Comparing Point-of-care-ultrasound (POCUS) to MRI for the Diagnosis of Medial Compartment Knee Injuries.

BACKGROUND: Ultrasound has become an increasingly utilized tool for the imaging of the musculoskeletal system, especially for imaging the components of the knee. Even though MRI is touted as being the golden standard for identifying knee pathologies, the use of ultrasound has gained popularity in this field given its ability for rapid diagnosis. This study aims to investigate the efficacy of point-of-care ultrasound (POCUS) to diagnose injuries to the medial knee compartment when compared to magnetic resonance imaging (MRI). METHODS: This was a prospective, observational study conducted at an orthopedic outpatient clinic. Prospective patients with medial knee pain scheduled for an MRI of the knee were evaluated by POCUS prior to the MRI. Sonographic findings were then compared to MRI results to assess correlation. RESULTS: Nine patients were enrolled in the study. Median age was 53 years and eight were male (89%). POCUS demonstrated 100% sensitivity and 50% specificity for medial meniscus tear and 67% sensitivity and 83% specificity for medial collateral ligament (MCL) tear. CONCLUSION: Ultrasound may have a role as the initial rapid imaging modality in patients with suspected medial meniscus or MCL tears as it is highly sensitive, and it may serve as an effective screening tool for patients with both acute and chronic knee pain.

Emergency medicine (EM) can safely manage geriatric trauma patients sustaining ground level falls: Fostering EM autonomy while safely offloading a busy trauma service.

OBJECTIVE: Limited data exists regarding different specialties care of geriatric (>74 years-old) trauma patients (GTPs). We created a "Tier-III" designation for ground-level fall (GLF) GTPs to be managed by EM, with a trauma consult as needed. MATERIALS AND METHODS: A single-center comparison of PRE (1/1/2013-4/30/2016) versus POST (5/1/2016-11/30/2019) Tier-III GTP GLFs. The primary outcome was mortality. Secondary outcomes included admissions, trauma bay procedures and length of stay (LOS). RESULTS: 1,652 patients (314-PRE vs. 1,338-POST) were included. The admission rate was lower in the POST (56.9% vs. 88.9%, p < 0.001) cohort. There were no differences in LOS or trauma bay procedures between cohorts (p > 0.05). On multivariable analysis there was similar associated risk of mortality between groups (p = 0.68). CONCLUSION: The associated risk of mortality was similar between GLF GTP cohorts managed initially by EM and trauma surgeons, however the admission rate was lower in the POST group suggesting EM management may improve hospital bed utilization.

Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis.

The antitumor effect and mechanisms activated by murine IL-12 and IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK murine mammary carcinoma cells. In syngeneic A/J mice, SCK cells expressing mIL-12 or mIL-18 were less tumorigenic and formed tumors more slowly than control cells. Neither SCK.12 nor SCK.18 cells protected significantly against tumorigenesis by distant SCK cells. However, inoculation of the two cell types together synergistically protected 70% of mice from concurrently injected distant SCK cells and 30% of mice from SCK cells established 3 d earlier. Antibody neutralization studies revealed that the antitumor effects of secreted mIL-12 and mIL-18 required IFN-gamma. Interestingly, half the survivors of SCK.12 and/or SCK.18 cells developed protective immunity suggesting that anti-SCK immunity is unlikely to be responsible for protection. Instead, angiogenesis inhibition, assayed by Matrigel implants, appeared to be a property of both SCK.12 and SCK.18 cells and the two cell types together produced significantly greater systemic inhibition of angiogenesis. This suggests that inhibition of tumor angiogenesis is an important part of the systemic antitumor effect produced by mIL-12 and mIL-18.

Myogenic differentiation triggered by antisense acidic fibroblast growth factor RNA.

Acidic fibroblast growth factor (FGF) and related family members regulate differentiation in organisms as diverse as Xenopus laevis and mammals. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in controlling differentiation. A role for endogenous FGF is suggested by the previous finding that acidic and basic FGF abundance in cultured myocytes decreases during differentiation. In this study we inhibited the endogenous production of FGF in murine Sol 8 myoblasts by using antisense RNA and observed precocious myogenic differentiation. Exogenously supplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part through inhibition of myogenin expression. These results demonstrate a direct role for endogenously synthesized growth factors in regulating myogenesis and provide support for a general role for related proteins in mammalian development.

The total synthesis of K-252c (staurosporinone) via a sequential C-H functionalisation strategy.

