Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis. Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity. Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection ( n = 14) and healthy lung tissue from control subjects without tuberculosis ( n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways. Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm 3 (15–389 cm 3 ). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation “sink” in the central caseum–fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid–mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden ( r > 0.6), whereas T-helper effector systems did not. Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis –related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions.
Background: Prostate cancer is an important cause of morbidity and mortality in South Africa, as it is in the rest of the world. In African men, however, prostate cancer tends to follow a more aggressive course when compared to their European counterparts. This is attributed to a plethora of diverse factors of which an underlying genetic component has been shown to be an important aspect. Such differences highlight the need for individualised therapy and for local guidelines. The aim of this guideline is to aid nuclear physicians and other clinicians who manage patients with prostate cancer in the correct identification and treatment of patients who are likely to benefit from receptor radioligand therapy. Recommendations: There are a multitude of treatment modalities available for the treatment of prostate cancer and these therapies may be required at various time points during the course of the disease in any individual patient. A multidisciplinary approach is crucial in deciding which therapy, or combination of therapies, would be most advantageous at particular time points. The multidisciplinary team should include a urologist, oncologist and nuclear medicine physician as a minimum, and should ideally also involve a palliative/pain specialist, a dietician and a psychologist. Conclusion: Treatment with 177 Lu-PSMA has emerged as a promising systemic modality, which involves the delivery of targeted radiation therapy in the form of β-particles to sites of tumour tissue. Therapy is provided on an outpatient basis, is well tolerated with relatively few side effects and has a positive effect on overall survival and quality of life. At present, it is used mostly in the setting of advanced, castrate-resistant cancer. Patients are selected (amongst other criteria) based on the prior PSMA-based SPECT/PET/CT imaging ( 99m Tc-, 68 Ga-or 18 F-PSMA), which should demonstrate sufficient receptor expression in order to consider PSMA-based targeted radionuclide therapy. Such imaging of an intended target prior to its therapeutic targeting is known as a theranostic approach.
SummaryObjectiveTo determine how two software packages, supplied by Siemens and Hermes, for processing gated blood pool (GBP) studies should be used in our department and whether the use of different cameras for the acquisition of raw data influences the results.MethodsThe study had two components. For the first component, 200 studies were acquired on a General Electric (GE) camera and processed three times by three operators using the Siemens and Hermes software packages. For the second part, 200 studies were acquired on two different cameras (GE and Siemens). The matched pairs of raw data were processed by one operator using the Siemens and Hermes software packages.ResultsThe Siemens method consistently gave estimates that were 4.3% higher than the Hermes method (p < 0.001). The differences were not associated with any particular level of left ventricular ejection fraction (LVEF). There was no difference in the estimates of LVEF obtained by the three operators (p = 0.1794). The reproducibility of estimates was good. In 95% of patients, using the Siemens method, the SD of the three estimates of LVEF by operator 1 was ≤ 1.7, operator 2 was ≤ 2.1 and operator 3 was ≤ 1.3. The corresponding values for the Hermes method were ≤ 2.5, ≤ 2.0 and ≤ 2.1. There was no difference in the results of matched pairs of data acquired on different cameras (p = 0.4933)ConclusionSoftware packages for processing GBP studies are not interchangeable. The report should include the name and version of the software package used. Wherever possible, the same package should be used for serial studies. If this is not possible, the report should include the limits of agreement of the different packages. Data acquisition on different cameras did not influence the results.
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