Farnesyl pyrophosphate synthase inhibitors with antiosteoporosis efficacy in ovariectomized rats: A mixed binding approach beyond bisphosphonates.

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach. Among the various compounds tested, compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC50 values of 1.108 and 1.24 µM, respectively. Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. In an in vivo study conducted on ovariectomized rats, various biochemical markers including osteocalcin, estradiol, osteoprotegerin, bone mineral content, and density were negatively impacted, while levels of bone specific alkaline phosphatase, receptor activator of nuclear factor kappa-Β ligand, serum/urinary calcium, and phosphate increased. Notably, compound 4a exhibited antiresorptive properties similar to zoledronate, effectively restoring most of the perturbed biochemical estimations. These findings suggest the potential of compound 4a, a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis.

Ranitidine degradation in layered double hydroxide activated peroxymonosulfate system: impact of transition metal composition and reaction mechanisms.

Ranitidine, a competitive inhibitor of histamine H2 receptors, has been identified as an emerging micropollutant in water and wastewater, raising concerns about its potential impact on the environment and human health. This study aims to address this issue by developing an effective removal strategy using two types of layered double hydroxide (LDH) catalysts (i.e., CoFeLDH and CoCuLDH). Characterization results show that CoFeLDH catalyst has superior catalytic properties due to its stronger chemical bond compared to CoCuLDH. The degradation experiment shows that 100% degradation of ranitidine could be achieved within 20 min using 25 mg/L of CoFeLDH and 20 mg/L of peroxymonosulfate (PMS). On the other hand, CoCuLDH was less effective, achieving only 70% degradation after 60 min at a similar dosage. The degradation rate constant of CoFeLDH was 10 times higher than the rate constant of CoCuLDH at different pH range. Positive zeta potential of CoFeLDH made it superior over CoCuLDH regarding catalytic oxidation of PMS. The catalytic degradation mechanism shows that sulfate radicals played a more dominant role than hydroxyl radicals in the case of LDH catalysts. Also, CoFeLDH demonstrated a stronger radical pathway than CoCuLDH. XPS analysis of CoFeLDH revealed the cation percentages at different phases and proved the claim of being reusable even after 8 cycles. Overall, the findings suggest that CoFeLDH/PMS system proves to be a suitable choice for attaining high degradation efficiency and good stability in the remediation of ranitidine in wastewater.

Prevalence of hepatitis B and C infections among HIV-positive men who have sex with men: A systematic review and meta-analysis.

Background: Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM. Methods: This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and I 2 along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764). Results: Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly. Conclusion: There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.

Early Inflatable penile prosthesis implantation offers superior outcomes compared to delayed insertion following ischemic priapism: a narrative review.

Ischemic priapism is a urological emergency which may lead to irreversible erectile dysfunction. One of the accepted treatments is penile prosthesis implantation. Given the scarcity of studies directly comparing timing of penile prosthesis insertion after ischemic priapism, consensus remains elusive. We aim to compare different studies in the literature concerning advantages and disadvantages of early versus delayed inflatable penile prosthesis following ischemic priapism. We analyzed 8 articles that investigated immediate and delayed inflatable penile prosthesis placement after ischemic priapism. Early inflatable penile prosthesis placement is associated with better outcomes, including pain relief, priapism resolution, penile shortening prevention, and quicker sexual activity resumption. However, it still carries a high risk of complications like edema, infection, and distal perforations. Delayed inflatable penile prosthesis insertion poses surgical challenges due to the potential for extensive corporal fibrosis. Comparative analyses have shown elevated complication rates in patients with ischemic priapism who undergo delayed inflatable penile prosthesis insertion, as opposed to those with early insertion. In studies reporting complications rates, the total complication rate in the early group was 3.37%, significantly lower than the delayed group (37.23%). Most studies support the superiority of early inflatable penile prosthesis placement following ischemic priapism over delayed placement. Further research is, however, needed to establish a global consensus on timing of prosthesis insertion.

Effect of Vitamin D Deficiency on Periprosthetic Joint Infection and Complications After Primary Total Joint Arthroplasty.

