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1.
Urol Pract ; : 101097UPJ0000000000000709, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39302185

ABSTRACT

INTRODUCTION: Patient-centered communication after surgery can enhance patient satisfaction and reduce unplanned clinical contact. However, patients information needs following kidney stone surgery are not well-understood, limiting quality improvement efforts. We aimed to characterize patient-reported needs in and preferences for postoperative communication following kidney stone surgery. METHODS: Patients undergoing common stone procedures were surveyed about the content, volume, and satisfaction with the communication they received after surgery. Patients indicated which information resources they consulted and found most helpful to address their postoperative care questions. RESULTS: Among 52 patients, the majority (75%) identified varying degrees of deficiencies in the communication they received after surgery. Regarding content, respondents were most interested in understanding how their surgery went (90%), the plan for follow-up care (85%), and the specific location of their stone (85%). Regarding volume, respondents consistently indicated interest in intra-operative findings (stone appearance and location) and postoperative care (stent symptoms and location) but the majority did not recall receiving enough information. To address their questions after surgery, respondents most commonly consulted their urologist (71%), discharge paperwork (42%), electronic health record (27%), and the person with whom their urologist spoke after surgery (25%); among these, the majority (54%) reported that their urologist was the single most helpful source of information. CONCLUSIONS: Following kidney stone surgery, patients report unmet communication needs related to specific intraoperative findings and follow-up care. Patients indicate high levels of satisfaction with urologist-provided resources. These exploratory findings support quality improvement efforts to optimize delivery of effective, patient-centered communication after surgery.

4.
Urology ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39153605

ABSTRACT

OBJECTIVE: To describe a new technique or adjunct-telescoping the dorsal hood-with a view to banking excess skin on the penile shaft in hypospadias surgery. This would help if redo surgery, not a rare occurrence, is required in the future. METHOD: A review of a prospectively maintained database of hypospadias surgeries conducted between 1997 and 2023 by a single surgeon. After the hypospadias repair, instead of excising the dorsal hood and suturing the ventral penile skin in the usual way, a skin hook is applied on the ventral penile skin in the midline. As the skin hook is pulled down towards the scrotum, anywhere from 1 to 4cm, it telescopes the dorsal hood down the penile shaft and also pulls in dorsal skin ventrally. (Technique described more fully in the manuscript) RESULTS: Around 1084 patients were operated for hypospadias over these 27 years. Telescoping of the dorsal hood was used in all patients, and in the 126 with proximal hypospadias, none had any skin of the dorsal hood excised! Sixty-two patients presented later with 73 fistulae which were operated on. Of note, no patient needed more than 2 surgical attempts for a cure. CONCLUSION: The dorsal hood is a useful source of not only skin but also underlying vascularised soft tissue. In hypospadias surgery where redo-operations are a predictable reality, preserving any excess skin on the phallus seems sensible. Our innovation of telescoping the dorsal hood achieves this goal nicely and takes only a few minutes to perform.

5.
Lancet Oncol ; 25(8): 1038-1052, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38942046

ABSTRACT

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Nephrectomy , Nivolumab , Humans , Nivolumab/administration & dosage , Nivolumab/therapeutic use , Nivolumab/adverse effects , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/mortality , Male , Female , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/mortality , Middle Aged , Aged , Canada , Chemotherapy, Adjuvant , Neoplasm Staging , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/administration & dosage
7.
Urology ; 186: 91-97, 2024 04.
Article in English | MEDLINE | ID: mdl-38387509

