Medium-term Treatment Research Articles

Interdisciplinary multimodal pain therapy: does the dose make adifference? : Acomparison from routine clinical care

Interdisciplinary multimodal pain therapy (IMPT) is an established treatment for patients with severe chronic pain. Little evidence is available on the role of treatment dosage and, in particular, on the association between the duration of IMPT and treatment outcome. The aim of this retrospective study was to compare the medium-term treatment success of ashort inpatient (SIT, 1week) and along outpatient (LOT, 4weeks) IMPT with acomparable treatment concept and comparable therapy intensity (20 h/week) in patients with severe chronic pain. Patients in both groups completed the German Pain Questionnaire at the beginning and end of IMPT as well as after 3months. Primary outcome measures included pain-related impairment and average pain intensity at follow-up in patients of comparable sex, age as well as pain intensity and impairment at the beginning of the therapy. While both groups initially showed significant treatment effects in pain-related impairment and average pain intensity, LOT patients (n = 32) reported significantly better values in both variables at 3‑month follow-up compared with SIT patients (n = 32). This was due to sustained positive effects in LOT patients and worsening in the SIT group. The results indicate that initial treatment effects can be observed in both treatment settings, but alonger duration of therapy seems to favour the long-term stability of treatment effects.

Tapering and Sustained Remission of Thrombopoietin Receptor Agonists (TPO-RAs): Is it Time for Paediatric ITP?

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.

State of the art treatment with Impella® in cardiac surgery inAustria.

Since 2022, the mechanical left ventricular support system Impella5.5® has been used in Austria for patients with cardiogenic shock, advanced heart failure, post-cardiotomy and low output syndrome. The surgical insertion of the Impella5.5 via the subclavian artery or alternatively via the ascending aorta has become an established procedure for medium-term treatment in patients with cardiogenic shock and bridging scenarios, such as bridge to recovery, bridge to left ventricular assist device (LVAD), bridge to decision, and bridge to heart transplant (HTx) in Austria. All Impella left ventricular heart pumps share the common feature of unloading the left ventricle, with the Impella5.5 achieving afull cardiac output of 5.5l/min. The stable positioning via transaxillary or transaortic insertion enables rapid extubation and mobilization of patients in the intensive care unit (ICU), leading to asignificantly shorter ICU stay. The combined support of Impella5.5 with venoarterial extracorporeal membrane oxygenation (VA-ECMO) has also proven effective in certain scenarios. Several nonrandomized studies demonstrated the effectiveness and safety of the Impella5.5 in practice, which have been included in multiple international guidelines. The advantages of the Impella5.5 in practice include the easy handling with high positional stability, and low complications rates. This article describes the significance of surgical Impella treatment in Austria from the perspective of Austrian clinical experts.

State of the art treatment with Impella® in cardiac surgery in Austria

Since 2022, the mechanical left ventricular support system Impella 5.5® has been used in Austria for patients with cardiogenic shock, advanced heart failure, post-cardiotomy and low output syndrome. The surgical insertion of the Impella 5.5 via the subclavian artery or alternatively via the ascending aorta has become an established procedure for medium-term treatment in patients with cardiogenic shock and bridging scenarios, such as bridge to recovery, bridge to left ventricular assist device (LVAD), bridge to decision, and bridge to heart transplant (HTx) in Austria. All Impella left ventricular heart pumps share the common feature of unloading the left ventricle, with the Impella 5.5 achieving a full cardiac output of 5.5l/min. The stable positioning via transaxillary or transaortic insertion enables rapid extubation and mobilization of patients in the intensive care unit (ICU), leading to a significantly shorter ICU stay. The combined support of Impella 5.5 with venoarterial extracorporeal membrane oxygenation (VA-ECMO) has also proven effective in certain scenarios. Several nonrandomized studies demonstrated the effectiveness and safety of the Impella 5.5 in practice, which have been included in multiple international guidelines. The advantages of the Impella 5.5 in practice include the easy handling with high positional stability, and low complications rates. This article describes the significance of surgical Impella treatment in Austria from the perspective of Austrian clinical experts.

