The microbiota of the bilio-pancreatic system: A cohort, STROBE-compliant study

Background: The gut microbiota play an essential role in protecting the host against pathogenic microorganisms by modulating immunity and regulating metabolic processes. In response to environmental factors, microbes can hugely alter their metabolism. These factors can substantially impact the host and have potential pathologic implications. Particularly pathogenic microorganisms colonizing pancreas and biliary tract tissues may be involved in chronic inflammation and cancer evolution. Purpose: To evaluate the effect of bile microbiota on survival in patients with pancreas and biliary tract disease (PBD). Patients and Methods: We investigated 152 Italian patients with cholelithiasis (CHL), cholangitis (CHA), cholangiocarcinoma (CCA), gallbladder carcinoma (GBC), pancreas head carcinoma (PHC), ampullary carcinoma (ACA), and chronic pancreatitis (CHP). Demographics, bile cultures, therapy, and survival rates were analyzed in cohorts (T1 death <6 months; T2 death <12 months; T3 death <18 months, T3S alive at 18 months). Results: The most common bacteria in T1 were E. coli, K. pneumoniae, andP. aeruginosa. In T2, the most common bacteria were E. coli and P. aeruginosa. InT3, there were no significant bacteria isolated, while in T3S the most common bacteria were like those found in T1. E. coli and K. pneumoniae were positive predictors of survival for PHC and ACA, respectively. E. coli, K. pneumoniae, andP. aeruginosa showed a high percentage of resistant bacteria to 3CGS, aminoglycosides class, and quinolone group especially at T1 and T2 in cancer patients. Conclusions: An unprecedented increase of E. coli in bile leads to a decrease in survival. We suggest that some strains isolated in bile samples may be considered within the group of risk factors in carcinogenesis and/or progression of hepato-biliary malignancy. A better understanding of bile microbiota in patients with PBD should lead to a multifaceted approach to rapidly detect and treat pathogens before patients enter the surgical setting in tandem with the implementation of the infection control policy

Complications and Solutions in Propeller Flap Surgery

open7siPropeller perforator flaps (PPFs) have long been proven as valid reconstructive tools for a wide range of soft tissue defects in different body regions. During the last decade, despite their numerous advantages, many authors have thoroughly analyzed outcomes of these flaps, sometimes discouraging their use mainly because of a high failure rate. Accurate patient selection, adequate preoperative planning, and an appropriate dissection technique seem to potentially improve outcomes. Our study provides a review of the relevant literature related to PPF complications and of our experience, describing reasons for failure, measures for preventing them, and approaches for a prompt evaluation and management of complications.embargoed_20210801Cajozzo, M; Jiga, LP; Jandali, Z; Muradov, M; Pignatti, M; Cordova, A; D'Arpa, SCajozzo, M; Jiga, LP; Jandali, Z; Muradov, M; Pignatti, M; Cordova, A; D'Arpa,

Surgical pathology and the diagnosis of invasive visceral yeast infection: two case reports and literature review

Invasive mycoses are life-threatening opportunistic infections that have recently emerged as a cause of morbidity and mortality following general and gastrointestinal surgery. Candida species are the main fungal strains of gut flora. Gastrointestinal tract surgery might lead to mucosal disruption and cause Candida spp. to disseminate in the bloodstream. Here we report and discuss the peculiar clinical and morphological presentation of two cases of gastrointestinal Candida albicans lesions in patients who underwent abdominal surgery. Although in the majority of cases reported in the literature, diagnosis was made on the basis of microbiological criteria, we suggest that morphological features of fungi in histological sections of appropriate surgical specimens could help to detect the degree of yeast colonization and identify patients at risk of developing severe abdominal Candida infection. Better prevention and early antifungal treatments are highlighted, and relevant scientific literature is reviewed

Porcine model for deep superior epigastric artery perforator flap harvesting: Anatomy and technique

BACKGROUND Microsurgical training on rats before starting with clinical practice is a well-established routine. Animal model training is less widespread for perforator flaps, although these flaps represent a technical challenge. Unlike other flaps, they require specific technical skills that need to be adequately trained on a living model 1 : a cadaver is not enough because no bleeding, vessel damage, or vasospasm can be simulated. 2 The purpose of this study was to assess the suitability of the porcine abdomen as a training model for the deep inferior epigastric artery perforator (DIEAP) flap, commonly used in human breast reconstruction. METHODS A female swine (Sus scrofa domesticus, ssp; weight 25kg) was used. The procedure was performed with the pig under general anesthesia and in the supine position. A deep superior epigastric artery perforator (DSEAP) flap was harvested on the left side of the abdomen, including the 3 cranial nipples and stopping in the midline to spare the contralateral flap for another dissection (as in bilateral breast reconstructions in humans; Fig. 1). All steps of a DIEAP harvest were simulated: superficial vein harvest, suprafascial perforator dissection, intramuscular perforator harvest with preservation of the nerves, and flap isolation. Observation of capillary refill was used to confirm flap viability at the end of the dissection. The procedure was recorded by means of a GoPro camera and simultaneously with a head mounted (4 7 magnification) Loupecam system. Photographs were taken using 2 cameras during surgery at relevant time points. RESULTS At the end of the dissection, the flap was viable. The subcutaneous adipose tissue of the pig is less represented than in human and pigs have an additional muscular layer, the panniculus carnosus, which is the analogue of the human Scarpa's fascia. The rectus fascia is thinner. The perforators are lined in 2 rows: 1 lateral and 1 medial, as in the DIEAP, and the intercostal nerves cross the vessels, as happens in humans. The porcine rectus abdominis muscle is thinner than the human one, but vessels' branching faithfully reproduces the human model. 1 We identified 5 perforating vessels of more than 1mm in diameter (2 lateral and 3 medial). We isolated a lateral perforator first and a medial one last: the latter was eventually used to nourish the flap (Fig. 2). CONCLUSIONS The DSEAP flap allows one to closely reproduce all the steps of DIEAP flap harvesting and also to carry out the intramuscular dissection of 2 perforators for each side (up to 4 for each animal), confirming the adequacy of this pig model for microsurgical training. The deep superior epigastric artery is dominant in pigs. 3 Despite this anatomical difference, the DSEAP allows one to reproduce the main steps of DIEAP flap harvesting, providing an excellent training model. Moreover, the presence of double perforating rows allows simulating the dissection twice on each side

