The Combination of Dupilumab with Other Monoclonal Antibodies.

INTRODUCTION: Dupilumab is an interleukin-4 (IL-4) receptor alpha antagonist indicated for the treatment of moderate-to-severe atopic dermatitis (AD), which could be associated with atopic and non-atopic comorbidities for which concomitant administration of targeted pharmacotherapy including monoclonal antibodies could be required. However, the safety of combining dupilumab with other monoclonal antibodies for different therapeutic indication may be debated. METHODS: We conducted an extensive search in MEDLINE via PubMed for original articles published from January 1, 2017 to October 22, 2022, reporting clinical cases in which dupilumab has been associated with other monoclonal antibodies. RESULTS: Four small case series were identified reporting data on a total of 16 patients. To them, we have added other patients (n = 8) derived from our clinical practice, achieving a total of 24 cases followed for a period of 2-22 months. Patients were receiving dupilumab mainly because of AD (except one patient for bullous pemphigoid and one for asthma) and other monoclonal antibodies for psoriasis treated with guselkumab (n = 7) and secukinumab (n = 1), asthma with omalizumab or benralizumab (n = 3), Crohn's disease with adalimumab (n = 3), chronic spontaneous urticaria with omalizumab (n = 3), primary familial hypercholesterolemia with evolocumab (n = 2), hidradenitis suppurativa with adalimumab (n = 1), psoriatic arthritis with secukinumab (n = 1), rheumatoid arthritis with abatacept (n = 1), ankylosing spondylitis with secukinumab (n = 1) and colorectal carcinoma with cetuximab (n = 1). No adverse events related to the combination of the two monoclonal antibodies were reported except for a mild injection site reaction (n = 1) and arthralgia, which resolved spontaneously within a few weeks (n = 1). CONCLUSIONS: Because the evidence is modest, the question remains open as to whether dupilumab can be safely combined with other monoclonal antibodies. Dupilumab does not exert immunosuppressive effects and does not impair the activity of cytochrome P450 isozymes.

An integrated approach to control Cystic Echinococcosis in southern Italy.

Cystic echinococcosis (CE) is a severe zoonosis, caused by the larval stage of the tapeworm Echinococcus granulosus. This helminth infection is of increasing public health and socio-economic concern due to the considerable morbidity rates that cause economic losses both in the public health sector and in the livestock industry. Control programmes against E. granulosus are considered long-term actions which require an integrated approach and high expenditure of time and financial resources. Since 2010, an integrated approach to control CE has been implemented in a highly endemic area of continental southern Italy (Campania region). Innovative procedures and tools have been developed and exploited during the control programme based on the following strategies: i) active and passive surveillance in livestock (using geospatial tools for georeferencing), ii) diagnosis in dogs (using the FLOTAC techniques and molecular analysis), iii) targeted treatment of farm dogs (using purpose-built confinement cages), iv) early diagnosis in livestock (by ultrasonography), v) surveillance in humans (through hospital discharge records analysis), vi) monitoring the food chain (analysing raw vegetables), vii) outreach activities to the general public (through dissemination material, e.g. brochures, gadgets, videos, virtual reality). Over eight years, the integrated approach and the new strategies developed have resulted in a noteworthy reduction of the parasite infection rates in livestock (e.g. up to 30 % in sheep). The results obtained so far highlight that using a one health multidisciplinary and multi-institution effort is of pivotal importance in preparing CE control programmes at regional level and could be extended to other endemic Mediterranean areas.

FLOTAC: an improved method for diagnosis of lungworm infections in sheep.

The FLOTAC techniques involve the spinning of faecal samples onto the surface of counting chambers to permit enumeration of parasitic elements (eggs, larvae, oocysts and cysts) to an accuracy of one parasitic element per gram of faeces. In the present study it is demonstrated that FLOTAC provides a rapid and very sensitive method for counting of lungworm larvae of sheep. The optimum flotation solution for lungworm larvae is zinc sulphate and mercury II iodide (s.g. 1.45) although zinc sulphate (s.g. 1.20 or 1.35) on its own also gave good results. Samples preserved in 5% formalin gave the highest counts but fresh, frozen and samples in 10% formalin also gave higher counts than McMaster and simple flotation. Larval counts of 307 field samples gave up to 1.27x more positives samples than use of Baermann funnels and up to 4.18x more larvae per sample. As FLOTAC is faster than Baermannisation of samples it offers a better method of counting larvae in ruminant faecal samples.

The role of cattle in the epidemiology of Echinococcus granulosus in an endemic area of southern Italy.

