Population pharmacokinetics of moxifloxacin in plasma and bronchial secretions in patients with severe bronchopneumonia

OBJECTIVE: Our objective was to construct a population pharmacokinetic model for moxifloxacin disposition in plasma and bronchial secretions in patients with severe bronchopneumonia who were mechanically ventilated. METHODS: Seventeen patients receiving 400 mg moxifloxacin intravenously daily were enrolled in this multicenter, prospective, open-label study. Blood and bronchial samples were collected on days 1 and 4. The population pharmacokinetic modeling was performed with NONMEM. RESULTS: Moxifloxacin rapidly appeared in bronchial secretions and reached maximum concentrations within 1 to 2 hours. The concentrations achieved in plasma and bronchial secretions showed parallel profiles versus time on days 1 and 4. The pharmacokinetics was best described by a 2-compartment model with a link to bronchial secretions. The population pharmacokinetic parameters were as follows (given as estimate with percent interindividual variability in parentheses except where otherwise indicated): clearance, 14.3 L/h (25%); central distribution volume, 62.9 L (14%); intercompartmental clearance, 27.2 L/h (36%); peripheral distribution volume; 71 L (32%); fraction of moxifloxacin clearance to bronchial secretions, 0.11 (range, 0.06-0.16); and elimination rate constant for bronchial secretions, 1.7 h(-1) (40%). The plasma terminal half-life was 6.7 hours. The bronchial-to-plasma exposure ratio was 1.0 (range, 0.6-2.0). With a conservative 90% minimum inhibitory concentration (MIC(90)) of 0.25 mg/L, the maximum concentration/MIC(90) ratios were higher than 10 and the area under the curve/MIC(90) ratios were roughly 100 for plasma and bronchial secretions. CONCLUSIONS: This study showed the fast diffusion of moxifloxacin into the lungs in ventilated patients with severe respiratory infection. The bronchial secretions reached bactericidal levels for common germs found in respiratory tract infections.     

Choc neurogénique traumatique

Traumatic neurogenic shock is a rare but serious complication of spinal cord injury. It associates bradycardia and hypotension caused by a medullary trauma. It is life-threatening for the patient and it aggravates the neurological deficit. Strict immobilization and a quick assessment of the gravity of cord injury are necessary as soon as prehospital care has begun. Initial treatment requires vasopressors associated with fluid resuscitation. Steroids are not recommended. Early decompression is recommended for incomplete deficit seen in the first 6 hours. We relate the case of secondary spinal shock to a luxation C6/C7 treated in prehospital care.     

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles

Research questionCan previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?DesignRetrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.ResultsIn addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log²(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.ConclusionsEvidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.     

Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Almost half of HCC cases are associated with hepatitis B virus (HBV) infections, which often lead to HBV sequence integrations in the human genome. Accurate identification of HBV integration sites at a single nucleotide resolution is critical for developing a better understanding of the cancer genome landscape and of the disease itself. Here, we performed further analyses and characterization of HBV integrations identified by our recently reported VIcaller platform in recurrent or known HCC genes (such as TERT, MLL4, and CCNE1) as well as non-recurrent cancer-related genes (such as CSMD2, NKD2, and RHOU). Our pathway enrichment analysis revealed multiple pathways involving the alcohol dehydrogenase 4 gene, such as the metabolism pathways of retinol, tyrosine, and fatty acid. Further analysis of the HBV integration sites revealed distinct patterns involving the integration upper breakpoints, integrated genome lengths, and integration allele fractions between tumor and normal tissues. Our analysis also implies that the VIcaller method has diagnostic potential through discovering novel clonal integrations in cancer-related genes. In conclusion, although VIcaller is a hypothesis free virome-wide approach, it can still be applied to accurately identify genome-wide integration events of a specific candidate virus and their integration allele fractions.     

Contraceptive vasectomy: does it have a future in France?

Despite its simplicity and freedom from complications, vasectomy in France faces significant legal, bureaucratic, political, ideologic, psychological, and medical obstacles. Legal obstacles are the most important inasmuch as a principal of French law holds that the individual does not have free disposition of his body. The sole existing French jurisprudence on the question equated male sterilization with premeditated assault and battery. Although no physician has been prosecuted for performing vasectomy since this 1936 Court of Appeals decision, physicians performing vasectomies remain somewhat at the mercy of the caprices of the magistrate. Social security refuses to pay for sterilization performed for contraceptive reasons, which may discourage low income candidates. The Council of the Order of Physicians opposes vasectomy because of its legal status and because article 22 of the Medical Code states that sterilization can only be performed for very serious medical indications. In 1983 the Council changed its recommendation to "very serious indications", dropping the word "medical", but it does not vigorously support vasectomy because of the legal question. Malpractice insurance coverage of vasectomy practitioners is based on whether the results of criminal trials indicate that the operator violated the penal code; the hazy legal status of vasectomy therefore makes insurance coverage unlikely. Political obstacles to vasectomy are far from resolved. No party has openly supported voluntary sterilization, less because of ideological or demagogic considerations than because of the fertility decline in France. Public opinion might question a law authorizing definitive contraception at a time when the replacement of generations is not even assured. Religious objections to contraception in general and sterilization in particular remain strong. A 1978 survey of 1273 French doctors showed that 35% of practicing Catholics but 61% of nonbelievers among them had favorable attitudes toward contraceptive sterilization. Psychological obstacles stem from the danger that vasectomy will be equated to castration. Careful preoperative screening is needed to exclude men likely to suffer impotence or other side effects. The major medical obstacle to vasectomy is its uncertain reversibility. For legal and other reasons, the vasectomy operator should carefully screen each couple, require a 2-3 month waiting period, obtain informed consent, provide a specimen for a sperm bank, limit the operation to men aged at least 35-40 years with 2 or 3 children, and obtain a psychiatric evaluation of the motivation and stability of the couple.     

Infection of the sperm in male sterility

Sperm infection is a classic cause of infertility. But, it cannot be considered without a minimum of precautions. First, infection of the sperm must be proven (presence of altered leucocytes, even higher than 10(5) or 10(6)/ml is not sufficient). What are the consequences of sperm infection? For many germs, especially chlamydiae and mycoplasma, the effect on sperm is not recognized or demonstrated. Once the infection is recognized, an etiology must be found: unrecognized chronic urethritis, prostatitis and/or chronic vesiculitis, chronic epididymitis. The infection must be adequately treated: according to the germ, according to the results of the resistance to antibiotics, according to the etiology. The author concludes that a true sperm infection is very rare; but it must be looked for as soon as it is suspected, especially in patients with a recent history of genital infection. Therefore an effective treatment of infertility is possible.     

Urethral stricture: single-stage urethroplasty by a free skin flap

A single-stage procedure involving the use of a free skin flap for the correction of urethral strictures was performed on eighteen patients. In this series, the strictures were mainly located in the region of the bulbar urethra. Good results were obtained in fourteen cases (80 per cent) out of the eighteen, with a two year followup, or less. The method is simple and effective. In the authors' experience, it has provided a higher success rate than any other procedure described to date. In view of this high success rate, and the equivalent successes reported in the literature, the authors consider that this technique, and urethrotomy, constitute the treatment of choice for urethral stenosis.