A systematic review of point-of-care abdominal ultrasound scans performed by general surgeons.

BACKGROUND: Ultrasound is an established imaging modality in general surgery. With the increasing use of bedside point-of-care ultrasounds, general surgeons have been incorporating this skill into their clinical practice. This systematic review provides an up-to-date summary of the evidence for abdominal ultrasound scans performed by general surgeons to diagnose intra-abdominal pathology. METHODS: Two independent reviewers searched the PubMed database between 1 January 1980 and 1 June 2020. Articles about surgeon-performed abdominal ultrasound in adult patients were included. Studies on trauma and vascular surgery were excluded. RESULTS: 26 articles met the inclusion criteria, presented as a narrative analysis. There was good evidence for the use of surgeon-performed ultrasound, particularly in gallstone-related diseases and moderate evidence for the use of ultrasound in appendicitis. Further evidence is required for point-of-care ultrasounds for other pathologies such as diverticulitis and groin hernias. Ultrasound training for general surgeons is variable with notable heterogeneity across studies. CONCLUSION: A standardised training programme for general surgeons will greatly improve confidence and skill. There is good evidence for the use of bedside ultrasound by general surgeons in the acute and elective setting with reduced time to definitive treatment and fewer unnecessary hospital admissions.

Engineering a platform for nerve regeneration with direct application to nerve repair technology.

The development of effective treatment options for repair of peripheral nerves is complicated by lack of knowledge concerning the interactions between cells and implants. A promising device, the multichannel scaffold, incorporates microporous channels, aligning glia and directing axonal growth across a nerve gap. To enhance clinical outcomes of nerve repair, a platform, representative of current implant technology, was engineered which 1) recapitulated key device features (porosity and linearity) and 2) demonstrated remyelination of adult neurons. The in vitro platform began with the study of Schwann cells on porous polycaprolactone (PCL) and poly(lactide co-glycolide) (PLGA) substrates. Surface roughness determined glial cell attachment, and an additional layer of topography, 40 µm linear features, aligned Schwann cells and axons. In addition, direct co-culture of sensory neurons with Schwann cells significantly increased neurite outgrowth, compared to neurons cultured alone (naive or pre-conditioned). In contrast to the control substrate (glass), on porous PCL substrates, Schwann cells differentiated into a mature myelinating phenotype, expressing Oct-6, MPZ and MBP. The direct applicability of this platform to nerve implants, including its response to physiological cues, allows for optimization of cell-material interactions, close observation of the regeneration process, and the study of therapeutics, necessary to advance peripheral nerve repair technology.

Microstructure and in vivo characterization of multi-channel nerve guidance scaffolds.

In a previous study, we demonstrated a novel manufacturing approach to fabricate multi-channel scaffolds (MCS) for use in spinal cord injuries (SCI). In the present study, we extended similar materials processing technology to fabricate significantly longer (5X) porous poly caprolactone (PCL) MCS and evaluated their efficacy in 1 cm sciatic peripheral nerve injury (PNI) model. Due to the increase in MCS dimensions and the challenges that may arise in a longer nerve gap model, microstructural characterization involved MCS wall permeability to assess nutrient flow, topography, and microstructural uniformity to evaluate the potential for homogeneous linear axon guidance. It was determined that the wall permeability dramatically varied from 0.02 ± 0.01 × 10-13 to 21.7 ± 11.4 × 10-13 m2 for 50% and 70% porous PCL, respectively. Using interferometry, the porous PCL surface roughness was determined to be 10.7 ± 1.2 µm, which is believed to be sufficient to promote cell integration. Using micro computed tomography, the 3D MCS microstructure was determined to be uniform over 1 cm with an open lumen volume of 44.6% ± 3.6%. In vivo implantation, in the rat sciatic nerve model, over 4 weeks, demonstrated that MCS scaffolds maintained structural integrity, were biocompatible, and supported linear axon guidance and distal end egress over 1 cm. Taken together, this study demonstrated that MCS technology previously developed for the SCI is also relevant to longer nerve gap PNI.

Knee Cartilage Regeneration with Umbilical Cord Mesenchymal Stem Cells Embedded in Collagen Scaffold Using Dry Arthroscopy Technique.

