Significant Correlation Between Regional Tissue Oxygen Saturation and Vital Signs of Critically Ill Infants

Background: Near-infrared spectroscopy (NIRS) has been used to noninvasively measure specific tissue oxygen saturation (StO2) continuously. Cerebral autoregulation status can be derived from NIRS and arterial blood pressure. The relationship of both cerebral and somatic StO2, fractional tissue oxygen extraction (FTOE), and cerebro-splanchnic oxygenation ratio (CSOR) to measured vital signs parameters for NICU patients has not been well studied. Objective: Determine if significant relationships between brain and somatic StO2, brain and somatic FTOE, and CSOR parameters to vital signs for neonates exist. Assess relationship between pressure passivity index, cerebral autoregulation and mean blood pressure (MBP). Design/Methods: Neonates weighing \u3c5 \u3ekg, preferentially with an arterial catheter, were enrolled in the study. FORE-SIGHT Elite (CASMED Inc., Branford, CT, USA) cerebral and somatic NIRS sensors were placed over the abdominal right upper quadrant and right frontal-temporal area of the forehead for 24 hours. Vital signs including arterial MBP were recorded simultaneously from the patients’ bedside monitor. Data was averaged into 60 second windows and analyzed using linear regression. Results were stratified by gestational age (GA), birth weight (BW), and presence of brain abnormality. Results: Data was obtained from 27 subjects (GA 22.2 to 42 weeks). Two subjects did not have an arterial line, thus they were not included in the MBP measurements. There were ~28000 to 31000 paired data points per comparison. Significant positive and negative correlations (p value1500g group (r=0.057). Brain and somatic FTOE in(r=0.172 and r=0.086, respectively). In patients with an abnormal brain scan, a positive correlation was noted between StO2B and MBP (r=0.354) and a negative correlation was noted between FTOE-B vs. MBP (r=0.305). Generated pressure passive index plots suggested good cerebral autoregulation at low normal MBP ranges for lower weight and GA subjects. Conclusions: There is a significant correlation between cerebral and somatic StO2 and FTOE to measured vital sign parameters in NICU patients

Use of Desipramine for the Treatment of Overactive Bladder Refractory to Antimuscarinic Therapy

Purpose: To evaluate the use of desipramine in the treatment of overactive bladder (OAB). Materials and Methods: We retrospectively evaluated 43 patients who were treated with desipramine for OAB refractory to antimuscarinic therapy. These OAB patients were stratified by the presence or absence of bladder pain. Results: Forty-three patients were evaluated with a mean follow up time of 12.2 +/- 4.6 months. The mean age of the patients was 71 16 years. Twelve patients (28%) discontinued desipramine, 9 due to perceived lack of efficacy, 2 due to central anticholinergic side effects, and 1 due to the development of oropharyngeal sores. Patients were stratified into two subgroups based upon treatment with desipramine for OAB alone (n = 29) or OAB and bladder pain (n = 14). There was no difference between the groups in regard to sex (P = .34), prior history of radiation (P = .19), side effects (P = .16), and specifically evaluated central anti-cholinergic side effects (P = .66). There was no statistical difference in the self-reported success rate of the medication (P = .48). In the OAB plus bladder pain subgroup, 71% of patients reported improvement in their pain. Overall, 13 (30%) patients had history of prior pelvic radiation and 10 of those (77%) reported improvement with desipramine. Conclusion: Desipramine is a potential useful treatment for patients with OAB. In addition, it can be used in patients with OAB and bladder pain and patients with complex OAB such as OAB caused by pelvic radiation

Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFβ-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFβ-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC

Genomics in premature infants: A non-invasive strategy to obtain high-quality DNA

We used a cost-effective, non-invasive method to obtain high-quality DNA from buccal epithelial-cells (BEC) of premature infants for genomic analysis. DNAs from BEC were obtained from premature infants with gestational age ≤ 36 weeks. Short terminal repeats (STRs) were performed simultaneously on DNA obtained from the buccal swabs and blood from the same patient. The STR profiles demonstrated that the samples originated from the same individual and exclude any contamination by external DNAs. Whole exome sequencing was performed on DNAs obtained from BEC on premature infants with and without necrotizing enterocolitis, and successfully provided a total number of reads and variants corroborating with those obtained from healthy blood donors. We provide a proof of concept that BEC is a reliable and preferable source of DNA for high-throughput sequencing in premature infants

Transarterial embolization of renal cell carcinoma as an adjunctive therapy prior to cryoablation: a propensity score matching analysis

