Objective: To document patient-reported interstitial cystitis/ bladder pain syndrome (IC/BPS) flare management strategies and triggers. Materials and Methods: 24 male and 29 female participants enrolled at the Washington University site of the MAPP Research Network completed a questionnaire on strategies they utilized to manage flares and factors they believed triggered their flares (e.g., specific food items, physical activities, sexual activities, infections, and stress). Participants were also asked about the diurnal timing of their flares. Results: 96.2% of participants reported having ever experienced a symptom flare. Participants treated or managed their flares using a wide variety of strategies, ranging from common strategies, such as drinking additional water or fluid (74.5%), to less common strategies, such as acupuncture/acupressure (5.9% of participants). Participants also reported a wide range of perceived flare triggers, including previously reported factors (citrus fruits, tomatoes, spicy food, alcoholic and caffeinated beverages, driving/sitting in forms of transportation, urinary tract infections, stress, and tight clothing), as well as some less common, previously undocumented factors (e.g., certain foods, non-genitourinary infections, wearing high-heeled shoes/boots or perfume, hair dye, and toothpaste). In general, female participants and those with somatic sensory hypersensitivity reported greater numbers of therapies and triggers. Finally, flares were reported most commonly in the afternoon or evening. Conclusion: IC/BPS participants reported diverse flare management strategies and numerous perceived triggers. These findings, together with those from the small body of literature to date, provide a wide array of candidates and hypotheses for future global and tailored flare management and prevention interventions.
OBJECTIVE To evaluate trends in urine aquaporin-1 (AQP1) and perilipin 2 (PLIN2) concentrations in patients with clear cell and papillary renal cell carcinoma (RCC) this investigation determined the relationship between the urine concentration of these biomarkers and tumor size, grade and stage. MATERIALS and METHODS Biomarker concentrations were determined by sensitive and specific Western blot procedures normalized to urine creatinine excretion. Analysis included 61 patients undergoing a partial or a radical nephrectomy for clear cell or papillary renal cancer and 43 age- and sex-matched control patients. Relationships between urine biomarker concentrations and tumor size, stage, and grade were assessed. RESULTS Patients with renal cell carcinoma had 35-fold and 9-fold higher median urinary AQP1 and PLIN2 concentrations, respectively, compared to controls (p values). Both tumor markers decreased following tumor resection, to concentrations equivalent to those of controls. The sensitivity and specificity were both 100% for AQP1, and 92% and 100% for PLIN2. There was a significant linear correlation between tumor size and prenephrectomy AQP1 (Spearman coefficient 0.78, P<0.001) and PLIN2 (Spearman coefficient 0.69, P<0.001) concentrations. There was a correlation of both markers with tumor stage (overall P=0.030), when stage was dependent primarily on tumor size (stages T1 and T2), but not with stage T3 which reflected extra-renal spread. Neither marker showed a significant correlation with tumor grade. CONCLUSIONS AQP1 and PLIN2 are significantly increased in patients with clear cell and papillary renal cell carcinoma compared to controls. Preoperative urinary concentrations of these markers reflect tumor size and stage.
PURPOSE Recombinant BMP-7 inhibits the pathogenesis of renal injury in response to a variety of stimuli. However, little is known about the molecular regulation of endogenous BMP-7 and its renal protective functions. This study examines the transcriptional regulation of Bmp-7 and its role in the pathogenesis of renal injuries resulting from urinary tract dysfunction. MATERIALS AND METHODS Obstruction-induced renal injury was modeled in vivo in mice by unilateral ureteral obstruction (UUO) and in vitro in primary kidney cells by treatment with TGF-β, a pro-fibrotic cytokine that is elevated in the obstructed kidney. RESULTS UUO results in the loss of BMP-7 expression in conjunction with histone deacetylation and transcriptional repression of the Bmp-7 promoter. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) stimulates Bmp-7 expression in primary kidney cells. Furthermore, TSA inhibits the expression of TGF-β-dependent pro-fibrotic genes in a manner that is dependent upon BMP receptor signaling. These findings extend to the obstructed kidney in vivo where treatment with TSA restores the expression of Bmp-7 along with the BMP-7-mediated suppression of TGF-β-dependent signaling pathways. Finally, the TSA-stimulated activation of the BMP-7 pathway ameliorates obstruction-induced renal injuries by preventing the disruption of renal architecture and the development of renal fibrosis. CONCLUSIONS Together, these findings demonstrate that the HDAC-dependent repression of Bmp-7 transcription is a critical event during the pathogenesis of renal injury in obstructive uropathies. Accordingly, treatment with HDAC inhibitors represents a potentially effective strategy to restore BMP-7 expression and its renal protective functions during the treatment of obstructive uropathies.
Robotic surgeries of long duration are associated with both increased risks to patients as well as distinct challenges for care providers. We propose a surgical checklist, to be completed during a second “time-out”, aimed at reducing peri-operative complications and addressing obstacles presented by lengthy robotic surgeries. A review of the literature was performed to identify the most common complications of robotic surgeries with extended operative times. A surgical checklist was developed with the goal of addressing these issues and maximizing patient safety. Extended operative times during robotic surgery increase patient risk for position-related complications and other adverse events. These cases also raise concerns for surgical, anesthesia, and nursing staff which are less common in shorter, non-robotic operations. Key elements of the checklist were designed to coordinate operative staff in verifying patient safety while addressing the unique concerns within each specialty. As robotic surgery is increasingly utilized, operations with long surgical times may become more common due to increased case complexity and surgeons overcoming the learning curve. A standardized surgical checklist, conducted three to four hours after the start of surgery, may enhance perioperative patient safety and quality of care.
Background Physiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM. Methods Inclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), Ktrans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria. Results Out of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, Ktrans, Vp, and Ve were not indicative of treatment response within 6 months. Conclusions In patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment. Key Points • In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response. • Interval change in rADC can be used as an imaging biomarker to determine PFS6. • Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.
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