Assessment of Anastomotic Viability With Spectroscopic Real-time Oxygen Saturation Measurement in a Porcine Study.

OBJECTIVE: Anastomotic leakage (AL) is a severe complication following intestinal procedures. Intra.Ox™ by ViOptix Inc (Newark, CA, USA) is a novel, FDA-approved spectroscopic device which enables real-time measurement of mixed tissue oxygen saturation (StO2). Using a porcine model, this study explores the correlation between StO2 measurements and AL formation as well as investigates the applicability of Intra.Ox™ in the clinical setting. METHODS: Eleven female swine were divided into 3 groups to explore AL formation in different ischemic conditions. Group 1: 100% mesenteric-vascular ligation, n = 3; Group 2: 50% ligation, n = 5; Group 3: No mesenteric ligation, n = 3. StO2 at the anastomotic line was measured before and after vessel ligation and anastomosis. Measurements were taken at 6 distinct locations along afferent and efferent loops. AL was evaluated on postoperative day 5 by re-laparotomy. RESULTS: AL rate was 100%, 60% and 0% in groups 1, 2 and 3, respectively. Post-anastomotic StO2 in group 1 (22.9 ± 18.5%) and 2 (39.2 ± 20.1%) were significantly lower than in group 3 (53.1 ± 8.3%, p<.0001). Post-anastomotic StO2 readings ≤40% indicated AL potential with 100% sensitivity,+ 80% specificity, positive predictive value of 85.7% and negative predictive value of 100%. CONCLUSION: This study demonstrates the value of Intra.Ox™ in assessing local perfusion and indicate the association between low StO2 and AL by providing accurate, real-time, noninvasive tissue oxygenation measurements at anastomotic sites. Further studies are required to investigate the clinical application of this novel device in intestinal surgery.

Current meta-analysis does not support the possibility of COVID-19 reinfections.

Coronavirus disease 2019 (COVID-19) reinfections could be a major aggravating factor in this current pandemic, as this would further complicate potential vaccine development and help to maintain worldwide virus pockets. To investigate this critical question, we conducted a clinical meta-analysis including all available currently reported cases of potential COVID-19 reinfections. We searched for all peer-reviewed articles in the search engine of the National Center for Biotechnology Information. While there are over 30,000 publications on COVID-19, only about 15 specifically target the subject of COVID-19 reinfections. Available patient data in these reports was analyzed for age, gender, time of reported relapse after initial infection and persistent COVID-19 positive polymerase chain reaction (PCR) results. Following the first episode of infection, cases of clinical relapse are reported at 34 (mean) ± 10.5 days after full recovery. Patients with clinical relapse have persisting positive COVID-19 PCR testing results until 39 ± 9 days following initial positive testing. For patients without clinical relapse, positive testing was reported up to 54 ± 24 days. There were no reports of any clinical reinfections after a 70-day period following initial infection.

Exploring Insulin Production Following Alveolar Islet Transplantation (AIT).

Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/- 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung.

Failure in initial stage containment of global COVID-19 epicenters.

With multiple virus epicenters, COVID-19 has been declared a pandemic by the World Health Organization. Consequently, many countries have implemented different policies to manage this crisis including curfew and lockdown. However, the efficacy of individual policies remains unclear with respect to COVID-19 case development. We analyzed available data on COVID-19 cases of eight majorly affected countries, including China, Italy, Iran, Germany, France, Spain, South Korea, and Japan. Growth rates and doubling time of cases were calculated for the first 6 weeks after the initial cases were declared for each respective country and put into context with implemented policies. Although the growth rate of total confirmed COVID-19 cases in China has decreased, those for Japan have remained constant. For European countries, the growth rate of COVID-19 cases considerably increased during the second time interval. Interestingly, the rates for Germany, Spain, and France are the highest measured in the second interval and even surpass the numbers in Italy. Although the initial data in Asian countries are encouraging with respect to case development at the initial stage, the opposite is true for European countries. Based on our data, disease management in the 2 weeks following the first reported cases is of utmost importance.

The structural effect of high intensity ultrasound on peritoneal tissue: a potential vehicle for targeting peritoneal metastases.