Porcine model for gluteal artery perforator flap: Anatomy and technique

Although flap anatomy is well studied on cadavers and microsurgical techniques are well practiced on rats, still there are few training models for learning the techniques of perforator flap harvesting. The cadaver has no bloodstream, so accuracy of dissection cannot be evaluated and flap viability cannot be verified. Training on humans carries a high risk of flap damage. A living model for perforator flap harvest is needed to learn the technique before starting with its clinical application

Small footprint optoelectrodes using ring resonators for passive light localization

The combination of electrophysiology and optogenetics enables the exploration of how the brain operates down to a single neuron and its network activity. Neural probes are in vivo invasive devices that integrate sensors and stimulation sites to record and manipulate neuronal activity with high spatiotemporal resolution. State-of-the-art probes are limited by tradeoffs involving their lateral dimension, number of sensors, and ability to access independent stimulation sites. Here, we realize a highly scalable probe that features three-dimensional integration of small-footprint arrays of sensors and nanophotonic circuits to scale the density of sensors per cross-section by one order of magnitude with respect to state-of-the-art devices. For the first time, we overcome the spatial limit of the nanophotonic circuit by coupling only one waveguide to numerous optical ring resonators as passive nanophotonic switches. With this strategy, we achieve accurate on-demand light localization while avoiding spatially demanding bundles of waveguides and demonstrate the feasibility with a proof-of-concept device and its scalability towards high-resolution and low-damage neural optoelectrodes

Review of the Management of Relapsed Small-Cell Lung Cancer with Amrubicin Hydrochloride

Lung cancer is the leading cause of cancer death, and approximately 15% of all lung cancer patients have small-cell lung cancer (SCLC). Although second-line chemotherapy can produce tumor regression, the prognosis is poor. Amrubicin hydrochloride (AMR) is a synthetic anthracycline anticancer agent and a potent topoisomerase II inhibitor. Here, we discuss the features of SCLC, the chemistry, pharmacokinetics, and pharmacodynamics of AMR, the results of in vitro and in vivo studies, and the efficacy and safety of AMR monotherapy and combination therapy in clinical trials. With its predictable and manageable toxicities, AMR is one of the most attractive agents for the treatment of chemotherapy-sensitive and -refractory relapsed SCLC. Numerous studies are ongoing to define the applicability of AMR therapy for patients with SCLC. These clinical trials, including phase III studies, will clarify the status of AMR in the treatment of SCLC

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

DNA topoisomerase I and II expression in drug resistantgerm cell tumours

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase IIα is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and IIα were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase IIα expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and IIα expression (P=0.004) and downregulation of topoisomerase IIα after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits

Methanosarcina acetivorans C2A Topoisomerase IIIα, an Archaeal Enzyme with Promiscuity in Divalent Cation Dependence

Topoisomerases play a fundamental role in genome stability, DNA replication and repair. As a result, topoisomerases have served as therapeutic targets of interest in Eukarya and Bacteria, two of the three domains of life. Since members of Archaea, the third domain of life, have not been implicated in any diseased state to-date, there is a paucity of data on archaeal topoisomerases. Here we report Methanosarcina acetivorans TopoIIIα (MacTopoIIIα) as the first biochemically characterized mesophilic archaeal topoisomerase. Maximal activity for MacTopoIIIα was elicited at 30–35°C and 100 mM NaCl. As little as 10 fmol of the enzyme initiated DNA relaxation, and NaCl concentrations above 250 mM inhibited this activity. The present study also provides the first evidence that a type IA Topoisomerase has activity in the presence of all divalent cations tested (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+). Activity profiles were, however, specific to each metal. Known type I (ssDNA and camptothecin) and type II (etoposide, novobiocin and nalidixic acid) inhibitors with different mechanisms of action were used to demonstrate that MacTopoIIIα is a type IA topoisomerase. Alignment of MacTopoIIIα with characterized topoisomerases identified Y317 as the putative catalytic residue, and a Y317F mutation ablated DNA relaxation activity, demonstrating that Y317 is essential for catalysis. As the role of Domain V (C-terminal domain) is unclear, MacTopoIIIα was aligned with the canonical E. coli TopoI 67 kDa fragment in order to construct an N-terminal (1–586) and a C-terminal (587–752) fragment for analysis. Activity could neither be elicited from the fragments individually nor reconstituted from a mixture of the fragments, suggesting that native folding is impaired when the two fragments are expressed separately. Evidence that each of the split domains plays a role in Zn2+ binding of the enzyme is also provided