Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization

Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists’ increased adherence to guidelines and “bundles”. The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment.Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization

Targeted online liquid chromatography electron capture dissociation mass spectrometry for the localization of sites of in vivo phosphorylation in human Sprouty2

We demonstrate a strategy employing collision-induced dissociation for phosphopeptide discovery, followed by targeted electron capture dissociation (ECD) for site localization. The high mass accuracy and low background noise of the ECD mass spectra allow facile sequencing of coeluting isobaric phosphopeptides, with up to two isobaric phosphopeptides sequenced from a single mass spectrum. In contrast to the previously described neutral loss of dependent ECD method, targeted ECD allows analysis of both phosphotyrosine peptides and lower abundance phosphopeptides. The approach was applied to phosphorylation analysis of human Sprouty2, a regulator of receptor tyrosine kinase signaling. Fifteen sites of phosphorylation were identified, 11 of which are novel

'Monolateral' superior vena cava syndrome: right internal jugular vein occlusion

Superior vena cava syndrome is characterised by dyspnoea, headache, facial oedema, and venous distention in the neck, upper chest and arms. These symptoms are bilateral. A 47-year-old woman reported the appearance of venous ectasias in the right side of her chest, face and neck. The patient was affected by systemic lupus erythematous with antiphospholipid syndrome and end-stage renal disease. She was on haemodialysis via a right subclavian central venous silicone, double-lumen, tunnelled catheter (central venous catheter, CVC) because of a previous thrombosis of arteriovenous fistula. Although this type of CVC has a higher risk of complications (ie, thrombosis), the reason of this choice was not clear, since the patient was treated at another haemodialysis service. At physical examination, the patient's clinical condition was discrete; right side of the face appeared slightly swollen; distension of the right external jugular vein and superficial ectasic veins of the right hemithorax were present (figure 1). Ultrasound scan showed a fibrotic right internal jugular vein, without Doppler signal. Neck and chest CT confirmed the lack of contrast enhancement of the right internal jugular vein in its distal tract (5.5 cm) until the confluence with the subclavian vein (figures 2A, B) and the presence of multiple ectasic veins of the subcutaneous tissue of the right anterior chest wall and neck (figures 3 and 4). The CVC was passing through the brachiocephalic vein to the right atrium

NCX 1236, a novel gabapentin endowed of nitric oxide-releasing properties, reverses the development of mechanical allodynia in streptozotocin-treated diabetic mice

NCX 1236 is a novel NO-donating gabapentin, shown to exert superior anti-allodynic activity compared to gabapentin in several models on neuropathic pain including streptozotocin (STZ)-induced painful diabetic neuropathy (PDN). Here we addressed whether the repeated daily dosing of NCX 1236 or gabapentin also affects the development of mechanical allodynia following STZ (200 mg/kg, ip) administration. More specifically, mechanical allodynia was monitored using the Dynamic Plantar Aesthesiometer prior to and after 7, 14 and 21days daily oral dosing with vehicle, gabapentin (30mg/kg, po) or equimolar NCX 1236 (71mg/kg, po) 24h after the last treatment to assure the absence of residual gabapentin exposure at the time the measurements were recorded. The latter was also confirmed by monitoring plasma gabapentin exposure after NCX 1236 and gabapentin treatment using a UPLC/MS/MS method. STZ increased plasma glucose levels within 24h post-injection and prompted the development of mechanical allodynia (threshold, 4.0±0.2 and 2.1±0.2 g, respectively in control and STZ-treated animals, p<0.05). Mechanical allodynia continued to decrease in animals receiving vehicle (threshold, 1.3±0.1g, at 21 days) or gabapentin (threshold, 1.8±0.3g, at 21 days). Conversely, NCX1236 resulted in a progressive reversal of the allodynic response which was evident 7 days after treatment (threshold, 3.2±0.2 g) and reached its maximum over the following weeks. Gabapentin and NCX1236 resulted in similar gabapentin plasma exposure following acute or repeated treatment schedule with an estimated Tmax of 30 min. Data suggest that NCX 1236, differently from gabapentin, hampers the development and maintenance of STZ-induced mechanical allodynia in mice. It remains to be established whether these effects are retained in higher species and diabetic patients