scholarly journals Sequential Application of Lugol’s Iodine Test after Acetic Acid for Detecting Cervical Dysplasia: A Prospective Cohort Study

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1598
Author(s):  
Günther A. Rezniczek ◽  
Samira Ertan ◽  
Sadia Rehman ◽  
Clemens B. Tempfer
Keyword(s):  
Acetic Acid ◽  
Clinical Management ◽  
Prospective Cohort ◽  
Staining Intensity ◽  
Study Endpoint ◽  
Primary Study ◽  
Low Grade ◽  
Iodine Solution ◽  
Lugol’S Iodine ◽  
Iodine Test

Applying Lugol’s iodine solution to the cervix followed by colposcopic assessment is an established standard test to identify low grade/high grade squamous intraepithelial lesions (LSIL/HSIL). Here, we assessed the performance of Lugol’s iodine test during colposcopy using a standardized protocol with 5% acetic acid followed by 5% Lugol’s iodine solution and recording the most severe acetowhite (MSAWL) and iodine-negative (MSINL) lesions in a prospective cohort of consecutive women referred to our specialized colposcopy unit. The primary study endpoint was the sensitivity/specificity of MSINL for the detection of LSIL/HSIL. Secondary endpoints were the time to first appearance of the MSINL, MSINL staining intensity, and fading of MSINL. Three hundred and twenty women were included. The sensitivity and specificity of MSINL for the detection of LSIL/HSIL was 81.4 (95%—confidence interval (CI) 77.3–85.0)% and 29.5 (24.2–35.5)%, respectively. Ninety-six MSINL were identified exclusively by Lugol’s iodine test (no pathology, n = 46; LSIL, n = 29; HSIL, n = 21) (number needed to biopsy to identify one additional LSIL/HSIL = 1.9). In 17/320 (5.3%) patients, the clinical management was changed based on the result of Lugol’s iodine test. Video analysis showed an instant appearance of the MSINL within 10 s in 100% of cases. Intensity of MSINL significantly correlated with the presence/absence of LSIL/HSIL (Spearman rank order correlation; p < 0.0001). Fading of iodine-induced staining intensity over time was not observed. Thus, Lugol’s iodine showed moderate sensitivity and poor specificity, but changed clinical management in 5% of cases when used in addition to acetic acid.

Finding a risk assessment model for thromboembolic events in hospitalized cancer patients: The Indicate Study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24108-e24108
Author(s):  
Marco Platania ◽  
Federico Nichetti ◽  
Leonardo Provenzano ◽  
Giulia Montelatici ◽  
Andrea Franza ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Cancer Patients ◽  
Assessment Model ◽  
Study Endpoint ◽  
Primary Study ◽  
Medical Illness ◽  
Low Grade ◽  
Thromboembolic Events ◽  
Primary Analysis ◽  
Increased Risk

e24108 Background: Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). Given the hemorrhagic risk associated with untailored thromboprophylaxis, the identification of patients at low TE risk who might not receive it during in-hospital stay would be clinically useful. Methods: The INDICATE study was a monocentric, observational study enrolling patients with active solid malignancy hospitalized for at least two nights for treatment administration, diagnostic procedures or acute medical illness (excluding TEs). The primary objective was to assess the Negative Predictive Value (NPV) of low-grade Khorana Score (e.g. KS = 0), evaluated at the time of patients’ in-hospital admission, for TEs prediction during and after (next 45 days) hospitalization. The primary analysis was conducted on patients with KS = 0. However, all-grade KS patients were enrolled for secondary outcomes analysis. Assuming a 7% of TEs as the unsatisfactory percentage and a 3% as the satisfactory percentage, expecting about 5% of collected data as incomplete, all consecutive patients who fulfil the inclusion criteria irrespective of the KS were enrolled, until a total of 149 patients with KS = 0 were included to detect the favorable NPV with one-sided alpha equal to 0.10 and power equal to 0.80. Results: Between November 2016 and May 2019, a total of 535 patients were enrolled. Among these, 153 (28.6%) had a KS = 0. The primary study endpoint was met: 29 (5.4%) patients received a diagnosis of TEs during or after hospitalization, with 7 (4.6%) cases in the KS = 0 group. However, patients with higher KS values did not show increasing TE incidence. Among the other evaluated risk assessment models, the ONKOTEV scoreshowed the best predictive potential, with significantly higher values in patients with TEs (p < 0.001).Of note, TEs were associated with poorer overall survival (median, 6.7 vs 24.8 months, log rank p < 0.001). Conclusions: The INDICATE study showed that hospitalized cancer patients with KS = 0 at admission have a low risk of TEs, and could thus be spared from routine thromboprophylaxis. Further studies are needed to better define a RAM in this population.

