Micromorphology of the Dental Pulp Is Highly Preserved in Cancer Patients Who Underwent Head and Neck Radiotherapy

Introduction

Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy.

Methods

Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed.

Results

The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples.

Conclusions

Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.     

Platysma Flap: An Alternative to Free Flaps

Objective

The objective of this paper is to show that platysma flaps have good results and should be an alternative in reconstructive surgery for oral tumors when microsurgery is not possible. It is a versatile, portable, and thin flap, is easy to perform, and can be obtained during neck dissection, with a primary closure of the donor site.

Methods

Five cases are presented, three men and two women, 51 and 71 years old, with medium size (2–4 cm) defects of oral cavity after the excision of squamous cell carcinomas. All of them were reconstructed with a platysma flap after neck dissection. This reconstruction technique was chosen because of the poor conditions of these patients to allow a microsurgical reconstruction.

Results

Non-local complications occurred with this technique. Overall aesthetic results were acceptable in all the patients. There were no cases of total necrosis flap, dehiscence, fistula or fibrosis. Only one case of partial necrosis occurred in one end of the flap, which was resolved with excision of necrotic tissue and closure by secondary intention.

Conclusion

The platysma flap is a good method to reconstruct small and medium sized defects of oral cavity, especially in patients where a microsurgery reconstruction is not possible.     

Lack of correlation between tubular dentine cement penetration, adhesiveness and leakage in roots filled with gutta percha and an endodontic cement based on epoxy amine resin

Objective

To analyze possible correlations among tubular dentine cement penetration, adhesiveness and apical leakage in fillings performed with gutta percha and an endodontic cement based on epoxy amine resin.

Material and Methods

Sixty similar, extracted human mandibular central incisors were irrigated, instrumented and filled following the same protocol. First, apical leakage was quantified by fluid filtration tests. Then, these same specimens were sectioned for analysis of tubular dentine cement penetration and the middle thirds were submitted to push-out tests to analyze the adhesiveness of the fillings.

Results

In brief, the means and standard deviations with a confidence interval of 95% were as follows: tubular dentine cement penetration (8.875±4.540), adhesiveness (4.441±2.683) and apical leakage (0.318±0.215). The data were confronted using the Pearson''s test (P>0.05), and it was possible to prove that there was no correlation between (1) tubular dentine cement penetration and apical leakage (r²: 0.08276), (2) tubular dentine cement penetration and adhesiveness (r²: -0.2412) and (3) adhesiveness and apical leakage (r²: 0.1340).

Conclusion

After analysis of these data, it could be observed that there exists no correlation among the variables analyzed in this study.     

Fibromyalgia and non-celiac gluten sensitivity: a description with remission of fibromyalgia

Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause, and only symptomatic treatment with limited benefit is available. Gluten sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with the manifestations of FM, including chronic musculoskeletal pain, asthenia, and irritable bowel syndrome. The aim of this report was to describe 20 selected patients with FM without CD who improved when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal biopsy, and HLA typing were performed in all cases. CD was ruled out by negative anti-transglutaminase assay results and absence of villous atrophy in the duodenal biopsy. All patients had intraepithelial lymphocytosis without villous atrophy. Clinical response was defined as achieving at least one of the following scenarios: remission of FM pain criteria, return to work, return to normal life, or the discontinuation of opioids. The mean follow-up period was 16 months (range 5–31). This observation supports the hypothesis that non-celiac gluten sensitivity may be an underlying cause of FM syndrome.     

