Ultrasound-Guided Scalp Blocks for an Awake Craniotomy: A Case Report.

Ultrasound-guided scalp blocks may revolutionize regional anesthesia for neurosurgery. In this report, we demonstrate that ultrasound-guided scalp blocks can be used effectively for a craniotomy. A 48-year-old patient with a brain tumor at the motor cortex was scheduled for an awake craniotomy. Ultrasound-guided scalp blocks targeting the bilateral supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, greater auricular, lesser occipital, greater occipital, and third occipital nerves were performed. A total of 29 mL of levobupivacaine 0.3% was used. No additional local anesthetic agent was given for skull pinning, skin incision, or the craniotomy. Postoperatively, the patient remained pain-free, and she was discharged without complications.

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.

Candida albicans aspects of binary titanium alloys for biomedical applications.

Titanium and its alloys are widely used in biomedical devices, e.g. implants, due to its biocompatibility and osseointegration ability. In fact, fungal (Candida spp.) infection has been identified as one of the key reasons causing the failure of the device that is inevitable and impactful to the society. Thus, this study evaluated the surface morphology, surface chemical composition and Candida albicans adhesion on specimens of 16 binary Ti-alloys (∼5 wt% of any one of the alloy elements: Ag, Al, Au, Co, Cr, Cu, Fe, In, Mn, Mo, Nb, Pd, Pt, Sn, V and Zr) compared with cp-Ti, targeting to seek for the binary Ti-alloys which has the lowest C. albicans infection. Candida albicans cultures were grown on the specimens for 48 h, and colony forming units (CFUs) and real-time polymerase chain reaction (RT-PCR) were used to evaluate the biofilm formation ability. Scanning electron microscopy and confocal laser scanning microscopy confirmed the formation of C. albicans biofilm on all specimens' surfaces, such that CFU results showed Ti-Mo, Ti-Zr, Ti-Al and Ti-V have less C. albicans formed on the surfaces than cp-Ti. RT-PCR showed Ti-Zr and Ti-Cu have significantly higher C. albicans DNA concentrations than Ti-Al and Ti-V (P < 0.05), whereas Ti-Cu has even showed a statistically higher concentration than Ti-Au, Ti-Co, Ti-In and Ti-Pt (P < 0.05). This study confirmed that Ti-Mo, Ti-Zr, Ti-Al and Ti-V have lower the occurrence of C. albicans which might be clinically advantageous for medical devices, but Ti-Cu should be used in caution.

Comparison of two laboratory extraction techniques for the detection of Epstein-Barr virus in the saliva of nasopharyngeal carcinoma patients.

AIM: The aim of the present study was to compare the effectiveness of DNA extraction using an extraction kit against the standard boiling technique for the detection of Epstein-Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC) patients. METHODS: Stimulated whole saliva samples from newly-diagnosed NPC patients were collected. EBV DNA was extracted by both techniques (n = 23) followed by quantitative real-time polymerase chain reaction (PCR) using the primer/probe set for BALF5. RESULTS: The results of the quantitative real-time PCR were reproducible in both groups. The two techniques were moderately correlated (r = 0.67, P < 0.05), and the degree of agreement was good. However, the mean EBV DNA level in the boiling group (3.02 ± 8.67 × 10(6) copies/µL) was significantly higher than the extraction kit group (1.15 ± 2.66 × 10(6) copies/µL) (P < 0.05). The EBV DNA level was higher in patients at an advanced overall stage (P = 0.05). CONCLUSION: The results of the present study showed that the performance of the extraction kit was not superior to the simple boiling technique for the detection of salivary EBV DNA in NPC patients using real-time PCR. The salivary EBV DNA level in patients at an advanced overall stage appeared to be higher than in patients at an early stage.

Salivary Epstein-Barr virus DNA level in patients with nasopharyngeal carcinoma following radiotherapy.