A synthesis of the bioactive indolocarbazole alkaloid K-252c (staurosporinone) via a sequential C-H functionalisation strategy is reported. The route exploits direct functionalisation reactions around a simple arene core and comprises of two highly-selective copper-catalysed C-H arylations, a copper-catalysed C-H amination and a palladium-catalysed C-H carbonylation, which build up the structural complexity of the natural product framework.

A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women.

OBJECTIVES: We sought to determine prospectively whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) was a predictor of future cardiovascular risk in women. BACKGROUND: Inflammatory markers may help predict cardiovascular risk. Lp-PLA(2) levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men. METHODS: We conducted a prospective, nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease, non-fatal myocardial infarction, and stroke associated with baseline levels of Lp-PLA(2) over a mean follow-up of three years. RESULTS: In univariate analysis, mean levels of Lp-PLA(2) correlated strongly with low-density lipoprotein cholesterol (r = 0.51; p = 0.0001), were lower among women currently using hormone replacement therapy (mean 0.98 mg/l vs. 1.23 mg/l; p = 0.0001) and were significantly higher at baseline among cases (n = 123) than controls (n = 123) (mean 1.20 mg/l vs. 1.05 mg/l; p = 0.016). However, the predictive value of Lp-PLA(2) was markedly attenuated after adjustment for these and other cardiovascular risk factors. Specifically, the multivariate relative risks of future cardiovascular events for women in the lowest (referent) to highest quartiles of Lp-PLA(2) were 1.00, 0.75, 0.64 and 1.17, respectively (all p values non-significant). In contrast, the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein (another marker of low-grade inflammation) were 1.00, 1.78, 2.02 and 4.66, respectively (p-value for trend = 0.002). Inclusion of Lp-PLA(2) levels did not significantly attenuate this latter observation. CONCLUSIONS: In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovascular risk among unselected women.

Comparison of the novel quantitative ARMS assay and an enriched PCR-ASO assay for K-ras mutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses.

BACKGROUND: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation analysis on brush cytology is a valuable adjunct, but specificity is low. A quantitative test for K-ras mutations has been developed: the amplification refractory mutation system (ARMS). AIM: To assess the test characteristics and additional value of ARMS in diagnosing the cause of EBS. METHODS: Brush samples from endoscopic retrograde cholangiopancreatography were collected from 312 patients with EBS. K-ras mutation analysis was performed using ARMS-allele specific amplification was coupled with real time fluorescent detection of PCR products. Results were compared with conventional cytology and K-ras mutation analysis using allele specific oligonucleotide (ASO) hybridisation, and evaluated in view of the final diagnosis. RESULTS: The test characteristics of ARMS and ASO largely agreed. Sensitivity for detecting malignancy was 49% and 42%, specificity 93% and 88%, and positive predictive value (PPV) 96% and 91%, respectively. The sensitivity of ARMS and cytology combined was 71%, and PPV was 93%. The specificity of ARMS could be increased to 100% by setting limits for the false positives, but reduced sensitivity from 49% to 43%. CONCLUSIONS: ARMS can be considered supplementary to conventional cytology, and comparable to ASO in diagnosing malignant EBS. A specificity of 100% can be achieved with ARMS, which should be considered in the surveillance of patients at risk for pancreatic cancer.

Ultrasound in medical education: listening to the echoes of the past to shape a vision for the future.

PURPOSE: Ultrasound in medical education has seen a tremendous growth over the last 10-20 years but ultrasound technology has been around for hundreds of years and sound has an even longer scientific history. The development of using sound and ultrasound to understand our body and our surroundings has been a rich part of human history. From the development of materials to produce piezoelectric conductors, ultrasound has been used and improved in many industries and medical specialties. METHODS: As diagnostic medical ultrasound has improved its resolution and become more portable, various specialties from radiology, cardiology, obstetrics and more recently emergency, critical care and proceduralists have found the added benefits of using ultrasound to safely help patients. The past advancements in technology have established the scaffold for the possibilities of diagnostic ultrasound's use in the present and future. RESULTS: A few medical educators have integrated ultrasound into medical school while a wealth of content exists online for learning ultrasound. Twenty-first century learners prefer blended learning where material can be reviewed online and personalize the education on their own time frame. This material combined with hands-on experience and mentorship can be used to develop learners' aptitude in ultrasound. CONCLUSIONS: As educators embrace this ultrasound technology and integrate it throughout the medical education journey, collaboration across specialties will synthesize a clear path forward when needs and resources are paired with vision and a strategic plan.

Provision of prognostic information in immunocompromised patients by routine application of the polymerase chain reaction for cytomegalovirus.

