Early transvaginal ultrasound following an accurately dated pregnancy: the importance of finding a yolk sac or fetal heart motion

Our goals were to determine the prognostic value of a yolk sac or fetal heart motion seen during an early accurately dated transvaginal ultrasound (TVU). We reviewed 225 consecutive pregnancies for fetal heart motion data. Furthermore, 63 pregnancies following in-vitro fertilization were reviewed for yolk sac information. The TVU was performed between 5 and 6 weeks following presumed conception (heart motion data) and between 22 and 32 days following in-vitro fertilization (yolk sac data). Pregnancies were followed until an ongoing pregnancy or spontaneous abortion was documented. The presence of a yolk sac between 22 and 32 days from fertilization was associated with the development of fetal heart motion in 94% of cases. The absence of the yolk sac by 32 days after fertilization was always associated with a poor outcome. In women < 36 years of age, the presence of fetal heart motion was associated with a spontaneous abortion in only 4.5% of the cases. However, the incidence of spontaneous abortion following fetal heart motion increased to 10% in women 36-39 years and 29% in women > or = 40 years of age. The presence of heart motion should not be considered a reassuring sign in the older woman. These data have implications regarding early embryology and the counselling of infertility patients.      

Watch and Wait Approach for Re-excision After Unplanned Yet Macroscopically Complete Excision of Extremity and Superficial Truncal Soft Tissue Sarcoma is Safe and Does Not Affect Metastatic Risk or Amputation Rate

Annals of Surgical Oncology - The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown. The aim of this study was to evaluate the...     

Potentiation of analgesic efficacy but not side effects: co-administration of an α4β2 neuronal nicotinic acetylcholine receptor agonist and its positive allosteric modulator in experimental models of pain in rats

Positive modulation of the neuronal nicotinic acetylcholine receptor (nAChR) α4β2 subtype by selective positive allosteric modulator NS-9283 has shown to potentiate the nAChR agonist ABT-594-induced anti-allodynic activity in preclinical neuropathic pain. To determine whether this benefit can be extended beyond neuropathic pain, the present study examined the analgesic activity and adverse effect profile of co-administered NS-9283 and ABT-594 in a variety of preclinical models in rats. The effect of the combined therapy on drug-induced brain activities was also determined using pharmacological magnetic resonance imaging. In carrageenan-induced thermal hyperalgesia, co-administration of NS-9283 (3.5 μmol/kg, i.p.) induced a 6-fold leftward shift of the dose–response of ABT-594 (ED₅₀ = 26 vs. 160 nmol/kg, i.p.). In the paw skin incision model of post-operative pain, co-administration of NS-9283 similarly induced a 6-fold leftward shift of ABT-594 (ED₅₀ = 26 vs. 153 nmol/kg). In monoiodo-acetate induced knee joint pain, co-administration of NS-9283 enhanced the potency of ABT-594 by 5-fold (ED₅₀ = 1.0 vs. 4.6 nmol/kg). In pharmacological MRI, co-administration of NS-9283 was shown to lead to a leftward shift of ABT-594 dose–response for cortical activation. ABT-594 induced CNS-related adverse effects were not exacerbated in presence of an efficacious dose of NS-9283 (3.5 μmol/kg). Acute challenge of NS-9283 produced no cross sensitization in nicotine-conditioned animals. These results demonstrate that selective positive allosteric modulation at the α4β2 nAChR potentiates nAChR agonist-induced analgesic activity across neuropathic and nociceptive preclinical pain models without potentiating ABT-594-mediated adverse effects, suggesting that selective positive modulation of α4β2 nAChR by PAM may represent a novel analgesic approach.     

Variation in the peritoneal cancer index scores between surgeons and according to when they are determined (before or after cytoreductive surgery)

Introduction

The prognosis of peritoneal carcinomatosis (PC) is highly dependent on the extent of the PC. This extent is calculated by the peritoneal cancer index (PCI). In the future, the indications for complete cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) should be partially based on the PCI. This raises the question of the concordance between the PCI scores calculated by different surgeons, and a possible variation before and after CRS.

Objective

To analyze variations in the PCI score between surgeons and according to when it is determined (before and after surgery).

Patients and methods

Prospective recording of the PCI score independently calculated by senior and junior surgeons, before CRS (when the surgeon decided to perform this procedure), and after CRS, in 75 consecutive patients. A concordance analysis was conducted.

Results

The origins of the PC were colorectal (n = 38), pseudomyxoma (n = 22), mesothelioma (n = 8) and miscellaneous lesions (n = 7). Concordance between the PCI score was very high (close to 90%) among the senior surgeons and junior surgeons before and after CRS. After CRS, the mean PCI score increased by 1.75 (IC-95%: 2.09–1.41). This high concordance was similar whatever the level of the PCI score and whatever the origin of the tumor.

Conclusion

The PCI is a reliable tool for measuring the extent of PC. It is easy to use and inter-surgeon concordance is high. It increases by approximately 2 before and after CRS.     

Spinal Nerve Ligation in Mouse Upregulates TRPV1 Heat Function in Injured IB4-Positive Nociceptors

Peripheral nerve injury leads to neuropathic pain, but the underlying mechanisms are not clear. The TRPV1 channel expressed by nociceptors is one receptor for noxious heat and inflammatory molecules. Lumbar 4 (L4) spinal nerve ligation (SNL) in mice induced persistent heat hyperalgesia 4 to 10 days after injury. The heat hypersensitivity was completely reversed by the TRPV1 antagonist A-425619. Furthermore, DRG neurons were isolated from the injured L4 ganglia or adjacent L3 ganglia 4 to 10 days after L4 SNL. Whole-cell patch-clamp recordings were performed and heat stimuli (22°C to 50°C/3 s) were applied to the soma. Neurons were classified by soma size and isolectin-B4 (IB4) binding. Among directly injured L4 neurons, SNL increased the percentage of small-diameter IB4-positive neurons that were heat-sensitive from 13% (naive controls) to 56% and conversely decreased the proportion of small IB4-negative neurons that were heat-sensitive from 66% (naive controls) to 34%. There was no change in IB4 binding in neurons from the injured ganglia. Surprisingly, in neurons from the adjacent L3 ganglia, SNL had no effect on the heat responsiveness of either IB4-positive or negative small neurons. Also, SNL had no effect on heat responses in medium-large–diameter neurons from either the injured or adjacent ganglia.PerspectiveTRPV1 function is upregulated in IB4-positive sensory neurons, and TRPV1 is responsible for the behavioral heat hypersensitivity in the spinal nerve ligation model. Because IB4-positive neurons may contribute to the emotional perception of pain, TRPV1 antagonists, targeting both sensory and affective pain components, could have broad analgesic effects.     

Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy.

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.