Five-Year Outcomes of Bariatric Surgery vs. Conservative Weight Management in People with HIV: A Single-Center Tertiary Care Experience

IntroductionIndividuals with human immunodeficiency virus (HIV) infection now have life expectancies similar to non-infected people but face increased obesity prevalence. The long-term effects of bariatric surgery (BS) and conservative weight therapy (CWT) in patients living with HIV (PLWH) remain unexplored.MethodsA retrospective review (2012–2018) at a Tertiary Centre for Bariatric Surgery and National Centre for HIV care examined the outcomes of BS and CWT. Parameters evaluated included weight loss and HIV metrics such as viral load and CD4 count.ResultsThe study included 24 chronic HIV patients, with 10 undergoing BS (5 laparoscopic adjustable gastric banding (LAGB), 3 laparoscopic sleeve gastrectomy (LSG), 2 Roux-en-Y gastric bypass (LRYGB) and 14 in CWT. The BS group showed significant BMI reduction (− 7.07, − 6.55, − 7.81 kg/m2 at 1, 3, and 5 years). The CWT group’s BMI reduction was non-significant. The BS group’s %TWL was 16%, 17.8%, and 15% at 1, 3, and 5 years, respectively; however, stapled procedures were more effective, at 1 year, %TWL was 17% LSG and 25% RYGB, at 3 years, 23% LSG, 30% RYGB and at 5 years 21% with LSG and 28% with RYGB. HIV outcomes remained stable with undetectable viral loads in the BS group.DiscussionBS appears to be a safe and effective medium-term treatment for obesity in PLWH, providing significant weight loss whilst maintaining the efficacy of HIV treatments. Although CWT has shown modest benefits, the outcomes from BS indicate that it could be a preferable option for managing obesity in PLWH based on this limited dataset.Graphical

Safety, effectiveness, and complications of the first-in-human minimally invasive transthoracic ventricular septal defect closure using a bioabsorbable occluder: a cohort study with 12-month follow-up.

Ventricular septal defect (VSD) is one of the most common congenital heart diseases. This study aims to evaluate the clinical value and benefit of transesophageal echocardiography (TEE) in transthoracic minimally invasive closure of VSDs using a completely biodegradable occluders, summarize the main points of surgical procedures, and analyze the follow-up results of short-term and medium-term treatment. We conducted a retrospective analysis of 24 pediatric cases of VSD, successfully treated with TEE-guided minimally invasive closure using fully biodegradable occluders between June 2019 and June 2022. The preoperative TEE meticulously examined the defect's location, size, and surrounding anatomical relationships, aiding in the selection of appropriate occluders and guiding the entire closure process. All patients were followed up for 1 year. In our cohort, 13 cases were perimembranous inlet VSDs, and 11 involved VSDs with membranous aneurysm formation. The effective shunt size of VSD measured by TEE preoperatively ranged from 2.8 to 4.9 mm, with the defect located 2-6 mm from the aortic valve. Occluders used were 6-8 mm in diameter. All 24 procedures were successful. TEE confirmed that the occluders were tightly fitted at the edges of the VSDs. Twenty-three cases had no residual shunt post-surgery, while one case exhibited a small left-to-right shunt (<1.5 mm) at the occluder's edge. Follow-up was conducted on postoperative day 3, and in months 1, 3, 6, and 12, showing that the occluder's position remained normal in all patients. Except for one child who had a 1.2 mm left-to-right shunt at the edge of the occluder, no residual shunts were observed in the others. The occluder started to degrade from month 6, and the sizes of the left and right occluder discs were significantly smaller compared to those on postoperative day 3 (P=0.003). TEE-guided minimally invasive VSD occlusion using fully biodegradable occluders has the advantages of minimal trauma, high safety, and few complications, with satisfactory recent efficacy, and good prospects for clinical safety applications.

