Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

Idiopathic inflammatory myositis-associated interstitial lung disease: ethnicity differences and lung function trends in a British cohort.

OBJECTIVE: Interstitial lung disease (ILD) is an important feature of idiopathic inflammatory myositis (IIM). Factors associated with its development and progression remain incompletely understood. The authors report ethnicity differences and lung function trends that characterize the predilection for and natural history of ILD in a group of British patients with IIM. METHODS: A 10-year retrospective analysis of patients with IIM at two hospitals was conducted. Demographic, clinico-radiological and laboratory features of cases with and without ILD were compared. Serial pulmonary function tests, including measurements of forced vital capacity, volume and diffusing capacity for carbon monoxide, were used to identify longitudinal patterns of lung disease. RESULTS: A total of 107 patients with IIM were identified. ILD was present in 37.4%, with non-specific interstitial pneumonia being the most common radiological pattern (75%). ILD was more common in IIM patients of Black ethnicity (OR 3.42), and in cases where ANA (OR 3.06) and anti-histidyl-tRNA synthetase (OR 3.2) antibodies were detected. In the ILD cohort, 50% deteriorated, defined as a drop in diffusing capacity of the lung for carbon monoxide by <15% or forced vital capacity <10% during the study period, occurring in all within a year of onset of ILD and significantly more frequently in those with a synchronous onset of IIM and ILD. Black ethnicity was not associated with poor lung function outcome. CONCLUSION: In IIM, the risk of developing ILD is significantly higher in patients of Black ethnicity. Progressive lung damage occurs in an appreciable subgroup of patients with IIM-ILD, heralded by functional lung decline at 1 year despite systemic immunomodulatory treatment.

Revisions to the TNM staging of non-small cell lung cancer: rationale, clinicoradiologic implications, and persistent limitations.

The International Association for the Study of Lung Cancer proposed changes to the 7th edition of the Tumor, Node, and Metastasis (TNM) staging manual of non-small cell lung cancer (NSCLC) to improve the prognostic relevance of its descriptors. These changes include the subdivision of T1 and T2 disease according to size cut points; reassignment of the T and M categories of same-lobe, ipsilateral, and contralateral malignant pulmonary nodules; reassignment of pleural disease to metastatic disease; and introduction of intra- and extrathoracic metastatic disease. Because of movement between T and M descriptors and resultant stage migration, new stage groupings that contain TNM subsets different from those of the previous edition were created. The new staging classification was created on the basis of statistical analysis of a large international database of cases of NSCLC. The new classification has many advantages; however, limitations remain. Problems with routine radiologic staging of NSCLC have not been addressed, the varied survival rates for patients with the different histologic subtypes is not reflected, the new classification is not compatible with the previous system, and application of treatment algorithms on the basis of evidence from the previous edition is less clear.

Can the completeness of radiological cancer staging reports be improved using proforma reporting? A prospective multicentre non-blinded interventional study across 21 centres in the UK.

OBJECTIVES: Following a diagnosis of cancer, the detailed assessment of prognostic stage by radiology is a crucial determinant of initial therapeutic strategy offered to patients. Pretherapeutic stage by imaging is known to be inconsistently documented. We tested whether the completeness of cancer staging radiology reports could be improved through a nationally introduced pilot of proforma-based reporting for a selection of six common cancers. DESIGN: Prospective interventional study comparing the completeness of radiology cancer staging reports before and after the introduction of proforma reporting. SETTING: Twenty-one UK National Health Service hospitals. PARTICIPANTS: 1283 cancer staging radiology reports were submitted. MAIN OUTCOME MEASURES: Radiology staging reports across the six cancers types were evaluated before and after the implementation of proforma-based reporting. Report completeness was assessed using scoring forms listing the presence or absence of predetermined key staging data. Qualitative data regarding proforma implementation and usefulness were collected from questionnaires provided to radiologists and end-users. RESULTS: Electronic proforma-based reporting was successfully implemented in 15 of the 21 centres during the evaluation period. A total of 787 preproforma and 496 postproforma staging reports were evaluated. In the preproforma group, only 48.7% (5586/11 470) of key staging items were present compared with 87.3% (6043/6920) in the postproforma group. Thus, the introduction of proforma reporting produced a 78% improvement in staging completeness . This increase was seen across all cancer types and centres. The majority of participants found proforma reporting improved cancer reporting quality for their clinical practice . CONCLUSION: The implementation of proforma reporting results in a significant improvement in the completeness of cancer staging reports. Proforma-based assessment of cancer stage enables objective comparisons of patient outcomes across centres. It should therefore become an auditable quality standard for cancer care.

A diagnostic approach to mediastinal abnormalities.

A number of mediastinal reflections are visible at conventional radiography that represent points of contact between the mediastinum and adjacent lung. The presence or distortion of these reflections is the key to the detection and interpretation of mediastinal abnormalities. Anterior mediastinal masses can be identified when the hilum overlay sign is present and the posterior mediastinal lines are preserved. Widening of the right paratracheal stripe and convexity relative to the aortopulmonary window reflection indicate a middle mediastinal abnormality. Disruption of the azygoesophageal recess can result from disease in either the middle or posterior mediastinum. Paravertebral masses disrupt the paraspinal lines, and the location of masses above the level of the clavicles can be inferred by their lateral margins, which are sharp in posterior masses but not in anterior masses. The divisions of the mediastinum are not absolute; however, referring to the local anatomy of the mediastinal reflections in an attempt to more accurately localize an abnormality may help narrow the differential diagnosis. Identification of the involved mediastinal compartment helps determine which imaging modality might be appropriate for further study.