Articular cartilage injuries lead to progressive degeneration of the joint with subsequent progression to osteoarthritis, which currently becomes a serious health and economic issue. Due to limited capability for self-regeneration, cartilage repair remains a challenge for the present-day orthopedics. Currently, available therapeutic methods fail to provide satisfactory results. A search for other strategies that could regenerate a hyaline-like tissue with a durable effect and adequate mechanical properties is underway. Tissue engineering strategies comprise the use of an appropriately chosen scaffold in combination with seeding cells. Mesenchymal stem cells (MSC) provide an interesting new option in regenerative medicine with solid preclinical data and first promising clinical results. They act not only through direct cartilage formation, but also due to paracrine effects, such as releasing trophic factors, anti-inflammatory cytokines, and promoting angiogenesis. The MSC can be applied in an allogeneic setting without eliciting a host immune response. Out of the various available sources, MSC derived from Wharton's jelly of an umbilical cord seem to have many advantages over their counterparts. This article details a novel, single-staged, and minimally invasive technique for cartilage repair that involves dry arthroscopic implantation of scaffold-embedded allogenic mesenchymal stem cells isolated from umbilical cord Wharton's jelly.

Collagen: a network for regenerative medicine.

The basic building block of the extra-cellular matrix in native tissue is collagen. As a structural protein, collagen has an inherent biocompatibility making it an ideal material for regenerative medicine. Cellular response, mediated by integrins, is dictated by the structure and chemistry of the collagen fibers. Fiber formation, via fibrillogenesis, can be controlled in vitro by several factors: pH, ionic strength, and collagen structure. After formation, fibers are stabilized via cross-linking. The final bioactivity of collagen scaffolds is a result of both processes. By considering each step of fabrication, scaffolds can be tailored for the specific needs of each tissue, improving their therapeutic potential.

Altering crystal growth and annealing in ice-templated scaffolds.

The potential applications of ice-templating porous materials are constantly expanding, especially as scaffolds for tissue engineering. Ice-templating, a process utilizing ice nucleation and growth within an aqueous solution, consists of a cooling stage (before ice nucleation) and a freezing stage (during ice formation). While heat release during cooling can change scaffold isotropy, the freezing stage, where ice crystals grow and anneal, determines the final size of scaffold features. To investigate the path of heat flow within collagen slurries during solidification, a series of ice-templating molds were designed with varying the contact area with the heat sink, in the form of the freeze drier shelf. Contact with the heat sink was found to be critical in determining the efficiency of the release of latent heat within the perspex molds. Isotropic collagen scaffolds were produced with pores which ranged from 90 µm up to 180 µm as the contact area decreased. In addition, low-temperature ice annealing was observed within the structures. After 20 h at -30 °C, conditions which mimic storage prior to lyophilization, scaffold architecture was observed to coarsen significantly. In future, ice-templating molds should consider not only heat conduction during the cooling phase of solidification, but the effects of heat flow during ice growth and annealing.

Ionic solutes impact collagen scaffold bioactivity.

The structure of ice-templated collagen scaffolds is sensitive to many factors. By adding 0.5 wt% of sodium chloride or sucrose to collagen slurries, scaffold structure could be tuned through changes in ice growth kinetics and interactions of the solute and collagen. With ionic solutes (sodium chloride) the entanglements of the collagen molecule decreased, leading to fibrous scaffolds with increased pore size and decreased attachment of chondrocytes. With non-ionic solutes (sucrose) ice growth was slowed, leading to significantly reduced pore size and up-regulated cell attachment. This highlights the large changes in structure and biological function stimulated by solutes in ice-templating systems.

The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.

Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs.

The Potential of Wharton's Jelly Derived Mesenchymal Stem Cells in Treating Patients with Cystic Fibrosis.

Cystic fibrosis (CF) is a life-threatening autosomal recessive multi-organ disorder with the mean incidence of 0.737 per 10,000 people worldwide. Despite many advances in therapy, patients fail to have a satisfactory quality of life. The end-stage lung disease still accounts for significant mortality and puts patients in the need of lung transplantation. Even though the disease is monogenic, the trials of topical gene transfer into airway epithelial cells have so far been disappointing. It is proven that stem cells can be differentiated into type II alveolar epithelial cells. Wharton's jelly-derived mesenchymal stem cells (MSC) from non-CF carrier third-party donors could be an effective alternative to bone marrow or embryonic stem cells. The harvesting process is an easy and ethically uncontroversial procedure. The MSC cell should be applied through repetitive infusions due to rapid lung epithelial cell turnover. However, the low stem cell incorporation remains a problem. Pre-clinical studies imply that even 6-10% of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) expression could be enough to restore chloride secretion. The route of administration, the optimal dose, as well as the intervals between infusions have yet to be determined. This review discusses the clinical potential of mesenchymal stem cell in CF patients.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

