Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of ...patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.
Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a ...weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
Understanding the mechanisms and abnormalities of respiratory function in neuromuscular disease is critical to supporting the patient and maintaining ventilation in the face of acute or chronic ...progressive impairment.
Retrospective clinical studies reviewing the care of patients with Guillain-Barré syndrome and myasthenia have shown a disturbingly high mortality following step-down from intensive care. This implies high dependency and rehabilitation management is failing despite evidence that delayed improvement can occur with long-term care. A variety of mechanisms of phrenic nerve impairment have been recognized with newer investigation techniques, including EMG and ultrasound. Specific treatment for progressive neuromuscular and muscle disease has been increasingly possible particularly for the treatment of myasthenia, metabolic myopathies, and Duchenne muscular dystrophy. For those conditions without specific treatment, it has been increasingly possible to support ventilation in the domiciliary setting with newer techniques of noninvasive ventilation and better airway clearance. There remained several areas of vigorous debates, including the role for tracheostomy care and the place of respiratory muscle training and phrenic nerve/diaphragm pacing.
Recent studies and systematic reviews have defined criteria for anticipating, recognizing, and managing ventilatory failure because of acute neuromuscular disease. The care of patients requiring long-term noninvasive ventilatory support for chronic disorders has also evolved. This has resulted in significantly improved survival for patients requiring domiciliary ventilatory support.
Dysphagia is a well-recognised, debilitating symptom of Motor Neurone Disease (MND) resulting from progressive bulbar dysfunction. Enteral feeding via gastrostomy is recommended for dysphagia and has ...been shown to improve quality of life.We retrospectively audited the clinical notes of patients at our MND specialist care centre who had been recommended for gastrostomy. Data was extracted over a 12-month period and included patient demographics, procedural outcomes and case-by-case analysis.46 gastrostomies were performed. 88% of patients were admitted electively, the remainder acute admis- sions. 52% of patients were limb-onset and 46% were bulbar on-set. There was no statistical difference in procedural success rate.65% of procedures performed were percutaneous endoscopic gastrostomies (PEG), 13% of procedures were radiologically inserted gastrostomies (RIG) and 33% were NIV supported RIG. Procedural success rates varied between methods. Procedural failures included intraoperative desaturations (33%) and pro- cedural difficulty (66%). Post-operative complications occurred in 33% of procedures, the most common being post-operative pain.We created a gastrostomy «checklist» to streamline the patient pathway. We aim to improve patient experience by reducing length of stay and minimising common post-operative complications, with the overall benefit of improving gastrostomy waiting times and access to services.A re-audit will follow after checklist implementation.
The clinical importance of extrathyroidal extension (ETE) on outcome of papillary thyroid cancer (PTC), particularly with respect to disease extending to the surgical margin is not well established. ...This study assessed the importance of surgical margin and extrathyroidal invasion relative to local control of disease and oncologic outcome.
A retrospective analysis of a prospective institutional endocrine database was conducted on 276 patients with PTC treated between 1955 and 2004 to determine the impact of margin-negative resection (n=199, 72%), disease up to within 1 mm of surgical margin (n=19, 7%), microscopic (n=39, 14%), and gross (n=19, 7%) ETE. Data were compared with Fisher's exact test or analysis of variance (ANOVA).
Median follow-up was 3.1-6.8 years per study group (disease-free survival, range 1-37 years). The proportion of those with age >45 years, prior radiation exposure, distant metastasis at presentation, and those undergoing total thyroidectomy was not significantly different between groups. Tumor size and multifocality correlated with extent of local disease, which in turn was significantly associated with regional nodal disease at time of primary operation as well as prevalence of persistence of disease after multimodality therapy. Extent of local disease correlated significantly with subsequent clinical recurrence after a disease-free period (p=0.006); however, recurrence rates were not significantly different between negative and close (≤1 mm) margin resection.
Oncological outcome correlates with the extent of extrathyroidal invasion. Outcome is worse in patients with gross extrathyroidal disease extension than in those with microscopic local invasion apparent on histopathological assessment. However, the risk of clinical recurrence appears similar between patients undergoing margin-negative and "close margin" resection.
Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including ...possible subclinical injury, has not been prospectively defined.
The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization.
New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).
New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group.
Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.
Summary Background Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a ...particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. Methods We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995–2012), the Netherlands (2006–12), Italy (1995–2004), Scotland (1989–98), and England (2002–09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. Findings We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r2 =0·95, Ireland r2 =0·99, Italy r2 =0·95, the Netherlands r2 =0·99, and Scotland r2 =0·97; overall r2 =0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5–5·0), with similar estimates for men (4·6, 4·3–4·9) and women (5·0, 4·5–5·5). Interpretation A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. Funding UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).
The neurological and psychological manifestations of trauma, confinement, and terror became apparent throughout Europe as soldiers were evacuated from the trenches of the Western Front. The response ...in the UK evolved as a result of the experience of medical staff embedded with the troops in base hospitals and the philosophy of those treating returned soldiers in specialist establishment. There were widely disparate approaches to the management encompassing simple supportive care, a psychanalytic approach and radical electric shock therapy. The latter was partially driven by the Queen Square experience in the UK but was also concurrently widely pursued throughout Europe. With experience, care was increasingly undertaken close to the front lines using a philosophy of immediacy and expectation of recovery. Post-war analysis was startlingly unsympathetic, yet the experiences and management of shell shock have guided psychiatric and medical understanding of functional illness and post-traumatic stress over the subsequent century. In this historical review, we have sought to present features of the UK response to the neurological manifestations of trauma, the way in which these changed as the war proceeded and the political and medical response in the aftermath of war.
Context:
Decisions regarding initial therapy and subsequent surveillance in patients with differentiated thyroid cancer (DTC) depend upon an accurate assessment of the risk of persistent or recurrent ...disease.
Objective:
The objective of this study was to examine the predictive value of a single measurement of serum thyroglobulin (Tg) just before radioiodine remnant ablation (preablation Tg) on subsequent disease-free status.
Data Sources:
Sources included MEDLINE and BIOSYS databases between January 1996 and June 2011 as well as data from the author's tertiary-care medical center.
Study Selection:
Included studies reported preablation Tg values and the outcome of initial therapy at surveillance testing or during the course of long-term follow-up.
Data Extraction:
Two investigators independently extracted data and rated study quality using the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews-2 (QUADAS-2) tool.
Data Synthesis:
Fifteen studies involving 3947 patients with DTC were included. Seventy percent of patients had preablation Tg values lower than the threshold value being examined. The negative predictive value (NPV) of a preablation Tg below threshold was 94.2 (95% confidence interval = 92.8–95.3) for an absence of biochemical or structural evidence of disease at initial surveillance or subsequent follow-up. The summary receiver operator characteristic curve based on a bivariate mixed-effects binomial regression model showed a clustering of studies using a preablation Tg below 10 ng/ml near the summary point of optimal test sensitivity and specificity.
Conclusion:
Preablation Tg testing is a readily available and inexpensive tool with a high NPV for future disease-free status. A low preablation Tg should be considered a favorable risk factor in patients with DTC. Further study is required to determine whether a low preablation Tg may be used to select patients for whom radioiodine remnant ablation can be avoided.
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