Evidências sobre fitoterapia para o tratamento da COVID-longa no âmbito da atenção primária à saúde do SUS

About 10% to 20% of patients considered cured of COVID-19 may have changes in the body that lead them to develop COVID-19. Therapeutic alternatives for treatment have been applied in post-COVID-19 clinical management, phytotherapy stands out as an important clinical path. The objective of this study was to carry out a descriptive analysis on the use and application of herbal medicines in the portion of the population affected by COVID-long. This is a narrative review, with data collection in an exploratory way by expertise in the clinical and phytotherapy area. The qualitative approach was carried out from the perspective of identifying and applying the use of herbal medicines within the scope of Primary Health Care (PHC) for the treatment of symptoms in COVID-long. The findings signal an important investigative niche for short- to medium-term treatments in long-term COVID-19. Uncaria tomentosa for cough treatment, Ginkgo biloba for cardiovascular involvement; Mangifera indica Linneaus for neuromuscular and Valeriana officinalis for the Central Nervous System. Some studies may suggest the standardization of herbal medicines in the Unified Health System for their use in PHC as an adjuvant to treatment associated with allopathic medicines.

Effectiveness of 3D visualization technologies in planning and performing reconstructive plastic surgeries in patients with elbow contractures caused by ossification

Background. Open reconstructive plastic surgeries are the most radical method of treating patients with elbow contractures caused by ossification. However, these surgeries pose a serious problem due to the large number of unsatisfactory results. The aim of the study is a comparative assessment of the effectiveness between standard techniques and 3D visualization technologies in the surgical treatment of patients with elbow contractures caused by ossification. Methods. Using random number generation, all patients (n = 71) were randomized into two groups. The first group included 34 patients with elbow contractures caused by ossification that underwent surgical intervention using 3D technologies to assess the ossification process. The second group enrolled 37 patients with a similar nosology that underwent standard examination and surgical treatment. The results were evaluated intraoperatively and 180 days after the surgery. The data were obtained from primary medical records and further survey. Results. The application of new planning technology and tactics for onstructive plastic surgeries made it possible to reduce the surgery time by 1.2 times (p0.05), reduce blood loss by 1.3 times (p0.05) and increase the relative number of patients with sufficient movement volume by 10.6% (p0.05). The assessment of various performance parameters (range of motion, pain syndrome, quality of life etc.) showed that after 6 months in the main group, the relative number of patients with problems related to the operated joint was significantly lower than in the control group: 20.5% vs 84.7% (p0.05). Conclusions. The data obtained indicate that the use of the new technique for planning and performing reconstructive plastic surgery in patients with elbow contractures caused by ossification contributes to a less invasive intervention and achievement of better intraoperative and medium-term treatment results.

PET-based radiomic feature based on the cross-combination method for predicting the mid-term efficacy and prognosis in high-risk diffuse large B-cell lymphoma patients.

This study aims to develop 7×7 machine-learning cross-combinatorial methods for selecting and classifying radiomic features used to construct Radiomics Score (RadScore) of predicting the mid-term efficacy and prognosis in high-risk patients with diffuse large B-cell lymphoma (DLBCL). Retrospectively, we recruited 177 high-risk DLBCL patients from two medical centers between October 2012 and September 2022 and randomly divided them into a training cohort (n=123) and a validation cohort (n=54). We finally extracted 110 radiomic features along with SUVmax, MTV, and TLG from the baseline PET. The 49 features selection-classification pairs were used to obtain the optimal LASSO-LASSO model with 11 key radiomic features for RadScore. Logistic regression was employed to identify independent RadScore, clinical and PET factors. These models were evaluated using receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was conducted to assess the predictive power of the models. The prognostic power of RadScore was assessed using cox regression (COX) and Kaplan-Meier plots (KM). 177 patients (mean age, 63 ± 13 years,129 men) were evaluated. Multivariate analyses showed that gender (OR,2.760; 95%CI:1.196,6.368); p=0.017), B symptoms (OR,4.065; 95%CI:1.837,8.955; p=0.001), SUVmax (OR,2.619; 95%CI:1.107,6.194; p=0.028), and RadScore (OR,7.167; 95%CI:2.815,18.248; p<0.001) independently contributed to the risk factors for predicting mid-term outcome. The AUC values of the combined models in the training and validation groups were 0.846 and 0.724 respectively, outperformed the clinical model (0.714;0.556), PET based model (0.664; 0.589), NCCN-IPI model (0.523;0.406) and IPI model (0.510;0.412) in predicting mid-term treatment outcome. DCA showed that the combined model incorporating RadScore, clinical risk factors, and PET metabolic metrics has optimal net clinical benefit. COX indicated that the high RadScore group had worse prognosis and survival in progression-free survival (PFS) (HR, 2.1737,95%CI: 1.2983, 3.6392) and overall survival (OS) (HR,2.1356,95%CI: 1.2561, 3.6309) compared to the low RadScore group. KM survival analysis also showed the same prognosis prediction as Cox results. The combined model incorporating RadScore, sex, B symptoms and SUVmax demonstrates a significant enhancement in predicting medium-term efficacy and prognosis in high-risk DLBCL patients. RadScore using 7×7 machine learning cross-combinatorial methods for selection and classification holds promise as a potential method for evaluating medium-term treatment outcome and prognosis in high-risk DLBCL patients.

