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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.

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

Pressurized intrathoracic aerosol chemotherapy (PITAC) has been introduced to the clinical setting as a novel treatment option for pleural metastasis (PM). For decades the therapeutic application of aerosols was limited to intrabronchial delivery. However, present studies suggest performing PITAC on patients with PM and malignant pleural effusion. Using an established ex vivo swine model, the present study aimed to introduce a facilitated intrathoracic chemoaerosol application via spray-catheter. Using an ex-vivo model of 3 postmortem swine, the feasibility of intrathoracic aerosol chemotherapy (ITC) with doxorubicin using a spray-catheter was evaluated in a normal pressure environment. Following thoracotomy, the spray-catheter was inserted via trocar. Tissue samples were retrieved and further analyzed by fluorescence microscopy to detect doxorubicin contact. Our data demonstrated that the application of ITC was technically feasible and did not exhibit any significant obstacles. By making a minimally invasive thoracotomy incision it was possible to create an adequate pneumothorax without the need of a double-lumen tube or intubation. ITC did not require the creation of a pressurized environment. Tissue samples revealed doxorubicin contact within the pleura. In conclusion, ITC is a fast and feasible procedure that could possibly be administered via bedside application, therefore eliminating the need of an operating room and surgical staff. However, further studies are required to evaluate the safety of patients and physicians regarding this novel applicational modality. Nevertheless, the present study demonstrated that ITC may potentially be applied at bedside, an option that is particularly important for patients who do not qualify for PITAC procedures.

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.

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.

The present ex vivo study was performed to analyze the impact of high intensity ultrasound (HIUS) on penetration depth and particle stability of liposomal doxorubicin (LD) on the peritoneal surface. Fresh post mortem swine peritoneum was cut into proportional sections and subjected to a previously established ex vivo model of pressurized intraperitoneal aerosol chemotherapy (PIPAC). Samples were treated with 50 ml NaCl (0.9%) containing 3 mg LD via PIPAC or lavage. In both groups, half of the samples received additional HIUS treatment. Samples treated via PIPAC were covered with a 30-mm-thick abdominal muscle wall tissue, fatty tissue and skin, followed by transcutaneous HIUS. Samples administered with LD via lavage received close-range contact HIUS. Doxorubicin tissue penetration was measured using fluorescence microscopy on frozen sections. Liposomal integrity on peritoneal surfaces was measured via electron microscopy (EM). Mean penetration rates of doxorubicin were significantly higher with HIUS in combination with PIPAC or lavage compared with PIPAC alone (P

Background: Ethylenediaminetetraacetic acid (EDTA), a commonly used compound in laboratory medicine, is known for its membrane-destabilization capacity and cell-detaching effect. This preliminary study aims to assess the potential of EDTA in removing residual tumor cell clusters. Using an in-vitro model, this effect is then compared to the cytotoxic effect of oxaliplatin which is routinely administered during HIPEC procedures. The overall cell toxicity and cell detaching effects of EDTA are compared to those of Oxaliplatin and the additive effect is quantified. Methods: HT-29 (ATCC® HTB-38™) cells were treated with A) EDTA only B) Oxaliplatin only and C) both agents using an in-vitro model. Cytotoxicity and cell detachment following EDTA application were measured via colorimetric MTS assay. Additionally, detached cell groups were visualized using light microscopy and further analyzed by means of electron microscopy. Results: When solely applied, EDTA does not exhibit any cell toxicity nor does it add any toxicity to oxaliplatin. However, EDTA enhances the detachment of adherent colon carcinoma cells by removing up to 65% (p Conclusions: Our data support EDTA’s potential to remove microscopical tumor cell clusters from the peritoneum and possibly act as a supplementary agent in HIPEC procedures with chemotherapy. While adding EDTA to HIPEC procedures may significantly decrease the risk of PM recurrence, further in-vivo and clinical trials are required to evaluate this effect.

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 0.05) 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.

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has been introduced to the clinical setting as a novel approach for the treatment of peritoneal metastasis. The local interaction of chemoaerosol droplets with the peritoneal surface as well as their distribution pattern is considered the main advantage over conventional liquid intraperitoneal chemotherapy. The aim of the present study was to investigate the behavior of these aerosol particles during PIPAC application via electron microscopy. Solutions of doxycycline, liposomal doxorubicin and macrophage cells were aerosolized using an established ex-vivo model. PIPAC was performed on peritoneum samples via microcatheter (MC) at a pressure of 12 mmHg C02 at 27°C. Following PIPAC the surface structure of applied particles was measured via electron microscopy. The aerosol particle contact of doxycyclin created a nanofilm of ~200 nm height on the peritoneal surface, and this height was revealed to be independent of the size of the initial particle hitting. These nanofilm blocks of ‘cylinders’ are of different diameters depending on the initial aerosol particle hitting that spot. Diameters of these ‘cylinders’ are far wider than the original diameter of the initial aerosol particle. However, coated particles such as liposomal doxorubicin and macrophages remained intact following contact with the peritoneal surface. Based on this and other data, the concept that aerosol particles exhibit a gas-like behavior in the abdomen creating a therapeutic capnoperitoneum should be revised. Fluid aerosol particles collide with the peritoneum creating a nanofilm. The interaction of pressurized intraperitoneal aerosol on the peritoneum is therefore closer to the distribution of a liquid film than to that of a gas. Further studies are required to further analyze the interaction of this nanofilm on the peritoneum.

Background. High‐intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. This treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. This study was performed to evaluate whether HIUS improves chemotherapy penetration rates. Methods. High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. Results. Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. Conclusion. Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.

Purpose Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. Methods Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. Results The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. Conclusions To the best of the authors’ knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.

Perineal hernia is an uncommon complication following abdominoperineal rectum resection. Several surgical procedures have been proposed for perineal hernia repair, including perineal, laparoscopic and abdominal approaches. Repair techniques can be classified into primary suture techniques, mesh placements and repairs with autogenous tissue. We report a 68-year-old man with a perineal hernia, who underwent a pelvic floor reconstruction with a transperineal composite mesh and a gluteal fasciocutaneous rotation flap. We conclude that a combined approach with transperineal mesh reconstruction and gluteal fasciocutaneous flap could be an alternative choice in perineal hernia repair after abdominoperineal resection.