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Cureus May 2024Desmoid tumors, also referred to as aggressive fibromatosis, represent an uncommon form of fibroblastic proliferation. These neoplasms may arise within any...
Desmoid tumors, also referred to as aggressive fibromatosis, represent an uncommon form of fibroblastic proliferation. These neoplasms may arise within any musculoaponeurotic structure throughout the body. They are classified as benign due to several distinctive features: histologically, they exhibit regular mitotic activity and are devoid of metastatic potential. Computed tomography (CT) remains the definitive modality for precise diagnosis, and surgical excision is strongly advised. This account details the manifestation of a desmoid tumor located in the anterior abdominal wall of a 31-year-old female patient who notably lacks any prior surgical interventions. The surgical intervention entailed the excision of the neoplasm and subsequent reconstruction of the abdominal wall utilizing a polypropylene mesh. Postoperatively, the patient was released from the medical facility after a period of three days, having experienced no post-surgical complications. This was followed by a six-month interval free of any adverse events.
PubMed: 38953071
DOI: 10.7759/cureus.61383 -
Frontiers in Immunology 2024Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR. In this first-in-human study, icanbelimod was investigated in healthy men in... (Randomized Controlled Trial)
Randomized Controlled Trial
Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.
BACKGROUND
Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR. In this first-in-human study, icanbelimod was investigated in healthy men in Australia.
METHODS
Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort.
RESULTS
Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (T 4-7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions.
CONCLUSION
Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT02280434.b.
Topics: Humans; Male; Adult; Australia; Double-Blind Method; Young Adult; Healthy Volunteers; Sphingosine 1 Phosphate Receptor Modulators; Middle Aged; Sphingosine-1-Phosphate Receptors; Lymphocyte Count; Adolescent
PubMed: 38953034
DOI: 10.3389/fimmu.2024.1380975 -
RSC Advances Jun 2024Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger...
Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including , , and have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.
PubMed: 38952927
DOI: 10.1039/d4ra00796d -
Cureus Jun 2024Background Postpartum depression (PPD) is a complex mix of physical, emotional, and behavioral changes that happen in some women after giving birth. Objectives The aim...
Background Postpartum depression (PPD) is a complex mix of physical, emotional, and behavioral changes that happen in some women after giving birth. Objectives The aim of the study is to determine the prevalence of PPD using the Edinburgh Postnatal Depression Scale (EPDS) and evaluate the predisposing factors for PPD. Methodology The present observational study was conducted in the Department of Community Medicine, Maharaja Krushna Chandra Gajapati (MKCG) Medical College and Hospital, Brahmapur, Odisha, India from May 2022 to November 2022. Using the EPDS, participants were assessed for postnatal depression. Every subject additionally filled out a risk factor questionnaire covering important sociodemographic and obstetric parameters. The prevalence of an EPDS score of 12 or above is the primary outcome measure. Results The study encompassed 121 mothers, with 8.26% scoring above the depression cutoff of 12 and 6.61% falling within the borderline range. Notably, all mothers surpassing the cutoff were from joint families, contrasting with those from nuclear families. A predominant portion of the depressive group was in their 20s, while the borderline group primarily consisted of mothers in their 30s. Urban residency and government hospital care were universal among the samples. Mode of delivery showed significance, with a higher prevalence of PPD observed among those who underwent a lower segment cesarean section. Additionally, maternal age, anemia, mode of delivery, educational status, adverse life events, and lack of partner support significantly correlated with depression scores. Notably, maternal age emerged as the most influential factor, followed by anemia and mode of delivery. Spearman correlation analysis revealed moderate negative associations between various aspects of maternal depression and the ages of their babies, indicating that younger infants were associated with greater maternal distress. However, the correlation between feeling sad or miserable and the baby's age was negligible. These findings emphasize the multifaceted nature of PPD, highlighting the interplay between sociodemographic factors, maternal well-being, and infant age.
PubMed: 38952605
DOI: 10.7759/cureus.61503 -
Cureus Jun 2024Guillain-Barré syndrome (GBS) resulting from the use of immune checkpoint inhibitors (ICIs) is relatively uncommon but has been reported. Herein, we discuss a case of...
Guillain-Barré syndrome (GBS) resulting from the use of immune checkpoint inhibitors (ICIs) is relatively uncommon but has been reported. Herein, we discuss a case of a 67-year-old patient who received neoadjuvant ICI for treatment of non-small cell lung cancer and then presented with lower extremity weakness and areflexia, progressing to respiratory muscle and upper extremity weakness. Given the increasing use of ICI in cancer management, awareness of neurological autoimmune side effects is essential. ICI-mediated GBS can be severe and fatal if not diagnosed promptly. We discuss a case of ICI-induced GBS and review literature on current management approaches.