Improving the Care of Severe, Open Fractures and Postoperative Infections of the Lower Extremities: Protocol for an Interdisciplinary Treatment Approach.

Patients with open fractures often experience complications during their injury. The treatments incur high costs. Interdisciplinary cooperation between different medical disciplines may improve treatment outcomes. Such cooperation has not yet been envisaged in the German health care system. The aim of the study is to improve the treatment of fractures with open soft tissue damage or postoperative complications in terms of duration and sustainability in a region in northwest Germany. Largely standardized diagnostics and therapy are intended to optimize processes in hospitals. In addition, a reduction in the duration of treatment and treatment costs is to be achieved. Using a digital platform, physicians from 31 hospitals present patient cases to an interdisciplinary group of experts from the fields of plastic surgery, infectiology, hygiene, and others. The group of experts from the environment of the University Hospital Münster promptly makes a joint treatment recommendation for the individual case. The plan is to examine 3300 patients with open fractures or surgical complications. As consortium partners, there are also 3 statutory health insurance companies. The extent to which the therapy recommendations are effective and contribute to cost reduction in the health care system will be empirically investigated in a stepped-wedge cluster-randomized design. In addition, medical and nonmedical professional groups involved in the project will be asked about their work in the project (in total, 248 clinic employees). The primary outcome is the complication rate of open fractures or the occurrence of postoperative complications. As secondary outcomes, the number of antibiotics administered, limb function, and quality of life will be assessed. The health economic evaluation refers to the costs of health services and absenteeism. For the work-related evaluation, workload, work engagement, work-related resources, readiness for technology, and ergonomic aspects of the new telemedical technology will be collected. In addition, clinic employees will give their assessments of the success of the project in a structured telephone interview based on scaled and open-ended questions. The project started in June 2022; data collection started in April 2023. As of mid-June 2024, data from 425 patients had been included. In total, 146 members of staff had taken part in the questionnaire survey and 15 had taken part in the interviews. Standardized treatment pathways in the standard care of patients with open fractures and postoperative infections will be established to reduce complications, improve chances of recovery, and reduce costs. Unnecessary and redundant treatment steps will be avoided through standardized diagnostics and therapy. The interdisciplinary treatment perspective allows for a more individualized therapy. In the medium term, outpatient or inpatient treatment centers specialized in the patient group could be set up where the new diagnostic and therapeutic pathways could be competently applied. German Clinical Trials Register DRKS00031308; https://drks.de/search/de/trial/DRKS00031308. DERR1-10.2196/57820.

Transepithelial Accelerated Crosslinking for Progressive Keratoconus: A Critical Analysis of Medium-Term Treatment Outcomes.

