Borrelia miyamotoi infection in nature and in humans.

Borrelia miyamotoi is a relapsing fever Borrelia group spirochete that is transmitted by the same hard-bodied (ixodid) tick species that transmit the agents of Lyme disease. It was discovered in 1994 in Ixodes persulcatus ticks in Japan. B. miyamotoi species phylogenetically cluster with the relapsing fever group spirochetes, which usually are transmitted by soft-bodied (argasid) ticks or lice. B. miyamotoi infects at least six Ixodes tick species in North America and Eurasia that transmit Lyme disease group spirochetes and may use small rodents and birds as reservoirs. Human cases of B. miyamotoi infection were first reported in 2011 in Russia and subsequently in the United States, Europe and Japan. These reports document the public health importance of B. miyamotoi, as human B. miyamotoi infection appears to be comparable in frequency to babesiosis or human granulocytic anaplasmosis in some areas and may cause severe disease, including meningoencephalitis. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Symptoms of B. miyamotoi infection generally resolve within a week of the start of antibiotic therapy. B. miyamotoi infection should be considered in patients with acute febrile illness who have been exposed to Ixodes ticks in a region where Lyme disease occurs. Because clinical manifestations are nonspecific, etiologic diagnosis requires confirmation by blood smear examination, PCR, antibody assay, in vitro cultivation, and/or isolation by animal inoculation. Antibiotics that have been used effectively include doxycycline for uncomplicated B. miyamotoi infection in adults and ceftriaxone or penicillin G for meningoencephalitis.

A survey of prescriber perceptions about the prevention of stress-related mucosal bleeding in the intensive care unit.

WHAT IS KNOWN AND OBJECTIVE: Practices vary between institutions and amongst prescribers regarding when to initiate stress ulcer prophylaxis (SUP), which agent to choose (including doses and frequencies) and rationale, and decisions about escalation or discontinuation of therapy. The purpose of this survey is to evaluate the perceptions of prescribers about risk assessment of stress-related mucosal bleeding (SRMB) and practice patterns of SUP. METHODS: A cross-sectional survey of 800 US critical care prescribers using the membership of the Society of Critical Care Medicine. The levels of agreement with specific statements were rated on a nine-point Likert scale. RESULTS: Of 712 eligible recipients, 245 (34·4%) completed the questionnaire. Respondents were primarily attending physicians (81·2%) working in adult medical or surgical (59·2%) intensive care units. Mucosal ischaemia was identified as the pathophysiological cause of SRMB by 110 (44·9%) respondents. Respondents agreed that risk factors for SRMB were acute hepatic failure, anticoagulant use, burns >35%, coagulopathy, absence of enteral feeding, recent gastroduodenal ulcer, corticosteroid use, Helicobacter pylori infection, neurologic injury, trauma, NSAID use, mechanical ventilation, shock and sepsis. Histamine subtype 2 receptor antagonists (58·4%) and proton pump inhibitors (39·6%) were the most frequently chosen agents. No consensus was reached about whether either class is associated with clostridium difficile infection or nosocomial pneumonia. Reasons to discontinue therapy included clinically improved patient status (73·1%), extubation (68·2%), reversal of 'nil-by-mouth' (68·6%) and transfer to a non-ICU setting (67·8%). WHAT IS NEW AND CONCLUSIONS: Considerable variability exists in the perceptions surrounding risk factors for SRMB and prescribing patterns for SUP therapy likely because limited or conflicting data are available addressing these issues. Opportunities exist to educate prescribers and conduct research about the pathologic cause and risk factors for SRMB, the preferred class of agents, and the appropriate discontinuation of therapy.

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound.

BACKGROUND: In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC). METHODS: 371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis. RESULTS: The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision. CONCLUSION: Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.

Primary thyroid-like follicular renal cell carcinoma: an emerging entity.

Primary thyroid-like follicular carcinoma of the kidney is a rare but newly emerging histological variant of renal cell carcinoma RCC, with only nine cases reported in the literature to date. We present a further case of this unique condition, discuss the workup and typical histological findings, and review the literature regarding this rare histological variant.

Frequency of electrocardiogram testing among HIV-infected patients at risk for medication-induced QTc prolongation.

