Incidental Intraoperative Diagnosis of Term Conjoined Twins: A Case Series.

Conjoined twins (Siamese twins) represent the rarest form of twin pregnancy. Reported here are two rare cases of conjoined term twins presented to the department of Obstetrics and Gynaecology within 3 months. The first case, 32 years of gravida 6 parity 5 referred from periphery after full trial of labour following multi-organ dysfunction and term intrauterine dead twins. Intraoperatively it was dead conjoined thoraco-omphalopagus females. The patient died after 3 days following multiorgan dysfunction syndrome and disseminated intravascular coagulation. The second case, 22 years gravida 2 parity 1 also referred from periphery in second stage of labour with diagnosis of 39 weeks intrauterine dead twins with obstructed labour, delivered by caesarean with intraoperative conjoined dead females of thoracophagus type. Twins are high-risk pregnancy. This rare diagnosis with complications could have been prevented by regular antenatal checkups, ultrasonography performed by radiologists and early referral antenatally in labour along with multidisciplinary approach. Keywords: conjoined; monozygotic twinning; siamese twins; twins.

Stroke in Pregnancy: A Case Report.

Reported here is a rare near-miss case of stroke in pregnancy presented to the Department of Obstetrics and Gynaecology. A 38 years gravida 8 was referred from a private hospital on 18 November 2022 with hemorrhagic stroke, a known case of chronic hypertension at 37 weeks of gestation with previous cesarean section and acute kidney injury. At a private hospital computed tomography head was done it showed intracerebral haemorrhage. On cesarean, intraoperatively it was a live female with thick meconium. The patient was kept in intensive care with a mechanical ventilator, antihypertensives, antibiotics, and analgesics. Serum creatinine was increasing daily. Suture was cut on the 7th postoperative and two times dialysis was done on the 8th and 9th postoperative days. Stroke in pregnancy is a rare diagnosis and it could have been prevented by regular antenatal visits and early referral antenatally along with a multidisciplinary approach. Keywords: case reports; hypertension; intracerebral haemorrhage; pregnancy; stroke.

Therapeutic inhibition of USP9x-mediated Notch signaling in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a breast cancer subtype that lacks targeted treatment options. The activation of the Notch developmental signaling pathway, which is a feature of TNBC, results in the secretion of proinflammatory cytokines and the recruitment of protumoral macrophages to the tumor microenvironment. While the Notch pathway is an obvious therapeutic target, its activity is ubiquitous, and predictably, anti-Notch therapies are burdened with significant on-target side effects. Previously, we discovered that, under conditions of cellular stress commonly found in the tumor microenvironment, the deubiquitinase USP9x forms a multiprotein complex with the pseudokinase tribbles homolog 3 (TRB3) that together activate the Notch pathway. Herein, we provide preclinical studies that support the potential of therapeutic USP9x inhibition to deactivate Notch. Using a murine TNBC model, we show that USP9x knockdown abrogates Notch activation, reducing the production of the proinflammatory cytokines, C-C motif chemokine ligand 2 (CCL2) and interleukin-1 beta (IL-1ß). Concomitant with these molecular changes, a reduction in tumor inflammation, the augmentation of antitumor immune response, and the suppression of tumor growth were observed. The pharmacological inhibition of USP9x using G9, a partially selective, small-molecule USP9x inhibitor, reduced Notch activity, remodeled the tumor immune landscape, and reduced tumor growth without associated toxicity. Proving the role of Notch, the ectopic expression of the activated Notch1 intracellular domain rescued G9-induced effects. This work supports the potential of USP9x inhibition to target Notch in metabolically vulnerable tissues like TNBC, while sparing normal Notch-dependent tissues.