Aggressive Protocol Research Articles

Quality of life among cervical cancer patients following completion of chemoradiotherapy at Ocean Road Cancer Institute (ORCI) in Tanzania

ObjectiveEffective cancer treatment involves aggressive chemo-radiotherapy protocols that alter survivors’ quality of life (QOL). This has recently aroused the attention not only to focus on clinical care but rather to be holistic and client-centered, looking beyond morbidity and mortality. The study assessed the QOL and associated factors among patients with cervical cancer (CC) after the completion of chemoradiotherapy.MethodsA cross-sectional analytical study was conducted at Ocean Road Cancer Institute (ORCI) from September to November 2020. A total of 323 CC patients were interviewed with a structured questionnaire of QOL, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and its cervical cancer module (EORTC QLQ-CX24). The QOL domains, socio-demographic and clinical variables were analyzed with Mann–Whitney and Kruskal–Wallis on SPSS version 23, and a P < 0.05 was considered significant.ResultsMore than half (54.8%) of the CC patients had a good overall QOL. Overall, QOL was affected by education (P = 0.019), smoking (0.044), sexual partner (P = 0.000), treatment modality (P = 0.018), and time since completion of treatment (P = 0.021). Patients who underwent external beam radiation suffered from significant side effect symptoms (P < 0.05) while those who underwent combined external beam radiation and brachytherapy had higher functioning in most domains (P < 0.05).ConclusionsA significant improvement in QOL was observed after chemoradiotherapy and was affected by socio-demographic and clinical variables. Thus, calls for individualized care in addressing these distressing symptoms.

P011: IPS-7 or IPS-3 to identify very-high risk patients in advanced Classical Hodgkin’s Lymphoma: Which score to choose

Figure 1: PFS and OS for both IPS-3 and IPS-7 scores Introduction: The survival of patients (pts) with classic Hodgkin Lymphoma (cHL) has been significantly increased due to refinement of therapeutic strategies. International Prognostic Score (IPS-7) is the most used risk stratification tool for patients with advanced-stage cHL but it may have decreased prognostic value in cHL pts treated in the contemporary era. A novel scoring system, IPS-3, comprising three of the seven IPS-7 indicators (age ≥45, stage IV, haemoglobin <105 g/L), was recently proposed to identify high-risk patients but require further validation. Aim: To validate IPS-3 and evaluate its discriminatory power in advanced stages cHL. Methods: Single centre retrospective analysis of adult pts with cHL diagnosed between 1990 and 2017 treated with ABVD, ABVD hybrid protocols or escalated BEACOPP. Advanced stage was defined according to the German Hodgkin Study Group classification system. Stratified models for IPS-3 and IPS-7 were compared using Akaike’s information criteria (AIC) and Harrell’s concordance index (C-index). Results: We included 227 pts, with similar gender proportion; median age was 32.3 (18–80). Nodular sclerosis was the most common histologic subtype (n=176 pts; 77.5%); 90 pts (39.6%) presented stage IV; 13 pts (5.7%) had IPS-3 high risk, 12 pts (5.3%) IPS-7 high risk and 8 pts (3.5%) had both. After a median follow-up of 123 months (m), the median overall survival (OS) was not reached. IPS-7 (HR 2.13 [95%IC 1.49–3.05]; p<0.001) and IPS-3 (HR 3.05 [95%IC 1.98–4.69]; p<0.001) identify different prognosis groups for OS, with IPS-3 (AIC 633; C-index 0.6547) providing best fit for data compared with IPS-7 (AIC 643; C-index 0.6403). Median progression free survival (PFS) was 295.6m. IPS-7 (HR 1.43 [95%IC 1.05–1.96]; p=0.025) and IPS-3 (HR 1.72 [95%IC 1.20–2.46]; p=0.003) identified different prognostic groups for PFS, with IPS-3 (AIC 917; C-index 0.5717) providing best fit for data compared with IPS-7 (AIC 921; C-index 0.5570). IPS-3 remained predictive for OS (HR 3.05; p<0.001) and PFS (HR 1.72; p=0.003) after adjustment for treatment protocol and had a good performance discriminating high vs intermediate/low risk for OS and PFS (HR 2.40; p=0.002 and PFS HR 3.03; p=0.001, respectively). Conclusion: IPS-3 had better performance predicting OS and PFS compared with IPS-7, allowing a better segregation of patients with worse prognosis, which suggests its value to identify patients that will benefit more aggressive treatment protocol.

