bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post hoc pooled analysis of first-line (1L) pembrolizumab (pembro) for advanced urothelial carcinoma (UC): Outcomes by response at week nine in KEYNOTE-052 and KEYNOTE-361.
Authors: Powles Thomas , Alva Ajjai Shivaram , Ozguroglu Mustafa , O'Donnell Peter H. , Loriot Yohann , Csoszi Tibor , Vuky Jacqueline , Morales-Barrera Rafael , Plimack Elizabeth R. , Matsubara Nobuaki , Fradet Yves , Geczi Lajos , Gunduz Seyda , Mamtani Ronac , Bajorin Dean F. , Liu Chih-Chin , Imai Kentaro , Homet Moreno Blanca , Bellmunt Joaquim , Balar Arjun Vasant 
Published: February 2022

519 Background: Pembro is a 1L treatment for cisplatin-ineligible pts with UC. This post hoc landmark analysis evaluated clinical outcomes by response at 9 wk to 1L pembro monotherapy in pts with advanced/unresectable or metastatic UC from the single-arm phase 2 KEYNOTE-052 (NCT02335424) and the randomized phase 3 KEYNOTE-361 (NCT02853305) trials. Methods: Cisplatin-ineligible pts with advanced UC were enrolled in KEYNOTE-052 and received pembro (200 mg Q3W for ≤2 y). Platinum-eligible pts with advanced UC who had not previously received systemic chemotherapy (chemo) were enrolled in KEYNOTE-361 and randomly assigned 1:1:1 to receive pembro (200 mg Q3W for ≤2 y), pembro + chemo (1000 mg/m2 gemcitabine on d1 and d8 + cisplatin [70 mg/m2] or carboplatin [AUC 5] on d1 of each 3-wk cycle), or chemo. The primary analysis group included pembro monotherapy–treated pts; the sensitivity analysis group included pembro monotherapy–treated pts from KEYNOTE-052 and the choice of carboplatin subpopulation of pembro monotherapy–treated pts from KEYNOTE-361. Landmark analyses of OS by pts with CR, PR, SD, or PD per RECIST v1.1 by BICR at first imaging assessment (wk 9) were pooled for the ITT populations. Duration of CR/PR/SD and OS were estimated using the Kaplan-Meier method. Data cutoffs were Sep 26, 2020 (KEYNOTE-052) and Apr 29, 2020 (KEYNOTE-361). Results: The primary analysis group included 681 pembro-treated pts (KEYNOTE-052, N = 374; KEYNOTE-361, N = 307); the sensitivity analysis group included 544 pembro-treated pts (KEYNOTE-052, N = 374; KEYNOTE-361, N = 170). Median time from randomization to cutoff was 51.9 mo (range, 22.0-65.3) and 53.7 mo (range, 22.0-65.3) for the primary and sensitivity analysis groups, respectively. Twenty-five pts (4.6%) had CR and 135 (24.6%) had PR (primary group); 17 pts (3.9%) had CR and 105 (24.1%) had PR (sensitivity group). Median DOR was 25.9 mo for pts with CR/PR at wk 9; pts with CR/PR or SD at wk 9 had longer OS than pts with PD at wk 9 (Table). Conclusions: In this post hoc analysis, pts with advanced UC in KEYNOTE-052 and KEYNOTE-361 with CR/PR at wk 9 had better clinical outcomes with pembro monotherapy than pts with SD or PD; 1L pembro monotherapy continues to show efficacy in advanced UC. Clinical trial information: NCT02335424 and NCT02853305. [Table: see text]
Prognostic impact of fibroblast growth factor receptor (FGFR) genomic alterations and outcomes in patients with metastatic urothelial.
Authors: Sevillano Elena , Madurga Rodrigo , Rodriguez Moreno Juan Francisco , Barquin Arantzazu , Yagüe Monica , Navarro Paloma , Barba María , Quiralte Miguel , García-Donas Jesús 
Published: February 2022

