Low-threshold heat receptor in chick sensory neurons is upregulated independently of nerve growth factor after nerve injury

In mammals, the cloned low-threshold heat receptor, vanilloid receptor subtype 1 (VR1), is involved in the genesis of thermal hyperalgesia after inflammation. However, there is evidence that VR1 is not involved in the thermal hyperalgesia that occurs after nerve injury. In search for other heat receptors which might be involved in this phenomenon, we previously demonstrated that chick dorsal root ganglion neurons, which are insensitive to capsaicin, respond to low-threshold heat. Here, we investigated whether expression of the low-threshold noxious heat receptor in chicks is regulated by nerve growth factor (NGF), as VR1 is in mammals. Heat (44 degrees C) responsiveness of isolated dorsal root ganglion neurons of chicks was investigated (i) under culture conditions for up to 4 days with and without NGF and (ii) after a tight ligation of the sciatic nerve for up to 6 days, using cobalt-uptake method. In every case, a significant upregulation in the proportion of heat-responsive neurons was observed. On the molecular level, there was an increase of chick VR1 mRNA level in dorsal root ganglion cells cultured for 3 days in medium lacking NGF. In rat dorsal root ganglion neurons cultured for 1-4 days without NGF, patch-clamp experiments revealed that after 1 day almost all neurons responding to heat also responded to capsaicin, whereas after 3-4 days, more than one-half of the heat-responsive neurons did not respond to capsaicin.These data suggest the existence of low-threshold heat receptors in chick dorsal root ganglion neurons, the expression of which is regulated independently of NGF.     

Indications for early revision surgery for material failure in spinal instrumentation: experience at a level 1 center for spinal surgery – a single-center study

Posterior instrumentation is an established treatment for a range of spinal disorders. Material failure is not uncommon, and the indications for a revision are very heterogeneous. This study aimed to evaluate the indications and timing for early revision spinal surgery due to material failure.In this retrospective, single-center cohort study, patients underwent spinal posterior instrumentation between January 2017 and July 2019. They were followed up at 3, 12, and 18 months postoperatively. The time of onset of material failure which led to revision surgery was analyzed. In addition, the relationship between the indications for revision surgery and independent variables was examined using a multivariate logistic regression model.A total of one hundred thirty-five patients were enrolled. Radiolucent zones were found in 30 patients (20%) after 3 months, whereas 48 patients (31%) had radiolucent zones after 12 months. Revision surgery was performed in 13 patients (8.5%). The peak time for revision due to instability was within the first four months of the primary surgery. Multivariate analysis revealed that location, pathology, ASA score, and smoking had no significant impact on the indication for revision surgery, and neither did BMI (P = .042). Non-fusion (P = .007) and radiolucent zones (P = .004), in combination with increased pain (P = .006), were predictors for revision.Our data show that the peak time for early revision of material failure after posterior instrumentation was within the first 4 months of primary surgery. The abnormalities (e.g., radiolucent zones) surrounding the screws without fusion, including persistence of pain, were predictors for revision surgery.     

SNAI1 Protein Expression is an Independent Negative Prognosticator in Muscle-Invasive Bladder Cancer

Background

The prognosis of muscle-invasive bladder cancer is poor. Molecular prognosticators have gained increasing attention for individualized therapeutic options because they can identify patients with different prognoses.

Methods

Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples from 206 bladder cancer patients treated with cystectomy and chemotherapy were studied for SNAI1 protein expression by immunohistochemistry. SNAI1 expression was evaluated using an immunoreactive score (IRS). For statistical analysis, the patients were separated into two groups: those with tumor specimens negative for SNAI1 expression (IRS = 0), and the other positive for SNAI1 expression (IRS ≥1).

Results

Tumor samples from 42 patients showed negative SNAI1 expression, whereas the nuclei of tumor cells from 164 patients showed detectable nuclear staining of SNAI1. A Kaplan–Meier analysis of the bladder cancer patients with negative SNAI1 expression showed significantly reduced disease-specific survival (DSS) and progression-free survival (PFS) compared to the patients with positive expression (p = 0.010 and 0.013). A multivariate Cox regression analysis (adjusted for gender, age, tumor stage, tumor grade, lymph node metastasis, chemotherapy, and histologic subtype) again showed a significant correlation between patients lacking SNAI1 expression and DSS (p = 0.005; relative risk 2.31; 95 % confidence interval 1.28–4.17) or PFS (p = 0.004; relative risk 2.20; 95 % confidence interval 1.29–3.78) compared to patients with positive SNAI1 staining.

Conclusions

Loss of SNAI1 protein expression is an independent prognosticator for PFS and DSS in bladder cancer patients treated by radical cystectomy and adjuvant chemotherapy. Its prognostic value for neoadjuvant or adjuvant chemotherapy must be evaluated in further prospective randomized controlled trials.     

Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants

Objective: To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24?h of life, and development of intraventricular haemorrhage (IVH) in extremely preterm infants.

Study design: Single centre retrospective cohort study of 108 preterm infants born less than 28 weeks’ gestation. Main outcome measure was degree of IVH at day 7 postnatal age.

Results: The mean GA of the study group was 25.4 weeks. Mean SVCF was lower (75?ml/kg/min) in infants later diagnosed with IVH (n?=?46) compared to infants, who did not develop IVH (87.7?ml/kg/min, p?=?0.055). PDA diameter was inversely associated with SVCF (p?=?0.024) and reversal of flow in the descending aorta (p?=?0.001). Sensitivity analysis did not confirm an independent association of SVCF with development of IVH [OR 0.990 (0.978–1.002), p?=?0.115].

Conclusion: Our study describes early SVCF in extremely preterm infants is associated with the extent of ductal shunting, but insensitive in predicting IVH.     

Tigecycline-based prolonged salvage therapy in patients presenting with complex bone and joint infection

Objectives

To assess the clinical experience of tigecycline-based salvage therapy in patients presenting with Bone and Joint Infections (BJI).