Diagnosing acute pulmonary embolism with computed tomography: imaging update.

Acute pulmonary embolism is recognized as a difficult diagnosis to make. It is potentially fatal if undiagnosed, yet increasing referral rates for imaging and falling diagnostic yields are topics which have attracted much attention. For patients in the emergency department with suspected pulmonary embolism, computed tomography pulmonary angiography (CTPA) is the test of choice for most physicians, and hence radiology has a key role to play in the patient pathway. This review will outline key aspects of the recent literature regarding the following issues: patient selection for imaging, the optimization of CTPA image quality and dose, preferred pathways for pregnant patients and other subgroups, and the role of CTPA beyond diagnosis. The role of newer techniques such as dual-energy CT and single-photon emission-CT will also be discussed.

Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but not in protein mass.

BACKGROUND: Tuberculosis is an important cause of wasting. The functional consequences of wasting and recovery may depend on the distribution of lost and gained nutrient stores between protein and fat masses. OBJECTIVE: The goal was to study nutrient partitioning, ie, the proportion of weight change attributable to changes in fat mass (FM) versus protein mass (PM), during antimycobacterial treatment. DESIGN: Body-composition measures were made of 21 men and 9 women with pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All subjects underwent dual-energy X-ray absorptiometry and deuterium bromide dilution tests, and a four-compartment model of FM, total body water (TBW), bone minerals (BM), and PM was derived. The ratio of PM to FM at any time was expressed as the energy content (p-ratio). Changes in the p-ratio were related to disease severity as measured by radiologic criteria. RESULTS: Patients gained 10% in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44% gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results were similar in men and women. The p-ratio decreased from baseline to month 1 and then fell further by month 6. Radiologic disease severity was not correlated with changes in the p-ratio. CONCLUSIONS: Microbiological cure of tuberculosis does not restore PM within 6 mo, despite a strong anabolic response. Change in the p-ratio is a suitable parameter for use in studying the effect of disease on body composition because it allows transformation of such effects into a normal distribution across a wide range of baseline proportion between fat and protein mass.

Pulmonary manifestations of systemic autoimmune disease.

Patients with systemic autoimmune disease may present with a number of different pulmonary manifestations. In order to recognise, diagnose and manage these manifestations, it is necessary to have a working knowledge of the anatomy and physiology of the thorax. This chapter will describe the clinical symptoms and clinical examination findings in patients who may have underlying pulmonary disease. It will describe the investigations that can be used to confirm or refute a possible diagnosis and describe approaches to managing these complex clinical cases. The importance of multidisciplinary team working using the skills of clinicians, radiologists and pathologists will be highlighted. The use of high-resolution computed tomography scanning of the thorax to help to delineate the type of interstitial lung disease will be described and some of the newer modalities available for the treatment of pulmonary hypertension introduced. By the end of the chapter, the reader should understand that patients with a single underlying autoimmune disease may present with one or more pulmonary manifestations and that different autoimmune diseases may present with similar pulmonary manifestations. This heterogeneity poses both diagnostic and treatment challenges, and many questions still remain regarding optimal treatment.

High-resolution CT and CT angiography of peripheral pulmonary vascular disorders.

Peripheral pulmonary vascular disorders that can be evaluated with computed tomography (CT) include various disease entities with overlapping imaging features and a wide range of clinical manifestations. The overall accuracy of CT in the diagnosis of pulmonary vascular disorders increases with improved spatial resolution, administration of a high-flow contrast material bolus, and the use of cardiac gating. The integration of high-resolution CT and CT angiographic techniques into one scanning protocol has important clinical implications for multisection CT and makes it the imaging modality of choice in the evaluation of this complex group of disorders.

MR evaluation of normal retroperitoneal and pelvic lymph nodes.

PURPOSE: To establish guidelines for normal retroperitoneal and pelvic lymph node size at magnetic resonance imaging (MRI) by correlation with computed tomographic (CT) and lymphangiographic (LAG) data. MATERIALS AND METHODS: Twelve patients previously studied with pre- and post-LAG CT to determine normal pelvic lymph node size [ 1 ] were examined with MRI. All were on surveillance for stage I testicular tumour (minimum follow-up 10 years). Three observers recorded blind the site, size and number of nodes in the retroperitoneum and pelvis at 11 sites. The results were validated with previous CT imaging. RESULTS: Eight hundred and fifteen nodes in 12 patients were visible on the MRI initially, and a further 44 nodes were identified after comparison with post-LAG CT. More nodes were seen on MRI than on CT. The 95th centile values for maximum short axis diameter (MSAD) of pelvic lymph nodes were common iliac and obturator 4 mm, external and internal iliac 5 mm and hypogastric 6 mm. In the retroperitoneum the 95th centile MSAD values were retrocrural, high left para-aortic, paracaval and interaortocaval 3 mm, post-caval 4 mm and low left para-aortic 5 mm. CONCLUSION: MRI criteria for normal retroperitoneal and pelvic lymph node size are defined. Adoption of these recommendations may improve the sensitivity of MRI for the detection of nodal metastases.