Nasopharyngeal carcinoma (NPC) is a solid tumor closely associated with Epstein-Barr virus (EBV) infection. The purpose of this investigation was to detect and quantify the EBV DNA level in salivary samples of NPC patients following treatment using real-time PCR. A total of 175 consecutive newly diagnosed NPC patients' whole saliva samples were collected before treatment, and the EBV DNA level was measured by real-time PCR, with the primers and probe targeting the BamHI-W region of the EBV genome. The post-treatment salivary EBV DNA level was also assessed in 46 patients. The change of EBV DNA level before and after treatment and relationship of EBV DNA level to demographic data and tumor staging were tested by Wilcoxon signed-rank test and Mann-Whitney U test, respectively with the level of significance set at 0.05. The EBV detection rate of pre-treatment saliva samples was 80%. The EBV DNA level of post-treatment saliva samples was significantly higher than the pre-treatment ones (P<0.01). There is a trend that patients with advanced-stage showed a higher EBV DNA level than patients with early-stage. The detection of EBV DNA in saliva using real-time PCR might be a feasible and non-invasive method for early diagnosis of NPC.

CBR1 and CBR3 pharmacogenetics and their influence on doxorubicin disposition in Asian breast cancer patients.

The present study aimed to identify polymorphic genes encoding carbonyl reductases (CBR1, CBR3) and investigate their influence on doxorubicin disposition in Asian breast cancer patients (n = 62). Doxorubicin (60 mg/m(2)) was administered every 3 weeks for four to six cycles and the pharmacokinetic parameters were estimated using non-compartmental analysis (WinNonlin). The Mann-Whitney U-test was used to assess genotypic-phenotypic correlations. Five CBR1 (-48G>A, c.219G>C, c.627C>T, c.693G>A, +967G>A) and CBR3 (c.11G>A, c.255C>T, c.279C>T, c.606G>A, c.730G>A) polymorphisms were identified. The CBR1 D2 diplotypes were characterized by the presence of at least one variant allele at the c.627C>T and +967G>A loci. Patients in the CBR1 D1 diplotype group had significantly higher clearance (CL) normalized to body surface area (BSA) (CL/BSA[L/h/m(2)]: median 25.09; range 16.44-55.66) and significantly lower exposure levels; area under curve (AUC(0-infinity)/dose/BSA [h/m(5)]; median 15.08; range 6.18-38.03) of doxorubicin compared with patients belonging to the CBR1 D2 diplotype group (CL/BSA[L/h/m(2)]; median 20.88; range 8.68-31.79, P = 0.014; and AUC(0-infinity)/dose/BSA[h/m(5)]; median 21.35; range 9.82-67.17, P = 0.007 respectively). No significant influence of CBR3 polymorphisms on the pharmacokinetics of doxorubicin were observed in Asian cancer patients. The present exploratory study shows that CBR1 D2 diplotypes correlate with significantly higher exposure levels of doxorubicin, suggesting the possibility of lowered intracellular conversion to doxorubicinol in these patients. Further evaluation of carbonyl reductase polymorphisms in influencing the treatment efficacy of doxorubicin-based chemotherapy in Asian cancer patients are warranted.

Efficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancer.

PURPOSE: This study (EGF20009) assessed the efficacy and tolerability of two lapatinib administration schedules as first-line monotherapy in women with ErbB2-amplified locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Patients with ErbB2-amplified, locally advanced or metastatic breast cancer previously untreated in the metastatic setting were randomly assigned to one of two lapatinib dose cohorts and received either 1,500 mg once daily or 500 mg twice daily. Clinical response was assessed at weeks 8 and 12 and every 12 weeks thereafter. RESULTS: A total of 138 patients were treated with lapatinib for a median of 17.6 weeks. The overall response rate (complete response [CR] plus partial response [PR]) was 24% in the intent-to-treat population, and 31% of patients derived clinical benefit (CR, PR, or stable disease for >or= 24 weeks). The median time to response was 7.9 weeks, and the progression-free survival rates at 4 and 6 months were 63% and 43%, respectively. The most common lapatinib-related adverse events (AEs) were diarrhea, rash, pruritus, and nausea, and these events were primarily grade 1 or 2. There were no significant differences in clinical activity or the AE profile between the dosing schedules. CONCLUSION: Lapatinib demonstrated clinical activity and was well tolerated as first-line therapy in ErbB2-amplified locally advanced or metastatic breast cancer. This study supports further evaluation of lapatinib in first-line and early-stage ErbB2-overexpressing breast cancer.