Stem cell experiments moves into clinic: new hope for children with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease with long-term complications that affects mainly preterm born children with low birth weights, especially those treated with mechanical ventilation and oxygen therapy. Successful treatment of BPD could reduce the incidence of other diseases of prematurity such as periventricular leukomalacia and retinopathy. The effects of current therapies are unsatisfactory; thus, searching for novel therapeutic is underway. One promising approach seems administration of mesenchymal stem cells (MSC). Preclinical data strongly support the role of progenitor cells in the preservation of lung structure. MSC can be found more often in pre-term than term umbilical cord and its isolation from Wharton's jelly carries a potential in treating diseases of prematurity. Several questions concerning the use of MSC in BPD remain to be answered, including the amount of transferred cells, intervals between infusions, the best route for administration and the timing. MSC can be administered as a treatment or prophylaxis. However, having in mind that not all prematurely born children are at risk of developing bronchopulmonary dysplasia, a search for laboratory markers identifying potential patients should be conducted. This review summarizes the latest achievements in MSC therapy in the context of BPD.

Understanding anisotropy and architecture in ice-templated biopolymer scaffolds.

Biopolymer scaffolds have great therapeutic potential within tissue engineering due to their large interconnected porosity and biocompatibility. Using an ice-templated technique, where collagen is concentrated into a porous network by ice nucleation and growth, scaffolds with anisotropic pore architecture can be created, mimicking natural tissues like cardiac muscle and bone. This paper describes a systematic set of experiments undertaken to understand the effect of local temperatures on architecture in ice-templated biopolymer scaffolds. The scaffolds within this study were at least 10mm in all dimensions, making them applicable to critical sized defects for biomedical applications. It was found that monitoring the local freezing behavior within the slurry was critical to predicting scaffold structure. Aligned porosity was produced only in parts of the slurry volume which were above the equilibrium freezing temperature (0°C) at the time when nucleation first occurs in the sample as a whole. Thus, to create anisotropic scaffolds, local slurry cooling rates must be sufficiently different to ensure that the equilibrium freezing temperature is not reached throughout the slurry at nucleation. This principal was valid over a range of collagen slurries, demonstrating that by monitoring the temperature within slurry during freezing, scaffold anisotropy with ice-templated scaffolds can be predicted.

A design protocol for tailoring ice-templated scaffold structure.

In this paper, we show, for the first time, the key link between scaffold architecture and latent heat evolution during the production of porous biomedical collagen structures using freeze-drying. Collagen scaffolds are used widely in the biomedical industry for the repair and reconstruction of skeletal tissues and organs. Freeze-drying of collagen slurries is a standard industrial process, and, until now, the literature has sought to characterize the influence of set processing parameters including the freezing protocol and weight percentage of collagen. However, we are able to demonstrate, by monitoring the local thermal events within the slurry during solidification, that nucleation, growth and annealing processes can be controlled, and therefore we are able to control the resulting scaffold architecture. Based on our correlation of thermal profile measurements with scaffold architecture, we hypothesize that there is a link between the fundamental freezing of ice and the structure of scaffolds, which suggests that this concept is applicable not only for collagen but also for ceramics and pharmaceuticals. We present a design protocol of strategies for tailoring the ice-templated scaffold structure.

Use of perfluorodecalin for pancreatic islet culture prior to transplantation: a liquid-liquid interface culture system--preliminary report.

Although the issue remains controversial, short-term culture is probably beneficial for islet graft quality. However, significant islet loss is invariably observed. This is related to reduced survival of large islets, which is compromised by hypoxia under standard culture conditions. We aimed to develop a method of culture, which would avoid exposure to relative hypoxia and hence maintain the quality of islets. Isolated rat islets cultured for 48 h in a liquid-liquid interface culture system (LICS) with a perfluorocarbon were compared to islets cultured under standard (C1) and suboptimal conditions (C2). Islets were tested for viability and response to a glucose challenge, and a marginal mass was transplanted into syngeneic diabetic recipients. The viability of islets after 24-h culture in LICS was higher than in C1 and C2 groups (89.0% vs. 77.5% and 64.6%, respectively) and decreased with time to reach 79.0%, 62.9%, and 53.4% after 72-h culture. The stimulation index in LICS-cultured islets was also significantly higher than in C1 and C2 groups (12.3 ± 0.4 vs. 5.8 ± 0.5 and 4.1 ± 0.2, respectively). Following transplantation of LICS-cultured islets 50% of recipients were rendered normoglycemic compared with 14.3% and 31.3% for C2 and fresh islets, respectively. Our liquid-liquid interface culture system using perfluorodecalin provides optimized culture conditions, which preserve both islet viability and their ability to engraft successfully after intraportal transplantation and could be used for islet transportation.