BACKGROUND: High-intensity ultrasound (HIUS) has been increasingly investigated as a possible tool in the treatment of multiple tumor entities. However, there is only little knowledge on the effect of HIUS on the peritoneum. This preliminary study aims to investigate HIUS' potential for altering the peritoneal surface and potentially improving current treatments for peritoneal metastases. For this purpose, HIUS' qualitative and quantitative structural effects on the peritoneal tissue were analyzed by means of light, fluorescence and electron microscopy. METHODS: Proportional sections were cut from the fresh postmortem swine peritoneum. Peritoneal surfaces were covered with a 6 mm thick liquid film of 0.9% NaCl. HIUS was applied in all tissue samples for 0 (control), 30, 60, 120 and 300 s. Peritoneal tissues were analyzed using light-, fluorescence and electron microscopy to detect possible structural changes within the tissues. RESULTS: Following HIUS, a superficial disruption of peritoneal tissue was visible in light microscopy, which amplified with increased time of HIUS' application. Fluorescence microscopy showed both peritoneal and subperitoneal disruption with tissue gaps. Electron microscopy revealed structural filamentation of the peritoneal surface. CONCLUSION: Our data indicate that HIUS causes a wide range of effects on the peritoneal tissue, including the formation of small ruptures in both peritoneal and subperitoneal tissues. However, according to our findings, these disruptions are limited to a microscopical level. Further studies are required to evaluate whether HIUS application can benefit current therapeutic regimens on peritoneal metastases and possibly enhance the efficacy of intraperitoneal chemotherapy.

Comparing the cytotoxicity of taurolidine, mitomycin C, and oxaliplatin on the proliferation of in vitro colon carcinoma cells following pressurized intra-peritoneal aerosol chemotherapy (PIPAC).

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Scintigraphic peritoneography reveals a non-uniform 99mTc-Pertechnetat aerosol distribution pattern for Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a swine model.

BACKGROUND: Although recent data are contradictory, it is still claimed that Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) would deliver an aerosol which distributes homogeneously throughout the entire abdominal cavity. METHODS: 99mTc-Pertechnetat was administered in four postmortem swine using either PIPAC or liquid intra-peritoneal chemotherapy (IPC). The animals were examined by planar scintigraphy and SPECT/CT. Planar distribution images were divided into four regions of interest (ROIs: right/left upper and lower abdominal quadrant). SPECT/CT slices were scanned for areas of intense nuclide accumulation ("hot spots"). The percentage of relative distribution for planar scintigraphy was calculated by dividing the summed individual counts of each ROI by total counts measured in the entire abdominal cavity. The relative distribution of the "hot spots" was analyzed by dividing the counts of the local volume of interest (VOI) by the summed volume counts measured in the entire abdominal cavity. RESULTS: In all four animals, planar scintigraphy showed inhomogeneous nuclide distribution. After PIPAC only 8-10% of the delivered nuclide was detected in one ROI with a mean deviation of 40% and 74% from a uniform nuclide distribution pattern. In all animals, SPECT/CT revealed "hot spots" beneath the PIPAC Micropump, catheter tip, and in the cul-de-sac region which comprise about 25% of the total amount of delivered nuclide in 2.5% of the volume of the entire abdominal cavity. CONCLUSIONS: Our present data indicate that the intra-abdominal aerosol distribution pattern of PIPAC therapy is non-homogeneous and that the currently applied technology has still not overcome the problem of inhomogeneous drug distribution of IPC.

Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing. ANALYTICAL METHODS: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated. RESULTS: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm. CONCLUSIONS: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.

Cytotoxic effect of different treatment parameters in pressurized intraperitoneal aerosol chemotherapy (PIPAC) on the in vitro proliferation of human colonic cancer cells.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Exploring the Spatial Drug Distribution Pattern of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach to delivering intraperitoneal chemotherapy (IPC) as a pressurized aerosol. One of the assumed advantages is the homogeneous drug distribution in the intraperitoneal cavity compared with conventional liquid in situ chemotherapy. However, to date, the spatial drug distribution pattern of PIPAC has not been investigated in detail. METHODS: Doxorubicin was aerosolized in an ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum at a pressure of 12 mmHg CO2 at 36 °C. In the center of the top cover of the PIPAC chamber, a PIPAC micropump was installed. Tissue specimens were placed as follows: (A) bottom of the plastic box, (B) margin of the aerosol jet covered with a bilaterally open tunnel, (C) side wall, and (D) top cover, respectively. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: The depth of doxorubicin penetration was found to be significantly higher in tissues directly exposed to the aerosol jet (A: 215 ± 79 µm) compared with the side wall (C: 77 ± 18 µm; p < 0.01) and the top of the box (D: 65 ± 17 µm; p < 0.01). The poorest penetration was observed for peritoneal tissue covered under a bilaterally open plastic tunnel (B: 34 ± 19 µm; p < 0.001). CONCLUSIONS: The study data suggest that the spatial drug distribution pattern of ex vivo PIPAC is heterogeneous.

Exploring the potential of taurolidine in inducing mobilization and detachment of colon cancer cells: a preliminary in-vitro study.

BACKGROUND: Recently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure. METHODS: HT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay. RESULTS: Both taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent. CONCLUSIONS: Beside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.

Evaluating the concept of gas­based intraperitoneal hyperthermia beyond 43˚C in the treatment of peritoneal metastasis: A pilot study.

While hyperthermic intraperitoneal applications have demonstrated high efficacy in treating peritoneal metastases (PM), these applications are limited to temperatures of 41-43˚C to prevent a harmful increase in core temperature. However, since gaseous substances display low specific heat capacities, gas-based hyperthermia could potentially increase surface temperatures without affecting the body's core temperature. To the best of our knowledge, the present study is the first to explore the in vivo feasibility of gas-based hyperthermia via spatial and time-based distribution. In the present study, a temperature-isolated, abdominal box model was created with fresh peritoneal tissue exposed to continuous high-volume airflow temperatures ranging between 47 and 69˚C. Heat conduction within the peritoneal tissues was measured using temperature microsensors. Temperature build-up at different time points during the procedure was calculated and the safest option to perform gas-based intraperitoneal hyperthermia beyond 43˚C was identified using an in vivo swine model. In subsequent experiments, viability and cytotoxicity of HT-29 colon cancer cells were measured following short-term hyperthermia. The present study demonstrated that the application of gas-based intraperitoneal hyperthermia with temperatures up to 50˚C is possible without increasing the core temperature to harmful levels. Gas-based intraperitoneal hyperthermia can induce a histological reaction on the peritoneal surface, and it can also result in decreased viability and increased cytotoxicity of HT-29 cells. The concept of extreme hyperthermia may be of great clinical importance as it could significantly increase local cytotoxicity in PM without increasing the body's core temperature. Further studies are required to investigate the benefits, as well as the restrictions, of this novel concept.

Safety, feasibility, and application of intraperitoneal gas-based hyperthermia beyond 43°C in the treatment of peritoneal metastasis: An in-vivo pilot study.

Background: 43°Celsius (C) is currently the highest temperature used in the treatment of peritoneal metastasis (PM). Despite sufficient data on water- based hyperthermic solutions in PM treatment, there is currently no information on gas-based hyperthermia extending beyond 43°C. This study is the first to provide in-vivo data on different organ systems during and after intraperitoneal gas-based hyperthermia beyond 43°C. The aim of this study is to explore in-vivo feasibility, safety, and efficacy of this novel concept from a biological perspective. Methods: For this study, three swine were subjected to laparoscopy and subsequent gas-based intraperitoneal hyperthermia at 48°, 49° and 50°C under a high-flow air stream. Intraoperative data from multiple temperature sensors were analysed. Additionally, intraoperative anaesthesiologic and gasometrical data was analysed. Postoperatively, swine were monitored for one week and laboratory work-up was performed on postoperative days 1, 3 and 7. Results: During gas-based intraperitoneal hyperthermia, anesthesiologic parameters did not exhibit critical values. No intra- or postoperative complications were observed. Distinct temperature measurements on the skin, cystohepatic triangle and esophagus did not display any temperature increase. Postoperative laboratory workup did not show any changes in hemoglobin, white blood cell count, platelets, or kidney function. Discussion: Based on our data, there are no safety concerns for the application of gas-based hyperthermia between 48 - 50°C. In fact, no critical systemic temperature increase was observed. With respect to possible limitations, further in-vivo studies are required to evaluate whether gas-based intraperitoneal hyperthermia may be a therapeutic option for PM patients.

