Evaluating the Impact of Eat, Sleep, Console in Neonatal Abstinence Syndrome Treatment for Infants Exposed to Substance Use In Utero.

OBJECTIVE: An increase in maternal use of licit or illicit substances, alcohol, and tobacco has resulted in an increased incidence of neonatal abstinence syndrome (NAS). In recent years, NAS management has shifted to initiating an Eat, Sleep, Console (ESC) approach prior to pharmacologic treatment. The objective of this study was to evaluate the impact of ESC in combination with pharmacologic treatment in the management of NAS for infants exposed to substance use in utero. METHODS: This single system, multisite, retrospective cohort study evaluated infants with known exposure to substance or polysubstance use in utero or those who had signs and symptoms of withdrawal with a positive toxicology screen. The primary outcome of rate of pharmacologic therapy initiated was evaluated pre and post implementation of ESC. Secondary outcomes included hospital length of stay, day of life that pharmacologic therapy was initiated, and an evaluation of the ESC guideline. A subgroup analysis with similar outcomes was also performed for patients with maternal polysubstance use. RESULTS: A total of 2843 patients were screened, and 50 patients were randomly selected for -inclusion in both pre- and post-groups. The rate of pharmacologic therapy initiated post implementation of ESC decreased from 58% to 30% (p < 0.01). In the post-group, there was a decrease in the number of -patients requiring scheduled morphine (33%, p < 0.01) and duration of pharmacologic therapy (14.6 days vs 6.47 days, p < 0.01). CONCLUSIONS: Implementing an ESC guideline decreased the length of stay and rate of pharmacologic intervention needed for infants with NAS at our institution.

Contact Tracing and Exposure Investigation in Response to the First Case of Monkeypox Virus Infection in the United States During the 2022 Global Monkeypox Outbreak.

BACKGROUND: In May 2022, the first case of monkeypox virus (MPXV) infection in the United States in the current global outbreak was identified. As part of the public health and health care facility response, a contact tracing and exposure investigation was done. OBJECTIVE: To describe the contact tracing, exposure identification, risk stratification, administration of postexposure prophylaxis (PEP), and exposure period monitoring for contacts of the index patient, including evaluation of persons who developed symptoms possibly consistent with MPXV infection. DESIGN: Contact tracing and exposure investigation. SETTING: Multiple health care facilities and community settings in Massachusetts. PARTICIPANTS: Persons identified as contacts of the index patient. INTERVENTION: Contact notification, risk stratification, and symptom monitoring; PEP administration in a subset of contacts. MEASUREMENTS: Epidemiologic and clinical data collected through standard surveillance procedures at each facility and then aggregated and analyzed. RESULTS: There were 37 community and 129 health care contacts identified, with 4 at high risk, 49 at intermediate risk, and 113 at low or uncertain risk. Fifteen health care contacts developed symptoms during the monitoring period. Three met criteria for MPXV testing, with negative results. Two community contacts developed symptoms. Neither met criteria for MPXV testing, and neither showed disease progression consistent with monkeypox. Among 4 persons with high-risk exposures offered PEP, 3 elected to receive PEP. Among 10 HCP with intermediate-risk exposures for which PEP was offered as part of informed clinical decision making, 2 elected to receive PEP. No transmissions were identified at the conclusion of the 21-day monitoring period, despite the delay in recognition of monkeypox in the index patient. LIMITATION: Descriptions of exposures are subject to recall bias, which affects risk stratification. CONCLUSION: In a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified. PRIMARY FUNDING SOURCE: None.

Pharmacologic Activation of STING in the Bladder Induces Potent Antitumor Immunity in Non-Muscle Invasive Murine Bladder Cancer.