A series of six uncanny orthokeratinized odontogenic cysts: Revisiting the literature

Orthokeratinized odontogenic cyst is a rare odontogenic cyst which was considered to be a variant of odontogenic keratocyst, but has been recognized as a separate entity due to its varied behavior and histology. Commonly associated with an unerupted tooth in the posterior mandible, it mimics various lesions like dentigerous cyst, odontogenic keratocyst, unicystic ameloblastoma etc. Orthokeratinized odontogenic cyst was thought to be less destructive compared to odontogenic keratocyst. This case series highlights the clinically aggressive nature of Orthokeratinized odontogenic cyst.In this case series six cases of diagnosed Orthokeratinized Odontogenic cyst have been described along with one case of multiple Orthokeratinized odontogenic cysts in a female patient. The clinical, radiographic and histopathologic features have been described in great detail in order to correlate with the previous literature and highlight their clinically aggressive behavior.Orthokeratinized odontogenic cyst can be deceptive and should be diagnosed appropriately to avoid aggressive treatment protocol. Most of these cysts are associated with inflammation which makes it harder to be diagnosed as the epithelium and connective tissue would have undergone structural changes. Differentiating the cystic lesions of the oral cavity is utmost important to devise appropriate treatment suitable for the patient and for assessing the prognosis, recurrence and rehabilitation to improve the quality of life.

P10.14.A Caught in a trap: Silk fibroin, hyaluronic acid, and heparin sponges to capture residual glioblastoma cells

Abstract Background Recurrent glioblastoma (GBM) is today inevitable, even using an aggressive treatment protocol (surgery, radiotherapy, and chemotherapy). It mostly occurs within 2 cm of the resection cavity due to the invasion ability of GBM cells. The aim of this work is to test and qualify a local integrative approach using a nano-based chemokine-cancer cell trap concept to lure the residual GBM cells by releasing chemoattractive molecules and, ultimately, confine and kill them in a biomimetic nanostructured polymeric scaffold. Material and Methods The stromal cell-derived factor 1α (SDF-1α) was used here as a chemoattractant due to its synergy with the CXCR4 receptor, and the correlation of this axis to the migration of infiltrating GBM cells. Freeze-dried sponges (20 to 140μm/pore size) composed of silk fibroin (SF), hyaluronic acid (HA), and heparin (hep) charged with SDF-1α was evaluated as a GBM cell trap. First, the cytocompatibility and biodegradability of the sponges were evaluated both in vitro and vivo. Secondly, molecular and functional responses of GBM cells to SDF-1α treatment were evaluated using U87MG-CXCR4+ cells, that constitutively and stably expressed both the CXCR4 receptor and RFP, as reporters. To assess the cell migration in response to the SDF-1α gradient in vitro, transwell, under-agarose, and agarose drop assays were used. U87MG-CXCR4+ spheroids were cultivated in the sponges to verify the hosting capacity of the scaffolds. Finally, syngeneic and xenogeneic models were developed to evaluate the bioperformance of the sponges in vivo. Results SF-HA-hep sponges presented low cytotoxicity and complete biodegradation after 4 months of implantation. Histological analysis revealed only local reaction, as an immune response in the short-term study, but no signs of acute inflammation or fibrotic process were found at the resection cavity-brain margin in the long-term study, demonstrating fine tolerability in vivo. Relevant molecules involved in chemotaxis (Akt, Erk, and Paxillin) were activated upon treatment with SDF-1α. U87MG-CXCR4+ cells were directionally attracted to the SDF-1α-loaded sponges, and also a larger neurosphere infiltration area was observed in these sponges compared to controls. Preliminary observations have shown cell clusters detached from the main tumor mass towards the cavity with the implanted SDF-1α-loaded sponge. This may be indicative of chemoattraction, as DAPI correlated with Ki67 staining in the migration front. Further analyses including CXCR4, CD44, paxillin, and galectin-1 immunolabeling will be performed to confirm this hypothesis. Conclusion Overall, the results showed that the sponges are biocompatible and the SDF-1α suitable to use as a chemoattractant for GBM cells. This strategy can be used to overcome the treatment resistance in GB, and potentially be transferred to the clinic in the future.

Risk Factors for Invasive Fungal Disease in Pediatric Oncology

Background: Invasive fungal infections are a major cause of death in pediatric oncology, especially among patients under chemotherapy. This study aims to identify risk factors for invasive fungal infections in pediatric oncology. Methods: We conducted a monocentric retrospective case-control multi-cohort study on a population of 30 patients with malignant hemopathies or solid cancers under chemotherapy, admitted in the Pediatric Oncology unit of Nafissa Hammoud Hospital in Algiers, amongst which 24 patients were controls, and 6 patients were cases. Results: In a total of 30 patients (53.3 % male), 13 patients developed a fever, from which 6 patients were identified as invasive fungal infection cases according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Infectious Diseases Mycoses Study Group (EORTC/MSG) guidelines, with an incidence of 20 %. The mean age was 7.47 years old at the admission date. Four statistically significant risk factors were identified (p-value &lt; 0.05, CI 95 %): mucositis with an odds ratio (OR) at 10 (1,34 – 74,51), the most aggressive chemotherapy protocol according to the ITR2 with an OR at 115 (6,10 – 2165,95), severe prolonged neutropenia with an OR at 7,6 (1,07 – 54,09) and severe prolonged lymphopenia with an OR at 25 (2,27 – 275,71). Conclusion: Many conditions were identified as risk factors for invasive fungal infections in pediatric oncology, especially severe lymphopenia and aggressive chemotherapy. These patients may have to receive close monitoring or even antifungal prophylaxis.

