Prostate biopsy sepsis prevention: external validation of an alcohol needle washing protocol.

PURPOSE: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is associated with a 1-8% risk of post-biopsy sepsis (PBS). A recent study described an isopropyl alcohol needle washing protocol that significantly decreased PBS rates. The current study examined the efficacy of this technique in our clinic population. MATERIALS AND METHODS: Data were reviewed for 1250 consecutive patients undergoing TRUS-Bx at the Charlie Norwood VA Medical Center from January 2017 to January 2023. Needle washing was adopted in February 2021. Complications occurring within 30 days after TRUS-Bx were recorded. RESULTS: There were 912 patients in group 1 (without needle washing) and 338 in group 2 (with needle washing). Groups had equivalent demographic features, and men of African descent comprised 70% of patients. Standard 12 core biopsies were done in 83% and 82% in groups 1 and 2, respectively (p = 0.788). Total complication rates were 4% and 2% in groups 1 and 2, respectively (p = 0.077). There were 13 sepsis events in group 1 (1.4%) and none in group 2 (p = 0.027). Clavien-Dindo Grade I-III complications occurred in 25 (2.7%) and 7 (2.1%) patients in groups 1 and 2, respectively (p = 0.505). Standard antibiotic prophylaxis (PO fluoroquinolone and IM gentamicin) was given in 80% and 86% of patients in groups 1 and 2, respectively (p = 0.030). Subset analysis limited to patients who received standard prophylaxis showed a significant difference in sepsis rates (1.5% vs 0%; p = 0.036). CONCLUSIONS: Adoption of isopropyl alcohol needle washing was associated with a significant decrease in PBS events.

A novel exosome based therapeutic intervention against neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a highly lethal variant of castration-resistant prostate cancer (CRPC) with poor survival rates. Current treatment options for NEPC are limited to highly toxic platinum drugs highlighting the urgent need for new therapies. This study aimed to develop a novel therapeutic approach using engineered exosomes against NEPC. Exosomes were modified to target CEACAM5, an NEPC surface antigen, by attaching CEACAM5 antibodies to HEK293T exosomes. These exosomes were loaded with drugs inhibiting EZH2 and the androgen receptor (AR) as recent research shows a persistent role of AR in NEPC wherein it plays a concerted role with EZH2 in driving neuronal gene programs. In vitro experiments with NEPC cell lines demonstrated that CEACAM5-targeted exosomes were specifically taken up by NEPC cells, leading to reduced cellular viability and decreased expression of neuronal markers. Further in vivo tests using a NEPC patient-derived xenograft model (LuCaP145.1) showed significant tumor regression in mice treated with engineered exosomes compared to control mice receiving IgG-labeled exosomes. These results suggest that CEACAM5-engineered exosomes hold promise as a targeted therapy for NEPC. Importantly, our exosome engineering strategy is versatile and can be adapted to target various surface antigens in prostate cancer and other diseases.

Transgender patient undergoing Rezum therapy: a case report.

Rezum is a relatively new, minimally invasive approach that utilizes vaporized water to ablate prostatic tissue surrounding the proximal urethra in patients with benign prostatic hyperplasia. However, of the many notable studies involving Rezum's effectiveness in men, none have documented use of Rezum in the transgender community. With a growing population of transgender patients in the USA, prostate treatments will be offered for transgender women on a more regular basis. To the best of our knowledge, we introduce the first case of Rezum being utilized to treat benign prostatic hyperplasia in a patient self-identifying as a woman.