Pediatric ganglioglioma of the brainstem and cervicomedullary junction: a retrospective cohort study

2020 ◽  
Vol 25 (1) ◽  
pp. 30-36
Author(s):  
Soliman Oushy ◽  
Avital Perry ◽  
Christopher S. Graffeo ◽  
Aditya Raghunathan ◽  
Lucas P. Carlstrom ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Significant Risk ◽  
Foot Drop ◽  
Cranial Neuropathy ◽  
Primary Study ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Low Grade ◽  
Surgical Morbidity ◽  
Cervicomedullary Junction

OBJECTIVEGanglioglioma is a low-grade central nervous system neoplasm with a pediatric predominance, accounting for 10% of all brain tumors in children. Gangliogliomas of the cervicomedullary junction (GGCMJs) and brainstem (GGBSs) present a host of management challenges, including a significant risk of surgical morbidity. At present, understanding of the prognostic factors—including BRAF V600E status—is incomplete. Here, the authors report a single-institution GGCMJ and GGBS experience and review the pertinent literature.METHODSA prospectively maintained neurosurgical database at a large tertiary care academic referral center was retrospectively queried for cases of GGCMJ pathologically confirmed in the period from 1995 to 2015; appropriate cases were defined by diagnosis codes and keywords. Secondary supplemental chart review was conducted to confirm or capture relevant data. The primary study outcome was treatment failure as defined by evidence of radiographic recurrence or progression and/or clinical or functional decline. A review of the literature was conducted as well.RESULTSFive neurosurgically managed GGBS patients were identified, and the neoplasms in 4 were classified as GGCMJ. All 5 patients were younger than 18 years old (median 15 years, range 4–16 years) and 3 (60%) were female. One patient underwent gross-total resection, 2 underwent aggressive subtotal resection (STR), and 2 underwent stereotactic biopsy only. All patients who had undergone STR or biopsy required repeat resection for tumor control or progression. Progressive disease was treated with radiotherapy in 2 patients, chemotherapy in 2, and chemoradiotherapy alone in 1. Immunostaining for BRAF V600E was positive in 3 patients (60%). All 5 patients experienced at least one major complication, including wound infection, foot drop, hemiparesis, quadriparesis, cranial neuropathy, C2–3 subluxation, syringomyelia, hydrocephalus, aspiration, and coma. Overall mortality was 20%, with 1 death observed over 11 years of follow-up.CONCLUSIONSGGBS and GGCMJ are rare, benign posterior fossa tumors that carry significant perioperative morbidity. Contemporary management strategies are heterogeneous and include combinations of resection, radiotherapy, and chemotherapy. The BRAF V600E mutation is frequently observed in GGBS and GGCMJ and appears to have both prognostic and therapeutic significance with targeted biological agents.

scholarly journals Mortality after cardiopulmonary resuscitation on a medical ICU

2021 ◽  
Author(s):  
Richard Rezar ◽  
Bernhard Wernly ◽  
Michael Haslinger ◽  
Clemens Seelmaier ◽  
Philipp Schwaiger ◽  
...  
Keyword(s):  
Cardiopulmonary Resuscitation ◽  
Neurological Outcome ◽  
Cox Regression ◽  
Cerebral Performance Category ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Study Endpoint ◽  
Primary Study ◽  
Postresuscitation Care ◽  
Significant Difference

Summary Background Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA). Methods A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U‑tests and χ2-tests, for survival analysis both univariate and multivariable Cox regression were fitted. Results A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6‑month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35–1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU. Conclusion In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

scholarly journals Natural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 630 ◽  
Author(s):  
Annalisa Noce ◽  
Manuela Di Lauro ◽  
Francesca Di Daniele ◽  
Anna Pietroboni Zaitseva ◽  
Giulia Marrone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Side Effects ◽  
Bioactive Compounds ◽  
Clinical Management ◽  
Endothelial Damage ◽  
Low Grade ◽  
Clinic Management ◽  
Pharmaceutical Therapy ◽  
Increased Risk

Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.

403 Early results from a phase 1 study to evaluate safety, pharmacokinetics, and efficacy of AMG 404, a programmed death-1 (PD-1) antibody, in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A428-A428
Author(s):  
Timothy Price ◽  
Sant Chawla ◽  
Gerald Falchook ◽  
Hans Prenen ◽  
Iwona Lugowska ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Clear Cell ◽  
Phase 1 ◽  
Cell Cancer ◽  
Objective Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Advanced Solid Tumors

