Adjunctive Medical Therapy Research Articles

Adenomyosis: A potential cause of surgical failure in treating dyspareunia in rectovaginal septum endometriosis.

Dyspareunia can severely impact the quality of life of patients with endometriosis. This symptom is often linked to a specific form of deep infiltrating endometriosis, such as rectovaginal septum endometriosis. Despite the radicality of surgery, persistence and recurrence of symptoms post-surgery are not uncommon. The aim of the present study was to determine whether adenomyosis contributes to the failure of surgical interventions for dyspareunia in these patients. A retrospective single-cohort study was conducted at the at tertiary care gynecologic center of the University Federico II of Naples, using medical records from January 2020 to July 2023. The study included patients who underwent surgery for dyspareunia associated with rectovaginal endometriosis and had a definitive histologic diagnosis. Pain and sexual quality of life were assessed using the visual analog scale (VAS) and the sexual quality of life-female (SQoL-F) questionnaire, both before and 6 months after surgery. Patients with isolated rectovaginal endometriosis were compared to those with concurrent adenomyosis. A total of 94 patients were included: thirty-five in group A (endometriosis with adenomyosis) and 59 in group B (isolated rectovaginal endometriosis). Histology confirmed deep infiltrating endometriosis (DIE) in all patients. Clinical characteristics such as age, BMI, abnormal uterine bleeding, and infertility, showed no significant differences between the groups. Multiparity was more common in group A (20%) compared to group B (5.1%) (P < 0.001). Pain VAS scores decreased significantly in both groups: from 7.11 to 5.40 in group A and from 7.34 to 3.31 in group B (both P < 0.001). Sexual quality of life (SQoL) scores improved significantly: from 42 to 57 in group A and from 41 to 66 in group B (both P < 0.001). Patients in group B showed a more significant improvement. Adjusted linear regression showed no significant association between parity and the severity of dyspareunia or sexual quality of life. Adenomyosis appears to reduce the effectiveness of surgical treatment for dyspareunia in patients with rectovaginal septum endometriosis. Comprehensive preoperative screening for adenomyosis is recommended to improve surgical outcomes and provide appropriate counseling. Future research should further explore the impact of adenomyosis on dyspareunia and the potential benefits of adjunctive medical therapies.

6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone

Abstract Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None. Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value &amp;lt;0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value &amp;lt;0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population. Presentation: 6/3/2024

The FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial: Study Design.

To report the design of FL uorometholone as A djunctive ME dical Therapy for TT Surgery (FLAME) Trial. Parallel design, double-masked, placebo-controlled clinical trial with 1:1 randomization to fluorometholone 0.1% eyedrops twice daily or placebo twice daily for four weeks in eyes undergoing trachomatous trichiasis (TT) surgery; assessing the efficacy, safety, and cost-effectiveness of fluorometholone 0.1% in preventing recurrent postoperative trichiasis. Up to 2500 eligible persons with trachomatous trichiasis (TT) undergoing lid rotation surgery will be enrolled in Jimma zone, Ethiopia. Participants, surgeons, study field staff, and study supervisors leading operational aspects of the trial are masked to treatment assignment. Randomization is stratified by surgeon, which simultaneously stratifies by the district. The study visits are at baseline/enrollment, at four-week post-enrollment, six months, and one year (study exit). The primary outcome is cumulative one-year postoperative TT (PTT) incidence, defined as: ≥1 lashes touching the globe, evidence of epilation, and/or repeat TT surgery. Secondary postoperative outcomes include number of trichiatic lashes, location thereof (touching the cornea or not), evidence of post-operative epilation, entropion, changes in corneal opacity, IOP elevation, need for cataract surgery, visual acuity change from baseline, eyelid contour abnormality, granuloma, eyelid closure defect, and occurrence of adverse events. Health economic analyses center on calculating the incremental cost per case of PTT avoided by fluorometholone treatment. The FLAME Trial is designed to provide evidence of the efficacy, safety, and cost-effectiveness of adjunctive topical peri-/postoperative fluorometholone 0.1% therapy with trichiasis surgery, which is hypothesized to reduce the risk of recurrent trichiasis while being acceptably safe. Trial Registration: ClinicalTrials.gov # NCT04149210.

