Background: With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a Public Health Emergency of International Concern by the World Health Organization (WHO). Consequently, many countries have implemented flight restrictions to China. China itself has imposed a lockdown of the population of Wuhan as well as the entire Hubei province. However, whether these two enormous measures have led to significant changes in the spread of COVID-19 cases remains unclear. Methods: We analyzed the available data on the development of confirmed domestic and international COVID-19 cases before and after lockdown measures. We evaluated the correlation of domestic air traffic to the number of confirmed COVID-19 cases and determined the growth curves of COVID-19 cases within China before and after lockdown as well as after changes in COVID-19 diagnostic criteria. Results: Our findings indicate a significant increase in doubling time from 2 days (95% CI: 1.9–2.6) to 4 days (95% CI: 3.5–4.3), after imposing lockdown. A further increase is detected after changing diagnostic and testing methodology to 19.3 (95% CI: 15.1–26.3), respectively. Moreover, the correlation between domestic air traffic and COVID-19 spread became weaker following lockdown (before lockdown: r = 0.98, P < 0.05 vs after lockdown: r = 0.91, P = NS). Conclusions: A significantly decreased growth rate and increased doubling time of cases was observed, which is most likely due to Chinese lockdown measures. A more stringent confinement of people in high risk areas seems to have a potential to slow down the spread of COVID-19.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been recently reported as a new approach for intraperitoneal chemotherapy (IPC). By means of a patented micropump, the liquid chemotherapy is delivered into the peritoneal cavity as an aerosol which is supposed to achieve “gas-like” distribution. However, recent data report that the fraction of the submicron aerosol (gas-like) is less than 3 vol% of the total amount of aerosolized chemotherapy. Until today, possible modifications of treatment parameters during PIPAC with the aim of improving therapeutic outcomes have not been studied yet. This study aims to establish an in vitro PIPAC model to explore the cytotoxic effect of the submicron aerosol fraction and to investigate the impact of different application parameters on the cytotoxic effect of PIPAC on human colonic cancer cells. An in vitro model using HCT8 colon adenocarcinoma wild-type cells (HCT8WT) and multi-chemotherapy refractory subline (HCT8RT) was established. Different experimental parameters such as pressure, drug dosage, time exposure, and system temperature were monitored in order to search for the conditions with a higher impact on cell toxicity. Cell proliferation was determined by means of colorimetric MTT assay 48 h following PIPAC exposures. Standard operational parameters applied for PIPAC therapy depicted a cytotoxic effect of the submicron aerosol fraction generated by the PIPAC micropump. We also observed that increasing pressure significantly enhanced tumor cell toxicity in both wild-type and chemotherapy-resistant cells. A maximum of cytotoxicity was observed at 15 mmHg. Pressure >15 mmHg did not show additional cytotoxic effect on cells. Increased oxaliplatin dosage resulted in progressively higher cell toxicity as expected. However, in resistant cells, a significant effect was only found at higher drug concentrations. Neither an extension of exposure time nor an increase in temperature of the aerosolized chemotherapy solution added an improvement in cytotoxicity. In this in vitro PIPAC model, the gas-like PIPAC aerosol fraction showed a cytotoxic effect which was enhanced by higher intra-abdominal pressure with a maximum at 15 mmHg. Similar findings were observed for drug dose escalation. A phase I dose escalation study is currently performed at our institution. However, increasing the intra-abdominal pressure might be a first and simple way to enhance the cytotoxic effect of PIPAC therapy which needs further clinical investigations.

Besides its known antibacterial effect commonly used in intraperitoneal lavage, taurolidine has been observed to possess antineoplastic properties. In order to analyse this antineoplastic potential in a palliative therapeutic setting, taurolidine (TN) was compared to mitomycin C (MMC) and oxaliplatin (OX), known antineoplastic agents which are routinely used in intraperitoneal applications, following pressurized intra-peritoneal aerosol chemotherapy (PIPAC). An in vitro model was established using a colon adenocarcinoma cell line (HT-29 human cells). Different experimental dosages of TN and combinations of TN, MMC, and OX were applied via PIPAC. To measure cell proliferation, a colorimetric tetrazolium reduction assay was utilized 24 h after PIPAC. We demonstrated a cytotoxic effect of TN and OX (184 mg/150 mL, p < 0.01) on tumor cell growth. An increasing dosage of TN (from 0.5 g/100 mL to 0.75 g/150 mL) correlated with higher cell toxicity when compared to untreated cells (p < 0.05 and p < 0.01, respectively). PIPAC with OX and both OX and TN (0.5 g/100 mL) showed the same cytotoxic effect (p < 0.01). No significant impact was observed for MMC (14 mg/50 mL, p > 0.05) or MMC with OX (p > 0.05) applied via PIPAC. The intraperitoneal application of TN is mostly limited to lavage procedures in cases of peritonitis. Our results indicate a substantial antineoplastic in vitro effect on colon carcinoma cells following PIPAC application. While this effect could be used in the palliative treatment of peritoneal metastases, further clinical studies are required to investigate the feasibility of TN application in such cases.

For decades, intraperitoneal chemotherapy (IPC) was delivered into the abdominal cavity as a liquid solution. This preliminary study aims to evaluate foam as a potential new drug carrier for IPC delivery. Foam-based intraperitoneal chemotherapy (FBIC) was produced with taurolidine, hydrogen peroxide, human serum, potassium iodide and doxorubicin/ oxaliplatin for both ex vivo and in vitro experiments. Analysis of FBIC efficacy included evaluation of cytotoxicity, tissue penetration, foam stability, temperature changes and total foam volume per time evaluation. FBIC showed penetration rates of about 275 ± 87 µm and higher cytotoxicity compared to controls and to conventional liquid IPC (p < 0.005). The volume of the generated foam was approximately 50-times higher than the initial liquid solution and temporarily stable. Foam core temperature was measured and increased to 47 °C after 9 min. Foam ingredients (total protein content) were evenly distributed within different locations. Our preliminary results are quite encouraging and indicate that FBIC is a feasible approach. However, in order to discuss a possible superior effect over conventional liquid or aerosolized chemo applications, further studies are required to investigate pharmacologic, pharmacodynamic and physical properties of FBIC.