Image-guided multiparametric magnetic resonance imaging-transrectal ultrasound fusion biopsy augmented with a sextant versus an extended template random biopsy: Comparison of cancer detection rates, complication and functional outcomes.

PURPOSE: To compare the efficacy of a novel fusion template "reduced six-core systemic template and multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion targeted biopsy" (TBx+6c), with mpMRI/TRUS fusion-targeted biopsy and 12-core systematic biopsy template (TBx+12c) in the diagnosis of prostate cancer (PCa). MATERIALS AND METHODS: This is an institutional review board approved single-center observational study involving adult men undergoing fusion-targeted biopsies for the diagnosis of PCa. Patients were sorted into cohorts of TBx+6c or TBx+12c based on the systematic biopsy template used. The study's main objective was to determine the cancer detection rate (CDR) for overall PCa and clinically significant PCa (csPCa) and the secondary objectives were to compare complication rates and functional outcome differences between the cohort. RESULTS: A total of 204 patients met study's inclusion criteria. TBx+6c group had 120 patients, while TBx+12c cohort had 84 patients. The groups had similar baseline characteristics and overall CDR in the TBx+6c cohort was 71.7% versus 79.8%, compared to the TBx+12c (p = 0.18) whereas, the csPCa detection rate in the TBx+6c group was 50.8% versus 54.8% in the TBx+12c group (p = 0.5). TBx+6c cohort had lower overall complication rate of 3% versus 13%, (p = 0.01) and ≥ grade 2 complication rates (1 (1%) vs. 3(4%), p = 0.03) compared to the TBx+12c cohort. There were no differences in IIEF-5 (p = 0.5) or IPSS (p = 0.1) scores at baseline and 2-weeks and 6-weeks post-biopsy. CONCLUSION: TBx+6c cohort, when compared to the TBx+12c cohort, demonstrated comparable diagnostic performance along with similar functional outcomes and lower complication rates. These results suggest the importance of further exploring the clinical implications of adopting a TBx+6c schema for PCa diagnosis in comparison to the widely used TBx+12c schema through a multicenter randomized controlled trial.

Detecting criminal intent in social interactions: The influence of autism and theory of mind.

OBJECTIVE: Defense attorneys sometimes suggest that social-cognitive difficulties render autistic individuals vulnerable to involvement in crime, often arguing that theory of mind (ToM) difficulties that undermine inferences about others' intentions underpin this vulnerability. We examined autistic adults' ability to respond adaptively to criminal intent during interactions and whether difficulties were associated with poor ToM. HYPOTHESES: Compared with nonautistic adults, autistic adults were expected to be less likely to respond adaptively to another's criminal intent and less likely to do so early in interactions, with poorer performance associated with ToM difficulties. METHOD: We developed the Suspicious Activity Paradigm, in which autistic (n = 102) and nonautistic (n = 95) adults listened (as if participating in an interaction) to audio scenarios in which cues suggesting their impending involvement in a crime gradually emerged. At periodic intervals, they were required to indicate how they would react toward the other person's behavior, with response coding reflecting detection of, and adaptive responding to, suspicious activity. RESULTS: We observed similar patterns of suspicion and adaptive responses in autistic and nonautistic adults as the scenarios progressed. Regardless of diagnostic status, pronounced ToM difficulties and low verbal ability were independently associated with a lower likelihood of reporting suspicion and responding adaptively. CONCLUSIONS: Our results do not support the perspective that autistic adults are uniquely vulnerable to crime involvement due to an inability to recognize and respond adaptively to suspicious behavior. The potential for heightened criminal vulnerability was associated with significant ToM difficulties (and verbal ability) regardless of autism diagnostic status, although such difficulties were more prevalent in the autistic sample. The finding that pronounced ToM difficulties may heighten criminal vulnerability for both autistic and nonautistic individuals challenges the validity of a generalized "autism" legal defense based on assumed rather than measured ToM difficulties. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Oncological and functional outcomes of men undergoing primary whole gland cryoablation of the prostate: A 20-year experience.