PURPOSE:We aimed to assess the safety and effectiveness of transarterial embolization (TAE) prior to percutaneous cryoablation (PCA) in the management of renal cell carcinoma (RCC) compared with PCA alone using a propensity score matching analysis to minimize confounding factors.METHODS:A retrospective review of all PCAs performed for renal masses identified 9 patients who underwent TAE prior to PCA. These patients were matched in a 2:1 ratio with patients who underwent PCA only using age, gender, and tumor size to create the propensity score model for matching. Other demographic, clinical, and outcomes data were collected.RESULTS:The TAE+PCA group included 5 males and 4 females with a mean age of 67.9 years and mean tumor diameter of 51.7 mm. The PCA only group included 11 males and 7 females with a mean age of 66.8 years and mean tumor diameter of 46.2 mm. No significant differences in these propensity score matched characteristics were identified. Further, the groups had no significant differences in tumor geometry (P = 0.831), R.E.N.A.L. nephrometry scores (P = 0.144), or comorbidity indices (P = 0.392). TAE was technically successful and without complication in all cases. PCA was technically successful in 8 of 9 patients in the TAE+PCA group and in 14 of 18 patients in the PCA only group (P = 0.483). No significant differences in the rate of complications (P = 0.483), change in eGFR (P = 0.691), or change in hematocrit (P = 0.152) were identified between the two groups.CONCLUSION:TAE of RCC prior to PCA is safe and technically feasible; however, no objective benefits over PCA alone were identified by propensity score matching analysis. Due to small sample size and limitations of the study, no definite conclusions should be drawn. Larger, prospective studies of this therapeutic approach are warranted

Comparison of Magnetic Resonance Imaging-Based Risk Calculators to Predict Prostate Cancer Risk

Importance: Magnetic resonance imaging (MRI)-based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms. Objective: To externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator-MRI [RPCRC-MRI]) in cohorts from Europe and North America. Design, Setting, and Participants: This multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy. Interventions: Prostate MRI followed by prostate biopsy. Main Outcomes and Measures: The primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated. Results: A total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort. Conclusions and Relevance: In this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.</p

MRI/US fusion-guided prostate biopsy allows for equivalent cancer detection with significantly fewer needle cores in biopsy-naive men

PURPOSE:We aimed to investigate the efficiency and cancer detection of magnetic resonance imaging (MRI) / ultrasonography (US) fusion-guided prostate biopsy in a cohort of biopsy-naive men compared with standard-of-care systematic extended sextant transrectal ultrasonography (TRUS)-guided biopsy.METHODS:From 2014 to 2016, 72 biopsy-naive men referred for initial prostate cancer evaluation who underwent MRI of the prostate were prospectively evaluated. Retrospective review was performed on 69 patients with lesions suspicious for malignancy who underwent MRI/US fusion-guided biopsy in addition to systematic extended sextant biopsy. Biometric, imaging, and pathology data from both the MRI-targeted biopsies and systematic biopsies were analyzed and compared.RESULTS:There were no significant differences in overall prostate cancer detection when comparing MRI-targeted biopsies to standard systematic biopsies (P = 0.39). Furthermore, there were no significant differences in the distribution of severity of cancers based on grade groups in cases with cancer detection (P = 0.68). However, significantly fewer needle cores were taken during the MRI/US fusion-guided biopsy compared with systematic biopsy (63% less cores sampled, P < 0.001)CONCLUSION:In biopsy-naive men, MRI/US fusion-guided prostate biopsy offers equal prostate cancer detection compared with systematic TRUS-guided biopsy with significantly fewer tissue cores using the targeted technique. This approach can potentially reduce morbidity in the future if used instead of systematic biopsy without sacrificing the ability to detect prostate cancer, particularly in cases with higher grade disease

Label-free high-resolution imaging of prostate glands and cavernous nerves using coherent anti-Stokes Raman scattering microscopy

A custom built coherent anti-Stokes Raman scattering (CARS) microscope was used to image prostatic glands and nerve structures from 17 patients undergoing radical prostatectomy. Imaging of glandular and nerve structures showed distinctive cellular features that correlated to histological stains. Segmentation of cell nucleus was performed to establish a cell feature-based model to separate normal glands from cancer glands. In this study, we use a single parameter, average cell neighbor distance based on CARS imaging, to characterize normal and cancerous glandular structures. By combining CARS with our novel classification model, we are able to characterize prostate glandular and nerve structures in a manner that potentially enables real-time, intra-operative assessment of surgical margins and neurovascular bundles. As such, this method could potentially improve outcomes following radical prostatectomy

Renal cell carcinoma in children and young adults: analysis of clinicopathological, immunohistochemical and molecular characteristics with an emphasis on the spectrum of Xp11.2 translocation-associated and unusual clear cell subtypes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74766/1/j.1365-2559.2008.03151.x.pd

Image-guided focal therapy for prostate cancer

The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ul­trasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer