The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-ß1 production and FcRL4 expression.

The humoral immune response after acute infection with HIV-1 is delayed and ineffective. The HIV-1 envelope protein gp120 binds to and signals through integrin α4ß7 on T cells. We found that gp120 also bound to and signaled through α4ß7 on naive B cells, which resulted in an abortive proliferative response. In primary B cells, signaling by gp120 through α4ß7 resulted in increased expression of the immunosuppressive cytokine TGF-ß1 and FcRL4, an inhibitory receptor expressed on B cells. Coculture of B cells with HIV-1-infected autologous CD4(+) T cells also increased the expression of FcRL4 by B cells. Our findings indicated that in addition to mediating chronic activation of the immune system, viral proteins contributed directly to HIV-1-associated B cell dysfunction. Our studies identify a mechanism whereby the virus may subvert the early HIV-1-specific humoral immune response.

Cutting Edge: Hyperinflammatory Monocytes Expressing CD56 Abound in Severe COVID-19 Patients.

Proinflammatory monocytes play a preponderant role in the development of a cytokine storm causing fatal consequences in coronavirus disease 2019 (COVID-19) patients, highlighting the importance of analyzing in more detail monocyte distribution in these patients. In this study, we identified an atypical monocyte subpopulation expressing CD56 molecules that showed a low level of HLA-DR and high level of l-selectin. They released higher amounts of TNF-α and IL-6 and expressed genes associated with an excessive inflammatory process. Remarkably, the frequency of CD56+ monocytes inversely correlated with that of CD16+ monocytes and a high CD56+/CD16+monocyte ratio was associated with both disease severity and mortality, as well as with serum concentration of type I IFN, a factor able to induce the appearance of CD56+ monocytes. In conclusion, severe COVID-19 is characterized by the abundance of hyperinflammatory CD56+ monocytes, which could represent a novel marker with prognostic significance and, possibly, a therapeutic target for controlling the inflammatory process occurring during COVID-19.

Diagnostic value of regional homogeneity and fractional amplitude of low-frequency fluctuations in the classification of schizophrenia and bipolar disorders.

Schizophrenia (SCZ) and bipolar disorders (BD) show significant neurobiological and clinical overlap. In this study, we wanted to identify indexes of intrinsic brain activity that could differentiate these disorders. We compared the diagnostic value of the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) estimated from resting-state functional magnetic resonance imaging in a support vector machine classification of 59 healthy controls (HC), 40 individuals with SCZ, and 43 individuals with BD type I. The best performance, measured by balanced accuracy (BAC) for binary classification relative to HC was achieved by a stacking model (87.4% and 90.6% for SCZ and BD, respectively), with ReHo performing better than fALFF, both in SCZ (86.2% vs. 79.4%) and BD (89.9% vs. 76.9%). BD were better differentiated from HC by fronto-temporal ReHo and striato-temporo-thalamic fALFF. SCZ were better classified from HC using fronto-temporal-cerebellar ReHo and insulo-tempo-parietal-cerebellar fALFF. In conclusion, we provided evidence of widespread aberrancies of spontaneous activity and local connectivity in SCZ and BD, demonstrating that ReHo features exhibited superior discriminatory power compared to fALFF and achieved higher classification accuracies. Our results support the complementarity of these measures in the classification of SCZ and BD and suggest the potential for multivariate integration to improve diagnostic precision.

Congenital herpes simplex with ophthalmic and multisystem features: a case report.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement. CASE PRESENTATION: A preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition. DISCUSSION: Neonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics. CONCLUSIONS: In the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.

Optimization of 5-CQA Extraction Conditions from Green Coffee By-Product (Coffea arabica) Using a Response-Surface Design and the Study of Its Extraction Kinetics.

To take advantage of the residues generated in the production of products from green coffee and due to the special interest in the compounds contained in the bean, a by-product obtained after the extraction of the oil was studied. The physical characterization of the green-coffee-bean by-product was carried out. Subsequently, the extraction of compound 5-CQA was carried out via leaching using central composition design 24 and evaluating factors such as temperature, time, solid/solvent ratio, and ethanol percentage, and its yield was quantified using HPLC. In addition, the response-surface methodology was used to maximize the efficiency of 5-CQA extraction and to perform the kinetic study. Yields of 59 ± 2 mg of 5-CQA/g from the by-product were obtained, and by selecting the best leaching conditions, the kinetic study was performed at 45, 60, and 75 °C, increasing the yield to a total of 61.8 ± 3 mg of 5-CQA/g. By applying the kinetic model of mass transfer, a fit of R2 > 0.97 was obtained, with KLa values between 0.266 and 0.320 min−1. This study showed an approach to optimize the 5-CQA extraction conditions, resulting in a simple, fast, reproducible, accurate, and low-cost method.