BACKGROUND: This study reports the oncological and functional outcomes in men with localized prostate cancer (Pca) who were treated with primary whole gland cryoablation (WGC) of the prostate. METHODS: The authors retrospectively reviewed their prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with WGC of the prostate at a tertiary referral center. Primary outcome includes biochemical recurrence-free survival (BRFS). Secondary outcomes include failure-free survival (FFS), metastasis-free survival (MFS) and adverse events. RESULTS: A total of 260 men were included in the study. Men having had prior treatment for Pca were excluded. Median follow-up was 107 months (interquartile range [IQR], 68.3-132.5 months). BRFS, FFS, and MFS at 10 years were 84%, 66%, and 96%, respectively. High risk D'Amico classification was associated with a lower BRFS and FFS on multivariable analysis. No patient had any Pca-related death during follow-up. American Urological Association symptoms score and bother index were unchanged following cryoablation. Median International Index of Erectile Function score precryoablation and post-cryoablation was 7 (IQR, 3-11) and 1 (IQR, 1-5), respectively. Stress urinary incontinence, defined as requiring any protective pads only occurred in five patients (2%). No patient developed a fistula. Grade > 2 Clavien-Dindo adverse events occurred in six (2.3%) patients. CONCLUSION: WGC of the prostate can achieve excellent oncological and functional outcomes in men with localized Pca at the 10-year mark. Primary WGC may be a good option for men who desire to preserve urinary continence and have an excellent oncologic outcome. LAY SUMMARY: Primary whole gland cryoablation is an alternative treatment option to radical prostatectomy and radiotherapy for men with organ-confined prostate cancer. Patients had excellent cancer outcomes 1 years after whole gland cryoablation, and patients with PSA nadir 0.1 ng/ml or lower after treatment were less likely to have disease recurrence.

Skeletal Muscle Dysfunction in Experimental Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a serious, progressive, and often fatal disease that is in urgent need of improved therapies that treat it. One of the remaining therapeutic challenges is the increasingly recognized skeletal muscle dysfunction that interferes with exercise tolerance. Here we report that in the adult rat Sugen/hypoxia (SU/Hx) model of severe pulmonary hypertension (PH), there is highly significant, almost 50%, decrease in exercise endurance, and this is associated with a 25% increase in the abundance of type II muscle fiber markers, thick sarcomeric aggregates and an increase in the levels of FoxO1 in the soleus (a predominantly type I fiber muscle), with additional alterations in the transcriptomic profiles of the diaphragm (a mixed fiber muscle) and the extensor digitorum longus (a predominantly Type II fiber muscle). In addition, soleus atrophy may contribute to impaired exercise endurance. Studies in L6 rat myoblasts have showed that myotube differentiation is associated with increased FoxO1 levels and type II fiber markers, while the inhibition of FoxO1 leads to increased type I fiber markers. We conclude that the formation of aggregates and a FoxO1-mediated shift in the skeletal muscle fiber-type specification may underlie skeletal muscle dysfunction in an experimental study of PH.

Carbonic anhydrase inhibition improves pulmonary artery reactivity and nitric oxide-mediated relaxation in sugen-hypoxia model of pulmonary hypertension.

Pulmonary hypertension (PH) is a serious disease with pulmonary arterial fibrotic remodeling and limited responsiveness to vasodilators. Our data suggest that mild acidosis induced by carbonic anhydrase inhibition could ameliorate PH, but the vascular mechanisms are unclear. We tested the hypothesis that carbonic anhydrase inhibition ameliorates PH by improving pulmonary vascular reactivity and relaxation mechanisms. Male Sprague-Dawley rats were either control normoxic (Nx), or injected with Sugen 5416 (20 mg/kg, sc) and subjected to hypoxia (9% O2) (Su + Hx), or Su + Hx treated with acetazolamide (ACTZ, 100 mg/kg/day, in drinking water). After measuring the hemodynamics, right ventricular hypertrophy was assessed by Fulton's Index; vascular function was measured in pulmonary artery, aorta, and mesenteric arteries; and pulmonary arteriolar remodeling was assessed in lung sections. Right ventricular systolic pressure and Fulton's Index were increased in Su + Hx and reduced in Su + Hx + ACTZ rats. Pulmonary artery contraction to KCl and phenylephrine were reduced in Su + Hx and improved in Su + Hx + ACTZ. Acetylcholine (ACh)-induced relaxation and nitrate/nitrite production were reduced in pulmonary artery of Su + Hx and improved in Su + Hx + ACTZ. ACh relaxation was blocked by nitric oxide (NO) synthase and guanylate cyclase inhibitors, supporting a role of NO-cGMP. Sodium nitroprusside (SNP)-induced relaxation was reduced in pulmonary artery of Su + Hx, and ACTZ enhanced relaxation to SNP. Contraction/relaxation were not different in aorta or mesenteric arteries of all groups. Pulmonary arterioles showed wall thickening in Su + Hx that was ameliorated in Su + Hx + ACTZ. Thus, amelioration of pulmonary hemodynamics during carbonic anhydrase inhibition involves improved pulmonary artery reactivity and NO-mediated relaxation and may enhance responsiveness to vasodilator therapies in PH.

Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension.

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

GLYCOSYLATED FIBRONECTIN AND INHIBIN ARE LOWER AND ANTI-MÜLLERIAN HORMONE IS HIGHER IN UMBILICAL CORD BLOOD WHEN MOTHERS HAVE PREECLAMPSIA.

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor axis, are altered in maternal plasma in the setting of preeclampsia; however, these molecules have not been previously measured in cord blood of infants born to mothers with preeclampsia, which may represent changes in fetal physiology. We evaluated potential biomarkers of preeclampsia in umbilical cord blood to fill the gap in knowledge. Methods: This is a case-control study of 196 neonates born at a tertiary teaching hospital in Boston from 2010-2017. Forty-nine neonates born to mothers with preeclampsia were matched 1:3 by gestational age, sex, and birth weight z-score with 147 controls. Eleven analytes were measured in cord blood by enzyme-linked immunosorbent assay. Binary logistic regression analyses were performed to evaluate associations between preeclampsia and analytes. Results: Mean cord blood levels of GlyFn and total inhibin were significantly lower in neonates born to mothers with preeclampsia compared to controls, and AMH levels were significantly higher in males born to mothers with preeclampsia than male controls. Associations remained significant after controlling for maternal and neonatal characteristics. Conclusion: Cord blood levels of GlyFn and inhibin are decreased and AMH (male) levels are increased in infants of preeclamptic mothers, which is opposite the pattern these biomarkers show in serum of mothers with preeclampsia. These molecules may be important in the pathophysiology and long-term effects of preeclampsia on the developing fetus. Abbreviations: AMH = anti-müllerian hormone; ELISA = enzyme-linked immunosorbent assay; GlyFn = glycosylated fibronectin; IGF = insulin-like growth factor; IGFBP5 = insulin-like growth factor binding protein 5; LOD = limit of detection; PAPP-A = pregnancy-associated plasma protein A; PAPP-A2 = pregnancy-associated plasma protein A2.

Carbonic Anhydrase Inhibition Ameliorates Inflammation and Experimental Pulmonary Hypertension.

Inflammation and vascular smooth muscle cell (VSMC) phenotypic switching are causally linked to pulmonary arterial hypertension (PAH) pathogenesis. Carbonic anhydrase inhibition induces mild metabolic acidosis and exerts protective effects in hypoxic pulmonary hypertension. Carbonic anhydrases and metabolic acidosis are further known to modulate immune cell activation. To evaluate if carbonic anhydrase inhibition modulates macrophage activation, inflammation, and VSMC phenotypic switching in severe experimental pulmonary hypertension, pulmonary hypertension was assessed in Sugen 5416/hypoxia (SU/Hx) rats after treatment with acetazolamide or ammonium chloride (NH4Cl). We evaluated pulmonary and systemic inflammation and characterized the effect of carbonic anhydrase inhibition and metabolic acidosis in alveolar macrophages and bone marrow-derived macrophages (BMDMs). We further evaluated the treatment effects on VSMC phenotypic switching in pulmonary arteries and pulmonary artery smooth muscle cells (PASMCs) and corroborated some of our findings in lungs and pulmonary arteries of patients with PAH. Both patients with idiopathic PAH and SU/Hx rats had increased expression of lung inflammatory markers and signs of PASMC dedifferentiation in pulmonary arteries. Acetazolamide and NH4Cl ameliorated SU/Hx-induced pulmonary hypertension and blunted pulmonary and systemic inflammation. Expression of carbonic anhydrase isoform 2 was increased in alveolar macrophages from SU/Hx animals, classically (M1) and alternatively (M2) activated BMDMs, and lungs of patients with PAH. Carbonic anhydrase inhibition and acidosis had distinct effects on M1 and M2 markers in BMDMs. Inflammatory cytokines drove PASMC dedifferentiation, and this was inhibited by acetazolamide and acidosis. The protective antiinflammatory effect of acetazolamide in pulmonary hypertension is mediated by a dual mechanism of macrophage carbonic anhydrase inhibition and systemic metabolic acidosis.