Identification of cultivable microorganisms from root canals with apical periodontitis following two-visit endodontic treatment with antibiotics/steroid or calcium hydroxide dressings.

The study was aimed at comparing the efficacy of disinfection of root canals with periapical radiolucencies when treated with either antibiotics/steroid medicaments (Ledermix or Septomixine) or a calcium hydroxide paste (Calasept). Microbiological samples were taken before and after two-visit endodontic treatment from 88 canals with apical periodontitis. All of the canals but one (87 of 88) had cultivable growth before treatment. After dressing with Ledermix, Septomixine, or Calasept, the percentages of canals remained with positive growth were 48% (13 of 27), 31% (8 of 26), and 31% (11 of 35), respectively. The chi(2) tests showed there were no significant differences in the number of canals with positive growth or mean colony forming units counts after instrumentation, irrigation and dressing. In the Ledermix group, 38 strains of bacteria were recovered. The Septomixine group had 25 strains, and the Calasept group had 25 strains. Gram-positive facultative anaerobic cocci (including staphylococci and streptococci) were more prevalent than the Gram-negative obligate anaerobic rods after treatment in all three groups. Similarities in the reduced number of canals with residual growth, and the prevalence of Gram-positive facultative anaerobic cocci suggest that the use of different inter-appointment dressings produced similar microbiological outcomes. However, factors other than the antimicrobial effectiveness of intracanal medicaments may also be responsible for the results observed.

Direct detection of Actinomyces spp. from infected root canals in a Chinese population: a study using PCR-based, oligonucleotide-DNA hybridization technique.

OBJECTIVES: The poor sensitivity of phenotypic identification techniques has hampered the taxonomic differentiation of Actinomyces. Hence we developed a sensitive and specific, PCR-based oligonucleotide-DNA hybridization technique to detect Actinomyces spp. and, used this method to detect these organisms in samples directly obtained from infected root canals. METHODS: A total of 32 samples from 28 Chinese patients, with primary root canal infections, aseptically exposed at the first patient visit, were studied. Whole bacterial genomic DNA was isolated directly from paper point samples. The variable regions of 16S ribosomal DNA of bacteria were amplified and labeled with digoxigenin for further hybridization and detection. A total of seven oligonucleotide probes specific for A. bovis, A. gerencseriae, A. israelii, A. meyeri, catalase-negative A. naeslundii (genospecies 1 and 2), catalase-positive A. naeslundii genospecies 2 and A. odontolyticus were used. RESULTS: 16 of the 32 teeth were infected with one or more Actinomyces species. The prevalence rates of the examined species were: A. odontolyticus 31.3%, A. meyeri 9.4%, A. naeslundii 9.4%, A. israelii 6.3% and A. gerencseriae 3.1%; no A. bovis was detected in any of the canals. Furthermore, A. odontolyticus was isolated more frequently from root canals with caries or a history of caries (Fisher's exact test: P=0.0496; Odds ratio=9.00, 95% confidence interval: 0.97-83.63), and A. naeslundii was significantly associated with traumatized teeth (Fisher's exact test: P=0.0121; Odds ratio=57.00, 95% confidence interval: 2.10-1546.90). However, no significant correlation was found between Actinomyces spp. and clinical symptoms and signs, such as pain, swelling, percussion to tenderness, sinus and periapical radiolucency. CONCLUSION: Actinomyces spp. may be important pathogens of root canal infections. A. naeslundii in particular may be related with traumatized teeth. A. odontolyticus appears to be involved in infections related to caries, exposure of dentinal tubules during cavity preparation and/or leaking restoration, but further clarification with large samples is necessary.

Detection of hyperoxaemia in neonates: data from three new pulse oximeters.