Stimulator of interferon genes (STING) is an innate immune receptor activated by natural or synthetic agonists to elicit antitumoral immune response via type I IFNs and other inflammatory cytokines. Bacillus Calmette-Guerin (BCG) is the standard of care as intravesical therapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC). There are limited options available for patients with NMIBC who developed BCG unresponsiveness. In this study, we characterized in vitro and in vivo antitumor effects of E7766, a macrocyle-bridged STING agonist, via intravesical instillation in two syngeneic orthotopic murine NMIBC tumor models resistant to therapeutic doses of BCG and anti-PD-1 agents. E7766 bound to recombinant STING protein with a Kd value of 40 nmol/L and induced IFNß expression in primary human peripheral blood mononuclear cells harboring any of seven major STING genotypes with EC50 values of 0.15 to 0.79 µmol/L. Intravesical E7766 was efficacious in both NMIBC models with induction of effective immunologic memory in the treated animals. Pharmacologic activation of the STING pathway in the bladder resulted in IFN pathway activation, infiltration of T cells and natural killer (NK) cells, dendritic cell activation, and antigen presentation in bladder epithelium, leading to the antitumor activity and immunity. In addition, measurements of the pharmacodynamic markers, Ifnß1 and CXCL10, in bladder, urine, and plasma, and of STING pathway intactness in cancer cells, supported this mode of action. Taken together, our studies reveal an antitumor immune effect of pharmacologic activation of the STING pathway in bladder epithelium and thus provide a rationale for subsequent clinical studies in patients with NMIBC.

Chronic bacterial prostatitis leading to intrascrotal abscess after transperineal prostate biopsy.

Transperineal biopsy is becoming more commonly used, driven by improved detection rates, better complication profile and increasing application of prostate MRI leading to guided biopsy. However, it can still lead to complications such as urinary retention, postoperative pain and erectile dysfunction. There is also a potential for adverse events such as severe infection, abscess and fistula. This article describes a case of an intrascrotal abscess post-transperineal biopsy, which required an orchidectomy.

First-in-human study of the PARP/tankyrase inhibitor E7449 in patients with advanced solid tumours and evaluation of a novel drug-response predictor.

BACKGROUND: This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor. METHODS: E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines. RESULTS: Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue, n = 4, 800 mg; anaphylaxis, n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50-800-mg oral dosing. CONCLUSION: The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov code: NCT01618136.

Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer.

Radical cystectomy is the gold-standard treatment option for muscle-invasive and metastatic bladder cancer. At the time of cystectomy, up to 25% of patients harbour metastatic lymph node deposits. These deposits most frequently occur in the obturator fossa, but can be as proximal as the interaortocaval region. Thus, the use of concurrent pelvic lymph node dissection (PLND) with cystectomy has been increasingly reported. Data from studies including many patients suggest substantial oncological benefit in PLND cohorts versus non-PLND cohorts, irrespective of pathological nodal status. Additionally, PLND provides useful prognostic information, including disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines advocate the use of PLND during radical cystectomy for muscle-invasive bladder cancer. Despite this recommendation, a lack of consensus exists regarding the optimal PLND template. Comparative series suggest that extended PLND provides improved recurrence-free survival and cancer-specific survival compared with more limited PLND templates. More extensive templates (such as super-extended PLND) provide no additional survival benefit at the potential cost of increased operative time and patient morbidity. In addition to extended PLND templates, increased nodal harvest confers an oncological benefit in patients with node-positive disease or in patients with node-negative disease. Accordingly, recommendations for a minimum nodal yield have been proposed. Despite the growing body of evidence, formal recommendations by oncological and urological authoritative bodies have been limited owing to the lack of randomized data and level I evidence.

CATCH-22: a manual bladder washout protocol to improve care for clot retention.