Association of Crohn's disease and ulcerative colitis with the risk of neurological diseases: a large-scale Mendelian randomization study.

Observational studies suggested increased risks of Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the causality for the associations of CD and UC with the risks of AD, PD, and MS through a two-sample Mendelian randomization (MR) study. Independent single nucleotide polymorphisms associated with CD (17,897 cases and 33,977 controls) and UC (13,768 cases and 33,977 controls) were identified as genetic instruments based on a European-descent genome-wide association study (GWAS) released by the International Inflammatory Bowel Disease Genetics Consortium. Summary statistics for AD (combined: 25,881 cases and 256,837 controls), PD (combined: 35,836 cases and 665,686 controls), and MS (combined: 48,477 cases and 285,515 controls) were obtained from the largest GWASs and FinnGen study of European ancestry, respectively. MR estimates were generated using the inverse-variance weighted method in the main analysis with a series of sensitivity analyses. MR analyses were conducted per outcome database and were subsequently meta-analyzed to generate combined estimates. Genetically predicted UC was significantly associated with increased risks of AD (combined: OR, 1.03; 95% CI, 1.01-1.05; P = 1.80 × 10-3) and MS (combined: OR, 1.37; 95% CI, 1.23-1.53; P = 1.18 × 10-8), while there was no association between genetically predicted UC and the risk of PD. In contrast, no significant associations were observed for genetically predicted CD with AD, PD, and MS. MR-Egger regression showed no directional pleiotropy for the identified associations, and sensitivity analyses with different MR methods further confirmed these findings. This study suggested significant adverse effects of UC on AD and MS, highlighting that UC patients should receive early intervention with optimal adjunctive medical therapy to reduce the risks of AD and MS.

The Impact of Adjunct Medical Therapy on Survival after Spine Metastasis: A Systematic Review and Pooled Data Analysis.

Targeted therapy has greatly improved the outlook for patients with spinal metastatic cancers. Scoring systems like the Tokuhashi or Tomita scores are commonly used to predict prognosis and inform surgical decisions, but they are outdated and fail to consider recent advancements. We aimed to investigate the current state of the literature and treatment options pertaining to advancements in targeted therapy compared to other forms of medical management for metastatic spinal tumors. This study represents the first comprehensive systematic review that encompasses the most common primary cancers that metastasize to the spine and evaluates the median overall survival (mOS) across five different medical treatment modalities as well as surgical intervention. Additionally, our study analyzes the tumor receptor status in conjunction with these treatments. A PubMed search was conducted, and according to the PRISMA guidelines, 28 articles out of 1834 met the inclusion criteria. The pooled data analysis highlighted the superior efficacy of targeted therapy, evidenced by a significant improvement in the mOS and lower hazard ratios in patients with lung and breast cancers who received targeted therapy compared to those who did not. Our study provides valuable insights into the recent advancements in the medical management of metastatic spinal tumors. Future indications include incorporating this literature into personalized treatment approaches for metastatic spinal tumors.

Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.

Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Ocular Surface Squamous Neoplasia: Changes in the Standard of Care 2003 to 2022.

The aim of this review was to elucidate treatment preferences for ocular surface squamous neoplasia and to examine the changes in treatment modalities over the past 2 decades. An electronic survey was distributed to members of The Cornea Society, Ocular Microbiology and Immunology Group, and 4 international corneal specialist listservs. Questions examined medical and surgical treatment preferences, and results were compared with surveys administered in 2003 and 2012. A total of 285 individuals responded to the survey; 90% of respondents were self-classified as corneal specialists. Seventy-three percent reported using primary topical monotherapy to treat ocular surface squamous neoplasia as compared with 58% in 2012 ( P = 0.008). Compared with 2003, the percentage use of topical interferon significantly increased ( P < 0.0001) from 14% to 55%, 5-fluorouracil increased ( P < 0.0001) from 5% to 23%, and mitomycin C decreased ( P < 0.0001) from 76% to 19% as a primary monotherapy. The frequency of performing excision without the use of postoperative adjunctive medical therapy decreased significantly ( P < 0.0001), from 66% to 26% for lesions <2 mm, 64% to 12% for lesions between 2 and 8 mm, and 47% to 5% for lesions >8 mm from 2003 to 2022. More clinicians initiated topical immuno/chemotherapy without performing a biopsy as compared to 2003 (31% vs. 11%, P < 0.0001). These results demonstrate a paradigm shift in the management of ocular surface squamous neoplasia. The use of primary medical therapy as a first approach has significantly increased, with a reduction in the frequency of performing surgical excision alone.