AIM: To determine the sensitivity and specificity of three newly developed pulse oximeters in the detection of hyperoxaemia, defined as an arterial partial pressure of oxygen (PaO(2)) of > 80 mm Hg. METHODS: SpO(2) readings from three oximeters (Agilent Viridia (AgV), Masimo SET (MaS), Nellcor Oxismart (NeO)) were documented in 56 infants (median gestational age at birth 35.5 weeks, range 24-41) whenever an arterial blood gas was taken for clinical purposes. Blood samples were analysed within one minute in a Radiometer ABL 505 blood gas analyser and OSM3 co-oximeter. RESULTS: Between 280 and 291 blood gases were analysed for each instrument; 105-112 showed a PaO(2) > 80 mm Hg. At an upper alarm limit of 95%, the three instruments detected hyperoxaemia with 93-95% sensitivity. Specificity at this alarm level ranged from 26 to 45%. The mean (SD) difference between arterial oxygen saturation and SpO(2) (bias) was -0.25 (2.5)% for AgV, -0.06 (2.5)% for MaS, and -0.91 (2.6)% for NeO (p < 0.01, NeO v AgV and MaS). CONCLUSION: These instruments detected hyperoxaemia with sufficient sensitivity at an upper alarm limit of 95%, but showed differences in their specificity, which was probably related to differences in measurement bias.

Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation.

AIM: To demonstrate that skin-to-skin care (SSC) has no detrimental effects on the frequency of episodes of bradycardia and/or hypoxemia. METHODS: Twenty-two spontaneously breathing preterm infants (median gestational age at birth, 29 weeks [range, 24-31 weeks]; age at study, 26 days [range, 7-72 days]; weight at study, 1310 g [range, 725-1890 g]) had three 2-hour recordings of breathing movements, nasal airflow, heart rate, and oxygen saturation as measured by pulse oximetry (SpO(2)) before, during, and after SSC. Rectal temperature was obtained every 2 hours. Recordings were analyzed for baseline heart and respiratory rates, bradycardia (heart rate < two thirds of baseline), and hypoxemia (SpO(2) < or =80%), as well as for breathing pattern (regular vs non-regular). RESULTS: Baseline heart rate and respiratory rate increased during SSC (P <.01), as did the combined frequency of bradycardia and hypoxemia (from 1.5/h [0-8] before to 2.8/h [0-15] during SSC; P<.05). Rectal temperature increased from 36.9 degrees C (36.2 degrees -37.4 degrees C) to 37.3 degrees C (36.6 degrees -38.6 degrees C; P <.01). The proportion of regular breathing pattern decreased from 14% (2%-28%) to 7% (3%-26%) with SSC (P<.01). CONCLUSION: SSC was associated with a significant increase in the combined frequency of bradycardia and hypoxemia and with less regular breathing. These changes were unexpected and may have been related to heat stress. Body temperature, heart rate, and oxygenation should be monitored during SSC.

Pulse oximeters' reliability in detecting hypoxemia and bradycardia: comparison between a conventional and two new generation oximeters.