537 Background: FGFR mutations/translocations are druggable targets in metastatic urothelial cancer (mUC). However, the prognostic effect of these genomic alterations (GA) and their role in the response to conventional therapy remain poorly characterized. Methods: We undertook an observational retrospective study in four Academic Hospitals in Madrid, Spain. Clinical and molecular information of patients diagnosed of Urothelial Cancer (UC) between January 2010 and December 2020 was systematically reviewed. The objective of this work was to compare the outcome of mUC patients with GA in the FGFR 2-3 genes versus wild type tumors. Analyses for detection of FGFR translocations and mutations using DNA isolated from formalin-fixed and paraffinized tumor tissue samples consisted of either next-generation sequencing (Foundation One test; n = 68) or qualitative real-time polymerase chain reaction–based assays (n = 9) with TFGFR or QIAGEN therascreen® tests that evaluated somatic mutations within the FGFR2-3 gene: R248C, S249C, G370C and Y373C and fusions: FGFR3-TACC3v3, FGFR3-TACC3v1 and FGFR3-BAIAP2L1, FGFR2-BICC1 and FGFR2-CASP7. Overall response rate (ORR), Progression Free Survival (PFS) and Overall Survival (OS) were determined and Cox-regression analysis were performed to assess the prognostic impact of these alterations. Results: We identified 201 patients diagnosed with UC. Genomic profiling was available in 77 mUC with 28 patients harboring any FGFR GA. Regarding ORR to first line a trend towards a better outcome was identified in FGFR GA (mutation/translocation/fusion) vs wild type cases (57,7% vs 45,5%, p=0,46). However, median OS was significantly worse among FGFR GA (mutation/translocation) vs FGFR wt tumours (13.8 vs 26.2 months, p=0,021). Prognostic factors associated with an unfavorable outcome in multivariable analysis were visceral metastases (HR 7,29 95% CI 1.6-32,3), ECOG >1 (HR 7,03 95% CI 2,59-19,1), first line treatment with checkpoint inhibitors (HR 2,67; 95% CI 1,06-6,74) and the presence of FGFR GAs (HR 2,98, 95% CI 1.37-6.5). Conclusions: Despite a better response to first line treatment, overall FGFR GA showed to be an independent risk factor in mUC. Thus, this determination should be included in new prognostic models.[Table: see text]
Immune characterization of urothelial bladder carcinoma integrating transurethral resection of bladder tumor (TURBT) samples and serum: A feasibility study.
Authors: Alvarez-Dominguez Carmen , Azueta Ainara , Muñoz Unceta Nerea , Gutierrez-Baños Jose Luis , Teran Hector , Ocejo-Viñals Javier , Gonzalez-Lopez Elena , Caramelo Belen , Marcos-Gonzalez Sara , Salcines-Cuevas David , Dominguez Mario , Madureira-Rivero Rebeca , Campos-Juanatey Felix , Sotelo Marta , Zeoli Andrea , Revuelta Laura , Duran Ignacio 
Published: February 2022

538 Background: Urothelial bladder cancer (UBC) is characterized by high immunogenicity. Multiple immunotherapies both in the perioperative and advanced setting are being developed. However, we lack good predictive biomarkers of response to immunotherapy in UBC. We aimed to characterize the immune profile of UBC patients using TURBT and serum samples. Methods: 13 UBC biopsies from TURBT samples were analyzed along with sera of these patients. Biopsy samples were divided in two equal parts. One part was formalin-fixed paraffin embedded and stained for immune histochemistry [IHC] for the following markers (CD3, CD4, CD8, CD20, CD68 and PD-L1 using SP142 antibody) and results expressed in percentages. The other part was homogenized and processed for immune cell isolation (human tumor isolation Miltenyi Kit). Tumor cells were stained with PHK and double positive CD8 and PHK were isolated using a MACSTM procedure. Different immune cell populations were analyzed by flow cytometry for the following markers (CD3, CD4, CD8, CD20 and CD68) and results expressed in percentages. Cytokines were examined in sera using the Luminex multiparametric procedure and results were expressed as pg/mL. Results: IHC and flow cytometry data were comparable and identified three groups according to the immune cells associated with the tumors (Table). Groups 1 and 2 showed high and moderate levels of tumor activated CD8+ T cells (1-4%) along with a higher expression of PD-L1 (40-20%). Group 3 lacked tumor activated CD8+ T cells and show lower expression of PD-L1 (15%). All groups showed significant levels of Th2 cytokines (IL-4, IL-6 or IL-10) while very low or lack of Th1 cytokines (IFN or IL-2) was observed except in group 2. Conclusions: TURBT biopsies and serum analysis of cytokines could represent a valid approach to further evaluate potential predictive biomarkers of response to immunotherapy in UBC. Different immune populations subgroups were identified in our series and could potentially predict for diverse responses to treatment. Further prospective validation in larger series is ongoing to confirm these results.[Table: see text]
Incidence and outcomes of nodal metastasis in clinically nonmuscle-invasive bladder cancer.
Authors: Alsyouf Muhannad , Ladi Seyedian Seyedeh Sanam , Ghoreifi Alireza , Douglawi Antoin , Schuckman Anne K. , Djaladat Hooman , Daneshmand Siamak 
Published: February 2022