A polymerase chain reaction (PCR) assay that amplifies a 149 base pair fragment of the cytomegalovirus glycoprotein B gene was used in the routine screening of 548 urine and 248 blood specimens from immunocompromised patients. The PCR results were compared with those obtained for the same specimens tested by the methods of conventional cell culture (CCC) and detection of CMV-specific immediate-early antigen fluorescent foci (DEAFF). For both urine and blood, PCR positivity correlated with a positive result in CCC (urine 93.2%; blood 86%). As expected for a more sensitive assay, PCR also identified CMV in samples that were negative by CCC and DEAFF such that there was no concordance between tests (Kappa test P > 0.05). The sensitivity, specificity, positive predictive value, and negative predictive values of PCR positivity in blood with respect to CMV disease were 0.8, 0.86, 0.62, and 0.94, respectively, with an associated relative risk of 5.84 (95% CI; 3.2-10.8). PCR detection of CMV in urine was more sensitive than either DEAFF or CCC (0.6 vs. 0.35 and 0.5, respectively) and had a high negative predictive value (0.89) but the positive predictive value was lower than either CCC or DEAFF (0.32 vs. 0.41 and 0.37, respectively) with respect to disease. Longitudinal data on patients with disease showed that CMV in blood was detected at a median of 5 days (range; -20 to +3 days) before disease onset whereas CMV was detected by CCC at a median of 13 days (range -4 to +20 days) after disease onset. In addition, the PCR assay was integrated into the battery of tests routinely performed on transplant patients in the diagnostic laboratory at this institution.

The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man.

Ten pigs, reared in an unmodified laboratory animal house environment, have been investigated to ascertain the incidence of diseases or disorders, including infection, neoplasia, or metabolic abnormalities, that might preclude the transplantation of major organs from the pig to man. Noninvasive studies were performed in the second month of life (study 1) and repeated after an interval that varied between 3 and 5 1/2 months (study 2). Necropsy was then performed as a means of assessing the accuracy of the 2 screening examinations. A total of 150 tests were performed on each pig. At both studies the feces contained cysts and/or trophozoites of several parasites, all of which were considered commensals. No other organisms potentially infective for man were identified either at study or at necropsy. Neither congenital anomalies nor malignant neoplasia was found at necropsy. However, in 2 pigs a vasculitis of uncertain etiology was present in the kidneys on microscopic examination, and in one of these the same condition affected the heart. This pathology was suspected neither from the screening examinations nor from the macroscopic appearance of these organs. Biopsy and microscopic examination would therefore appear to be essential before any organ is transplanted into a human.

Human cutaneous leishmaniasis acquired in Texas.

Four cases of autochthonous human cutaneous leishmaniasis have been identified in south-central Texas since 1980. The patients presented with chronic ulcerating papules on the face, earlobe, and lateral thigh. In two patients, the infections healed without treatment. In the other two patients, the lesions healed following treatment with intramuscular sodium stibogluconate or topical antimony potassium tartrate. Serologic testing of family members, using four different techniques, indicates that asymptomatic infections may occur. These are the first reported cases of cutaneous leishmaniasis acquired in Texas since 1974. Organisms isolated from patients in 1974 and 1980 belonged to the Leishmania mexicana complex when tested by the isoenzyme technique. Although no animal reservoir or insect vector has been identified, six species of sand flies belonging to the genus Lutzomyia do inhibit this part of Texas. Accumulated evidence strongly suggests that cutaneous leishmaniasis is endemic in south-central Texas.

Amplification refractory mutation system linear extension: a novel, gel-free, enzyme-linked immunoassay method for DNA genotyping.

A single synthesis cycle of the amplification refractory mutation system (ARMS) was applied to the analysis of K-ras alleles amplified by polymerase chain reaction and immobilized in streptavidin-coated microtiter plates. The ARMS cycle provided the specificity and molecular switch characteristics of a conventional ARMS assay. This allowed linear extension from an allele-specific primer and the incorporation of digoxigenin-labeled deoxyuridine monophosphate from digoxigenin-11-deoxyuridine triphosphate in the presence of the appropriate K-ras allele. Any digoxigenin-labeled deoxyuridine monophosphate substitution was then demonstrated by enzyme-linked immunoassay with colorimetric endpoint. This method is capable of detecting underrepresented acquired mutations, and this has been shown by the unambiguous detection of specific K-ras mutations in cell line DNA/normal human genomic DNA admixtures. The characterization of K-ras mutations in frozen colorectal tumor samples and histologic material is also described.

Eliminating PCR contamination: is UV irradiation the answer?