Endonasal Endoscopic and Hybrid Surgery Techniques for Blunt Trauma Fractures of the Skull Base With Cerebrospinal Fluid Leaks.

ABSTRACT: Cerebrospinal fluid (CSF) leakage caused by skull base fracture represents high risks of bacterial meningitis, and a rate of mortality of 8.9%. Endoscopic endonasal repair of CSF leaks is quite safe and effective procedure with high rates of success. The aim of this study is to describe our technique for management of skull base CSF leaks secondary to craniofacial trauma based on the anatomic location of the leak. This is a retrospective case series of 17 patients with diagnosis of craniofacial trauma, surgically treated with sole endonasal endoscopic and combined endonasal/transcranial approaches with diagnosis of CSF leak secondary to skull base fractures. Seventeen patients met inclusion criteria for this study. Mean age was 46 years old. Most common etiology was motor vehicle. Early surgery was performed in 8 patients, and late surgery in 9 patients. The most common site of CSF leak was at ethmoid cells or at the fronto-ethmoid junction in 9 patients. Thirteen patients (76.4%) were treated only with endonasal endoscopic technique, and 4 (23.5%) with hybrid surgery, combining endonasal endoscopic and cranial bicoronal approaches with nasal and pericranial vascularized flaps, and nasal mucosal free flaps. Mean hospital stay was 23.7 days.The mean follow-up time was 25.6 months. When surgical reconstruction is indicated for CSF leaks secondary to skull base fractures, endonasal endoscopic techniques should be part of the surgical management either as a sole procedure, or in combination with classical transcranial approaches with high rates of success and low morbidity.

Cannabis, schizophrenia and cognition: the contribution of brain connectivity. / Cannabis, esquizofrenia y cognición, aportes de la conectividad cerebral.

The lack of consensus on the issue of whether the consumption of cannabis favors neurocognition among schizophrenia-diagnosed patients or not, plus methodological problems found in available evidence and the limitations of studies focused on diagnosis and treatment for positive symptoms are sufficient reason for designing new research proposals based on recent brain connectivity models. The objective of this paper is to review available literature databases, selected for neurocognition in cannabis-using schizophrenia patients and to analyze contributions made by functional connectivity studies. Cognitive impairment among schizophrenia patients is found even before the appearance of the first psychotic symptoms. Measuring cognitive function in these patients, techniques such as fMRI and EEG have found brain impairment. Furthermore, regarding schizophrenia-diagnosed patients who use cannabis, some studies have shown less deterioration among cognitive domains, which may apparently be related with one of its components (CBD). Measuring brain connectivity can be useful for clarifying neurophysiological mechanisms of cognition in marihuana-using schizophrenia patients. Cognitive decline is generalized in schizophrenia patients and is considered fundamental for disease physiopathology.

La falta de consenso sobre si el consumo de cannabis favorece la neurocognición en pacientes con diagnóstico de esquizofrenia consumidores de esta sustancia, más los problemas metodológicos encontrados en la evidencia disponible y las limitaciones de los estudios, los cuales se centran en el diagnóstico y tratamiento de los síntomas positivos, son elementos suficientes para diseñar nuevas propuestas de investigación desde los modelos recientes de conectividad cerebral. El objetivo de este trabajo es revisar la literatura disponible en las bases de datos seleccionadas sobre la neurocognición en pacientes con diagnóstico de esquizofrenia consumidores de cannabis y los aportes de los estudios de conectividad funcional. Alteraciones cognitivas en los pacientes con esquizofrenia, se evidencian incluso antes de la aparición de los primeros síntomas psicóticos; técnicas como RMFI y EEG han encontrado alteraciones en los cerebros de los pacientes con esquizofrenia. En los pacientes con esquizofrenia consumidores de cannabis, algunos estudios evidencian menores deterioros en los diferentes dominios cognitivos, que al parecer podian estar relacionados con uno de sus componentes, el CBD. La medición de la conectividad cerebral, puede ser útil para aclarar los mecanismos neurofisiológicos de la cognición en los pacientes con diagnóstico de esquizofrenia consumidores de cannabis.

Noninvasive continuous arterial pressure monitoring with Clearsight during awake carotid endarterectomy: A prospective observational study.