OBJECTIVES: HIV-infected patients are commonly prescribed several medications and are thus at risk for drug interactions that may result in QTc prolongation. We sought (1) to identify the frequency of electrocardiogram (ECG) monitoring (2), to determine the prevalence of drug interactions involving QTc-prolonging medications, and (3) to quantify the prevalence of QTc prolongation. METHODS: A cross-sectional study was conducted among HIV-infected adults. Demographics, medications, drug interactions and comorbidities were abstracted from patients' medical records. Abnormal QTc interval was defined per the UK Committee for Proprietary Medicinal Products. Clinical characteristics were compared among ECG recipients and nonrecipients. Among ECG recipients, the prevalence and predictors of QTc prolongation were assessed. RESULTS: Among the 454 patients included in the study, 80.8% were prescribed a medication associated with QTc prolongation and 39% had drug interactions expected to increase QTc prolongation risk. There were 138 patients (30.3%) who received ECG testing. Receipt of ECG monitoring was associated with increasing age, diabetes, increasing total number of medications and gastroesophageal reflux disease. Among ECG recipients, the prevalence of abnormal QTc interval was 27.5%. Chronic kidney disease [prevalence ratio (PR) 3.47; 95% confidence interval (CI) 1.37-8.83; P = 0.009], hepatitis C virus coinfection (PR 2.26; 95% CI 0.97-5.27; P = 0.06) and hypertension (PR 2.11; 95% CI 0.93-4.81; P = 0.07) were independently associated with an abnormal QTc interval. CONCLUSIONS: A low frequency of ECG testing was observed, despite a high use of medications associated with QTc prolongation. The risk of abnormal QTc interval was highest among patients with chronic kidney disease, hypertension and hepatitis C virus coinfection.

Pharmacodynamic modelling of intravenous antibiotic prophylaxis in elective colorectal surgery.

Surgical-site infections are the leading cause of post-operative morbidity and mortality as well as increased costs following colorectal surgery. The purpose of this study was to evaluate different ß-lactam antimicrobial dosing regimens currently used for prophylaxis in elective colorectal procedures with the aim of identifying optimal antibiotics and dosing regimens. Serum pharmacokinetic (PK) parameters specific to each drug for use in pharmacodynamic (PD) modelling were obtained from the published literature. Susceptibility data for Escherichia coli, Bacteroides fragilis and Staphylococcus aureus for use in modelling simulations were obtained from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Monte Carlo simulation was used to evaluate the influence of dose and dosing frequency of tested antibiotics to achieve a prophylaxis target fT>MIC (time during which the free drug concentration exceeds the pathogen minimum inhibitory concentration) of 100% for up to 4h. Ertapenem 1g, cefuroxime 1.5 g and cefazolin 2 g were the only antibiotic regimens that consistently yielded target fT>MIC of 100% for the entire 4-h post-dose interval and against all targeted organisms more than 90% of the time. In contrast, cefoxitin, cefotetan and ampicillin/sulbactam yielded very poor predicted PK/PD performances. In conclusion, this study demonstrates the value of, and need for, applied PD research in the area of surgical prophylaxis. Whether cefoxitin, cefotetan or ampicillin/sulbactam should continue to be advocated as first-line agents for prophylaxis during elective colorectal surgery, particularly at the standard doses currently being used, is debatable.

Clinically palpable breast abnormalities with normal imaging: is clinically guided biopsy still required?

AIM: To determine the need for a fine-needle or core biopsy in patients with clinically palpable breast abnormalities who have negative mammographic and sonographic findings. METHOD AND MATERIALS: Over a 12-year period, 251 patients with a palpable abnormality at presentation and who had a negative ultrasound and mammogram underwent clinically guided biopsy (CGB) by breast surgeons. This was 2.7% (251/9313) of all breast biopsies performed from January 1999 to December 2010. Physical findings were qualitatively categorized into five groups as clinically "normal", "benign", "probably benign", "suspicious", and "malignant" at the time of initial assessment. The number of biopsies for each category and biopsy results were analysed retrospectively. RESULTS: Three (1.2%) of the 251 CGBs were reported as malignant; two (0.8%) of which were invasive. Forty-six (18.3%) of the 251 cases were regarded as clinically suspicious or malignant while the remaining 215 examinations were categorized as benign or probably benign. All three malignancies were in the clinically suspicious or malignant group. CONCLUSION: A negative ultrasound and mammogram in patients with a palpable abnormality does not exclude breast cancer; however, the likelihood is very low (1.2%). In this study, 81.7% of biopsies (205/251) could have been avoided if CGB was reserved for the clinically suspicious or malignant group only without missing any malignancies.

