The Global Burden of Surgical Management of Osteoporotic Fractures

World Journal of Surgery - Osteoporosis is an epidemic in the developed world. Fracture is a major burden associated with osteoporosis. Surgical management is recommended for particular anatomical...     

Rapid in silico selection of an MCHR1 antagonists’ focused library from multi-million compounds’ repositories: biological evaluation

Target-focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds’ databases if structures of active compounds are available. In the present study, a multi-step virtual and in vitro screening cascade is used to select melanin-concentrating hormone receptor-1 antagonists. The 2D similarity search combined with physico-chemical parameter filtering is suitable for selecting candidates from multimillion compounds’ repository. The seeds of the first round of virtual screening were collected from literature commercial databases, whereas the seeds of the second round were the hits the first round of biological testing In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9 %), applying a strict requirement for hit selection, and also this cascade-like screening method was appropriate for selecting several compounds reaching efficacies even below 10 nM.     

Surgical treatment of lumbar spondylodiscitis: a comparison of two methods

Purpose

This study evaluates two basic hypotheses: (1) the risk of an isolated dorsal approach to ventral lumbar spondylodiscitis based on clinical and radiographic results and (2) the risk of anterior radical debridement due to using a titanium implant in the site of bone infection.

Methods

Group A consisting of 23 patients was treated only by a dorsal transmuscular approach and group B consisting of eight patients was treated by two-stage posteroanterior surgery. Both evaluated groups were assessed before surgery, six weeks and one year after surgery with the Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) and Kirkaldy-Willis functional criteria. To evaluate the sagittal balance restoration, measurement by the Cobb modified angle of the affected segment was performed.

Results

Differences (p < 0.001) in group A were found between JOA values before surgery (average 9.30) and at six weeks after surgery (average 11.82) and 12 months after surgery (13.27) and VAS differences before surgery (average 7.39), six weeks after surgery (average 3.82) and 12 months after surgery (average 2.36) in group A. According to the Kirkaldy-Willis functional criteria, 11 patients were evaluated as excellent, nine patients as good and two patients as poor. The values of the JOA score in group B showed an improvement compared with the JOA values before surgery (average 9.38) at six weeks after surgery (average 11.75) and 12 months after surgery (average 13.63), and the VAS score before surgery (average 7.38) was found to have improved six weeks after surgery (average 4.63) and 12 months after surgery (average 2.25). The functional evaluation according to the Kirkaldy-Willis functional criteria assessed three patients as excellent, four patients as good and one patient as fair. Radiographic examinations of group A revealed the following findings before surgery (average 1.75), six months after surgery (average −3.73) and 12 months after surgery (average −0.79) and in group B before surgery (average 3.71), six weeks after surgery (average −8.21) and 12 months after surgery (average −6.45).

Conclusions

The results demonstrate the minimum serious surgical complications and greater loss of sagittal balance without clinical correlation in group A. We did not find any relapse or persistence of the infection in the post-operative period in group B.     

Hand-assisted laparoscopic radical nephrectomy in pregnancy

Purpose

To demonstrate the beneficial results of hand-assisted laparoscopic tumor nephrectomy in pregnancy and to emphasize the proper timing of such surgery for its crucial importance attempting to avoid fatal cancer-related outcomes as a result of late interventions of aggressive tumors.

Methods

A report of a 32-year-old woman with a 61 × 41 mm chromophobe renal cell carcinoma (RCC) successfully treated with laparoscopic transperitoneal hand-assisted nephrectomy during the 20th week of gestation is presented.

Results

The fetus was stable during the intervention; the postoperative period was uneventful; she had a normal vaginal delivery at term and gave birth to a healthy female child. The patient remained tumor-free at her 34-month follow-up.

Conclusion

Although the pure laparoscopic interventions have become recognized in the treatment of RCC over the last decade, these methods have their limitations and dangers as well. The hand-assistance method makes the procedure faster and safer which is especially important during second or third trimester. Renal biopsy may play a specifically important role in predicting the malignant potential of a renal tumor, whereas postponement of this surgery until after delivery, may lead to the mother’s death. To our knowledge, this is the first report on hand-assisted laparoscopic nephrectomy in pregnancy.     

