Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance.

Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin.     

New optimized piperamide analogues with potent in vivo hypotensive properties

We describe herein the structural optimization of new piperamide analogues, designed from two natural prototypes, piperine 1 and piperdardine 2, obtained from Piper tuberculatum Jacq. (Piperaceae). Molecular modeling studies using semiempirical AM1 method were made in order to establish rational modifications to optimize them by molecular simplification. The targeted compounds (10) and (11) were respectively obtained using benzaldehyde (12) and para-anisaldehyde (13) as starting materials. ¹H NMR spectra showed that the target compounds were diastereoselectively obtained as the (E)-isomer, the same geometry of the natural prototypes. These new synthetic amides presented significant hypotensive effects in cardiovascular essays using in vivo methodologies. Compound 11 (N-[5-(4′-methoxyphenyl)-2(E)-pentenoyl]thiomorpholine) showed a potency 10,000 times greater than its prototype 5, evidencing an optimization of the molecular architecture for this class of hypotensive drug candidates.     

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.     

Intrauterine fallopian tube incarceration: an uncommon complication of termination of pregnancy by vacuum aspiration

A 34-year-old woman presented with an intermittent abdominal pain 5 years after voluntary vacuum aspiration for interruption of a first-trimester pregnancy. Magnetic resonance imaging demonstrated complete septate uterus and a cystic mass that infiltrated the posterior myometrial wall of the right side of the uterus. Laparoscopy and hysteroscopy revealed an intra uterine fallopian tube incarceration.     

Age at sexual initiation and number of sexual partners in the female Spanish population Results from the AFRODITA survey

Objectives

The AFRODITA study was designed to describe patterns relating to the number of lifetime sexual partners (SP) and age at first sexual intercourse (AFSI) by geographic region in a representative sample of Spanish women.

Study design

A representative sample of the female Spanish population was obtained using the Access Panel Technique. Postal questionnaires were sent to 11,086 women aged 18–70 years. Data were collected on AFSI, number of sexual partners, contraceptive methods, cervical cancer screening and socio-demographic characteristics.

Results

The average AFSI was 20.9 years. AFSI below the age of 19 years was reported by 30.8% of the women. Among sexually active women, 70.6% reported being monogamous and 6.4% reported ≥5 lifetime sexual partners. Younger age at interview was strongly related to earlier AFSI and to higher number of lifetime sexual partners. Women younger than 25 were 39 times more likely to have an AFSI before age 18 than women over age 55. The percentage of women aged less than 25 reporting two or more sexual partners was four times higher than that of women 56 and older. In the multivariate analysis, having two or more sexual partners was independently associated with young age, early AFSI, having ever used oral contraceptives, living in an urban area, having had a screening Pap test in the last 3 years, having a sexually transmitted infection and nuliparity.

Conclusions

This study confirms important changes in the sexual behaviour of Spanish women. Younger cohorts show a younger age at sexual initiation and higher number of sexual partners. These are key factors that may induce changes in the human papillomavirus (HPV) prevalence and the cervical cancer incidence in Spain.     

Mode of delivery and fecal incontinence at midlife: a study of 2,640 women in the Gazel cohort

OBJECTIVE: To estimate obstetric risk factors of fecal incontinence among middle-aged women. METHODS: We conducted a mail survey of the Gazel cohort of volunteers for epidemiologic research. In 2000, a questionnaire on anal incontinence was mailed to 3,114 women who were then between the ages of 50 and 61 years; 2,640 (85%) women returned the completed questionnaire. Fecal incontinence was defined by involuntary loss of stool. Logistic regression was used to estimate the effect of obstetric and general risk factors. RESULTS: Prevalence of fecal incontinence in the past 12 months was 9.5% (250). Significant risk factors for fecal incontinence were completion of high school (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.0), self-reported depression (OR 2.1, 95% CI 1.6-2.7), overweight or obesity measured by body mass index (BMI) (OR 1.5 for BMI of 25-30, 95% CI 1.1-2.0; OR 1.6 for BMI more than 30, 95% CI 1.1-2.5), surgery for urinary incontinence (OR 3.5, 95% CI 2.0-6.1), and anal surgery (OR 1.7, 95% CI 1.1-2.9). No obstetric variable (parity, mode of delivery, birth weight, episiotomy, or third-degree perineal tear) was significant. Prevalence of fecal incontinence was similar for nulliparous, primiparous, secundiparous, and multiparous women (11.3%, 9.0%, 9.0%, and 10.4%, respectively), and among parous women, it was similar for women with spontaneous vaginal, instrumental (at least one), or only cesarean deliveries (9.3%, 10.0%, and 6.6%, respectively). CONCLUSION: In our population of women in their 50s, fecal incontinence was not associated with either parity or mode of delivery.     

DRESS syndrome: a detailed insight

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious and potentially fatal adverse effect to therapeutic medications. The incidence of this condition varies among different ethnicities because of the difference in the genetic makeup. Though fever, rash and eosinophilia are essential features for the diagnosis of this syndrome, these vary from patient to patient along with the involvement of various organs such as liver, kidney, lungs, pancreas, etc. Some of the atypical features are dysphagia, agranulocytosis, and chylous ascites. Phenytoin, phenobarbitone, carbamazepine, and allopurinol are the most common drugs responsible for developing this syndrome, although the list is fairly long. Among the criteria used for the diagnosis of DRESS syndrome, European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) criteria is the most commonly used one. The management of this syndrome involves early removal of the causative agent and treatment with anti-histamines and emollients in the mild form, corticosteroids in the moderate form and plasmapheresis in the severe form along with other alternatives drugs. Healthcare professionals should be more vigilant about the early manifestations of this syndrome, as early diagnosis and treatment improve outcomes considerably.     

Exploring Reticular Pseudodrusen Extent and Impact on Mesopic Visual Sensitivity in Intermediate Age-Related Macular Degeneration

PurposeTo explore the impact of the extent of reticular pseudodrusen (RPD) on mesopic visual sensitivity in individuals with intermediate age-related macular degeneration (AMD).MethodsIn total, 570 eyes from 285 participants with bilateral large drusen underwent microperimetry testing to assess the visual sensitivity of the central 3.6-mm region and multimodal imaging to determine the extent of RPD in the central 20° × 20° region (at the eye level). Mean visual sensitivity within five sectors in the central 3.6-mm region sampled on microperimetry and the extent of RPD in these sectors were derived. Linear mixed models were used to examine the association between the extent of RPD on overall mean visual sensitivity and sector-based mean sensitivity.ResultsAn increasing extent of RPD at the eye level and within sectors was associated with a significant reduction in overall and sector-based mean sensitivity, respectively (P < 0.001 for both). However, when both RPD parameters were considered together in a multivariable model, only an increasing extent of RPD at the eye level (P < 0.001) and not within each sector (P = 0.178) was independently associated with reduced sector-based mean sensitivity.ConclusionsMesopic visual sensitivity is generally reduced in eyes with large drusen and coexistent RPD compared to eyes without RPD, with greater reductions with an increasing extent of RPD. However, reduced sector-based visual sensitivities are explained by the overall extent of RPD present, rather than their extent within the sector itself. These findings suggest that there are generalized pathogenic changes in eyes with RPD accounting for the observed mesopic visual dysfunction.