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Haematologica Mar 2024Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study.
Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23rd 2022 (data cut-off date). In total, 54 of 240 planned patients were randomized (melflufen group, N=27; daratumumab group, N=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (Hazard Ratio: 0.18 [95% Confidence Interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies.
Topics: Humans; Antibodies, Monoclonal; Dexamethasone; Hematopoietic Stem Cell Transplantation; Melphalan; Multiple Myeloma; Neoplasms, Plasma Cell; Neutropenia; Phenylalanine; Proteasome Inhibitors; Transplantation, Autologous; United States; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37646660
DOI: 10.3324/haematol.2023.283509 -
BMJ Open Ophthalmology Aug 2023Prophylactic laser peripheral iridotomy (LPI) and cataract surgery are considered the primary treatments for primary angle closure suspect (PACS) as they have proven...
INTRODUCTION
Prophylactic laser peripheral iridotomy (LPI) and cataract surgery are considered the primary treatments for primary angle closure suspect (PACS) as they have proven effectiveness in widening the iridocorneal angle and addressing the underlying anatomical issues associated with this condition. The objective of this study is to compare the impact of LPI and cataract surgery on anterior chamber angle parameters, aiming to fill the existing research gap.
METHODOLOGY
A prospective comparative study was conducted, involving 76 eyes of 61 patients. The study focused on patients diagnosed with PACSs and early cataract. The patients received treatment either through LPI or cataract surgery. Comprehensive eye examination was performed, including gonioscopy and anterior segment parameters were measured using anterior segment ocular coherence tomography (ASOCT). Follow-up examinations were conducted at 1 week and 1 month after the procedures, which included ASOCT and gonioscopy performed during the 1-month follow-up.
RESULTS
All anterior chamber angle parameters increased significantly after treatment in both groups, including trabecular iris angle (TIA), angle opening distance at 250, 500 and 750 µm (AOD 250, AOD500, AOD750), trabecular iris surface area at 500 and 750 µm (TISA500, TISA750) and angle recess area at 500 and 750 µm from scleral spur (ARA500, ARA750) (p<0.05 for all). Moreover, all these parameters were greater after cataract surgery than after LPI (p<0.05 for all).
CONCLUSION
Compared with LPI, cataract extraction resulted in a wider anterior chamber angle. Moreover, no residual angle closure was observed after cataract extraction, which could morphologically prevent the progress of angle closure. Thus, cataract extraction is superior to LPI in PACSs with early cataract in widening the anterior chamber angle.
Topics: Humans; Prospective Studies; Cataract Extraction; Iris; Atrial Premature Complexes; Anterior Chamber; Cataract; Lasers
PubMed: 37620109
DOI: 10.1136/bmjophth-2023-001339 -
Annals of Hematology Oct 2023The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI)...
Step-in dosing of bosutinib in pts with chronic phase chronic myeloid leukemia (CML) after second-generation tyrosine kinase inhibitor (TKI) therapy: results of the Bosutinib Dose Optimization (BODO) Study.
The approved dose of bosutinib in chronic phase CML is 400 mg QD in first-line and 500 mg QD in later-line treatment. However, given that gastrointestinal (GI) toxicity typically occurs early after treatment initiation, physicians often tend to start therapy with lower doses although this has never been tested systematically in prospective trials in the Western world. The Bosutinib Dose Optimization (BODO) Study, a multicenter phase II study, investigated the tolerability and efficacy of a step-in dosing concept of bosutinib (starting at 300 mg QD) in chronic phase CML patients in 2 or 3 line who were intolerant and/or refractory to previous TKI treatment. Of 57 patients included until premature closure of the study due to slow recruitment, 34 (60%) reached the targeted dose level of 500 mg QD following the 2-weekly step-in dosing regimen. While the dosing-in concept failed to reduce GI toxicity (grade II-IV, primary study endpoint) to < 40% (overall rate of 60%; 95% CI: 45-74%), bosutinib treatment (mean dosage: 403 mg/day) showed remarkable efficacy with a cumulative major molecular remission (MMR) rate of 79% (95% CI: 66 to 88%) at month 24. Of thirty patients refractory to previous therapy and not in MMR at baseline, 19 (64%) achieved an MMR during treatment. GI toxicity did not significantly impact on patient-reported outcomes (PRO) and led to treatment discontinuation in only one patient. Overall, the results of our trial support the efficacy and safety of bosutinib after failure of second-generation TKI pre-treatment. Trial registration: NCT02577926.