The sensitivity of the polymerase chain reaction (PCR) can mean that even very low levels of contamination with the target DNA will result in a positive signal. At present this aspect is a major limitation in the use of PCR as a routine diagnostic method. By exposing PCR reagents to UV light, contaminating DNA can be inactivated, thus providing an opportunity to eradicate false positive reactions. UV irradiation was applied to PCR systems used for the detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) and shown to be effective in eradicating both laboratory encountered contamination and plasmid DNA (below 100 pg) added to PCR systems prior to UV exposure. The sensitivity of a PCR system to amplify the long terminal repeat (LTR) sequence of HIV-1 was not affected by the irradiation procedure; however, the ultimate sensitivity of a PCR system for the amplification of an early gene promotor sequence of the CMV genome was reduced 1000-fold. UV irradiation did not affect the size of the PCR product as determined by strand separating polyacrylamide gel electrophoresis of a 32P-labelled amplimer. Thus, a simple pre-exposure to UV light would seem a worthwhile step to incorporate into PCR protocols provided that the effects on sensitivity have been determined empirically for each PCR system.

Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjects.

The reproducibility of tests widely utilized to assess anorectal sensorimotor functions is not well established. Our aims were to assess the intra-individual day-to-day reproducibility of these parameters in healthy subjects. Anal sphincter pressures were assessed by perfusion manometry on two separate days in 19 healthy subjects. Rectal pressure-volume (p-v) curves and sensory thresholds were assessed in 12/19 subjects by inflating a highly compliant polyethylene balloon from 0 to 32 mmHg in 4 mmHg steps. Subjects also rated intensity of perception by visual analogue scale (VAS) during phasic distentions 8, 16 and 24 mmHg above operating pressure, in randomized sequence. Resting and squeeze anal pressures and rectal compliance were highly reproducible (r(s) > or = 0.7) in the same subject on separate days. Pressure thresholds for urgency appeared less reproducible than thresholds for initial perception and the desire to defecate. VAS scores were highly reproducible only during the 24-mmHg distention. Thus, anal pressures and rectal compliance are highly reproducible within healthy subjects on separate days, while sensory thresholds are reproducible to a variable degree, dependent on the intensity of stimulation and the perception being assessed.

Cell survival and DNA double-strand break repair following X-ray or neutron irradiation of V79 cells.

We have investigated the effects of 250kVp X-rays and 2.3 MeV (mean energy) neutrons on the cell survival, DNA double-strand break (dsb) induction and repair (using the Kohn neutral elution technique) in V79 cells. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays (RBE = 3.55 at 10 per cent survival). However, the RBE for dsb induction, in a dose range of 10-50 Gy, was 1. On investigating the repair of DNA dsb induced by either X-ray or neutron irradiation, clear differences in the pattern of repair were found. Both a fast and a slow component of repair were seen in both cases; the former, however, was reduced following neutron irradiation and, since the amount of slow repair was similar in both cases, this resulted in proportionally more unrejoined breaks after neutrons. These experiments were carried out with elution buffer at pH 9.6; however, when similar experiments were performed at pH 7.2 the results obtained support our earlier findings. We suggest that these differences in DNA dsb repair reflect basic differences in the nature of the lesions induced by high- and low-LET ionizing radiations.

The rejoining of DNA double-strand breaks following irradiation with 238Pu alpha-particles: evidence for a fast component of repair as measured by neutral filter elution.

The induction and repair of DNA double-strand breaks (DSB) following exposure to 238Pu alpha-particles was examined in V79-379A cells. The technique of neutral filter elution was used in these investigations at both pH 9.6 and pH 7.2. The initial dsb yield was found to be similar to that seen after 250 kVp X-ray or 2.3 MeV neutron exposure. However, the pattern of dsb rejoining after alpha-particle irradiation did not follow that seen after X-rays or neutrons. A very fast initial component, complete within 2 min of incubation following irradiation, removed 70 per cent of the dsb seen after 40 Gy alpha-particles; very little slow rejoining was seen. This contrasts sharply with the dsb rejoining seen after X-ray or neutron exposure, and presumably reflects the differences in the nature of the dsb induced and the way they are repaired.

Failure to transmit Ehrlichia canis (Rickettsiales: Ehrlichieae) with Otobius megnini (Acari: Argasidae).

An ear tick, Otobius megnini (Dugès) recovered from a child who had serologic evidence of ehrlichiosis, was examined for Ehrlichia species microscopically and by inoculation into a susceptible dog; no evidence of infection was found in the tick. Experimental transmission of E. canis by laboratory-reared O. megnini was attempted; neither transstadial nor transovarial transmission occurred.

