Thoracic spinal anesthesia with intrathecal sedation for lower back surgery: a retrospective cohort study.

Background: Spinal anesthesia (SA) is a good alternative to general anesthesia (GA) for spine surgery. Despite that, a few case series concern the use of thoracic spinal anesthesia for short-duration surgical interventions. In search of an alternative approach to GA and a better opioid-free modality, we aimed to investigate the safety, feasibility, and patient satisfaction of thoracic SA for spine surgery. Materials and methods: We analyzed retrospectively a cohort of 24 patients operated on for a degenerative and osteoporotic pathology of the lower thoracic and lumbar spine. Data was collected from medical records, including clinical notes, operative and anesthesia records, and patient questionnaires. Results: Twenty-one surgeries for herniated discs, two for degenerative spinal stenosis, and one for multi-level osteoporotic vertebral body fractures were performed under spinal anesthesia with intrathecal sedation. In all cases, we applied 0.5% isobaric bupivacaine and the following adjuvants: midazolam, clonidine or dexmedetomidine, and dexamethasone. We boosted the anesthesia with local ropivacaine due to inefficient sensory block in two patients. Nobody in the cohort received intravenous opioids, non-steroidal anti-inflammatory drugs, or additional sedation intraoperatively. Postoperative painkillers were upon the patient's request. No significant complications were detected. Conclusion: Thoracic spinal anesthesia incorporating adjuvants such as midazolam, clonidine or dexmedetomidine, and dexamethasone demonstrates not only efficient conditions for spine surgery, a favorable safety profile, high patient satisfaction, and intrathecal sedation but also effective opioid-free pain management.

Common differential diagnosis of low back pain in contemporary medical practice: a narrative review.

With a wide range of etiologies, low back pain (LBP) presents a true clinical challenge, finding its origins both in intrinsic spinal and systemic conditions, as well as referred ones. This review categorizes the LBP into these three groups and aims to offer a comprehensive look at the tools required to diagnose and differentiate them. The intrinsic etiologies are based on conditions that affect the musculoskeletal components of the lumbar spine, such as intervertebral disc disease, stenosis, muscular imbalance, and facet joint degeneration. The systemic causes usually extend beyond local structures. Such are the cases of neoplasia, infections, and chronic inflammation. The diagnosis is rendered even more complex by adding the referred pain, which only manifests in the lower back yet arises in more distant locations. By synthesizing the literature that encompasses the problem, this review aims to augment the understanding of the differential diagnoses of LBP by showcasing the subject's nuances. This categorization provides a structured approach to a patient-centered diagnosis, which could facilitate the medical practitioners' efforts to navigate this pathology more effectively.

Evaluation of multidetector CT Hounsfield unit measurements as a predictor of efficacy and complications in percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

Introduction: More than 30 years after the initial experience of Galibert and Deramond with percutaneous vertebroplasty, the procedure has gone through countless refinements and clinical evaluations. Predictors for the success and failure of the procedure in the literature vary and are focused on the duration of complaints, type of fracture, presence of edema on MRI scans, etc. We propose using a quantitative method based on a standard CT examination of the thoracic or lumbar spine to assess the risks and potential success of performing vertebroplasty. Materials and methods: This is a single-center prospective observational study on 139 patients treated with percutaneous vertebroplasty (pVPL) for a single symptomatic osteoporotic vertebral compression fracture (OVCF). We measured the levels of disability and pain preoperatively and again at the 3-, 6- and 12-month marks using the standardized VAS and ODI questionnaires. Every patient in the study was evaluated with postoperative multidetector CT (MDCT) to determine the presence, extent, and localization of vertebral cement leakage and to measure the adjacent vertebrae's minimal and mean density in Hounsfield units (HUmin and HUmean, respectively). Results: We determined that a slight (r = -0.201) but statistically significant (p = 0.018) correlation existed between HU measurements taken from radiologically intact adjacent vertebrae and the procedure's effect concerning the pain levels at the 3-month follow-up. This correlation failed to reach statistical significance at 12 months (p = 0.072). We found no statistically significant relationship between low vertebral cancellous bone density and cement leakage on postoperative scans (p = 0.6 for HUmin and p = 0.74 for HUmean). Conclusion: We have moderately strong data that show a negative correlation between the mean values of vertebral cancellous bone density in patients with OVCF and the effect of pVPL in reducing pain. Lower bone densities, measured this way, showed no increased risk of cement leakage.

