Cold plasma treatment is safe for diabetic foot ulcers and decreases Staphylococcus aureus bacterial load.

AIM: Cold atmospheric plasma (CAP) has antimicrobial properties. We studied the safety of a novel CAP device (PLASOMA prototype; Plasmacure, The Netherlands) that is simple to use and could be applied at a patient's home for the treatment of diabetic foot ulcers (DFUs). Secondary objectives were to investigate the effect of CAP on bacterial load and on ulcer size. METHOD: We included subjects with non-infected, superficial DFUs and treated them with CAP on a daily basis for 10 days. The primary endpoint was the occurrence of serious adverse device effects (SADE). We defined safety as: ≤10% of patients experiencing a SADE other than infection (non-infectious SADE), and ≤60% of patients developing infection of the foot (infectious serious adverse event (SAE)). RESULTS: We enrolled 20 patients. No SADE occurred, but three infectious SAEs occurred at the site of application within one month of treatment; three SAEs unrelated to treatment occurred, and 55% of subjects reported transient mild adverse device effects. Staphylococcus aureus bacterial load decreased directly after CAP application (p=0.01). The mean decrease of ulcer surface area was 43% (95% confidence interval: 20.2%-65.9%). CONCLUSION: CAP treatment in DFUs was safe and well tolerated. Ulcer size and Staphylococcus aureus colonisation decreased during treatment.

The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis.

In this study, we assessed the effectiveness of inflammatory markers to diagnose and monitor the treatment of osteomyelitis in the diabetic foot. We evaluated 35 consecutive patients admitted to our hospital with infected foot ulcers. Patients were divided in two groups based on the results of bone culture and histopathology: osteomyelitis and no osteomyelitis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNFα), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP1α) were measured at baseline after 3 and 6 weeks of standard therapy. PCT levels in the osteomyelitis group were significantly higher at baseline than in the group with no osteomyelitis (P = 0·049). There were no significant differences between the two groups in the levels of the other markers. CRP, ESR, PCT and IL-6 levels significantly declined in the group with osteomyelitis after starting therapy, while MCP-1 increased (P = 0·002). TNFα and MIP1α levels were below range in 80 out of 97 samples and therefore not reported. Our results suggest that PCT might be useful to distinguish osteomyelitis in infected foot ulcers. CRP, ESR, PCT and IL-6 are valuable when monitoring the effect of therapy.

How does SARS-CoV-2 targets the elderly patients? A review on potential mechanisms increasing disease severity.

IMPORTANCE: Among COVID-19 cases, especially the (frail) elderly show a high number of severe infections, hospital admissions, complications, and death. The highest mortality is found between 80 and 89 years old. Why do these patients have a higher risk of severe COVID-19? In this narrative review we address potential mechanisms regarding viral transmission, physical reserve and the immune system, increasing the severity of this infection in elderly patients. OBSERVATIONS: First, the spread of COVID-19 may be enhanced in elderly patients. Viral shedding may be increased, and early identification may be complicated due to atypical disease presentation and limited testing capacity. Applying hygiene and quarantine measures, especially in patients with cognitive disorders including dementia, can be challenging. Additionally, elderly patients have a decreased cardiorespiratory reserve and are more likely to have co-morbidity including atherosclerosis, rendering them more susceptible to complications. The aging innate and adaptive immune system is weakened, while there is a pro-inflammatory tendency. The effects of SARS-CoV-2 on the immune system on cytokine production and T-cells, further seem to aggravate this pro-inflammatory tendency, especially in patients with cardiovascular comorbidity, increasing disease severity. CONCLUSIONS AND RELEVANCE: The combination of all factors mentioned above contribute to the disease severity of COVID-19 in the older patient. While larger studies of COVID-19 in elderly patients are needed, understanding the factors increasing disease severity may improve care and preventative measures to protect the elderly patient at risk for (severe) COVID-19 in the future.

Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine.

OBJECTIVE: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. METHODS: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. RESULTS: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. CONCLUSIONS: After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.