Impaired Pulmonary Arterial Vasoconstriction and Nitric Oxide-Mediated Relaxation Underlie Severe Pulmonary Hypertension in the Sugen-Hypoxia Rat Model.

Pulmonary vasoreactivity could determine the responsiveness to vasodilators and, in turn, the prognosis of pulmonary hypertension (PH). We hypothesized that pulmonary vasoreactivity is impaired, and we examined the underlying mechanisms in the Sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were injected with Sugen (20 mg/kg s.c.) and exposed to hypoxia (9% O2) for 3 weeks, followed by 4 weeks in normoxia (Su/Hx), or treated with Sugen alone (Su) or hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was assessed for right ventricular hypertrophy (Fulton's index); the pulmonary artery, aorta, and mesenteric arteries were isolated for vascular function studies; and contractile markers were measured in pulmonary arteries using quantitative polymerase chain reaction (PCR). Other rats were used for morphometric analysis of pulmonary vascular remodeling. Right ventricular systolic pressure and Fulton's index were higher in Su/Hx versus Su, Hx, and Nx rats. Pulmonary vascular remodeling was more prominent in Su/Hx versus Nx rats. In pulmonary artery rings, contraction to high KCl (96 mM) was less in Su/Hx versus Nx and Su, and phenylephrine-induced contraction was reduced in Su/Hx versus Nx, Hx, and Su. Acetylcholine (ACh)-induced relaxation was less in Su/Hx versus Nx and Hx, suggesting reduced endothelium-dependent vasodilation. ACh relaxation was inhibited by nitric oxide synthase (NOS) and guanylate cyclase blockade in all groups, suggesting a role of the NO-cGMP pathway. Nitrate/nitrite production in response to ACh was less in Su/Hx versus Nx, supporting reduced endothelial NO production. Sodium nitroprusside (10-8 M) caused less relaxation in Su/Hx versus Nx, Hx, and Su, suggesting a decreased responsiveness of vascular smooth muscle (VSM) to vasodilators. Neither contraction nor relaxation differed in the aorta or mesenteric arteries of all groups. PCR analysis showed decreased expression of contractile markers in pulmonary artery of Su/Hx versus Nx. The reduced responsiveness to vasoconstrictors and NO-mediated vasodilation in the pulmonary, but not systemic, vessels may be an underlying mechanism of severe PH in Su/Hx rats and appears to involve attenuation of the NO relaxation pathway and a switch of pulmonary VSM cells to a synthetic less reactive phenotype.

Tocolysis with the ß2-sympathomimetic fenoterol does not increase the occurrence of infantile hemangioma in preterm and term infants.

PURPOSE: ß2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the ß2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other ß2-mimetic tocolytic agents like fenoterol. METHODS: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. RESULTS: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005). CONCLUSIONS: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different ß2-sympathomimetic tocolytic drugs.

Intratumoural immunotherapy plus focal thermal ablation for localized prostate cancer.

Major advances have been made in the use of immunotherapy for the treatment of solid tumours, including the use of intratumourally injected immunotherapy instead of systemically delivered immunotherapy. The success of immunotherapy in prostate cancer treatment has been limited to specific populations with advanced disease, which is thought to be a result of prostate cancer being an immunologically 'cold' cancer. Accordingly, combining intratumoural immunotherapy with other treatments that would increase the immunological heat of prostate cancer is of interest. Thermal ablation therapy is currently one of the main strategies used for the treatment of localized prostate cancer and it causes immunological activation against prostate tissue. The use of intratumoural immunotherapy as an adjunct to thermal ablation offers the potential to elicit a systemic and lasting adaptive immune response to cancer-specific antigens, leading to a synergistic effect of combination therapy. The combination of thermal ablation and immunotherapy is currently in the early stages of investigation for the treatment of multiple solid tumour types, and the potential for this combination therapy to also offer benefit to prostate cancer patients is exciting.