(Invited, Digital Presentation) Nanostructured Thin Film (NSTF) Iridium Catalyst Powder for Proton Exchange Membrane Water Electrolyzers

Proton exchange membrane water electrolyzers (PEMWEs) are electrochemical devices which generate hydrogen (H2) gas from water and electrical energy feedstocks. PEMWEs produce H2 renewably and carbon-free when the electricity is from renewable sources, and are a pathway to enable deep decarbonization across multiple industrial and energy sectors[1]. However, commercial deployment of PEMWEs is currently limited to megawatt-scale due to relatively higher H2 production costs and capital costs than hydrocarbon reforming [2]. The higher costs are due in part to the use of significant quantities of expensive materials (Pt and Ir electrocatalysts and perfluorinated ionomers), insufficient operating performance and durability, and high manufacturing costs. Additionally, commercial PEMWEs additionally use high Ir loadings [3] for the oxygen evolution reaction (OER), and the limited abundance of Ir [4] may limit PEMWE annual deployment of those technologies to gigawatt (GW) scale.3M Nanostructured Thin Film (NSTF) PEMWE OER powder catalysts and electrodes are a unique approach to address the cost and Ir utilization barriers noted above. NSTF catalysts [5] are comprised of nm-scale catalyst metal thin films on a high aspect ratio inert support (Fig. A). NSTF Ir OER catalysts enable high efficiency and high durability due to high OER mass activity and intrinsic resistance to dissolution, imparted by the unique agglomerated thin film catalyst structure. NSTF OER electrodes [6] consist of a dispersed matrix of NSTF catalyst powder particles within a perfluorosulfonic acid (PFSA) ionomer binder (Fig. B), which have high catalyst utilization due to the high electronic conductivity of the primary catalyst particles.One of the key challenges associated with development of OER catalysts and electrodes is the lack of qualified accelerated stress tests (ASTs) to enable rapid assessments of durability under conditions relevant for end-use. The challenge is in part magnified by the long lifetime requirements of 80,000 hours and low required decay rates of single microvolts per hour, which traditionally has required long testing times and multiple replicates to obtain needed statistical significance. Additionally, evaluations of durability have often occurred under steady state testing with fixed current densities, which do not reflect anticipated use profiles when integrated with renewables such as wind and solar with significant power production variability over time. Lastly, operation at increased stack power densities is considered a key strategy to reduce stack capital costs and Ir requirements on a gram per kW basis.In this paper, we will report recent work on our durability assessment of NSTF OER powder catalysts and electrodes under aggressive testing protocols with low catalyst loadings relevant for PEM electrolyzers at large scale. Assessments included steady state durability tests, an accelerated stress test, and a protocol intended to simulate integration with a wind variable renewable energy (VRE) load profile. An example of results from the wind VRE protocol are summarized in Figs. C and D. The wind VRE protocol generated by Alia et al. [7] was modified from voltage control to current control and the maximum current density was scaled to 4.5A/cm2. The protocol was applied to a 3M laboratory CCM comprising a 0.20 mg/cm2 of 78wt% Ir/NSTF powder catalyst OER electrode, 0.09 mg/cm2 of 78wt% Pt/NSTF powder hydrogen evolution reaction (HER) electrode, and a 100 micron thick PEM (800EW 3M PFSA). After 500 hours of the wind VRE protocol, the cell performance was essentially unchanged (1mV voltage decrease at 2A/cm2). S. Dept. of Energy “H2@Scale”, https://www.energy.gov/eere/fuelcells/h2scale.S. Dept. of Energy H2USA Model, Current Forecourt Hydrogen Production v. 3.101.Ayers et al., Catalysis Today 262 121-132 (2016).Babic et al., Electrochem. Soc. 164 F387 (2017).Debe et al., ECS Trans. 45(2) 47-68 (2012).Steinbach et al., 2019 U.S. DOE Annual Merit Review, Project ta026.Alia et al., Electrochem. Soc. 166 F1164 (2019). Figure 1

35 Years of Advances in Skin & Wound Care: Celebrating the Evolution of the Wound Care Team.

35 Years of Advances in Skin & Wound Care: Celebrating the Evolution of the Wound Care Team.

Options in the treatment of superficial and deep venous disease in patients with Klippel-Trenaunay syndrome