Therapeutic potential of pomegranate juice-derived nanovesicles in nude mouse benign prostatic hyperplasia (BPH) xenograft model.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms affect a large percentage of the male population and places a substantial burden on the world health system. Current therapies include 5-alpha reductase inhibitors and alpha-blockers that are only partially effective and pose a huge economic burden, emphasizing the urgent need for effective, economical therapies. We isolated nanovesicles from pomegranate juice (Punica Granatum) (referred to as 'POM-NVs') and report to our knowledge for the first time, that these vesicles possess therapeutic potential against BPH. Following extensive characterization of POM-NVs, we tested their therapeutic potential in vitro using BPH1 cell line and identified a potential anti-proliferative and pro-apoptotic effect. We further tested these vesicles using a clinically relevant xenograft mouse BPH model derived from human BPH tissues. Remarkably, POM-NVs could reverse the BPH phenotype conferred by TGF-ß mediated signaling and induced epithelial-to-mesenchymal (EMT) reversal, leading to the restoration of prostate epithelial states in vivo and in vitro. Furthermore, these vesicles attenuated bone morphogenic protein 5 (BMP5) signaling, a cardinal alteration that is instrumental in driving BPH. Considering the large incidences of BPH and its associated economic burdens, our study has important implications and can potentially improve the clinical management of BPH.

Statin Induced Immune Mediated Necrotizing Myopathy: More Than Just Sore Muscles.

Statin drugs are commonly used to decrease levels of triglycerides and cholesterol. Common side effects of this medication class are generally mild and include headache, nausea, diarrhea, and myalgia. Rarely, statins have been associated with autoimmune disease resulting in a potentially serious inflammatory myopathy known as statininduced immune-mediated necrotizing myopathy (IMNM). Here, we describe a case of statin-induced IMNM in a 66-year-old man placed on atorvastatin several months prior to CABG surgery. We review the relevant laboratory results, imaging, immunologic, histopathologic findings and treatment strategy of this important disorder.

Less Common Focal Neuropathies: A Brief Review.

Focal peripheral neuropathies (FPN) will be encountered by clinical practitioners in all disciplines. While bedside exam skills are greatly beneficial in the diagnostic approach, new options are improving diagnostic accuracy. A variety of management options are available to assist patients with these diverse disorders. Ten less common focal neuropathies are featured in this review.

miR-410 Is a Key Regulator of Epithelial-to-Mesenchymal Transition with Biphasic Role in Prostate Cancer.

The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa. Functional studies were performed in a series of PCa cell lines. In LNCaP cells, miR-410 overexpression led to decreases in cellular viability, proliferation, invasiveness, and migration. On the other hand, miR-410 overexpression in PC3 and C42B cells led to increased viability, proliferation, and invasiveness. Our data suggest that miR-410 represses epithelial-to-mesenchymal transition (EMT) in LNCaP cells by directly repressing SNAIL. However, it promotes EMT and upregulates PI3K/Akt signaling in PC3 and C42B cells. In vivo studies with PC3 xenografts support an oncogenic role of miR-410. These data suggest that miR-410 acts as a tumor suppressor in the initial stages of PCa and play an oncogenic role in advanced PCa. Our findings have important implications in understanding the molecular basis of PCa progression with potential translational implications.

Antibiotic-functionalized gold nanoparticles for the detection of active ß-lactamases.

Antimicrobial resistance (AMR) continues to threaten the effective treatment and prevention of bacterial infections. The spread of resistant infections is accelerated by the lack of fast and cost-effective tests for the detection of AMR at the point-of-care. We aimed to address this challenge by developing a diagnostic tool to detect one of the major forms of AMR, the ß-lactamase enzymes. Antibiotic-functionalized gold nanoparticles (AuNPs) have been successfully developed for the detection of ß-lactamases in challenging biological media, namely undiluted urine. Furthermore, these tools are compatible with samples containing a urine sample preservative (boric acid) or hematuria (blood). The functionalized AuNPs interact with the active ß-lactamases, resulting in the hydrolysis of the surface-bound antibiotics, which then inhibits binding of the AuNPs to a capture protein (a penicillin-binding protein) to indicate the presence of active ß-lactamases. We successfully integrated the antibiotic-functionalized AuNPs into a new lateral flow assay (LFA), which can be used to detect active ß-lactamases down to the detection limit of 11 nM. While we demonstrate the use of antibiotic-functionalized AuNPs in an LFA format to provide a novel method of detecting active ß-lactamases, these functionalized AuNPs are amenable to a range of alternative diagnostic technologies and could lead to vital point-of-care diagnostics for the early detection of multi-drug resistant infections.