Reactivity Graph Yields Interpretable IgM Repertoire Signatures as Potential Tumor Biomarkers.

Combining adaptive and innate immunity induction modes, the repertoire of immunoglobulin M (IgM) can reflect changes in the internal environment including malignancies. Previously, it was shown that a mimotope library reflecting the public IgM repertoire of healthy donors (IgM IgOme) can be mined for efficient probes of tumor biomarker antibody reactivities. To better explore the interpretability of this approach for IgM, solid tumor-related profiles of IgM reactivities to linear epitopes of actual tumor antigens and viral epitopes were studied. The probes were designed as oriented planar microarrays of 4526 peptide sequences (as overlapping 15-mers) derived from 24 tumor-associated antigens and 209 cancer-related B cell epitopes from 30 viral antigens. The IgM reactivity in sera from 21 patients with glioblastoma multiforme, brain metastases of other tumors, and non-tumor-bearing neurosurgery patients was thus probed in a proof-of-principle study. A graph representation of the binding data was developed, which mapped the cross-reactivity of the mixture of IgM (poly)specificities, delineating different antibody footprints in the features of the graph-neighborhoods and cliques. The reactivity graph mapped the major features of the IgM repertoire such as the magnitude of the reactivity (titer) and major cross-reactivities, which correlated with blood group reactivity, non-self recognition, and even idiotypic specificities. A correlation between an aspect of this image of the IgM IgOme, namely, small cliques reflecting rare self-reactivities and the capacity of subsets of the epitopes to separate the diagnostic groups studied was found. In this way, the graph representation helped the feature selection in its filtering step and provided reduced feature sets, which, after recursive feature elimination, produced a classifier containing 51 peptide reactivities separating the three diagnostic groups with an unexpected efficiency. Thus, IgM IgOme approaches to repertoire studies is greatly augmented when self/viral antigens are used and the data are represented as a reactivity graph. This approach is most general, and if it is applicable to tumors in immunologically privileged sites, it can be applied to any solid tumors, for instance, breast or lung cancer.

Grisel's syndrome in adults: A case report.

BACKGROUND: The non traumatic, post inflammatory atlantoaxial rotatory instability, also known as Grisel's syndrome is a relatively rare condition usually affecting children. Adult cases are rare and even less frequently reported with separate case reports describing a single patient. Although antibiotic treatment and close neurological monitoring seem to be the gold standard of care, there is no general consensus on the optimal timing and extent of the surgical treatment. CASE DESCRIPTION: We present a case of C1-C2 spondylitis, secondary to retropharyngeal abscess, without atlantoaxial instability on initial evaluation that progressed to C1-C2 subluxation with rapidly developing myelopathy 3 months after optimal antibiotic therapy and complete clinical and biochemical remission. CONCLUSION: Grisel's syndrome is a rare condition in adults with secondary instability in spite of successful antibacterial treatment, which requires decompression and delayed surgical fixation in our case.

Diagnostic Profiling of the Human Public IgM Repertoire With Scalable Mimotope Libraries.

Specific antibody reactivities are routinely used as biomarkers, but the antibody repertoire reactivity (igome) profiles are still neglected. Here, we propose rationally designed peptide arrays as efficient probes for these system level biomarkers. Most IgM antibodies are characterized by few somatic mutations, polyspecificity, and physiological autoreactivity with housekeeping function. Previously, probing this repertoire with a set of immunodominant self-proteins provided a coarse analysis of the respective repertoire profiles. In contrast, here, we describe the generation of a peptide mimotope library that reflects the common IgM repertoire of 10,000 healthy donors. In addition, an appropriately sized subset of this quasi-complete mimotope library was further designed as a potential diagnostic tool. A 7-mer random peptide phage display library was panned on pooled human IgM. Next-generation sequencing of the selected phage yielded 224,087 sequences, which clustered in 790 sequence clusters. A set of 594 mimotopes, representative of the most significant sequence clusters, was shown to probe symmetrically the space of IgM reactivities in patients' sera. This set of mimotopes can be easily scaled including a greater proportion of the mimotope library. The trade-off between the array size and the resolution can be explored while preserving the symmetric sampling of the mimotope sequence and reactivity spaces. BLAST search of the non-redundant protein database with the mimotopes sequences yielded significantly more immunoglobulin J region hits than random peptides, indicating a considerable idiotypic connectivity of the targeted igome. The proof of principle predictors for random diagnoses was represented by profiles of mimotopes. The number of potential reactivity profiles that can be extracted from this library is estimated at more than 1070. Thus, a quasi-complete IgM mimotope library and a scalable representative subset thereof are found to address very efficiently the dynamic diversity of the human public IgM repertoire, providing informationally dense and structurally interpretable IgM reactivity profiles.

