Use of colchicine in pregnancy: a systematic review and meta-analysis.

OBJECTIVES: Colchicine is an anti-inflammatory agent used in the treatment of several rheumatological conditions. The use of colchicine in pregnancy is controversial. The current study aimed to systematically review and meta-analyse the existing data in the literature regarding the safety of colchicine in pregnancy. METHODS: A systematic review was carried out using six electronic databases, identifying all relevant studies where colchicine was administered to pregnant women, and where pregnancy-related outcomes were measured. The primary endpoints were miscarriage and major foetal malformation. Secondary endpoints included birthweight and gestational age at birth. RESULTS: Four studies were included for meta-analysis. Use of colchicine throughout pregnancy was not associated with an increased incidence of miscarriage or major foetal malformations. The incidence of miscarriage was significantly lower in women who took colchicine compared with those that did not. In women with FMF who took colchicine throughout the pregnancy, there was no significant difference in birthweight or gestational age compared with those who did not take colchicine. When not limited to FMF, colchicine use was associated with a significantly lower birthweight and gestational age compared with a control group including healthy women who did not take colchicine. CONCLUSIONS: Colchicine therapy did not significantly increase the incidence of foetal malformations or miscarriage when taken during pregnancy. Colchicine therapy for FMF should not be withheld on this basis during pregnancy.

Late diagnosis of hepatic mesenchymal hamartoma and placental mesenchymal dysplasia.

Placental mesenchymal dysplasia (PMD) is a rare condition characterised by placental enlargement, oedematous villi and multiple anechoic cysts. Hepatic mesenchymal hamartoma (HMH) is a benign proliferation of mesenchymal tissue, commonly seen in infants below the age of 2. We report the case of a 28 years old female who was noted to have a fetus with a well-circumscribed cyst on the liver, suggestive of HMH and a large, thickened placenta, with multiple anechoic cysts, consistent with PMD during the third trimester. There were no other structural abnormalities and at 38 weeks she underwent an induction of labour with normal vaginal delivery of a live female infant. While the aetiology is poorly understood, the increased incidence of HMH with PMD and the morphological similarities of the changes seen in both the placenta and liver, suggests a possible common developmental mechanism. There are only 12 other cases of this concurrent pathology in the literature and only one of these had resulted in a term delivery, and ours is the second one to date.

Opportunistic bilateral salpingectomy during gynaecological surgery for benign disease: A survey of current Australian practice.

BACKGROUND: Recent evidence supports the fallopian tube as the site of origin for many pelvic serous cancers (PSC) including epithelial ovarian cancers (EOC). As a result, a change in practice with opportunistic bilateral salpingectomy (OBS) at the time of hysterectomy has been advocated as a preventative strategy for PSC in a low-risk population. AIMS: The aim of this study was to assess current clinical practice in Australia with respect to OBS during gynaecological surgery for benign indications. MATERIALS AND METHODS: An anonymous online survey was sent to all active Royal Australian and New Zealand College of Obstetrics and Gynaecology (RANZCOG) Fellows in Australia. Data regarding clinician demographics and the proportion of clinicians offering OBS were collected. Reasons for and against offering or discussing OBS were sought. A descriptive analysis was performed. RESULTS: The response rate was 26% (280/1490) with 70% of respondents offering or discussing OBS to women undergoing gynaecological surgery for benign indications, usually at the time of abdominal (96%) or laparoscopic (76%) hysterectomy. The main reason for offering or discussing OBS was current evidence to suggest the fallopian tubes as the site of origin for most EOC. Main reasons for not offering OBS were insufficient evidence to benefit the woman (36%) or being unaware of recent evidence (33%). CONCLUSIONS: The survey responses indicate that OBS is frequently discussed or offered in Australia, usually at the time of hysterectomy. Given the lack of robust evidence to suggest a benefit at a population-based level, a national registry is recommended to monitor outcomes.

Design, synthesis and evaluation of 1,2,3-triazole-adamantylacetamide hybrids as potent inhibitors of Mycobacterium tuberculosis.

A series of novel 1,2,3-triazole-adamantylacetamide hybrids 5a-u, designed by combining bioactive fragments from antitubercular I-A09 and substituted adamantyl urea, were synthesized using copper catalyzed click chemistry. N-(1-Adamantyl)-2-azido acetamide 3 prepared from 1-adamantylamine was reacted with a series of alkyl/aryl acetylenes in the presence of copper sulfate and sodium ascorbate to give new analogues 5a-u in very good yields. Evaluation of all new compounds for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted N-(1-adamantan-1-yl)-2-(4-(phenanthren-2-yl)-1H-1,2,3-triazol-1-yl)acetamide (5t) as most promising lead MIC: 3.12 µg/mL) with selectivity index >15.

Rational design, synthesis and antitubercular evaluation of novel 2-(trifluoromethyl)phenothiazine-[1,2,3]triazole hybrids.

Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synthesized in very good yields using click chemistry. Among the all '22' compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb), three analogs 5c, 5l and 5o were found to be most potent (MIC: 6.25µg/mL) antitubercular agents with good selectivity index.