Statistical thermodynamics and kinetics of DNA multiplex hybridization reactions.

A general analytical description of the equilibrium and reaction kinetics of DNA multiplex hybridization has been developed. In this approach, multiplex hybridization is considered to be a competitive multichannel reaction process: a system wherein many species can react both specifically and nonspecifically with one another. General equations are presented that can consider equilibrium and kinetic models of multiplex hybridization systems comprised, in principle, of any number of targets and probes. Numerical solutions to these systems for both equilibrium and kinetic behaviors are provided. Practical examples demonstrate clear differences between results obtained from more common simplex methods, in which individual hybridization reactions are considered to occur in isolation; and multiplex hybridization, where desired and competitive cross-hybrid reactions between all possible pairs of strands are considered. In addition, sensitivities of the hybridization process of the perfect match duplex, to temperature, target concentration, and existence of sequence homology with other strands, are examined. This general approach also considers explicit sequence-dependent interactions between targets and probes involved in the reactions. Sequence-dependent stabilities of all perfect match and mismatch duplex complexes are explicitly considered and effects of relative stability of cross-hybrid complexes are also explored. Results reveal several interdependent factors that strongly influence DNA multiplex hybridization behavior. These include: relative concentrations of all probes and targets; relative thermodynamic stability of all perfect match and mismatch complexes; sensitivity to temperature, particularly for mismatches; and amount of sequence homology shared by the probe and target strands in the multiplex mix.

Scar formation after stereotactic vacuum-assisted core biopsy of benign breast lesions.

AIM: To evaluate scar formation of impalpable breast lesions with benign histological outcome using stereotactic 11-gauge vacuum-assisted core biopsy (VACB). MATERIALS AND METHODS: Two hundred and ten lesions with benign histology for which follow-up mammograms were available, were assessed for scar formation at the biopsy site. All biopsies were performed using stereotactic VACB with 11-gauge needle. The incidence of post-biopsy scar formation and the number of specimens removed were determined. RESULTS: In 4.3% (9/210) of the lesions for which a biopsy was performed with 11-gauge directional vacuum-assisted technique, the follow-up mammogram revealed a scar formation. Of these, six were minimal scars, two were moderate scars and one was a marked scar. Minimal and moderate scars were diagnosed on imaging only. However, the case with marked scar formation required tissue diagnosis to rule out malignancy. CONCLUSION: Although uncommon, scar formation can be seen in the follow-up mammograms after percutaneous breast biopsies. It is important that the radiologist interpreting follow-up mammograms is aware of the features of this lesion and its relationship to the biopsy procedure.

Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari: Ixodidae) in the United States.

The risk of Lyme disease for humans in the eastern United States is dependent on the density of host-seeking Ixodes scapularis Say nymphal stage ticks infected with Borrelia burgdorferi. Although many local and regional studies have estimated Lyme disease risk using these parameters, this is the first large-scale study using a standardized methodology. Density of host-seeking I. scapularis nymphs was measured by drag sampling of closed canopy deciduous forest habitats in 95 locations spaced among 2 degrees quadrants covering the entire United States east of the 100th meridian. Sampling was done in five standardized transects at each site and repeated three to six times during the summer of 2004. The total number of adults and nymphs of the seven tick species collected was 17,972, with 1,405 nymphal I. scapularis collected in 31 of the 95 sites. Peak global spatial autocorrelation values were found at the smallest lag distance (300 km) and decreased significantly after 1,000 km. Local auto-correlation statistics identified two significant high-density clusters around endemic areas in the northeast and upper Midwest and a low-density cluster in sites south of the 39th parallel, where only 21 nymphs were collected. Peak nymphal host-seeking density occurred earlier in the southern than in the most northern sites. Spatiotemporal density patterns will be combined with Borrelia prevalence data as part of a 4-yr survey to generate a nationwide spatial risk model for I. scapularis-borne Borrelia, which will improve targeting of disease prevention efforts.

Effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections in infants.

