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BackgroundClarithromycin clinical efficacy has not been described in COVID-19.Research questionIs oral clarithromycin beneficial for treating patients diagnosed with COVID-19?Study and methodsAn open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted at four study sites in Greece between May and October 2020. Ninety participants with respiratory tract infections received clarithromycin 500 mg every 12 hours for 7 days; another 90 standard-of-care (SOC) propensity score-matched concurrent controls received azithromycin plus hydroxychloroquine. The composite primary endpoint was defined for patients with upper respiratory tract infection as: (a) no need for hospital re-admission or (b) lack of progression into lower respiratory tract infection and, for patients with lower respiratory tract infection, as at least 50% decrease of the score of respiratory symptoms at the end-of-treatment (EOT) without progression into severe respiratory failure (SRF). The incidence SRF at the test-of-cure (TOC) on day 14 was a secondary endpoint. For clarithromycin-treated patients, viral load of SARS-CoV-2, biomarkers, the function of mononuclear cells, and safety were assessed; biomarkers were also measured in SOC comparators.ResultsThe primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%) and 73.3% of concurrent SOC comparators (95%CIs; 63.4-81.4%). The odds ratio for the primary endpoint with clarithromycin treatment in univariate analysis was 2.36 (95%CIs 1.09-5.08; P: 0.039). Results were confirmed after multivariate stepwise logistic regression analysis (odds ratio 3.30; 95% CI 1.10-9.87; P: 0.033). At the TOC visit, the incidence of SRF was 12.2% (n = 11 ; 95%CIs 6.9-20.6%) among patients treated with clarithromycin (odds ratio for SRF 0.38; 95%CIs 0.17-0.84) versus 26.7% (n= 24; 95%CIs 18.6-36.6%) among concurrent SOC comparators (P: 0.023). Clarithromycin use was associated with decreases in circulating levels of C-reactive protein, of tumour necrosis factor-alpha and of interleukin (IL)-6; by an increase of the ratio of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 relative viral load. No safety concerns were reported. Patients starting clarithromycin with the first five days from symptoms onset achieved better responses.InterpretationClarithromycin treatment is associated with early clinical improvement in patients with moderate COVID-19. Modulation of the Th1/Th2 responses is proposed as the mechanism of action.Trial RegistrationClinicalTrials.gov, NCT04398004

Bordetella bronchiseptica is a gram-negative coccobacillus that colonizes the respiratory system of mammals such as dogs, cats, rabbits and others and might cause upper respiratory tract infections. Although it can be rarely pathogenic in humans, there are several case reports describing infections in humans. We describe the case of a patient without prolonged immunosuppression or underlying diseases, with bacteremia from Bordetella bronchiseptica, while being treated in a tertiary hospital for COVID-19 infection.

Additive Manufacturing (AM) has been widely considered a key factor for innovative design. However, the utilization of AM has not been as high as expected, although the technology offers key innovative design capabilities, weight reduction, parts count and assembly consolidation as well as material saving. This low utilization is attributed to the lack of AM understanding, mature CAE/CAM software tools addressing AM specific issues such as design support structure generation and removal, residual stresses, surface quality. In most cases, Design for AM (DfAM) is a crucial requisite for a “Design Right Once” approach. Such an approach is shown in the current study using three parts as example: an arthropod’s leg, a gearshift drum and an electric motor mounting frame. The implementation of geometrical conformal lattice structures and lattices with variable density are discussed. A structured design approach is presented and design dilemmas are solved in terms of a DfAM approach. Primary design optimizations are evaluated. Weight reduction is considered throughout the design and free form surfaces are being used. “Freedom to Design” principle is also portrayed and assembly parts consolidation occurs as a natural process of DfAM in comparison with previous design practices. It is concluded that, even from the primary design phase the design engineer can reveal his creativity because of the absence of constraints set by the traditional manufacturing technologies.

Previous studies suggest an association between celiac disease and anorexia nervosa. Research has mainly focused on children and adolescents, and studies among adults are limited. The similar clinical manifestations that characterize both diseases can complicate the diagnosis, and a thorough diagnostic workup is necessary. A focused medical history remains the cornerstone of diagnosis. A delayed diagnosis can lead to a worse quality of life and severe complications. We present the case of a 43-year-old woman with anorexia nervosa who was thereafter diagnosed with celiac disease. The later diagnosis occurred after a long period of persistent diarrhea. Based on the patient's history of autoimmune disease, celiac disease was suspected. Our case highlights the importance of additional work-up in patients with anorexia nervosa who have persistent gastrointestinal symptoms. A further investigation should be based on the medical history, clinical presentation, and laboratory findings.