577 Background: Radical cystectomy (RC) is recommended in NMIBC patients with high risk of progression or persistent disease despite intravesical therapy. The role and extent of lymphadenectomy is controversial and not universally performed in this population. The objective of this study is to evaluate the incidence and pattern of nodal metastasis in patients undergoing radical cystectomy for treatment of clinically non-muscle invasive bladder cancer. Methods: Prospectively collected data of patients who underwent RC and ‘super-extended’ LND with intent-to-cure for urothelial carcinoma of the bladder between 2002 and 2019 were examined. Inclusion criteria were(a) clinical stage Ta, Tis,or T1, (b) muscle present and not involved,(c) no prior diagnosis of T2 disease, (d) no prior neoadjuvant therapy, and (e) super-extended lymphadenectomy performed to level of IMA with mapping information available. Logistic regression analysis was used to evaluate for predictors of node metastasis. Results: A total of 223 patients met inclusion criteria with a median follow up of 8.2 years (IQR 4.1-10.7). Lymph node metastasis was identified in 8.1% (18/223) of the cohort. Nodal metastasis was present in 0 patients with cTis, 0 patients with cTa, and 11.6% (18/155) of patients with cT1 disease. Of the 18 patients with LNM in cT1 disease, 61% (11/18) had positive nodes below the common ileac vessel bifurcation, 6% (1/18) had positive nodes below the level of aortic bifurcation, and 33% (6/18) had distant metastasis to lymph nodes beyond aortic bifurcation. No skip metastasis were identified. After RC, 89% of cT1 with nodal metastasis had muscle invasive disease. On logistic regression analysis, presence of LVI on TURBT specimen was a significant predictor of LNM (OR 6.8, CI 2.2-20.9). Five-year RFS was 91%, 82%, and 61% in patients with pNMIBC, cNMIBC, and pMIBC, respectively. Conclusions: Routine lymph node dissection is necessary in patients undergoing RC for cT1 disease due to risk of upstaging and LNMs. Presence of LVI in TURBT specimen of cNMIBC is a predictor of nodal metastasis. In patients with nodal disease, metastasis beyond the limits of a standard lymph node template occurred in two-thirds of patients, however a standard pelvic node dissection would have identified all patients with node positive disease.
PSMAddition: A phase 3 trial to compare treatment with 177Lu-PSMA-617 plus standard of care (SOC) versus SOC alone in patients with metastatic hormone-sensitive prostate cancer.
Authors: Sartor A. Oliver , Tagawa Scott T. , Saad Fred , De Bono Johann S. , Feng Felix Y , Fizazi Karim , Sakharova Olga V. , Morris Michael J. 
Published: February 2022

TPS210 Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy that delivers β-particle radiation to PSMA-expressing cells and the surrounding microenvironment. Androgen receptor pathway inhibitors (ARPI) may alter PSMA expression and radiosensitivity. PSMAddition will assess the efficacy and safety of 177Lu-PSMA-617 plus standard of care (SOC) versus SOC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: PSMAddition ( NCT04720157 ) is an international, prospective, open-label, randomized, phase 3 trial in adults with mHSPC. Eligible patients are treatment-naïve or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by [68Ga]Ga-PSMA-11 PET/CT), Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate major organ function. Patients are excluded if they have rapidly progressing tumors that require chemotherapy. Approximately 1126 patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks, ≤6 cycles) plus SOC or SOC alone (control arm). SOC is ARPI and androgen deprivation therapy. Stratification factors are tumor volume (high/low), age (≥70/ < 70 years) and previous/planned prostatectomy or radiation treatment of the primary prostate tumor (yes/no). The primary endpoint is radiographic progression-free survival (rPFS), as assessed by blinded independent centralized review. Upon centrally confirmed radiographic progression, participants in the control arm can cross over to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.7 for rPFS after 418 events with an overall one-sided significance level of 0.025. The key secondary endpoint is overall survival. Other secondary endpoints are the proportion of patients with a prostate-specific antigen (PSA) decline of ≥90% from baseline, time to development of metastatic castration-resistant prostate cancer, composite progression-free survival (radiographic, clinical or PSA progression), safety and tolerability, and health-related quality of life. Previously presented at the 2021 European Society for Medical Oncology Congress, FPN 3035, Tagawa S et al. Reused with permission. Clinical trial information: NCT04720157.
Spatio-temporal characteristics of Tuberculosis in Ghana
Authors: Iddrisu Abdul-Karim , A. Amikiya Emmanuel , Kwame Bukari Francis 
Published: February 2022