An epidemiological and molecular survey was conducted to investigate the role of cattle in the transmission chain of cystic echinococcosis (CE) in the Campania region of southern Italy. Out of a total of 434 cattle examined for CE, 45 (10.4%) were found infected. A total of 363 cysts were collected from the infected animals: 239 in the liver and 124 in the lungs. The cysts were either sterile (42.7%) or calcified/caseous (57.3%); no fertile cysts were found. Most of the cysts had sizes <3 cm (77.1%) and were unilocular (78.8%). The results of the linear regression model did not show any significant correlation between the age of infected cattle and the number of cysts. The sequencing of the mitochondrial cytochrome C oxidase subunit 1 (CO1) gene of 40 hydatid cysts produced sequences of 419 bp for each sample analyzed. Alignment of the obtained sequences with those present in GenBank showed 100% identity with the common sheep G1 (n=21 cysts), the Tasmanian sheep G2 (n=2 cysts), and the buffalo G3 (n=17 cysts) strains, which constitute the species Echinococcus granulosus sensu stricto. The findings reported in the present study show that CE is widespread in cattle bred in the Campania region of southern Italy. However, the absence of fertile cysts and of the cattle strain (G5, E. ortleppi) suggests that cattle would not have any role in the persistence of this important zoonosis but rather a role as indicators of CE infection in this endemic area.

Molecular update on cystic echinococcosis in cattle and water buffaloes of southern Italy.

Cystic echinococcosis (CE)--caused by the larval stage (hydatid cyst) of the cestode Echinococcus granulosus--is one of the most widespread zoonoses of veterinary and medical importance. Molecular techniques have allowed the identification of 10 different genotypes (G1-G10) of the parasite. The present paper is an update regarding the E. granulosus genotypes infecting water buffaloes and cattle bred in the Campania region of southern Italy. The molecular study was performed on 30 hydatid cysts (11 from water buffaloes and 19 from cattle). Two different mitochondrial DNA genes, namely the cytochrome c oxidase subunits 1 and the 12S ribosomal DNA (12S rDNA) were used as genetic markers. Three different genotypes of E. granulosus were unequivocally identified, i.e. the G1 (common sheep), G2 (Tasmanian sheep) and G3 (buffalo) genotypes, as well as some G1 and G2 variants. It should be noted that the present study demonstrated for the first time: (i) the presence of the G2 genotype in water buffaloes from a Mediterranean area; and (ii) the fact that the analysed portion of the 12S rDNA gene can not discriminate between the G2 and G3 genotypes of E. granulosus. The finding of the G1, G2 and G3 genotypes in large ruminants from southern Italy is of epidemiological relevance and immediate public health importance because of their recognized infectivity in humans.

Cystic echinococcosis in water buffaloes: epidemiological survey and molecular evidence of ovine (G1) and buffalo (G3) strains.

A survey of cystic echinococcosis (CE) in the water buffalo (Bubalus bubalis) of the Italian Mediterranean breed was carried out in Campania, a region of southern Italy. In addition, a molecular study was performed on 48 hydatid cysts coming from 48 water buffaloes in order to determine the Echinococcus granulosus strain(s) present in this host. Out of a total of 722 water buffaloes examined for CE, 76 (10.5%) were found infected. The average number of cysts per buffalo was 4.3 (minimum 1, maximum 45). Seventeen buffaloes had hydatid cysts only in the liver (with an average of 5 cysts/liver), 34 only in the lungs (with an average of 1.8 cysts/lungs), and 25 buffaloes had cysts both in the liver and in the lungs. Fertile cysts were found in 10 (13.2%) out of the 76 positive buffaloes. The sequencing of the mitochondrial cytochrome C oxidase subunit 1 (CO1) gene of the 48 hydatid cysts produced sequences of 419 bp for each sample analysed. For 33 samples, alignment of the obtained sequences with those present in GenBank showed a total homology with the common domestic sheep strain G1; for 15 samples, sequences obtained showed 100% homology with buffalo strain G3. The findings of the present survey represent the first epidemiological and molecular comprehensive studies on CE in water buffalo from an endemic area for E. granulosus.

Monitoring aspects during port-access cardiac surgery.

