Regenerated Nerve Defects with a Nerve Conduit Containing Dental Pulp Stem Cells in Pigs: An Immunohistochemical and Electrophysiological Evaluation.

BACKGROUND: Dental pulp stem cells (DPSCs) present an exciting new tool in the field of peripheral nerve regeneration due to their close embryonic origin. In this study, we examined their potential in pigs, using biodegradable collagen conduits filled with DPSCs. To our knowledge, this is the first time DPCSs are tested for peripheral nerve regeneration in such large animal model. MATERIALS AND METHODS: The second lateral incisor was extracted from every animal's lower jaw and stem cells were isolated and cultured. The collagen nerve conduits containing the DPSCs were subsequently transplanted into the transected fifth and sixth intercostal nerves, while the seventh intercostal nerve was used as a control and no stem cells were added on the respective collagen conduit. RESULTS: A histological examination was performed on the 3rd and 6th postoperative months and showed the gradual development of neural tissue and immunohistochemical expression of neuron-specific enolase. An electrophysiological study was performed on the 6th postoperative month and showed similar potentials between the stem cell infusion region (5 ± 0.04 units) and their proximal stumps (5 ± 0.05 units) and slightly smaller potentials in the respective distal stumps (4 ± 0.045 units). CONCLUSION: The nerves where DPSCs were injected exhibited morphological and functional recovery, in contrast to the control nerves where no recovery was detected; thus, there is a first evidence of the therapeutic potential of DPSCs in peripheral nerve regeneration.

A simple method for the quantitation of the stem cells derived from human exfoliated deciduous teeth using a luminescent cell viability assay.

Stem cells from human exfoliated deciduous teeth are a population of highly proliferative postnatal stem cells and have been characterized as multipotent stem cells. In this study we developed a fast and sensitive method for stem cells derived from human exfoliated deciduous teeth count, using a luminescent viability assay. We isolated stem cells from normal exfoliated deciduous teeth using collagenase/dispase digestions solutions. Separated stem cells were placed in opaque-walled multiwall plates in culture alpha Modified Eagle's Medium. For dental pulp stem cells quantitation we used a simple method for determining the number of viable cells based on ATP concentration. Cells attached to the bottom of the multiwall plates were counted with the luminescent assay and were cultured for mesenchymal markers expression. Moreover cells attached to the bottom of the multiwall plates were directed toward the osteogenic, adipogenic, lineages at the respective passages. Flow cytometry was used for immunophenotyping of cultured dental stem cells from exfoliated deciduous teeth. Cells that were counted with the luminescent assay, after culture formed fibroblastic morphology and were expressed the mesenchymal stem cell markers CD29, CD105, CD146, CD44. There was a correlation between the number of cells plated for culture and the number of mesenchymal stem cells after culture. Osteogenic and adipogenic differentiation of the cells counted with the luminescent assay was performed. The luminescent signal of viable mesenchymal dental stem cells isolated from dental pulp of exfoliated teeth represents an ideal method for mesenchymal stem cells count before culturing.

Investigative MRI cholangiopancreatography for primary sclerosing cholangitis-type lesions in children with IBD.

OBJECTIVES: The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. METHODS: Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. RESULTS: Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. CONCLUSIONS: The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.

Post embolization syndrome in doxorubicin eluting chemoembolization with DC bead.

BACKGROUND/AIMS: The investigation of post embolization syndrome (PES) in patients with hepatocellular carcinoma (HCC) after treatment with doxorubicin loaded DC Bead (DEB-DOX). METHODOLOGY: The study included 237 patients treated with sequential DEB-TACE performed at set time intervals every two months until 3 sessions/6 month f-u. Patients were ECOG 0-1, Child-Stage-A (n=116, 48.9%) and B (n=121, 51%). Embolizations were as selective as possible with DC Bead of 100-300µm in diameter followed by 300-500µm loaded with doxorubicin at 37.5mg/mL of hydrated bead (max:150mg). RESULTS: PES regardless of severity was observed in up to 86.5%. However grade 2 PES ranged between 25% and 42.19% across treatments. Temperatures above 38°C were seen in 22.7% to 38.3% across treatments. No statistically significant increase of PES was seen in beads of 100-300µm in diameter; incidence of fever and pain presented correlation with the extent of embolization (p=0.0001-0.006 across treatments). Baseline tumor diameter was associated with incidence of fever (p=0.0001-0.001). Duration of fever correlated with the extent of embolization (p=0.008). PES was not associated with elevation of liver enzymes and was correlated with degree of necrosis (p<0.001). CONCLUSIONS: PES after DEB-DOX represents tumor response to treatment and does not represent collateral healthy liver damage.