Background: The number of Tuberculosis (TB) cases or deaths is declining, however, the rate of decline is not adequate to meet the World Health Organization's (WHO's) mitigation. TB remains a public health problem in Ghana with a significant economic and health burden on its citizens and health care system. Consequently, there is a need for further studies about the disease aimed at accelerating the rate of decline in cases. Methods: The spatio-temporal characteristics of TB in Ghana using Bayesian spatial and spatio-temporal regression models was analysed in this study. Data were obtained from Ghana National Tuberculosis Programme (NTP) for the 10 regions of Ghana, collected over a six-year period. The study also examines some baseline predictors of TB infections to ascertain their effects on the TB risk across the ten regions in Ghana. Results: Hot-spots of TB cases are observed in the Upper East, Upper West, Volta, Western, and Central regions and low risk in the Northern, Ashanti, Greater Accra, Brong Ahafo, Eastern and Western regions. The results indicated a clustering of risk between neighboring regions. TB cure rate, TB success rate, knowledge about TB, awareness that TB is airborne, HIV prevalence, percentage of literacy, and high income are important predictors of detection for this disease across the ten regions of Ghana. Conclusion: Most regions in Ghana have similar TB risks. A substantial reduction in TB cases requires measures that will increase detection, success and cure rates, awareness, knowledge about how this disease spreads as well adequate health facilities with easy access.
Bayes Lines Tool (BLT): a SQL-script for analyzing diagnostic test results with an application to SARS-CoV-2-testing
Authors: Aukema Wouter , Malhotra Bobby Rajesh , Goddek Simon , Kämmerer Ulrike , Borger Peter , McKernan Kevin , Klement Rainer Johannes 
Published: February 2022

The performance of diagnostic tests crucially depends on the disease prevalence, test sensitivity, and test specificity. However, these quantities are often not well known when tests are performed outside defined routine lab procedures which make the rating of the test results somewhat problematic. A current example is the mass testing taking place within the context of the world-wide SARS-CoV-2 crisis. Here, for the first time in history, laboratory test results have a dramatic impact on political decisions. Therefore, transparent, comprehensible, and reliable data is mandatory. It is in the nature of wet lab tests that their quality and outcome are influenced by multiple factors reducing their performance by handling procedures, underlying test protocols, and analytical reagents. These limitations in sensitivity and specificity have to be taken into account when calculating the real test results. As a resolution method, we have developed a Bayesian calculator, the Bayes Lines Tool (BLT), for analyzing disease prevalence, test sensitivity, test specificity, and, therefore, true positive, false positive, true negative, and false negative numbers from official test outcome reports. The calculator performs a simple SQL (Structured Query Language) query and can easily be implemented on any system supporting SQL. We provide an example of influenza test results from California, USA, as well as two examples of SARS-CoV-2 test results from official government reports from The Netherlands and Germany-Bavaria, to illustrate the possible parameter space of prevalence, sensitivity, and specificity consistent with the observed data. Finally, we discuss this tool’s multiple applications, including its putative importance for informing policy decisions.
Case Report: Cutaneous metastases indicative of endometrial cancer: A case report and review of the literature
Authors: Zoukar Olfa , Haddad Anis , Jemaa Yosra , Zouari Ines , Issa Rahma , Bayar Amel , Khouildi Ghada , Sebri Amal , Naguez Dalel , Boukadida Asma , Ghannouchi Mossaab , Faleh Raja 
Published: February 2022

Secondary localizations of cutaneous metastases from endometrial cancer are rarely observed with a prevalence of 0.8% and can be indicative of deep pelvic cancer (ovarian or endometrial). The prognosis is usually poor, with skin metastases most often indicating advanced disease. This work, based on a case observed in our department and a review of the literature, aims to highlight the existence of this dramatic form of cutaneous extension of a common disease. Dermatologists are often consulted due to the non-specific nature of the lesions and should be aware of this entity. As with other cutaneous metastases, an accurate diagnosis is based on a the patient’s thorough medical and surgical history in conjunction with histopathology
Canonical analysis of neuroendocrine-metabolic and neuroendocrine-immune relationships at female rats
Authors: Mel’nyk Oksana , Zukow Walery , Hrytsak Myroslava , Popovych Dariya , Zavidnyuk Yuriy , Bilas Volodymyra , Popovych Igor 
Published: February 2022

