Monoclonal gammopathy of undetermined significance (MGUS) in patients with solid tumors: effects of chemotherapy on the monoclonal protein

The aim of this study was to assess the effect of systemic chemotherapy on the monoclonal protein levels of patients with solid tumors who also have a monoclonal gammopathy of undetermined significance (MGUS). All patients with solid tumors who were referred to our department for consideration of systemic chemotherapy were evaluated with serum protein electrophoresis (SPEP) for the presence of MGUS. When MGUS was confirmed with immunofixation, serial SPEP was performed during and after completion of chemotherapy. Over a 6-year period, 21 patients with solid tumors and MGUS were prospectively identified and assessed. At least 50% reduction of serum monoclonal protein was noted in 4 of 11 patients treated with paclitaxel or docetaxel with a platinum analogue and in 5 of 7 patients who received an irinotecan-containing regimen. Our data indicate that in MGUS patients treated with irinotecan-containing chemotherapy regimens, a high incidence of reduction in their monoclonal protein levels is observed. Since topotecan, another topoisomerase I inhibitor, has some activity in multiple myeloma, further evaluation of irinotecan may be warranted. Evaluation of larger numbers of MGUS patients treated with chemotherapy for their underlying malignancy may help identify in vivo potentially active agents and regimens for patients with overt myeloma.     

Deferoxamine infusion during coronary artery bypass grafting ameliorates lipid peroxidation and protects the myocardium against reperfusion injury: immediate and long-term significance.

AIMS: Previous reports have demonstrated enhanced myocardial protection and better post-ischaemic recovery using the oxygen free radical scavenger deferoxamine (DEF) during cardioplegia. The aim of this study was to test whether, in patients undergoing coronary artery bypass grafting (CABG), DEF i.v. infusion can reduce reperfusion injury on a short- and long-term basis. METHODS AND RESULTS: Forty-five consecutive male patients were randomly allocated to two groups: in group D (n=25, age 60.8+/-8.6 years), 4 g of DEF were infused for 8 h starting immediately after the induction of anaesthesia; in group C (n=20, age 62.2+/-6.4 years) dextrose solution was given for the same time as placebo. Haemodynamic monitoring and measurement of oxygen free radical production [by measuring thiobarbituric acid reactive substances (TBARS)] were carried out before and after CABG. Left ventricular ejection fraction (EF) and wall motion score index (WMSI) were measured before and after CABG and 12 months later. Haemodynamic measurements were similar in both groups before and after CABG. TBARS peaked at 4.8+/-1.1 nmol/mL in group C, but remained unchanged (2.4+/-0.9 nmol/mL) in group D (P=0.01). At baseline, both the EF and WMSI were similar between the groups. Following CABG, EF increased more in group D (8.8+/-8.4%) than in group C (1.3+/-6.7%), P=0.008, while WMSI decreased more in group D (-0.7+/-0.3) than in group C (-0.2+/-0.2), P=0.0001. Dividing group D according to the pre-operative median EF value (38%), we observed that after 1 year follow-up, DEF infusion conferred more protection in patients with a lower EF (EF increased by 19.3+/-6.2%, WMSI decreased by -1.1+/-0.2) than in those with a higher EF (EF increased by 7.7+/-4.5%, WMSI decreased by -0.8+/-0.2), P=0.001, respectively. CONCLUSION: In patients undergoing CABG, DEF i.v. infusion ameliorates oxygen free radical production and protects the myocardium against reperfusion injury. Patients with a lower EF seem to benefit more by DEF i.v. infusion.     

Comparison of the Lupus Foundation of America–Rapid Evaluation of Activity in Lupus to More Complex Disease Activity Instruments As Evaluated by Clinical Investigators or Real‐World Clinicians

Objective

Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America–Rapid Evaluation of Activity in Lupus (LFA‐REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA‐REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians.

Methods

Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA‐REAL, while the clinicians scored the LFA‐REAL. The level of agreement between physicians and instruments was determined.

Results

The study included 99 patients (93% women, 31% white, mean ± SD ages 43.4 ± 13.2 years). At the first visit, the mean ± SD SLEDAI score was 5.5 ± 4.5, BILAG score 6.7 ± 7.8, and PGA score 33.6 ± 24.5. The mean ± SD investigator LFA‐REAL score was 46.2 ± 42.9, and clinician LFA‐REAL score 56.1 ± 53.6. At the second visit, the mean ± SD investigator LFA‐REAL score was 41.3 ± 36.7, and clinician LFA‐REAL score 48.3 ± 42.6. Total LFA‐REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ = 0.58–0.88, P < 0.001). LFA‐REAL scores produced correlation coefficients of ρ > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA‐REAL scores of investigators and clinicians was 0.79 for visit 1 (P < 0.001) and 0.86 for visit 2 (P < 0.001).

Conclusion

The LFA‐REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.

     

Neuroendocrine differentiation in embryonal type hepatoblastoma

Hepatoblastoma, a malignant tumor which arises occasionally in older children but very rarely in adults, exhibits divergent differentiation with embryonal cells, fetal hepatocytes and immature elements. This report describes an embryonal type hepatoblastoma with neuroendocrine differentiation in a 16‐year‐old patient, which was diagnosed postoperatively. Clinical and radiologic work‐up failed to reveal a primary gastrointestinal malignancy and no primary lesions were detected in any other organ. This feature of hepatoblastoma is considered to be a multidirectional differentiation of the small epithelial or stem cells of the liver. At 2‐year follow up, the patient remains symptom‐free, with normal laboratory and diagnostic imaging studies, and no recurrent or metastatic disease identified.     

An Early Warning System for Hypoglycemic/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models

Introduction

Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia/hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy.

Methods

The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) auto-regressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models′ outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS.

Results

The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms.

Conclusion

Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.     

Acute respiratory distress syndrome: new definition,current and future therapeutic options

Since acute respiratory distress syndrome (ARDS) was first described in 1967 there has been large number of studies addressing its pathogenesis and therapies. Despite this intense research activity, there are very few effective therapies for ARDS other than the use of lung protection strategies. This lack of therapeutic modalities is not only related to the complex pathogenesis of this syndrome but also the insensitive and nonspecific diagnostic criteria to diagnose ARDS. This review article will summarize the key features of the new definition of ARDS, and provide a brief overview of innovative therapeutic options that are being assessed in the management of ARDS.KEY WORDS : Acute respiratory distress syndrome (ARDS), pathogenesis, therapeutic options     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.