Correlates of bird collisions with buildings across three North American countries.

Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management.

Correlaciones de las Colisiones de Aves contra Edificios en Tres Países de América del Norte Resumen Las colisiones contra los edificios causan hasta mil millones de fatalidades de aves al año en los Estados Unidos y en Canadá. Sin embargo, los esfuerzos por reducir estas colisiones se beneficiarían con estudios realizados a grandes escalas espaciales en varios sitios de estudio con métodos estandarizados y considerando las variaciones relacionadas a la historia de vida y a la especie y las correlaciones de las colisiones. Abordamos estas necesidades de investigación por medio de una recolección coordinada de datos sobre las colisiones de aves contra edificios en los Estados Unidos (35), Canadá (3) y México (2). Recolectamos todos los cadáveres y los identificamos hasta especie. Después de retirar los registros de cadáveres no identificados, las especies sin estimaciones poblacionales a nivel distribución y las especies con distribuciones traslapadas en menos de diez sitios, nos quedamos con 269 cadáveres de 64 especies para el análisis. Estimamos la vulnerabilidad a colisiones para 40 especies con ≥2 fatalidades con base en la abundancia poblacional para América del Norte, el traslape de su distribución entre los sitios de estudio y el esfuerzo de muestreo. De las diez especies que identificamos como las más vulnerables a las colisiones, algunas han sido identificadas previamente (Setophaga caerulescens), y otras aparecieron por primera vez (Sitta carolinensis), posiblemente debido a que usamos una estrategia de muestreo más estandarizada que en los estudios previos. El tamaño del edificio y el área del vidrio estuvieron asociados positivamente con el número de colisiones para cinco de ocho especies con suficientes observaciones para ser analizadas independientemente. La vegetación alrededor de los edificios influyó sobre las colisiones solamente para una de esas ocho especies Catharus ustulatus). Las historias de vida pronosticaron las colisiones; el número de colisiones fue mayor para las especies migratorias, insectívoras y aquellas que habitan en las zonas boscosas. Nuestros resultados proporcionan una nueva perspectiva hacia las especies más vulnerables a las colisiones contra edificios, lo que las pone en una necesidad potencialmente mayor de atención conservacionista para reducir estas colisiones y de estudio de las variaciones relacionadas con la especie y la historia de vida y las correlaciones de las colisiones contra edificios, información que puede ayudar a refinar el manejo de colisiones.

Self-Sustaining 3D Thin Liquid Films in Ambient Environments.

Thin liquid films (TLF) have fundamental and technological importance ranging from the thermodynamics of cell membranes to the safety of light-water cooled nuclear reactors. The creation of stable water TLFs, however, is very difficult. In this paper, the realization of thin liquid films of water with custom 3D geometries that persist indefinitely in ambient environments is reported. The wetting films are generated using microscale "mounts" fed by microfluidic channels with small feature sizes and large aspect ratios. These devices are fabricated with a custom 3D printer and resin, which were developed to print high resolution microfluidic geometries as detailed in Reference 26. By modifying the 3D-printed polymer to be hydrophilic and taking advantage of well-known wetting principles and capillary effects, self-sustaining microscale "water fountains" are constructed that continuously replenish water lost to evaporation while relying on surface tension to stabilize their shape. To the authors' knowledge, this is the first demonstration of stable sub-micron thin liquid films (TLFs) of pure water on curved 3D geometries.

Aptamer-Based Detection of Ampicillin in Urine Samples.

The misuse of antibiotics in health care has led to increasing levels of drug resistant infections (DRI's) occurring in the general population. Most technologies developed for the detection of DRI's typically focus on phenotyping or genotyping bacterial resistance rather than on the underlying cause and spread of DRI's; namely the misuse of antibiotics. An aptameric based assay has been developed for the monitoring of ampicillin in urine samples, for use in determining optimal antibiotic dosage and monitoring patient compliance with treatment. The fluorescently labelled aptamers were shown to perform optimally at pH 7, ideal for buffered clinical urine samples, with limits of detection as low as 20.6 nM, allowing for determination of ampicillin in urine in the clinically relevant range of concentrations (100 nM to 100 µM). As the assay requires incubation for only 1 h with a small sample volume, 50 to 150 µL, the test would fit within current healthcare pathways, simplifying the adoption of the technology.