In-vivo thermodynamic exploration of gas-based intraperitoneal hyperthermia.

Background: While hyperthermic intraperitoneal (i.p) applications are highly efficient in treating peritoneal metastases (PM), they are currently limited to temperatures of 41 - 43° Celsius (C). First data on gas-based i.p. hyperthermia is promising, as this novel method allows a significant temperature rise in superficial peritoneal layers without increasing core temperatures. Until now, key mechanisms of this novel tool, e.g. thermodynamic energy transfer, have not been investigated. This study aims to explore the volume of thermodynamic energy transfer during gas-based i.p. hyperthermia at 48-50°C and its peritoneal effects. Methods: For this study, three swine were subjected to gas-based i.p. hyperthermia at varying temperatures (48°, 49° and 50°C) in a diagnostic laparoscopy setting with a high-flow air stream. Temperatures of the i.p. cavity, in- and outflow airstream at the trocar were measured and the thermodynamic energy transfer was calculated. Tissue samples were collected on postoperative day 7 for histopathologic analyses. Results: According to our data, temperatures within the intraabdominal cavity and at the outflow site remain relatively stable at < 40°C. An increase in thermodynamic energy transfer is observed with increasing applied temperatures. Gas-based i.p. hyperthermia induced capillary coagulation and white blood cell infiltration within peritoneal layers. Conclusions: Gas-based i.p. hyperthermia is an innovative approach which enables the i.p. delivery of specific amounts of thermodynamic energy. Following this procedure, our data indicate remarkable histologic changes on the superficial peritoneal layer most likely attributable to the applied thermodynamic energy. Further studies are required to investigate how these findings can be applied in PM management.

The Onset of In-Vivo Dehydration in Gas -Based Intraperitoneal Hyperthermia and Its Cytotoxic Effects on Colon Cancer Cells.

Background: Peritoneal metastasis (PM) is an ongoing challenge in surgical oncology. Current therapeutic options, including intravenous and intraperitoneal (i.p.) chemotherapies display limited clinical efficacy, resulting in an overall poor prognosis in affected patients. Combined hyperthermia and dehydration induced by a high-flow, gas-based i.p. hyperthermic procedure could be a novel approach in PM treatment. Our study is the first to evaluate the therapeutic potential of i.p. dehydration, hyperthermia, as well as the combination of both mechanisms in an in-vivo setting. Methods: For this study, three swine were subjected to diagnostic laparoscopy under a high-flow air stream at 48°, 49° and 50°Celsius (C). Hygrometry of the in- and outflow airstream was measured to calculate surface evaporation and i.p. dehydration. To analyze the effects of this concept, in vitro colon cancer cells (HT-29) were treated with hyperthermia and dehydration. Cytotoxicity and cell viability were measured at different time intervals. Additionally, structural changes of dehydrated cells were analyzed using scanning electron microscopy. Results: According to our results, both dehydration and hyperthermia were cytotoxic to HT-29 cells. However, while dehydration reduced cell viability, hyperthermia did not. However, dehydration effects on cell viability were significantly increased when combined with hyperthermia (p<0.01). Conclusions: Changes to the physiological milieu of the peritoneal cavity could significantly reduce PM. Therefore, limited dehydration of the abdominal cavity might be a feasible, additional tool in PM treatment. Further studies are required to investigate dehydration effects and their applicability in PM management.

Structural risk analysis of a potential Ebola outbreak with respect to infrastructural aspects amid the current COVID-19 pandemic.

