the cationic metal synthon during labeling. The trial optimized protein, a scFv targeted to the PSMA antigen expressed in prostate cancer, was readily labeled in >95% radiochemical yield, without the need for subsequent purification. Labeling occurred more quickly and to higher specific activity than comparable non-optimized proteins, while retaining specific binding to PSMA and prostate cancer in vivo. Thus, optimized His-tags greatly simplify radiolabeling of recombinant proteins making them potentially more widely and economically available for imaging and treating patients.
Introduction and Objectives: Percutaneous management of large bladder calculi with the use of a laparoscopic entrapment sac is a minimally invasive procedure that may have advantages over open cystolithotomy and transurethral cystolithotripsy, as well as standard percutaneous cystolithotomy. We first performed this procedure in 2008, and refined it after our initial publication in 2013 by changing the position from lithotomy to supine by using a urethral catheter postoperatively instead of a suprapubic (SP) catheter, by using ultrasound guidance for access, and by changing the procedure from being inpatient to outpatient. Our objective is to assess the continued feasibility of percutaneous entrapment sac cystolithotomy (PESC) and describe modifications that simplify the technique (mPESC), comparing outcomes and complications. Methods: Forty seven male patients underwent PESC from 2008 to 2019, 16 who had PESC and 31 who had mPESC. After extraction of calculi, either an SP catheter was placed, or the wound was closed and a urethral catheter was placed. Operative and follow-up parameters were compared between the two cohorts. Results: All patients were rendered stone free. Procedure time and length of stay were both significantly shorter in the mPESC cohort. Stone burden and estimated blood loss were equivalent between cohorts. There were no complications of urethral trauma in either cohort. The PESC cohort had higher rates of leakage from the SP site (25% vs 0%), increased need for catheter over 5 days (18.8% vs 0%), and greater likelihood of recurrent retention (12.5% vs 6%). Conclusions: Modifications of PESC, mPESC, leads to fewer complications and reduced length of stay compared with the original PESC procedure. This safe and efficacious technique can reduce morbidity during the management of large bladder calculi and is well suited for an outpatient procedure.
You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Quality of Life and Shared Decision Making I (MP02)1 Apr 2020MP02-18 MALPRACTICE TRENDS IN THE SETTING OF PROSTATE CANCER SCREENING Peter Sunaryo*, Gregory Mullen, Christine W Liaw, Eric Bortnick, and Jay Motola Peter Sunaryo*Peter Sunaryo* More articles by this author , Gregory MullenGregory Mullen More articles by this author , Christine W LiawChristine W Liaw More articles by this author , Eric BortnickEric Bortnick More articles by this author , and Jay MotolaJay Motola More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000816.018AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medical malpractice (MP) is an important issue in our country. There has been controversy surrounding PSA testing and prostate cancer screening, specifically the United States Preventive Services Task Force (USPSTF) whose 2012 guidelines advised against PSA testing and were modified in 2018. The purpose of this study is to identify factors leading to litigation and recent trends related to the screening of prostate cancer. METHODS: The Westlaw database was used to search for jury verdicts ranging from January 2000 to December 2018. Each case was examined for year of trial, patient age, specialty of defendant, alleged cause of MP, and the case outcome. RESULTS: Of 129 examined cases, 66% went to trial and of those, 69% were decided for the defendant. The mean settlement was $967,000 (K) while the mean verdict was $2.0 million (M). Primary care physicians (PCP) (73.7%) were the most cited defendants followed by urologists (U) (21.2%). There were no significant differences (NSD) between the mean verdict or settlement amount between U and PCP ($1.1M vs. $2.2 M, p = 0.23; $803K vs. $1.0M, p =0.47). The most common cause was failure to follow up for an elevated PSA (37%), followed by failing to get an initial PSA (31%). Lack of follow up for an elevated PSA led to significantly higher settlements when compared to failing to get an initial PSA, but verdicts were NSD ($1.0 M vs. $240K, p = 0.007; $1.8 M vs. $970K, p = 0.12). There was NSD between the mean amount of MP cases per year before and after the USPSTF recommendations (7.9 vs. 4.3, p = 0.03) as well as the mean settlement and mean plaintiff award ($970k vs. $970k, p =0.99; $2.1 M vs. $2.6 M, p = 0.44 respectively). CONCLUSIONS: PSA testing is commonly cited in MP. There were no significant changes seen in the incidence of MP. This may be due to lag time from the time of filing a MP claim until its resolution. Limitations on testing may have future consequences and need to be monitored. Both PCP and U must continue to educate patients in order to minimize malpractice claims made in this setting. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e19-e19 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter Sunaryo* More articles by this author Gregory Mullen More articles by this author Christine W Liaw More articles by this author Eric Bortnick More articles by this author Jay Motola More articles by this author Expand All Advertisement PDF downloadLoading ...
PURPOSE:To examine the outcomes of sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy who were experiencing the symptoms of GSM for which they were treated with fractional microablative CO2 laser.MATERIALS AND METHODS:From July 2015 to October 2016, a retrospective chart review of women who underwent fractional microablative CO2 laser therapy (MonaLisa Touch, DEKA) for GSM was conducted. Several validated questionnaires were used to assess changes in symptoms and sexual function including the Female Sexual Function Index (FSFI), the Wong-Baker Faces Scale (WBFS), and the Female Sexual Distress Scale-Revised (FSDSR). Comparisons of mean symptom scores were described at baseline and six weeks after each treatment.RESULTS:There was a statistically significant improvement in every domain of FSFI, WBFS, and FSDS-R when comparing baseline symptom scores to after treatment three symptom scores for all patients. The secondary outcome was to evaluate the differences, if any, in outcomes of sexual function between postmenopausal women and women with a history of breast cancer treated with endocrine therapy. Both groups had statistically significant improvements in many domains studied.CONCLUSIONS:Fractional microablative CO2 laser therapy (MonaLisa Touch, DEKA) is an effective modality in treating the symptoms of GSM in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.
AIM:To determine whether heterogeneity of cardiac scar, as assessed by cardiovascular magnetic resonance (CMR) texture analysis, may provide insight into better risk stratification for patients with previous myocardial infarction (MI). MATERIALS AND METHODS:Patients with previous MI (n=76) were followed for a median of 371.5 days after late gadolinium enhancement (LGE) CMR. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, or unexplained syncope. Areas of LGE were identified and manually segmented on a short-axis projection. The characteristics of the scar heterogeneity were evaluated via CMR texture analysis. This is a filtration-histogram technique, where images are filtered using the Laplacian of a Gaussian filter to extract features different sizes (2-6 mm in radius) corresponding to fine, medium, and coarse texture scales followed by a quantification step using histogram analysis (skewness and kurtosis). RESULTS:Patients suffering arrhythmic events during the follow-up period demonstrated significantly higher kurtosis (coarse-scale, p=0.005) and lower skewness (fine-scale, p=0.046) compared to those suffering no arrhythmic events. Furthermore, Kaplan-Meier analysis showed significantly higher coarse kurtosis (p=0.004), and lower fine skewness (p=0.035) were able to predict increased incidence of ventricular arrhythmic events. CONCLUSIONS:In this pilot study, indices of texture analysis reflecting textural heterogeneity were significantly associated with a greater incidence of arrhythmic events. Further work is required to delineate the role of texture analysis techniques in risk stratification post-MI.