Acute Abdominal Situations as Presenting or Flaring Manifestations of Systemic Lupus Erythematosus: A Case Series.

Systemic lupus erythematosus (SLE)is a multisystem autoimmune disease, characterized by clinical heterogeneity, ranging from mild to severe, life-threatening manifestations. Although gastrointestinal (GI) symptoms are frequently encountered during disease course (mainly associated with complications of medication or infection), primary GI involvement due to SLE is rare. Among variable presentations, lupus abdominal serositis (defined as peritonitis if accompanied by symptoms and signs of acute abdomen) and lupus enteritis/mesenteric vasculitis are causes of SLE-related acute abdominal pain. They occur, although not always, in the context of high disease activity and prompt diagnosis and treatment is necessary due to their potential severe complications. However, the diagnosis of these manifestations remains challenging even for experts, especially in cases of "organ-dominant" lupus flares. Exclusion of these rare manifestations from classification criteria increases the likelihood of misdiagnosis and highlights the inherent limitations of classification criteria when the latter are used for diagnosis. Urgent abdominal computed tomography can lead to a prompt diagnosis of these lupus manifestations, especially characteristic for lupus mesenteric vasculitis. Herein, we describe four cases of patients with lupus flare, presenting with acute abdominal manifestations and highlight the potential complexity of diagnostic approach in such situations.

Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients-seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands-with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept.

Inverse association of leptin levels with renal cell carcinoma: results from a case-control study.

OBJECTIVE: Leptin is primarily produced in adipose tissue and appears to play a modulatory role between metabolism and immunity. Given that obesity, a state of chronic inflammation, is an established risk factor for Renal Cell Carcinoma (RCC), we investigated the association between plasma leptin levels and RCC risk. DESIGN: This case-control study included 70 patients with newly diagnosed, histologically confirmed RCC and 280 age-, gender- and district of residence-matched controls. Anthropometric data, socio-demographic variables, medical history, lifestyle habits and dietary data were derived from a personal interview. Serum leptin and adiponectin levels were determined using standard commercial kits. Adjusted odds ratios for RCC risk were derived through multiple logistic regression analyses. RESULTS: Leptin levels were inversely associated with RCC risk (OR: 0.53, CI: 0.28- 0.99, p = 0.05), even after controlling for potential confounding factors, such as Body Mass Index (BMI), recent weight change, history of diabetes mellitus and other obesity related hormones, notably adiponectin. CONCLUSIONS: The precise mechanism linking obesity with RCC remains unclear; however, the inverse association of leptin with RCC might be attributed, at least in part, to hormonal cross-talk with complex neuron-endocrine and immune circuits. These findings, if confirmed in prospective and interventional studies, might further elucidate the underlying mechanisms.

MABp1 Targeting IL-1α for Moderate to Severe Hidradenitis Suppurativa Not Eligible for Adalimumab: A Randomized Study.

Patients with moderate to severe hidradenitis suppurativa failing adalimumab therapy, or those ineligible to receive it, remain a population with an unmet need. Twenty patients not eligible for adalimumab were randomized to receive 12 weeks of blind treatment with placebo or MABp1, a true human antibody targeting IL-1α. Hidradenitis suppurativa clinical response score at week 12 was the primary endpoint. The primary endpoint was met in 10% and 60% of placebo- and MABp1-treated patients, respectively (odds ratio = 13.50, 95% confidence interval = 1.19-152.51). Clinical efficacy was maintained at 24 weeks in 0% and 40%. Improvement in the visual analog scale was reported by 20% and 85.7%, respectively, of patients failing previous anti-TNF treatment. Ultrasonography showed decreased neovascularization and lesion skin depth in the MABp1 group. MABp1 treatment was associated with decrease of circulating IL-8 and of stimulated production of IL-8 by whole blood. Whole blood production for hBD-2 was negatively associated with changes on ultrasonography in the placebo group but not in the MABp1 group. MABp1 is a promising treatment for patients with hidradenitis suppurativa not eligible for adalimumab. Inhibition of neovascularization and modulation of the production of IL-8 and hBD-2 are suggested mechanisms of action.

Multi-slice CT (MSCT) imaging in pretrans-catheter aortic valve implantation (TAVI) screening. How to perform and how to interpret.

Aortic valve stenosis (AS) is the most common valvular heart disease among elderly. Trans-catheter aortic valve implantation (TAVI) has become an established and effective alternative therapeutical procedure for inoperable and high-risk patients with symptomatic AS. The procedural success is greatly dependent on a thorough pre-TAVI imaging screening. This requires a comprehensive and multi-modality approach, in which multi-slice computed tomography (MSCT) is the cornerstone in the selection of eligible patients, in choosing the appropriate prosthesis and size, and in mapping the safest access route for the intervention. From our experience of more than 400 TAVI procedures and many more MSCTs for screening purposes, we provide clinical and technical details on the use of MSCT pre-TAVI and brief review of the knowledge so far.

