Reversed distal laterodigital adipofascial flap for nail-bed reconstruction.

BACKGROUND: Lesions of the distal phalanges of the fingers frequently involve the nail bed. There are few therapeutic options for nail-bed reconstruction and they often lead to painful scars and onychodystrophy. We present our experience with the distal adipofascial laterodigital reverse flap. METHODS: Fifteen patients (average age 46.33 years, range 28-73) with tumors or traumatic injuries (crush injuries, nail avulsion, and partial fingertip amputations) of the nail bed, underwent digital reconstruction through the distal adipofascial laterodigital reverse flap from June 2018 to August 2019. The size of the fingertip defect covered with the flap was ranged between 1.1 × 1.1 and 1.6 × 1.2 cm (average size 1.4 × 1.2 cm). The flap was harvested enrolling subcutaneous tissue from the lateral aspect of the middle and distal phalanx from the less damaged side. RESULTS: The average size of the harvested flaps was 1.3 × 1.2 cm (range 1.1 × 1.0 to 1.4 × 1.1 cm). All adipofascial flaps survived entirely and the nail bed healed in all patients, with an average healing time of 21 days and a subsequent regrowth of the nail. The follow up ranged from 6 to 12 months, with a mean of 7 months. CONCLUSIONS: The distal reverse adipofascial flap provides a very versatile and reliable coverage of the distal finger and its nail bed. It is a rapid and reproducible surgical procedure with poor morbidity for the donor site. LEVEL OF EVIDENCE: IV.

Pathological Fracture of the Proximal Humerus Occurred on Metastases of Probable Kidney Origin in the Absence of Primary Lesions: A Case Report.

Cancer of unknown primary (CUP) origin represents a diagnostic and therapeutic challenge. These tumours spread to different parts of the body even if the site of origin has not been identified. When renal metastases are observed without an obvious primary lesion, it is important to exclude the possibility of a primary kidney tumour that may be unknown or too small to be detected. The diagnosis of CUP is established after a careful clinical evaluation and diagnostic tests, including blood chemistry and laboratory tests, instrumental exams (CT, MRI, PET, bone scan), biopsy, and molecular and cytogenetic analysis. Once the diagnosis of CUP with kidney metastases is confirmed, treatment depends on the location of the metastases, the patient's health status, and available treatment options. The latter includes surgery to remove metastases, radiation therapy, or systemic treatment such as chemotherapy or immunotherapy. It is important that patients with CUP are evaluated by a multidisciplinary team of specialists, who can contribute to planning the most appropriate treatment. In this article, we report the clinical case of a patient with a pathological fracture of the proximal humerus which occurred on metastases of probable renal origin in the absence of primary lesions.

A case of critical ischemia of the lower limbs: critical elements and possible medico-legal implications.

Peripheral arterial disease (PAD) is an atherosclerotic process that causes stenosis and occlusion of non-cerebral and non-coronary arteries. Critical ischemia of the lower limbs is the most advanced and severe state of arterial disease. The purpose of this work is to underline the importance of a timely diagnostic-therapeutic framework in case of critical ischemia of the lower limbs, through a precise, coordinated, and multidisciplinary teamwork. A significant example is represented by the presentation of a clinical case that came to our observation following a request for compensation and which required an adequate evaluation in the medical-legal field. This work will make possible to clarify any profiles of medical professional responsibility, with specific reference to the predictability and preventability of the unfavorable events that have occurred, and which have led to a progressive worsening of the patient's clinical condition, which then resulted in the amputation of the lower limb, associated to organic deterioration and progressive complete permanent disability. In these cases, the collection of semeiological data must be careful, meticulous, and completed by suitable instrumental investigations. These data, with the exhaustive compilation of the medical record, play a decisive role even in the presence of adverse events and/or infrequent complications, in order to demonstrate from a medico-legal point of view that despite the implementation of all precautions codified by the specialized discipline, the adverse event, however foreseeable, is not always concretely preventable and therefore avoidable, being included in the non-negligent "complication" and not necessarily attributable to professional responsibility.

