Amniotic bladder therapy: six-month follow up treating interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by chronic pelvic pain and usually accompanies lower urinary tract symptoms. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory IC/BPS patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. MATERIALS AND METHODS: Consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized amniotic membrane. Clinical evaluation and patient-reported outcome measurements including Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB) were assessed. RESULTS: Twenty-five consecutive recalcitrant IC/BPS patients were included in the study with an average age of 47.4 ± 14.4 years (29-67 years). After ABT, the IC/BPS symptoms improved gradually up to 3 months in all patients with an average improvement in ICSI, ICPI, BPIC-SS and OAB score of 72.8%, 71.9%, and 66.6%, (p < 0.001) respectively, at 3 months. At 4 months after ABT, 7 patients experienced a rebound in symptoms and requested another injection which resulted in a significant improvement in IC/BPS symptoms after 2, 4, and 8 weeks (p < 0.01). For the 18 patients who received only one injection, the IC/BPS symptoms were still significantly lower at 5 and 6 months compared to baseline (p < 0.01), suggesting a possible durable effect based on the ICSI, ICPI, BPIC-SS, and OAB questionnaire scores. CONCLUSIONS: ABT provided an improvement in pain and lower urinary tract symptoms up to 6 months post-treatment in some refractory IC/BPS patients.

Competing neural representations of choice shape evidence accumulation in humans.

Making adaptive choices in dynamic environments requires flexible decision policies. Previously, we showed how shifts in outcome contingency change the evidence accumulation process that determines decision policies. Using in silico experiments to generate predictions, here we show how the cortico-basal ganglia-thalamic (CBGT) circuits can feasibly implement shifts in decision policies. When action contingencies change, dopaminergic plasticity redirects the balance of power, both within and between action representations, to divert the flow of evidence from one option to another. When competition between action representations is highest, the rate of evidence accumulation is the lowest. This prediction was validated in in vivo experiments on human participants, using fMRI, which showed that (1) evoked hemodynamic responses can reliably predict trial-wise choices and (2) competition between action representations, measured using a classifier model, tracked with changes in the rate of evidence accumulation. These results paint a holistic picture of how CBGT circuits manage and adapt the evidence accumulation process in mammals.

A preliminary report assessing the feasibility and effectiveness of amniotic bladder therapy in patients with chronic radiation cystitis.

INTRODUCTION: Chronic radiation cystitis (CRC) can develop between 6 months and 20 years after radiation therapy that presents with symptoms of urinary frequency, urgency, bladder pain, and nocturia. Amniotic membrane (AM) is known to contain pro-regenerative properties and could thereby be a potential therapeutic modality for radiation-induced tissue injury of the bladder. MATERIALS AND METHODS: CRC patients recalcitrant to previous treatments received amniotic bladder therapy (ABT) comprised of intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 mL 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder (OAB) Assessment Tool, and SF-12 Health Survey) were repeated at preop and 2, 4, 8 and 12 weeks post-injection. RESULTS: Five consecutive female patients aged 64.4 ± 20.1 years with a median CRC disease duration of 10 years were included. After ABT, BPIC-SS scores improved from baseline to 12 weeks (36.6 ± 1.1 to 12.6 ± 3.1) and this was associated with an improvement in ICSI, ICPI, OAB, and SF-12 scores. One patient had an acute urinary tract infection at 2 weeks but was successfully treated with oral antibiotics. No other adverse events related to micronized AM injections were observed. Uroflow assessments showed increases in voided volume for all five patients. CONCLUSIONS: This data provides additional evidence for the potential benefit of ABT in patients with chronic inflammatory conditions of bladder such as CRC.

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS. METHODS: Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12 weeks post-op. RESULTS: Ten females (47.4 ± 14.4 years) who had recalcitrant IC/BPS for 7.8 years (5.2-12.1 years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3 months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3 months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention. CONCLUSION: ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3 months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.

The Use and Short-term Outcomes of Active Surveillance in Men With National Comprehensive Cancer Network Favorable Intermediate-risk Prostate Cancer: The Initial Michigan Urological Surgery Improvement Collaborative Experience.

