Dose optimization of moxifloxacin and linezolid against tuberculosis using mathematical modeling and simulation

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Intraoperative transfusion-related acute lung injury in a child during calvarial vault remodeling

Transfusion-related acute lung injury (TRALI) is currently recognized by the US Food and Drug Administration as the number one cause of mortality related to blood transfusion. Although various pathophysiologic mechanisms have been proposed, it is thought to be related to the presence of anti-HLA antibodies or bioactive lipid components in the donor blood product, which results in activation of recipient leukocytes and the resultant pulmonary damage from the release of bioactive substances including cytokines. As TRALI manifests as acute lung injury with signs and symptoms consistent with acute respiratory distress syndrome, it is frequently underdiagnosed, as the acute lung injury may be attributed to other factors. Transfusion-related acute lung injury is an important clinical entity for anesthesia providers to recognize and diagnose accurately, as many transfusions occur in the surgical patient. We present a case report of a pediatric patient who developed intraoperative TRALI during calvarial vault remodeling to treat craniosynostosis. The history, pathophysiology, and treatment of TRALI are discussed. Potential preventive measures are reviewed.     

Computer-aided direct ceramic restorations: a 10-year prospective clinical study of Cerec CAD/CAM inlays and onlays

PURPOSE: The objective of this follow-up study was to examine the performance of Cerec inlays and onlays in terms of clinical quality over a functional period of 10 years. MATERIALS AND METHODS: Of 200 Cerec inlays and onlays placed in a private practice between 1989 and early 1991, 187 restorations were observed over a period of 10 years. The restorations were fabricated chairside using the Cerec-1 computer-aided design/manufacturing (CAD/CAM) method and Vita MK I feldspathic ceramic. An adhesive technique and luting composite resin were used for seating the restorations. After 10 years, the clinical performance of the restorations was evaluated using modified USPHS criteria. The results were used to classify success and failure. RESULTS: According to Kaplan-Meier analysis, the success rate of Cerec inlays and onlays dropped to 90.4% after 10 years. A total of 15 (8%) failures were found in 11 patients. Of these failures, 73% were caused by either ceramic fractures (53%) or tooth fractures (20%). The reasons for the remaining failures were caries (20%) and endodontic problems (7%). The three-surface Cerec reconstructions were found to have the most failures. CONCLUSION: The failure rate of 8% and the drop of the survival probability rate to 90.4% after 10 years of clinical service of Cerec-1 CAD/CAM restorations made of Vita MK I feldspathic ceramic appear to be acceptable in private practice. This is particularly true in light of the very high patient satisfaction.     

Immunhistochemische Untersuchung des Kollagen-Typ-I-Gehalts der Gingiva bei Dysostosis cleidocranialis

Background

Patients with cleidocranial dysplasia (CCD) present a thickend and fibrotic gingiva.

Purpose

To the best of our knowledge it was analysed for the first time, whether this is correlated with an increased rate of collagen I in oral mucosa.

Patients and methods

27 soft tissue biopsies of six CCD-patients and 17 tissue samples of 12 healthy persons were labled with a monoclonal antibody against collagen I and the bound antibodies were detected with alkaline phosphatase-anti-alkaline phophatase-kit. The histological slices were analysed by a digital image recognition software under a fully automated microscope and the rate of collagen I was converted into amounts of grey tones.

Results

The amount of grey tones reached from 11.909 to 15.319 in the CCD-group, and from 2752 to 12.556 in the control group. The U-Test of Mann, Whitney and Wilcoxon for two independent samples generated a rank sum of 91,50 for CCD-patients, and of 79,50 for the control group. The Z-value was 3,246, the p-value 0,005. “Fisher`s exact test” identified a p-value of 0,0003.

Conclusions

The rate of collagen I in the oral mucosa seems to be increased significantly in CCD. This could explain the typical thick and fibrotic consistency of the gingiva and could be one reason for the delayed or missing dentition.     

Expression of cyclooxygenase-2 (COX-2) in an advanced metastasized hypopharyngeal carcinoma and cultured tumor cells

Purpose

The inducible enzyme cyclooxygenase-2 (COX-2) catalyzes PGE₂ production and plays an important role in the progression of many solid cancers. However, the role of COX-2 expression in cervical lymph node metastases of head and neck cancer has not been clarified yet.

Patient and methods

We comment on a male patient aged 53 who was admitted to an ENT-department with acute bleeding from an advanced hypopharyngeal carcinoma and a frontotemporal mass. Prior to palliative intended radiotherapy, the metastasis was resected. During the procedure, a small amount of tumor tissue was harvested for primary tumor cell culture.

Results

COX-2 overexpression was demonstrated in the primary tumor tissue, the metastasis, in the cultured tumor cells by standard immunohistochemistry, as well as cytochemistry.

Conclusions

A simultaneous expression of COX-2 in head and neck carcinoma was presented for the first time. Besides the prognostic impact in oral carcinogenesis, this COX-2 role of biomarker for aggressive head and neck squamous cell carcinomas should be further evaluated. Additionally, treatment of hypopharyngeal carcinomas with selective COX-2 inhibitors could be beneficial when administered in combination with radiochemotherapy.     