Atrophic pseudarthrosis of humeral diaphyseal fractures: medico-legal implications and methodological analysis of the evaluation.

Humeral shaft fractures account for 1- 3% of all fractures and about 20-27% of those involving the humerus. In the past they were often conservatively treated, with an acceptable consolidation rate. Open reduction and internal fixation (ORIF) is the best choice in polytrauma patients, in complex or pathological fractures and in those associated with vascular injuries. Regardless the type of fixation used, these fractures can evolve into delayed union or pseudarthrosis (PSA). It should be noted that the humeral shaft itself has a high intrinsic healing potential, due to the blood supply provided by the surrounding muscles. The aim of this work is to evaluate whether the causes that led to the development of atrophic pseudarthrosis in a humeral diaphyseal fracture are attributable to inadequate management of this fearful complication and to highlight the possible medico-legal repercussions. We will try to verify whether the currently used forensic evaluation parameters of permanent disability are appropriate and adequate in relation to the complexity of such injuries. This complexity also includes the repercussions on the ergonomic efficiency of the entire limb, the relative possible postural alterations, the inevitable extension of the period of traumatic illness and the relative repercussions on the overall compromised structure of the subject.

A case of infection and severe soft tissue loss of the elbow. Planning surgical treatment in compliance with good clinical-care practices and medico-legal implications.

Soft tissue loss around  the elbow, with tendons, nerves and bone exposure,  represents a challenging condition, often requiring a complex and accurate surgical reconstruction. Inadequate repair of soft tissue defects may in fact compromise further reconstructive orthopedic procedures, including  osteosynthesis and joint replacement. A correct reparative sequence of these lesions usually starts with an appropriate debridement and removal of all non-viable and infected tissues, followed by soft tissues management through plastic and reconstructive techniques. Here we present a case report, showing a successful surgical solution, using a local muscular flap. The results are discussed in light of their functional and medico-legal implications, considering the frequent occurrence of partial functional recovery, the disabling impact on social and work activities and the aesthetic sequelae of these lesions, even in spite of a successful treatment.

Nerve lesions during arthroscopic procedure: a literature overview.

Arthroscopy is more and more popular. Although minimally-invasive, it's not completely free of complications as nerves lesions which can be invalidating for the patient and frustrating for the surgeon with significant economic, psychological and medico-legal implications. The purpose was to review the literature about nerve injuries related to arthroscopy. A scientific literature review was performed in PubMed/Medline, including articles dealing with cases of iatrogen lesions of the peripheral nerves occurred during arthroscopic procedures. These lesions are mainly due to direct damage by nerve section while cutting for making the portals or during surgical maneuvers, or indirect damage due to traction or pressure mechanisms especially for errors in patient positioning. Also the tourniquet can lead to compression and ischemic nerve injury. Arthroscopy can cause both transient and permanent neurological lesions manifested with dysesthesia up to paralysis according to Seddon's classification in neuroapraxia, axonotmesis and neurotmesis. Incidence of complications in general and of nerve injuries during arthroscopy are reported by joint. A rigorous respect for surgical technique and all perioperative precautions, particularly in relation to the positioning of the patient, greatly reduce the risk of nerve injury. The suggested waiting time before surgical nerve revision is 6 months. In the meanwhile the patient should perform physiotherapy constantly and improvements should be evaluated with clinical examination and electromyography 15-20 days after the lesion, and thereafter at 3 and 6 months.

Ion-Mediated Cross-linking of Biopolymers Confined at Liquid/Liquid Interfaces Probed by In Situ High-Energy Grazing Incidence X-ray Photon Correlation Spectroscopy.