ABSTRACT

OBJECTIVE: To compare clinically significant prostate cancer detection with TP-TBx utilizing software vs cognitive fusion. It is established that MRI prior to prostate biopsy improves detection of clinically significant cancer (csPCa, Grade Group ≥2). MRI/US fusion targeted biopsy via a transperineal approach (TP-TBx) is increasing in utilization due to the clean percutaneous approach that greatly reduces postbiopsy infection. However, the comparative effectiveness of formal software fusion over cognitive fusion remains under studied. MATERIALS AND METHODS: We performed a retrospective multicenter study from June 2020 to July 2022 including age, race, prostate-specific antigen (PSA), prostate volume, PI-RADS, lesion size(s), number of cores sampled, indication (elevated PSA, prior negative, active surveillance) and anesthesia type. Surgeon preference determined use of cognitive (PrecisionPoint) vs software fusion techniques. Multivariable logistic regression determined factors associated with TP-TBx detection of csPCa. RESULTS: We identified 490 patients (201 cognitive, 289 software fusion) who underwent TP-TBx. Patient age, PSA, number of targets, and PI-RADS were similar (all P > .05). Software fusion TP-TBx had 4 [95% confidence interval (CI) 3-5] more (estimated median difference) systematic cores sampled. csPCa was detected in 44% of all patients. In adjusted analysis, cognitive vs software fusion was similar in detection of csPCa (odds ratio 1.46, 95% CI 0.82-2.58). CONCLUSION: Cognitive vs software fusion TP-TBx has similar csPCa detection, despite fewer systematic cores taken with cognitive fusion. The expense, additional time requirement, and similar outcomes of software fusion platforms confers higher value to cognitive TP-Bx.


Subject(s)
Prostatic Neoplasms , Humans , Male , Cognition , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostate/diagnostic imaging , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/pathology , Retrospective Studies , Software
8.
Eur Urol ; 86(1): 61-68, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38212178

ABSTRACT

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.


Subject(s)
Antibiotic Prophylaxis , Image-Guided Biopsy , Perineum , Prostate , Prostatic Neoplasms , Rectum , Humans , Male , Image-Guided Biopsy/methods , Image-Guided Biopsy/adverse effects , Aged , Antibiotic Prophylaxis/methods , Middle Aged , Rectum/microbiology , Prostate/pathology , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging, Interventional , Prospective Studies
10.
Sci Rep ; 14(1): 1458, 2024 01 17.
Article in English | MEDLINE | ID: mdl-38228729

ABSTRACT

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Nivolumab/pharmacology , Carcinoma, Renal Cell/drug therapy , Neoadjuvant Therapy , Prospective Studies
11.
J Nucl Med ; 65(1): 87-93, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38050147

ABSTRACT

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.


Subject(s)
Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Male , Humans , Positron Emission Tomography Computed Tomography/methods , Prostate/pathology , Prostatic Neoplasms/pathology , Prostatectomy , Algorithms
12.
J Urol ; 211(3): 407-414, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38109699

ABSTRACT

PURPOSE: We sought to examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with Grade Group (GG) 1 and GG2 prostate cancer (PCa) treated with radical prostatectomy. MATERIALS AND METHODS: We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and GG (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival. RESULTS: The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow-up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution HR = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (subdistribution HR = 1.97, 95% CI: 1.54-2.52). CONCLUSIONS: Although there is a subset of GG1 PCas capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2, EPE connotes a worse prognosis.


Subject(s)
Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostate/surgery , Prostate/pathology , Prostatectomy , Neoplasm Grading , Prognosis
13.
Article in English | MEDLINE | ID: mdl-37168063

ABSTRACT

A 35-year-old male greenhouse worker presented with myalgia, fatigue, and fever. Initially, he was thought to have an unspecified viral infection and was treated with conservative therapy. However, the patient's symptoms persisted, and he reported additional symptoms of mild abdominal pain and headaches. Laboratory evaluation was significant for elevated liver enzymes. Due to concern for acute hepatitis and persistent fever the patient was hospitalized. During his hospital course, no infectious etiology was found to explain his symptoms. After discharge from the hospital, additional testing showed positive serology for Q fever IgG phase II antibody (1:8192) and phase II antibody IgM (>1:2048). He was treated with doxycycline and had a good clinical response. Upon follow-up, he had worsening Phase I IgG serologies. Transesophageal echo demonstrated vegetations consistent with endocarditis.