Inflammatory bowel disease-the role of cross-sectional imaging techniques in the investigation of the small bowel.

BACKGROUND: The diagnosis of inflammatory bowel disease (IBD) in children and adolescents is based on the integration of clinical, biological, endoscopic, histological and radiological data. METHODS: The most important part of the diagnosis is the histology, which is acquired by endoscopy. Imaging of the small bowel has changed in recent years, but the imaging goals are primarily to determine the extent of small bowel involvement, assess complications and define candidates for surgery. Imaging techniques are divided into conventional and cross-sectional ones. RESULTS: The spectrum of imaging findings of cross-sectional techniques is discussed, emphasising the advantages and limitations of each technique, acknowledging the specificities of the paediatric population. Cross-sectional techniques have advanced the ability to diagnose and monitor inflammatory disease of the small bowel. CONCLUSION: MR enterography is the technique of choice in children with known IBD, for the investigation of the small bowel and the whole GI tract. US should be the first choice examination in children with suspected IBD, while CT should be reserved for cases in which MRI is contraindicated or in acute emergency situations when US is inadequate. TEACHING POINTS: • Cross-sectional imaging of the small bowel is essential in paediatric IBD. • Endoscopy is unable to assess extramural disease and examine the entire small bowel. • US should be the first choice examination in children with suspected IBD. • MR enterography is the technique of choice in children with known IBD. • There are still controversies regarding the prediction of disease activity or fibrosis.

Chemoembolization of hepatocellular carcinoma with HepaSphere 30-60 µm. Safety and efficacy study.

BACKGROUND: This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material. METHODS: Forty-five patients with documented HCC (Child-Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30-60 µm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed. RESULTS: TACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30-60 µm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30-60 µm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002). CONCLUSION: HepaSphere 30-60 µm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.

Insulin resistance and risk of renal cell cancer: a case-control study.

OBJECTIVE: Obesity and diabetes are considered risk factors for Renal Cell Carcinoma (RCC). We aimed to explore whether insulin resistance (IR) plays an independent role in the development of RCC. DESIGN: In a hospital-based case-control study, we analyzed serum glucose, insulin, leptin and adiponectin levels among 60 incident RCC patients and 236 age- and gender-matched healthy controls. We assessed insulin resistance according to insulin levels, alone or controlled for diabetes mellitus (DM). An alternative measure of insulin resistance, such as the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index, was also assessed with and without controlling for history of DM. We used logistic regression to estimate odds ratios (ORs) adjusted for possible confounders. RESULTS: The positive association of DM and waist to hip ratio as a measure of obesity with RCC was evident in the data set. Insulin levels controlled or not controlled for DM, however, were inversely associated with the risk for RCC; notably, an approximately 40% higher risk was observed in the 1st tertile when compared with the 2nd and 3rd tertile levels of insulin resistance. Similar results were obtained when HOMA-IR was alternatively used. The inverse associations persisted and were even strengthened after controlling for potential confounding factors in multivariate analyses. CONCLUSIONS: Our curdata suggest that insulin resistance may be inversely associated with RCC risk, independently of obesity, DM, lifestyle and hormonal confounding variables. Given the close interconnections among metabolic, inflammatory and immune pathways in RCC causation, it is difficult to infer which process actually initiates a pathologic cascade. The findings should be considered as preliminary data that need to be further confirmed in more appropriate study designs.

Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer.

Adiponectin has been associated with colorectal cancer (CRC) risk. This study aims to investigate the association of both adiponectin and tissue expression of its receptors with CRC risk as well as clinicopathological characteristics, notably stage and grade. Determination of serum adiponectin and immunohistochemical expression of adiponectin receptors in adenocarcinoma/normal colorectal tissue was performed in samples from 104 newly diagnosed CRC patients and 208 age- and sex-matched controls. Multiple logistic regression odds ratios and 95% confidence intervals for CRC risk were derived, controlling for a series of covariates. Serum adiponectin was negatively associated with CRC risk (odds ratio, 0.72; confidence interval, 0.53-0.99) and also with tumor grade (P = .05). Expression of both adiponectin receptors was stronger in adenocarcinoma vs normal tissue (P = .001). AdipoR1 expression was negatively associated with nodal stage (P = .03); AdipoR2 expression was positively associated with tumor, node, metastasis stage (P = .01). Established positive associations with red meat consumption and diabetes, and negative associations with physical exercise and plant food consumption were confirmed along with a more than 60% higher risk associated with central obesity. Adiponectin levels and tissue expression of hormonal receptors seem to be associated not only with CRC risk but also with components of clinicopathological characteristics; given power limitations, these results should be interpreted with caution. The exact nature of the association and the underlying pathophysiological mechanisms need to be further examined in large prospective studies assessing adiponectin and its receptors as novel targets for exploring CRC growth.