A Comprehensive Assessment of the Utility of Transperineal Template Prostate Mapping Biopsy: A 13-year Experience.

OBJECTIVE: To assess Duke's experience on the utility of transperineal template mapping biopsy (TTMB) for re-evaluating patients with persistently elevated prostate-specific antigen after prior negative biopsy, with pre-existing prostate cancer (PCa) already on active surveillance (AS), or considering focal therapy (FT). METHODS: We retrospectively reviewed Duke patients undergoing TTMB. Functional outcomes were evaluated using International Index of Erectile Function-5 (IIEF-5) and International Prostate Symptom Score (IPSS). Complications within 30 days were recorded. Nonparametric statistical analyses compared functional measures from baseline to 2 and 6 weeks post-TTMB. RESULTS: From 8/2009 to 1/2021, 218 patients underwent TTMB, with 57-month median follow-up. Complication rate was 17.4%, with the majority Clavien I. Overall PCa detection was 72.9%, with clinically significant PCa in 53.2%; for those without prior PCa diagnosis (n = 117), overall detection was 64.1% with clinically significant PCa in 49.5%. Of those on AS at TTMB (n = 86), 36 (41.8%) had Gleason upgrading. TTMB changed management for 59 (68.6%) patients, with 38 (44.2%) proceeding to whole-gland therapy and 21 (24.4%) electing FT. Regarding functional outcomes, IPSS were insignificantly different from baseline at 6 weeks (P = NS). Overall functional score impacts were minimal across subgroups; in groups with significant declines in IIEF-5, median score drops were ≤1 point and caused minimal/no movement in IIEF-5 scoring category. CONCLUSION: In this cohort, TTMB offered enhanced cancer detection with overall minimal impact to functional outcomes. We conclude from this comprehensive assessment that TTMB provides value to rule out PCa, prevent overtreatment of those that can remain on AS, evaluate FT candidacy, and identify those needing whole-gland management.

Reconciling discordance between PI-RADS 4 lesions and targeted biopsy: Early experience of a multidisciplinary quality improvement protocol with PI-RADS 4 subcategorization.

PURPOSE: PI-RADS 4 lesions are considered to have a "high" likelihood of clinically-significant prostate cancer (csPCa). However, patients undergoing targeted biopsy have a range of histologic findings. Understanding discordant cases is critical to improve diagnostic accuracy and inform subsequent management. We studied early findings from implementation of a multidisciplinary Quality Improvement (QI) protocol for reconciling discordance and evaluate the potential heterogeneity of PI-RADS 4. METHODS: Patients with mpMRI PI-RADS 4 lesions undergoing fusion-targeted biopsy from January 2017 to May 2021 were retrospectively reviewed. The discordant targeted biopsy pathology (benign/GG1) was evaluated utilizing a QI protocol and all lesions were subcategorized based on ADC values. Positive Predictive Value (PPV) for PI-RADS 4 lesions overall and the Cancer Detection Rate (CDR) for subcategorized lesions were calculated. RESULTS: 248 patients with 286 lesions were reviewed. Prior to re-review, PI-RADS 4 PPV for ≥ GG1 and ≥ GG2 lesions were 0.55 and 0.34, increasing to 0.67 and 0.43 following reconciliation. Lesion subcategorization based on ADC value as higher suspicion (4+) and lower suspicion (4-) resulted in 158 and 117 lesions, with reverse-fusion analysis revealing that 61% and 17% of lesions contained csPCa, respectively. Subgroup analysis among PI-RADS 4+ lesions led to an increase in the CDR to 75% and 61% for ≥ GG1 and ≥ GG2. CONCLUSION: Use of multidisciplinary QI protocol to review discordance cases of PI-RADS 4 improves diagnostic accuracy and guides subsequent management. Our findings highlight the known heterogeneity of this category with reference to csPCa CDR, suggesting the potential value of PI-RADS 4 subcategorization.