ObjectiveKlippel-Trenaunay syndrome (KTS) is a congenital mixed mesenchymal malformation syndrome that includes varicose veins, capillary and venous malformations, lymphatic abnormalities, and hypertrophy of various connective tissue elements. The purpose of the present study was to describe the clinical characteristics and outcomes in a subset of patients with KTS in whom venous interventions, including iliofemoral venous stenting, were performed after failure of conservative therapy. MethodsA single-center retrospective data review of 34 patients with KTS who had undergone interventions for venous disease between January 2000 and December 2020 was performed. ResultsTheir mean age was 38.4 ± 17.5 years (range, 12-80 years). No gender predilection was found. Of the 34 patients, 61% had had all three features of the classic triad for KTS. Varicose veins were present in all 34 patients (100%), and 30% had had a history of bleeding varicosities. Most patients (79%) had CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) class ≥C4. Of the 34 patients, 30% had a history of deep vein thrombosis and/or pulmonary embolism. Factor VIII elevation was the most common thrombophilia condition (12%). The venous filling index was elevated at baseline (5.9 ± 5.1 mL/s) and did not normalize despite intervention (3.5 ± 2.3 mL/s; P = .04). The superficial venous interventions (n = 35) included endovenous laser therapy; stripping of the great saphenous vein, small saphenous vein, anterior thigh vein, or marginal vein; ultrasound-guided sclerotherapy; and stab avulsion of varicose veins. One coil embolization of a perforator vein was performed. Deep interventions (n = 19) included endovenous stenting (n = 15), popliteal vein release (n = 3), and valvuloplasty (n = 1). The venous clinical severity score had improved from 9.4 ± 4.5 to 6.2 ± 5.6 (P = .04). The visual analog scale for pain score had improved from 5.5 ± 2.7 to 2.5 ± 3.3 (P = .008). Healing of ulceration was noted in 75% of the patients. Significant improvements in the total pain (P = .04) and total psychological (P = .03) domains were noted in the 20-item chronic venous disease quality of life questionnaire. ConclusionsSuperficial and deep venous interventions are safe and effective in patients with KTS when conservative therapy has failed. Iliofemoral venous stenting is a newer option that should be considered in the treatment of chronic deep venous obstructive disease in patients with KTS in the appropriate clinical context. An aggressive perioperative deep vein thrombosis prophylaxis protocol should be in place to reduce thromboembolic complications in these patients.

Gene expression profiling of Group 3 medulloblastomas defines a clinically tractable stratification based on KIRREL2 expression

Medulloblastomas (MB) molecularly designated as Group 3 (Grp 3) MB represent a more clinically aggressive tumor variant which, as a group, displays heterogeneous molecular characteristics and disease outcomes. Reliable risk stratification of Grp 3 MB would allow for appropriate assignment of patients to aggressive treatment protocols and, vice versa, for sparing adverse effects of high-dose radio-chemotherapy in patients with standard or low-risk tumors. Here we performed RNA-based analysis on an international cohort of 179 molecularly designated Grp 3 MB treated with HIT protocols. We analyzed the clinical significance of differentially expressed genes, thereby developing optimal prognostic subdivision of this MB molecular group. We compared the transcriptome profiles of two Grp 3 MB subsets with various outcomes (76 died within the first 60 months vs. 103 survived this period) and identified 224 differentially expressed genes (DEG) between these two clinical groups (Limma R algorithm, adjusted p-value < 0.05). We selected the top six DEG overexpressed in the unfavorable cohort for further survival analysis and found that expression of all six genes strongly correlated with poor outcomes. However, only high expression of KIRREL2 was identified as an independent molecular prognostic indicator of poor patients’ survival. Based on clinical and molecular patterns, four risk categories were outlined for Grp 3 MB patients: i. low-risk: M0-1/MYC non-amplified/KIRREL2 low (n = 48; 5-year OS—95%); ii. standard-risk: M0-1/MYC non-amplified/KIRREL2 high or M2-3/MYC non-amplified/KIRREL2 low (n = 65; 5-year OS—70%); iii. high-risk: M2-3/MYC non-amplified/KIRREL2 high (n = 36; 5-year OS—30%); iv. very high risk—all MYC amplified tumors (n = 30; 5-year OS—0%). Cross-validated survival models incorporating KIRREL2 expression with clinical features allowed for the reclassification of up to 50% of Grp 3 MB patients into a more appropriate risk category. Finally, KIRREL2 immunopositivity was also identified as a predictive indicator of Grp 3 MB poor survival, thus suggesting its application as a possible prognostic marker in routine clinical settings. Our results indicate that integration of KIRREL2 expression in risk stratification models may improve Grp 3 MB outcome prediction. Therefore, simple gene and/or protein expression analyses for this molecular marker could be easily adopted for Grp 3 MB prognostication and may help in assigning patients to optimal therapeutic approaches in prospective clinical trials.

