Role of ultrasound in detection of lymph-node metastasis in gynecological cancer: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic performance of transvaginal sonography (TVS) for the preoperative evaluation of lymph-node metastasis in gynecological cancer. METHODS: This was a systematic review and meta-analysis of studies published between January 1990 and May 2023 evaluating the role of ultrasound in detecting pelvic lymph-node metastasis (index test) in gynecological cancer, using histopathological analysis as the reference standard. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity, specificity and diagnostic odds ratio were estimated. RESULTS: The literature search identified 2638 citations. Eight studies reporting on a total of 967 women were included. The mean prevalence of pelvic lymph-node metastasis was 24.2% (range, 14.0-65.6%). The risk of bias was low for most domains assessed. Pooled sensitivity, specificity and diagnostic odds ratio of TVS were 41% (95% CI, 26-58%), 98% (95% CI, 93-99%) and 32 (95% CI, 14-72), respectively. High heterogeneity was found between studies for both sensitivity and specificity. CONCLUSION: TVS showed a high pooled specificity for the detection of pelvic lymph-node metastasis in gynecological cancer, but pooled sensitivity was low. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells.

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well as for designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols for the directed differentiation of hESC/iPSC into dopamine (DA) neurons with the specific characteristics of the cell population lost to PD, i.e., A9-subtype ventral midbrain DA neurons. Here we use lentiviral vectors to drive the expression of LMX1A, which encodes a transcription factor critical for ventral midbrain identity, specifically in neural progenitor cells. We show that clonal lines of hESC engineered to contain one or two copies of this lentiviral vector retain long-term self-renewing ability and pluripotent differentiation capacity. Greater than 60% of all neurons generated from LMX1A-engineered hESC were ventral midbrain DA neurons of the A9 subtype, compared with ∼10% in green fluorescent protein-engineered controls, as judged by specific marker expression and functional analyses. Moreover, DA neuron precursors differentiated from LMX1A-engineered hESC were able to survive and differentiate when grafted into the brain of adult mice. Finally, we provide evidence that LMX1A overexpression similarly increases the yield of DA neuron differentiation from human iPSC. Taken together, our data show that stable genetic engineering of hESC/iPSC with lentiviral vectors driving controlled expression of LMX1A is an efficient way to generate enriched populations of human A9-subtype ventral midbrain DA neurons, which should prove useful for modeling PD and may be helpful for designing future cell-replacement strategies.

Efficacy and tolerability of human fibrinogen concentrate administration to patients with acquired fibrinogen deficiency and active or in high-risk severe bleeding.

BACKGROUND AND OBJECTIVES: Fibrinogen deficiency is a cause for massive haemorrhage whose management in emergency situations is the subject of debate. Plasma-derived fibrinogen concentrates are indicated for reversing the haemorrhagic diathesis found in congenital and acquired deficiencies. MATERIALS AND METHODS: We report on the results of an observational study that evaluated the effects of fibrinogen concentrates in patients suffering from various forms of acquired severe hypofibrinogenaemia with life-threatening consumptive thrombo-haemorrhagic disorders (surgery, trauma and digestive haemorrhage), or underlying disease states that limit fibrinogen synthesis (hepatic dysfunction, haematological malignancies). RESULTS: Sixty-nine patients were identified and included, in whom most of the processes (62%) corresponded to consumptive hypofibrinogenaemia. After a median dose of 4 g, a mean absolute increase of 1.09 g/l in plasma fibrinogen was measured and coagulation parameters were significantly improved (P < 0.001). Mortality rates of 32.3% and 44.2% were reported after 24 h and 72 h, respectively. CONCLUSION: We conclude that the administration of fibrinogen concentrates in unresponsive, life-threatening haemorrhage with acquired hypofibrinogenaemia improves laboratory measures of coagulation, and may also be life saving. Although observational in nature, our data indicate a direct relationship between plasma fibrinogen levels and survival in acquired fibrinogen deficiency. Further studies are warranted to ascertain a clear relationship between fibrinogen levels and survival.