Comprehensive long-term safety of adalimumab from 18 clinical trials in adult patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Adalimumab (Humira® , AbbVie Inc., North Chicago, IL, U.S.A.) is a fully human monoclonal antibody specific for tumour necrosis factor-α that is approved to treat adults with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To assess long-term safety for patients with psoriasis receiving adalimumab in clinical studies. METHODS: Adalimumab safety data from adults with psoriasis who received at least one adalimumab dose in 18 clinical trials were evaluated. Adalimumab was delivered subcutaneously in all treatment regimens. Treatment-emergent adverse events (AEs) were collected from the first dose to 70 days after the last dose or cut-off date (31 December 2015). AE incidence rates were expressed as events per 100 patient-years (E/100 PYs) of adalimumab exposure. Standardized incidence ratios (SIRs) for malignancies and standardized mortality ratios (SMRs) were calculated. RESULTS: Cumulative exposure was 5429·7 PYs in 3727 patients. Overall, there were 16 536 AEs (304·6 E/100 PYs). The most common AEs were nasopharyngitis, upper respiratory infection and headache (23·7, 12·9 and 7·9 E/100 PYs, respectively). Incidence rates for serious infections, tuberculosis and opportunistic infections were 1·8, 0·3 and 0·02 E/100 PYs, respectively. Incidence of malignancy excluding nonmelanoma skin cancer (NMSC) was 0·8 E/100 PYs [SIR 0·86, 95% confidence interval (CI) 0·58-1·23]. Incidences of NMSC and melanoma were 0·6 and 0·2 E/100 PYs, respectively. The SIR was 1·55 (95% CI 1·10-2·13) for NMSC and 3·04 (95% CI 1·11-6·62) for melanoma. The SMR was 0·34 (95% CI 0·16-0·65). CONCLUSIONS: AE rates remained stable in this analysis of patients with psoriasis receiving adalimumab; no new safety signals were identified compared with earlier analyses.

Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.

Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on-treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in four studies. Cardiovascular-related events were reported in three studies: ≤0.1/100PY per major cardiac event in ESPRIT, <0.5/100PY major cardiac events in PsoBest and serious cardiovascular events in two patients (<1%) in DERMBIO. Malignancies were reported in three studies (any malignancy, 0.9/100PY; malignancies excluding non-melanoma skin cancer [NMSC], <0.6/100PY; NMSC, 0.6-<0.5/100PY). These findings suggest that real-world safety of adalimumab is consistent across different psoriasis registries, which supports the existing long-term safety profile of adalimumab from clinical studies.

A randomised controlled study comparing valethamate bromide and placebo in shortening the duration of active labour.

The aim of this study is to compare the efficacy and safety of valethamate bromide and placebo against placebo in shortening the duration of active labour. A prospective randomised trial of 158 low-risk women in spontaneous labour was conducted. After evaluation of the patients according to exclusion criteria 30 women were given valethamate bromide (Group 1) and 32 women were given placebo (Group 2). Labour duration was the main outcome measure. The duration of the active phase after starting the treatment was similar in the two groups at 225 and 219 min, respectively. However, differences were not significant between the 2 groups. Side effects such as tachycardia, flushing of the face and dryness of mouth were noted with valethamate bromide administration. In conclusion, valethamate bromide did not significantly shortened the duration of active labour in nulliparous women with a singleton pregnancy at term.

Is the Left Kidney the Right One for Kidney Donation in Women Planning on Future Pregnancy?

The kidney transplantation surgery requires left nephrectomy because of the anatomical disadvantages. But hydroureteronephrosis is the most significant renal functional alteration of pregnancy, accounted for by both hormonal and mechanical factors. Dilatation of the ureters and renal pelvis is more prominent on the right side than the left side and is seen in up to 80% of pregnant women. A 23-year-old woman who become pregnant after 4 months from left kidney donation was admitted to our emergency department with acute right kidney injury during her 39(th) week of pregnancy. She did not response to conservative treatment and required emergency delivery because of the progressive increase in her serum creatinine levels. After delivery, progressive decrease at creatinine level had been observed and in one month, it had reached the normal level. Mother candidates should be advised they donate their kidneys after completing their childbearing if possible, or undergo right nephrectomy.

Serum human epididymis protein 4 can be a useful tumor marker in the differential diagnosis of adnexal masses during pregnancy: a pilot study.

PURPOSE: The purpose of this study was to evaluate serum concentrations of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) in healthy women and their pregnant counterparts to determine the influence of pregnancy on these biomarkers. MATERIALS AND METHODS: Serum concentrations of CA 125 and HE4 were measured in 27 healthy non-pregnant women and 26 healthy pregnant women in the first and second trimesters. RESULTS: Higher concentration of CA 125 was found in pregnants than in non-pregnant women (p = 0.002). There was no difference in CA 125 concentrations between first and second trimesters (p = 0.13). Serum HE4 concentration was not different in pregnant group compared to non-pregnant women (p = 0.510). Likewise, no difference was found in HE4 levels between the trimesters (p = 0.485). There was a positive correlation between increasing parity and CA 125 (p = 0.023), but not HE4 (p = 1.0). CONCLUSION: HE4 serum biomarker is unaffected by pregnancy status and may be useful for evaluation of doubtful pelvic masses in pregnancy. Contrarily, increased serum levels of CA 125 could yield increased number of false-positive results.

A randomised controlled study comparing valethamate bromide and placebo in shortening the duration of active labour.