BACKGROUND: Continuous noninvasive blood pressure (CNBP) measurement using the volume-clamp method is a less invasive alternative compared with invasive intra-arterial monitoring for awake patients during carotid endarterectomy (CEA) under regional anaesthesia. OBJECTIVE: We investigated the agreement of blood pressure (BP) recorded with invasive and CNBP methods during awake CEA. DESIGN: A prospective observational study for assessing agreement with Bland-Altman plots, agreement-tolerability indices (ATI), concordance and interchangeability. SETTING: Azienda Ospedaliera Universitaria G. Martino, Messina, a University tertiary referral centre in Italy. PATIENTS: In 30 consecutive patients, we recorded continuously ipsilateral invasive and noninvasive BPs, from 3 min before carotid cross-clamping to 5 min after unclamping. MAIN OUTCOME MEASURES: Primary outcome was bias, 95% limits of agreement, ATI, concordance and interchangeability for mean arterial pressure (MAP). Secondary outcomes were agreements for systolic arterial pressure and diastolic arterial pressure. Tracking of changes was assessed with four-quadrant polar plots and the trend interchangeability method. Optimal bias was defined as 5 mmHg or less. RESULTS: A total of 2672 invasive and CNBP paired measurements (93% of overall data) were analysed, with a median of 92 readings per patient [IQR 76 to 100]. Mean (SD) bias for MAP, systolic arterial pressure and DAP were -6.8 (6.7), -3.0 (9.7) and -9.0 (5.4) mmHg, respectively. The ATIs were 0.88, 0.95 and 0.71, respectively, where ATI of 1.0 or less and at least 2.0 defined acceptable, marginal and unacceptable agreements. The four-quadrant plot analysis for beat-to-beat differences showed concordance rates of 97.3%, 99.98% and 96.4%, respectively. Polar plot analysis showed 95% limits of agreement of -3 to 3, -2 to 2 and -2 to 2 mmHg respectively. Trend interchangeability method showed an interchangeability rate of 95% for MAP. CONCLUSION: During CEA performed under regional anaesthesia, CNBP offers a less invasive approach for BP monitoring. We found acceptable agreement for MAP defined by an ATI of 0.88 and an excellent 95% global interchangeability rate. A suboptimal bias of 7 mmHg was found with CNBP for MAP.

Initial clinical experience with a polytetrafluoroethylene vascular dialysis graft reinforced with nitinol at the venous end.

OBJECTIVE: The purpose of this study was to examine the outcomes of a vascular hybrid polytetrafluoroethylene (PTFE) graft, provided with a nitinol-reinforced section (NRS) on one end, in hemodialysis vascular access placement. METHODS: A retrospective study was conducted including all the consecutive patients who underwent Gore Hybrid Vascular Graft (GHVG; W. L. Gore & Associates, Flagstaff, Ariz) implantation for hemodialysis access placement between October 2013 and November 2015. A propensity-matched control group was obtained from consecutive patients who underwent standard PTFE arteriovenous graft implantation between January 2010 and July 2013. The selection criteria were inadequate venous material for autogenous arteriovenous fistula placement, patent deep venous circulation, and vein diameter of 4 to 8.5 mm. The implantation technique involves the insertion of the NRS some centimeters into the target vein. Fluoroscopic guidance helps deploy the device in the desired landing zone (ie, position of the proximal end of the NRS), based on anatomic landmarks. Survival, functional patency rates, and complications were compared with a propensity-matched historical control group. Vein diameter, previous vascular access placement, and diabetes were tested as predictors of reintervention with a logistic regression analysis. RESULTS: There were 32 patients (14 men; mean age, 69 ± 14 years) who received the GHVG graft. The historical control group included 43 patients. Technical success was 100%. The graft configuration was brachial-axillary (n = 22 [69%]), brachial-basilic loop (n = 5 [16%]), brachial-antecubital loop (n = 3 [9%]), axilloaxillary loop (n = 1 [3%]), and femoral-femoral loop (n = 1 [3%]). Mean NRS oversize was 20% ± 7% (range, 3%-34%; median, 19%). Perioperative complications requiring revision included acute limb ischemia treated with thrombectomy (n = 1 [3%]) and graft infection requiring explantation (n = 2 [6%]). Two patients (6%) died in the hospital of unrelated causes. The mean follow-up was 15 ± 11 months (range, 0-33 months; median, 15.5). The propensity-matched groups included 25 patients each. Survival estimates at 24 months for the GHVG and standard PTFE groups were 91% ± 6% and 82% ± 9% (P > .05), respectively. The 12-month patency estimates were as follows: functional primary patency, 66% ± 10% vs 51% ± 10% (P > .05); functional assisted primary patency, 75% ± 9% vs 51% ± 10% (P > .05); and functional secondary patency, 79% ± 9% vs 67% ± 10% (P > .05). Reduction in vein diameter was associated with reintervention. CONCLUSIONS: The GHVG is a safe and effective alternative to standard PTFE in hemodialysis access surgery. Careful planning for the landing zone is advisable, especially for small outflow veins. Larger studies and randomized trials are needed to define the role for this device. A study including a greater number of centers experienced with this device is currently under way.