The Impact of Gastroparesis on Medical Therapy for Gastroesophageal Reflux Disease

Symptoms suspicious for gastroesophageal reflux disease (GERD) represent frequent indications for medical presentation, as do symptoms potentially compatible with delayed gastric emptying. In this clinical setting, care must be taken to characterize patient symptoms accurately, and also appropriately evaluate for pathophysiologic processes including visceral hypersensitivity, rumination syndrome, supragastric belching, cannabinoid hyperemesis, and cyclic vomiting syndrome. While proton pump inhibitors (PPI) are the foundation of medical management of GERD, delayed gastric emptying is a downstream factor that can promote gastroesophageal reflux and warrants tailored clinical management. Specifically, patients with refractory symptoms in the setting of GERD and delayed gastric emptying may benefit from personalized adjunct medical therapy with prokinetics.

Abstract PO-099: Short-term outcomes of an extended endoscopic endonasal resection of a clival giant cell tumor with adjuvant RANK-L inhibitor therapy: Case report

Abstract Background Clival giant cell tumors (GiCT) are rare neoplasms that commonly target the epiphysis. Recently, skull base GiCTs have been reported, predominantly in the sphenoid and temporal bones. Although typically benign, GiCTs of the skull-base can cause neurologic deficits due to compression of cranial nerves or intracranial contents. The efficacy of adjuvant chemotherapy in treating GiCTs is not known. One potential treatment option neoplastic mononuclear stromal cells in GiCTs express NF-κB ligands (RANK-L), which can be therapeutically targeted with Denosumab, a monoclonal antibody against RANK-L. Here, we describe the case of a GiCT invasive to the clivus, an extended endoscopic endonasal resection of the tumor, and management of the lesion with Denosumab. Methods A retrospective chart review was performed on the patient of interest. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were used to assess disease growth and response to surgical and therapeutic intervention. Case presentation A previously healthy seventeen-year-old female presented with headaches and numbness of the left V2 and V3. A diagnosis of a clival giant cell tumor was confirmed with strict pathologic, radiographic, and clinical correlation. She was found to have a clival mass extending into the sphenoid sinus. Surgical excision was performed by both the otolaryngology and neurosurgery departments at a single institution. She underwent an extended endoscopic endonasal resection of the clival mass. Following surgery, the numbness on the left V2 and V3 distribution improved. She occasionally reported bilateral V3 distribution symptoms without definite anatomic correlates for right sided complaints. Due to the presence of residual tumor, we recommended adjunctive medical therapy. We performed adjunctive medical therapy with Denosumab, a RANKL inhibitor. Discussion When complete surgical excision with negative margins is not feasible in lesions of the skull base, adjuvant treatment is commonly required to achieve local disease control. Our case demonstrates the efficacy of a combined approach where surgery is used to achieve a histologic diagnosis, decompression and evaluate for respectability. Adjuvant medical therapy using RANKL inhibitors is a promising approach that may be effective to achieve lifelong disease control but requires continued maintenance on therapy. Citation Format: Myra A. Zaheer, Abhisri Ramesh, Aadit P. Mehta, Adriana S. Fonseca, Daniel A. Donoho. Short-term outcomes of an extended endoscopic endonasal resection of a clival giant cell tumor with adjuvant RANK-L inhibitor therapy: Case report [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-099.