To report the 4-year outcomes of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) in the treatment of eyes with progressive keratoconus (KC). Eyes of patients who underwent TE-ACXL (6mW/cm2 for 15 minutes) for progressive KC and presented 48 months of follow-up were included. Corrected distance visual acuity (CDVA), keratometry measurements (Kmax, maximum keratometry, Kmean, mean keratometry and Astg, corneal astigmatism), thinnest corneal thickness (PachyMin), and topographic, and tomographic indices (specifically the posterior radius of curvature from the 3.0 mm centered on the thinnest point of the cornea (PRC), and the D-index) were analysed preoperatively and every 12 months after TE-ACXL, up to 48 months. Progression after TE-ACXL was considered when eyes presented ≥1 criteria: (1) increase of ≥1D in Kmax or increase of ≥0.75D in Kmean or increase of ≥1D in Astg; (2) reduction of ≥0.085 mm in PRC; (3) decrease ≥5% in PachyMin. 41 eyes from 30 patients were included, with a mean age at crosslinking of 20.90±4.69 years. There was a significant increase in Kmean (+0.64±1.04 D, p<0.001; +0.98 ± 1.49 D, p<0.001; +1.27±2.01 D, p<0.001; +1.13±2.00 D, p=0.006) and a significant decrease in PRC throughout follow-up (-0.12±0.22, p=0.002; -0.15±0.24, p<0.001; -0.17±0.43, p=0.021; -0.16±0.43, p=0.027). PachyMin decreased significantly at 36 and 48 months (-8.50±15.93 μm, p=0.004; -7.82±18.37, p=0.033). According to our progression criteria, there was a major progression rate throughout follow-up (57.1%, 61.1%, 58.8%, and 67.9%, respectively). Surgery and follow-up were uneventful in all subjects. Eleven eyes (26.8%) required further procedures, ≥36 months after the initial TE-ACXL, due to persistent progressive disease. TE-ACXL proved to be a safe therapeutic option for progressive KC. However, its efficacy is deemed unsatisfactory, as a notable proportion of affected eyes may continue to advance within a 4-year timeframe, necessitating additional procedures to halt the disease's course.

Finding predictors for successful opioid response in cancer patients: An analysis of data from four randomized controlled trials.

There is no consensus on which "strong" (or step 3 WHO analgesic ladder) opioid to prescribe to a particular patient with cancer-related pain. A better understanding of opioid and patient characteristics on treatment response will contribute to a more personalized opioid treatment. Assessment of potential predictors for successful opioid treatment response in patients with cancer pain. An international partnership between four cancer pain research groups resulted in a combined individual-level database from four relevant randomized controlled trials (RCTs; n = 881). Together, these RCTs investigated the short-term (1 week) and medium-term (4 or 5 weeks) treatment responses for morphine, buprenorphine, methadone, oxycodone, and fentanyl. Candidate predictors for treatment response were sex, age, pain type, pain duration, depression, anxiety, Karnofsky performance score, opioid type, and use of anti-neuropathic drug. Opioid type and pain type were found statistically significant predictors of short-term treatment success. Sex, age, pain type, anxiety, and opioid type were statistically, significantly associated with medium-term treatment success. However, these models showed low discriminative power. Fentanyl and methadone, and mixed pain were found to be statistically significant predictors of treatment success in patients with cancer-related pain. With the predictors currently assessed our data did not allow for the creation of a clinical prediction model with good discriminative power. Additional - unrevealed - predictors are necessary to develop a future prediction model.

Short-Term and Medium-Term Radiological and Clinical Assessment of Patients with Symptomatic Flexible Flatfoot Following Subtalar Arthroereisis with Spherus Screw.

There have been no reports on arthroereisis screw insertion into the talus in patients with flexible flatfoot. We aimed to conduct a clinical and radiological assessment in patients with symptomatic pes planovalgus deformity treated with a talar screw. This study involved a prospective assessment of 27 patients treated surgically for symptomatic flexible flatfoot deformity in the period 2021-2022. The following parameters were assessed in this study: Meary's angle, the Costa-Bartani angle, the calcaneal pitch angle, surgery duration, the length of hospital stay, patient satisfaction, patients' retrospective willingness to consent to the treatment they received, postoperative complications, and the use of analgesics. The mean follow-up period was 14.76 months. Meary's angle decreased from 18.63° before surgery to 9.39° at follow-up (p = 0.004). The Costa-Bartani angle decreased significantly from 154.66° before surgery to 144.58° after surgery (p = 0.012). The calcaneal pitch angle changed from 16.21° before to 19.74°. Complications were reported in three patients (11.11%). The mean surgery duration was 32 min. The mean hospital stay was 2.2 days. Fourteen patients (51.85%) were highly satisfied with the treatment, and 12 patients (44.44%) were quite satisfied with treatment. Twenty-five (92.59%) of the evaluated patients would choose the same type of treatment again. Six patients (22.22%) needed to use analgesics prior to surgical treatment, whereas none of the patients needed to use them by the final follow-up. Spherus screw arthroereisis helps improve radiological parameters in patients with flexible flatfoot. We observed good clinical outcomes after treatment with a talar screw, with a majority of patients reporting moderate-to-high levels of satisfaction with treatment. Both short- and medium-term treatment outcomes of pes planovalgus treatment with the use of Spherus screw are good.