Containment of a Multi-facility Outbreak of Candida Auris in a Texas Metropolitan Area During COVID-19 Pandemic

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, healthcare facilities are experiencing shortages of staff, personal protective equipment (PPE), environmental disinfectants, and patient beds. Candida auris, a fungus often resistant to common antifungals, requires staff to wear gown and gloves and use the correct surface disinfectant. A regional epidemiology approach is needed when a multi-facility outbreak occurs.MethodsIn May 2021, an acute care hospital reported a clinical C. auris case to the local health department (LHD). Discussions were initiated between LHD and state partners on the Centers for Disease Control and Prevention (CDC) tiered C. auris approach. Infection Control Assessment Responses (ICARs) were conducted at identified facilities and point prevalence studies were initiated upon identification of infection control gaps. LHD implemented aggressive colonization testing and isolation protocol after discussions with CDC and state partners. Active surveillance was implemented throughout the jurisdiction. An interfacility transfer form helped communicate isolation needs during patient transfers. C. auris isolates confirmed at the state laboratory were sent to the Antibiotic Resistance (AR) Laboratory Network laboratory. Whole genome sequencing (WGS) was performed by the CDC Laboratory.ResultsFrom May through October 2021, the LHD received 149 C. auris case reports. Collection dates ranged from May 1, 2021, to October 15, 2021. Sixteen were clinical cases and 133 were colonized cases. Of the 149 cases, 55% (n=82) were males. Ages ranged from 24 years to 90 years with a mean and median of 65 years. Of the 1725 screening swabs tested, 8% (n=133) were positive for C. auris. Twenty-two ICARs were conducted. WGS was performed on 15 isolates, which showed relatedness between the isolates.ConclusionsAR testing helped epidemiologists identify colonized C. auris cases that would have otherwise not been identified. WGS results supported the epidemiology data showing relatedness between the cases and indicated transmission within and between facilities.

Variations in Ewing sarcoma and rhabdomyosarcoma patient outcomes based on treatment center volume.

e18530 Background: Due to their rarity and requirement for multi-modality care, evidence suggests (and guidelines recommend) patients (pts) with Ewing Sarcoma (ES) and rhabdomyosarcoma (RMS) treated at high volume centres (HVC) with multidisciplinary tumour board discussions (MTDs) have improved outcomes. However, access to care at HVC is challenging for pts who live remotely, such as many pts in British Columbia (BC), Canada. Our study explores the difference in outcomes of patients with ES and RMS based on location of diagnosis and treatment in BC. Methods: A multi-center retrospective chart review of adults diagnosed with ES and RMS Jan 1st 2000 to Dec 31st 2020 was performed for pts undergoing curative intent therapy at one of six provincial cancer centers. All pts underwent expert pathology review. Descriptive statistics were performed. Fisher’s exact and chi-squared tests were used to evaluate associations. Cox proportional hazards model was used to assess for predictors of better survival outcomes by treatment centre. HVCs was defined as those that saw ≥15 patients. Results: 77 patients were included in this analysis; 46 (60%) and 31 (40%) were treated at HVC and LVC respectively. By HVC and LVC respectively, mean age was 36 and 35, 14 (45%) and 20 (43%) were female, 23 (74%) and 26 (57%) had ES, and 11 (35%) and nine (20%) had localized disease. Pts treated at HVCs were more likely to: receive curative intent radiation (p = 0.006), be presented at MTDs (p = 0.042), and less likely to experience disease progression on fist line therapy (p = 0.04) (Table). Time from biopsy to start of chemotherapy (chemo) was 13 days sooner at HVCs vs LVCs (34 vs 47 days, p = 0.12). Initial chemo regimen (p = 0.25) and surgical treatment (p = 0.75) were not significantly different between HVCs vs LVCs. Age, ECOG, stage, and Charlson Comorbidities Index (CCI) were all significant contributors to overall survival (OS). There was no statistically significant difference in OS by treatment center (HR 0.68, 95% CI 0.36 – 1.29). Conclusions: Variations in care exist for both treatment and outcomes amongst ES and RMS pts treated at HVC vs LVC in BC. Pts treated at HVCs were more likely to be presented at MTDs, to receive curative intent radiation, and less likely to experience disease progression. This may reflect differences in access to resources, sarcoma-specific clinician specialists, and familiarity with upfront aggressive treatment protocols. This study can be used to better inform decisions regarding triaging and centralization of curable ES and RMS patients.[Table: see text]

The First Step in Standardizing an Artificial Aging Protocol for Dental Composites—Evaluation of Basic Protocols

The clinical performance of a dental restoration is strongly influenced by the complex and dynamically-changing oral environment; however, no standard procedure exists to evaluate this lifetime. This research provides an in-depth analysis of the effect of different aging procedures on the flexural strength (FS), diametral tensile strength (DTS) and hardness (HV) of selected dental materials (Resin F, Flow-Art and Arkon). Material structure was evaluated by scanning electron microscopy. It was found that each aging protocol had some influence on the tested properties, with continual erosion and degradation being observed. Greater mechanical degradation was observed for Resin F (neat resin) after the applied aging protocols, suggesting that a resin matrix is more susceptible for degradation. The most aggressive aging protocol was Protocol 5: 0.1 M NaOH, seven days, 60 °C. Further studies on the effect of artificial aging on dental materials should include a study of the thermal and chemical factors. A standardized aging procedure is crucial for improving the resistance of dental resin composite to oral conditions and their clinical performance.