Performance limitations of resonant refractive index sensors with low-cost components.

Resonant biosensors are attractive for diagnostics because they can detect clinically relevant biomarkers with high sensitivity and in a label-free fashion. Most of the current solutions determine their detection limits in a highly stabilised laboratory environment, which does, however, not apply to real point-of-care applications. Here, we consider the more realistic scenario of low-cost components and an unstabilised environment and consider the related design implications. We find that sensors with lower quality-factor resonances are more fault tolerant, that a filtered LED lightsource is advantageous compared to a diode laser, and that a CMOS camera is preferable to a CCD camera for detection. We exemplify these findings with a guided mode resonance sensor and experimentally determine a limit of detection of 5.8 ± 1.7×10-5 refractive index units (RIU), which is backed up by a model identifying the various noise sources. Our findings will inform the design of high performance, low cost biosensors capable of operating in a real-world environment.

A Case of Copper Deficiency Myeloneuropathy Precipitated by Zinc Ingestion and Bariatric Surgery.

In this report, we present a case of acquired copper deficiency which initially presented as progressive pain and numbness in the patient's lower extremities. The acquired copper deficiency is attributed to a previous bariatric surgery exacerbated by zinc toxicity. A 42-year-old female with a past medical history of type 2 diabetes mellitus, anemia, hypertension, bipolar disorder, attention deficit disorder, pulmonary embolus, fibromyalgia, migraine headaches, and chronic pain as well as a remote past surgical history of gastric bypass procedure presented with progressive pain and numbness in her lower extremities. The patient reported chronic use of zinc supplements. Clinical evaluation revealed abnormal neurologic exam consistent with a myeloneuropathy and anemia. A cervical spine MRI showed increased signal intensity primarily affecting the posterior columns from C2-C6. Laboratory studies confirmed low copper, low ceruloplasmin, and elevated zinc levels. This case is an example of acquired copper deficiency due to previous bariatric surgery exacerbated by zinc ingestion. With an increased prevalence of bariatric surgery, it is important to monitor patients postoperatively for neurologic symptoms potentially due to copper deficiency.

Glossopharyngeal Neuralgia: A Multidimensional Challenge.

Glossopharyngeal neuralgia is an underreported condition characterized by discomfort elicited through involvement of the ninthcranial nerve. Triggering phenomena and associated vagal nerve involvement creates the potential for an unexpected clinical presentation. In this case report, we present a 60-year-old male who described a shock-like pain throughout his neck and jaw. The patient initially responded to carbamazepine but the clinical course was complicated by cardiac pauses with syncope requiring pacemaker implantation. Failure of pharmacologic treatment led to surgical intervention.

Successful Clearance of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia with Daptomycin, Linezolid, and Meropenem Salvage Therapy.

Staphylococcus aureus is one of the most virulent Gram-positive organisms responsible for a multitude of infections, including bacteremia. Methicillin-resistant Staphylococcus aureus (MRSA) is of special concern in patients with bacteremia. Due to its associated poor clinical outcomes, morbidity, and mortality, the superlative salvage regimen for persistent MRSA bacteremia remains uncertain. An 85-year-old white female presented with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Empiric antibiotic therapy with linezolid was initiated prior to blood culture results. Once MRSA bacteremia was confirmed, alternative antibiotic therapy with daptomycin was initiated. Blood cultures remained positive for MRSA despite three days of daptomycin therapy after which ceftaroline was added to the antibiotic regimen. Blood cultures remained positive for MRSA despite seven days of combination therapy with daptomycin and ceftaroline. Salvage therapy was then initiated with daptomycin, linezolid, and meropenem. One day following initiation of salvage therapy, blood cultures revealed no bacterial growth for the remainder of the length of stay. This report supports the effectiveness of salvage therapy consisting of daptomycin, linezolid, and meropenem in patients with persistent MRSA bacteremia.