As manifested in biological cell membranes, the confinement of chemical reactions at the 2D interfaces significantly improves the reaction efficacy. The interface between two liquid phases is used in various key processes in industries, such as in food emulsification and floatation. However, monitoring the changes in the mechanics and dynamics of molecules confined at the liquid/liquid interfaces still remains a scientific challenge because it is nontrivial to access the interface buried under a liquid phase. Herein, we report the in situ monitoring of the cross-linking of polyalginate mediated by Ca2+ ions at the oil/water interface by grazing incidence X-ray photon correlation spectroscopy (GIXPCS). We first optimized the reaction conditions with the aid of interfacial shear rheology and then performed GIXPCS using a high-energy synchrotron X-ray beam (22 keV) that guarantees sufficiently high transmittance through the oil phase. The intensity autocorrelation functions implied that the formation of a percolated network of polyalginate is accompanied by increasing relaxation time. Moreover, the relaxation rate scales linearly with the momentum transfer parallel to the interface, suggesting that the process is driven by hyperdiffusive propagation but not by Brownian diffusion. Our data indicated that high-energy GIXPCS has potential for in situ monitoring of changes in the dynamics of polymers confined between two liquid phases.

New Class of Crosslinker-Free Nanofiber Biomaterials from Hydra Nematocyst Proteins.

Nematocysts, the stinging organelles of cnidarians, have remarkable mechanical properties. Hydra nematocyst capsules undergo volume changes of 50% during their explosive exocytosis and withstand osmotic pressures of beyond 100 bar. Recently, two novel protein components building up the nematocyst capsule wall in Hydra were identified. The cnidarian proline-rich protein 1 (CPP-1) characterized by a "rigid" polyproline motif and the elastic Cnidoin possessing a silk-like domain were shown to be part of the capsule structure via short cysteine-rich domains that spontaneously crosslink the proteins via disulfide bonds. In this study, recombinant Cnidoin and CPP-1 are expressed in E. coli and the elastic modulus of spontaneously crosslinked bulk proteins is compared with that of isolated nematocysts. For the fabrication of uniform protein nanofibers by electrospinning, the preparative conditions are systematically optimized. Both fibers remain stable even after rigorous washing and immersion into bulk water owing to the simultaneous crosslinking of cysteine-rich domains. This makes our nanofibers clearly different from other protein nanofibers that are not stable without chemical crosslinkers. Following the quantitative assessment of mechanical properties, the potential of Cnidoin and CPP-1 nanofibers is examined towards the maintenance of human mesenchymal stem cells.

Hybrid coating of alginate microbeads based on protein-biopolymer multilayers for encapsulation of probiotics.

A hybrid coating based on multilayers of proteins and biopolymers was developed to enhance the protection performance of alginate microbeads against acidic conditions for delivery of probiotics (Lactobacillus rhamnosus GG). Zeta potential measurements and quartz crystal microbalance with dissipation confirmed layer-by-layer deposition of protein-polymer layers. The stability of protein-based coatings during simulated gastric fluid (SGF) treatment was monitored by microscopy. Protein-coated microbeads were partially dismantled, whereas polymer-coated microbeads were intact after a sequential treatment in simulated gastric and intestinal fluids. This suggests that hybrid formulation offers an advantage over the coatings based on biopolymer multilayers in terms of better release of bacteria. Uncoated alginate microbeads completely dissolved and could not protect bacteria after SGF treatment whereas microbeads with hybrid coating showed increased physical stability and a modest decrease of culturability of 3.8 log units. Therefore, this work provides a concept for future protein-based hybrid coatings for bacterial delivery systems.

Shear-Enhanced Dynamic Adhesion of Lactobacillus rhamnosus GG on Intestinal Epithelia: Correlative Effect of Protein Expression and Interface Mechanics.