Comparison of procedural anxiety and pain associated with conventional transrectal ultrasound prostate biopsy to magnetic resonance imaging-ultrasound fusion-guided biopsy: a prospective cohort trial.

BACKGROUND: Prostate cancer (PCa) diagnosis relies on biopsies, with transrectal ultrasound (TRUS) biopsies being common. Fusion biopsy (FB) offers improved diagnostic accuracy, but the pain and anxiety experienced by patients during biopsies is often overlooked. This study aims to compare pain and anxiety levels between standard TRUS-guided biopsy (STB) and systematic plus MRI/US fusion biopsy (STB + FB). MATERIALS AND METHODS: The study involved adult men undergoing biopsies, receiving identical peri-procedural care, including 2% lidocaine jelly in the rectum and subsequent 1% lidocaine injections (10cc per side) into the prostate-seminal vesicle junction and prostatic apical areas bilaterally. The biopsy technique was chosen based on clinical and imaging findings. Pre- and post-biopsy anxiety levels were assessed using the State-Trait Anxiety Inventory (STAI) questionnaire, categorized as mild (20-37), moderate (38-44), or severe (45-80). Post-biopsy pain was evaluated on a numerical rating scale, ranging from 0 to 10. RESULTS: Of the 165 patients, 99 underwent STB, and 66 underwent STB + FB. No significant differences were observed in age, race, prostate-specific antigen, prostate volume, or prior biopsies between the groups. The STB + FB group had more biopsy cores taken (16.2 vs. 12, p = 0.001) and a longer procedure time (23 vs. 10 min, p = 0.001). STB biopsy patients experienced lower post-procedural anxiety compared to STB + FB, with a mean difference of -7 (p = 0.001, d = 0.92). In the STB + FB group, 89% experienced severe post-procedural anxiety compared to 59% in STB (p = 0.002). There was no significant difference in post-procedural pain (p = 0.7). Patients with prior biopsies had significantly higher STAI(S) anxiety scores (p = 0.005), and the number of prior biopsies correlated with anxiety severity (p = 0.04) in STB + FB group. CONCLUSION: In summary, STB + FB group demonstrated higher post-procedural anxiety levels than the STB group, with no difference in pain levels. Additionally, patients with a history of repeat biopsies were more likely to exhibit higher STAI(S) anxiety scores.

Oncological and Functional Outcomes for Men Undergoing Salvage Whole-gland Cryoablation for Radiation-resistant Prostate Cancer.

BACKGROUND: There is no consensus on the optimal approach for salvage local therapy in radiation-resistant/recurrent prostate cancer (RRPC). OBJECTIVE: To investigate oncological and functional outcomes for men treated with salvage whole-gland cryoablation (SWGC) of the prostate for RRPC. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed our prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with SWGC of the prostate at a tertiary referral center. INTERVENTION: SWGC of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was biochemical recurrence-free survival (BRFS) according to the Phoenix criterion. Secondary outcomes included metastasis-free survival, cancer-specific survival, and adverse events. RESULTS AND LIMITATIONS: A total of 110 men with biopsy-proven RRPC were included in the study. Median follow-up for patients without biochemical recurrence (BCR) after SWGC was 71 mo (interquartile range [IQR] 42.3-116). BRFS was 81% at 2 yr and 71% at 5 yr. A higher prostate-specific antigen (PSA) nadir after SWGC was associated with worse BRFS. The median International Index of Erectile Function-5 score was 5 (IQR 1-15.5) before SWGC and 1 (IQR 1-4) after SWGC. Stress urinary incontinence, strictly defined as the use of any pads after treatment, was 5% at 3 mo and 9% at 12 mo. Clavien-Dindo grade ≥3 adverse events occurred in three patients (2.7%). CONCLUSIONS: In patients with localized RPPC, SWGC achieved excellent oncological outcomes with a low rate of urinary incontinence, and represents an alternative to salvage radical prostatectomy. Patients with fewer positive cores and lower PSA tended to have better oncological outcomes following SWGC. PATIENT SUMMARY: For men with prostate cancer that persists after radiotherapy, a freezing treatment applied to the whole prostate gland can achieve excellent cancer control. Patients who did not have elevated prostate-specific antigen (PSA) at 6 years after this treatment appeared to be cured.

