Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study.

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan-Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03-1.88) and 89% (OR = 0.11; 95%CL = 0.02-0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02-19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39-0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients.

Birch allergy and oral allergy syndrome: The practical relevance of serum immunoglobulin E to Bet v 1.

BACKGROUND: Birch allergy (BA) may frequently be associated with fruit-vegetables oral allergy syndrome (OAS). Bet v 1 is the major birch allergen. Previously, it was reported that serum-specific immunoglobulin E (IgE) level could differentiate allergy from sensitization. Thus, this study aimed to investigate the practical role of Bet v 1 IgE. METHODS: A total of 245 subjects (128 women, 117 men; mean age, 41 years) with suspected allergic rhinitis and sensitization to Bet v 1 were evaluated. Serum IgE to Bet v 1 was assessed by using immuno-enzymatic. BA and OAS were diagnosed according to validated criteria. Symptom severity perception was measured by the visual analog scale. RESULTS: A total of 158 patients (64.5%) had BA. Patients with BA had higher serum Bet v 1 IgE levels than subjects who were sensitized (p < 0.0001). A cutoff value of 8.94 kUA/L predicted BA (area under the curve, 0.76; odds ratio, 6.18). Fifty-three patients with BA (33.5%) had OAS. Patients positive for OAS had higher Bet v 1 levels (p < 0.0001) and more-severe symptoms (p < 0.0001) than patients with BA and negative for OAS. A cutoff value of 17.4 kUA/L predicted OAS (area under the curve, 0.59; odds ratio, 3.19). CONCLUSIONS: The present study demonstrated that serum IgE levels to Bet v 1 could be a useful marker for differentiating between different birch pollen sensitization phenotypes.

Use of a Transarticular Calcaneo-Tibial Locking Plate for Temporary Immobilization of the Tarsocrural Joint following Surgical Repair of Common Calcaneal Tendon Rupture in Eight Dogs.

OBJECTIVE: The purpose of this clinical communication is to report the management of common calcaneal tendon rupture in dogs using a transarticular calcaneo-tibial locking plate as a method of temporary immobilization of the tarsocrural joint to support primary repair of the common calcaneal tendon. STUDY DESIGN: Dogs presented with partial or complete common calcaneal tendon rupture treated with primary tendon repair supported by the transarticular calcaneo-tibial locking plate technique from July 2016 to December 2019 were included. The tarsus was placed at a standing angle of 150 degrees and the pre-contoured Fixin locking 'L' or 'T' plate was medially applied with two locking screws inserted in the calcaneus and two screws inserted in the distal tibia. Tendon healing judgement was mostly based on clinical palpation and ultrasound examination was not performed in all the cases. Plates were removed in all dogs 6 weeks postoperatively. RESULTS: All tendons healed and no complications at the level of the tenorrhaphy were noted in the postoperative period. All dogs returned to hunting activity with full function of the affected limb. No major complications requiring revision surgery were observed. Minor complications occurred in two cases; osteomyelitis and screw pull-out. CONCLUSION: The use of a transarticular calcaneo-tibial locking plate for temporary immobilization of the tarsocrural joint after surgical repair of common calcaneal tendon rupture appears to be an effective technique with comparable results to other reported techniques.

Fracture Repair in Cats Using a Conical Coupling Mini 1.9 to 2.5 mm Locking Plate System.

OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical application of the Fixin mini 1.9 to 2.5 system for the treatment of long bone fractures in cats. We proposed that the Fixin mini system would successfully stabilize long bone fractures in cats with a healing time and complication rate similar to those previously reported for feline fractures using other locking bone plate systems. MATERIALS AND METHODS: Medical records and radiographs of cats with long bone fractures stabilized with the Fixin mini 1.9 to 2.5 system were retrospectively reviewed. Signalment, body weight, bone(s) fractured, region of bone fractured, fracture classification, concurrent orthopaedic injuries, complications, time to functional union, if minimally invasive plate osteosynthesis techniques were used, plate size, number of plates, bone graft use and ancillary methods of fixation were recorded. RESULTS: Fifty-six fractures in 54 cats were included. Mean time to radiographic union was 8.8 weeks. Complications were recorded in 8 out of 56 fractures. Major complications occurred in 4 of 56 fractures and minor complications occurred in 4 of 56 fractures. CONCLUSION: The Fixin mini 1.9 to 2.5 system had an overall complication rate and time to functional union similar to that of other implant systems used to treat feline long bone fractures and it appears suitable for repair of a wide variety of long bone fracture configurations in cats.