BACKGROUND: Vitamin D deficiency is a global problem, and 13 to 75% of patients undergoing total joint arthroplasty (TJA) have vitamin D deficiency. Several studies have shown that low preoperative vitamin D levels may increase the risk of postoperative complications, including periprosthetic joint infection (PJI), in patients undergoing primary TJA. Most of the studies are underpowered. This study aimed to investigate the relationship between vitamin D deficiency and surgical and medical complications after primary TJA, with a specific focus on PJI. METHODS: Prospectively collected institutional multicenter arthroplasty databases were reviewed to identify patients who underwent primary total knee and hip arthroplasty. The study group was defined as patients whose vitamin D level is < 30 ng/dL and who received a single oral dose of 7.5 mg (300,000 IU) D3 within two weeks before index surgery (n = 488; mean age 63 years). Patients in the control group were those whose preoperative vitamin D levels were unknown and who did not receive vitamin D supplementation (n = 592, mean age 66). The groups were compared regarding 90-day medical and surgical complications, including PJI, mortality, and readmission rates. RESULTS: The total number of complications (8.6 and 4.3%; respectively; P = .005), superficial wound infection (2.5 and 0.2%, respectively; P < .001), and postoperative cellulitis (2.2 and 0% respectively; P < .001) were statistically significantly higher in the patient group who did not receive vitamin D supplementation. However, 90-day mortality (P = .524), PJI (P = .23), and readmission rate (P = .683) were similar between the groups. CONCLUSIONS: This study demonstrated that preoperative optimization of vitamin D levels may be beneficial in reducing postoperative complications, including superficial wound infection and postoperative cellulitis. Administering an oral 300,000 U single-dose vitamin D regimen to correct vitamin D deficiency can positively impact outcomes following primary TJA.

Search traffic for inflatable penile prosthesis increased following the COVID-19 pandemic in the United States: a Google Trends analysis.

We aimed to determine the impact of the COVID-19 pandemic on search trends for inflatable penile implants in the US. Search trends for inflatable penile implants ranging from 2016 through 2023 were analyzed utilizing Google Trends. Associations between search trends and US Census Bureau data, including average household income and per capita income, were analyzed. Pre- and post- COVID-19, the interest in inflatable penile implants has been steadily increasing on average in the US. The average household income for counties with the highest interest in inflatable penile implants during the pre-COVID era was $53,136, whereas for the counties with the highest interest in inflatable penile implants in the post-COVID era, the average decreased to $50,940. Similarly, the average per capita median decreased from $35,209 to $34,547. Search traffic for inflatable penile prosthesis increased following the pandemic in the US. Nevertheless, post-pandemic, individuals with lower income levels showed no change in interest in penile implant searches compared to the pre-pandemic period. Understanding this steadiness in interest can inform healthcare professionals and policymakers to tailor interventions and educational efforts to reach a broader audience, ensuring equitable access to information and healthcare resources.

LINE-1 retrotransposons contribute to mouse PV interneuron development.

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineages or therein promote neurodevelopmental gene expression. Here we report programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV) interneuron development. Mouse PV interneurons permit L1 mobilization in vitro and in vivo, harbor unmethylated L1 promoters and express full-length L1 mRNAs and proteins. Using nanopore long-read sequencing, we identify unmethylated L1s proximal to PV interneuron genes, including a novel L1 promoter-driven Caps2 transcript isoform that enhances neuron morphological complexity in vitro. These data highlight the contribution made by L1 cis-regulatory elements to PV interneuron development and transcriptome diversity, uncovered due to L1 mobility in this milieu.

Reactive layered hydroxide membrane for advanced water treatment: Micropollutant degradation and antifouling potential.