Experimental transmission of Ehrlichia chaffeensis (Rickettsiales: Ehrlichieae) among white-tailed deer by Amblyomma americanum (Acari: Ixodidae).

Ehrlichia chaffeensis Anderson, Dawson & Wilson, causative agent of human (predominantly monocytic) ehrlichiosis, was successfully transmitted experimentally by Amblyomma americanum (L.) to white-tailed deer, Odocoileus virginianus (Zimmerman). Deer were needle-exposed intravenously to E. chaffeensis in tissue-culture canine macrophage (DH82) cells, and 11 d later were exposed to laboratory-reared A. americanum larvae, nymphs, and adults for acquisition feeding. Three months after this feeding, naive deer and dogs were exposed to recently molted nymphs and adults. Attempted reisolation of the pathogen by way of tissue culture was successful from one needle-exposed deer but not from the tick-exposed deer or dogs. Based on serologic evidence and polymerase chain reaction data, both nymphal and adult ticks transmitted E. chaffeensis to naive deer but not to dogs.

Evidence to support the existence of efficient DNA double-strand break rejoining in a radiosensitive mutant of V79-4 following irradiation with 250 kVp X-rays or neutrons.

The repair of ionising-radiation-induced DNA double-strand break type damage was measured by Kohn neutral elution in an X-ray-sensitive mutant of V79-4, irs1. This was done in order to investigate further the likelihood that irs1 carries a defect which leads to error-prone repair of DNA damage, and not simply a reduced ability to rejoin DNA double-strand breaks. The mutant displayed an equal increase in sensitivity to the lethal effects of neutrons, as compared to X-rays. Both irs1 and V79-4 showed an increased sensitivity to the killing effects of neutrons of around 2 at 10% survival. irs1 also showed an exponential survival after either X-rays or neutrons. The induction of DNA double-strand breaks was measured in both cell lines over a dose range of 10-40 Gy using Kohn neutral filter elution. Induction of breaks by X-rays in irs1 seemed to increase slightly with dose, relative to induction in V79-4, so that at 40 Gy 1.5 times more DNA double-strand breaks were measured in irs1 cells than in V79-4. Neutron irradiation resulted in a more similar level of induction in either strain after 10-40 Gy. This difference in induction of damage may be due to a different cell-cycle composition in either cell line. The rejoining of X-ray induced double-strand breaks showed a very similar pattern (on a percentage rejoined basis) in both cell lines, although from the induction data at 40 Gy, the dose at which rejoining was measured, fewer breaks were rejoined in V79-4 but also fewer breaks remained unsealed. Neutron-induced breaks, however, were rejoined more efficiently in irs1 again on a percentage basis, but also in absolute terms since similar induction was seen after 40 Gy. This data, together with the differences seen in the rejoining of X-ray compared to neutron induced breaks, may indirectly support the proposal that irs1 is a misrepair mutant.

Outcome in cardiac arrest patients found to have cardiac standstill on the bedside emergency department echocardiogram.

UNLABELLED: Patients presenting in cardiac arrest frequently have poor outcomes despite heroic resuscitative measures in the field. Many emergency medical systems have protocols in place to stop resuscitative measures in the field; however, further predictors need to be developed for cardiac arrest patients brought to the emergency department (ED). OBJECTIVE: To examine the predictive value of cardiac standstill visualized on bedside ED echocardiograms during the initial presentations of patients receiving cardiopulmonary resuscitation (CPR). METHODS: The study took place in a large urban community hospital with an emergency medicine residency program and a high volume of cardiac arrest patients. As part of routine care, all patients arriving with CPR in progress were subject to immediate and brief subxiphoid or parasternal cardiac ultrasound examination. This was followed by brief repeat ultrasound examination during the resuscitation when pulses were checked. A 2.5-MHz phased-array probe was used for imaging. Investigators filled out standardized data sheets. Examinations were taped for review. Statistical analysis included descriptive statistics, positive and negative predictive values, and likelihood ratios. RESULTS: One hundred sixty-nine patients were enrolled in the study. One hundred thirty-six patients had cardiac standstill on the initial echocardiogram. Of these, 71 patients had an identifiable rhythm on monitor. No patient with sonographically identified cardiac standstill survived to leave the ED regardless of his or her initial electrical rhythm. Cardiac standstill on echocardiogram resulted in a positive predictive value of 100% for death in the ED, with a negative predictive value of 58%. CONCLUSIONS: Patients presenting with cardiac standstill on bedside echocardiogram do not survive to leave the ED regardless of their electrical rhythms. This finding was uniform regardless of downtime. Although larger studies are needed, this may be an additional marker for cessation of resuscitative efforts.