[Rare superinfection in a COVID-19 patient-A chronology]. / Seltene Superinfektion bei einem COVID-19-Patienten ­ Eine Chronologie.

After a resuscitation situation a SARS-CoV­2 sample from a 55-year-old man who had been in the hospital for elective ablation for atrial fibrillation was tested positive. The patient history revealed that there had been a previous confirmed contact with a COVID-19 positive patient. The patient developed the complete set of symptoms of COVID-19 pneumonia with extensive intensive care treatment. After about 2 weeks of treatment, weaning had to be stopped due to the deterioration of the severe septic condition of the patient and he showed microbiological evidence of a superinfection with Cryptococcus neoformans and later Leclercia adecarboxylata. The patient was treated successfully and survived the disease.

Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis.

In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose (P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.).

Expanding the use of monoclonal antibody therapy of cancer by using ionising radiation to upregulate antibody targets.

BACKGROUND: Monoclonal antibody (mAb) therapy for the treatment of solid and haematologic malignancies has shown poor response rates as a monotherapy. Furthermore, its use is limited to tumours expressing certain molecular targets. It has been shown that single-dose radiation can induce immunogenic modulation that is characterised by cell-surface phenotypic changes leading to augmented tumour cell/cytotoxic T-cell interaction. METHODS: We examined radiation's ability to upregulate mAb therapy targets. We also used radiation to sensitise tumour cells to antibody-dependent cell-mediated cytotoxicity (ADCC). RESULTS: Radiation significantly increased cell-surface and total protein expression of mAb targets HER2, EGFR, and CD20. Focusing on HER2, targeted by trastuzumab, we observed significant upregulation of HER2 following radiation of 3 out of 3 breast cancer cell lines, one of which was triple negative, as well as in residential stem-cell populations. HER2 upregulation was sustained up to 96 h following radiation exposure and was largely dependent on intracellular reactive oxygen species. Improved ADCC and sensitisation to the antiproliferative effects of trastuzumab demonstrated the functional significance of radiation-induced HER2 upregulation. CONCLUSIONS: We show that single-dose radiation enhances mAb therapy. These findings highlight a mechanism for combining radiation with immunotherapy and expand the patient population that can be treated with targeted therapy.

The Cough Cylinder: a tool to study measures against airborne spread of (myco-) bacteria.

BACKGROUND: 'Covering your cough' reduces droplet number, but its effect on airborne pathogen transmission is less clear. The World Health Organization specifically recommends cough etiquette to prevent the spread of Mycobacterium tuberculosis, but implementation is generally poor and evidence supporting its value is lacking. METHODS: We constructed a model to assess 'real life' transmission risk by counting viable pathogens from aerosols produced by coughing patients, thus allowing the assessment of outward protection measures in a standardised fashion. During the validation process, we focused on rod-shaped bacteria as surrogates for M. tuberculosis. RESULTS: The Cough Cylinder enabled us to sample Pseudomonas aeruginosa, Escherichia coli and mycobacteria from aerosols produced by patients with cystic fibrosis, primary ciliary dyskinesia and tuberculosis. Pathogens in droplets and in airborne particles could be sampled. Delayed air sampling allowed specific measurement of persistent airborne particles. CONCLUSION: This novel experimental system allows measurement of aerosol pathogen spread in a highly standardised fashion. It also offers the possibility to assess the impact of different interventions to limit aerosol transmission.

Exotic trees.

We discuss the scaling properties of free branched polymers. The scaling behavior of the model is classified by the Hausdorff dimensions for the internal geometry, d(L) and d(H), and for the external one, D(L) and D(H). The dimensions d(H) and D(H) characterize the behavior for long distances, while d(L) and D(L) for short distances. We show that the internal Hausdorff dimension is d(L)=2 for generic and scale-free trees, contrary to d(H), which is known to be equal to 2 for generic trees and to vary between 2 and infinity for scale-free trees. We show that the external Hausdorff dimension D(H) is directly related to the internal one as D(H)=alphad(H), where alpha is the stability index of the embedding weights for the nearest-vertex interactions. The index is alpha=2 for weights from the Gaussian domain of attraction and 0