The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH) catalytic membrane for peroxymonosulfate (PMS) activation to achieve efficient micropollutant removal with improved mass transfer rate and reaction kinetics. This study found that the CoFeLDH membrane/PMS system achieved an impressive above 98% degradation of the probe chemical ranitidine at 0.1 mM of PMS including five more micropollutants (Sulfamethoxazole, Ciprofloxacin, Carbamazepine, Acetaminophen and Bisphenol A) at satisfactory level (above 80%). Moreover, significant improvements in water flux and antifouling properties were observed, marking the membrane as a specific advancement in the removal of membrane fouling in water purification technology. The membrane demonstrated consistent degradation efficiency for several micropollutants and across a range of pH (4-9) as well as different anionic environments, thereby showing it suitability for scale-up application. The key role of reactive species such as SO4•-, and O2• - radicals in the degradation process was elucidated. This is followed by the confirmation of the occurrence of redox cycling between Co and Fe, and the presence of CoOH+ that promotes PMS activation. Over the ten cycles, the membrane could be operated with a flux recovery of up to 99.8% and maintained efficient performance over 24 h continuous operation. Finally, the efficiency in degrading micropollutants, coupled with reduced metal leaching, makes the CoFeLDH membrane as a promising technology for application in water treatment.

The relationship between hematologic malignancies on male hypogonadism: a scoping review.

INTRODUCTION: The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature. OBJECTIVE: In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM). METHODS: This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone." RESULTS: The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density. CONCLUSION: There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.

Traditional and nontraditional lipid parameters in Helicobacter pylori infection.

Aims: This study sought to evaluate the relationship between Helicobacter pylori infection and traditional and nontraditional lipid parameters, including atherogenic index of plasma, cardiogenic risk ratio, atherogenic coefficient and remnant cholesterol. Methods: After the application of exclusion criteria, 309 patients were allocated according to the absence (n = 52) or presence (n = 257) of H. pylori infection. Results: Total cholesterol, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were nonsignificantly higher, and HDL-C levels were nonsignificantly lower, in the H. pylori-infected patient group. Triglyceride-to-HDL-C ratio, LDL-C-to-HDL-C ratio, atherogenic index of plasma, cardiogenic risk ratio, atherogenic coefficient and remnant cholesterol were comparable among groups. Conclusion: There was no significant association between H. pylori infection and traditional and nontraditional novel lipid parameters and indices.

[Box: see text].

RETRACTED: Alhakamy et al. Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats. Biomolecules 2020, 10, 1006.

The journal retracts the article, "Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats" [...].

Transfusion strategies for neonates: current perspectives.

Background: Blood transfusion intervention has been proven to be a crucial therapeutic aid for preterm infants with serious morbidities such as sepsis, intraventricular hemorrhage, and cardiopulmonary insufficiencies. However, blood transfusion practices have also been shown to cause significant adverse outcomes, which may negate the therapeutic effect of the intervention. To address the varying policies regarding the administration of blood products, healthcare professionals have adopted a consensus-based approach. The absence of a standard protocol has resulted in conflicting outcomes in previous clinical studies. Objective: This study aimed to evaluate the effectiveness of blood transfusion practices in preterm infants by analyzing past clinical research and identifying the current trends that have emerged as a result of recent trials. Results: Recent trials have demonstrated comparable trends in mortality rates and other primary outcomes, including retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, and brain injury, following transfusion of blood products in both groups. Nevertheless, employing restrictive thresholds rather than adopting a liberal approach can reduce these outcomes. Conclusion: The current literature does not provide clear support for either technique as opposing and contradictory results are evident. However, there is a slight inclination toward the restrictive transfusion threshold due to recent trials, which warrants further in-depth investigation into this issue.

Cervical radiculopathy secondary to vertebral artery dissection: clinical features and outcomes.

PURPOSE: Cervical radiculopathy due to various mechanical causes is commonly seen, however, cervical vertebral artery dissection (cVAD)-related radiculopathy is very rare with poorly characterized clinical outcomes. Thus, we conducted a systematic review of published literature and reported an institutional case to provide a better illustration of this rare entity. METHODS: We systematically reviewed the PubMed literature and queried the clinical database at our center for cVAD-related radiculopathy. We described the baseline characteristics of patients with cVAD-related radiculopathy, the involved segment, diagnostic approach and treatment options. RESULT: 14 previously published studies met the inclusion criteria and along with the case we identified in our center, our study included 17 patients total (median age: 35 years, 9 females). C5 was the most commonly affected root and ipsilateral shoulder/arm pain along with shoulder abduction weakness was most common presentation. Antiplatelet or anticoagulant therapy was the treatment of choice. Most cases managed conservatively (82%). Majority of the cases (92%) had either complete or partial resolution of their symptoms. CONCLUSION: Despite its limitations, this study show that cVAD related radiculopathy is a relatively benign entity with excellent clinical outcomes when managed medically.

