-
Annals of Oncology : Official Journal... Aug 2023The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO)... (Randomized Controlled Trial)
Randomized Controlled Trial
Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized AGO-B WSG PreCycle trial.
BACKGROUND
The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations.
PATIENTS AND METHODS
Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy-General (FACT-G) score], using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL.
RESULTS
In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform).
CONCLUSIONS
PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Quality of Life; Antineoplastic Combined Chemotherapy Protocols; Pyridines; Receptor, ErbB-2
PubMed: 37201751
DOI: 10.1016/j.annonc.2023.05.003 -
Cancers Jul 2023In appendiceal cancers, the most frequently mutated genes are (i) , which, when reactivated, restores signal transduction via the RAS-RAF-MEK-ERK signaling pathway and... (Review)
Review
In appendiceal cancers, the most frequently mutated genes are (i) , which, when reactivated, restores signal transduction via the RAS-RAF-MEK-ERK signaling pathway and stimulates cell proliferation in the early stages of tumor transformation, and then angiogenesis; (ii) , whose inactivation leads to the inhibition of programmed cell death; (iii) , which, when reactivated, links the cAMP pathway to the RAS-RAF-MEK-ERK signaling pathway, stimulating cell proliferation and angiogenesis; (iv) , exhibiting typical tumor-suppressive activity, blocking the transmission of oncogenic TGFB signals via the SMAD2/SMAD3 heterodimer; and (v) , which is part of the RAS-RAF-MEK-ERK signaling pathway. Diverse mutations are reported in other genes, which are part of secondary or less critical signaling pathways for tumor progression, but which amplify the phenotypic diversity of appendiceal cancers. In this review, we will present the main genetic mutations involved in appendix tumors and their roles in cell proliferation and survival, and in tumor invasiveness, angiogenesis, and acquired resistance to anti-growth signals.
PubMed: 37509254
DOI: 10.3390/cancers15143591 -
World Journal of Gastrointestinal... Apr 2024In this editorial, we comment on the article published in the recent issue of the . We focused on the understanding of appendiceal disease, and the various options for...
In this editorial, we comment on the article published in the recent issue of the . We focused on the understanding of appendiceal disease, and the various options for diagnosis and treatment via endoscopy. Some factors affecting the diagnosis and management of appendiceal diseases are also discussed. The existence of any organ has its natural rationality, and the appendix is such a magical organ. A growing number of experts and scholars have gradually come to a consensus that the appendix is not a useless evolutionary relic. There are many lymphocytes and lymph nodes in the appendix wall, which has a strong immune function, and this function is particularly important for children and adolescents. Many intestinal probiotics in the appendix are very helpful for maintaining the balance of the intestinal flora. With the continuous progress of endoscopic technology, endoscopic treatment involving preservation of the appendix has shown great advantages over surgery. In the diagnosis of appendiceal inflammation and neoplasms, colonoscopy, endoscopic retrograde appendicography and choledochoscopy help assess conditions of the appendix. Endoscopic retrograde appendicitis therapy, abscess drainage under colonoscopy, fenestration of abscess under colonoscopy, and endoscopic or natural orifice transluminal endoscopic surgery resection of appendiceal neoplasms are safe and effective endoscopic treatments for appendiceal disease. New breakthroughs in the application of endoscopy in the appendix are expected to occur in the near future.
PubMed: 38680200
DOI: 10.4253/wjge.v16.i4.187 -
Cureus Jan 2024Appendectomy remains the gold standard for treating appendicitis, but advancements in laparoscopic techniques have shifted the paradigm. Natural orifice transluminal... (Review)
Review
Appendectomy remains the gold standard for treating appendicitis, but advancements in laparoscopic techniques have shifted the paradigm. Natural orifice transluminal endoscopic surgery (NOTES) and transvaginal appendectomy (TVA) offer a potentially less invasive alternative to traditional laparoscopic appendectomy (LA). This article systematically reviews the procedures, perceptions, and complications of TVA to assess its viability as a surgical option. Between January 1, 2003, and November 1, 2023, 4832 case reports, case series, and experimental and observational peer-reviewed publications were examined and filtered using the keyword "Transvaginal Laparoscopic Appendectomy." The publications were screened using PRISMA guidelines, and 20 studies were included for analysis and review. Survey results showed that women's acceptance of TVA was 43%, citing reduced invasiveness as a major reason for positive reception. TVA procedures exhibited consistency, with variations in appendectomy methods, appendix removal, and posterior fornix incision closure. Positive outcomes included shorter operation times, reduced postoperative pain, and minimal scarring. Complications were uncommon but included bladder puncture, urinary tract infections, and intra-abdominal abscesses. Indications primarily focused on surgical safety, reduced scarring, and postoperative benefits. Sexual function post-TVA exhibited no significant differences in most cases, with a recovery period of two to four weeks. This systematic review suggests that TVA is a promising alternative to traditional LA, offering potential advantages in terms of postoperative complications. While the existing literature indicates positive outcomes, further research with larger sample sizes and long-term follow-ups is needed to validate the efficacy and safety of TVA and assess how the procedure impacts the reproductive function of patients.
