Hidradenitis Suppurativa: Proposal of Classification in Two Endotypes with Two-Step Cluster Analysis.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disorder of the pilosebaceous unit. Currently, several attempts have been made to classify this disease according to its pathogenesis and clinical manifestations. We attempted at classifying 103 patients using two-step cluster analysis. METHODS: The final model included body mass index, C-reactive protein (CRP), and serum concentrations of IL-1, IL-6, IL-17, and IL-10 as continuous variables, and sex, later/early onset, anterior/posterior lesion sites, presence/absence of sinus tracts, nodules and abscesses, positive/negative history of pilonidal sinus, and presence/absence of mutations in gamma-secretase subunits (APH1A, APH1B, MEFV, NCSTN, PSEN1, PSEN2, PSENEN, PSTPIP1) as qualitative variables. RESULTS: The resultant model defined two groupings or clusters: cluster 1 (64.9% of patients) characterized by nonobese males, with nodular lesions in posterior sites, early-onset HS, higher IL-10, presence of gamma-secretase mutations, and history of pilonidal sinus; and cluster 2 (35.1% of patients) characterized by obese females or males, with lesions in anterior sites, more presence of sinus tracts and abscesses and less nodules, later-onset HS, and higher concentrations of IL-1, CRP, IL-17, and IL-6. Severity measures (Hurley, HS-PGA, and IHS4) and tobacco use were discarded because the analysis found them to be less relevant for clustering. CONCLUSION: Our resultant model confirms the clinical impression that HS is a disease spectrum with two pathogenic poles defining two clusters or endotypes. The probability of having severe disease was equally distributed in the two clusters. The variable with the highest predictive value for clustering was involvement of typical anterior sites (axillae, submammary) or atypical posterior sites (back, gluteal). Serum concentrations of interleukins, tobacco use, and sex had a lower predictive power for clustering.

mTOR intersects antibody-inducing signals from TACI in marginal zone B cells.

Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB. Disruption of TACI-mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-κB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs.

Evidence Based Medicine (EBM) and Evidence Based Radiology (EBR) in the follow-up of the patients after surgery for lung and colon-rectal carcinoma.

PURPOSE: A) To define the role of diagnostic imaging modalities in the follow-up of patients after surgery for solid cancer, using an Evidence Based Medicine (EBM) approach; B) to assess the possible discrepancies between the theoretical model and the clinical protocols currently used for the follow-up of treated patients; c) to compare the real costs of the radiological examinations performed in a group of cancer patients followed up after surgery and the theoretical costs that would have been incurred had the patients been followed up according to the theoretical (evidence-based) follow-up programme. MATERIALS AND METHODS: We searched traditional and secondary databases for research papers and guidelines by international scientific societies published in the last 10 years and concerning the clinical impact of follow-up programs in patients operated on for colorectal and lung carcinoma. The papers were selected based on level of evidence using the systematic review approach of EBM. In each paper selected, we considered the overall survival and disease-free survival, quality of life, side and toxic effects of therapy, costs and psychological aspects to formulate a judgement on the usefulness of the radiological tests. Subsequently, the clinical and imaging follow-up of 40 patients who had undergone surgical resection for colorectal cancer (20 patients) and lung cancer (20 patients) between 1998 and 2004 were retrospectively reviewed, and the costs of the follow-up programs for the two groups were analysed and compared with those of the theoretical evidence-based programmes. RESULTS: Of the 41 papers selected after systematic review only nine datasets were considered for our final analysis. The majority of papers (7 out of 9) and all the guidelines published by international Scientific Societies agreed on the poor value of closed imaging in the follow-up of patients who have undergone surgery for colorectal and lung cancer. A significant difference was found between the real costs of the follow-up programmes implemented in the 40 patients considered and the theoretical costs derived from the guideline recommendations (an excess of 99.06% for lung cancer, and 93.6% for colon cancer). CONCLUSIONS: Our findings can serve as a basis to start a discussion within the scientific community about the role of radiological follow-up in cancer patients with the aim of defining a more rational use of resources.