Topics: Humans; Tyrosine Kinase Inhibitors; Prospective Studies; Aniline Compounds; Leukemia, Myeloid, Chronic-Phase
PubMed: 37592092
DOI: 10.1007/s00277-023-05394-0 -
Journal of Perinatology : Official... Oct 2023This study describes 3-year follow-up of 200 infants weighing ≥ 700 grams who underwent transcatheter patent ductus arteriosus (PDA) closure with the Amplatzer...
OBJECTIVE
This study describes 3-year follow-up of 200 infants weighing ≥ 700 grams who underwent transcatheter patent ductus arteriosus (PDA) closure with the Amplatzer Piccolo™ Occluder.
STUDY DESIGN
Between June 2017 and February 2019, 200 children were enrolled in this U.S. study (NCT03055858). PDA closure, survival, and device- or procedure-related events were evaluated. A total of 156 of the available 182 patients (86%) completed the study.
RESULTS
The implant success rate was 95.5% (191/200). At 3 years, PDA closure was observed in 100% (33/33) of patients. Survival was >95% with 9 reported deaths. No deaths were adjudicated as device- or procedure-related. Notable events included aortic obstruction (2) requiring stent placement and tricuspid regurgitation (5), for which no interventions were required.
CONCLUSIONS
This follow-up study demonstrates high rates of PDA closure, low serious complication rates, and survival > 95% at 3 years. The Amplatzer Piccolo™ Occluder is a safe and effective therapy for PDA treatment in premature infants.
CLINICALTRIALS
gov identifier: NCT0305585.
Topics: Infant; Humans; Child; Follow-Up Studies; Ductus Arteriosus, Patent; Prospective Studies; Cardiac Catheterization; Septal Occluder Device; Treatment Outcome
PubMed: 37587183
DOI: 10.1038/s41372-023-01741-1 -
Animals : An Open Access Journal From... Jul 2023Few studies have established the normal radiographic anatomical development of the donkey foal and, to date, no data are available for mules. Our aim was thus to...
Few studies have established the normal radiographic anatomical development of the donkey foal and, to date, no data are available for mules. Our aim was thus to evaluate the radiographic development of the fore digit and carpal joint in the mule foal from 0 to 3 months of age. Ten forelimbs of five healthy full-term mule foals were included. Radiographs of the fore digit lateromedial and dorsopalmar and the carpus dorsopalmar were performed weekly for the first month of age, and bi-monthly during the following two months. Fore digit growth plate closure times, morphological, angular, and linear radiographic parameters, and also carpal cuboidal bone mineralization were evaluated. Growth plates were graded as open, closing, and closed. Carpal bone appearance was graded as mature, slightly immature, or immature. Growth plate closure times showed the following: middle phalangeal distal physis (DP) closed at birth, and proximal physis (PP) started to close at around two months; first phalanx DP closed at seven days, and PP started to close at three months; and third metacarpal bone DP started to close at two months. Carpal bones were immature at birth. Distal phalanx (PD) was triangular at birth, palmar processes had developed by one month, and proximal sesamoid bones were trapezoidal by three months. The hoof wall, PD dorsal wall, and palmar angles values changed in parallel, and hoof capsule thickness increased. No PD remodeling evidence within the hoof capsule or variations in the hoof axis with growth were found. We identified a baseline for the interpretation of forelimb radiological features in mule foals. The specific features found were intermediate between those found in horses and donkeys.
PubMed: 37570226
DOI: 10.3390/ani13152417 -
Diagnostics (Basel, Switzerland) Aug 2023Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of...
Association of the rs7557402 Polymorphism with Hemodynamically Significant Patent Ductus Arteriosus Closure Failure in Premature Newborns under Pharmacological Treatment with Ibuprofen.