Effective Management of Hyperglycemia Improve the Outcome of Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage is one of the most commonly known life-threating disease. Many neurological outcomes are associated with SAH. The poor outcomes are associated with the hyperglycemia in the aneurysmal subarachnoid hemorrhage patients. The major risk factor associated with the aneurysmal subarachnoid hemorrhage is hyperglycemia. Objective: The purpose of this research work was to get in-depth understanding of the effect of glycemic control on changes in the outcomes associated aneurysmal subarachnoid hemorrhage. Study design: It is a prospective study with the statistical approach, conducted at Department of Neurology, Fauji Foundation Hospital, Rawalpindi. Methods: The 365 patients visited the neurology department of our institute were included in the study. The duration of this study was March 2020 March 2022. The 56 ± 14 years was the mean age of the patients included in this study. The 106 (29%) out of 365 were male candidates. The half of the patients were treated with the aggressive hyperglycemic management AHM protocol, while other half were treated with the standard glycemic management SGM protocols. The patients was labelled with good glycemic outcome if the mean glucose burden is less than 1.1, and labelled as poor outcome if mean glucose burden is greater than 1.1. The outcomes of the AHM and SGM group were compared. Different logistic regression models were used to quantify the poor outcome effects. Results: The result depicted that the patients treated with the AHM protocols showed lower poor outcomes (28%) as compared to the other treated with SGM. The values remain insignificant after correction of temporal trends. The incidence of the poor outcome can be reduced by the good glycemic control. The clinical vasospasm rates remain same before or after the implementation of AHM controls. Conclusion: The poor outcomes associated with the SAH can be reduced by good glycemic control of the patients. The study depicted the not only the blood glucose level will remain in the range but also better neurological health of the patients’ will be promoted by an effective use of aggressive glucose management on the patients suffering from SAH. Keywords: Aneurysmal subarachnoid hemorrhage, AHM glycemic control, Hyperglycemic outcomes, Vasospasm, logistic regression models.

High-risk Disease and Poor Follow-up: The Importance of Renal Mass Biopsy in a Cohort of Veterans

ObjectiveTo assess the clinical utility of renal mass biopsy (RMB) in our multistate system. RMB is useful in the management of masses ≤4 cm (T1a), but evaluation of RMB in the uniquely vulnerable Veteran population is lacking. MethodsAbout 136 RMB in 130 patients performed between 06/2015 and 11/2020 were identified in this Quality Improvement analysis. Demographics, size, pathology, treatment, and biopsy complications were analyzed. Of 101 T1a masses, 89 were either diagnostic or not decompressed cysts and 77 met inclusion criteria for follow-up imaging compliance analysis. ResultsThe median age was 66 years. The diagnostic rate was 94.1% (128/136) for all masses and 94.1% (95/101) for T1a renal masses, with a complication rate of 2.2%. Among solid T1a masses, unexpectedly aggressive lesions (Fuhrman Grade 4, Type 2 papillary or sarcomatoid features) were identified in 8/89 (9.0%). Fifty-seven (64%) patients were treated with cryoablation or surgery and 32 (36%) patients elected active surveillance (AS). A neoplastic finding (oncocytoma or renal cell carcinoma (RCC)) was present in 16 patients choosing AS (50%) compared to 52 patients choosing treatment (91%). Compliance with National Comprehensive Cancer Network-recommended imaging was 50% and 47% for AS and treatment groups, respectively. ConclusionIn this VA cohort, we found a significant incidence of high-risk lesions and poor compliance with follow-up imaging. Aggressive biopsy protocols with high consideration of treatment may be appropriate to limit risk in those lost to follow-up. Given that 9% of our small renal masses were highly aggressive, biopsy may be critical in the selection of AS candidates

Abstract PR001: Deciphering clonal evolution under chemotherapy in high-risk neuroblastoma using patient derived models

