Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Renal impairment (RI) is common in patients with multiple myeloma (MM) and new therapies that can improve renal function are needed. The phase III IKEMA study (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03275285","term_id":"NCT03275285"}}NCT03275285) investigated isatuximab (Isa) with carfilzomib and dexamethasone (Kd) versus Kd in relapsed MM. This subgroup analysis examined results from patients with RI, defined as estimated glomerular filtration rate <60 mL/min/1.73 m². Addition of Isa prolonged progression-free survival (PFS) in patients with RI (hazard ratio: 0.27; 95% confidence interval [CI]: 0.11–0.66; median PFS not reached for Isa-Kd versus 13.4 months for Kd [20.8-month follow-up]). Complete renal responses occurred more frequently with Isa-Kd (52.0%) versus Kd (30.8%) and were durable in 32.0% versus 7.7% of patients, respectively. Treatment exposure was longer with Isa-Kd, with median number of started cycles and median duration of exposure of 20 versus 9 cycles and 81.0 versus 35.7 weeks for Isa-Kd versus Kd, respectively. Among patients with RI, the incidence of patients with grade ≥3 treatment-emergent adverse events was similar between the two arms (79.1% in Isa-Kd vs. 77.8% in Kd). In summary, the addition of Isa to Kd improved clinical outcomes with a manageable safety profile in patients with RI, consistent with the benefit observed in the overall IKEMA study population.     

Predictors of malignancy in patients with solitary pulmonary nodules undergoing pulmonary resection

BackgroundThe management of a solitary pulmonary nodule is a challenging issue in pulmonary disease. Although many factors have been defined as predictors for malignancy in solitary pulmonary nodules, the accurate diagnosis can only be established with the permanent histological diagnosis.ObjectiveWe tried to clarify the possible predictors of malignancy in solitary pulmonary nodules in patients who had definitive histological diagnosis.MethodsWe made a retrospective study to collect the data of patients with solitary pulmonary nodules who had histological diagnosis either before or after surgery. We made a statistical analysis of both the clinic and radiological features of these nodules with respect to malignancy both in contingency tables and with logistic regression analysis.ResultsWe had a total of 223 patients with a radiological diagnosis of solitary pulmonary nodule. Age, smoking status and pack years of smoking, maximum standardized uptake value (SUVmax), and radiological features such as solid component, spiculation, pleural tag, lobulation, calcification, and higher density were significant predictors of malignancy in contingency tables. Age, smoking status and smoking (pack/year), SUVmax, and radiological features including spiculation, pleural tag, lobulation, calcification, and higher density were the significant predictors in univariate analysis. However, multivariate analysis revealed only SUVmax greater than 2.5 (p < 0.0001), spiculation (p = 0.009), and age older than 61 years (p = 0.015) as the significant predictors for malignancy.ConclusionAge, SUVmax, and spiculation are the independent predictors of malignancy in patients with solitary pulmonary nodules.     

Comparison of nighttime and daytime operation on outcomes of supracondylar humeral fractures: A prospective observational study

Supracondylar humeral fractures are seen in children and treatment is usually closed reduction and percutaneous pinning (CRPP). This surgery can be performed at night, depending on its urgency. Fatigue and sleep deprivation can impact performance of doctors during night shifts. The purpose of this study is to investigate the association between night shifts postoperative morbidity and mortality of supracondylar fracture operations compared to daytime procedures.This prospective observational study included 94 patients who were aged 5 to 12 years with ASA I to III who had supracondylar humeral fractures, underwent CRPP under general anesthesia. Patients were stratified by the time of surgery using time of induction of anesthesia as the starting time of the procedure, into 2 groups: day (07:30 am–06:29 pm) and night (06:30 pm–07:29 am). In total, 82 patients completed the study: 43 in Group Day and 39 in Group Night.The operation duration in Group Night (114.66 ± 29.46 minutes) was significantly longer than in Group Day (84.32 ± 25.9 minutes) (P = .0001). Operation duration (OR: 0.007; P = .0001) and morbidities (OR: 0.417; P = .035) were independent risk factors in Group Night.Children who had supracondylar humeral fractures, undergoing urgent CRPP surgery, in-hospital mortality was associated with the time of day at which the procedure was performed. Patient safety is critically important for pediatric traumatic patient population. Therefore, we suggested to increase the number of healthcare workers and improve the education and experience of young doctors during night shifts.     

Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induced arthritis

The goal of this investigation was to study the protective effects of thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in rats. On day 0 under ether anesthesia, the experimental groups were immunized with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and emulsified in Freund's incomplete adjuvant. Control rats were gavaged with vehicle, whereas CII was administered intradermally. In addition, arthritis treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3 weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a week for 3 weeks starting on day 0). A significant decrease in the incidence and severity of arthritis by clinical and radiographic assessments was found in recipients of therapy, compared with that of controls. The MTX treatment significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in arthritic rats. Likewise, TQ treatment was also able to reduce significantly (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The histopathologic abnormalities are consistent with the hydropic epithelial cell degenerations and moderate tubular dilatation in the some proximal and distal tubules. The severity of the degenerative changes in most of the shrunken glomerules and vascular congestion were also observed in arthritic animals. Preventive treatment of TQ and especially MTX significantly inhibited kidney dysfunction and this histopathologic alterations. These studies indicate that TQ can be used similar to MTX as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.     

CYP1A1 gene polymorphism and polycystic ovary syndrome

The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).     

Factors affecting live birth rate in intrauterine insemination cycles with recombinant gonadotrophin stimulation

The objective of this cross-sectional study was to identify the prognostic factors that influence the outcome of ovarian stimulation with intrauterine insemination (IUI) cycles using gonadotrophins in couples with unexplained and mild male-factor subfertility. A total of 838 cycles in 456 women with unexplained and mild male-factor subfertility attending a university-based infertility clinic was evaluated. Of these cycles, 139 resulted in pregnancy (16.6% per cycle) and 96 out of 98 ongoing pregnancies resulted in live term birth. Live birth rate per patient and per cycle was 21.1% and 11.4%, respectively. Multivariate logistic regression analysis demonstrated that duration of infertility (P = 0.034), type of infertility (P = 0.003), aetiology of infertility (P = 0.004), number of treatment cycles (P = 0.0001) and number of dominant follicles before human chorionic gonadotrophin (HCG; P = 0.024) were significant independent factors to predict clinical pregnancy. The duration of infertility (P = 0.043), number of treatment cycles (P = 0.0001) and number of dominant follicles before HCG (P = 0.024) were significant independent factors to predict live birth. In conclusion, for subfertile couples having shorter duration of subfertility, multifollicular response to gonadotrophins and in their first treatment cycle are more likely to succeed a live birth with IUI treatment using recombinant gonadotrophins.