A real-world evaluation of the diagnostic accuracy of radiologists using positive predictive values verified from deep learning and natural language processing chest algorithms deployed retrospectively.

Objectives: This diagnostic study assessed the accuracy of radiologists retrospectively, using the deep learning and natural language processing chest algorithms implemented in Clinical Review version 3.2 for: pneumothorax, rib fractures in digital chest X-ray radiographs (CXR); aortic aneurysm, pulmonary nodules, emphysema, and pulmonary embolism in CT images. Methods: The study design was double-blind (artificial intelligence [AI] algorithms and humans), retrospective, non-interventional, and at a single NHS Trust. Adult patients (≥18 years old) scheduled for CXR and CT were invited to enroll as participants through an opt-out process. Reports and images were de-identified, processed retrospectively, and AI-flagged discrepant findings were assigned to two lead radiologists, each blinded to patient identifiers and original radiologist. The radiologist's findings for each clinical condition were tallied as a verified discrepancy (true positive) or not (false positive). Results: The missed findings were: 0.02% rib fractures, 0.51% aortic aneurysm, 0.32% pulmonary nodules, 0.92% emphysema, and 0.28% pulmonary embolism. The positive predictive values (PPVs) were: pneumothorax (0%), rib fractures (5.6%), aortic dilatation (43.2%), pulmonary emphysema (46.0%), pulmonary embolus (11.5%), and pulmonary nodules (9.2%). The PPV for pneumothorax was nil owing to lack of available studies that were analysed for outpatient activity. Conclusions: The number of missed findings was far less than generally predicted. The chest algorithms deployed retrospectively were a useful quality tool and AI augmented the radiologists' workflow. Advances in knowledge: The diagnostic accuracy of our radiologists generated missed findings of 0.02% for rib fractures CXR, 0.51% for aortic dilatation, 0.32% for pulmonary nodule, 0.92% for pulmonary emphysema, and 0.28% for pulmonary embolism for CT studies, all retrospectively evaluated with AI used as a quality tool to flag potential missed findings. It is important to account for prevalence of these chest conditions in clinical context and use appropriate clinical thresholds for decision-making, not relying solely on AI.

Antiretroviral therapy with or without protease inhibitors impairs postprandial TAG hydrolysis in HIV-infected men.

Mechanisms underlying the lipodystrophy syndrome associated with antiretroviral therapy (ART) for HIV infection are not completely understood. We investigated the effect of ART on blood lipid concentrations in the fasting state and after consumption of a meal containing [1-13C]palmitic acid in HIV-positive men receiving nucleoside reverse transcriptase inhibitors (NRTI, n 7), NRTI combined with protease inhibitors (PI; NRTIPI, n 6), in HIV-positive but therapy-naïve men (noART, n 5) and in HIV-seronegative men (controls, n 6). HIV-positive subjects had higher fasting TAG concentrations and resting energy expenditure than controls. Subjects receiving NRTIPI therapy had higher fasting NEFA concentrations than the other groups. There were no significant differences in postprandial lipid metabolism between noART subjects and controls. NRTI therapy impaired hydrolysis of meal-derived TAG, most evidently when combined with PI (the NRTIPI group). Accumulation of 13C-label in the NEFA fraction was not different between groups. In the NRTIPI group, fasting and postprandial NEFA concentrations were significantly higher than other groups. Postprandial glucose and insulin responses in HIV-positive subjects did not differ from controls. These findings suggest that ART dyslipidaemia is associated with impaired postprandial TAG clearance, which is exacerbated by NRTIPI therapy. If dyslipidaemia is to be minimised in ART, the specific adverse effects of particular combinations during the fed state should be considered.

Case report. Severe cutaneous ulceration secondary to cytomegalovirus inclusion disease during successful immune reconstitution with HAART.

Restoration of the immune system following HAART is not without its adverse effects. We describe a case of severe cutaneous ulceration secondary to cytomegalovirus (CMV) infection in an HIV-1-seropositive man following the initiation of HAART in the absence of active CMV retinitis and discuss the likely mechanisms associated with its development.

The acute-phase protein response to infection in edematous and nonedematous protein-energy malnutrition.