Abstract Neuroblastoma is a pediatric tumor originating from the developing sympathetic nervous system, most often arising in the adrenal medulla in children below 5 years of age. After diagnosis, children with high-risk neuroblastoma are treated with COJEC, which is an aggressive chemotherapeutic treatment protocol encompassing five different chemotherapeutic agents. This is followed by surgical resection of the remaining tumor tissue. The aim of this project was to decipher how the subclonal landscape in the tumor changes during treatment with COJEC. To do this, three different patient derived xenograft (PDX) models were used by implanting dissociated tumor organoids subcutaneously in nude and NSG mice. The mice were subsequently randomized into either obtaining a mock treatment with saline solution (n=16), or treatment with the COJEC protocol (n=18). In PDX1 (3 controls, 4 treated) and in PDX2 (3 controls, 3 treated), progression or moderate response during treatment was seen respectively. In PDX3 (10 controls, 9 treated who went through surgical removal of remaining tumor tissue, 5 treated mice that didn’t undergo tumor resection) late relapses were seen in two of the mice who underwent surgery as well as two mice who did not. In the control group all tumors progressed. SNP-array analysis and RNA-sequencing was conducted on the parental sample as well as the tumors after treatment and relapses, in addition to single cell whole genome sequencing (scWGS) on a subset of samples. Array analysis was followed by computation of the proportion of cells in each sample harboring each genetic alteration, allowing phylogenetic reconstruction with DEVOLUTION. This revealed extensive convergent evolution of specific chromosomal regions across the PDX models. In PDX3 PTPRD deletions (also seen in PDX1) were found in all cells across samples before treatment. Deletions of the second PTPRD allele were detected in a total of six unique ways. Four of these were only seen in the relapses, while the remaining two were found after surgical resection. Other genes affected by convergent deletions were e.g., MACROD2 and LSAMP that were convergent in all three PDX models. High RNA expression of the genes encompassed by the affected chromosomal regions correlated with good treatment response both in the PDX models and patients, but not the copy number. Surprisingly, no significant increase in the number of genetic alterations was found after compared to before treatment. Phylogenetic reconstruction was conducted on scWGS-data for PDX1 and 3. PDX1 displayed a vast genetic diversity across tumors. In PDX3 parallel evolution of unique 1pq+ and 17q+ alterations and genetic bottlenecks with a selective sweep of 1pq/17q++ were seen in several tumors. In conclusion, both COJEC treatment and surgical resection induced bottlenecks and selective sweeps in the subclonal landscape and extensive convergent evolution was seen across tumors. Combined with the expression results, it supports the relevance of these specific genes in the evolution of neuroblastoma under treatment pressure. Citation Format: Natalie Andersson, Adriana Mañas Nuñez, Kristina Aaltonen, Karin Hansson, Alexandra Seger, Katarzyna Radke, Javanshir Esfandyari, Daniel Bexell, David Gisselsson. Deciphering clonal evolution under chemotherapy in high-risk neuroblastoma using patient derived models [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr PR001.

Olmstead's implementation: Differences in enforcement approaches.

Olmstead v. L.C. ex rel Zimring (1999) was a landmark U.S. Supreme Court decision holding that unjustified segregation of people with disabilities is impermissible discrimination; specifically, if the clinician and client believe community integration to be appropriate, the state must have reasonable accommodations in place for the client to be in the community. Enforcement of the Olmstead decision for people with serious mental illness (SMI) has taken many shapes, from the U.S. Department of Justice's (DOJ) settlement agreements requiring substantive development of community mental health services and aggressive community integration protocols, to the Third Circuit approach which requires only lower census numbers in the state psychiatric hospital (SPH). The question of whether Olmstead is being differentially enforced is addressed in an empirical, qualitative analysis of legal documents, including court opinions and settlement agreements. Through legal research spanning all U.S. jurisdictions, five distinct Olmstead enforcement approaches in ten different states were identified. The enforcement approaches are described, and limitations and future directions are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Improved Peyronie's Disease curvature outcomes using a more aggressive collagenase technique

ABSTRACT Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. Objective To report outcomes of a more aggressive CCH injection / traction protocol in men with PD. Methods A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. Results A total of 320 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8 (SD 10.4), with a mean PD duration of 27.8 months (SD 53) and a median baseline composite curvature of 64 degrees (IQR 45-80). Curvature improvements (most recent minus baseline) improved over time, correlating with increased injection experience and implementation of more aggressive traction protocols: 2014-2020 (20 degrees, 29% improvement) vs 2020-mid 2021 (27.8 degrees, 50%, p&amp;lt;0.001). When men were stratified by those who either completed 8 injections or indicated that they were satisfied with outcomes (n=147), median results were more pronounced: 2014-2017 (29% improvement), 2018 (38%), 2019 (47%), 2020-mid 2021 (59%), p&amp;lt;0.01. Conclusions Progressive implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Disclosure Work supported by industry: no.

PD23-01 IMPROVED PEYRONIE’S DISEASE CURVATURE OUTCOMES USING A MORE AGGRESSIVE COLLAGENASE TECHNIQUE

You have accessJournal of UrologyCME1 May 2022PD23-01 IMPROVED PEYRONIE’S DISEASE CURVATURE OUTCOMES USING A MORE AGGRESSIVE COLLAGENASE TECHNIQUE Alissa Tyler, Benjamin Green, Joshua Savage, Klinton Brearton, and Landon Trost Alissa TylerAlissa Tyler More articles by this author , Benjamin GreenBenjamin Green More articles by this author , Joshua SavageJoshua Savage More articles by this author , Klinton BreartonKlinton Brearton More articles by this author , and Landon TrostLandon Trost More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002565.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. The objective of the current study was to report outcomes of a more aggressive CCH injection/traction protocol in men with PD. METHODS: A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. RESULTS: A total of 438 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8, with a mean PD duration of 32 months and a median baseline composite curvature of 64 degrees. Using the definition of most recent curve assessment, mean composite curve improvements were 27.1 degrees (41%) with the new technique vs 17.8 (24.6%, p<0.001). Of men who completed all 8 injections or stopped early due to satisfaction, the mean improvements were 36.4 degrees (59%) vs 19.8 (30.5%, p<0.001). Despite the more aggressive stretching and traction protocol, erectile function was similar to baseline (IIEF-EFD +0.5). CONCLUSIONS: Implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Source of Funding: NA © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e409 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alissa Tyler More articles by this author Benjamin Green More articles by this author Joshua Savage More articles by this author Klinton Brearton More articles by this author Landon Trost More articles by this author Expand All Advertisement PDF DownloadLoading ...