Non-tuberculous mycobacterial skin and soft tissue infections in the Northern Territory, Australia, 1989-2021

BackgroundA previous review demonstrated that the majority of NTM infections in the Northern Territory (NT) are pulmonary in nature [1], however skin and soft tissue (SST) are likely the next most common sites of disease. The current epidemiology of NTM SST infections across the NT is not known. We aimed to establish the current and historical incidence rates, and the organisms involved. MethodsAll NTM cases reported to the Centre for Disease Control in Darwin from 1989-2021 were retrospectively reviewed. Results226 NTM notifications were reviewed. 73 (32%) cases were SST infections. The incidence of SST cases increased over the study period. Female cases were more common (p=0·002). Disease occurred across a wide age range (1-85 years). Only 16% of cases occurred in Aboriginal individuals which may reflect immunological factors requiring further investigation. Many cases had no clear provocation, but localised skin trauma was the most common risk factor. The most common organism identified was M. fortuitum (41%). Diagnosis was often delayed, with a median time to diagnosis of 69 days (IQR=31-149). Most cases (60%) underwent surgical intervention with adjunctive anti-mycobacterial medical therapy. ConclusionNTM SST incidence rates increased over the study period. NTM SST infections are a rare but important differential diagnosis for non-healing cutaneous wounds.

Management of patients with chronic mesenteric ischemia across three consecutive eras

BackgroundEndovascular intervention (EI) is the most commonly used modality for chronic mesenteric ischemia (CMI). Since the inception of this technique, numerous publications have reported the associated clinical outcomes. However, no publication has reported the comparative outcomes over a period of time in which both the stent platform and adjunctive medical therapy have evolved. This study aims to assess the impact of the concomitant evolution of both the endovascular approach and optimal guideline-directed medical therapy (GDMT) on CMI outcomes over three consecutive time eras. MethodsA retrospective review at a quaternary center from January 2003 to August 2020 was performed to identify patients who underwent EIs for CMI. The patients were divided into three groups based on the date of intervention: early (2003-2009), mid (2010-2014), and late (2015-2020). At least one angioplasty/stent was performed for the superior mesenteric artery (SMA) and/or celiac artery. The patients' short- and mid-term outcomes were compared between the groups. Univariable and multivariable Cox proportional hazard models were also conducted to evaluate the clinical predictors for primary patency loss in SMA only subgroup. ResultsA total of 278 patients were included (early, 74; mid, 95; late, 109). The overall mean age was 71 years, and 70% were females. High technical success (early, 98.6%; mid, 100%; late, 100%; P = .27) and immediate resolution of symptoms (early, 86.3%; mid, 93.7%; late, 90.8%; P = .27) were noted over the three eras. In both the celiac artery and SMA cohorts, the use of bare metal stents (BMS) declined over time (early, 99.0%; mid, 90.3%; late, 65.5%; P < .001) with a proportionate increase in covered stents (CS) (early, 0.99%; mid, 9.7%; late, 28.9%; P < .001). The use of postoperative antiplatelet and statins has increased over time (early, 89.2%; mid, 97.9%; late, 99.1%; P = .003) and (early, 47%; mid, 68%; late, 81%; P = .001), respectively. In the SMA stent-only cohort, no significant differences were noted in primary patency rates between BMS and CS (hazard ratio, 0.95; 95% confidence interval, 0.26-2.87; P = .94). High-intensity preoperative statins were associated with fewer primary patency loss events compared to none/low- or moderate-intensity statins (hazard ratio, 0.30; 95% confidence interval, 0.11-0.72; P = .014). ConclusionsConsistent outcomes were observed for CMI EIs across three consecutive eras. In the SMA stent-only cohort, no statistically significant difference in early primary patency was noted for CS and BMS, making the use of CS at additional cost controversial and possibly not cost effective. Notably, the preoperative high-intensity statins were associated with improved SMA primary patency. These findings demonstrate the importance of guideline-directed medical therapy as an essential adjunct to EI in the treatment of CMI.

Laughter as medicine: A systematic review and meta-analysis of interventional studies evaluating the impact of spontaneous laughter on cortisol levels.