We conducted a prospective, cohort study at two affiliated level III neonatal intensive care units to evaluate the effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections (CRBSI) in infants. A total of 300 infants (n=150 at each site) were enrolled over a 4-year study period. There was no difference in the rate of CRBSI per 1000 catheter days between the two sites (16.2+/-39 vs. 8.9+/-24, P=0.054, 95% CI-14.8 to 0.13). Infants at site A (closed drug-delivery system) had a higher rate of infectious nosocomial respiratory complications per 100 hospital days than infants at site B (open delivery system) (1.1+/-2.2 vs. 0.5+/-1.5, P=0.009), however, there was no difference in the overall number of confirmed or suspected nosocomial infection events per patient between study sites. Logistic regression revealed that the number of additional peripheral catheters, gestational age and duration of parenteral nutrition all significantly contributed to the risk of developing one or more CRSBI. The closed drug-delivery system failed to reduce the incidence of CRBSI or overall rate of nosocomial infections in premature infants.

fMRI temporal clustering analysis in patients with frequent interictal epileptiform discharges: comparison with EEG-driven analysis.

Temporal clustering analysis (TCA) is an exploratory data-driven technique that has been proposed for the analysis of resting fMRI to localise epileptiform activity without need for simultaneous EEG. Conventionally, fMRI of epileptic activity has been limited to those patients with subtle clinical events or frequent interictal epileptiform EEG discharges, requiring simultaneous EEG recording, from which a linear model is derived to make valid statistical inferences from the fMRI data. We sought to evaluate TCA by comparing the results with those of EEG correlated fMRI in eight selected cases. Cases were selected with clear epileptogenic localisation or lateralisation on the basis of concordant EEG and structural MRI findings, in addition to concordant activations seen on EEG-derived fMRI analyses. In three, areas of activation were seen with TCA but none corresponding to the electro-clinical localisation or activations obtained with EEG driven analysis. Temporal clusters were closely coincident with times of maximal head motion. We feel this is a serious confound to this approach and recommend that interpretation of TCA that does not address motion and physiological noise be treated with caution. New techniques to localise epileptogenic activity with fMRI alone require validation with an appropriate independent measure. In the investigation of interictal epileptiform activity, this is best done with simultaneous EEG recording.

Maintaining high autopsy rates in a Canadian blood and marrow transplant program: preserving a diagnostic and research tool.

Autopsy series have revealed patterns of injury in graft-versus-host disease and provided insight into infectious and toxic complications following hematopoietic stem cell transplantation (HSCT). Overall autopsy rates have declined significantly in recent decades including specialized services such as neonatal medicine and cardiac care. However, rates of post-mortem exams at HSCT centers have not been specifically documented. We reviewed hospital records between 1992 and 2002 to determine overall autopsy rates at our hospital and within the HSCT program. Although the overall autopsy rate declined steadily from 24% in 1992 to 9% in 2002, rates of post-mortem exams in the HSCT program remained relatively stable at 32% (24-46%). Autopsy rates were not significantly different for recipients of allogeneic vs autologous transplants and no clear difference was observed for the proportion of autopsies requested on weekdays compared with weekends. Autopsies confirmed major clinical diagnoses and/or suspected causes of death in 45 of 61 autopsies (74%) and yielded major or minor disagreements in clinical diagnosis in 10 cases (16%) and seven cases (11%), respectively. The preservation of high rates of autopsy within our HSCT program demonstrates that specialized programs are able to maintain elevated rates of post-mortem examinations despite overall declining rates.

Surveillance of multi-drug resistant Pseudomonas aeruginosa in an urban tertiary-care teaching hospital.

Antimicrobial resistance in Pseudomonas aeruginosa is a serious clinical problem. To determine the incidence of multi-drug resistant P. aeruginosa, resistance rates of P. aeruginosa clinical isolates against commonly used antibiotics were evaluated for the period 1998 to 2002. Multi-drug resistance was defined as resistance to at least three of the four drugs, ceftazidime, imipenem, ciprofloxacin, and tobramycin. Resistance to most anti-pseudomonal agents has increased by >20% over the five-year period, with dramatic increases observed with fluoroquinolones, tobramycin, and imipenem (resistance increased by 34-37%). In 1998, 78% of isolates were susceptible to all four anti-pseudomonal agents and no isolate was considered multi-drug resistant. However, in 2002, only 27% of isolates were sensitive to all four of the drugs and 32% were considered multi-drug resistant. Multi-drug resistance in individual institutions may be significantly higher than rates reported in nationwide surveillance studies and may more accurately reflect the true magnitude of local resistance problems. On-going surveillance within individual institutions is critical for the selection of appropriate empiric antimicrobial therapy.