PURPOSE: To review current practices in manual bladder washouts (MBW) for haematuria with clot retention, comparing those conducted by a urology unit to other inpatient services. Secondly, to describe a standardised protocol for MBWs. METHODS: Prospective data were collected for patients treated for clot retention, from initial management by referral units through to implementation of a standardised MBW by the urology service. Outcomes measured included re-catheterisation, MBW volumes, clot evacuated and time to discharge or subsequent intervention. RESULTS: Initial catheters inserted by referral teams were sized 16 Fr-20 Fr, all except one requiring upsizing. Mean washout volumes of 145 ml (SD 125) and 5392 ml (SD 847) were used by referring units and the urology service, respectively. Mean volume of clot evacuated by the standardised MBW was 617 ml (SD 313). Continuous bladder irrigation (CBI) was commenced in 16 patients (66%) prior to referral to urology. Median time to discharge was 48 h. CONCLUSION: Initial catheter insertion is of inadequate size, as is the volume of washout performed. Referring services fail to clear adequate amounts of clot with washouts posing potential risks to patients. The standard management of clot retention should involve the use of at least a 22 F catheter, implement best practice infection control and adopt the last Clot + 1L rule with catheter manipulation. The key points of our recommended MBW are summarised with the acronym CATCH-22. This protocol can guide initial management of clot retention and be used as an educational tool.

Carbon Footprint in Flexible Ureteroscopy: A Comparative Study on the Environmental Impact of Reusable and Single-Use Ureteroscopes.

PURPOSE: There are no comparative assessments on the environmental impact of endourologic instruments. We evaluated and compared the environmental impact of single-use flexible ureteroscopes with reusable flexible ureteroscopes. PATIENTS AND METHODS: An analysis of the typical life cycle of the LithoVue™ (Boston Scientific) single-use digital flexible ureteroscope and Olympus Flexible Video Ureteroscope (URV-F) was performed. To measure the carbon footprint, data were obtained on manufacturing of single-use and reusable flexible ureteroscopes and from typical uses obtained with a reusable scope, including repairs, replacement instruments, and ultimate disposal of both ureteroscopes. The solid waste generated (kg) and energy consumed (kWh) during each case were quantified and converted into their equivalent mass of carbon dioxide (kg of CO2) released. RESULTS: Flexible ureteroscopic raw materials composed of plastic (90%), steel (4%), electronics (4%), and rubber (2%). The manufacturing cost of a flexible ureteroscope was 11.49 kg of CO2 per 1 kg of ureteroscope. The weight of the single-use LithoVue and URV-F flexible ureteroscope was 0.3 and 1 kg, respectively. The total carbon footprint of the lifecycle assessment of the LithoVue was 4.43 kg of CO2 per endourologic case. The total carbon footprint of the lifecycle of the reusable ureteroscope was 4.47 kg of CO2 per case. CONCLUSION: The environmental impacts of the reusable flexible ureteroscope and the single-use flexible ureteroscope are comparable. Urologists should be aware that the typical life cycle of urologic instruments is a concerning source of environmental emissions.

Laparoscopic lens fogging: solving a common surgical problem in standard and robotic laparoscopes via a scientific model.

BACKGROUND: Laparoscopic lens fogging (LLF) hampers vision and impedes operative efficiency. Attempts to reduce LLF have led to the development of various anti-fogging fluids and warming devices. Limited literature exists directly comparing these techniques. We constructed a model peritoneum to simulate LLF and to compare the efficacy of various anti-fogging techniques. MATERIALS AND METHODS: Intraperitoneal space was simulated using a suction bag suspended within an 8 L container of water. LLF was induced by varying the temperature and humidity within the model peritoneum. Various anti-fogging techniques were assessed including scope warmers, FREDTM, ResoclearTM, chlorhexidine, betadine and immersion in heated saline. These products were trialled with and without the use of a disposable scope warmer. Vision scores were evaluated by the same investigator for all tests and rated according to a predetermined scale. Fogging was assessed for each product or technique 30 times and a mean vision rating was recorded. RESULTS: All products tested imparted some benefit, but FREDTM performed better than all other techniques. Betadine and ResoclearTM performed no better than the use of a scope warmer alone. Immersion in saline prior to insertion resulted in decreased vision ratings. The robotic scope did not result in LLF within the model. CONCLUSIONS: In standard laparoscopes, the most superior preventative measure was FREDTM utilised on a pre-warmed scope. Despite improvements in LLF with other products FREDTM was better than all other techniques. The robotic laparoscope performed superiorly regarding LLF compared to standard laparoscope.

