OBJECTIVETo investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disordersspinal bulbar muscular atrophy (SBMA) ...and amyotrophic lateral sclerosis (ALS).
METHODSWe applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA.
RESULTSQuantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thighp < 0.001; calfp = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA.
CONCLUSIONSOur findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.
Howard presents information on the ongoing attempt of the WHO to eradicate poliomyelitis, which is still endemic in some countries. The eradication policy involves mass immunization, but concerns ...about vaccine-associated polio have led to increased use of inactivated polio vaccine in immunization strategies.
Background The accurate clinical assessment of melanocytic neoplasms is a challenge for clinicians. Currently, obtaining a biopsy specimen and conducting a histologic examination is the standard of ...care. The incidence of melanoma in white populations is high, resulting in a large number of biopsy specimens. Objective The objective of this study is to develop a noninvasive genomic method using mRNA to classify pigmented skin lesions as either benign or malignant. Methods An adhesive patch method was used to obtain cells from the surface of melanocytic lesions. mRNA was extracted and a genomic signature was formulated in a training set of benign and malignant melanocytic neoplasms and subsequently tested in a validation set. Results A 2-gene signature assessing the expression levels of CMIP and LINC00518 was able to differentiate melanomas from nevi in an independent validation set of 42 melanomas and 22 nevi with a sensitivity of 97.6% and specificity of 72.7%. Limitations Larger and more diverse sets of melanomas and nevi are needed for additional validation of the molecular expression profiling in various subsets of melanocytic neoplasms. Conclusion Our data suggest that mRNA molecular signatures can serve as a highly useful noninvasive method of differentiating melanoma from nevi and decrease the number of unnecessary biopsies.
Objective To investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS). ...Methods A cross-sectional study involving 136 clinically heterogeneous patients with ALS and 104 healthy and neurological controls was extended to include a prospective analysis of 74 of these ALS cases, with samplings at approximately 3-month intervals in a follow-up period of up to 3 years. We analysed the correlation between longitudinal NfH-phosphoform levels and disease progression. Temporal patterns of NfH changes were evaluated using multilevel linear regression. Results Baseline plasma NfH levels were higher than controls only in patients with ALS with short disease duration to baseline sampling. Compared with controls, fast-progressing patients with ALS, particularly those with a short diagnostic latency and disease duration, had higher plasma NfH levels at an early stage and lower levels closer to end-stage disease. Lower NfH levels between visits were associated with rapid functional deterioration. We also detected antibodies against NfH, NfH aggregates and NfH cleavage products. Conclusions Disease progression in ALS involves defined trajectories of plasma NfH levels, reflecting speed of neurological decline and survival. Intervisit plasma NfH changes are also indicative of disease progression. This study confirms that longitudinal measurements of NfH plasma levels are more informative than cross-sectional studies, where the time of sampling may represent a bias in the interpretation of the results. Autoantibodies against NfH aggregates and NfH cleavage products may explain the variable expression of plasma NfH with disease progression. Trail registration number NIHRID6160.
IMPORTANCE: The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and ...leukemia in BCG-vaccinated populations. OBJECTIVE: To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. INTERVENTIONS: Single intradermal injection of either BCG vaccine or saline placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. RESULTS: A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. CONCLUSIONS AND RELEVANCE: Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.
OBJECTIVE:To report the occurrence of an unusual neurologic disorder requiring admission to the intensive care unit.
DESIGN:Analysis of an observational cohort study of 31 patients with encephalitis ...admitted over a 4-yr period.
SETTING:Neurologic intensive care unit in a tertiary referral center.
PATIENTS:We identified N-methyl-D-aspartate receptor antibodies in six patients (two male and four female). All seropositive patients presented with a psychiatric prodrome, before developing seizures and obtundation requiring intensive care unit admission. They exhibited limb and truncal stereotypies and orofacial dyskinesias upon weaning sedation. Two patients had ovarian tumors.
INTERVENTIONS:Patients were treated with sedation, antiepileptic drugs, and immunotherapy. One patient received a magnesium infusion and ketamine.
MEASUREMENTS AND MAIN RESULTS:N-methyl-D-aspartate receptor antibodies were identified in serum samples by an immunofluorescent cell-based assay. Three patients made a good but slow recovery; two were left with severe neurologic deficits; and one died after return to the referring hospital. These patients accounted for approximately 20% of all patients admitted with encephalitis to this referral center.
CONCLUSIONS:N-methyl-D-aspartate receptor antibodies should be tested in patients with hyperkinetic encephalitis and neuropsychiatric prodrome admitted to the intensive care unit. The disorder is probably not rare and is potentially treatable.
TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in ...subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-type. Next-generation sequencing analysis was performed on the cell lines and select cases, in which there was discordance in p53 expression pattern interpretation. Next-generation sequencing analysis demonstrated low-frequency variant mutations in some cases in which there was reviewer discordance. This study suggests the addition of a p53 cell line expression pattern control panel could potentially increase p53 interpretation accuracy for ovarian cancer subtypes. We developed a cell line-based p53 control panel that has the potential to increase individual interrater reliability for p53 immunohistochemical expression pattern determination, support immunohistochemical optimization, and direct submission of difficult to interpret p53 staining cases to next-generation sequencing.
Background
Postoperative urinary retention (POUR) is a common entity following surgery, particularly after laparoscopic inguinal hernia repair. Here the intent is to investigate the incidence of POUR ...in all comers at a single institution following laparoscopic inguinal hernia repair.
Methods
A retrospective chart review of all patients who underwent laparoscopic hernia repair at our institution from January 2010 through December 2013 was performed. POUR was defined as the inability to spontaneously urinate following surgery, requiring straight catheterization or placement of a Foley catheter. Perioperative data including narcotic use, operative time, type of mesh, and intraoperative fluid use were also recorded for each patient.
Results
A total of 346 patients underwent laparoscopic inguinal hernia repair in the specified time period, 340 patients were included in this study. The incidence of POUR after laparoscopic inguinal hernia repair at our institution was 8.2 % (
n
= 28) with the most common presentation of POUR being failure to void (
n
= 23). Postoperative narcotic use of 6.5 mg or greater of morphine or morphine equivalent was associated with higher risk of POUR via ROC analysis (OR 2.5, 95 % CI 1.2–5.6,
p
= 0.025). In univariate analysis, age greater than 50 years was also a risk factor for developing POUR (OR 2.8, 95 % CI 1.2–6.4,
p
= 0.02). Factors not found to be significant included intraoperative IV fluids, history of BPH, unilateral versus bilateral repair, and preoperative void time in relation to surgery start.
Conclusions
Minimizing postoperative narcotic medications may reduce the risk of developing POUR after laparoscopic inguinal hernia repairs. If possible surgeons should consider non-steroidal anti-inflammatory drugs, acetaminophen, or regional anesthetic blocks to minimize postoperative narcotic requirements.
The management of ischaemic stroke Howard, Robin S
Anaesthesia and intensive care medicine,
12/2016, Letnik:
17, Številka:
12
Journal Article
Recenzirano
Abstract Ischaemic stroke often leads devastating long-term neurological sequelae. There are five interventions that improve the outcome after a stroke: management within a stroke unit, intravenous ...thrombolysis, mechanical clot retrieval, aspirin within 48 hours, and decompressive hemicraniectomy for malignant middle cerebral artery (MCA) stroke. The benefits of intravenous thrombolysis up to 4.5 hours are now well established, but the recent development of clot retrieval has radically altered the acute management of stroke. The development of late complications remains the most important factor determining outcome and it is essential to ensure homoeostasis is maintained during the acute phase of care to reduce the risk of late deterioration.
OBJECTIVE:To examine whether blast exposure alone and blast-associated concussion result in similar neurologic and mental health symptoms.
METHODS:A 14-item questionnaire was administered to male US ...Marines on their return from deployment in Iraq and/or Afghanistan.
RESULTS:A total of 2,612 Marines (median age 22 years) completed the survey. Of those, 2,320 (88.9%) reported exposure to ≥1 blast during their current and/or prior deployments. In addition, 1,022 (39.1%) reported ≥1 concussion during the current deployment, and 731 (28.0%) had experienced at least 1 prior lifetime concussion. Marines were more likely to have sustained a concussion during the current deployment if they had a history of 1 (odds ratio OR 1.5, 95% confidence interval CI 1.2–2.0) or ≥1 (OR 2.3, 95% CI 1.7–3.0) prior concussion. The most common symptoms were trouble sleeping (38.4%), irritability (37.9%), tinnitus (33.8%), and headaches (33.3%). Compared to those experiencing blast exposure without injury, Marines either experiencing a concussion during the current deployment or being moved or injured by a blast had an increased risk of postinjury symptoms.
CONCLUSIONS:There appears to be a continuum of increasing total symptoms from no exposure to blast exposure plus both current deployment concussion and past concussion. Concussion had a greater influence than blast exposure alone on the presence of postdeployment symptoms. A high blast injury score can be used to triage those exposed to explosive blasts for evaluation.
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