Life (and death) in Pink: The dangerous rise of synthetic opioids in the new psychoactive substances panorama.

Novel psychoactive substances represent a recent and unprecedented challenge in the global health panorama. Recently, among these, synthetic opioids are growing in number and prevalence of use, leaving behind them severe intoxications and victims, and fuelling the illicit drug market, particularly on the Dark Net. Further attention should be drawn to this alarming phenomenon, from both clinicians and policymakers.

A Real Life Comparison between Allergenic Extracts and Allergenic Molecules.

Serum IgE assay is a mainstay step in the allergy work up. Allergenic extracts and molecular components are available at present. This real life study compared the serum specific IgE levels against allergenic extracts with allergenic molecules in patients allergic to Parietaria, Betulaceae, and mites. This retrospective real life study included 489 subjects with respiratory allergy. Inclusion criteria were 1) documented diagnosis of allergic rhinitis (AR) and/or allergic asthma, and 2) documented allergy to Parietaria judaica (Par j) 2 (216 patients: 112 females, mean age 42 years), or to Betula verrucosa (Bet v) 1 (62 patients: 35 females, mean age 3 years), or Dermatophagoides pteronyssinus (Der p) 1 (211 patients: 107 females, mean age 34 years); and mono-allergy. Serum IgE, specific both for total/crude allergen extracts and individual purified/recombinant allergens, were assessed by ImmunoCap system. The serum IgE levels to birch extract were very strongly (R2=0.96) related to IgE to Bet v 1. There was a strong (R2=0.71) correlation between Dermatophagoides pteronyssinus IgE and Der p 1. A very strong (R2=0.87) correlation also existed between Parietaria extract IgE and Par j 2 IgE levels. However, there was discrepancy between percentages of positivity between allergenic extracts and molecules. Therefore, allergen molecular diagnostics may represent a useful way in allergy work up, but deserves caution in particular circumstances.

Can serum white birch (Betula verrucosa) pollen antigen (Bet v 1) immunoglobulin E measurement distinguish between sensitization and allergy?

BACKGROUND: In clinical practice, it is fundamental to distinguish between sensitization and allergy, mainly with respect to polysensitized patients. The aim of this study was to evaluate whether serum immunoglobulin E (IgE) to white birch (Betula verrucosa) pollen antigen (Bet v 1) assessment might be able to differentiate simple sensitization from true allergy. METHODS: In total, 197 subjects (100 females; mean age 44.9 years) with serum Bet v 1 IgE positivity and history of nasal symptoms were evaluated. Subjects were subdivided in 2 groups: allergic and sensitized. RESULTS: Allergic patients were 58.4% of the total; they had higher serum Bet v 1 IgE levels than sensitized subjects (p < 0.001). A serum IgE to Bet v 1 value >8.94 kilo units of allergen per liter (kUA/L) was able to differentiate between sensitization and allergy (area under the receiver operating characteristic curve [AUC] = 0.76; diagnostic odds ratio, ie, degree of agreement between health status and dichotomized IgE levels [DOR] = 6.5). Gender and season when the blood was drawn influenced IgE levels. CONCLUSION: Serum Bet v 1 IgE measurement may be able to differentiate sensitization from allergy in subjects with sensitization to Betulaceae pollen allergens. Thus, Bet v 1 IgE measurement should be considered a useful step in the management of patients with allergic rhinitis due to Betulaceae pollen allergens.