Evaluation of rat alveolar bone response to Angelus MTA or experimental light-cured mineral trioxide aggregate using fluorochromes

Introduction

The aim of this study was to evaluate the rat alveolar bone response after the implantation of experimental light-cured mineral trioxide aggregate (MTA) or Angelus MTA (Angelus, Londrina, Paraná, Brazil) by histological and fluorescence analysis.

Methods

Thirty Wistar Albino rats were divided into three groups. In the control group, empty polyethylene tubes were inserted into the rat alveolar sockets immediately after extraction. In the other groups, the tubes were filled with light-cured MTA or Angelus MTA. Five animals from each group were injected with calcein on day 7, alizarin on day 14, and oxytetracycline on day 21. On day 30, these animals were killed, and the right hemimaxillas were removed and histologically processed. Half of the maxillas were processed and stained with hematoxylin and eosin. The remaining maxillas were processed for fluorescence analysis and stained with Stevenel blue and alizarin red. New bone was histomorphometrically evaluated using a Merz grid.

Results

The light-cured MTA presented a similar response when compared with Angelus MTA; it was characterized by a mild inflammatory response and complete bone healing. In the light-cured MTA group, the fluorescence areas were more evident at 21 days, showing an increase in bone formation. However, dystrophic mineralization was observed only with Angelus MTA.

Conclusions

It was concluded that both materials present a similar inflammatory response and bone healing, but dystrophic mineralization was observed only with Angelus MTA.     

Laparoscopic mesh-augmented hiatoplasty without fundoplication as a method to treat large hiatal hernias

Purpose

Laparoscopic hiatal hernia repair with additional fundoplication is a commonly recommended standard surgical treatment for symptomatic large hiatal hernias with paraesophageal involvement (PEH). However, due to the risk of persistent side effects, this method remains controversial. Laparoscopic mesh-augmented hiatoplasty without fundoplication (LMAH), which combines hiatal repair and mesh reinforcement, might therefore be an alternative.

Methods

In this retrospective study of 55 (25 male, 30 female) consecutive PEH patients, the perioperative course and symptomatic outcomes were analyzed after a mean follow-up of 72 months.

Results

The mean DeMeester symptom score decreased from 5.1 to 1.8 (P < 0.001) and the gas bloating value decreased from 1.2 to 0.5 (P = 0.001). The dysphagia value was 0.7 before surgery and 0.6 (P = 0.379) after surgery. The majority of the patients were able to belch and vomit (96 and 92 %, respectively). Acid-suppressive therapy on a regular basis was discontinued in 68 % of patients. In 4 % of patients, reoperation was necessary due to recurrent or persistent reflux. A mesh-related stenosis that required endoscopic dilatation occurred in 2 % of patients.

Conclusions

LMAH is feasible, safe and provides an anti-reflux effect, even without fundoplication. As operation-related side effects seem to be rare, LMAH is a potential treatment option for large hiatal hernias with paraesophageal involvement.     

Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening

Summary

We identified that use of VFA may be cost-effective in either selected women from primary care or women attending after a low trauma fracture.

Introduction

Lateral DXA scanning of the spine for vertebral fracture assessment (VFA) is used for research, but its wider role is unclear. We aimed to establish whether VFA is cost-effective in women based on two different scenarios: following a low-trauma fracture, and after screening of high-risk women identified in primary care.

Methods

The fracture cohort (FC) consisted of 377 women and the primary care cohort (PCC) of 251. Vertebral fractures were identified on VFA images by quantitative morphometry (QM). Outcome was cost-effectiveness of VFA, based on predicted change in clinical management defined as the identification of a vertebral fracture in a patient who otherwise falls below the threshold for treatment. FRAX treatment thresholds assessed were (1) 20/3 % thresholds and (2) National Osteoporosis Guidelines Group (NOGG) thresholds.

Results

As a result, 9.8 % from FC and 13.9 % from PCC were identified with vertebral fractures. Management was changed in 21 to 22/377 (5.6–5.8 %) in FC and 12 to 26/251 (4.8–10.4 %) from PCC depending on which thresholds were used. Sensitivity analyses identified medication adherence as the assumption which most influenced the model. The best-estimate cost-per-QALY for use of VFA in FC was £3,243 for 20/3 threshold and £2,130 for NOGG; for PCC, this was £7,831 for 20/3 and was cost-saving for NOGG. Further analyses to adjust for potential false-positive vertebral fracture identification with QM showed VFA was no longer cost-effective.

Conclusion

VFA appears to be cost-effective in routine clinical practise, particularly when relatively inaccurate methods of identification of vertebral fractures are used such as QM.     

Significance of Biofilm for the Prosthetic Surgeon

Biofilm formation on implanted medical devices is becoming more recognized as both a common finding and a potential problem. Although seen frequently in nature, these sequestered bacterial communities are proving to be an assiduous enemy as medical device technologies advance. The penile prosthesis has gone through many improvements, now with a more reliable mechanical function and a reduced infection rate. However, there remains a notable increase in infectious risk in revisions compared to novel cases, with many implants found to harbor a subclinical bacterial presence isolated in biofilms. This article focuses on recent updates in implant technology and surgical technique to combat infection, and reviews current research on biofilm prevention and treatment.