Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up

Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios=1.9–3.4); deep venous thrombosis and pulmonary embolism (rate ratios=2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios =1.3–1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios =1.8–6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios =1.6–3.0); pulmonary embolism and coronary artery disease (rate ratios =1.4–4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios =1.3–4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.     

Smoldering multiple myeloma: present position and potential promises

Since smoldering multiple myeloma (SMM) was first described over three decades ago based on a case series of six patients, its definition and our understanding of the entity have evolved considerably. The risk of progression to symptomatic myeloma (MM) varies greatly among individuals diagnosed with myeloma precursor disease. Epidemiologic, molecular, flow cytometric and radiological techniques have demonstrated that this transformation to MM from precursor states is not sudden but rather a continuous overlapping series of events with evidence of end‐organ damage that could manifest in the earliest stages of disease. Contemporary antimyeloma therapies can yield rapid, deep, and durable responses with manageable toxicities, and molecular‐cell‐based measures are now available to rule out minimal residual disease. With this information, clinical studies with correlative measures can now be developed to test the fundamental hypothesis that intervention in early myeloma may provide a measurable clinical benefit to patients by either delaying progression or eradicating plasma cell clones.     

Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes

Metabolic Brain Disease - Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with...     

The acetabulum in Perthes’ disease: Inter-observer agreement and reliability of radiographic measurements

Background and purpose

Perthes’ disease leads to radiographic changes in both the femoral head and the acetabulum. We investigated the inter-observer agreement and reliability of 4 radiographic measurements assessing the acetabular changes.

Patients and methods

We included 123 children with unilateral involvement, femoral head necrosis of more than 50%, and age at diagnosis of 6 years or older. Radiographs were taken at onset, and 1 year and 5 years after diagnosis. Sharp’s angle, acetabular depth-width ratio (ADR), lateral acetabular inclination (LAI), and acetabular retroversion (ischial spine sign, ISS) were measured by 3 observers. Before measuring, 2 of the observers had a consensus meeting.

Results

We found good agreement and moderate to excellent reliability for Sharp’s angle for all observers (intra-class correlation coefficient (ICC) > 0.80 with consensus, ICC = 0.46–0.57 without consensus). There was good agreement and substantial reliability for ADR between the observers who had had a consensus meeting (ICC = 0.62–0.89). Low levels of agreement and poor reliability were found for observers who had not had a consensus meeting. LAI showed fair agreement throughout the course of the disease (kappa = 0.28–0.52). The agreement between observations for ISS ranged from fair to good (kappa = 0.20–0.76).

Interpretation

Sharp’s angle showed the highest reliability and agreement throughout the course of the disease. ADR was only reliable and showed good agreement between the observers when landmarks were clarified before measuring the radiographs. Thus, we recommend both parameters in clinical practice, provided a consensus is established for ADR. The observations for LAI had only fair agreement and ISS showed inconclusive agreement in our study. Thus, LAI and ISS can hardly be recommended in clinical practice.Perthes’ disease leads to typical radiographic changes of the femoral head. Several authors have described simultaneous changes of the acetabular anatomy, such as hypertrophy, bicompartmental development, retroversion, and dysplastic changes (Yngve and Roberts 1985, Joseph 1989, Ezoe et al. 2006).Most measurements describing the radiographic changes of the acetabulum on anteroposterior (AP) pelvic radiographs have been validated in children with hip dysplasia. As the hip pathology and the morphological changes in Perthes’ disease are different from those in hip dysplasia, we wanted to assess inter-observer reliability and agreement of 4 commonly used acetabular measurements at the different stages of skeletal maturity in Perthes’ disease.     

Increasing circulating levels of Tenascin C in response to the Wingate anaerobic test

Aim

Tenascin C (TNC) is a large extracellular matrix glycoprotein. It is involved in development and upregulated both during tissue repair and in several pathological conditions, including cardiovascular disease. Extracellular matrix proteins play a role in promoting exercise responses, leading to adaptation, regeneration, and repair. The main goal of this study was to investigate whether a short anaerobic effort leads to increased levels of TNC in serum.

Methods

Thirty-nine healthy men performed a Wingate test followed by a muscle biopsy. Myoblasts were isolated from the muscle biopsies and differentiated to myotubes ex vivo. TNC RNA was quantified in the biopsies, myotubes and myoblasts using RNA sequencing. Blood samples were drawn before and 5 min after the Wingate test. Serum TNC levels were measured using enzyme-linked immunosorbent assay.

Results

After the Wingate test, serum TNC increased on average by 23% [15–33], median [interquartile range]; P_Wilcoxon < 0.0001. This increase is correlated with peak power output and power drop, but not with VO_2max. TNC RNA expression is higher in myoblasts and myotubes compared to skeletal muscle tissue.

Conclusion

TNC is secreted systemically as a response to the Wingate anaerobic test in healthy males. The response was positively correlated with peak power and power drop, but not with VO_2max which implicates a relation to mechanical strain and/or blood flow. With higher expression in undifferentiated myoblast cells than muscle tissue, it is likely that TNC plays a role in muscle tissue remodelling in humans. Our findings open for research on how TNC contributes to exercise adaptation.     

G tolerance and the vasoconstrictor reserve

Purpose

Because leg arterial stiffness is higher in subjects with high G tolerance, we hypothesized that subjects with high G tolerance would have larger capacity for vasoconstriction.

Methods

Sixteen subjects, eight with high and eight with low G tolerance (H and L group, respectively), were exposed to a cold pressor test (CPT) in supine and upright posture. Heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured, and total peripheral resistance (TPR) and stroke volume (SV) were calculated.

Results

In the supine position, CPT increased TPR more in the H group; 31 ± 18 % than in the L group; 11 ± 7 % (p < 0.05). The L group had larger increases in CO than the H group; 17 ± 16 vs. 3.4 ± 7 % (p = 0.06). In the upright position, the H group had a larger MAP response to CPT than the L group; 26 ± 14 vs. 14 ± 7 % (p = 0.06). The H group, but not the L group, had significant increases in TPR whereas the L group had significant increases in CO and SV.

Conclusions

In response to CPT, the high G tolerance group elevated MAP by increasing TPR, whereas the low G tolerance group showed a dependency on increased CO. The H group seemed to have a larger vasoconstrictor reserve. The results further suggest that vasoconstrictor reserve capacity could constitute the link between the recent finding that indicates a relationship between G tolerance and arterial distensibility in the legs.     

Evaluation of T and B lymphocyte function in clinical practice using a flow cytometry based proliferation assay

The golden standard for functional evaluation of immunodeficiencies is the incorporation of [³H]-thymidine in a proliferation assay stimulated with mitogens. Recently developed whole blood proliferation assays have the advantage of parallel lymphocyte lineage analysis and in addition provide a non-radioactive alternative. Here we evaluate the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) in a comparison with [³H]-thymidine incorporation in four patients with severe combined immunodeficiency. The threshold for the minimum number of lymphocytes required for reliable responses in FASCIA is determined together with reference values from 100 healthy donors when stimulated with mitogens as well as antigen specific stimuli. Finally, responses against PWM and SEA + SEB stimuli are conducted with clinically relevant immunomodulatory compounds. We conclude that FASCIA is a rapid, stable and sensitive functional whole blood assay that requires small amounts of whole blood that can be used for reliable assessment of lymphocyte reactivity in patients.