Rejected

Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ~6.5M people and cost ~$40B/year in the US alone. Although a significant effort has been invested in understanding how chronic wounds develop in humans, fundamental questions remain unanswered. Recently, we developed a novel mouse model for diabetic chronic wounds that have many characteristics of human chronic wounds. Using db/db mice, we can generate chronic wounds by inducing high levels of oxidative stress (OS) in the wound tissue immediately after wounding, using a one-time treatment with inhibitors specific to the antioxidant enzymes catalase and glutathione peroxidase. These wounds have high levels of OS, develop biofilm naturally, become fully chronic within 20 days after treatment and can remain open more for more than 60 days. This novel model has many features of diabetic chronic wounds in humans and therefore can contribute significantly to advancing fundamental understanding of how wounds become chronic. This is a major breakthrough because chronic wounds in humans cause significant pain and distress to patients and result in amputation if unresolved. Moreover, these wounds are very expensive and time-consuming to treat, and lead to significant loss of personal income to patients. Advancements in this field of study through the use of our chronic wound model can significantly improve health care for millions who suffer under this debilitating condition. In this protocol, we describe in great detail the procedure to cause acute wounds to become chronic, which has not been done before.

We describe here the case of a young patient, employed in agriculture, who entered the emergency room with fever, headache, hematuria and a worsening of renal function; we diagnosed leptospirosis with renal involvement. As the patient lamented very generic symptoms, the anamnesis was fundamental in leading us to suspect an infection, execute the right laboratory analysis, and correctly diagnose a pathology which is currently very rare in Italy.

Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD).

The number of laparoscopic cholecystectomies in the Netherlands has increased significantly in recent years. However, there is a large variation in practice. This is a sign of inefficient use of cholecystectomy. Cholecystectomy is the treatment of choice in patients with uncomplicated symptomatic gallstones, but 30% of the patients has persistent pain after surgery. In a large prospective multicentre randomised trial, a restrictive strategy was compared to usual care in patients with symptomatic gallstones. The results show suboptimal pain reduction in both groups. There were fewer cholecystectomies in the restrictive strategy group and no difference in gallstone related complications between the groups. It is therefore still unclear which patients with gallstones and abdominal symptoms should undergo cholecystectomy. The data could be used in new studies to construct algorithms for patient selection. In the meantime, the use of a decision aid is recommended. Well-informed patients can, in consultation with their doctors, opt for cholecystectomy or a conservative approach. This strategy will lead to fewer unnecessary cholecystectomies.

Lumbar spondylolisthesis is usually asymptomatic. However, symptomatic spondylolisthesis results in back and/or leg pain such as radicular syndrome or neurogenic claudication. Variation in symptoms is caused by different types of spondylolisthesis. Lytic spondylolisthesis, most common at L5S1, is caused by spondylolysis of the pars interarticularis. This results in foraminal nerve compression and radicular symptoms. Degenerative spondylolisthesis, most common at L4L5 in patients >50 years old, is caused by slippage of the vertebral body and lamina, resulting in lumbar spinal stenosis and neurogenic claudication. Iatrogenic spondylolisthesis develops in 1.6-32.0% of patients after decompression surgery, causing recurrent neurogenic symptoms. It is important to understand the main symptoms patients experience: back or leg pain. In both cases, the preferred treatment is conservative. Surgery is only an option if patients have persistent/progressive leg pain. Shared decision-making is necessary to select the most accurate surgery for each individual patient while also taking into account age, comorbidities and symptoms. Further research is necessary to determine the advantages of each surgery in order to improve advice to patients.

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal dysfunction after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) and CKD upstaging were compared between general anesthetic agent groups (propofol, sevoflurane, and desflurane). Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs. sevoflurane; propofol vs. desflurane; sevoflurane vs. desflurane; propofol vs. volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of new-onset CKD between groups up to 36 months after nephrectomy. Propofol was associated with a lower incidence of AKI (propofol 23.2% vs. sevoflurane 39.5%, = 0.004; vs. propofol 21.0% vs. desflurane 34.3%, = 0.031), a lower incidence of CKD upstaging (propofol 27.2% vs. sevoflurane 58.4%, < 0.001; propofol 32.4% vs. desflurane 48.6%, = 0.017) and better three-year renal survival after nephrectomy compared to sevoflurane or desflurane group (Log-rank test propofol vs. sevoflurane < 0.001; vs. desflurane = 0.015) after matching. Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching ( < 0.001). There were no significant differences between sevoflurane and desflurane. However, subgroup analysis of partial nephrectomy showed a significant difference only in CKD upstaging. In conclusion, propofol, compared to volatile agents, could be a better general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. However, limitations of the retrospective study design and inconsistent results of the subgroup analysis preclude firm conclusions.

Acne vulgaris is a common inflammatory pilosebaceous condition that affects 80-90% of adolescents. Since the introduction of tretinoin over 40 years ago, topical retinoid products have been a mainstay of acne treatment. The retinoids are very effective in addressing multiple aspects of the acne pathology as they are comedolytic and anti-inflammatory, and do not contribute to antibiotic resistance or microbiome disturbance that can be associated with long-term antibiotic therapies that are a common alternative treatment. However, topical retinoids are associated with skin dryness, erythema and pain, and may exacerbate dermatitis or eczema. Thus, there is a clear need to target delivery of the retinoids to the pilosebaceous units to increase efficacy and minimise side effects in surrounding skin tissue. This paper reviews the current marketed topical retinoid products and the research that has been applied to the development of targeted topical delivery systems of retinoids for acne.

Cervical spondylotic myelopathy (CSM) is a progressive degenerative pathology that frequently affects older individuals and causes spinal cord compression with symptoms of neck pain, radiculopathy, and weakness. Anterior decompression and fusion is the primary intervention to prevent neurological deterioration; however, in severe cases, circumferential decompression and fusion is necessary. Published data regarding perioperative morbidity associated with these complex operations are scarce. In this study, the authors sought to add to this important body of literature by documenting a large single-surgeon experience of single-session circumferential cervical decompression and fusion.

Students re-entering the academic setting after a concussion is commonly referred to as return-to-learn and, to date, very few studies have examined the return-to-learn aspect of concussion recovery.

Tranexamic acid (TXA) is an antifibrinolytic drug. Topical administration of TXA during total knee arthroplasty (TKA) is favored for certain patients because of concerns about thrombotic complications, despite a lack of supporting literature. We compared local and systemic levels of thrombogenic markers, interleukin (IL)-6, and TXA between patients who received intravenous (IV) TXA and those who received topical TXA.