PubMed: 38333466
DOI: 10.7759/cureus.51962 -
Seminars in Hearing Feb 2024Speech-in-noise testing has been proposed as a useful part of the audiometric test battery dating back to the earliest years of the field of audiology. Many... (Review)
Review
Speech-in-noise testing has been proposed as a useful part of the audiometric test battery dating back to the earliest years of the field of audiology. Many speech-in-noise tests have been developed and used to varying degrees. However, multiple barriers have prevented speech-in-noise testing from being used widely in the clinic. The purpose of this article is to provide a resource to audiologists and other hearing health professionals who want to know (1) what tests are available for use, (2) the rationale behind specific tests, and (3) important considerations when selecting one or more tests to use clinically. In addition, data are presented for four speech-in-noise tests with the purpose of comparing outcomes as a function of age and hearing status. The four tests (QuickSIN, Words in Noise [WIN], Listening in Spatialized Noise-Sentences [LiSN-S], and Coordinate Response Measure [CRM]) were completed by 30 individuals from three groups: 10 young adults with normal hearing, 10 older adults with normal hearing, and 10 older adults with hearing loss. The results suggest that, despite significant differences in performance between groups, group overlap was present such that some individuals from one group performed similar to some individuals of other groups; therefore, individual performance was more important than associated group. When selecting an appropriate speech-in-noise test to use clinically, audiologists should carefully consider the purpose of their testing and the type of information they desire as an outcome. A quick-resource table and appendix is provided to aid audiologists and other health professionals in their selection of an appropriate speech-in-noise test.
PubMed: 38370518
DOI: 10.1055/s-0043-1770155 -
Revista Espanola de Enfermedades... May 2024A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was...
A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.
PubMed: 38767030
DOI: 10.17235/reed.2024.10500/2024 -
Viruses Sep 2023Appendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is...
Appendix has a distinct abundance of lymphatic cells and serves as a reservoir of microbiota which helps to replenish the large intestine with healthy flora. And it is the primary site of IgA induction, which shapes the composition of the intestinal microbiota. Recent population-based cohort studies report that appendectomy is associated with an increased risk of acute myocardial infarction and ischemic heart disease. Here, whether appendectomy has an effect on the occurrence and development of coxsackievirus B3 (CVB3)-induced viral myocarditis is studied. 10 TCID CVB3 was inoculated i.p. into appendectomized and sham-operated mice. RNA levels of viral load and pro-inflammatory cytokines in the hearts and the intestine were detected by RT-PCR. Compared to sham-operated mice, appendectomized mice exhibited attenuated cardiac inflammation and improved cardiac function, which is associated with a systemic reduced viral load. Appendectomized mice also displayed a reduction in cardiac neutrophil and macrophage infiltration and pro-inflammatory cytokine production. Mechanistically, we found that CVB3 induced an early and potent IL-10 production in the cecal patch at 2 days post infection. Appendectomy significantly decreased intestinal IL-10 and IL-10 CD4 Treg frequency which led to a marked increase in intestinal (primary entry site for CVB3) anti-viral IFN-γ CD4 T and IFN-γ CD8 T response and viral restriction, eventually resulting in improved myocarditis. Our results suggest that appendix modulates cardiac infection and inflammation through regulating intestinal IL-10 Treg response.