From the Cover: A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs

The recent success of antibody–drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer.Microtubule-targeting agents such as the taxanes and the vinca alkaloids represent a successful class of anticancer drugs (1). Vinblastine, for example, is a microtubule-destabilizing agent (MDA) that is widely used in combination therapy for the treatment of childhood and adult malignancies (2). The broad clinical application of MDAs, however, is hampered by their severe adverse effects (3). This problem has been very recently addressed by the use of antibody–drug conjugate (ADC) approaches, which have revived interest in the development of highly potent MDAs for therapeutic use (4–6).For several important MDAs, the molecular mechanism of action on tubulin and microtubules has so far remained elusive. Rhizoxin, for example, is a potent MDA that has been investigated in phase 2 clinical trials, but for reasons poorly understood, it has demonstrated only very limited clinical efficacy (7). At the molecular level, it is well established that rhizoxin interferes with the binding of vinblastine to tubulin; however, the exact location of its binding site has been a matter of debate (8–10). Interestingly, biochemical and mutagenesis data suggest that the structurally unrelated MDA maytansine (9, 11), which is part of an ADC that was recently approved by the FDA for the treatment of advanced breast cancer (11, 12), and the phase 1 drug PM060184 (13, 14) (Fig. 1A) share a common tubulin-binding site with rhizoxin (9, 13, 14). These two latter drugs have also been reported to interfere with the binding of vinblastine; however, as for rhizoxin, the exact binding sites and modes of action of maytansine and PM060184 have not been elucidated (9, 14–16).Open in a separate windowFig. 1.Structure of the tubulin–rhizoxin F complex. (A) Chemical structures of rhizoxin F, maytansine, and PM060184. (B) Overall view of the T₂R-TTL–rhizoxin F complex. Tubulin (gray), RB3 (light green), and TTL (violet) are shown in ribbon representation; the MDA rhizoxin F (orange) and GDP (cyan) are depicted in spheres representation. As a reference, the vinblastine structure (yellow, PDB ID no. 1Z2B) is superimposed onto the T₂R complex. (C) Overall view of the tubulin–rhizoxin F interaction in two different orientations. The tubulin dimer with bound ligand (α-tubulin-2 and β-tubulin-2 of the T₂R-TTL–rhizoxin F complex) is shown in surface representation. The vinblastine structure is superimposed onto the β-tubulin chain to highlight the distinct binding site of rhizoxin F. All ligands are in sphere representation and are colored in orange (rhizoxin F), cyan (GDP), and yellow (vinblastine). (D) Close-up view of the interaction observed between rhizoxin F (orange sticks) and β-tubulin (gray ribbon). Interacting residues of β-tubulin are shown in stick representation and are labeled.To establish the exact tubulin-binding site of rhizoxin, maytansine, and PM060184 and to clarify their specific interactions with the protein, we have investigated the structures of the corresponding ligand–tubulin complexes by X-ray crystallography. Our data reveal a new tubulin-binding site and pharmacophore for small molecules, and binding to this site is associated with a distinct molecular mechanism for the inhibition of microtubule formation.     

Cost analysis and effectiveness comparing the routine use of intraoperative fluorescent cholangiography with fluoroscopic cholangiogram in patients undergoing laparoscopic cholecystectomy

Background

Despite the standardization of laparoscopic cholecystectomy (LC), the rate of bile duct injury (BDI) has risen from 0.2 to 0.5 %. Routine use of intraoperative cholangiography (IOC) has not been widely accepted because of its cost and a lack of evidence concerning its use in preventing BDI. Fluorescent cholangiography (FC), which has recently been advocated as an alternative to IOC, is a novel intraoperative procedure involving infrared visualization of the biliary structures. This study evaluated costs and effectiveness of routinely implemented FC and IOC during LC.

Materials and methods

Between February and June 2013, the authors prospectively collected the data of all patients undergoing laparoscopic cholecystectomy. We retrospectively reviewed and compared the use of FC and IOC. Procedure time, procedure cost, and effectiveness of the two methods were analyzed and compared. The surgeons involved in the cases completed a survey on the usefulness of each method.

Results

A total of 43 patients (21 males and 22 females) were analyzed during the study period. Mean age was 49.53 ± 14.35 years and mean body mass index was 28.35 ± 8 kg/m². Overall mean operative time was 64.95 ± 17.43 min. FC was faster than IOC (0.71 ± 0.26 vs. 7.15 ± 3.76 min; p < 0.0001). FC was successfully performed in 43 of 43 cases (100 %) and IOC in 40 of 43 cases (93.02 %). FC was less expensive than IOC (US$14.10 ± 4.31 vs. US$778.43 ± 0.40; p < 0.0001). According to the survey, all surgeons found routine use of FC useful.