Due to the ease and increased volume of global interaction, it remains unclear whether the current coronavirus disease (COVID-19) pandemic will be a one-off event or whether the world is at risk of recurrent pandemics as a result of globalization. To address this important issue, the present study assessed the risk of a possible future Ebola pandemic. The risk profile of Hubei province in China was compared with that of the Democratic Republic of Congo (DRC) in terms of travel and infrastructure, since DRC is considered a major epicenter for Ebola outbreaks. Recurrence patterns of previous Ebola outbreaks were analyzed in a cumulative outbreak model. Internationally available data on air traffic, flight destinations, passenger numbers, population density, distribution and domestic traffic routes were all analyzed and compared between the DRC and Hubei province. DRC is a major epicenter for Ebola outbreaks, with 13 recorded outbreaks from 1976 until 2020. International airports at both Kinshasa, the capital city of the DRC and Wuhan, the capital city of Hubei province, are heavily frequented destinations and represent major transfer hubs on their respective continents. Volumes of flights to and from extracontinental destinations account for <25% of total flights at both airports with similar total international passenger volumes. However, the volume of domestic commuting by aviation is >30-fold higher at Hubei province compared with that of the DRC. This finding is also reflected by the higher population density and homogeneity in terms of population per square kilometer in Hubei. Following the analysis of decades of Ebola reports, it became evident that the DRC remains a hotspot for potential Ebola outbreaks in the future due to constantly recurrent local outbreaks. In terms of the international aviation network, numerous important similarities between Kinshasa and Hubei Province were observed as regards connectivity. The present comparative analysis extends beyond biological factors underlying Ebola and COVID-19 transmissions and confirms that the DRC, Kinshasa in particular, is not a remote location. Although internal commuting and population density may be lower in the DRC compared with those in Hubei province, integration into the international aviation network is similarly extensive. The international community must increase its focus and efforts in preventing another possible global pandemic commencing in Africa, and in particular the DRC.

The positive impact of lockdown in Wuhan on containing the COVID-19 outbreak in China.

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.

Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure.

Background: Nanocrystallization is a promising field for the development of new drugs. This study aims to present the use of nanocrystallization via intraperitoneal nanoaerosol therapy (INAT) for the treatment of peritoneal metastases. Methods: A continuous aerosol generation device was used to aerosolize a highly concentrated doxorubicin solution within a dry CO2 environment. The produced nanoaerosol was directed into an ex vivo abdominal model and collision of aerosol particles with placed samples was subject to further analysis via scanning-electron microscopy (SEM). SEM detected structural changes of particles caused by migration to different locations. Results: It was possible to visualize the contact of doxorubicin aerosol particles with the surface. Larger particles as well as particles closer to the aerosol generation chamber collided with the glass sample creating liquid drops, while smaller particles with more distance to the aerosol chamber collided as highly concentrated nanocrystals. The amount of nanocrystal particles outweighed the amount of fluid aerosol particles by far. Conclusions: Under optimal conditions, the formation of nanocrystals via aerosol creation device is possible. While a wide range of possible applications of nanocrystals is conceivable, surface coating with drug particles is especially interesting as it may serve as an alternative to conventional liquid intraperitoneal chemotherapy. Further studies are required to investigate nanocrystallization of chemotherapeutic solutions as well as its physical and pharmacological properties and side effects.

Intraperitoneal chemotherapy of the peritoneal surface using high-intensity ultrasound (HIUS): investigation of technical feasibility, safety and possible limitations.

Introduction: The penetration of chemotherapeutic drugs into peritoneal nodules remains at levels well below 1 mm, thus significantly limiting the antitumor effect of intraperitoneal chemotherapy (IPC). Recently, high-Intensity ultrasound (HIUS) has been discovered as a potential tool to significantly improve peritoneal diffusion rates. Despite promising preliminary data, basic aspects regarding its technical feasibility, safety and possible limitations remain unclear. This study aims to enhance our current understanding of HIUS and test its applicability using an ex-vivo swine model. Methods: Three postmortem swine were subject to laparotomy and consecutive lavage with 0.9%NaCl saline and HIUS application. For this purpose, a large HIUS radiating pen was introduced into the abdominal cavity and HIUS was applied on two of the four abdominal quadrants for 300 seconds each at an output power of 70 W, 50 % amplitude and 20 kHz frequency. Following the procedure, small intestinal tissue samples were retrieved for further analyses. Results: Peritoneal and subperitoneal layers showed structural changes only visible on a microscopic level. The peritoneal layer was transformed into a mesh-like structure while the subperitoneal layer (depth of 142 +/- 28 µm) exhibited microcavities and vascular detachment from surrounding tissues. No bowel rupture or vascular perforations were observed. Conclusions: Our data indicate that HIUS is a technically feasible and safe add-on procedure for intraperitoneal chemotherapy (IPC) with measurable microscopic changes on the peritoneal surface. Pretreatment of the abdominal cavity with HIUS could significantly improve IPC efficacy. Further studies are required to optimize and evaluate this novel approach.