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Investigating the utility of saliva immunoglobulins for the detection of myeloma and using myeloma proteins to clarify partition between oral and systemic immunity.
No full textOBJECTIVES
Myeloma is characterised by the presence of monoclonal immunoglobulin (M-protein) and the free light chain (FLC) in blood. We investigated whether these M-proteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non-invasive screening and monitoring of haematological malignancies.
METHODS
A total of 57 patients with monoclonal gammopathy and 26 age-matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification.
RESULTS
Myeloma patients had IgG or IgA M-protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M-proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA.
CONCLUSIONS
Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity
Retroperitoneal and Mesenteric Liposarcomas.
No full textRetroperitoneal liposarcomas are a rare entity and are comprised mostly of the well-differentiated and dedifferentiated subtypes. Eight-year survival ranges from 30% to 80% depending on histologic subtype and grade. Surgery is the cornerstone of treatment and compartment resection is the current standard. Mesenteric liposarcomas are extremely rare and comprise more high-grade lesions, with poorer prognosis of 50% 5-year overall survival. They are managed with a similar aggressive surgical approach. This review presents the current management of retroperitoneal and mesenteric liposarcomas
Decreased renal function is associated with incident dementia: An IMRD-THIN retrospective cohort study in the UK.
No full textINTRODUCTION
Decreased renal function is a potential risk factor for dementia.
METHODS
This retrospective cohort study of 2.8 million adults aged ≥50 years used the IMRD-THIN database, representative of UK primary care, from January 1, 1995 to February 24, 2020. The associations between estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) with incident all-cause dementia were analyzed using Cox regression.
RESULTS
In the eGFR cohort (n = 2,797,384), worsening renal dysfunction was associated with increased hazard of all-cause dementia, with greatest hazard at eGFR 15-30 ml/min/1.73min (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19-1.33). In the ACR cohort (n = 641,912), the hazard of dementia increased from ACR 3-30 mg/mmol (HR 1.13, 95% CI 1.10-1.15) to ACR > 30 mg/mmol (HR 1.25, 95% CI 1.18-1.33).
DISCUSSION
Worsening eGFR and albuminuria have graded associations with the risk of dementia, which may have significant implications for the care of patients with kidney disease
Outcome of Simple Decompression of Primary Cubital Tunnel Syndrome Based on Patient-Reported Outcome Measurements.
No full textPURPOSE
To evaluate the patient-reported outcome measures of patients with primary cubital tunnel syndrome and to assess whether they are affected by preoperative symptom severity.
METHODS
Patients who underwent simple decompression for primary cubital tunnel syndrome were selected from a prospectively maintained database. Outcome measurements consisted of the Boston Carpal Tunnel Questionnaire at intake and at 3 and 6 months after surgery. Also, 6 months after surgery, the patients received a question about their satisfaction with the treatment result. To determine a possible influence of preoperative symptom severity on postoperative outcomes, the sample was divided into quartiles based on symptom severity at intake.
RESULTS
One hundred and forty-five patients were included in the final analysis. On average, all patients improved on the Boston Carpal Tunnel Questionnaire. The subgroup of patients with the mildest symptoms at intake did not improve significantly on symptom severity but did improve significantly on their functional status. In addition, the patients with the most severe symptoms at intake did improve on both aspects. Moreover, no difference in satisfaction with treatment result between the severity of symptoms at intake was found.
CONCLUSIONS
The patients with the mildest symptoms at intake may not improve on symptom severity, but they do improve on functional status after simple decompression for cubital tunnel syndrome. In addition, patients with the most severe symptoms at intake do improve on both symptom severity and functional status. Moreover, all patients reported to be equally satisfied with the treatment result, which suggests that satisfaction is not dependent on the symptom severity at intake. Even those patients with both the mildest symptoms before surgery and the least improvement still seem to benefit from simple decompression.
TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic IV
Single stage versus two-stage orthoplastic management of bone infection.
No full textINTRODUCTION
Bone infection cases with major soft tissue loss have conventionally been treated with a staged orthoplastic approach, addressing the infection first followed by definitive management to achieve bony stability and soft tissue cover. In the last few decades, specialist centers have advocated for single stage bony stabilization with soft tissue coverage. We aimed to investigate the outcomes of patients that underwent a single stage versus a two-stage orthoplastic intervention.
METHODS
Using an existing 2009-2019 database from a single major trauma centre, we identified all adults with a diagnosis of fracture related infection (FRI) or osteomyelitis (OM). The primary outcome was resolution of infection. Secondary outcomes included time to bony union, amputation, failure of orthopaedic fixation, mortality, and return to theatre.
RESULTS
A total of 96 patients were included. 71 patients (74%) underwent a single stage procedure; out of which 61 were FRI. 25 patients (26%) underwent a two-stage procedure; out of which 24 were FRI. The average follow up for the single stage and two-stage cohorts was 32.1 and 30.3 months, respectively. Resolution of infection without the need for an amputation was achieved in 67 (94.4%) patients in the single stage cohort and in 23 (92%) patients in the two-stage cohort. When compared to the two-stage group, the single stage cohort had less recurrence of infection (9.9% versus 12%, p = 0.72), lower rates of amputation (8.5% versus 12%, p = 0.69), lower rates of failure of orthopaedic fixation (11.1% versus 13%, p = 0.82), but higher average time to bony union (15.25 months versus 12.35, p = 0.42). The differences were not statistically significant. A total of 37 patients (52.1%) had an unplanned return to theatre in the single stage compared to 12 (48%) in the two-stage cohort. In subgroup analysis of FRI cases, open fractures had a longer time to bony union when compared to closed fractures (19.7 versus 11.6 months, p = 0.01). No mortality was observed in both cohorts.