Enhanced Transdermal Peptide Delivery and Stability by Lipid Conjugation: Epidermal Permeation,Stereoselectivity and Mechanistic Insights

Purpose

Efficient delivery of therapeutic peptides to the skin will facilitate better outcomes in dermatology. The tetrapeptide AAPV, an elastase inhibitor with potential utility in the management of psoriasis was coupled to short chain lipoamino acids (Laa: C6-C10) to enhance the peptide permeation into and through human epidermis.

Methods

AAPV was conjugated to Laas by solid phase synthesis. Peptide stability, skin distribution and permeation, elastase activity and surface activity were determined.

Results

Laas increased peptide permeation into the skin. The permeation lag time and amount of peptide remaining in the skin increased with the carbon chain length of the Laa conjugate. We also demonstrated stereoselective permeation enhancement in favour of the D-diastereomer. Importantly, the elastase inhibition activity of the peptide was largely retained after coupling to the Laa conjugates, showing potential therapeutic utility. The Laa-peptide structures were shown to be surface active, suggesting that this surfactant-like activity coupled with enhanced lipophilicity may contribute to their interaction with and permeation through the lipid domains of the stratum corneum.

Conclusions

This study suggests that the Laa conjugation approach may be useful for enhancing the permeation of moderately sized peptide drugs with potential application in the treatment of skin disorders.     

Combining parallel pattern generation of electrohydrodynamic lithography with serial addressing

Electrohydrodynamic lithography (EHDL) is a parallel patterning process which typically makes use of topographically structured electrodes to guide pattern formation along areas of higher electrical field strength. The main driving force for pattern formation is an electrostatic pressure acting on a thin film polymer surface caused by a voltage applied between a top and bottom electrode. We here demonstrate that the principle can be applied using an addressable electrode composed of interdigitated fingers. Depending on the applied voltages, line patterns with different periodicities were fabricated. Our proof-of-concept experiments pave the way for a parallel pattern replication process where a serially addressed master is used. We complement the experiments by modelling the potentials across the electrodes and electrostatic forces acting on the polymer surface using different addressing schemes. Numerical simulations of the experimental setup pointed to some critical issues we experienced during the design of the experiments.

Via different electrode addressing schemes in electrohydrodynamic lithography, different patterns were generated.     

Mortality and Long-Term Outcome of Neonates with Congenital Heart Disease and Acute Perinatal Stroke: A Population-Based Case-Control Study

Objective: Neonates with congenital heart disease (CHD) and perinatal stroke have high mortality and survivors are at risk for poor long-term neurodevelopmental outcome. The aim of this study was to assess the risk factors and outcome of neonates with both CHD and MRI-confirmed perinatal stroke (Study Group) and compare those to the risk factors and outcome of infants matched for CHD without stroke (Control-1) and of infants matched for MRI-confirmed stroke without CHD (Control-2). Methods: We conducted a population-based case-control study enrolling 28 term neonates with CHD and MRI-confirmed acute perinatal stroke born between 2007–2017 in the Central-Hungarian Region. Each of the control groups included 56 infants. The Bayley Scales of Infant Development-II, the Brunet-Lézine test and the Binet Intelligence scales-V were used for neurodevelopmental follow-up at a median age of 61 months. Results: Mortality was highest in the Study Group (25% compared to 5% and 2%, respectively, p = 0.001). Adverse neurodevelopmental outcome was prevalent in the Study (53%) and Control-2 Groups (52%, p = 0.03). Significantly different parameters among the three groups included Apgar scores, mode of delivery, gestational age at birth, cardiac interventions and twin pregnancy. In a multivariable regression analysis adjusted for clinically relevant parameters, patients in the Study Group had significantly higher odds for mortality compared to patients in the Control-1 Group (OR: 6.5 95% CI: 1.1–39.4). Conclusions: Neonates with perinatal stroke and CHD are at a higher risk for dying compared to neonates with CHD without stroke. In addition, the stroke-associated direct insult to the brain likely plays an important role in the development of neurodevelopmental morbidity in these patients.