Interpreting Prostate Multiparametric Magnetic Resonance Imaging: Urologists' Guide Including Prostate Imaging Reporting and Data System.

OBJECTIVE: To review and explain the development of multiparametric MRI and its use in prostate cancer diagnosis while educating on the implication of certain radiological findings. METHODS: The physics of magnetic resonance imaging is reviewed befor the explanation of different phase technologies in "multiparametric" scanning. Sample images of the prostate are used to display phenomena described. RESULTS: Modalities of multiparametric magnetic resonance imaging (mpMRI) of the prostate were reviewed and the interpretation of certain findings were displayed on sample images to educate clinicians about their presence and significance. CONCLUSION: Diagnosis, biopsy targeting, surveillance, operative planning and staging has led to endorsement of mpMRI and it is imperative that treating urologists have an understanding of mpMRI to appreciate the power and limitations of its findings.

Minimally invasive surgical therapies for benign prostatic hypertrophy: The rise in minimally invasive surgical therapies.

The prevalence of benign prostatic hypertrophy (BPH) causing bothersome lower urinary tract symptoms increases with our ageing population. Treatment of BPH traditionally begins with medical therapy and surgical intervention is then considered for those whose symptoms progress despite treatment. Minimally invasive surgical therapies have been developed as an intermediary in the treatment of BPH with the aim of decreasing the invasiveness of interventions. These therapies also aim to reduce morbidity and dysfunction related to invasive surgical procedures. Multiple treatment options exist in this group including mechanical and thermo-ablative strategies. Emerging therapies utilizing differing technologies range from the established to the experimental. We review the current literature related to these minimally invasive therapies and the evidence of their effectiveness in treating BPH. The role of minimally invasive surgical therapies in the treatment of BPH is still yet to be strongly defined. Given the experimental nature of many of the modalities, further study is required prior to their recommendation as alternatives to invasive surgical therapy. More mature evidence is required for the analysis of durability of effect of these therapies to make robust conclusions of their effectiveness.

Exploratory analysis of biomarkers associated with clinical outcomes from the study of lenvatinib in differentiated cancer of the thyroid.

BACKGROUND: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in the phase III Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid (SELECT) of patients with radioiodine-refractory differentiated thyroid cancer. This exploratory analysis investigated potential predictive biomarkers of lenvatinib efficacy and target engagement. PATIENTS AND METHODS: Circulating cytokine/angiogenic factors (CAFs) in blood samples collected at baseline and throughout treatment were analysed from patients randomised to receive lenvatinib or placebo from August 5, 2011 to October 4, 2012. For CAF biomarker analyses, patients were dichotomised by baseline levels. Tumour tissues were analysed for BRAF and NRAS/KRAS/HRAS mutations. RESULTS: Tumours and CAFs were analysed from 183/392 (47%) and 387/392 (99%) patients, respectively. Lenvatinib PFS benefit was maintained in all assessments. For lenvatinib-treated patients, interaction-term analyses revealed that low baseline Ang2 level was predictive of tumour shrinkage (Pinteraction = 0.016) and PFS (Pinteraction = 0.018). Vascular endothelial growth factor and fibroblast growth factor 23 (FGF23) were significantly upregulated with lenvatinib, and FGF23 upregulation on cycle 1/day 15 was associated with longer PFS. In mutation analyses, no significant differences in clinical outcomes were observed. BRAFWT may be a negative prognostic factor for PFS in placebo-treated patients with papillary thyroid cancer (P = 0.019). CONCLUSION: The lenvatinib PFS benefit was maintained regardless of baseline CAF or BRAF/RAS status. Baseline Ang2 was predictive of PFS in a subgroup of lenvatinib-treated patients, indicating that Ang2 may be predictive of lenvatinib sensitivity. BRAFWT may be a poor prognostic factor in patients with radioiodine-refractory papillary thyroid cancer. Improved PFS associated with upregulated FGF23 suggests that lenvatinib-induced FGF receptor inhibition contributes to lenvatinib efficacy. Trial registration ID of the main study, SELECT: ClinicalTrials.gov: NCT01321554.