Pharmacokinetics, efficacy, and safety of cannabidiol in dogs: an update of current knowledge.

In the last 5 years, interest has grown in using phytocannabinoids, particularly cannabidiol (CBD), in veterinary medicine to treat several pathologies, including pain, epilepsy, anxiety, nausea, anorexia, skin lesions, and even some types of cancer, among others. Indeed, due to a positive perception of CBD use, many pet owners are increasingly requesting this option to relieve their pets, and many veterinarians are exploring this possibility for their patients. Besides the widespread empiric use of CBD in pets, the research is trying to obtain proof of its efficacy and lack of adverse effects and to know its pharmacokinetics to define an appropriate posology. This review summarizes all data published so far about the canine pharmacokinetics, efficacy, and tolerability of CBD and cannabidiolic acid (CBDA). Despite a certain number of available pharmacokinetic studies, the kinetic profile of CBD has yet to be fully known, probably because of the very different experimental conditions. In terms of efficacy, most studies have tested CBD' ability to relieve osteoarthritic pain. In contrast, few studies have evaluated its role in epilepsy, behavioral disorders, and skin lesions. From obtained results, some evidence exists supporting the beneficial role of CBD. Nevertheless, the limited number of published studies and the occurrence of bias in almost all require caution in interpreting findings. From tolerability studies, CBD' side effects can be classified as mild or unremarkable. However, studies were prevalently focused on short- to medium-term treatment, while CBD is usually employed for long-term treatment. Further studies are warranted to define better whether CBD could be a valid adjunct in canine treatment.

MP55-20 OUTCOMES OF PRIMARY CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: 14-YEARS SINGLE INSTITUTION EXPERIENCE

You have accessJournal of UrologyCME1 May 2022MP55-20 OUTCOMES OF PRIMARY CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: 14-YEARS SINGLE INSTITUTION EXPERIENCE Andrew Wang, Greg Mansour, and Robert Given Andrew WangAndrew Wang More articles by this author , Greg MansourGreg Mansour More articles by this author , and Robert GivenRobert Given More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cryoablation, a minimally invasive ablative therapy, is recommended as an alternative treatment for localized prostate cancer (PCa) given its favorable side effect profiles on bladder and bowel function, especially in those with low- and intermediate-risk disease who are not suitable for surgery or radiation therapy. Long-term outcomes are not well characterized in the literature. We aim to report our experience with the procedure at our institution. METHODS: We retrospectively reviewed all men who underwent primary whole-gland cryoablation for localized prostate cancer at our institution from 2005 through 2019. Functional and oncologic outcomes were assessed. Recurrence-free survival was studied using Kaplan-Meier survival analysis. RESULTS: Of the 276 patients, 80% had D’Amico high- (22.8%) or intermediate- (57.6%) risk disease. Average age was 71.2 years while median follow-up was 4.7 years. Majority of the patients (83%) achieved prostate-specific antigen (PSA) nadir <0.4 ng/ml. This was associated with improved disease-free survival (p <0.00001). De novo incontinence (2%) and De novo ED rates (12%) were relatively low, and complications such as urethral stricture (n=1) and rectal urethral fistula (n=0) were extremely rare. 5 year clinical recurrence-free survival was 70% overall and 94% for low-, 86% for intermediate-, and 63% for high-risk patients in our cohort. CONCLUSIONS: Primary whole-gland cryoablation is a safe and durable medium-term treatment alternative to radiation therapy and radical prostatectomy for patients with low- and intermediate risk disease. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e946 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Wang More articles by this author Greg Mansour More articles by this author Robert Given More articles by this author Expand All Advertisement PDF DownloadLoading ...