The oral uptake of probiotic microorganisms as food additives is one widely used strategy to sustain and improve the homeostasis of intestinal microbiota that protect the intestinal epithelia from attack by pathogenic bacteria. Once delivered to the ileum and colon, probiotics must adhere and form colonies on mucus that coats the surface of intestinal epithelial cells. Although an increasing amount of knowledge about the genetic and molecular level mechanisms of probiotics-mucus interactions has been accumulated, little is known about the physicochemical aspects of probiotics-mucus interactions under physiological shear in intestines. In this study, we established well-defined models of intestinal epithelial cell monolayers based on two major constituents of gut epithelia, enterocytes and goblet cells. First, the formation of a polarized cell monolayer sealed by tight junctions was monitored by transepithelial electrical resistance over time. The establishment of tight junctions and secretion of mucus proteins (mucin) was confirmed by immunofluorescence staining. In the next step, we measured the elasticity of cell monolayer surfaces by indentation using particle-assisted atomic force microscopy. The effective elastic modulus of goblet cell-like cells was 30 times smaller compared to that of enterocyte-like cells, which can be attributed to the secretion of a 3 µm thick mucin layer. As probiotics, we used Lactobacillus rhamnosus GG (LGG), which is one of the most widely used strains as food additives. To investigate the dynamic adhesion of LGG to the intestine model surface, we transferred the epithelial cell monolayer into a microfluidic chamber. A distinct difference in dynamic adhesion between two cell types was observed, which could be attributed to the difference in the mucin expression amount. Remarkably, we found that the dynamic LGG adhesion is enhanced by the increase in shear stress, showing a maximum binding efficiency at 0.3 Pa. Finally, we examined the persistence of LGG adhesion by a stepwise increase in the shear stress exerted on adherent LGG, demonstrating that LGG could withstand high shear stress even beyond that of physiological stress. The obtained results present a large potential to quantitatively understand the influence of engineered foods and probiotics on the homeostasis of microbiota on the surface of intestinal epithelia.

Nonclassical Interactions of Phosphatidylcholine with Mucin Protect Intestinal Surfaces: A Microinterferometry Study.

Albeit many studies demonstrated that the accumulation of phospholipids in the intestinal mucosal surfaces is essential for the protection of colon epithelia against pathogenic bacteria, the mechanism of interactions between phospholipids and the surface protein mucin is not well understood. In this study, the significance of interfacial interactions between phospholipids and mucin proteins was quantified by the combination of an in vitro intestinal surface model and label-free microinterferometry. The model of intestinal surfaces consists of planar lipid membranes deposited on solid substrates (supported membranes) that display mucin proteins at defined surface densities. Following the quantitative characterization of the systems, we monitored the vertical fluctuation of 10 µm-large particles on model intestinal surfaces by using microinterferometry, and calculated the effective interfacial interaction potentials by analytically solving the Langevin equation. We found that the spring constant of interfacial potentials calculated based on a harmonic approximation increased concomitantly with the increase in surface potentials, indicating the dominant role of electrostatic interactions. Intriguingly, the spring constants of particles coated with phospholipids do not follow electrostatic interactions. The spring constant of particles coated with zwitterionic phosphatidylcholine was larger compared to membranes incorporating positively or negatively charged lipids. Our data suggested the presence of another underlying molecular level interaction, such as phosphocholine-saccharide interactions. The fact that phosphatidylcholine sustains the binding capability to enzymatically degraded mucin suggests that the direct delivery of phosphatidylcholine to the damaged mucus is a promising strategy for the better treatment of patients affected by inflammatory bowel diseases.

Nonlinear Viscoelasticity of Highly Ordered, Two-Dimensional Assemblies of Metal Nanoparticles Confined at the Air/Water Interface.

In this study, we investigated the viscoelastic properties of metal nanoparticle monolayers at the air/water interface by dilational rheology under periodic oscillation of surface area. Au nanoparticles capped with oleylamine form a stable, dense monolayer on a Langmuir film balance. The stress response function of a nanoparticle monolayer was first analyzed using the classical Kelvin-Voigt model, yielding the spring constant and viscosity. The obtained results suggest that the monolayer of nanoparticles is predominantly elastic, forming a two-dimensional physical gel. As the global shape of the signal exhibited a clear nonlinearity, we further analyzed the data with the higher modes in the Fourier series expansion. The imaginary part of the higher mode signal was stronger than the real part, suggesting that the dissipative term mainly causes the nonlinearity. Intriguingly, the response function measured at larger strain amplitude became asymmetric, accompanied by the emergence of even modes. The significance of interactions between nanoparticles was quantitatively assessed by calculating the potential of mean force, indicating that the lateral correlation could reach up to the distance much larger than the particle diameter. The influence of surface chemical functions and core metal has also been examined by using Au nanoparticles capped with partially fluorinated alkanethiolate and Ag nanoparticles capped with myristic acid. The combination of dilational rheology and correlation analyses can help us precisely control two-dimensional colloidal assembly of metal nanoparticles with fine-adjustable localized surface plasmon resonance.