Topics: Humans; Mice; Animals; Myocarditis; Interleukin-10; Appendectomy; Coxsackievirus Infections; Inflammation; Enterovirus B, Human; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37896753
DOI: 10.3390/v15101974 -
Blood Transfusion = Trasfusione Del... Nov 2023Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count....
BACKGROUND
Most public cord blood (CB) banks currently discard more than 80% of umbilical CB units not suitable for hemopoietic stem cell transplant due to low stem cell count. Although CB platelets, plasma, and red blood cells have been used for experimental allogeneic applications in wound healing, corneal ulcer treatment, and neonatal transfusion, no standard procedures for their preparation have been defined internationally.
MATERIALS AND METHODS
A network of 12 public CB banks in Spain, Italy, Greece, the UK, and Singapore developed a protocol to validate a procedure for the routine production of CB platelet concentrate (CB-PC), CB platelet-poor plasma (CB-PPP), and CB leukoreduced red blood cells (CB-LR-RBC) using locally available equipment and the commercial BioNest ABC and EF medical devices. CB units with >50 mL volume (excluding anticoagulant) and ≥150×10/L platelets were double centrifuged to obtain CB-PC, CB-PPP, and CB-RBC. The CB-RBC were diluted with saline-adenine-glucose-mannitol (SAGM), leukoreduced by filtration, stored at 2-6°C, and tested for hemolysis and potassium (K+) release over 15 days, with gamma irradiation performed on day 14. A set of acceptance criteria was pre-defined. This was for CB-PC: volume ≥5 mL and platelet count 800-1,200×10/L; for CB-PPP: platelet count <50×10/L; and for CB-LR-RBC: volume ≥20 mL, hematocrit 55-65%, residual leukocytes <0.2×10/unit, and hemolysis ≤0.8%.
RESULTS
Eight CB banks completed the validation exercise. Compliance with acceptance criteria was 99% for minimum volume and 86.1% for platelet count in CB-PC, and 90% for platelet count in CB-PPP. Compliance in CB-LR-RBC was 85.7% for minimum volume, 98.9% for residual leukocytes, and 90% for hematocrit. Compliance for hemolysis ≤0.8% decreased from 89.0 to 63.2% from day 0 to 15. K+ release increased from 3.0±1.8 to 25.0±7.0 mmol/L from day 0 to 15, respectively.
DISCUSSION
The MultiCord12 protocol was a useful tool to develop preliminary standardization of CB-PC, CB-PPP, and CB-LR-RBC.
Topics: Infant, Newborn; Humans; Hemolysis; Blood Banking; Erythrocytes; Blood Banks; Blood Platelets
PubMed: 37146297
DOI: 10.2450/BloodTransfus.492 -
Indian Journal of Cancer Oct 2023Histopathological examination of appendectomy specimens may reveal malignancies. Based on these results, either appendectomy is sufficient or sometimes a further...
BACKGROUND
Histopathological examination of appendectomy specimens may reveal malignancies. Based on these results, either appendectomy is sufficient or sometimes a further treatment protocol can be needed. In this study, malignancy-diagnosed cases on appendectomy specimen were examined.
METHODS
Patients who underwent appendectomy between January 2013 and December 2018 with a pre-diagnosis of acute appendicitis were evaluated retrospectively and those cases with malignancy were included in the study. Patients' age, sex, tumor type, tumor diameter, tumor grade, tumor localization, surgical margin, Ki-67 index, state of lymphovascular invasion, state of peri-neural invasion, and follow-up period duration were recorded.
RESULTS
On examination of 2336 appendectomy specimens, 16 patients (0.7%) were found to have neuroendocrine tumors (NET), 11 patients (0.5%) were found to have low-grade mucinous neoplasm (LAMN), and five patients (0.2%) were found to have primary appendix carcinomas. Appendix tumors usually present with acute appendicitis symptoms. Despite re-operation with right hemicolectomy (RHC) being required in the treatment of adenocarcinoma cases, appendectomy provides adequate treatment in most cases with NET and LAMN. With these tumors, which usually have a benign prognosis, it is important to perform the necessary screening in the postoperative period and not to interrupt follow-up.
Topics: Humans; Appendiceal Neoplasms; Appendicitis; Retrospective Studies; Appendectomy; Neuroendocrine Tumors
PubMed: 38159212
DOI: 10.4103/ijc.IJC_450_20