155 Effects on sacubitril/valsartan on natriuretic peptides in patients with a reduced ejection fraction

Abstract Aims The PARADIGM-HF trial proved the superiority of sacubitril/valsartan (Sa/Va) vs. enalapril in reducing mortality and hospitalization for heart failure (HF). Sacubitril/valsartan, new drug used in treatment of heart failure with reduced systolic function (HFrEF) has recently been shown to improve tolerance to exercise and cardiovascular performance. Methods and results We prospectively enrolled 40 outpatient patients with HFrEF with indication for therapy with sacubitril/valsartan and subjected to serial controls with blood tests, echocardiogram before and during gradual optimization of therapy, with the aim of evaluating the effects of the drug on left ventricular remodelling. We studied 40 patients treated with sacubitril/valsartan for at least 3 months. After a mean follow-up of 120 ± 40 days, 95% of patients reached the maximum dose of the drug without major side effects. The ejection fraction increased while end-diastolic and end-systolic volumes of the left ventricle decreased. We also observed a significant reduction in NT-proBNP values without significant worsening of renal function or hyperkalaemia. There NYHA functional class has improved with a positive impact on the prognosis of heart failure at 2 years (P = 0.006). Conclusions In our population, medium-term treatment with sacubitril/valsartan demonstrated a favourable effect on left ventricular remodelling and functional status, confirming the data of previous clinical trials in real life. One more follow-up long and a larger population will help confirm these to confirm these positive effects of the drug on patients with HfrEF.

Chronic Obstructive Pulmonary Disease as a Phenotype of Bronchiectasis for Long-Term Clinical Presentation and Treatment.

Background and Objectives: Bronchiectasis and chronic obstructive pulmonary disease (COPD) often coexist, although the causality is not currently clear. Currently, the clinical influence of COPD on patients with major bronchiectasis over time has not yet been investigated. Material and Methods: This retrospective study recruited consecutive patients with bronchiectasis from outpatient clinic between January 2006 and December 2007. Under the setting of quantification with HRCT, patients who should undergo multiple pulmonary function and exercise tests with regularclinic follow-up were included. The final analysis consisted of 66 eligible patients who were evaluated for clinical status, treatment, and sputum culture from up to 10-year electronic medical records. Results: Of these 66 patients, 45 (68%) had bronchiectasis without COPD and 21 (32%) had COPD. Patients with COPD group had a higher bronchiectasis extent score (32.21 ± 13.09 points vs. 21.89 ± 10.08 points, p = 0.001). Sputum production was reported more frequently by patients with COPD; however, no significant difference was observed after 3 years of follow-up (82.4% vs. 81.6%, p = 0.945). Bronchiectasis extent score correlated with positive sputum culture with Pseudomonas without a synergistic effect from COPD (odds ratio: 1.06, confidence interval: 1.00–1.12, p = 0.031). Regardless of COPD, after 10 years, the proportion of patients using inhaled corticosteroids and/or long-acting β2-agonist between the two groups was not significantly different. Conclusion: COPD aggravated bronchiectasis extension, which was correlated with chronic Pseudomonas aeruginosa colonisation. Moreover, COPD would affect the medium-term (in 3–5 years) bronchiectasis treatment. Therefore, the COPD phenotype of bronchiectasis could be a clinical predictor of the course of treatment.