Delayed graft function and chronic allograft nephropathy: diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin.

CONTEXT: Available markers are not reliable parameters to early detect kidney injury in transplanted patients. OBJECTIVE: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome. PATIENTS AND METHODS: NGAL was evaluated in 124 transplanted patients. RESULTS: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04-1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09-1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively. CONCLUSION: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression.

Ventilation strategies for preventing oxidative stress-induced injury in preterm infants with respiratory disease: an update.

Reactive oxygen and nitrogen species are produced by several inflammatory and structural cells of the airways. The lungs of preterm newborns are susceptible to oxidative injury induced by both reactive oxygen and nitrogen species. Increased oxidative stress and imbalance in antioxidant enzymes may play a role in the pathogenesis of inflammatory pulmonary diseases. Preterm infants are frequently exposed to high oxygen concentrations, infections or inflammation; they have reduced antioxidant defense and high free iron levels which enhance toxic radical generation. Multiple ventilation strategies have been studied to reduce injury and improve outcomes in preterm infants. Using lung protective strategies, there is the need to reach a compromise between satisfaction of gas exchange and potential toxicities related to over-distension, derecruitment of lung units and high oxygen concentrations. In this review, the authors summarize scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the strategies of ventilation.

Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia.

Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral and central nervous system play a role in the occurrence and persistence of pain in the amputated lower limb. The classical treatment of PLP can be divided into pharmacologic, surgical, anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new method of treatment for this condition. However, the concomitant treatment of PLP and critical lower limb ischemia by using SCS therapy has not yet been described in the current literature. The aim of the present article is to highlight the possibility of apply SCS for the simultaneous treatment of PLP and critical lower limb ischemia on the contralateral lower limb after failure of medical therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular or surgical revascularization. After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the left side in all our patients. The main indications for permanent SCS therapy after 1 week of test stimulation were represented by transcutaneous oxygen (TcPO2) increase >75%, decrease of opioids analgesics use of at least 50% and a pain maintained to within 20-30/100 mm on visual analog scale.

Metformin-related lactic acidosis: is it a myth or an underestimated reality?

Metformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma metformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating metformin as the cause of lactic acidosis if low plasma levels occurred. Renal replacement therapies have been successfully employed to achieve the correction of metabolic acidosis and rapidly remove metformin and lactate, but the optimal treatment modality for MALA is still controversial.

Spinal cord stimulation to achieve wound healing in a primary lower limb critical ischaemia referral centre.

Critical lower limb ischaemia is a diffuse pathology that could cause claudication, severe ischaemic pain and tissue loss. The common treatment includes modification of risk factors, pharmacological therapy and endovascular or surgical revascularisation of the lower limb to restore a pulsatile flow distally. Spinal cord stimulator is seen as a valid alternative in patients unsuitable for revascularisation after endovascular or surgical revascularisation failure and as adjuvant therapy in the presence of a functioning bypass in patients with extensive tissue loss and gangrene presenting a slow and difficult wound healing. We report our experience on spinal cord stimulation (SCS) indication and implantation in patients with critical lower limb ischaemia, at a high-volume centre for the treatment of peripheral arterial disease.

Adjuvant spinal cord stimulation improves wound healing of peripheral tissue loss due to steal syndrome of the hand: clinical challenge treating a difficult case.

Hand ischaemia due to arterial steal syndrome is an infrequent, but potentially serious complication of arteriovenous fistula (AVF) for haemodialysis. We present a case of hand ischaemia caused by steal syndrome in a 69-year-old haemodialysis patient, 10 months after a brachiobasilic fistula creation. The patient underwent multiple operations without resolution of hand pain and tissue loss. The implantation of an adjuvant cervical spinal cord stimulator allowed the patient to obtain complete hand pain relief and wound healing. Probably, the diffuse microangiopathy typical of haemodialysis patients could be responsible for the persistence of ischaemic signs and symptoms after a surgical revascularisation. The effect of sympathetic blockade and the subsequent improvement of the arterial blood flow and tissue oxygenation because of spinal cord stimulation (SCS) can be useful to achieve complete ischaemic pain relief in order to enhance wound healing and to limit the tissue loss. In conclusion, the association of cervical spinal cord stimulation and surgical revascularisation could represent a valid option to treat a critical upper limb ischaemia following steal syndrome due to AVF.