OBJECTIVE: To report the experience gained at our Cardiosurgical Centre with the recently introduced port-access technique. EXPERIMENTAL DESIGN: Prospective collection of data from the month of October 1997. SETTING: Regional University HospitaL Patients: Adult patients undergoing coronary bypass graft or mitral valve surgery. INTERVENTIONS: Port-access technique makes it possible to carry out open-heart procedures through a minithoracotomy and extrathoracic cardiopulmonary bypass with a set of properly designed catheters (Heartport EndoCPB system) for cardioplegia delivery and heart venting. MEASURES: Transesophageal echography and pressure traces are the main monitoring tools used for the correct placement of these catheters and for the clinical management of the patient. RESULTS: Sixty-two cases have been performed so far. A complete description of the procedure, with monitoring aspects and problems encountered is thoroughly presented. CONCLUSIONS: The major differences with traditional cardiac surgery are that interruption of myocardial perfusion is not achieved through a transversal clamp but through an endovascular occlusive balloon and that thoracic access is by minithoracotomy. Unlike traditional open surgery, the surgeon has no direct vision of the position of the clamp and the anesthesiologist can not visually inspect the contractile state of the heart. The operative team has to cope with a multifaceted system of monitored variables that must be continuously integrated and interpreted. Tight cooperation and continuous communication between anaesthesiologist, surgeons and perfusionist appear to be more important than in any other cardiac operation.

[Minimally invasive surgery with the Port-Access method. Preliminary experience]. / La chirurgia mini-invasiva con la metodica Port-Access. Esperienza preliminare.

METHODS: Data from the initial experience of 40 patients operated on with the Port-Access technique are reported. Indication to surgery was mitral disease in 24 patients and coronary stenosis in 16 patients. Mean age was 52 years (range 32-75). Operations performed were: 8 mitral valvuloplasties, 16 valve replacements, 9 single CABG (associated with an MVR in one case), 1 double CABG, 6 triple CABG and one quadruple CABG. Coronary endarterectomy was performed in 5 patients and left atrial isolation was associated with MV surgery in 5 cases. RESULTS: There were no operative deaths and every patient was discharged after a mean postoperative stay of 5.5 days (range 3-30). Postoperative course was complicated in 7 patients: surgical revision was necessary in 4 patients due to bleeding (through the mini-thoracotomy incision in 3 cases), 1 pacemaker was implanted for A-V block, one retained pulmonary catheter was removed through the mini-thoracotomy without the aid of cardiopulmonary bypass and in one case, there was an emergency conversion to median sternotomy due to a ventricular fibrillation unresponsive to usual resuscitative maneuvers a few hours after surgery. Some of these complications can be ascribed to the learning phase of this new technique and should disappear as experience is increased. CONCLUSIONS: Port-Access surgery is a new minimally invasive technique that utilizes a cardiopulmonary bypass with femoral access and a specialized catheter system that provides endoaortic clamping, pulmonary artery venting and myocardial preservation with infusion of cardioplegic solution in the aortic bulb or in the coronary sinus. Major contraindications to this technique are iliac-femoral disease or severe dilatation of ascending aorta. The aim of the Port-Access technique is to combine the aesthetic and functional advantages of the minimally invasive surgery with the wide range of surgical options that cardiopulmonary bypass can afford (to operate on atrioventricular valves and perform all the CABG that the patient need), without the limitations characteristic of the classic minimally invasive direct coronary artery bypass (MIDCAB) technique.

Lipoprotein (a) serum levels in patients with hepatocarcinoma.

Lipoprotein (a) [Lp(a)] is synthesised by liver cells, and patients with liver cirrhosis (LC) show low serum levels of Lp(a) associated with the degree of liver failure. On the contrary, increased serum levels of Lp(a) have been reported in patients with cancer. In this report, the behaviour of Lp(a) serum levels in patients with hepatocarcinoma (HC), a complication of LC, has been evaluated with the aim to study whether HC cells were able to cause an increase of serum concentrations of this lipoprotein when impaired liver protein synthesis is present. We selected eighteen patients affected by LC + HC, eighteen patients matched for sex, age and degree of liver failure with LC only, and eighteen patients with other cancer types. A significant increase of serum levels of Lp(a) was observed in patients affected by LC + HC or other cancer types compared with healthy subjects. Forty-four percent of LC + HC patients showed Lp(a) values more than 70.4 Units/dl, i.e., the upper limit of values observed in patients with LC only. Lp(a) serum concentrations were significantly associated with serum albumin both in LC and in LC + HC but not in other cancer-type patients. Thus, comparing patients with similar serum albumin concentrations, Lp(a) serum levels were significantly higher in patients with LC + HC than in patients with only LC and quite similar to those observed in patients with other cancer types. In conclusion, HC cells, in vivo, seem able to produce a greater amount of Lp(a) despite the reduced liver protein synthesis typical of LC.