Visual Occlusion During Minimally Invasive Surgery: A Contemporary Review of Methods to Reduce Laparoscopic and Robotic Lens Fogging and Other Sources of Optical Loss.

BACKGROUND: Maintenance of optimal vision during minimally invasive surgery is crucial to maintaining operative awareness, efficiency, and safety. Hampered vision is commonly caused by laparoscopic lens fogging (LLF), which has prompted the development of various antifogging fluids and warming devices. However, limited comparative evidence exists in contemporary literature. Despite technologic advancements there remains no consensus as to superior methods to prevent LLF or restore visual acuity once LLF has occurred. We performed a review of literature to present the current body of evidence supporting the use of numerous techniques. METHODS: A standardized Preferred Reporting Items for Systematic Reviews and Meta-Analysis review was performed, and PubMed, Embase, Web of Science, and Google Scholar were searched. Articles pertaining to mechanisms and prevention of LLF were reviewed. We applied no limit to year of publication or publication type and all articles encountered were included in final review. Limited original research and heterogenous outcome measures precluded meta-analytical assessment. RESULTS: Vision loss has a multitude of causes and although scientific theory can be applied to in vivo environments, no authors have completely characterized this complex problem. No method to prevent or correct LLF was identified as superior to others and comparative evidence is minimal. Robotic LLF was poorly investigated and aside from a single analysis has not been directly compared to standard laparoscopic fogging in any capacity. CONCLUSIONS: Obscured vision during surgery is hazardous and typically caused by LLF. The etiology of LLF despite application of scientific theory is yet to be definitively proven in the in vivo environment. Common methods of prevention of LLF or restoration of vision due to LLF have little evidence-based data to support their use. A multiarm comparative in vivo analysis is required to formally assess these commonly used techniques in both standard and robotic laparoscopes.

"Plug and Play": a novel technique utilising existing technology to get the most out of the robot.

We describe a simple technique in which current and freely available technology can be utilised by surgeons while operating the Da Vinci Si/Xi Surgical Robotic systems. This technique allows for a parallel intraoperative display within the surgical console of any desired subject material from a standard computer, utilising commercially available cabling. The ability to view 3D reconstructed images, patient radiology and patient results within the console whilst operating, has the potential to increase operative efficiency, reduce error and aid in adequate resection of tissues. The ease with which our technique is achieved, the benefits of its use and the low cost associated with its implementation support our suggestion that all robotic surgeons incorporate this into their regular operative setup.

Prostate cancer screening with prostate-specific antigen: A guide to the guidelines.

BACKGROUND: Prostate cancer remains the most common non-skin cancer malignancy in men. Prostate-specific antigen (PSA) is recognized as a biomarker for the diagnosis, monitoring, and risk prediction of prostate cancer. Its use in the setting of prostate cancer screening has been controversial due to the risk of over diagnosis and over treatment. OBJECTIVE: Within Australia, there are inconsistent recommendations surrounding the use of PSA screening in clinical practice. In light of the 2016 PSA-screening guidelines by the major Australian health authorities, the current review aims to highlight the controversies and objectively outline the current recommendations within Australia. DISCUSSION: Health-care authorities across Australia have issued conflicting guidelines for prostate cancer screening culminating in confusion amongst health care practitioners and members of the public alike. A general consensus is held by other countries across the globe but differences amongst the specific details in how to best employ a PSA screening program still exist.