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Journal of Hematology & Oncology Jun 2024It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of...
It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.
Topics: Humans; Multiple Myeloma; Aged; Prospective Studies; Male; Female; Aged, 80 and over; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Frailty; Lenalidomide; Bortezomib; Precision Medicine; Frail Elderly; Geriatric Assessment; Antibodies, Monoclonal
PubMed: 38915117
DOI: 10.1186/s13045-024-01569-y -
Scientific Reports Jun 2024Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro... (Meta-Analysis)
Meta-Analysis Comparative Study
Despite the proven superiority of various luteal phase support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration. The aim of the present study was to identify the optimal LPS under six core aspects of ART success, clinical pregnancy, live birth as primary outcomes and biochemical pregnancy, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) events as secondary outcomes. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023, (PROSPERO Registration: CRD42022358986). Only Randomised Controlled Trials (RCTs) were included. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS given its' clinical relevance. Seventy-six RCTs, comparing 22 interventions, and including 26,536 participants were included in the present NMA. Overall CiNeMa risk of bias was deemed moderate, and network inconsistency per outcome was deemed low (Multiple pregnancy χ: 0.11, OHSS χ: 0.26), moderate (Clinical Pregnancy: χ: 7.02, Live birth χ: 10.95, Biochemical pregnancy: χ: 6.60, Miscarriage: χ: 11.305). Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP + OE + SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP + SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP + OE + SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP + SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95% CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95% CrI 0.75, 3.71)]. The combination of intramuscular and vaginal progesterone was associated with higher multiple pregnancy events, [OR 7.09 (95% CrI 2.49, 31.)]. Of all LPS protocols, VP + SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP + SCGnRH-a, with an OR 2.89 [95% CrI 1.08, 2.96] and OR 2.84 [95% CrI 1.35, 6.26] respectively. Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.
Topics: Humans; Female; Sperm Injections, Intracytoplasmic; Pregnancy; Network Meta-Analysis; Fertilization in Vitro; Luteal Phase; Pregnancy Rate; Progesterone; Live Birth; Bayes Theorem; Ovulation Induction; Randomized Controlled Trials as Topic; Ovarian Hyperstimulation Syndrome; Abortion, Spontaneous
PubMed: 38914570
DOI: 10.1038/s41598-024-64804-z -
International Ophthalmology Jun 2024Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO).
METHODS
This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups.
RESULTS
At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections.
CONCLUSION
Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications.
TRIAL REGISTRATION INFORMATION
The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).
Topics: Humans; Retinal Vein Occlusion; Ranibizumab; Male; Female; Dexamethasone; Intravitreal Injections; Macular Edema; Prospective Studies; Drug Implants; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Glucocorticoids; Tomography, Optical Coherence; Treatment Outcome; Aged; Drug Therapy, Combination; Follow-Up Studies
PubMed: 38913192
DOI: 10.1007/s10792-024-03158-x -
BMJ Open Jun 2024Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and...
INTRODUCTION
Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series.
METHODS AND ANALYSIS
This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over.
ETHICS AND DISSEMINATION
This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians.
TRIAL REGISTRATION NUMBER
jRCTs041210027.
Topics: Humans; Histiocytosis, Langerhans-Cell; Child; Adolescent; Japan; Adult; Dexamethasone; Young Adult; Zoledronic Acid; Male; Female; Clinical Trials, Phase II as Topic; Child, Preschool; Bone Density Conservation Agents
PubMed: 38910000
DOI: 10.1136/bmjopen-2024-084159 -
The Journal of Steroid Biochemistry and... Jun 2024Steroids are potential anti-leukemia agents, and Epigynum auritum is a Yunnan folk medicine with high levels of androsterone, pregnane, and steroid derivatives. However,...