Patent ductus arteriosus (PDA) is frequent in preterm newborns, and its incidence is inversely associated with the degree of prematurity. The first choice of pharmacological treatment is ibuprofen. Several genes, including , have been proposed as probable markers associated with a genetic predisposition for the development of PDA in preterm infants. 1 NG_016000.1:g.84131C>G or rs7557402 has been reported to be probably benign and associated with familial erythrocytosis by the Illumina Clinical Services Laboratory. Other variants of have been previously reported to be benign for familial erythrocytosis because they decrease gene function and are positive for familial erythrocytosis because the overexpression of is a key factor in uncontrolled erythrocyte proliferation. However, this could be inconvenient for ductal closure, since for this process to occur, cell proliferation, migration, and differentiation should take place, and a decrease in gene activity would negatively affect these processes. Single-nucleotide polymorphisms (SNPs) in and genes were searched with high-resolution melting and Sanger sequencing in blood samples of preterm infants with hemodynamically significant PDA treated with ibuprofen at the National Institute of Perinatology. The variant rs7557402, present in the gene eighth intron, was associated with a decreased response to treatment ( = 0.007, OR = 3.53). The SNP rs7557402 was associated with an increased risk of pharmacological treatment failure. A probable mechanism involved could be the decreased activity of the product of the gene.
PubMed: 37568921
DOI: 10.3390/diagnostics13152558 -
Turkish Archives of Pediatrics Sep 2023The timing of surgical patent ductus arteriosus ligation in preterm infants remains controversial. Early ligation (<2 or 3 weeks of life) benefits preterm infants with a...
OBJECTIVE
The timing of surgical patent ductus arteriosus ligation in preterm infants remains controversial. Early ligation (<2 or 3 weeks of life) benefits preterm infants with a lower incidence of bronchopulmonary dysplasia and necrotizing enterocolitis. We present patent ductus arteriosus ligation experience in premature infants who had been transported for closure to an outside centre other than the hospital they were hospitalized.
MATERIALS AND METHODS
We retrospectively evaluated 17 consecutive patients who had undergone surgery of premature infant patent ductus arteriosus closure during the period of March 2009-December 2020. Patent ductus arteriosus had been clipped in 17 patients.
RESULTS
The median birth weight and age were 930 g and 28 gestation weeks, respectively. The birth age of the sub-groups were A: ≤28 weeks and B: >28 weeks and birthweight were group I: ≤800 g and group II: >800 g. The median day of PDA ligation wasa 20 days, and patients with birthweight ≤800 g were ligated later than patients weighing >800 g. Two patients had intracranial hemorrhage, 6 had bronchopulmonary dysplasia, and 2 were dead. We found that exposure to large patent ductus arteriosus and low birth age in preterm babies was associated with longer hospitalization duration, preoperative mechanical ventilation time, and sepsis.
CONCLUSION
Infants exposed to moderate-to-large patent ductus arteriosus requiring intubation and resistant to medical therapy for more than 2 weeks should have surgical ligation as soon as possible.
PubMed: 37563951
DOI: 10.5152/TurkArchPediatr.2023.23066 -
Clinical Oral Investigations Sep 2023The aim was to provide epidemiological and clinical data on patients with orofacial clefts in Lower Saxony in Germany.
OBJECTIVE
The aim was to provide epidemiological and clinical data on patients with orofacial clefts in Lower Saxony in Germany.
MATERIALS AND METHODS
The records of 404 patients with orofacial clefts treated surgically at the University Medical Center Goettingen from 2001 to 2019 were analyzed in this retrospective study. Prevalence of orofacial clefts in general, orofacial clefts as manifestation of a syndrome, sex distribution, and prevalence of different cleft types was evaluated and associated with the need for corrective surgery, family history, pregnancy complications, and comorbidities.
RESULTS
The prevalence of orofacial clefts for Goettingen in Lower Saxony was 1:890. 231 patients were male and 173 were female. CLP was most common (39.1%) followed by CP (34.7%), CL (14.4%), CLA (9.9%), and facial clefts (2%). The left side was more frequently affected and unilateral cleft forms occurred more often than bilateral ones. Almost 10% of the population displayed syndromic CL/P. 10.9% of all patients had a positive family history regarding CL/P, predominantly from the maternal side. Pregnancy abnormalities were found in 11.4%, most often in the form of preterm birth. Comorbidities, especially of the cardiovascular system, were found in 30.2% of the sample. 2.2% of patients treated according to the University Medical Center Goettingen protocol corrective surgery was performed in form of a velopharyngoplasty or residual hole closure.
CONCLUSIONS
The epidemiological and clinical profile of the study population resembled the expected distributions in Western populations. The large number of syndromic CL/P and associated comorbidities supports the need for specialized cleft centers and interdisciplinary cleft care.
Topics: Pregnancy; Humans; Male; Infant, Newborn; Female; Cleft Lip; Cleft Palate; Retrospective Studies; Premature Birth; Sex Distribution
PubMed: 37542681
DOI: 10.1007/s00784-023-05187-9