14.
Eur Urol Open Sci ; 50: 78-84, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37101773

ABSTRACT

Background: As the adoption of active surveillance (AS) for small renal masses (SRMs) grows, the number of elderly patients enrolled for a prolonged period of time will increase. However, our understanding of comparative growth rates (GRs) in aging patients with SRMs remains poor. Objective: To examine whether particular age cutoffs are associated with an increased GR for patients undergoing AS for SRMs. Design setting and participants: We identified all patients with SRMs enrolled in the multi-institutional, prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry since 2009 who elected for AS. Outcome measurements and statistical analysis: Two definitions of GR were examined: GR from the initial image (GRi) and GR from the prior image (GRp). Image measurements were dichotomized based on patient age at the time of imaging. Multiple age cutoffs were examined: 65, 70, 75, and 80 yr. Mixed-effect linear regression examined the associations between age and GR, with controlling to account for multiple measurements from the same individual. Results and limitations: We examined 2542 measurements from 571 patients. The median age at enrollment was 70.9 yr (interquartile range [IQR] 63.2-77.4) with a median tumor diameter of 1.8 cm (IQR 1.4-2.5). As a continuous variable, age was not associated with GRi (-0.0001 cm/yr, 95% confidence interval [CI] -0.007 to 0.007, p = 0.97) or GRp (0.008 cm/yr, 95% CI -0.004 to 0.020, p = 0.17) after adjustment. The only age thresholds associated with an increased GR were 65 yr for GRi and 70 yr for GRp. Limitations include the one-dimensional nature of the measurements used. Conclusions: Increased age for patients on AS for SRMs is not associated with increased GRs. Patient summary: We examined whether patients undergoing active surveillance (AS) exhibited accelerated growth of their small renal masses (SRMs) after a certain age. No demonstrable change was seen, suggesting that AS is a safe and durable management option for aging patients with SRMs.

15.
Nat Med ; 29(4): 888-897, 2023 04.
Article in English | MEDLINE | ID: mdl-37012549

ABSTRACT

B7 homolog 3 (B7-H3; CD276), a tumor-associated antigen and possible immune checkpoint, is highly expressed in prostate cancer (PCa) and is associated with early recurrence and metastasis. Enoblituzumab is a humanized, Fc-engineered, B7-H3-targeting antibody that mediates antibody-dependent cellular cytotoxicity. In this phase 2, biomarker-rich neoadjuvant trial, 32 biological males with operable intermediate to high-risk localized PCa were enrolled to evaluate the safety, anti-tumor activity and immunogenicity of enoblituzumab when given before prostatectomy. The coprimary outcomes were safety and undetectable prostate-specific antigen (PSA) level (PSA0) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA0 with reasonable precision. The primary safety endpoint was met with no notable unexpected surgical or medical complications, or surgical delay. Overall, 12% of patients experienced grade 3 adverse events and no grade 4 events occurred. The coprimary endpoint of the PSA0 rate 1 year postprostatectomy was 66% (95% confidence interval 47-81%). The use of B7-H3-targeted immunotherapy in PCa is feasible and generally safe and preliminary data suggest potential clinical activity. The present study validates B7-H3 as a rational target for therapy development in PCa with larger studies planned. The ClinicalTrials.gov identifier is NCT02923180.


Subject(s)
Antineoplastic Agents , Prostatic Neoplasms , Male , Humans , Prostate-Specific Antigen/therapeutic use , Neoadjuvant Therapy , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , B7 Antigens
16.
Am Heart J ; 258: 168-176, 2023 04.
Article in English | MEDLINE | ID: mdl-36682596

ABSTRACT

BACKGROUND: The long-term use of ß-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether ß-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure. METHODS: The Assessment of ß-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a ß-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their ß-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the ß-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed. CONCLUSION: The ABYSS trial evaluates the cardiovascular safety of ß-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of ß-blockers life-long therapy in stable post-MI patients without reduced LVEF. CLINICAL TRIAL REGISTRATION: NCT03498066 (clinicaltrials.gov).