Improved Peyronie's Disease Curvature Outcomes Using a More Aggressive Collagenase Technique

ABSTRACT Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie's Disease (PD), several investigators have reported outcomes of CCH, with improvements ranging from approximately 15-30%. More recently, we reported improved results (49% mean improvement) when CCH was combined with RestoreX penile traction therapy (RxPTT). Since then, we have made additional modifications to create a more aggressive injection / traction protocol to further optimize outcomes. Objective To report outcomes of a more aggressive CCH injection / traction protocol in men with PD. Methods A prospective database has been maintained of all individuals undergoing CCH injections since 2014. Our CCH injection protocol has evolved from the one described in the IMPRESS trials to a more aggressive use of injections and manual and mechanical traction. Currently, the protocol consists of injecting 0.9 mg of CCH in 0.7 ml of saline into approximately 15-20 sites around the point of maximal curvature (pharmacologically-induced erection performed with the first injection of each series). Injections are only performed on subsequent days (not 2-3 days apart), and very aggressive (i.e. 10-15 lbs of force) modeling is performed with the 2nd injection. Patients are counseled to begin RestoreX traction at 24-48 hours after the 2nd injection for 30-60 minutes daily, and to continue aggressive manual modeling for at least the first week post injection. Penile wraps are applied for 5 days post injection. A descriptive analysis was subsequently performed to review outcomes. Results A total of 320 men underwent at least 1 series of CCH and had baseline and follow-up curve assessment data available. Mean age was 55.8 (SD 10.4), with a mean PD duration of 27.8 months (SD 53) and a median baseline composite curvature of 64 degrees (IQR 45-80). Curvature improvements (most recent minus baseline) improved over time, correlating with increased injection experience and implementation of more aggressive traction protocols: 2014-2020 (20 degrees, 29% improvement) vs 2020-mid 2021 (27.8 degrees, 50%, p&amp;lt;0.001). When men were stratified by those who either completed 8 injections or indicated that they were satisfied with outcomes (n=147), median results were more pronounced: 2014-2017 (29% improvement), 2018 (38%), 2019 (47%), 2020-mid 2021 (59%), p&amp;lt;0.01. Conclusions Progressive implementation of a more aggressive CCH injection protocol has resulted in improved curvature outcomes. Given the specialized nature of technique modifications described, these results would argue for a center-of-excellence model for CCH administration to achieve optimal outcomes. Disclosure No

Effect of Culling Management Practices on the Seroprevalence of Johne's Disease in Holstein Dairy Cattle in Central Italy.

A study was performed in Umbria, central Italy, to find out whether different culling strategies adopted by farms to control Johne’s disease (JD) infection exerted effects on the seroprevalence in dairy cattle. Fifty Fresian dairy herds in the Perugia and Assisi districts were visited and an audit of herd management was conducted. Among the 50 herds, 20 were selected for the consistency of management practices and, according to the culling strategy, two groups were created: group A (aggressive culling protocol, with average herd productive life <1100 days) and group B (lower culling rate, with productive life greater than 1500 days). The presence of antibodies to Mycobacterium avium subspecies paratuberculosis (Map) in the serum was determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit. It was found that 3.3% (n = 14) of the cows of group B (n = 422, from 17 herds) were positive for Map antibodies, in comparison with 5.7% (n = 21) of the cows from group A (n = 366, from three herds). The odds ratio from multiple logistic regression (adjusted odds ratio 2.446, 95% confidence interval 0.412 to 14.525) showed that Johne’s disease prevalence in herds with a greater productive life was not higher than in herds with typical modern management characterized by more aggressive culling. This is a significant finding, indicating that aggressive culling may not be necessary. Current JD control recommendations are derived from data obtained in high-prevalence paratuberculosis areas (northern Europe, including northern Italy), while methods of information transfer to dairy farms in low-prevalence areas should be reassessed to ensure that the correct measures, including basic calving management and calf-rearing practices, are thoroughly implemented. Using the manufacturer’s suggested cut-off for a positive ELISA test and the sensitivity and specificity claimed, the overall true prevalence in Umbria dairy cattle was calculated as 7% (95% confidence interval 5.2% to 8.8%).