Impact of Dexamethasone on Length of Stay and Early Pain Control in Direct Anterior Approach Total Hip Arthroplasty With Neuraxial Anesthesia

BackgroundDexamethasone has been shown to reduce postoperative pain and opioid consumption for total joint arthroplasty patients; however, its impact on patients who received neuraxial anesthesia (NA) is not well described. We examined the impact of perioperative dexamethasone on outcomes for patients undergoing direct anterior approach total hip arthroplasty (THA) under NA.MethodsA retrospective review was conducted for 376 THA patients from a single institution. Univariate analysis was used to compare postoperative outcomes for 164 THA patients receiving dexamethasone compared to 212 who did not receive dexamethasone.ResultsNo differences in age, gender, body mass index, or American Society of Anesthesiologists (ASA) Score were observed between the groups. Patients receiving perioperative dexamethasone reported statistically significantly lower postanesthesia care unit (PACU) pain numeric rating scale (Dexamethasone 1.6 vs No dexamethasone 2.3, P = .014) and received lower PACU morphine milligram equivalents (MME) (Dexamethasone 8.57 vs No dexamethasone 11.44, P < .001). Patients receiving dexamethasone had significantly shorter LOS (Dexamethasone 29.40 vs No dexamethasone 35.26 hrs., P < .001).ConclusionPerioperative dexamethasone is associated with decreased postoperative pain and narcotic consumption, and shorter length of stay for patients undergoing primary direct anterior approach THA with NA.     

The utility of in-bore multiparametric magnetic resonance-guided biopsy in men with negative multiparametric magnetic resonance-ultrasound software-based fusion targeted biopsy

ObjectivesTo evaluate the utility of in-bore multiparametric magnetic resonance-guided biopsy of the prostate (IB) in patients with visible lesion/s and previous negative software-based multiparametric magnetic resonance imaging/ultrasonography fusion-targeted biopsy of the prostate (FTB).Patients and methodsWe retrospectively analysed prospectively maintained database including consecutive men undergoing IB from March 2013 to October 2017 in 2 European centres expert in this procedure. We selected men with the following criteria: No previous treatment for prostate cancer (CaP), multiparametric magnetic resonance imaging (mpMRI) lesion(s) PIRADS score ≥ 3, FTB showing no clinically significant cancer (csCaP), and subsequent IB. Patient's characteristics, mpMRI findings, biopsy technique, and histopathological results were extracted. The primary outcome was to determine the detection rate of csCaP, defined as any Gleason pattern ≥ 4. A multivariable analysis was performed to identify predictors of positive findings at IB.ResultsFifty-three men were included. Median age was 68 years (interquartile range [IQR] 64–68), median Prostate-Specific Antigen (PSA) was 7.6 ng/ml (IQR 5.2–10.9), and median prostate volume was 59 ml (IQR 44–84). Fifty-six lesions with PIRADS score 3 in 9 cases (16%), 4 in 30 cases (54%), and 5 in 17 cases (30%) were detected. FTB was performed in all cases using a transrectal approach with 3 different platforms (Toshiba, Koelis, and Artemis). Median time between FTB and IB was 3 months (IQR 1–7). A median of 2 cores per lesion were collected with IB (IQR 2–3). No cancer, clinically insignificant and clinically significant cancer were found in 33 (59%), 9 (16%), and 14 (25%) targeted lesions, respectively. Median maximum cancer core length and maximum positive percentage were 9 mm (3–13) and 55% (21%–80%). The only predictor of csCaP on IB was prostate volume (P = 0.026) with an ideal cut-off at 70 ml.ConclusionOne in 4 patients with previous negative FTB, IB was able to detect csCaP. According to this study, IB would be of particularly useful in patients with large glands.     

Amoeboid Microglial Cells and not Astrocytes Synthesize TNF-alpha in Swiss Mouse Brain Cell Cultures

The role of tumour necrosis factor (TNF-alpha) in brain physiology and pathology has been the focus of several studies. However, the source of this lymphokine in the central nervous system and the regulation of its synthesis is still poorly understood. We have therefore used purified astrocytes and brain macrophages in culture to compare the abilities of these two cell types to synthesize TNF-alpha and its mRNA. We find that, in the Swiss mouse, no significant TNF activity or TNF-alpha mRNA are produced by astrocytes, even following activation with lipopolysaccharides (LPS). On the other hand, purified microglial cells express a cytotoxic activity able to kill TNF-sensitive LM cells. Part of this activity is released into the culture medium and part remains bound to the membrane after mild paraformaldehyde treatment, demonstrating the existence in the culture of the soluble and membrane-bound forms of TNF activity. The fact that amoeboid microglial cells, and not astrocytes, are the actual source of TNF in brain cultures was further demonstrated by Northern blot analysis and in situ hybridization using a TNF-alpha specific oligonucleotide probe. The definition of the cell type which, in the CNS, is responsible for TNF synthesis will allow the regulation of this lymphokine to be analysed and opens the way for a better understanding of the interactions between amoeboid microglial cells and the other cell types which make up the nervous system.     

Methods for in vivo haematoporphyrin derivative quantification: a review

Photodynamic therapy is a new treatment for early carcinomas. Although undergoing phase 1/2 clinical assays, clinical indications for this therapy remain rare mainly because of the approximate dosimetry of HPD uptake by tumour tissues in human beings.In this review we present the potential interest and limits of both direct fluorescence detection or dosimetry of HPD and in vivo measurements of singlet oxygen, produced during photodynamic therapy. Clinical applications of such measurements should represent one of the main conditions for the future development of photodynamic therapy.

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Résumé La photochimiothérapie est un nouveau traitement des cancers débutants. Alors que des essais cliniques de phase 1–2 sont entrepris, les indications pour ce type de traitement demeurent rares, principalement du fait d'une dosimétrie approximative de la captation de l'hématoporphyrine dérivée par les tissus cancéreux humains. La fluorescence émise par l'HPD peut Être utilisée in-vivo pour un diagnostique topographique de la répartition de l'HPD, mais aussi le dosage quantitatif des espèces fluorescentes présentes dans le mélange HPD. Le dosage de l'oxygène singulet, généré lors de la réaction photochimique, est nettement plus difficile à réaliser mais a été proposé pour le dosage in-vivo des formes porphyriniques actives présentes dans le milieu. Les applications cliniques de telles mesures représentent une condition essentielle pour le developpement de la photochimiothérapie car à côté des possibilités de diagnotiques offertes par l'analyse de la répartition intratumorale de l'HPD, un dosage précis permettrait d'optimiser le moment du traitement, arbitrairement fixé aujourd'hui à 72 heures.

     

Haemodynamic consequences and uterine contractions following 0.5 or 1.0 litre crystalloid infusion before obstetric epidural analgesia

Purpose

The efficacy of infusion of 0.5 L and 1.0 L Ringer’s lactate (LR) to prevent hypotension during induction of obstetric analgesia was studied. The effect of the different fluid boluses on fetal heart rate (FHR) and frequency of uterine contractions were also determined.

Methods

Ninety-two ASA 1–2 parturients were randomized to receive 0.5 L (Group 1) and 1.0 L (Group 2) LR immediately before incremental epidural injections with lidocaine to achieve T₁₀ sensory block. Systolic blood pressure (SBP) was measured with an automated BP cuff every two minutes for 30 min after infusion of fluid bolus. Fetal heart rate monitoring and tocometry were used continuously. The number of uterine contractions were recorded 30 min before and 60 min after iv bolus.

Results

The SBP decreased in both groups, but there was no difference between groups in mean SBP or maternal heart rate. The incidence of hypotension (SBP < 90 mmHg or decrease of 20%) was 4% in both groups. The FHR record of a patient in Group 1 showed a single late deceleration, and a decrease in beat-to-beat variability occured in one patient in Group 2. A decrease in the frequency of uterine contractions of two or more contractions per 30 min was noted more frequently in Group 2 (P < 0.05). The duration of iv bolus was longer in Group 2 than Group 1 (18.8 ± 4.3 min vs 12.3 ± 4.5 min, P < 0.01).

Conclusion

Administration of 1.0 L LR iv does not provide added protection against maternal hypotension, and is associated with delay in providing pain relief and a risk of decreasing uterine contraction frequency.     

Pulmonary gas exchange capacity is reduced during normovolaemic haemodilution in healthy human subjects

Purpose

To test the hypothesis that a physiological compensatory mechanism maintains respiratory gas exchange during normovolaemic haemodilution.

Methods

Pulmonary gas exchange capacity was evaluated in seven healthy subjects by measuring the lung diffusion of carbon monoxide (DLCO). During the measurement, various breath-holding times, inspiratory volumes, and sitting or supine positions, were randomly selected in an attempt to alter pulmonary capillary perfusion. KCO was calculated as the percentage of theoretical values of the ratio of DLCO by alveolar volume and normalized by sex, age, and height. Normovolaemic haemodilution (NH) was performed by bleeding an average blood volume of 1 L with simultaneous Dextran 60 replacement to obtain an haematocrit below 35%.

Results

After NH, haemoblogin concentration [Hb] decreased from 14.94 ± 0.96 to 12.5 ± 0.98 g · dl^?1 (P < 0.001). KCO decreased (P < 0.02) but remained closely correlated to [Hb] at every lung volume (< 0.02). Breathholding time and body position had no effect.

Conclusion

Moderate NH impairs pulmonary gas exchange capacity in awake, resting healthy subjects. There is no evidence of any compensatory mechanism since the KCO vs [Hb] relationship is unchanged.     

Induction of CYP1A in the beagle dog by an inhibitor of kinase insert domain-containing receptor: differential effects in vitro and in vivo on mRNA and functional activity.

Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A.     

Molecular mechanisms of platinum resistance: still searching for the Achilles' heel.

The platinum compounds cisplatin and carboplatin are commonly used in cancer chemotherapy. However, tumors frequently develop resistance to these compounds, significantly decreasing their usefulness in the clinic. In the past few years, basic research has unraveled novel and unexpected mechanisms for the development of platinum resistance. For example, it has been reported that MUC1 expression and particularly the localization of its C-terminal subunit to the mitochondria may affect cisplatin resistance. Another recent finding suggests that cisplatin damage may activate DNA-dependent protein kinase (DNA-PK) to initiate a death signal that can be transmitted to neighboring cells through gap junctions, adding to a growing belief that the interactions of cancer cells with their surroundings may be important to the outcome of chemotherapy. While most clinical efforts have focused on identifying alternative regimens for drug-resistant cancer, it might be possible to exploit our knowledge of the mechanism of platinum resistance to specifically reverse resistance and increase platinum efficacy. The strategy of drug resistance reversal therapy (DRRT) may have significant impact on our approaches to the treatment and management of drug-resistant tumors.