Background. It has been shown before that drinking mineral waters of different composition has a significant effect on the neuroendocrine, metabolic and immune parameters of healthy rats. We analyzed the canonical correlations between neuroendocrine parameters, on the one hand, and metabolic and immune parameters, on the other hand. Materials and Methods. Experiment was performed on 58 healthy female Wistar rats 240-290 g. HRV parameters, major adaptation hormones, metabolism and immunity parameters were recorded. Results. The method of canonical correlation analysis revealed causal relationships between neuroendocrine and metabolic and neuroendocrine and immune parameters of the organism. The degree of neuroendocrine determination of individual sets of metabolic parameters ranges from 60% to 92%, and immune status from 87% to 96,5%. Conclusion. Effects of mineral waters on metabolism and immunity are realized through nervous and hormonal mechanisms.
Orthodontic retainers: now you have finished your orthodontic treatment how do you manage long-term post-orthodontic retention?
Authors: Shah Rupal , Noar Joseph 
Published: February 2022

Retention is a key phase of orthodontic treatment that aims to maintain teeth in their corrected position following active orthodontic treatment. Although the evidence base is limited, there is now general consensus that orthodontic patients should wear their retainers life-long. This poses serious questions as to who is responsible for ensuring that the retainers are in good working order and fit for purpose. This article aims to set out some guidance for specialists, general dental practitioners and patients on the management of long-term retention, taking into consideration the best available knowledge. This article also aims to provide some guidance and rationale for retention wear and regimens. It is understood of course that these should be modified and individually assessed for each patient and their malocclusion. CPD/Clinical Relevance: A knowledge of how to assess and maintain orthodontic retainers is essential for the practising dentist.
Cervical necrotizing fasciitis of odontogenic origin
Authors: Chai Aaron , Chandran Anupam , Crank Stephen 
Published: February 2022

Cervical necrotizing fasciitis (CNF) is a rare, but serious condition that can develop as a result of an odontogenic infection spreading into the deep fascial planes of the neck. The infection is associated with significant morbidity and mortality due to septic shock, disseminated intravascular coagulation (DIC) and consequent multiple organ failure. A case of CNF affecting a 42-year-old woman who was treated with rapid surgical debridement and intravenous antibiotics is presented. She subsequently required further head and neck reconstruction as a result of morbidity from the disease. CPD/Clinical Relevance: Although rare, it is pertinent that dental practitioners recognize that untreated dental infection might trigger necrotizing fasciitis, especially in high-risk patients.
Palatal hyperplasia associated with hereditary gingival fibromatosis
Authors: Patrick Amy , Savla Adesh , Eyeson Josiah 
Published: February 2022

Hereditary gingival fibromatosis (HGF) is a benign, non-haemorrhagic, fibrous gingival overgrowth of unknown cause. Clinically, gingivae can be seen to partially or fully cover teeth, and can limit oral function, for example eating, speaking, and maintaining oral hygiene. HGF normally starts in the transition between the primary and secondary dentition. Surgical excision is often required. This case describes the management of a 37-year-old male with generalized HGF with extensive bilateral palatal growths extending into the oropharynx; not a reported presentation of HGF. Awareness of the condition and familial history could aid management at an earlier stage. CPD/Clinical Relevance: This article describes the management of an uncommon presentation of hereditary gingival fibromatosis in the palate that affected the patient's oral function.
Using inhalation sedation in practice
Authors: Anand Prabhleen Singh , Adams Leah Rachel 
Published: February 2022

This article outlines considerations for use of inhalation sedation (IS) in a primary care setting. It looks at indications, contra-indications and case selection for use of IS in practice. The article also considers relevant rules, regulations and guidelines a practitioner should be aware of if practicing inhalation sedation. Some useful practical tips are included on setting up an inhalation sedation practice and being compliant with the Care Quality Commission (CQC) regulations. Standard requirements for staff and patient safety in practice setting are discussed, as are training, governance and CPD requirements for the dental team providing sedation in accordance with latest guidelines on conscious sedation.CPD/Clinical Relevance: This article will be useful for clinicians looking to update their knowledge on the use of inhalation sedation in the primary care setting.