Initial Longitudinal Outcomes of Risk-Stratified Men in Their Forties Screened for Prostate Cancer Following Implementation of a Baseline Prostate-Specific Antigen.

PURPOSE: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. MATERIALS AND METHODS: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017-2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. RESULTS: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). CONCLUSIONS: Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination.

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Device-related complications during renal cryoablation: insights from the Manufacturer and User Facility Device Experience (MAUDE) database.

INTRODUCTION AND OBJECTIVES: Cryoablation offers a treatment option for small renal masses ideally suited ≤3 cm. In well-selected candidates, it is associated with less perioperative morbidity compared to more invasive options, such as partial or radical nephrectomy. However, little is known regarding device-related complications associated with the procedure. We provide an analysis of reports on renal cryoablation from the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: Reports on renal cryoablation submitted to the MAUDE database from 2015 through 6/2021 were analyzed. Cases not pertaining to renal cryoablation were excluded (n = 33). Reports were examined to identify patient morbidity related to a potential device malfunction, as well as manufacturer assessment. Complications were graded based on an established MAUDE complication-reporting stratification. Fisher's Exact test was utilized to analyze for associations between device-related adverse events and severity of post-treatment sequelae. RESULTS: Two hundred and thirty-nine unique cases were identified. Adverse events were related to issues with the needles or system (212 cases), technical error (12 cases), or complication related to patient or tumor complexity (14 cases). There were 187 (78.6%) minor complications (MAUDE 1-2) and 52 (21.4%) major complications (MAUDE 3-4). The manufacturer performed formal device review in 164 (68.6%) cases, accepting responsibility for malfunction in 41. Notable MAUDE 3 complications included 29 (12.1%) cases aborted due to instrument/system malfunction and 14 (5.9%) cases of hemorrhage requiring a subsequent procedure. All 3 reported patient deaths (MAUDE 4) appeared to be a consequence of poor baseline health. On statistical analysis, major complications were seen in a significantly higher proportion of non-device related adverse events compared to device related events (85.2% vs. 13.7%, P < .001). CONCLUSION: While renal cryoablation is associated with low overall perioperative morbidity, there is a diverse set of device-related and procedural complications reported in recent years. Device-related adverse events were often associated with minor complications, and major complications were often seen in higher risk patients with comorbidities, more complex tumors, and after technical error. These findings highlight the need for standardized reporting of complications, optimized patient selection and counseling to ensure the best outcomes.

A Quick Measure of Theory of Mind in Autistic Adults: Decision Accuracy, Latency and Self-Awareness.

Autistic adults often experience difficulties in taking the perspective of others, potentially undermining their social interactions. We evaluated a quick, forced-choice version of the Adult Theory of Mind (A-ToM) test, which was designed to assess such difficulties and comprehensively evaluated by Brewer et al. (2017). The forced-choice version (the A-ToM-Q) demonstrated discriminant, concurrent, convergent and divergent validity using samples of autistic (N = 96) and non-autistic adults (N = 75). It can be administered in a few minutes and machine-scored, involves minimal training and facilitates large-scale, live, or web-based testing. It permits measurement of response latency and self-awareness, with response characteristics on both measures enhancing understanding of the nature and extent of perspective taking difficulties in autistic individuals.

Reconciling Discordance Between Prostate Biopsy Histology and Magnetic Resonance Imaging Suspicion - Implementation of a Quality Improvement Protocol of Imaging Re-review and Reverse-fusion Target Analysis.

There is uncertainty with how to proceed when targeted prostate biopsy of suspicious multiparametric magnetic resonance imaging (mpMRI) lesions return without clinically significant prostate cancer (csPCa). While possible, there are error sources that could contribute to such discordance including the mpMRI read, mpMRI-ultrasound fusion, biopsy technique, and histologic classification. Consequences are potentially significant; mistakenly missing csPCa can lead to delays in curative treatment. Conversely, in cases of incorrect mpMRI interpretation, the patient may be subjected to unnecessary workup/burden. At our institution, we implemented a quality improvement (QI) initiative triggered after a discordant case occurs. This multidisciplinary review process incorporates mpMRI re-review and assessment of accurate lesion-sampling, termed "reverse-fusion." Herein, we describe the protocol, present sample cases, and discuss clinical implications.