Conclusion

In this study, FC was effective in delineating important anatomic structures. It required less time and expense than IOC, and was perceived by the surgeons to be easier to perform, and at least as useful as IOC. Further prospective studies are warranted to evaluate the effectiveness of FC in decreasing BDI.     

Baseline glycated hemoglobin levels are associated with duodenal-jejunal bypass liner-induced weight loss in obese patients

Introduction

Endoscopic treatment with the duodenal-jejunal bypass liner (DJBL) leads to significant weight loss in obese patients. We sought to identify clinical factors associated with weight loss in obese patients treated with the DJBL for 1 year.

Methods

Subjects with morbid obesity were enrolled in a single-arm, open-label, prospective trial and implanted with the DJBL. Patient demographics along with baseline comorbidities, anthropometrics, and biochemical variables were selected for univariate and multivariate analysis.

Results

The DJBL was implanted in 79 subjects and 61 completed 12 months of follow-up. There were 18 early removals. Baseline mean age and body mass index (BMI) were 35.4 ± 9.7 years and 43 ± 5.6 kg/m², respectively. Forty-four (72 %) were women. This population included 22 subjects with type 2 diabetes (T2DM). Twelve months after treatment, patients had a mean excess body weight loss (%EBWL) of 46 ± 18 %. Univariate analysis identified that fasting glycemia (r ² = ?0.303, p < 0.013), insulin-resistance determined by HOMA-IR (r ² = ?0.457, p < 0.019), and glycated hemoglobin (HbA1c) (r ² = ?0.471, p < 0.013) were associated inversely with %EBWL at 1 year. In this cohort of patients, the multivariate analysis indicated that only baseline HbA1c levels were associated inversely with %EBWL after 1 year of treatment (β adjusted coefficient ?0.758, p < 0.016). Importantly, no differences at 1 year in %EBWL were observed between patients with or without T2DM (%EBWL T2D 46.7 ± 20 % vs. non-T2DM 46.8 ± 18.6 %, p = 0.988).

Conclusions

This analysis indicates that higher baseline HbA1c levels are associated independently with diminished body weight loss in obese patients treated with the DJBL independent of their diabetic status. These results show that DJBL induces clinically significant weight loss in both T2DM and non-T2DM patients.     

Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience

Background

Supportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS®).

Methods

Retrospective data from children receiving therapy using MARS® from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS® session, technical modalities and adverse events were recorded.

Results

A total of six children underwent 17 MARS® sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX® and four infants were treated with the MiniMARS® filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11–33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS® from an initial 89?±?29 to 58?±?35 mcmol/L (p?=?0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation.

Conclusion

In our experience, treatment with MARS® is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.     

Point prevalence of pressure ulcers in three second‐level hospitals in Mexico

Pressure ulcers (PU) are the source of multiple complications and even death. To our knowledge, there is no available data about PU prevalence in Mexico. The objective of this study was to determine the point prevalence of PU in three second‐level hospitals in Mexico. Every adult hospitalised patient was included in each hospital. Age, gender, hospitalisation ward, Braden score, and the number, location and stage of the ulcers encountered were recorded, as well as any pressure relief measures. In total, 294 patients were examined (127 were male); of these, 63 were considered to be at risk. The average age was 48·6 years. The overall prevalence of the PU was 17%. The service with the highest prevalence was the ICU. The most frequent stage was II (32%) and they were most commonly found in the sacrum (74%). The average Braden score of the patients with ulcers was 10, and 21·4% of the patients obtained moderate‐ to high‐risk Braden scores. Of them, 60·3% had ulcers and only 46% had any preventive measures. The prevalence of PU in three hospitals in Mexico is 17%. The most common stage is II and the most commonly affected site is the sacrum. Only 46% of patients with PU had at least one pressure release measure.