Platelet composition and function in patients undergoing cardiopulmonary bypass for heart surgery.

BACKGROUND: Previous studies showed severe biochemical and functional damage to platelets in patients undergoing cardiopulmonary bypass for cardiac surgery, and suggested that this derived from the proteolytic action of plasmin on the platelet surface. METHODS: A double-blind study was carried out to compare platelet function and composition in patients randomized to receive the protease inhibitor aprotinin or placebo during reoperation for valvular prosthesis replacement or coronary artery bypass grafting. RESULTS: Flow cytometry with specific monoclonal antibodies and polyacrylamide gel electrophoresis did not show any significant proteolysis of platelet glycoprotein Ib and IIb-IIIa either in the placebo or the aprotinin group. Functional studies were consistent with these results, since ristocetin-induced platelet agglutination was unchanged and platelet aggregation and ATP release induced by collagen and ADP were only slightly reduced by cardiopulmonary bypass. These mild defects in platelet function were partially prevented by aprotinin infusion. CONCLUSIONS: On the basis of our data and those from literature, we suggest that platelets may be affected very little or severely damaged during cardiopulmonary bypass for cardiac surgery, probably depending on some aspects of the technical procedure which remain to be identified. Aprotinin infusion significantly protects platelets in the latter condition, while its role is obviously slight in the former.

[Co-involvement of catecholaminergic and gabaergic transmission in the electro-cortical response to central galanin administration in the rabbit]. / Coinvolgimento della trasmissione catecolaminergica e gabaergica nella risposta elettrocorticale alla somministrazione centrale di galanina nel coniglio.

The involvement of catecholaminergic and gabaergic transmission in the electrocortical pattern induced by centrally administered galanin was investigated in the rabbit. The inhibition of catecholamine synthesis by both DDC and alphaMPT potentiated the EEG effect of the peptide. Baclofen and muscimol significantly enhanced the EEG response to GAL. However the interaction between the peptide and gabaergic transmission seemed mainly to involve the type A receptor system.

[EEG and autonomic effects of centrally administered galanin in the rabbit]. / Effetti EEG ed autonomici della galanina somministrata centralmente nel coniglio.

The effects of centrally administered galanin (10 and 20 mcg) on the EEG, somatic behaviour and some autonomic parameters have been studied in unanesthetized rabbits. In this species the peptide induced a dose related increase in electrocortical power spectrum density and behavioural sedation. Autonomic changes, consisting in moderate hyperthermia and bradypnea, were seen only after the highest dose of the peptide. These data support a central action of the peptide and suggest a role for galanin as sedative neuropeptide.

[Drepanocytosis in patients undergoing heart surgery. Anesthesiologic problems]. / Drepanocitosi in pazienti sottoposti a chirurgia cardiaca. Problematiche anestesiologiche.

The authors report their experience with the management of patients with sickle cell trait undergoing open heart surgery. They focus their attention mainly on those factors potentially able to precipitate episodes of sickling, i.e. hypoxia, hypothermia, vascular stasis and acidosis.

[Comparison between propofol and isoflurane in patients undergoing aorto-coronary bypass. Effect on systemic and coronary circulation]. / Confronto tra propofol e isoflurano in pazienti sottoposti ad intervento di bypass aorto-coronarico. Effetti sul circolo sistemico e coronarico.

The Authors report their experience with the use of two different anaesthetic techniques (propofol-fentanil versus isoflurane-fentanyl) for induction and maintenance of anaesthesia in patients undergoing coronary artery surgery. Haemodynamic data (regarding systemic and coronary circulation) showed an almost similar pattern of change after induction, intubation, skin incision and sterotomy, except for a greater decrease of systemic vascular resistances after induction in patients who received propofol. Cardiac output decreased more in the isoflurane group while changes in coronary sinus flow were equal in the two groups.

Quantitative EEG and autonomic patterns of synthetic peptides related to dermorphin.

The effects of dermorphin on EEG and autonomic variables are compared with the effects of 2 analogues and 2 homologues, all administered intracerebroventricularly in the rabbit. Dermorphin was the most effective in modifying all considered parameters: increase of cortically derived and calculated total power, bradycardia, respiratory depression and hypothermia. The dibenzylated heptapeptide was essentially inactive. The electrocortical pattern induced by the administration of L-dermorphin suggests a functional correlation between the amino acid D-ala 2 and the effects on EEG. Comparison between the effects produced by the N-terminal tetrapeptide and pentapeptide led us to hypothesize that amino acid Tyr 5 may be specifically involved in inducing the autonomic effects.