PURPOSE: National Comprehensive Cancer Network favorable intermediate-risk prostate cancer is a heterogeneous disease with varied oncologic and survival outcomes. We describe the Michigan Urological Surgery Improvement Collaborative's experience with the use of active surveillance and the short-term oncologic outcomes for men with favorable intermediate-risk prostate cancer.Materials and Methods:We reviewed the Michigan Urological Surgery Improvement Collaborative registry for men diagnosed with favorable intermediate-risk prostate cancer from 2012-2020. The proportion of men with favorable intermediate-risk prostate cancer managed with active surveillance was calculated by year of diagnosis. For men selecting active surveillance, the Kaplan-Meier method was used to estimate treatment-free survival. To assess for the oncologic safety of active surveillance, we compared the proportion of patients with adverse pathology and biochemical recurrence-free survival between men undergoing delayed radical prostatectomy after a period of active surveillance with men undergoing immediate radical prostatectomy. RESULTS: Of the 4,275 men with favorable intermediate-risk prostate cancer, 1,321 (31%) were managed with active surveillance, increasing from 13% in 2012 to 45% in 2020. The 5-year treatment-free probability for men with favorable intermediate-risk prostate cancer on active surveillance was 73% for Gleason Grade Group 1 and 57% for Grade Group 2 disease. More men undergoing a delayed radical prostatectomy had adverse pathology (46%) compared with immediate radical prostatectomy (32%, P < .001), yet short-term biochemical recurrence was similar between groups (log-rank test, P = .131). CONCLUSIONS: The use of active surveillance for men with favorable intermediate-risk prostate cancer has increased markedly. Over half of men with favorable intermediate-risk prostate cancer on active surveillance remained free of treatment 5 years after diagnosis. Most men on active surveillance will not lose their window of cure and have similar short-term oncologic outcomes as men undergoing up-front treatment. Active surveillance is an oncologically safe option for appropriately selected men with favorable intermediate-risk prostate cancer.

Impact of Race and Socioeconomic Status on Outcomes in Patients Hospitalized with COVID-19.

BACKGROUND: The impact of race and socioeconomic status on clinical outcomes has not been quantified in patients hospitalized with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the association between patient sociodemographics and neighborhood disadvantage with frequencies of death, invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission in patients hospitalized with COVID-19. DESIGN: Retrospective cohort study. SETTING: Four hospitals in an integrated health system serving southeast Michigan. PARTICIPANTS: Adult patients admitted to the hospital with a COVID-19 diagnosis confirmed by polymerase chain reaction. MAIN MEASURES: Patient sociodemographics, comorbidities, and clinical outcomes were collected. Neighborhood socioeconomic variables were obtained at the census tract level from the 2018 American Community Survey. Relationships between neighborhood median income and clinical outcomes were evaluated using multivariate logistic regression models, controlling for patient age, sex, race, Charlson Comorbidity Index, obesity, smoking status, and living environment. KEY RESULTS: Black patients lived in significantly poorer neighborhoods than White patients (median income: $34,758 (24,531-56,095) vs. $63,317 (49,850-85,776), p < 0.001) and were more likely to have Medicaid insurance (19.4% vs. 11.2%, p < 0.001). Patients from neighborhoods with lower median income were significantly more likely to require IMV (lowest quartile: 25.4%, highest quartile: 16.0%, p < 0.001) and ICU admission (35.2%, 19.9%, p < 0.001). After adjusting for age, sex, race, and comorbidities, higher neighborhood income ($10,000 increase) remained a significant negative predictor for IMV (OR: 0.95 (95% CI 0.91, 0.99), p = 0.02) and ICU admission (OR: 0.92 (95% CI 0.89, 0.96), p < 0.001). CONCLUSIONS: Neighborhood disadvantage, which is closely associated with race, is a predictor of poor clinical outcomes in COVID-19. Measures of neighborhood disadvantage should be used to inform policies that aim to reduce COVID-19 disparities in the Black community.

Prostate cancer with comedonecrosis is frequently, but not exclusively, intraductal carcinoma: a need for reappraisal of grading criteria.

AIMS: Comedonecrosis in prostate cancer has always been Gleason pattern 5. However, we aimed to evaluate how intraductal carcinoma (not graded) with comedonecrosis should be considered. METHODS AND RESULTS: From 52 radical prostatectomy patients, 40 were informative and evaluated with immunohistochemistry for basal cells. Clinical outcome was assessed for biochemical recurrence, metastatic disease and the need for adjuvant therapy. Comedonecrosis was predominantly located in intraductal carcinoma (24, 60%). However, nine (23%) had comedonecrosis within invasive cancer and seven (18%) within both invasive and intraductal carcinoma. Extraprostatic extension rarely showed comedonecrosis (5, 13%), but rather perineural invasion within cribriform glands. Tumours were largely high-stage (15, 38% pT3a and 19, 48% pT3b), with 15 (37%) having positive lymph nodes and four distant metastases. Most cases (25, 63%) had other patterns of Gleason pattern 5 (single cells, solid), although 10 were reclassified as containing no invasive pattern 5. Of these, most were pT3 (eight of 10), but none had positive lymph nodes. Lymph node metastases were more common in patients with invasive cancer containing comedonecrosis (P = 0.02), and the need for androgen deprivation was near significance (P = 0.07), but biochemical recurrence was not significantly different (P = 0.58). CONCLUSIONS: Prostate cancer with comedonecrosis is often intraductal; however, these tumours are largely high-stage, showing a higher rate of positive lymph nodes with invasive comedonecrosis. Immunohistochemistry may be considered when comedonecrosis may significantly change the tumour grade. However, it is not clear at present that excluding intraductal carcinoma from the grade is superior to including it in grading when it is associated with high-grade invasive cancer.

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

BACKGROUND: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. METHODS: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). RESULTS: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). CONCLUSION: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.