CONCLUSIONS
The single stage orthoplastic approach to bone infection is effective if planned carefully with clinical outcomes comparable to the two-stage approach. Further research should examine factors associated with unplanned return to theatre and any variation in treatment of bone infection across regions
Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial.
No full textBackground
It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke.
Methods
We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression.
Findings
Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01-2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24-3.79). Other outcomes (disability - Barthel Index, quality of life - EQ-visual analogue scale, cognition - telephone mini-mental state examination, and mood - Zung depression scale) were also worse with continuing treatment.
Interpretation
In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse functional outcome, disability, cognition, mood, quality of life and increased death. Future studies assessing continuing or stopping prior antihypertensives in the context of thrombectomy are awaited
The paradigm shift from NAFLD to MAFLD: A global primary care viewpoint.
No full textIn 2020, a group of international experts reached a consensus to comprehensively revisit the current definition of fatty liver disease. In clinical settings, most of the patients with fatty liver disease are first identified and subsequently followed up in the community by primary care practitioners (PCPs). Therefore, it is crucial to understand PCPs perspectives regarding the proposed redefinition of fatty liver disease as well as the implications on primary care of patients. Thus, the aim of this paper is for an international team of experts in primary care to provide perspective regarding the proposed redefinition of metabolic-dysfunction associated fatty liver disease (MAFLD). Currently, numerous systemic barriers exist for PCPs who are managing fatty liver disease. These include the diagnosis and screening, efficient referral pathway, restrictive policies, disease awareness and continuum of care. The revolutionary simplification in diagnosis and evaluation that the MAFLD definition is providing, we believe can help to overcome some of these barriers and may facilitate the implementation of effective fatty liver disease management, prevent overdiagnosis and overtreatment in secondary and tertiary care but also reduce underdiagnosis in primary care by PCPs by promoting widespread active case findings of MAFLD and reaching to a balance on behalf of public health
Subcutaneous Gammanorm® by pump or rapid push infusion: Impact of the device on quality of life in adult patients with primary immunodeficiencies.
No full textMany patients with immunodeficiencies require lifelong immunoglobulin replacement therapy (IgRT). In a multicenter, randomized, open-label, crossover, non-inferiority 3-month-trial, we compared the impact of the subcutaneous immunoglobulin Gammanorm® administered via pump or syringe (rapid push). Primary endpoint was the life quality index (LQI), secondary endpoints were QoL (SF36v2), satisfaction (TSQM-11), disease and treatment burden (PRISM), incidence of infections and adverse events (AE), treatment costs, and IgG levels. 28/30 patients completed the study. Most of the endpoints were comparable. Drug administrations with rapid push were more frequent, but reduced total time expenditure and some costs. Of the TSQM-11/LQI/SF36 components only "treatment interference with daily activities" was superior with pump and two QoL domains with rapid push. Both delivery devices showed favorable safety. Rapid push was preferred by 34.5% of patients. It proved to be an efficacious and cost-effective alternative to pumps adding to patient choice and increasing flexibility during long-term IgRT
Microscopic changes in the spinal extensor musculature in people with chronic spinal pain: a systematic review.
No full textBACKGROUND CONTEXT
Chronic spinal pain is one the most common musculoskeletal disorders. Previous studies have observed microscopic structural changes in the spinal extensor muscles in people with chronic spinal pain. This systematic review synthesizes and analyses all the existing evidence of muscle microscopic changes in people with chronic spinal pain.
PURPOSE
To assess the microscopy of spinal extensor muscles including the fiber type composition, the area occupied by fiber types, fiber size/cross sectional area (CSA) and narrow diameter (ND) in people with and without chronic spinal pain. Further, to compare these outcome measures across different regions of the spine in people with chronic neck, thoracic and low back pain.
STUDY DESIGN
Systematic review with meta-analysis METHODS: MEDLINE (Ovid Interface), Embase, PubMed, CINAHL Plus and Web of Science were searched from inception to October 2020. Key journals, conference proceedings, grey literature and hand searching of reference lists from eligible studies were also searched. Two independent reviewers were involved in the selection process. Only studies examining the muscle microscopy of the spinal extensor muscles (erector spinae (ES) and/or multifidus (MF)) between people with and without chronic spinal pain were selected. The risk of bias from the studies was assessed using modified Newcastle Ottawa Scale and the level of evidence was established using the GRADE approach. Data were synthesized based on homogeneity on the methodology and outcome measures of the studies for ES and MF muscles and only four studies were eligible for analysis.
RESULTS
All the five studies included were related to chronic low back pain (CLBP). Meta-analysis (inverse variance method for random effect to calculate mean difference and 95% CI) was performed for the ES fiber type composition by numbers for both type I and type II fibers (I=43% and 0% respectively indicating homogeneity of studies) and showed no difference between the people with and without CLBP with an overall effect estimate Z= 1.49 (p=0.14) and Z=1.06 (p=0.29) respectively. Meta-analysis was performed for ES fiber CSA for both type I and type II fibers (I=0 for both) and showed no difference between people with and without CLBP with an overall effect estimate Z= 0.08 (p=0.43) and Z=0.75 (p=0.45) respectively. Analysis was not performed for ES area occupied by fiber types and ND due to heterogeneity of studies and lack of evidence respectively. Similarly, meta-analysis was not performed for MF fiber type composition by numbers due to heterogeneity of studies. MF analysis for area occupied by fiber type, fiber CSA and ND did not yield sufficient evidence.
CONCLUSIONS
For the ES muscle, there was no difference in fiber type composition and fiber CSA between people with and without CLBP and no conclusions could be drawn for ND for the ES. For the MF, no conclusions could be drawn for any of the muscle microscopy outcome measures. Overall, the quality of evidence is very low and there is very low evidence that there are no differences in microscopic muscle features between people with and without CLBP