Laughter as an expression of humor has been recognized as good medicine for centuries. The health benefits of humor-induced well-being remain unclear and thus we conducted a systematic review and meta-analysis of interventional studies to evaluate the impact of spontaneous laughter on stress response as measured by cortisol levels. Systematic review and meta-analysis. MEDLINE/PubMed, EMBASE, PsycINFO, Scopus, and Clinicaltrials.gov. Interventional studies, which could be either randomized placebo-controlled trials (RCTs) or quasi-experimental studies, conducted in adults that compared any spontaneous laughter intervention to a controlled setting and reported changes in cortisol levels were selected. We examined the impact of laughter on percentage change in cortisol levels by calculating pooled estimates of the absolute differences between arithmetic means before and after interventions as compared to control using random-effects model. Eight studies (315 participants; mean age 38.6) met our inclusion criteria; four were RCTs and four were quasi-experiment studies. Five studies evaluated the impact of watching a humor/comedy video, two studies evaluating laughter sessions administered by a trained laughter therapist, and one study evaluating a self-administered laughter program. Pooling these data showed a significant reduction in cortisol levels by 31.9% (95%CI -47.7% to -16.3%) induced by laughter intervention compared to control group with no evidence of publication bias (P = 0.66). Sensitivity analyses demonstrated that even a single laughter session induced a significant reduction of 36.7% in cortisol (95%CI -52.5% to -20.8%). In addition, analyses including the four RCTs reinforced these results by demonstrating a significant reduction in cortisol levels promoted by laughter as compared to the placebo arm [-37.2% (95%CI -56.3% to -18.1%)]. Current evidence demonstrates that spontaneous laughter is associated with greater reduction in cortisol levels as compared with usual activities, suggesting laughter as a potential adjunctive medical therapy to improve well-being. Registration number: CRD42021267972.

Evaluation of the safety and efficacy of a Polyzene-F nanocoated coronary stent system: A systematic review and single-arm meta-analysis.

A stent for patients with coronary heart disease (CHD) provides a requirement for a long-term antiplatelet therapy because of the high possibility of the development of stent thrombosis. It was against this background that both Cobra and Catania Polyzene-F (PzF) stents were designed to reduce the occurrence of stent thrombosis (ST). In this study, we review the safety and effectiveness of a PzF-nanocoated stent. This systematic review with the title was registered in PROSPERO (No.398781). The inclusion criteria were including studies among patients with PzF-nanocoated coronary stents and reported target vessel failure (TVF) and ST as the outcomes, and the exclusion criteria were excluding reported patients who could not receive the adjunctive medical therapies or without the necessary endpoints. Reports about PzF-nanocoated stents were searched in PubMed, Embase, and Web of Science and other sources. Because of the existence of few reports and a lack of comparison groups, a single-arm meta-analysis was conducted in R software (v3.6.2), using a random-effects model with the generic inverse variance method. After a heterogeneity test, assessment of evidence quality was conducted by using GRADE software. A funnel plot Egger's test was performed to evaluate publication bias, and a sensitivity analysis was done to determine the robustness of the overall effects. Six studies of 1,768 subjects were included. The primary endpoint that pooled the TVF rate was 8.9% (95% CI 7.5%-10.2%), which comprised the pooled cardiac death (CD) rate (1.5%, 95% CI 0%-3%), myocardial infarction (MI) rate (2.7%, 95% CI 0.4%-5.1%), target vessel revascularization (TVR) (4.8%, 95% CI 2.4%-7.2%), or target lesion revascularization (TLR) (5.2%, 95% CI 4.2%-6.4%), while the secondary endpoint ST was 0.4% (95% CI 0.1%-0.9%). The funnel plots of TVF, CD, TVR, and TLR did not show any serious publication bias, and TVF, TVR, and TLR showed evidence of moderate quality in GRADE assessment. The sensitivity analysis showed that TVF, TLR, and ST exhibited good stability (I 2 = 26.9%, 16.4%, and 35.5%, respectively), while the other endpoints showed moderate instability. These data indicated that the PzF-nanocoated coronary stents of the Cobra and Catania systems demonstrated good safety and efficacy in clinical application. However, the sample size of patients included in the reports was relatively small, and this meta-analysis will be updated if more studies are published in the future. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023398781.

