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AbstractBackgroundThe mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine reactivity.MethodsWe prospectively collected blood before (D0) and at multiple time points after splenectomy (7 days - D7, 30 days - D30, 90 days - D90, 180 days - D180, and 360 days - D360) and measured the cytokines releasing capacity of IL-6, TNF-alpha and IL-10 from whole blood under LPS stimulation which we normalized to the monocytes number.ResultsWhen analyzing all splenectomies at D0, D7 and D30, normalized ΔTNF-alpha significantly dropped after splenectomy (p= .0038) and normalized ΔIL-6 and ΔIL-10 did not significantly change. More specifically, normalized ΔTNF-alpha dropped after TS (p= .0568) and significantly increased after S/PS (p= .0388). Open surgery induced a decrease in normalized ΔTNF-alpha (p= .0970), whereas minimally invasive (MI) surgery significantly increased the normalized ΔTNF-alpha releasing capacity (p= .0178). The cytokine levels were heterogenous between pathologies at D0, and ΔIL-6 dropped mainly in cirrhotic patients after splenectomy (all underwent TS), ΔTNF-alpha dropped in immune thrombocytopenic purpura patients (all underwent TS), but increased in spherocytosis (91% underwent S/PS) after splenectomy.ConclusionsSplenectomy induces a decrease of the pro-inflammatory cytokine TNF-alpha and if splenic parenchyma is spared and the surgery is performed MI, this change is hindered.

Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities. Biomarkers are potentially valuable clinical tools in this context, but to date, no single biomarker has been shown to perform adequately. Hence, in an effort to discover novel diagnostic and prognostic markers in sepsis, new genomic approaches have been employed. As a result, a number of small regulatory molecules called microRNAs (miRNAs) have been identified as key regulators of the inflammatory response. Although deregulated miRNA expression is increasingly well described, the pathophysiological roles of these molecules in sepsis have yet to be fully defined. Moreover, non-human miRNAs, including two Kaposi Sarcoma herpesvirus-encoded miRNAs, are implicated in sepsis and may drive enhanced secretion of pro-inflammatory and anti-inflammatory cytokines exacerbating sepsis. A better understanding of the mechanism of action of both cellular and viral miRNAs, and their interactions with immune and inflammatory cascades, may therefore identify novel therapeutic targets in sepsis and make biomarker-guided therapy a realistic prospect.

ABSTRACTAlthough the therapeutic efficacy and commercial success of monoclonal antibodies (mAbs) are tremendous, the design and discovery of new candidates remain a time and cost-intensive endeavor. In this regard, progress in the generation of data describing antigen binding and developability, computational methodology, and artificial intelligence may pave the way for a new era of in silicoon-demand immunotherapeutics design and discovery. Here, we argue that the main necessary machine learning (ML) components for an in silicomAb sequence generator are: understanding of the rules of mAb-antigen binding, capacity to modularly combine mAb design parameters, and algorithms for unconstrained parameter-driven in silicomAb sequence synthesis. We review the current progress toward the realization of these necessary components and discuss the challenges that must be overcome to allow the on-demand ML-based discovery and design of fit-for-purpose mAb therapeutic candidates.

Abstract: Background: This study was designed to compare the laparoscopic subtotal splenectomy with the robotic approach in patients with hereditary spherocytosis. Methods: Thirty-two consecutive subtotal splenectomies by minimal approach in patients with hereditary spherocytosis were analyzed (10 robotic vs. 22 laparoscopic subtotal splenectomies). Results: A significant difference was found for the robotic approach regarding blood loss, vascular dissection duration, and splenic remnant size. Follow-up for 4–103 months was available. Conclusions: Subtotal splenectomy seems to be a suitable candidate for robotic surgery, requiring a delicate dissection of the splenic vessels and a correct intraoperative evaluation of the splenic remnant. Robotic subtotal splenectomy is comparable to laparoscopy in terms of hospital stay and complication. The main benefits are lower blood loss rate, vascular dissection time, and a better evaluation of the splenic remnant volume.

We present an entirely robotic total pelvic exenteration and extended lymphadenectomy with “barreled ureterocutaneostomy” and end colostomy for recurrent endometrial cancer. In 1948, Brunschwig first described a pelvic exenteration as treatment of advanced recurrent malignancy in the pelvis. Currently it represents the only potentially curative option for patients with recurrent endometrial cancer.