Total Knee Arthroplasty Wound Complication Treatment Algorithm: Current Soft Tissue Coverage Options.

BACKGROUND: Wound complications associated with soft tissue defects following total knee arthroplasty present challenges for the orthopedic surgeon. The scale of early complications include less morbid problems, such as quickly resolving drainage and small superficial eschars, to persistent drainage and full-thickness tissue necrosis, which may require advanced soft tissue coverage. METHODS: This review outlines current wound management strategies and provides an algorithm to help guide treatment and clinical decision-making. CONCLUSION: A surgeon's understanding of soft tissue coverage options is essential in protecting the knee prosthesis from a deep infection and to obtain an optimal functional outcome.

Reduced Risk of Sepsis after Prostate Biopsy Using a Cephalosporin-Fluoroquinolone Antibiotic Regimen and Isopropyl Alcohol Needle Washing.

OBJECTIVE: To compare 3 prophylactic regimens to assess their impact on postbiopsy sepsis incidence. METHODS: Data were reviewed for 829 consecutive patients who underwent prostate biopsy in a community practice setting between January 2013 and October 2017. Group 1 patients received ciprofloxacin 500 mg two times a day orally for 4 days starting the day prior to biopsy and gentamicin 80 mg intramuscularly 20 minutes prior to biopsy. From April 2015 to October 2017, 2 groups of patients were followed in parallel in a randomized manner. Group 2 received ciprofloxacin 500 mg two times a day orally for 4 days starting the day prior to biopsy and ceftriaxone 1 g intramuscularly 20 minutes prior to biopsy. Group 3 received the same antibiotic regimen as group 2 and also underwent isopropyl alcohol needle washing. RESULTS: All study groups were demographically equivalent. Microscopic bacterial counts were substantially decreased after isopropyl alcohol needle washing. Incidence of postbiopsy sepsis in groups 1 (n = 313), 2 (n = 259), and 3 (n = 257) was 3.8%, 2%, and 0%, respectively (analysis of variance; P = .006). Risk factors for sepsis included elevated body mass index, Charlson Comorbidity Score, and presence of type 2 diabetes mellitus. CONCLUSION: There was a significant reduction in the incidence of sepsis after prostate biopsy using a combination of a ciprofloxacin-ceftriaxone antibiotic regimen and isopropyl alcohol needle washing. The technique for needle washing is inexpensive and quick, and can be easily adopted into current biopsy protocols.

Outcomes and Complications of Robotic-assisted Laparoscopic Prostatectomy in a Community Hospital Setting.

OBJECTIVE: To evaluate outcomes for 144 robotic-assisted laparoscopic prostatectomies (RALPs) conducted upon introduction of a robotic surgery program in a community hospital. METHODS: Patient data were reviewed for 144 patients who underwent RALP from January 2013 to February 2015. Complications and oncologic and functional outcomes were assessed. Student t test and analysis of variance were used to compare differences among study groups. RESULTS: Median age was 64 (IQR 60-68) and median prostate-specific antigen was 5.61 (interquartile range [IQR] 4.3-7.7). Stage pT2, pT3a, and 3b pathology was present at rates of 77%, 21%, and 8%, respectively. Median operative blood loss was 200 mL (IQR 150-300), median operative time was 1.75 hours (IQR 1.5-2.3), and median length of stay was 2 days (IQR 1-2). Overall, there were 9 complications (6.8%); 2 were classified as major and 7 as minor events. The overall positive surgical margin rate was 19%, with positive surgical margin rates of 11% and 46.8% in patients with pT2 and pT3 disease, respectively (P < .001). The overall biochemical recurrence rate at 12 months was 12.5% occurring in 10% and 20% of patients with pT2 and pT3 disease, respectively (P = .32). Continence success at 1, 6, and 12 months was 67%, 90%, and 93%, respectively. Potency success in men with normal to mild erectile dysfunction at baseline was 76% and 83% at 6 and 12 months, respectively. CONCLUSION: RALP in this community hospital practice was both safe and effective. Complication rates and oncologic and functional outcomes in this study were commensurate with those reported by high volume centers.