T-cell mediated responses against alpha-foetoprotein in hepatocellular carcinoma: Relationship with hepatitis C virus infection, tumour phenotype and patients’ survival

Background Alpha-foetoprotein (AFP) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). However, T-cell response (TR) to AFP is suppressed in HCC due to immune evasion. It is unknown whether HCV infection may pre-condition TR against AFP, or whether TR may influence the clinical course of HCC. Methods We prospectively enrolled 18 HCV+ treatment-naïve patients with cirrhosis (CC), 18 HCV+ HCC cases and 17 HCV- HCC cases. TR was quantified by ELISPOT using assays specific to interleukin (IL) 2, IL10 and granulocyte-monocyte colony stimulating factor (GM-CSF) on ex-vivo peripheral blood mononuclear cells (PBMC) stimulated in vitro with AFP peptides. Cytokine ratios were compared between groups and with clinicopathological features of HCC, including overall survival (OS). Results The proportion of AFP-specific responses was not different across the studied groups for any of the assayed cytokines. AFP-specific IL-2 responses were increased in larger (P = .02), multifocal tumours (P = .01) and correlated with advanced disease (P = .01). TRs did not correlate with other clinicopathological factors and did not predict for OS. Conclusion Tumour stage but not HCV infection is related to the emergence of anti-AFP TRs. These data enable formulation of a rationale for the further development of anti-AFP immunotherapy in HCC, facilitating optimal patient selection for future studies

Profiling the patients visiting the emergency room for musculoskeletal complaints: characteristics and outcomes

Non-traumatic musculoskeletal complaints are often dealt with by emergency room (ER) physicians. We aimed to quantify how many patients with such complaints have conditions requiring immediate recognition and treatment, versus specialist referral, versus primary care. We retrieved the clinical records of all the patients admitted to the ER department of our hospital along 1\ua0year. Pediatric (age <14\ua0years) and obstetrics/gynecology cases were excluded. Data from all patients visiting the ER for non-traumatic musculoskeletal complaints were classified as follows: true emergencies (i.e., conditions associated with high morbidity/mortality risk), urgencies (i.e., conditions requiring prompt referral to a specialist), and non-urgent conditions (to be dealt with in primary care). Out of 54,915 patients evaluated in the ER of our hospital, 1652 patients complained of non-traumatic musculoskeletal symptoms (3.0\ua0%): Back pain accounted for 944/1652 ER visits (57.1\ua0%), including 6 emergencies (0.6\ua0%) and 105 urgent conditions (11.1\ua0%). Among the remaining 708 patients (42.9\ua0%) who presented with complaints concerning a peripheral joint, true emergencies were 2/708 (0.3\ua0%) while 210/708 were urgent conditions (29.7\ua0%). Although patients who present to ER physicians with musculoskeletal complaints have rarely true emergencies, many of them are in need of urgent treatment and prompt specialist referral

Overlapping polyclonal lymphoproliferative disorders

Multicentric Castleman disease (MCD) is a rare clinical entity characterized by a polyclonal lymphoid proliferation, leading to generalized lymphadenopathy, organomegaly and systemic symptoms. It has been reported in association with either other monoclonal or polyclonal lymphoid disorders, such as POEMS syndrome and immunoglobulin (Ig)G4-related disease. We present a patient showing a variant of MCD, sharing common features with POEMS syndrome and associated with the proliferation of IgG4-producing plasma cells

Increased plasma levels of Gas6 and its soluble tyrosine kinase receptors Mer and Axl are associated with immunological activity and severity of lupus nephritis

Growth arrest-specific 6 (Gas6) and its receptors have been shown to play a crucial role in the homeostasis of the innate immune system by regulating apoptosis and inflammation. We aimed to verify whether an impairment of this system is associated with systemic lupus erythematosus (SLE) disease activity and with lupus nephritis (LN)