The aim of this study is to compare the efficacy and safety of valethamate bromide and placebo against placebo in shortening the duration of active labour. A prospective randomised trial of 158 low-risk women in spontaneous labour was conducted. After evaluation of the patients according to exclusion criteria 30 women were given valethamate bromide (Group 1) and 32 women were given placebo (Group 2). Labour duration was the main outcome measure. The duration of the active phase after starting the treatment was similar in the two groups at 225 and 219 min, respectively. However, differences were not significant between the 2 groups. Side effects such as tachycardia, flushing of the face and dryness of mouth were noted with valethamate bromide administration. In conclusion, valethamate bromide did not significantly shortened the duration of active labour in nulliparous women with a singleton pregnancy at term.

The effect of ovariectomy on the skin flap viability and myeloperoxidase levels.

OBJECTIVES: Estrogen could affect the rate and quality of wound healing in skin. We aimed to investigate the effects of ovariectomy on skin flap viability and myeloperoxidase (MPO) levels in a rat model. BACKGROUND: Estrogens have many important beneficial and protective roles in skin that they improve collagen content and quality, maintain skin thickness and enhance vascularization. It has been shown that estrogen supplementation accelerates cutaneous wound healing in elderly patients. METHODS: Forty-eight cycling female Wistar albino rats were randomly divided into three groups (n = 16); ovariectomy (Group 1), sham (Group 2), and control (Group 3). Rats were subjected to bilateral ovariectomy in the Group 1, and only laparotomy in the Group 2. Twenty-one days later in the Group 1 and 2, a dorsal caudally based skin flap elevation was done. In the Group 3, the rats had a dorsal skin flap without any surgical intervention. Ten days later, the flaps were harvested for histopathologic examination and biochemical analyses. RESULTS: The rats in the Group 1 had significantly larger necrotic area and lower flap viability than in the Group 2 and 3 (p<0.05). Histopathologic examination showed that necrotic flap regions contained muscle necrosis with an abundant neutrophil infiltration, and severe edema in the Group 1. The MPO activity in the distal of skin flaps was significantly higher in the Group 1 compared to the Group 2 and 3 (p<0.05). CONCLUSION: This study shows that ovariectomy has deleterious effects on skin flap viability in a rat model (Tab. 1, Fig. 6, Ref. 44).

Does ovarian endometrioma affect the number of oocytes retrieved for in vitro fertilization?

OBJECTIVE: To investigate the effects of ovarian endometrioma on the number of oocytes retrieved for in vitro fertilization (IVF). BACKGROUND: The presence of endometrioma may be the most important predictor of a poor reproductive outcome. Literature data suggest that ovarian endometriomas might affect the response to ovarian stimulation and oocyte retrieval. METHODS: The present retrospective study evaluates 2,023 women who applied to our center with an infertility complaint. Twenty-nine women with endometriomas (group 1) who were treated with IVF were included in the study. They were compared with 51 women with unexplained infertility (group 2) regarding the number of retrieved oocytes after egg retrieval and number of metaphase II oocytes. The diagnosis of endometrioma was made via ultrasound examination with the identification of low-density cystic masses in the ovaries. The patients underwent a controlled ovarian hyperstimulation (COH) with either the long agonist mini-dose protocol or the multi-dose antagonist protocol. RESULTS: The incidence of endometrioma in infertile women was found to be 1.4 %. The women's ages ranged between 24 and 45 years, and the duration of their infertility ranged between 12 and 216 months. The endometrioma was bilateral in 24 % of the cases. The mean endometrioma diameter was 26.2±7.3 mm for the right ovary and 23.2±6.1 mm for the left ovary. The average number of retrieved oocytes after egg retrieval in groups 1 and 2 was 12.4±8.3 and 12.2±8.6, respectively. The average number of metaphase II oocytes in groups 1 and 2 was 8.6±6.1 and 9.4±7.3, respectively. The number of retrieved oocytes after egg retrieval and the number of metaphase II oocytes in both endometrioma group and unexplained infertile group were similar (p >0.05). CONCLUSION: Endometrioma did not reduce the number of retrieved oocytes in a COH cycle for IVF treatment. However it should be noted that the ovarian response is affected by the size of endometriomas, bilaterality, previous surgeries, recurrence, and the patient's age (Tab. 1, Ref. 31).

A case with diffuse uterine leiomyomatosis and review of the literature.

Leiomyomas and diffuse uterine leiomyomatosis are smooth muscle tumors of the uterus. Diffuse uterine leiomyomatosis is a benign and extremely rare condition in which the uterus is symmetrically enlarged as a result of the almost complete replacement of the myometrium by innumerable poorly defined, confluent nodules. The etiology of these neoplasms is not completely understood. Initial symptoms of the diffuse uterine leiomyomatosis usually are abdominal pain and abnormal uterine bleeding. Similar to uterine leiomyomas, patients with leiomyomatosis present with menorrhagia, dysmenorrhea, abdominal pain, infertility, and pelvic pressure. Hormonal treatment usually fails to control the symptoms, anemia, or tumor growth after treatment is stopped. As a result, despite patients being in the third or fourth decades of life, hysterectomy has been the only permanent treatment option offered to patients for treatment of the symptoms related to uterine fibroids in diffuse leiomyomatosis. A case of a patient with a huge uterine mass (2,650 g in weight) who underwent hysterectomy due to diffuse uterine leiomyomatosis is presented together with a review of the literature.