BackgroundEnhancement of antitumor immunity through inhibition of the checkpoint PD-1 receptor has been effective in the treatment of many malignancies. AMG 404 is a monoclonal antibody (mAb) targeting PD-1. This phase 1, open-label, multicenter first-in-human study (NCT03853109) will evaluate the safety, tolerability, pharmacokinetics, and efficacy of AMG 404 monotherapy in adult patients with advanced solid tumors.MethodsThe primary study endpoint is dose-limiting toxicity (DLT) and safety; key secondary endpoints include pharmacokinetic parameters, objective response rate (assessed Q8W), duration of response, and progression-free survival. Key inclusion criteria include histologically or cytologically proven metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation for which standard therapies have been exhausted or not available. Prior anti-PD-(L)1 or other checkpoint inhibitors were not allowed. Five dose-finding cohorts, including 2 expansion cohorts, ranged from 3–20 patients each. AMG 404 was given until disease progression, intolerance, or consent withdrawal.ResultsAs of the data cutoff date of May 4, 2020, 62 patients received at least 1 dose of AMG 404 and were included in the safety and efficacy analysis sets. Fifty percent were men, 72% had ECOG 1 performance status, median age was 62 years (range: 28–83), and 42% had ≥3 lines of prior anticancer therapy. Median AMG 404 exposure was ~3 months (maximum: ~12 months). No DLTs were observed. Treatment-related adverse events (TRAEs) were reported for 29 patients (47%): those reported for ≥2 patients were fatigue (n=7); hypothyroidism (n=6); increased blood thyroid stimulating hormone and nausea (n=4 each); increased aspartate aminotransferase, decreased appetite, and pyrexia (n=3 each); and increased alanine aminotransferase, arthralgia, diarrhea, and increased weight (n=2 each). AEs leading to withdrawal of AMG 404 were reported for 3 patients (5%); all were serious and considered to be not related to AMG 404. Sixteen (26%) patients died on study; no deaths were considered related to AMG 404. Preliminary pharmacokinetic results were consistent with those of other therapeutic anti-PD-1 mAbs. Three patients had a confirmed partial response (pancreatic cancer, clear cell cancer, and pleomorphic sarcoma); an additional 4 patients had one scan with a partial response and are pending a confirmatory scan (clear cell renal carcinoma, undifferentiated nasopharyngeal carcinoma, sarcomatoid carcinoma of unknown primary, and colon cancer).ConclusionsAMG 404 is tolerable at the tested doses with no DLTs reported. All observed TRAEs are consistent with other anti-PD-1 therapies. Encouraging anti-tumor activity has been observed in heavily pretreated patients. The study is continuing enrollment into additional cohorts.Trial RegistrationNCT03853109Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.

scholarly journals Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study

2019 ◽  
pp. 1-18
Author(s):  
Olga Kondrashova ◽  
Gwo-Yaw Ho ◽  
George Au-Yeung ◽  
Leakhena Leas ◽  
Tiffany Boughtwood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real Time ◽  
Targeted Therapies ◽  
Clinical Management ◽  
Clinical Utility ◽  
Advanced Ovarian Cancer ◽  
Molecular Profiling ◽  
Molecular Testing ◽  
Low Grade ◽  
Ovarian Carcinomas

PURPOSE The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. PATIENTS AND METHODS A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C. RESULTS Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy samples of two patients, consistent with clinical platinum/poly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling. CONCLUSION ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain

2020 ◽  
Vol 43 (2) ◽  
pp. 79-86
Author(s):  
Ignasi Puig ◽  
Erwin Sanabria ◽  
Faust Feu ◽  
Ignacio Couto ◽  
Marta Blanco ◽  
...  
Keyword(s):  
Clinical Management ◽  
Lymphoid Tissue ◽  
Gastric Lymphoma ◽  
Low Grade

A phase 3 study to evaluate the efficacy and safety of tafasitamab plus lenalidomide and rituximab versus placebo plus lenalidomide and rituximab in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7568-TPS7568
Author(s):  
Laurie Helen Sehn ◽  
Christian W Scholz ◽  
Stefano Luminari ◽  
Antonio Salar ◽  
Bjorn E. Wahlin ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Benefit ◽  
B Cell Lymphoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Cns Lymphoma ◽  
Phase 2 ◽  
Phase 3 ◽  
Potential Clinical Benefit ◽  
Anti Cd20

TPS7568 Background: Most patients with the indolent non-Hodgkin lymphoma (NHL) subtypes FL or MZL respond to first-line treatment but relapse is common, and there is no single standard treatment for patients with R/R FL or MZL. Tafasitamab is an Fc-engineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B-cell proliferation via B-cell receptor signaling. In preclinical studies, tafasitamab has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). Tafasitamab monotherapy has shown promising clinical activity in a phase 2a study in patients with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in patients with FL and 33% (n/N = 3/9) in patients with MZL. In an ongoing phase 2, single-arm study (L-MIND, NCT02399085), tafasitamab plus LEN followed by tafasitamab alone demonstrated an ORR of 57.5% (n/N = 46/80) in patients with R/R diffuse large B-cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of tafasitamab plus LEN and rituximab for patients with R/R FL or MZL. Methods: This phase 3 double-blind, placebo-controlled, randomized study is designed to investigate whether tafasitamab plus LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in patients with R/R FL or R/R MZL. Patients will be randomized 1:1 to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) plus LEN (20 mg PO QD, days 1–21/ cycle for 12 cycles) and rituximab (375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or placebo (0.9% saline solution IV) plus LEN and rituximab. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for patients with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET-CR rate (INV) at end of treatment (4–8 weeks after last treatment) and OS in patients with FL. Inclusion criteria include age ≥18 y, histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including anti-CD20 refractory disease), ECOG PS ≤2, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab plus LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF < 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling patients; planned enrollment is 528 patients with R/R FL and 60–90 patients with R/R MZL. Clinical trial information: NCT04680052.

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