Safety profile of sequential transcatheter chemoembolization with DC Bead™: results of 237 hepatocellular carcinoma (HCC) patients.

INTRODUCTION: Complications of chemoembolization performed with DC Bead(™) loaded with doxorubicin (DEBDOX) of diameters 100-300 µm and 300-500 µm are presented in this paper. These diameters are currently the smallest available in drug-eluting technology. METHODS: Included are 237 patients who were treated with sequential DEBDOX with doxorubicin loaded at 37.5 mg/ml of DC Bead. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) were used to categorize complications. RESULTS: Thirty-day mortality was 1.26% (3/237). Incidence of grade 5 complications was 1.26% (3/237). Overall, grade 4 complications resulted in 5.48% (13/237) (irreversible liver failure, cholecystitis). Grade 2 liver function deterioration developed in 10 patients (4.2%). Cholecystitis/grade 2 and 4 incidents were observed in 3.6-5.06% across sessions (overall 13 patients; 5.48%). Postembolization Syndrome (PES) grade 1 or 2 was observed in up to 86.5%; however, grade 2 was observed in 25-42.19% across treatments. Pleural effusion was seen in eight patients (overall 3.37%; grade 1 in 1.8-3.7% across treatments; grade 3 in 0.42%). Grade 1 procedure-related laboratory pancreatitis was seen in 0.45%, and grade 2 gastrointestinal bleeding was seen in 0.84%. Procedure-associated skin erythema/grade 1 was seen in 0.84%. There was no correlation of liver failure or transient liver function deterioration with the diameter of the beads (p = 0.25-0.37 and p = 0.14-0.89, respectively). Stratifying with the diameter of the beads correlation values was: for cholecystitis (p = 0.11-0.96 across treatments), PES (p = 0.35-0.83), temporary/grade 1 elevation of liver enzymes (p = 0.002-0.0001), and bilirubin (p = 0.04-0.99). CONCLUSIONS: DEBDOX chemoembolization is safe and small calibres do not result in increased complication rates compared with results of series using larger diameters of beads.

Ultrasound as a first line screening tool for the detection of renal artery stenosis: a comprehensive review.

Renal artery stenosis (RAS) is the most common underlying medical condition in secondary hypertension among adults, representing about 5% of all cases of hypertension. Early diagnosis of RAS is an important clinical objective since interventional therapy may improve or cure hypertension and preserve renal function. Contrast angiography is the currently reference standard for the diagnosis of RAS; however, its invasive nature renders it unsuitable for screening purposes. Among screening tests used for the detection of RAS (computed tomography angiography, magnetic resonance angiography, radionuclide scanning), multiple studies have shown that color Doppler ultrasound (CDUS), although highly operator-dependent, can be an effective tool in the diagnosis of RAS. CDUS imaging is a simple, safe (noninvasive) and widely available technique; in addition, the procedure is painless and well tolerated by patients. In this concrete review we will underline the established color Doppler ultrasound criteria used for the detection of RAS, highlight their limitations and see how their combination may improve the diagnostic accuracy of this method.

Renal artery rupture following cutting balloon angioplasty for fibromuscular dysplasia: a case report.

INTRODUCTION: Angioplasty with the use of cutting balloons has been suggested by some case reports and small series for the treatment of renal artery stenoses that are resistant to conventional balloon catheters. Based on this limited experience, the use of this technology has been suggested as safe. Herein, we report a renal artery rupture following angioplasty with a cutting balloon. The complication was salvaged with a stent graft. CASE PRESENTATION: A 30-year-old white female patient with resistant hypertension caused by a severe renal artery stenosis attributed to fibromuscular dysplasia, was submitted to conventional balloon angioplasty without success. Dilatation of the lesion with a cutting balloon resulted in arterial rupture, with concomitant retroperitoneal hematoma. CONCLUSION: Cutting balloon angioplasty of renal artery lesions resistant to conventional balloon angioplasty should not be considered as safe as previously thought. When proceeding with such a procedure, a stent graft should be available for immediate use.

Low adiponectin levels are associated with renal cell carcinoma: a case-control study.

Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case- control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32-month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR=0.76, p=0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra-abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans.