Cervical necrotizing fasciitis: descriptive, retrospective analysis of 59 cases treated at a single center.

To provide retrospective, descriptive information on patients with cervical necrotizing fasciitis treated at a single center during the years 1998-2014, and to evaluate the outcome of a newly introduced treatment strategy. Retrospective analysis of clinical data obtained from medical records. Mortality, pre-morbidity, severity of illness, primary site of infection, type of bacteria, time parameters. The observed 3-month mortality was 6/59 (10 %). The most common initial foci of the infection were pharyngeal, dental or hypopharyngeal. The most common pathogen was Streptococcus milleri bacteria within the Streptococcus anginosus group (66 % of the cases). Using a combined treatment with early surgical debridement combined with hyperbaric oxygen treatment, it is possible to reduce the mortality rate among patients suffering from cervical necrotizing fasciitis, compared to the expected mortality rate and to previous historical reports. Data indicated that early onset of hyperbaric oxygen treatment may have a positive impact on survival rate, but no identifiable factor was found to prognosticate outcome.

Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.

BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.

Nitrox permits direct exit for attendants during extended hyperbaric oxygen treatment.

BACKGROUND: Intermittent breathing of oxygen-enriched air, nitrox (1:1 air:oxygen, 60.5% O2), for attendants in multiplace hyperbaric chambers should enable treatment protocols (HOPAN - hyperbaric oxygen protocol attendants' nitrox) of up to 200 minutes at 2.8 atmospheres absolute (ATA), while retaining the option of a direct decompression and exit. METHODS: HOPAN with cycles of 15 minutes of nitrox breathing followed by 10 minutes of chamber air for attendants were occasionally used from 2007-2009. HOPAN vs. LTP (local treatment protocols) were evaluated via an anonymous enquiry among attendants; patients' medical records were followed six months post-HBO2 treatment (HBO2T). RESULTS: 88 HOPANs, with 59 chamber attendants assisting 30 patients, were documented. HOPAN duration ranged from 55-167 minutes (median 140 minutes). 31/59 attendants answered the enquiry. Perceived comfort of each protocol (HOPAN vs. LTP) by attendants was reported as equal. Symptoms, both minor (parestesias) and severe (joint pain), were reported in connection with LTP, while only one occurrence (mild joint pain) was reported in connection with HOPAN. No complications were documented among the attendants or the patients. It is suggested that nitrox breathing for chamber attendants provide flexible HBO2T for patients at 2.8 ATA for up to 200 minutes within no-decompression limits, facilitating future studies of HBO2T dosage.

Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of the new anticancer agent picropodophyllin (AXL1717) and its isomer podophyllotoxin levels in human serum has been developed. Monitoring of hexylamine adducts rather than proton adducts was used to optimize sensitivity. The chromatography system was an Acquity BEH C18, 2.1 mm × 50 mm 1.7 µm column with gradient elution (mobile phase A: 2.5 mM hexylamine and 5 mM formic acid in Milli-Q water and mobile phase B: methanol). The retention times were 1.4 min for picropodophyllin, 1.5 min for podophyllotoxin and 1.9 min for internal standard deoxypodophyllotoxin. The isomers were base-line separated. The analytes were detected after electrospray ionization in positive mode with selected reaction monitoring (SRM) with ion transitions m/z 516→102 for picropodophyllin and podophyllotoxin and m/z 500→102 for internal standard. The sample preparation was protein precipitation with acetonitrile (1:3) containing internal standard followed by dilution of the supernatant with mobile phase A (1:1). The limit of quantification (LOQ) was 0.01 µmol/L for picropodophyllin and podophyllotoxin. The limit of detection (LOD) at 3 times the signal to noise (S/N) was estimated below 0.001 µmol/L for picropodophyllin and podophyllotoxin. The quantification range of the method was between 0.01 µmol/L and 5 µmol/L for both isomers. The accuracy was within ±15% of the theoretical value for both picropodophyllin and podophyllotoxin and inter-assay precision did not exceed ±15%, except for the 0.016 µmol/L level of podophyllotoxin, which was 18%. The selectivity of the method was verified by analysis of two different product ions for each analyte and by analysis for interference of seven different batches of blank human serum. The combined recovery and matrix effects were about 83% for picropodophyllin and podophyllotoxin. The new LC-MS/MS method showed sufficient sensitivity and selectivity for determination of picropodophyllin and its isomer podophyllotoxin levels in human serum from subjects receiving therapeutic doses of AXL1717.

Tissue oxygenation measured with near-infrared spectroscopy during normobaric and hyperbaric oxygen breathing in healthy subjects.

To evaluate the possibility of using near-infrared spectroscopy (NIRS) to measure tissue oxygenation (StO(2)) during hyperbaric oxygen (HBO) therapy. Nine healthy volunteers (1 female) age 25-37 years, breathed air or oxygen. Tissue oxygenation was measured using NIRS on the thumb. Subjects were blinded to breathing gas. A range of partial pressures of oxygen were administered in 10-min intervals: 21, 101, 21 kPa (compression to 280 kPa), 59, 280, 59 (decompression), 21 kPa. Data were averaged over last 5 min at each pressure. When switching from air to normobaric oxygen (NBO 101 kPa) StO(2) increased from 83% (82-85%, median and interquartile range) to 85% (84-87%) (P < 0.01), while when switching from air at pressure (59 kPa O(2)) to HBO (280 kPa), StO(2) increased from 85% (85-86%) to 88% (87-89%) (P < 0.001). There was no difference between baseline StO(2) while air breathing before NBO or after decompression. Values did not reach the maximal value of 100% at any point. The changes in hemoglobin oxygen saturation in tissue registered by the NIRS monitor when switching from air to oxygen followed inspired PO(2) under normobaric and hyperbaric conditions.

Therapeutic drug monitoring of methotrexate on the pediatric oncology ward: can blood sampling from central venous accesses substitute for capillary finger punctures?

Intravenous methotrexate therapy with subsequent calcium folinate rescue is widely used for treatment of various neoplastic diseases, both in adults and in children. The optimization of the methotrexate dose and/or the calcium folinate rescue is based on pharmacokinetic data calculated from plasma concentrations collected after cessation of the methotrexate infusion. The aim of the present study was to evaluate the possibility of substituting capillary blood samples with blood samples drawn from central venous catheters (PORT-A-CATH) for therapeutic drug monitoring of methotrexate on the pediatric oncology ward. Nine cancer patients (4 females and 5 males; median age: 15 years; range: 5-20 years) were included. The quantitative analysis of methotrexate was carried out by fluorescence polarization immunoassay (FPIA). The concentrations of methotrexate in venous and capillary samples were closely correlated (rs = 0.98; P < 0.0001; n = 71). The venous/capillary plasma concentration ratio was 1.00 [median value; interquartile range (IQR): 0.882-1.094]; for 85% of the data points the ratio was 0.8 to 1.2, independent of drug concentration. The observed plasma concentration differences in blood samples drawn from central venous accesses and obtained from capillary blood samples in this study could have altered the calcium folinate rescue at 1 treatment occasion only. Plotting all measured methotrexate concentration time data for the individual patients during the elimination phase, on a chart including a normal elimination curve, is mandatory to enable proper handling of the subsequent rescue after high-dose methotrexate therapy. Blood sampling from the central venous access can be used only under certain circumstances for therapeutic drug monitoring of methotrexate. Carefully evaluated standardized instructions regarding rinsing, flushing, and discarding waste volumes, as well as precautions to minimize the required blood volume, are needed.