Severe skin and soft tissue infection in cohort patients admitted in a teaching hospital in Belgium: identification of risk factors for surgery.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are associated with significant mortality if not promptly diagnosed and surgically treated. AIM: This study aims to compare patients with severe skin and soft tissue infection treated with or without a surgical intervention and to identify risk factors that can predict the need for early surgery. METHODS: Demographics, clinical, laboratory, Risk Indicator for Necrotizing Fasciitis (LRINEC) and imaging results were retrospectively collected. RESULTS: There were 91 non-NSTI (group 1), 26 NSTI who were operated (group 2) and eight suspected NSTI who were not operated (group 3). In the multivariate analysis, skin necrosis, tachycardia, CRP value and hyperglycemia were predictive for surgery. A performance analysis revealed AUC of 0.65 (95%CI: 0.52-0.78) as to the LRINEC score for the use of surgery. The AUC for a predictive model associating four variables (heart rate, skin necrosis, CRP and glycemia at admission) was 0.71 (95%CI: 0.59-0.84). In terms of outcome, the median length of stay (LOS) was statistically higher in group 2 vs. group 1 (seven days (5-15) vs. 34 days (20-42), p < .001) and in group 2 vs. group 3 (34 days (20-42) vs. 14 days (11-19), p = .005). The overall in-hospital mortality at 30 days was 3.2% and did not statistically differ between the three groups. CONCLUSIONS: Although the LRINEC score performed well in predicting surgery, the AUC of a model combining four predictive variables (glycemia, skin necrosis, CRP and heart rate) was superior. Further research is needed to validate this model.

Long COVID and return to work: a qualitative study.

BACKGROUND: The COVID-19 pandemic has given rise to an increasing number of patients with 'long COVID'. Long COVID is the persistence of symptoms for weeks or months after an infection by SARS-CoV-2. It often impacts on the professional life of affected people. AIMS: The aim of this study is to understand the experiences and needs of people with long COVID in relation to their return to work. METHODS: A qualitative study, combining individual interviews and online forum discussions, was performed early 2021, as part of a larger mixed method study on the needs of long COVID patients in Belgium. RESULTS: One hundred and thirty-four people participated in the study. Participants described various clinical symptoms precluding their return to work. They also face sceptical reactions from employers and colleagues and a lack of support from the social welfare system to facilitate their return to work. These barriers have various impacts, including psychological ones, likely to compromise the professional future of long COVID patients. CONCLUSIONS: While the analysis of patients' experiences shows variation in long COVID patients' experiences with return to work, it may help occupational physicians and healthcare practitioners to better take up their crucial role in the return to work of long COVID patients, including raising employers' and colleagues' awareness of the specific difficulties related to long COVID.

Pathophysiology and mechanism of long COVID: a comprehensive review.

BACKGROUND: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as "long COVID", and it was defined more recently as "Post COVID-19 condition" by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic. AIM: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID. METHOD: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation. RESULTS: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far. CONCLUSION: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGESLong-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.

Spontaneous Cervical Epidural Hematoma.

BACKGROUND: A 65-year-old woman was admitted to the emergency department for sudden onset of neck pain and dysesthesia of both upper limbs. The pain occurred spontaneously, without any history of recent trauma. Rapidly after her admission, she developed tetraparesia. The patient had a past medical history of long standing hypertension correctly controlled as confirmed at admission. Neurological examination confirmed the tetraparetic status with a sensory level at Th3. Moreover, a saddle anesthesia with impaired bladder control was observed. Cranial nerve examination and consciousness of the patient remained normal. Laboratory coagulation tests and platelets count were all within normal limits.

Toll-like receptor 4 modulation as a strategy to treat sepsis.

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

Adjunctive therapies for severe sepsis.

Severe sepsis-associated mortality may still be improved by earlier recognition, faster and adequate source control, and targeted resuscitation. Patients who may benefit from the administration of drotrecogin alfa (activated) are currently those at high risk of death, and other indications should be better defined by ongoing trials. Use of low-dose steroids for the treatment of severe sepsis must be re-clarified by new studies and should be restricted to patients with refractory septic shock. Trials exploring the role of natural anticoagulants and Toll-like receptor inhibitors are ongoing and should be completed in the coming 3 years. Future trials in severe sepsis should target more homogeneous populations with a well-defined focus of infection and severity, receiving appropriate standard of care, and the tested intervention should be administered in a timely fashion according to the expected host response.

The tetraspanin CD9 associates with the integrin alpha6beta4 in cultured human epidermal keratinocytes and is involved in cell motility.

Integrins are involved in several ways in keratinocyte physiology, including cell motility. CD9 is a member of the tetraspanin protein family which is found in association with other transmembrane proteins like the integrins. CD9 is expressed in the epidermal tissue, but this expression is not regulated by differentiation. The present work focuses on association of CD9 with the integrin alpha6beta4 in keratinocytes. In vivo, CD9 does not co-localize with alpha6beta4, and is not internalized with the integrin upon basal detachment with dispase. In vitro, CD9 is found partly in co-localization with alpha6beta4 and is internalized with the integrin after keratinocyte detachment with dispase. Using blocking antibodies in a phagokinetic tracks assay, we show that CD9, and to a lesser extent alpha6beta4, but not the tetraspanin CD82, promote motility of subconfluent keratinocytes on collagen I. Our observations also suggest that CD9 is involved in the formation of lamellipodia. We also report that the phorbol ester TPA has no effect on CD9 expression and association with alpha6beta4, but increases keratinocyte motility, possibly through modulation of integrin subunits expression, or through upregulation of collagenase-1 expression. Together, these results confirm that CD9 associates with alpha6beta4 in cultured keratinocytes, possibly in order to regulate the function of the integrin, and that CD9 is involved in keratinocyte motility on collagen. The data suggest that regulation of adhesion characteristics by CD9 in keratinocytes may play a role in epidermal repair.

A crown for clinically investigating microleakage.

This investigation evaluated a cast crown with an access port for in vivo microleakage studies. Fifteen complete cast crowns containing an access port in the facial surface were cast. The gingival margins of the crowns were modified to test the sealing ability of the access port. Each casting was thermocycled 750 times at 5 degrees to 60 degrees C over a 24-hour period. Air pressure of 90 psi followed by 28 mm Hg vacuum was applied for 1 hour each during immersion of the devices in silver nitrate solution. Castings were embedded in acrylic resin and sectioned with a diamond saw through the sealing device. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed no leakage with the 13 test devices and 100% leakage with the controls. The device should be effective for use in human subjects.

Pharmacokinetic approach of plafibride in rat.

The serum concentration of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) and its metabolites was measured in the rat after oral and intravenous administration of the drug. Plafibride was distributed in the rat according to an open two-compartment model. Moreover, 2-(p-chlorophenoxy)isobutyrylurea and clofibric acid were detected. In the urine, 81.7% of the administered dose was recovered in the form of free clofibric acid, 0.8% as plafibride itself and 1.1% as 2-(p-chlorophenoxy)isobutyrylurea. The amount of plafibride and its metabolites present in the feces was practically negligible. A mechanistic scheme for the degradation of plafibride is proposed, which agrees with the observed pharmacological and pharmacokinetic data.