The Gln223Arg polymorphism of the leptin receptor gene and peripheral blood/bone marrow leptin level in leukemic children.

Leptin is an adipocyte-derived hormone regulating energy homeostasis and body weight. Leptin also plays a role in hematopoiesis, cell cycle regulation, and in oncogenesis. The leptin receptor is a single transmembrane protein belonging to the superfamily of cytokine receptors, structurally related to the hemopoietin receptor family. The aim of the study was to evaluate bone marrow and peripheral blood leptin level and frequency of distribution of leptin receptor gene polymorphism Gln223Arg in children with acute leukemia. The examined group included 92 children with acute leukemia (83 ALL and 9 AML) and 39 non-leukemic control children. Leptin level was measured by ELISA method at the day of leukemia diagnosis. Genomic DNA was isolated with the use of a column method and the genotyping of DNA sequence variation was carried out by the restriction enzyme analysis of PCR - amplified DNA. The samples were then electrophoresed on 2.5% agarose gel. Leptin level in leukemic children was lower than in healthy children. Bone marrow leptin level was significantly lower than that in the blood in leukemic children with ALL-T and AML. An analysis of frequency distribution of the Gln233Arg polymorphism in the leptin receptor gene in leukemic children showed lack of differences between the patients and controls. There was no difference in the genotype frequencies between the leukemic AML and ALL groups either. The results indicate a possible relation between the leptin level and leukemia development in children. The effectory effect of the hormone seems not related to Gln223Arg polymorphism of its receptor.

Questionnaire regarding the knowledge of the rules of organ procurement from cadaveric donors for transplantation directed to the directors of medical institutions in Poland.

We assessed the level of knowledge of organ procurement regulations among the directors of medical institutions in Poland. We also sought to promote the objection form, and the activity of the Central Register of Objections. A questionnaire consisting of 10 questions was sent to 381 random medical health care institution directors countrywide. In 89% of surveyed institutions, the written text of the organ procurement regulations was available and 94% of directors knew the forms of objection, but in 26% of institutions the form was not available and in 14% it was never obtainable. In the medical institutions directors' opinions, the estimated number of objections is 13% of the population in Poland. Organ transplantation is a form of treatment most medical institutions are familiar with, but the matter of donation is not as well known as transplantation, as observed in 48% of questioned institutions.

Geography of the referred potential liver recipients and donors in Poland in 2004.

Our aim was to assess the accessibility of potential liver recipients to cadaveric organs and the ability of transplant teams to realize recipients needs in Poland in 2004. Our calculations revealed that in Poland the number of cadaveric liver transplants was two to three times lower than in other countries and is insufficient to meet the needs, also the number of referred potential liver recipients is two to three times lower than expected.

[High risk acute lymphoblastic leukaemia in children. Preliminary report after introducing a new version of New York (1997) protocol adjusted to the age of the patients. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Ostra bialaczka limfoblastyczna u dzieci w grupie duzego ryzyka. Wstepne obserwacje po wprowadzeniu kolejnej modyfikacji (1997) protokolu Nowy York dostosowanej do wieku. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczki i Chloniaków.

The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed.

Incidence and treatment of hepatitis C virus infection in children with haemophilia in Poland.

In 80% of children with haemophilia treated in our department, screening tests showed the presence of antibodies against the hepatitis C virus (HCV). HCV RNA was detected in serum in 41% of cases. In 20% of cases there were periodic increases in the level of alanine aminotransferase (ALT) activity, and in these cases liver biopsy was performed after factor concentrate replacement. No haemorrhagic complications or pain complaints were reported either during the biopsy or immediately afterwards. In all cases histopathological examination revealed chronic hepatitis type C - chronic mild hepatitis and chronic minimal hepatitis. Eight boys were treated with interferon (INF) alpha. In two cases this therapy was successful. No HCV RNA was detected in serum and transaminase activity was normal during the year following interferon treatment.