Distal üreter taşı olan hastalarda taş düşürmede medikal ekspulsif tedavi olarak tamsulosinin silodosine karşı etkinliği: Geriye dönük tek merkezli bir çalışma

Objective: This study aimed to compare the efficacy of tamsulosin and silodosin as medical expulsive therapy in patients with symptomatic uncomplicated distal ureteric stones. Material and Methods: The data of adult patients who had distal ureteric stones in size between 4 and 10 mm and were treated with medical expulsive therapy between June 2019 and January 2022 were retrospectively documented. Patients were divided into two groups. Patients in Group 1 received silodosin 4 mg, and Group 2 received tamsulosin 0.4 mg. Therapy was given for a maximum of 3 weeks. Stone expulsion rate, time to stone expulsion, stone burden, and stone size were recorded. The efficacy of tamsulosin and silodosin as adjunctive medical therapy was determined. Results: A total of 152 patients were included in the study. Demographic profiles were comparable between the 2 groups. 116 (76.3%) patients were stone-free at the end of the follow-up. The stone expulsion rate was calculated in 47 patients (73.4%) in Group 1, and 69 patients (78.4%) in Group 2 (P = 0.477). The distance of the stone to the ureterovesical junction was significantly associated with successful stone expulsion in multivariate analysis (P=0.032). Conclusion: There was no significant superiority between tamsulosin and silodosin as medical expulsive therapy for distal ureteral stones. The distance of the stone to the ureterovesical junction was the only independent predictor of stone expulsion in multivariate analysis. Keywords: Medical expulsive therapy,

Diagnostic and Therapeutic Strategies for Stable Coronary Artery Disease Following the ISCHEMIA Trial.

Until recently, coronary revascularization with coronary artery bypass grafting or percutaneous coronary intervention has been regarded as the standard choice for stable coronary artery disease (CAD), particularly for patients with a significant burden of ischemia. However, in conjunction with remarkable advances in adjunctive medical therapy and a deeper understanding of its long-term prognosis from recent large-scale clinical trials, including ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), the approach to stable CAD has changed drastically. Although the updated evidence from recent randomized clinical trials will likely modify the recommendations for future clinical practice guidelines, there are still unresolved and unmet issues in Asia, where prevalence and practice patterns are markedly different from those in Western countries. Herein, the authors discuss perspectives on: 1) assessing the diagnostic probability of patients with stable CAD; 2) application of noninvasive imaging tests; 3) initiation and titration of medical therapy; and 4) evolution of revascularization procedures in the modern era.

Examining the Long-Term Efficacy and Tolerability of Netarsudil as an Adjunctive Glaucoma Medical Therapy

Background and Hypothesis:Glaucoma is a group of progressive optic nerve neuropathies that commonly cause vision loss or blindness. The most prevalent of these neuropathies is known as primary open-angle glaucoma. POAG is caused by increased intraocular pressure (IOP) in the anterior chamber of the eye, due to increased resistance to outflow of aqueous humor. Netarsudil is a recently developed novel medication for lowering intraocular pressure. The aim of this study is to assess the long-term efficacy and tolerability of netarsudil as an adjunctive therapy in patients with POAG.&#x0D; Methods:In this study data was collected through a retrospective chart review of patients being treated for POAG. Efficacy was measured by using the difference in intraocular pressure over the course of treatment. Tolerability was assessed using a Kaplan-Meier estimator, measuring the time to failure of treatment. Failure in this case is defined as either a termination in treatment due to adverse effects, or termination in treatment from lack of efficacy in lowering IOP. Data was separated into groups of either 2nd, 3rd, or 4th line treatments. In patients where both eyes were treated, one eye was randomly selected to be followed for measurements.&#x0D; Results:Probability of failure curves, based on the tolerability and efficacy of netarsudil treatment, were constructed for each group. IOP reduction (mmHg) was found to be: 3.00 (3.09 95% CI) for 2nd line, 7.05 (4.65 95% CI) for 3rd line, and 5.31 (1.38 95% CI) for 4th line.&#x0D; Conclusion and Impact:These results give context to netarsudil as a therapy in terms of its long-term implications. As the drug was only approved for use in late 2018, there is limited data on its long-term efficacy and tolerability, and this information helps to give clinicians a better idea of whether it will be a helpful treatment for patients.