Structure-Property Relationships of Hydrogel-based Atmospheric Water Harvesting Systems.

Atmospheric water harvesting (AWH) is considered one of the promising technologies to alleviate the uneven-distribution of water resources and water scarcity in arid regions of the world. Hydrogel-based AWH materials are currently attracting increasing attention due to their low cost, high energy efficiency and simple preparation. However, there is a knowledge gap in the screening of hydrogel-based AWH materials in terms of structure-property relationships, which may increase the cost of trial and error in research and fabrication. In this study, we synthesised a variety of hydrogel-based AWH materials, characterized their physochemcial properties visualized the electrostatic potential of polymer chains, and ultimately established the structure-property-application relationships of polymeric AWH materials. Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) hydrogel is able to achieve an excellent water adsorption capacity of 0.62 g g-1 and a high water desorption efficiency of more than 90 % in relatively low-moderate humidity environments, which is regarded as one of the polymer materials with potential for future AWH applications.

Multiple sclerosis and hypogonadism: is there a relationship?

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is widely recognized as a disease primarily affecting women. The relationship between MS and hypogonadism is complex and not fully understood, with recent evidence showing that hypogonadism may have a significant impact on the quality of life and disease progression of patients with MS. OBJECTIVES: This review aims to provide an overview of the current knowledge regarding the relationship between MS and hypogonadism, including the mechanisms underlying this relationship; the effects of hypogonadism on patients with MS; and the potential benefits and drawbacks of testosterone replacement therapy for patients with MS and hypogonadism. METHODS: This scientific review analyzed 19 articles that investigated the potential relationship among MS, testosterone levels, and hypogonadism. The articles were published between November 2008 and March 2022 and were identified through a comprehensive search of the PubMed database. The search terms used included "multiple sclerosis," "testosterone," "hypogonadism," and "MS and testosterone levels." RESULTS: Of the 19 articles reviewed, 11 described a positive correlation between low testosterone levels and dysfunction within the hypothalamic-pituitary-gonadal axis in individuals with MS. These findings suggest that low testosterone levels may contribute to dysfunction within the hypothalamus-pituitary-gonadal axis, which plays a crucial role in regulating testosterone production. The results also showed a relationship between sexual dysfunction and low testosterone levels, as well as a positive correlative relationship between these factors. CONCLUSION: The reviewed articles indicate a complex relationship among MS, testosterone levels, and the hypothalamic-pituitary-gonadal axis, with low testosterone levels potentially contributing to dysfunction in this axis and to sexual dysfunction. Further research is needed to better understand the effects of testosterone therapy on MS and sexual dysfunction in patients with MS.

Successful bladder-sparing partial cystectomy for muscle-invasive domal urothelial carcinoma with sarcomatoid differentiation: a case report.

High-grade (HG) urothelial carcinoma (UC) with variant histology has historically been managed conservatively. The presented case details a solitary lesion of muscle-invasive bladder cancer (MIBC) with sarcomatoid variant (SV) histology treated by partial cystectomy (PC) and adjuvant chemotherapy. A 71-year-old male with a 15-pack year smoking history presented after outside transurethral resection of bladder tumor (TURBT). Computerized tomography imaging was negative for pelvic lymphadenopathy, a 2 cm broad-based papillary tumor at the bladder dome was identified on office cystoscopy. Complete staging TURBT noted a final pathology of invasive HG UC with areas of spindle cell differentiation consistent with sarcomatous changes and no evidence of lymphovascular invasion. The patient was inclined toward bladder-preserving options. PC with a 2 cm margin and bilateral pelvic lymphadenectomy was performed. Final pathology revealed HG UC with sarcomatoid differentiation and invasion into the deep muscularis propria, consistent with pathologic T2bN0 disease, a negative margin, and no lymphovascular invasion. Subsequently, the patient pursued four doses of adjuvant doxorubicin though his treatment was complicated by hand-foot syndrome. At 21 months postoperatively, the patient developed a small (<1 cm) papillary lesion near but uninvolved with the left ureteral orifice. Blue light cystoscopy and TURBT revealed noninvasive low-grade Ta UC. To date, the patient has no evidence of HG UC recurrence; 8 years after PC. Patient maintains good bladder function and voiding every 3-4 h with a bladder capacity of around 350 ml. Surgical extirpation with PC followed by adjuvant chemotherapy may represent a durable solution for muscle invasive (pT2) UC with SV histology if tumor size and location are amenable. Due to the sparse nature of sarcomatous features within UC, large multicenter studies are required to further understand the clinical significance and optimal management options for this variant histology.