BACKGROUND: Immune structure and function are more compromised in edematous protein-energy malnutrition (PEM) than in nonedematous PEM. Whether the positive acute-phase protein (APP) response to infection is affected remains unknown. OBJECTIVE: We assessed whether children with edematous PEM can mount a general APP response and compared the kinetic mechanisms of the response in children with edematous PEM with those in children with nonedematous PEM. DESIGN: Plasma C-reactive protein, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and fibrinogen concentrations and the fractional and absolute synthesis rates of alpha(1)-antitrypsin, haptoglobin, and fibrinogen were measured in 14 children with edematous PEM, aged 11.4 +/- 2 mo, and 9 children with nonedematous PEM, aged 10.1 +/- 1.4 mo, at 3 times: approximately 2 d after hospital admission (period 1), when they were malnourished and infected; approximately 8 d after admission (period 2), when they were malnourished but free of infection; and approximately 54 d after admission (period 3), when they had recovered. RESULTS: Children with edematous and nonedematous PEM had higher plasma concentrations of 4 of 5 APPs in period 1 than in period 3. The magnitude of the difference in concentration and in the rate of synthesis of the individual APPs was less in the children with edematous PEM than in those with nonedematous PEM. The kinetic data show that the characteristics of the APP response were different in the 2 groups. CONCLUSIONS: These results suggest that severely malnourished children can mount only a partial APP response to the stress of infection and that the magnitude of this response is less in those with edema.

Lopinavir/ritonavir (ABT-378/r).

Despite major advances in HIV research, eradication of HIV from the body is not yet possible. However, current antiretroviral (ARV) therapy can achieve disease control via viral suppression below the limits of detection of currently available assays. This has led to a marked decline in morbidity and mortality associated with the development of opportunistic infections and malignancies. Since viral suppression appears to be the most achievable goal of current therapy, there arises a need for new and more potent ARV agents in order to maintain viral suppression. Many of the currently available protease inhibitors (PIs) have a high protein-binding ability, short plasma half-life [1] and pharmacokinetic interactions with food or other drugs [2]. This can result in sub-optimal plasma drug concentrations, which may allow the virus to break through and replicate, leading to the development of resistant mutants [1]. Lopinavir/ritonavir (LPV/r; Kaletra, Abbott Laboratories) is a new PI consisting of a co-formulation of lopinavir and low-dose ritonavir. The sub-therapeutic dose of ritonavir (a potent cytochrome P450 [CYP] 3A4 inhibitor) inhibits the metabolism of lopinavir, resulting in higher lopinavir concentrations than when lopinavir is administered alone [3]. This pharmacokinetic interaction is associated with a high lopinavir trough level:wild type median effective concentration (EC(50)) ratio and good general tolerability when compared with other currently licensed PIs [4]. The concept of pharmacokinetic enhancement - boosting - is not new as ritonavir has previously been utilised in this context with other PIs. The relationship between plasma and intracellular drug levels has yet to be clarified. What has been ascertained from pharmacokinetic studies thus far is the correlation between ARV trough plasma concentrations (C(min)) and virological outcome [5,6]. LPV/r exemplifies how the pharmacokinetic profile of a drug can be modified to attain sufficient C(min) to suppress pheno- and genotypically resistant viral strains, as well as provide a pharmacological barrier to the emergence of resistance [7]. LPV/r reduces pill-burden and aids compliance, as shown by encouraging results in the treatment of both ARV-naive and -experienced patients.

Acute-phase protein response to infection in severe malnutrition

It is not known whether malnourished infant can mount a comprehensive acute-phase protein (APP) response and, if so, whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the plasma concentrations of five APPs (C-reactive protein, O1-acid glycoprotein, O1-antitrypsin, haptoglobin, and fibrinogen) and 2) the synthesis rates of three APPs (O1-antitrypsin, haptoglobin, and fibrinogen) using a constant intragastric infusion of [2H3] leucine in nine infected marasmic children at 2 days postadmission (study 1), 9 days postadmission when infections had cleared (study 2), and 59 days postadmission at recovery (study 3). Except for fibrinogen, the plasma concentrations of all APPs were higher in study 1 than in studies 2 and 3. Although the rate of synthesis of haptoglobin was significantly greater in study 1 than in study 2, the rates of fibrinogen and O1-antitrypsin synthesis were similar in all three studies. These results show that 1) severely malnourished children can mount an APP response to infection which does not include fibrinogen and 2) the APP response is accomplished through different mechanisms. (AU)

Albumin kinetics in edematous and nonedematous protein-energy malnourished children

The kinetic changes responsible for decreased plasma albumin and the relation between plasma albumin and the edema of protein-energy malnutrition (PEM) were investigated by measuring the plasma concentration, fractional (FSR) and intravascular absolute (ASR) synthesis rates of albumin in seven edematous and seven nonedematous children with PEM by using constant intragastric infusions of [2H3] leucine. Studies were done 2 d postadmission (study 1), 8 d postadmission (study 2), and at recovery (study 3). In study 1 there were no significant differences in plasma albumin concentrations in nonedematous and edematous children. In both groups, albumin concentrations but not FSRs were lower in studies 1 and 2 than in study 3. The ASR was lower only in edematous patients. These results suggest that repletion of the albumin pool of children with PEM is not mediated by changes in the FSR, and the edema of malnutrition is not solely due to hypoalbuminemia. (AU)