Matrix metalloproteinases and risk stratification in patients undergoing surgical revascularisation for critical limb ischaemia.

Critical limb ischaemia (CLI) is the most advanced form of peripheral artery disease (PAD) and it is often associated with foot gangrene, which may lead to major amputation of lower limbs, and also with a higher risk of death due to fatal cardiovascular events. Matrix metalloproteinases (MMPs) seem to be involved in atherosclerosis, PAD and CLI. Aim of this study was to evaluate variations in MMP serum levels in patients affected by CLI, before and after lower limb surgical revascularisation through prosthetic or venous bypass. A total of 29 patients (7 females and 22 males, mean age 73·4 years, range 65-83 years) suffering from CLI and submitted to lower extremity bypass (LEB) in our Institution were recruited. Seven patients (group I) underwent LEB using synthetic polytetrafluoroethylene (PTFE) graft material and 22 patients (group II) underwent LEB using autogenous veins. Moreover, 30 healthy age-sex-matched subjects were also enrolled as controls (group III). We documented significantly higher serum MMPs levels (P < 0·01) in patients with CLI (groups I and II) with respect to control group (group III). Finally, five patients with CLI (17·2%) showed poor outcomes (major amputations or death), and enzyme-linked immunosorbent assay (ELISA) test showed very high levels of MMP-1 and MMP-8. MMP serum levels seem to be able to predict the clinical outcomes of patients with CLI.

Thalassaemia major and infectious risk: High Mobility Group Box-1 represents a novel diagnostic and prognostic biomarker.

High mobility group box -1 (HMGB1) represents a common causal agent for various types of diseases, including infective pathologies. This study aimed to investigate the role of HMGB1 in ß-thalassemia major (TM) by evaluating its diagnostic and prognostic role. Fifty-one TM patients and 30 healthy subjects (HS) were enrolled. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1 to determine the best cut-off values capable of identifying infectious episodes. Adjusted risk estimates for infective events were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Serum HMGB1 levels were higher in TM patients than in HS (14·6 ± 8·7 vs. 2·08 ± 0·9 ng/ml, P < 0·0001). Patients who underwent splenectomy were characterized by lower levels of HMGB1, when compared with patients with an intact spleen (10·2 ± 8 vs. 19·1 ± 7 ng/ml, P = 0·004). ROC analyses revealed an AUC for serum HMGB1 of 0·801, with a sensitivity and specificity of 92·3% and 68·2% to detect an infectious episode. Low HMGB1 levels predicted high risk of infective events (HR: 0·81; P = 0·006). HMGB1 represents a prognostic marker for TM patients and a predictive factor for infectious events.

IL-33/IL-31 axis: a new pathological mechanisms for EGFR tyrosine kinase inhibitors-associated skin toxicity.

The dermatologic side effects are the most common adverse effects associated with Epidermal Growth Factor Receptor tyrosine kinase inhibitors. Although the mechanisms underlying the development of the skin toxicity remain unclear, immunological mechanisms are considered to be involved. A possible correlation between plasma levels of certain cytokines and development of skin toxicity has been reported. The aim of this work was to investigate the possible contribution of IL-31 and IL-33, cytokines involved in disorders associated with itching, in the pathogenesis of pruritus in patients undergoing EGFR-TK inhibitors. We report a significant increase of IL-31 and IL-33 serum levels in a patient with a bronchioalveolar carcinoma, who had showed previous skin rash, xerosis, and pruritus during treatment with different EGFR-TK inhibitors. She developed intense iching during gefitinib therapy. Therefore, we had collected patient blood sample to evaluate IL-31 and IL-33 serum levels compared to controls, reporting a significant increase in serum of patient. In the light of these findings, EGFR-TK inhibitors-related symptoms of dermatologic toxicities might be related to the release of IL-31 and IL-33. In particular, it is supposable that EGFR-TK inhibitors could cause keratinocytes injury, the release of IL-33 and the consequent interaction with its receptor on mast cells, that induces the secretion of several factors capable to cause skin manifestations, included IL-31, a known pruritus-inducing cytokine. This report, to the best of our knowledge, is the first work describing a possible involvement of IL-31/IL-33 axis in the pathogenesis of skin side effects related to EGFR-TK inhibitors treatment.