Biopolymer-Based Minimal Formulations Boost Viability and Metabolic Functionality of Probiotics Lactobacillus rhamnosus GG through Gastrointestinal Passage.

The delivery of probiotic microorganisms as food additives via oral administration is a straightforward strategy to improve the intestinal microbiota. To protect probiotics from the harsh environments in the stomach and small intestine, it is necessary to formulate them in biocompatible carriers, which finally release them in the ileum and colon without losing their viability and functions. Despite major progresses in various polymer-based formulations, many of them are highly heterogeneous and too large in size and hence often "felt" by the tongue. In this study, we established a new formulation for probiotics Lactobacillus rhamnosus GG (LGG) and systematically correlated the physicochemical properties of formulations with the functions of probiotics after the delivery to different gastrointestinal compartments. By reducing the stirring speed by 1 order of magnitude during the emulsification of polyalginate in the presence of xanthan gum, we fabricated microparticles with a size well below the limit of human oral sensory systems. To improve the chemical stability, we deposited chitosan and polyalginate layers on particle surfaces and found that the deposition of a 20 nm-thick layer is already sufficient to perfectly sustain the viability of all LGG. Compared to free LGG, the colony-forming units of LGG in these formulations were by factors of 107 larger in stomach fluid and 104 larger in small intestine fluid. The metabolic functionality of LGG in polymer formulations was assessed by measuring the amount of lactate produced by LGG in a human gastrointestinal simulator, showing 5 orders of magnitude larger values compared to free LGG. The obtained results have demonstrated that the minimal formulation of LGG established here boosts not only the viability but also the metabolic functionality of probiotics throughout oral uptake, passage through the gastrointestinal tract, and delivery to the ileum and colon.

Lipid-coated mesoporous silica microparticles for the controlled delivery of ß-galactosidase into intestines.

ß-Galactosidase has been drawing increasing attention for the treatment of lactose intolerance, but its delivery has been impeded by degradation under gastric conditions. We have demonstrated that the coating of mesoporous silica microparticles (diameter ≈ 9 µm, pore size ≈ 25 nm) with dioleoylphosphatidylcholine membranes significantly improved the loading capability and protected the enzymes from the loss of function under simulated gastric conditions. Once the particles are transferred to simulated intestinal conditions, the digestion of phosphatidylcholine with pancreatin led to the release of functional ß-galactosidase. The coating of mesoporous silica nanoparticles with a single phospholipid bilayer opens up a large potential towards the controlled release of orally administrated drugs or enzymes to the intestines.

Accumulation of phosphatidylcholine on gut mucosal surface is not dominated by electrostatic interactions.

The accumulation of phosphatidylcholine (PC) in the intestinal mucus layer is crucial for the protection of colon epithelia from the bacterial attack. It has been reported that the depletion of PC is a distinct feature of ulcerative colitis. Here we addressed the question how PC interacts with its binding proteins, the mucins, which may establish the hydrophobic barrier against colonic microbiota. In the first step, the interactions of dioleoylphosphatidylcholine (DOPC) with two mucin preparations from porcine stomach, have been studied using dynamic light scattering, zeta potential measurement, and Langmuir isotherms, suggesting that mucin binds to the surface of DOPC vesicles. The enthalpy of mucin-PC interaction could be determined by isothermal titration calorimetry. The high affinity to PC found for both mucin types seems reasonable, as they mainly consist of mucin 2, a major constituent of the flowing mucus. Moreover, by the systematic variation of net charges, we concluded that the zwitterionic DOPC has the strongest binding affinity that cannot be explained within the electrostatic interactions between charged molecules.