Comparison of the gut microbiome composition between men with erectile dysfunction and a matched cohort: a pilot study.

BACKGROUND: To-date there have been minimal studies to investigate an association between the gut microbiome and erectile dysfunction. There have been many inflammatory diseases linked to gut microbiome dysbiosis; such as cardiovascular disease and metabolic syndrome. These same inflammatory diseases have been heavily linked to erectile dysfunction. Given the correlations between both conditions and cardiovascular disease and the metabolic syndrome, we believe that it is worthwhile to investigate a link between the two. OBJECTIVE: To investigate the potential association between the gut microbiome and erectile dysfunction. METHODS: Stool samples were collected from 28 participants with erectile dysfunction and 32 age-matched controls. Metatranscriptome sequencing was used to analyze the samples. RESULTS: No significant differences were found in the gut microbiome characteristics, including Kyoto Encyclopedia of Genes and Genomes richness (p = 0.117), Kyoto Encyclopedia of Genes and Genomes diversity (p = 0.323), species richness (p = 0.364), and species diversity (p = 0.300), between the erectile dysfunction and control groups. DISCUSSION: The association of gut microbiome dysbiosis and pro-inflammatory conditions has been well studied and further literature continues to add to this evidence. Our main limitation for this study was our small-sample size due to recruitment issues. We believe that a study with a larger population size may find an association between the gut microbiome and erectile dysfunction. CONCLUSIONS: The results of this study do not support a significant association between the gut microbiome and erectile dysfunction. Further research is needed to fully understand the relationship between these two conditions.

Comparative evaluation of multiple nomograms for predicting postoperative vault after implantable collamer lens surgery.

PURPOSE: To compare the vault predictability of most available implantable collamer lens (ICL) sizing nomograms and identify which preoperative measurements are predictive of vault. SETTING: Private practice in Draper, Utah. DESIGN: Retrospective chart review. METHODS: This study was a retrospective analysis of 209 eyes of 106 patients who underwent STAAR Surgical ICL implantation. Analyses were performed based on the availability of preoperative parameters, varying the number of eyes for each test. Mean absolute error (MAE) of predicted vs actual postoperative vault was calculated for each nomogram. The frequency of Kim, Rocamora (least absolute shrinkage and selection operator-optical coherence tomography), Russo, and Reinstein recommending the correct ICL size in instances when Parkhurst, optimized white-to-white (WTW), and STAAR could not recommend a definitive ICL size was determined. Univariate and multivariate linear regression analysis was performed between preoperative measurements and vault. RESULTS: The Kim, Rocamora, Russo, and Reinstein nomograms had significantly lower MAE of predicted vs actual postoperative vault than the KSV2 and Nakamura V3 nomograms. The Russo formula most frequently recommended the correct ICL size when the Parkhurst, Optimized WTW, and STAAR nomograms could not provide ICL size recommendations. At the 0.05 significance level, anterior chamber depth (ACD), ciliary body inner diameter (CBID), and pupil diameter were the parameters found to have significant correlation with postoperative vault. CONCLUSIONS: The Kim, Rocamora, Russo, and Reinstein nomograms were the most predictive of vault. Additionally, ACD, CBID, and pupil diameter were found to be significantly correlated with vault and should be considered for use in future ICL sizing nomograms.

Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.