Medications Activating Tubular Fatty Acid Oxidation Enhance the Protective Effects of Roux-en-Y Gastric Bypass Surgery in a Rat Model of Early Diabetic Kidney Disease.

BackgroundRoux-en-Y gastric bypass surgery (RYGB) improves biochemical and histological parameters of diabetic kidney disease (DKD). Targeted adjunct medical therapy may enhance renoprotection following RYGB.MethodsThe effects of RYGB and RYGB plus fenofibrate, metformin, ramipril, and rosuvastatin (RYGB-FMRR) on metabolic control and histological and ultrastructural indices of glomerular and proximal tubular injury were compared in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of DKD. Renal cortical transcriptomic (RNA-sequencing) and urinary metabolomic (1H-NMR spectroscopy) responses were profiled and integrated. Transcripts were assigned to kidney cell types through in silico deconvolution in kidney single-nucleus RNA-sequencing and microdissected tubular epithelial cell proteomics datasets. Medication-specific transcriptomic responses following RYGB-FMRR were explored using a network pharmacology approach. Omic correlates of improvements in structural and ultrastructural indices of renal injury were defined using a molecular morphometric approach.ResultsRYGB-FMRR was superior to RYGB alone with respect to metabolic control, albuminuria, and histological and ultrastructural indices of glomerular injury. RYGB-FMRR reversed DKD-associated changes in mitochondrial morphology in the proximal tubule to a greater extent than RYGB. Attenuation of transcriptomic pathway level activation of pro-fibrotic responses was greater after RYGB-FMRR than RYGB. Fenofibrate was found to be the principal medication effector of gene expression changes following RYGB-FMRR, which led to the transcriptional induction of PPARα-regulated genes that are predominantly expressed in the proximal tubule and which regulate peroxisomal and mitochondrial fatty acid oxidation (FAO). After omics integration, expression of these FAO transcripts positively correlated with urinary levels of PPARα-regulated nicotinamide metabolites and negatively correlated with urinary tricarboxylic acid (TCA) cycle intermediates. Changes in FAO transcripts and nicotinamide and TCA cycle metabolites following RYGB-FMRR correlated strongly with improvements in glomerular and proximal tubular injury.ConclusionsIntegrative multi-omic analyses point to PPARα-stimulated FAO in the proximal tubule as a dominant effector of treatment response to combined surgical and medical therapy in experimental DKD. Synergism between RYGB and pharmacological stimulation of FAO represents a promising combinatorial approach to the treatment of DKD in the setting of obesity.

Comparison of outcomes between medical and surgical treatment in dogs with prostatic adenocarcinoma: a retrospective study