Subject(s)
Heart Failure , Myocardial Infarction , Humans , Stroke Volume , Quality of Life , Ventricular Function, Left , Myocardial Infarction/complications , Adrenergic beta-Antagonists , Heart Failure/drug therapy , Treatment Outcome
17.
Arch Oral Biol ; 145: 105585, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36403440

ABSTRACT

OBJECTIVE: This study was carried out in submandibular salivary glands of rats to demonstrate the changes induced by cadmium intoxication and the possible prophylactic and therapeutic effects of bone marrow mesenchymal stem cells (BMSCs). DESIGN: Sixty-five rats were divided into five groups. Rats in Group I were controls while those of Group II received daily dose of 10 mg/kg cadmium for 24 days. Rats in Group III received single prophylactic dose of 1 × 106 BMSCs one week before cadmium administration. Rats of Group IV were concomitantly administered cadmium and BMSCs, while those of Group V received cadmium for 24 days and were then treated with single dose of 1 × 106 BMSCs. Rats of Groups I, II, III, and IV were euthanized at the end of the experiment while those of Group V were euthanized one week later. Salivary gland specimens were processed and stained with H&E and inducible nitric oxide synthase; other specimens were used to demonstrate metallothionein gene expression using RT-PCR, malondialdehyde and catalase enzymes were detected by ELISA. RESULTS: Groups III and IV had nearly comparable findings to Group I regarding histological pattern with normal gland features. Group III recorded a lower fold of change for metallothionein gene (1.14 ± 0.20), a lower malondialdehyde enzyme (21.67 ± 1.63 nmol/mg), and a higher catalase enzyme (66.33 ± 2.16 mmol/mg). Regarding all variables, significant differences were found between the different groups (P < 0.001). CONCLUSION: BMSCs have prophylactic and therapeutic effects against cadmium-induced cytotoxicity in rat salivary glands.


Subject(s)
Mesenchymal Stem Cells , Submandibular Gland , Male , Rats , Animals , Submandibular Gland/metabolism , Catalase , Cadmium Chloride/toxicity , Cadmium/toxicity , Chlorides , Mesenchymal Stem Cells/metabolism , Malondialdehyde/metabolism , Metallothionein , Bone Marrow Cells/metabolism
18.
Toxicon ; 222: 107003, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36535530

ABSTRACT

A comprehensive assessment of the literature on strategies for the detection and removing endotoxin from biotechnological preparations was conducted. This study highlighted the brief history of endotoxin. After that, a review of endotoxin's chemical and physical features, as well as its pathophysiological consequences when the body is exposed to LPS excessively or systemically, is presented. The procedures for determining endotoxin and the interaction of endotoxin with proteins are also discussed, considering both known approaches and cutting-edge technology in this sector. This review presented the endotoxin detection and removal approaches from antisera with an economical approach using several processes documented in the literature (e.g., adsorption, ultrafiltration, and chromatography). Different methods with relatively high protein recoveries are mentioned. This review concludes that heat activation at 70 °C-80 °C for 10 min and rehydration of the LAL reagent with endotoxin-specific buffer solution is the best technique to control the enhancement problem when testing polyvalent snake venom antiserum samples by the LAL method. The most efficient method for eliminating endotoxins has proven to be affinity resin-based chromatography.


