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Introduction: Superobesity (SO) is defined as a BMI > 50 Kg/m 2 , and represents the extreme severity of the disease, resulting in a challenge for the surgeons., Methods: In this retrospective study we aimed to compare the outcomes of SO patients compared to morbidly obese (MO) patients., Results: We included in this study 154 MO patients, with a median preoperative BMI of 40.8 kg/m 2 , and 19 SO patients with median preoperative BMI of 54.9 kg/m 2 . The MO patients underwent sleeve gastrectomy (SG) in 62 (40.3%) cases, laparoscopic Roux-and-Y gastric bypass (LRYGBP) in 85 (55.2%) cases and One-Anastomosis Gastric Bypass (OAGB) in 7 (4.5%) cases. underwent OAGB. The patients in the SO group were submitted to SG in 11 (57.9%) cases, LRYGBP in 5 (26.3%) cases, and OAGB in 3 (15.8%). At 24-month follow-up, an excess weight loss (EWL) >50% was achieved in 129 (83.8%) patients in the MO group and in 15 (78.9%) in the SO group ( p  = 0.53). A BMI < 35 kg/m 2 was achieved in 137 (89%) patients in the MO group and from 8 (42.2%) patients in the SO group ( p  < 0.001). The total weight loss was significantly directly related to the initial BMI. Superobesity was identified as independent risk factor for surgical failure when considering the outcome of BMI < 35 kg/m 2 ., Discussion: Our study confirms that, although SO patients tend to gain a greater weight loss than MO patients, they less frequently achieve the desired BMI target. In this setting, it should be necessary to re-consider malabsorptive procedures as first choice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Medas, Moroni, Deidda, Zorcolo, Restivo, Canu, Cappellacci, Calò, Pintus and Fantola.)

Affitins constitute a class of small proteins belonging to Sul7d family, which, in microorganisms such as Sulfolobus acidocaldarius , bind DNA preventing its denaturation. Thanks to their stability and small size (60-66 residues in length) they have been considered as ideal candidates for engineering and have been used for more than 10 years now, for different applications. The individuation of a mutant able to recognize a specific target does not imply the knowledge of the binding geometry between the two proteins. However, its identification is of undoubted importance but not always experimentally accessible. For this reason, computational approaches such as protein-protein docking can be helpful for an initial structural characterization of the complex. This method, which produces tens of putative binding geometries ordered according to a binding score, needs to be followed by a further reranking procedure for finding the most plausible one. In the present paper, we use the server ClusPro for generating docking models of affitins with different protein partners whose experimental structures are available in the Protein Data Bank. Then, we apply two protocols for reranking the docking models. The first one investigates their stability by means of Molecular Dynamics simulations; the second one, instead, compares the docking models with the interacting residues predicted by the Matrix of Local Coupling Energies method. Results show that the more efficient way to deal with the reranking problem is to consider the information given by the two protocols together, i.e. employing a consensus approach., Competing Interests: Author AM is employed by Bracco S.p.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ranaudo, Cosentino, Greco, Moro, Bonardi, Maiocchi and Moroni.)

Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers. The recent years have witnessed significant research efforts to facilitate drug discovery on LH/PLODs, including molecular structure characterizations and development of reliable high-throughput enzymatic assays. Using a combination of biochemistry and in silico studies, we characterized the dual role of Fe 2+ as simultaneous cofactor and inhibitor of lysyl hydroxylase activity and studied the effect of a promiscuous Fe 2+ chelating agent, 2,2'-bipyridil, broadly considered a lysyl hydroxylase inhibitor. We found that at low concentrations, 2,2'-bipyridil unexpectedly enhances the LH enzymatic activity by reducing the inhibitory effect of excess Fe 2+ . Together, our results show a fine balance between Fe 2+ -dependent enzymatic activity and Fe 2+ -induced self-inhibited states, highlighting exquisite differences between LH/PLODs and related Fe 2+ , 2-oxoglutarate dioxygenases and suggesting that conventional structure-based approaches may not be suited for successful inhibitor development. These insights address outstanding questions regarding druggability of LH/PLOD lysyl hydroxylase catalytic site and provide a solid ground for upcoming drug discovery and screening campaigns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scietti, Moroni, Mattoteia, Fumagalli, De Marco, Negro, Chiapparino, Serapian, De Giorgi, Faravelli, Colombo and Forneris.)

Laparoscopy is the surgical standard of care for bariatric procedures; however, during the last two decades, the robotic approach has gained increasing interest. It is currently considered a safe and effective alternative to laparoscopy. This literature review investigates the role of the robotic approach for primary and revisional bariatric procedures, with the particular aim of comparing this technique with the standard-of-care laparoscopic approach. The feasibility of robotic dissection and suturing could have potential advantages: robotics may prevent the risk of leak and bleeding and other surgical complications, determining potential benefits in terms of operative time, length of hospital stay, and learning curve. Considering primary procedures, the literature reveals no advantages in robotic versus the laparoscopic approach for adjustable gastric banding and sleeve gastrectomy. Robotic Roux-en-Y gastric bypass is associated with a longer operative time and a shorter hospital length of stay than laparoscopy. The robotic approach in revisional surgery has been proven to be safe and effective. Despite the longer operative time, the robotic platform could achieve a lower bleeding rate compared with laparoscopy. The surgeon's selection criteria related to referrals to the robotic approach of difficult-perceived cases could represent a bias. In conclusion, robotic surgery can be considered a safe and effective approach in both primary and revisional bariatric surgery, despite the lack of evidence to support its routine use in primary bariatric surgery. However, in revisional bariatric surgery and in surgical complex procedures, the robotic approach could have potential benefits in terms of surgical complications and learning curves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fantola, Moroni, Runfola, Lai, Pintus, Gallucci, Pennestrì and Raffaelli.)