Complex polymorphisms in the plasmodium falciparum Multidrug Resistance Protein 2 Gene and Its Contribution to Antimalarial Response

Complex Polymorphisms in the Plasmodium falciparum Multidrug Resistance Protein 2 Gene and Its Contribution to Antimalarial ResponsePlasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance.This work was supported by project grants from the Swedish Development Cooperation Agency, Department for Research Cooperation (SWE 2007-174 and SWE-2009-165). M.I.V. and N.S.O. are recipients of post-doctoral fellowship from Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Ciencia e Ensino Superior, Portugal, MCES (SFRH/BPD/76614/2011 and UMINHO/BPD/15/2014, respectively). The Shoklo Malaria Research Unit is part of the Mahidol Oxford University Tropical Medicine Research Unit and is supported by the Wellcome Trust of Great Britain

The Evolution of Minimally Invasive Spine Tumor Resection and Stabilization: From K-Wires to Navigated One-Step Screws

Minimization of the surgical approaches to spinal extradural metastases resection and stabilization was advocated by the 2012 Oncological Guidelines for Spinal Metastases Management. Minimally invasive approaches to spine oncology surgery (MISS) are continually advancing. This paper will describe the evolution of minimally invasive surgical techniques for the resection of metastatic spinal lesions and stabilization in a single institute. A retrospective analysis of patients who underwent minimally invasive extradural spinal metastases resection during the years 2013–2019 by a single surgeon was performed. Medical records, imaging studies, operative reports, rates of screw misplacement, operative time and estimated blood loss were reviewed. Detailed description of the surgical technique is provided. Of 138 patients operated for extradural spinal tumors during the study years, 19 patients were treated in a minimally invasive approach and met the inclusion criteria for this study. The mortality rate was significantly improved over the years with accordance of improve selection criteria to better prognosis patients. The surgical technique has evolved over the study years from fluoroscopy to intraoperative 3D imaging and navigation guidance and from k-wire screw insertion technique to one-step screws. Minimally invasive spinal tumor surgery is an evolving technique. The adoption of assistive devices such as intraoperative 3D imaging and one-step screw insertion systems was safe and efficient. Oncologic patients may particularly benefit from the minimization of surgical decompression and fusion in light of the frailty of this population and the mitigated postoperative outcomes associated with MIS oncological procedures

Short-term post-operative complications in 207 patients with multi-level degenerative cervical myelopathy: the effect of surgical approach

Introduction. Degenerative cervical myelopathy (DCM) is a common condition often treated by surgical decompression and fusion. The objective of this paper was to compare short-term post-operative complication rates of patients with multi-level DCM treated with decompression and fusion using either an anterior or a posterior cervical approach.Material and methods. A retrospective evaluation of patients’ charts, imaging studies and operative reports of patients operated for multilevel subaxial DCM from 2011 to 2016 at a single institution was performed. Patients who were operated upon for the treatment of three stenosed spinal levels or above and who underwent anterior cervical discectomy and fusion, or anterior cervical corpectomy and fusion, or posterior cervical laminectomy and fusion, were included. Short-term post-operative complications were compared between the anterior and posterior approaches.Results. Overall, 207 patients were included in this study. 156 were operated via an anterior approach and 51 via a posterior approach. The mean number of treated levels was 3.4 and 4.3 for the anterior and posterior approach groups, respectively (p < 0.001). In the posterior approach group, the proportion of stenosed spinal levels within all operated levels was significantly lower than in the anterior approach group (p = 0.025). Early post-operative neurological status change was favourable for both groups. Deep wound infection rate was significantly higher in the posterior approach group (7.8% vs. none; p = 0.001).Conclusions. Posterior cervical laminectomy and fusion is significantly associated with an increased rate of deep wound infection and wound revision surgery compared to the anterior approach. We recommend the anterior approach as the valid option in treating multi-level DCM

TN-RS: a novel scoring system predicts Gamma Knife Radiosurgery outcome for trigeminal neuralgia patients.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) is an effective treatment option for medically refractory trigeminal neuralgia (TN). This study examines GKRS outcome in a large cohort of TN patients and highlights pretreatment factors associated with pain relief. METHODS: This is a single-center retrospective analysis of patients treated with GKRS for TN between 2011 and 2019. Pain relief was assessed at 1 year, and 2-3 years following GKRS. Multivariable analysis identified several factors that predicted pain relief. These predicting factors were applied to establish a pain relief scoring system. RESULTS: A total of 162 patients met inclusion criteria. At 1 year post-GKRS, the breakdown of Barrow Neurological Institute (BNI) score for pain relief was as follows: 77 (48%) score of I, 13 (8%) score of II, 37 (23%) score of III, 22 (14%) score of IV, and 13 (8%) score of V. Factors that were significantly associated with pain-free outcome at 1 year were: Typical form of TN (OR = 2.2 [1.1, 4.9], p = 0.049), No previous microvascular decompression (OR = 4.4 [1.6, 12.5], p = 0.005), Response to medical therapy (OR = 2.7 [1.1, 6.1], p = 0.018), and Seniority \u3e 60 years (OR = 2.8 [1.4, 5.5], p = 0.003). The term Trigeminal Neuralgia-RadioSurgery was used to create the TN-RS acronym representing the significant factors. A stepwise increase in the median predicted probability of pain-free outcome at 1 year from 3% for patients with a score of 0 to 69% for patients with a maximum score of 4. CONCLUSION: The TN-RS scoring system can assist clinicians in identifying patients that may benefit from GNRS for TN by predicting 1-year pain-free outcomes