Subject(s)
Antivenins , Endotoxins , Animals , Endotoxins/analysis , Antivenins/analysis , Proteins , Adsorption , Snakes
19.
Gait Posture ; 100: 132-138, 2023 02.
Article in English | MEDLINE | ID: mdl-36521257

ABSTRACT

BACKGROUND: More than half of patients with lower-limb amputation who use socket prostheses experience at least one fall annually. These falls are primarily attributed to reduced proprioception which negatively affects balance. A promising alternative to socket prostheses are osseointegrated prostheses that involve direct fixation of the prosthetic limb to the residual limb through a bone-anchored implant, yet its effect on balance remains unknown. RESEARCH QUESTION: Do osseointegrated prostheses change static and dynamic balance, as well as patient reported measures of balance confidence, compared to a socket prosthesis? METHODS: A sample of 10 patients with unilateral transfemoral amputation scheduled to undergo prosthesis osseointegration were enrolled (6 F/4 M, BMI: 26.7 ± 2.9 kg/m2, Age: 46.1 ± 6.3 years). Motion capture data during quiet standing (eyes opened and eyes closed) and overground walking at a self-selected speed, and the Activities-Specific Balance Confidence (ABC) scale, were collected before (with socket prosthesis) and 12-months following osseointegration. Postural sway via the center of pressure (COP), variability of spatiotemporal parameters, and ABC scores were compared using a repeated measures design before and after osseointegration. RESULTS: Following prosthesis osseointegration, COP path length and 95 % confidence ellipse area were reduced during quiet standing (d = 0.75, P = 0.09; d = 0.52, P = 0.29, respectively) and the variability of step width and length were reduced during overground walking (d = 0.50, P = 0.06; d = 0.72, P = 0.06, respectively). Furthermore, patients reported significantly improved ABC scores with an osseointegrated prosthesis compared to a socket prosthesis (d = -1.36, P = 0.01). SIGNIFICANCE: Improvements in postural sway, reductions in gait variability, and greater balance confidence indicate that osseointegrated prostheses improve balance for people with unilateral transfemoral amputation.


Subject(s)
Amputees , Artificial Limbs , Humans , Adult , Middle Aged , Artificial Limbs/adverse effects , Osseointegration , Prosthesis Implantation/adverse effects , Amputation, Surgical , Prosthesis Design
20.
Eur Urol Open Sci ; 43: 28-34, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36353070

ABSTRACT

Background: Renal cell carcinoma (RCC) can exhibit a unique vascular tropism that enables tumor thrombus extension into the inferior vena cava (IVC). While most RCC subtypes that form tumor thrombi are of clear cell (cc) histology, non-clear cell (ncc) subtypes can also exhibit this unique growth pattern. Objective: To characterize clinicopathologic differences and survival outcomes among patients with IVC tumor thrombus arising from ccRCC versus nccRCC. Design setting and participants: Patients diagnosed with IVC tumor thrombus secondary to RCC in our institutional experience from 2003 to 2021 were identified. Outcome measurements and statistical analysis: Clinicopathologic characteristics were compared by histology. Perioperative and oncologic outcomes including recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survival were assessed using multivariable Cox regression analyses. Results and limitations: The analyzed cohort included 103 patients (82 ccRCC and 21 nccRCC). There were no significant differences in baseline demographic parameters. Patients with nccRCC were more likely to have regional lymph node involvement (42.9% vs 20.7%, p = 0.037). No differences in perioperative outcomes, IVC resection, or IVC reconstruction were observed between groups. The median follow-up time was 30 mo. The median RFS was 30 (nccRCC) versus 53 (ccRCC) mo (p = 0.1). There was no significant difference in OS or CSS. This study was limited by its small sample size. Conclusions: Patients with IVC tumor thrombus arising from ccRCC and nccRCC exhibit similar perioperative and oncologic outcomes. While surgical appropriateness was not impacted by histologic subtype, multimodal strategies are needed to improve outcomes for patients with tumor thrombus. Patient summary: Renal cell carcinoma (RCC) can uniquely invade vasculature and form a tumor thrombus. This study examined the difference in outcomes of patients with tumor thrombus based on RCC subtype (clear cell vs non-clear cell). We found that patients exhibited similar surgical and survival outcomes regardless of RCC type.

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