Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry.

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.

Applications of abduction: hypothesis testing of neuroendocrinological qualitative compartmental models.

It is difficult to assess hypothetical models in poorly measured domains such as neuroendocrinology. Without a large library of observations to constrain inference, the execution of such incomplete models implies making assumptions. Mutually exclusive assumptions must be kept in separate worlds. We define a general abductive multiple-worlds engine that assesses such models by (i) generating the worlds and (ii) tests if these worlds contain known behaviour. World generation is constrained via the use of relevant envisionment. We describe QCM, a modeling language for compartmental models that can be processed by this inference engine. This tool has been used to find faults in theories published in international refereed journals; i.e. QCM can detect faults which are invisible to other methods. The generality and computational limits of this approach are discussed. In short, this approach is applicable to any representation that can be compiled into an and-or graph, provided the graphs are not too big or too intricate (fanout < 7).

Prophylactic use of antithrombin III concentrate following surgery in congenital antithrombin III deficiency.

Antithrombin III is the major physiological inhibitor of thrombin, and congenital deficiency of antithrombin III is associated with increased risk of venous thrombosis either spontaneously or following trauma, surgery or pregnancy. The successful use of antithrombin III concentrate during and following surgery to prevent venous thrombosis is described in a previously asymptomatic man with familial antithrombin III deficiency.

Clinical examination as a screening method for breast cancer.

A five-year experience of a breast cancer screening clinic in a Scottish urban area is reported. During this period 28 per cent of the female population aged 25 to 70 years was screened by clinical examination alone. The pick-up rate for cancers was 7.8 per 1,000 'well' women examined, and 21 per cent of all patients with cancer were under 40 years old. Clinical examination is an effective and economical method of screening for breast cancer. The establishment of similar clinics to detect breast disease in women of all age groups is recommended.

Microbial flora in carcinoma of oesophagus.

The microbial flora associated with carcinoma of the oesophagus was studied in 12 patients. Oesophageal mucosa was biopsied at thoracotomy and cultured under both aerobic and anaerobic conditions. A heavy mixed growth of aerobic and anaerobic organisms was obtained in all patients. One-third of isolates were anaerobic. The flora was of oral origin. The most appropriate antibiotic combination in this study was ampicillin or penicillin with gentamicin and metronidazole.