Recombinant human DNase I for the treatment of cancer-associated thrombosis: A pre-clinical study

Cancer patients are more likely to develop thrombosis, and this co-morbidity is related to the worse prognosis of the disease. The increased formation of neutrophil extracellular traps (NETs) has been proposed as one of the mechanisms to explain cancer-associated thrombosis. In vivo, degradation of NETs with recombinant human DNase I (rhDNase I) prevents thrombus formation in mouse models. In this work, we evaluated the effect of two different chronic treatments with rhDNase I in a murine NET-dependent prothrombotic state in breast cancer model. Medium-term treatment (2.5 mg/kg rhDNase I for eight consecutive days) did not interfere with the primary growth of 4T1 tumors. On the other hand, it effectively prevented thrombus formation in the inferior vena cava stenosis model. Remarkably, medium-term treatment with rhDNase I showed minor impact in the tail-bleeding model. Different from the medium-term, the long-term treatment with rhDNase I (2.5 mg/kg for 18 successive days) drastically reduced the overall survival. Remarkably, the concomitant use of Ertapenem, a carbapenem antibiotic, and rhDNase I significantly attenuated the mortality observed in the long-term treatment. Our results suggest the therapeutic potential of rhDNase I to treat cancer-associated thrombosis, although its chronic use should be carefully evaluated and potentially harmful.

Can road user delays at urban railway level crossings be reduced? Evaluation of potential treatments through traffic simulation

Railway level crossing closures can disrupt traffic flow significantly, especially in peak hours. The current increases in road and rail traffic worsen the situation and can result in congestion known to significantly increase road users’ travel times. In this study, seven of the most problematic level crossings around Brisbane, Australia, were surveyed. The effectiveness of a set of treatments was tested and discussed using computer simulation models. The study found that the variability of warning times is the major cause of unnecessary boom gate downtime. Our observations showed that warning times could be reduced by 10–40 s on average for each crossing activation at the investigated sites. A major cause for the variability in warning times are trains stopping at stations that are not equipped with express train identification, and actual train speeds being lower than posted line speeds. Various tested treatments were found to be effective at reducing level crossing closure duration and reducing the variability in warning times, resulting in travel times reducing by 7–57% for road users, depending on the level crossing considered. This study shows the potential for the short to medium-term treatment of congestion issues at active level crossings, which are necessary with the current increased rail and road traffic flows.

Clinical Trials Required to Assess Potential Benefits and Side Effects of Treatment of Patients With Anorexia Nervosa With Recombinant Human Leptin.

The core phenotype of anorexia nervosa (AN) comprises the age and stage dependent intertwining of both its primary and secondary (i.e., starvation induced) somatic and mental symptoms. Hypoleptinemia acts as a key trigger for the adaptation to starvation by affecting diverse brain regions including the reward system and by induction of alterations of the hypothalamus-pituitary-“target-organ” axes, e.g., resulting in amenorrhea as a characteristic symptom of AN. Particularly, the rat model activity-based anorexia (ABA) convincingly demonstrates the pivotal role of hypoleptinemia in the development of starvation-induced hyperactivity. STAT3 signaling in dopaminergic neurons in the ventral tegmental area (VTA) plays a crucial role in the transmission of the leptin signal in ABA. In patients with AN, an inverted U-shaped relationship has been observed between their serum leptin levels and physical activity. Albeit obese and therewith of a very different phenotype, humans diagnosed with rare congenital leptin deficiency have starvation like symptoms including hypothalamic amenorrhea in females. Over the past 20 years, such patients have been successfully treated with recombinant human (rh) leptin (metreleptin) within a compassionate use program. The extreme hunger of these patients subsides within hours upon initiation of treatment; substantial weight loss and menarche in females ensue after medium term treatment. In contrast, metreleptin had little effect in patients with multifactorial obesity. Small clinical trials have been conducted for hypothalamic amenorrhea and to increase bone mineral density, in which metreleptin proved beneficial. Up to now, metreleptin has not yet been used to treat patients with AN. Metreleptin has been approved by the FDA under strict regulations solely for the treatment of generalized lipodystrophy. The recent approval by the EMA may offer, for the first time, the possibility to treat extremely hyperactive patients with AN off-label. Furthermore, a potential dissection of hypoleptinemia-induced AN symptoms from the primary cognitions and behaviors of these patients could ensue. Accordingly, the aim of this article is to review the current state of the art of leptin in relation to AN to provide the theoretical basis for the initiation of clinical trials for treatment of this eating disorder.