PubMed: 38952584
DOI: 10.7759/cureus.61489 -
Cureus Jun 2024This case report presents a rare but severe complication of polyethylene glycol (PEG) used for colonoscopic bowel preparation. A 71-year-old male developed cardiac...
This case report presents a rare but severe complication of polyethylene glycol (PEG) used for colonoscopic bowel preparation. A 71-year-old male developed cardiac arrest secondary to hypovolemic shock following consumption of GoLytely. Despite being hemodynamically stable prior to ingestion, the patient experienced extreme weakness, dizziness, and orthostatic hypotension post-consumption. Evaluation ruled out other causes of arrest. While serious complications from PEG are rare, this case underscores the importance of vigilance. Further investigation is warranted to elucidate the relationship between PEG use and cardiac events and to identify potential risk factors for adverse outcomes associated with bowel preparation regimens.
PubMed: 38952579
DOI: 10.7759/cureus.61486 -
Cureus Jun 2024Introduction Filgotinib is a JAK-1 selective inhibitor approved for ulcerative colitis (UC) treatment in Japan. Its effectiveness has been confirmed but remains unknown...
Introduction Filgotinib is a JAK-1 selective inhibitor approved for ulcerative colitis (UC) treatment in Japan. Its effectiveness has been confirmed but remains unknown in actual clinical practice. Therefore, we aimed to evaluate the effectiveness and safety of filgotinib and identify suitable patients in the Japanese population. Methods We retrospectively reviewed the background, clinical course, and laboratory data of patients treated with filgotinib 200 mg for UC between May 2022 and December 2023. Results The median observation period for the 25 patients was 232 days (interquartile ranges (IQR) 102-405). The median age of the patients was 43 years (IQR 29-55), disease duration was nine years (IQR 2-12), and 36% (9/25) of patients were biologic or small molecule naïve. The median patient-reported outcome (PRO2) and partial Mayo (pMayo) scores at agent initiation were 3 (IQR 1-4) and 4.5 (IQR 3-6), respectively. The PRO2 and pMayo scores improved significantly two weeks after treatment initiation (p < 0.05). Clinical remission rates at 24 weeks after treatment initiation were 60% (15/25) for PRO2 ≤ 1 and 52% (13/25) for pMayo ≤ 1. The Mayo endoscopic subscore significantly improved after filgotinib initiation (p=0.04), and the endoscopic remission rate was 47% (8/17). At 24 weeks, patients in clinical remission, compared to those not in remission, had significantly lower baseline PRO2 and pMayo scores and longer disease duration (p=0.03, p=0.03, and p=0.04, respectively). The filgotinib persistence rate was 68% (17/25), with no discontinuation because of adverse events. Patients who continued treatment had significantly lower PRO2, pMayo scores, and blood neutrophil counts at initiation than those who discontinued (p=0.02, p=0.03, and p=0.02, respectively). Conclusion Filgotinib appears to be effective and safe in Japanese patients with UC. Effectiveness and persistence were high in patients whose PRO2 and pMayo scores were low at the time of treatment initiation.
PubMed: 38952578
DOI: 10.7759/cureus.61496 -
Frontiers in Oncology 2024Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials...
BACKGROUND
Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials in the 3rd-line setting. This large-scale, prospective observational study evaluated the safety and effectiveness of regorafenib in Japanese patients with GIST in a real-world clinical setting.
METHODS
Patients with GIST received oral regorafenib at a maximum daily dose of 160 mg for weeks 1-3 of each 4-week cycle (dose could be modified at investigator's discretion). The primary objective was to assess safety, particularly significant adverse drug reactions (ADRs), as well as the frequency of occurrence of ADRs, hand and foot syndrome (HFS), discontinuation of treatment due to disease progression and adverse events. A Cox proportional hazards model was used to evaluate associations between OS or time to treatment failure (TTF) and baseline characteristics or HFS.
RESULTS
Between August 2013 and March 2021, 143 evaluable patients were enrolled. ADRs occurred in 90.2% of patients and led to treatment discontinuation in 28.3%. The most frequent ADRs were HFS, hypertension, and liver injury. The overall response rate was 11.3% and disease control rate 56.5% (RECIST) based on investigators' assessments. Median OS was 17.4 months (95% CI 14.24-23.68). Median TTF was 5.3 (95% CI 4.0-6.5) months. Improved OS and TTF responses occurred in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1.
CONCLUSION
The outcomes in this real-world study were consistent with those seen in clinical trials. No new safety concerns were identified.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov, identifier NCT01933958.
PubMed: 38952554
DOI: 10.3389/fonc.2024.1412144 -
Frontiers in Oncology 2024Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors...
Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.
PubMed: 38952547
DOI: 10.3389/fonc.2024.1331472 -
Frontiers in Oncology 2024Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients...
BACKGROUND
Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.
METHODS
Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis.
RESULTS
1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.
CONCLUSION
1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.
PubMed: 38952544
DOI: 10.3389/fonc.2024.1390820