Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department

Clinical and Experimental Medicine - The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This...     

Atrioventricular canal defect in patients with RASopathies

Congenital heart defects affect 60-85% of patients with RASopathies. We analysed the clinical and molecular characteristics of atrioventricular canal defect in patients with mutations affecting genes coding for proteins with role in the RAS/MAPK pathway. Between 2002 and 2011, 101 patients with cardiac defect and a molecularly confirmed RASopathy were collected. Congenital heart defects within the spectrum of complete or partial (including cleft mitral valve) atrioventricular canal defect were diagnosed in 8/101 (8%) patients, including seven with a PTPN11 gene mutation, and one single subject with a RAF1 gene mutation. The only recurrent mutation was the missense PTPN11 c.124 A>G change (T42A) in PTPN11. Partial atrioventricular canal defect was found in six cases, complete in one, cleft mitral valve in one. In four subjects the defect was associated with other cardiac defects, including subvalvular aortic stenosis, mitral valve anomaly, pulmonary valve stenosis and hypertrophic cardiomyopathy. Maternal segregation of PTPN11 and RAF1 gene mutations occurred in two and one patients, respectively. Congenital heart defects in the affected relatives were discordant in the families with PTPN11 mutations, and concordant in that with RAF1 mutation. In conclusion, our data confirm previous reports indicating that atrioventricular canal defect represents a relatively common feature in Noonan syndrome. Among RASopathies, atrioventricular canal defect was observed to occur with higher prevalence among subjects with PTPN11 mutations, even though this association was not significant possibly because of low statistical power. Familial segregation of atrioventricular canal defect should be considered in the genetic counselling of families with RASopathies.     

Reconstruction of a complex pelvic perineal defect with pedicled anterolateral thigh flap combined with bilateral lotus petal flap: A case report

Reconstructing extensive perineal defects represents a challenge, and reconstructive choice requires a careful physical assessment of previous radiotherapy, pre‐existing scars, the presence of stomas, and the availability of donor sites. We report a case of a patient affected by an anal carcinoma who underwent a pelvic exenteration and bilateral inguinal iliac obturator lymph node dissection. We performed a pedicled anterolateral thigh flap (ALT) combined with bilateral lotus petal flaps (LPF) to reconstruct the pelvic–perineal area. The result was good, and no major post‐operative complications were reported. Bilateral LPF, combined with a pedicled ALT, may represent a valid option in pelvic–perineal reconstruction following a wide oncological resection. © 2014 Wiley Periodicals, Inc. Microsurgery 35:154–157, 2015.     

Raynaud’s phenomenon in undifferentiated connective tissue disease (UCTD)

The aim of this study was to ascertain which clinical and immunological factors are associated with Raynauds phenomenon (RP) in patients with undifferentiated connective tissue disease (UCTD) and to investigate microvascular involvement. A total of 78 patients were evaluated. They all showed symptoms suggestive of a connective tissue disorder (CTD), but did not fulfil the criteria for any of the defined CTDs. They all had a disease duration of at least 1 year. Nailfold capillaroscopy (NC) was performed using a computerised videomicroscope. We diagnosed RP in 52.5% of our patients. Patients with RP showed a higher occurrence of oesophageal dysmotility (p=0.001) and anti-ribonucleoprotein (RNP) antibodies (p=0.004) than those without RP. The distinguishing capillaroscopic characteristics of UCTD patients with RP were widened and irregularly enlarged loops (75 and 55%, respectively), giant capillaries (35%), and less than two haemorrhages per finger (40%). The combination of features indicative of a slow scleroderma pattern was present in 18 of 40 patients with UCTD and RP (p=0.0003). Only 3 of the original 78 patients (3.8%) developed a definite CTD. In none of our patients did we observe avascular areas or changes from the original capillaroscopic pattern during follow-up examination. Our study indicates that patients with UCTD would seem to have a benign form of RP, since they show the absence of cutaneous complications, the existence of a mild microvascular damage and a stable nailfold capillary pattern. Further examinations of these patients will be required in order to confirm our findings.     

Risk of Adverse Pregnancy Outcomes in Women with CKD

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.     

Regulation of murine arthritis by systemic,spinal, and intra-articular adrenoceptors

BackgroundThe regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and β-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis.MethodsMurine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity.ResultsTreatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia).ConclusionWhereas the β-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively.     

Gastrointestinal complications after kidney transplantation

Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease(IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.