BackgroundProstatic cancer is uncommon in dogs. Dogs with prostatic carcinoma have been reported to have a poor prognosis. Information regarding prognosis with various surgery options as well as prognosis with surgical vs. medical treatment is lacking. This retrospective study compares the outcomes of medical management to surgical treatment in dogs with prostatic adenocarcinoma and assesses the surgical outcomes of patients who underwent total prostatectomy (TP) and prostatocystectomy (TPC). The medical records of 41 dogs with prostatic adenocarcinoma, between February 2008 and June 2019, were reviewed for information on signalment, clinical signs in the initial evaluation, preoperative diagnostic imaging findings, treatment type (non-surgical or surgical), surgery type, postoperative complications, adjunctive medical therapy, and survival time. The dogs were divided into non-surgical (n = 12) or surgical (n = 29) groups. The surgical group was subdivided into the TP (n = 20) and TPC (n = 9) subgroups.ResultsAge was not significantly different between the surgical (median 13.1 years [8.4–15.4] years) and the non-surgical groups (median 10.8 [7.7–15.3] years). Body weight (BW) was also not significantly different between the surgical (median 6.8 kg [2.4–34.5 kg]) and non-surgical groups (median 6.4 kg [3.7–9.12 kg]). The overall median survival time (MST) from the initial evaluation was significantly longer in the surgical than in the non-surgical group (337 vs. 90.5 days). The postoperative MST was significantly longer in the TP group than in the TPC subgroup (510 vs. 83 days). As TPC was performed in cases of tumor progression, its postoperative complications were severe, resulting in a shorter MST. Ten (50%) and 6 patients (30%) in the TP subgroup postoperatively showed mild and severe urinary incontinence, respectively, whereas all patients in TPC subgroup did show severe incontinence.ConclusionResults of the study suggest that surgical treatment of prostatic carcinoma results in longer survival times over medical management alone. In particular, TP might be recommended for improving survival time and quality of life in canine prostatic adenocarcinoma that does not infiltrate the bladder. Early detection is key for a survival advantage with surgical treatment.

THE USE OF INTRADERMAL ALLERGY TESTING FOR ALLERGIC DERMATITIS IN PTEROPID BATS AND TREATMENT WITH ALLERGEN SPECIFIC IMMUNOTHERAPY: A CASE SERIES.

This case series describes the diagnosis of allergic dermatitis and management with allergen-specific immunotherapy (ASIT) based on intradermal allergy testing (IDAT) and adjunctive medical therapy in six pteropid bats; five large flying foxes (Pteropus vampyrus); and one variable flying fox (Pteropus hypomelanus). The cases ranged from 2 to 15 yr of age at the time of presentation. Clinical signs varied between individuals and included moist ulcerative cutaneous lesions in nonhaired skin, blepharoconjunctivitis, alopecia, and pruritus. All bats underwent IDAT under general anesthesia, and reactive allergens included a mixture of grasses, trees, weeds, and biting insects. Three of the six cases (50%) had reformulation of the ASIT before control of clinical signs was seen, and two bats were treated with the addition of oclacitinib (Apoquel). Severe adverse effects were not identified; however, one bat had self-limiting swelling at the immunotherapy injection site. All six cases showed improvement of clinical signs and perceived comfort level, including in subsequent allergy seasons.

Abstract 13014: Sex-Differences in Nonagenarians With ST Elevation Myocardial Infarction

Introduction: Longevity of the population continues to increase but frequently elderly patients are excluded from clinical trials. Women with STEMI have been reported to have higher mortality, delay to treatment, and suboptimal prescription of goal directed medical therapy compared to men. We recently demonstrated higher utilization of PCI with improved outcomes in elderly patients treated in regional STEMI systems with standardized protocols. We evaluated sex-differences in nonagenarians with STEMI. Methods: The Midwest STEMI Consortium (MSC) consists of four regional STEMI centers includes 15,039 consecutive STEMI activations between March 2003 and December 2020. Sex differences were assessed in the subgroup of patients ≥ 90 years old (n=303, 2%), including baseline demographic, intervention, mortality outcomes, and pre/post hospitalization residence status. Results: Of 303 nonagenarians, women (N=194, 64%) were less likely to have a smoking history, family history of coronary artery disease (CAD), and personal history of CAD (including MI, PCI or CABG). Surprisingly, there were no sex differences in time to treatment, use of PCI (84 vs 78%), adjunctive medical therapy or clinical outcomes including in-hospital and 1-year mortality (Table). Conclusions: In 4 established regional STEMI systems, in elderly patients ≥ 90 years old women were more common (64%) and although the risk profiles were different, there were no sex differences in reperfusion strategy, time to treatment, or adjunctive therapy. Importantly, there were no differences in clinical outcomes including mortality. The high rate of PCI, excellent treatment times and clinical outcomes compared to historical data likely reflect the benefit of regional STEMI programs using standardized protocols.