OBJECTIVE: Pulse oximeters are increasingly used for patient monitoring; however, they are traditionally very prone to motion artifact. Newly developed instruments have lower false alarm rates. We wanted to know whether this is achieved at the expense of an increased proportion of false negative alarms such as missed or delayed identification of hypoxemia and/or bradycardia. DESIGN: Observational study. SETTING: Neonatal intensive care unit. PATIENTS: A total of 17 unsedated preterm infants (median gestational age at birth, 25 wks; range, 24-30 wks). INTERVENTION: Long-term recordings of transcutaneous partial pressure of oxygen (P(Tc)O2), heart rate, pulse oximeter saturation (SpO2), and pulse rate from a conventional oximeter and two new generation oximeters. MEASUREMENTS: Recordings were analyzed for episodes with P(Tc)O2 <40 torr or with heart rate <80 beats/min for >5 secs. Hypoxemia was considered identified if SpO2 had fallen to <85% within 2 mins of P(Tc)O2 reaching 40 torr, and bradycardia was considered identified if pulse rate had fallen to <80 beats/min within 2 mins of the heart rate reaching this threshold. MAIN RESULTS: A total of 202 falls in P(Tc)O2 to <40 torr occurred; 174 (86%) were identified by all three oximeters. Of the remaining episodes, manual analysis of red and infrared absorption signals confirmed that SpO2 had indeed been <85% for > or =10 secs in 11 episodes; therefore, these episodes should have been identified by all three oximeters. None of these had been missed by the conventional oximeter, but 10 (5.4% of the total) were missed by one of the new generation instruments (Nellcor), and one (0.5%) was missed by the other (Masimo). Of 54 bradycardias, only 14 were identified by all three oximeters; 17 (32%) were missed by the conventional, 37 (69%) by the Nellcor, and 4 (7%) by the Masimo instrument. CONCLUSION: One of the two new generation instruments investigated in this study missed 5.4% of hypoxemic episodes and 69% of bradycardias. It thus appears that this instrument's reduced false alarm rate is achieved at the expense of an unreliable and/or delayed identification of hypoxemia and bradycardia. The other instrument identified both conditions equally as or more reliably than a conventional pulse oximeter.

False alarms in very low birthweight infants: comparison between three intensive care monitoring systems.

UNLABELLED: Monitor alarms are a major burden on both patients and staff in intensive care units. We compared alarm rates from three different monitor systems (Hewlett Packard (HP), Kontron Instruments (KI), Marquette-Hellige (MH)) in a tertiary neonatal intensive care unit. Monitors were used in random order on three consecutive days over 8 h each in 16 preterm infants (median gestational age at birth 29 wk (range 24-34), age at study 18 d (8-53), weight at study 1,160g (595-1,430)). Alarms were classified as true or false using flow sheets based on continuous observation of both the patient and related parameters. There was one alarm every 9 min of monitoring. The median number of true alarms did not differ significantly between systems, being 28 per 8 h (range 9-87) for HP, 26 (3-81) for KI, and 30 (5-135) for MH. The median number of false alarms differed widely, with the HP system generating 32 (7-77) such alarms per 8 h, compared to 8 (0-19) for KI and 15 (2-32) for MH (p < 0.01 HP vs KI and MH, p < 0.05 KI vs MH). These differences between systems were mainly due to differences in pulse oximeter and transcutaneous PO2 monitor alarm rates. CONCLUSIONS: In conclusion, this study shows marked differences between both parameters and manufacturers in the frequency with which false alarms occur. It may provide a basis from which reductions in alarm rates can be sought.

Necrotising enterocolitis: is there a relationship to specific pathogens?

UNLABELLED: Outbreaks of necrotising enterocolitis (NEC) have often been related to specific pathogens such as Enterobacteriaceae. This relationship, however, remains uncertain because of the retrospective nature of the studies addressing this issue. We performed a prospective study to investigate whether there is indeed an association between NEC and specific pathogens. Between April 1993 and March 1997, stools of neonates of < 36 weeks admitted to our neonatal unit were investigated for bacteria in weekly intervals. Clinical and bacteriological data from each infant who developed NEC were compared with those from two control infants matched for gestational age and date of admission. Eighteen infants developed 19 episodes of NEC (clinical signs + air in portal vein); 8 of these had laparotomy; two died. Occurrences of NEC were homogeneously distributed over the 4-year study period. The only significant differences in the clinical course prior to NEC were a more severe stage of respiratory distress syndrome [median 2 (0-4) vs. 0 (0-3), P < 0.05] and a higher proportion of infants who had only been formula fed (63 vs. 32%, P < 0.05) in the cases. Within the last week prior to NEC, potentially pathogenic bacteria were identified in stools of all cases and 79% of controls (P < 0.05). However, there was no significant difference in the occurrence of specific pathogens or groups of pathogens in cases compared with controls. CONCLUSION: Although gut colonisation with potential pathogens appeared to be a prerequisite for the development of NEC, there were no specific bacteria associated with this disease if data from infants with NEC were compared with those from time- and gestational age-matched controls.