Steroids are potential anti-leukemia agents, and Epigynum auritum is a Yunnan folk medicine with high levels of androsterone, pregnane, and steroid derivatives. However, the underlying therapeutic mechanism of androsta-4,6,8,14-tetraene-3,11,16-trione (ATT), an androsterone isolated from Epigynum auritum, is not yet clear. This study aimed to explore the anti-leukemia mechanism of ATT using molecular biology, network pharmacology, and molecular docking technology. The cell viability results showed that ATT had an anti-proliferation effect in acute lymphoblastic leukemia cells (CEM/C1, MOLT-4, Jurkat, BALL-1, Nalm-6, and RS4;11). Further studies showed that ATT reduced the mitochondrial membrane potential in B-cell acute lymphoblastic leukemia cell lines (BALL-1, Nalm-6, and RS4;11) and induced cell cycle arrest in MOLT-4 and BALL-1. ATT induced BALL-1 cell apoptosis by activating Caspase 3/7 activity and causing DNA fragmentation. Network pharmacology results suggested that ATT exerts its anti-leukemia activity via the PI3K/Akt signaling pathway. In addition, molecular docking analysis showed that ATT had high scores in docking with PTGS2, NR3C1, and AR. Western blotting results showed that ATT reduced the relative protein level of P-PI3K and P-Akt, thereby increasing the relative level of pro-apoptosis protein Bax and reducing the relative level of anti-apoptosis protein Bcl-2, the apoptosis downstream protein pro-caspase3, and cell proliferation-related proteins (P-GSK3B and CyclinD1). In conclusion, these results demonstrated that ATT could be a potential candidate drug with apoptosis-induction and cell cycle arrest effects for further investigation in acute lymphoblastic leukemia therapy.
PubMed: 38909867
DOI: 10.1016/j.jsbmb.2024.106573 -
European Journal of Dermatology : EJD Apr 2024
Topics: Humans; Triamcinolone Acetonide; Cicatrix; Female; Drug Packaging; Glucocorticoids; Adult; Male; Face; Combined Modality Therapy
PubMed: 38907566
DOI: 10.1684/ejd.2024.4659 -
International Ophthalmology Jun 2024To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based...
OBJECTIVE
To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme.
METHODS
Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups.
RESULTS
After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10).
CONCLUSION
Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.
Topics: Humans; Epiretinal Membrane; Retrospective Studies; Intravitreal Injections; Male; Female; Visual Acuity; Tomography, Optical Coherence; Glucocorticoids; Fovea Centralis; Vitrectomy; Triamcinolone Acetonide; Case-Control Studies; Aged; Middle Aged; Follow-Up Studies; Treatment Outcome
PubMed: 38907177
DOI: 10.1007/s10792-024-03188-5 -
Nature Communications Jun 2024Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to...
Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.
Topics: Humans; Female; Pregnancy; China; Maternal Exposure; Adult; Premature Birth; Pregnancy Trimester, First; Prospective Studies; Pregnancy Outcome; Dydrogesterone; Progesterone; Birth Cohort; Infant, Newborn; Abortion, Spontaneous; Stillbirth; Infant, Low Birth Weight; Longitudinal Studies; Incidence; Young Adult
PubMed: 38906856
DOI: 10.1038/s41467-024-49623-0 -
The Medical Letter on Drugs and... Jun 2024
Topics: Humans; Eosinophilic Esophagitis; Budesonide; Administration, Oral; Suspensions; Treatment Outcome; Glucocorticoids
PubMed: 38905533
DOI: 10.58347/tml.2024.1704c -
Medicine Jun 2024Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH...
INTRODUCTION
Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection.
PATIENT CONCERNS
We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated.
DIAGNOSIS
The patient fulfilled diagnostic criteria for HLH.
INTERVENTIONS
Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed.
OUTCOMES
After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized.
LESSIONS
The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Child, Preschool; Otitis Media; Acute Disease; Dexamethasone; Cyclosporine; Etoposide; Immunoglobulins, Intravenous
PubMed: 38905364
DOI: 10.1097/MD.0000000000038616