Neurosurgical training programme in selected European countries: from the young neurosurgeons' point of view.

AIM: In this paper we discuss the Neurosurgical Training Programme (NTP) in some European countries. MATERIAL AND METHODS: Although there is no official data on how many neurosurgeons are certified in Europe, our calculation shows that this number is somewhat lower than in the United States of America and even 3 times lower than in Japan (per 100.000 population). It is also evident that there is no consensus in the Programme duration or in the official NTP content, despite the recommendations of the EANS (The European Association of Neurosurgical Societies). Trainees from outside the European Union (EU) are under-represented in the EANS training courses. We believe that in the eastern part of Europe there is the most space for improvement in neurosurgical training. Solving of all these problems requires first and foremost their recognition and consideration - then devising a solution. CONCLUSION: The purpose of this paper is to compare and contrast several NTP's in Europe in order to promote a more coherent medical education. Some remarks and suggestions from the perspective of young neurosurgeons are given.

Prevalence of JC polyomavirus genomic sequences from the large T-antigen and non-coding control regions among Bulgarian patients with primary brain tumors.

A total of 111 fresh brain biopsies from patients with primary brain tumors were examined for JC polyomavirus sequences from the Large T antigen encoding region (LT) and the viral non-coding control region (NCCR). SYBR Green and TaqMan real-time polymerase chain reaction assays were used. In the glioblastoma group of 39 patients 48.7% were positive for LT sequences. Among the astrocytoma group (19 patients) and the oligodendroglioma group (12 patients) 31.6% and 33.3% were also positive. The prevalence of LT genomic sequences among the other groups was as follows: in 2 out of 3 oligoastrocytomas; in 3 out 5 gangliogliomas; in 2 out of 5 meduloblastomas; in 1 out 3 pineocytomas; and in none of the tested 5 ependimomas. All positive samples had a late threshold cycle that varied from 36 to 49, indicative of very low starting viral number. Only 21 of all the 111 samples were positive for NCCR. Low copy number in range of 10-1,000 was present. Notably, only 8 of all NCCR positive specimens were also LT positive. It might be suggested that the disproportion between the results for LT and NCCR is either due to clonally integrated LT fragments, with loss of genetic material, or changes in the NCCR. The latter would alter the productive course of the infection and may establish a premise for continuous interaction of viral regulatory proteins with cell molecules that are responsible for the control of the cell cycle. This may lead subsequently to malignant transformation.

Neuronavigation in cranioorbital neurosurgery - do we really need it?

AIM: The value of neuronavigation in cranioorbital neurosurgery is controversial and relatively unstudied. The aim of this study was to evaluate the application, the usefulness and the reliability of neuronavigation in the neurosurgical treatment of orbital tumours. MATERIAL AND METHODS: A frameless armless infrared-based neuronavigation system was applied in the microsurgical removal of 7 orbital tumors. Image guidance was CT-based in 3 cases, MRI-based in another 3 cases and based on image fusion between CT and MRI image sets in one patient. The extradural fronto-orbital approach was performed in 3 cases, lateral orbitotomy in 2 cases, trans-supraciliar approach in 1 case and inferomedial orbitotomy in 1 case. RESULTS: The surgical procedures were successful in all cases. The procedure-related morbidity and mortality rate in the series was zero. The registration accuracy of the neuronavigation ranged between 1.0 and 1.7 mm, with an average of 1.3 mm. Neuronavigated image guidance was evaluated as useful in all patients. Total tumour removal was achieved in 5 patients and partial tumour excision in 1 case. One patient was only biopsied. CONCLUSION: Neuronavigation is not a substitute for surgical knowledge and experience, but it is a valuable complement with significant intraoperative potential in cranioorbital surgery.

In vitro biochemical and pharmacological evaluation of a novel cytotoxic dinuclear platinum(II) complex with 3-amino-5-methyl-5-phenylhydantoin.

An in vitro pharmacological evaluation of a novel dinuclear platinum complex ([KL(2)](2)[Pt(2)I(6)], where L is 3-amino-5-methyl-5-phenylhydantoin; Ad-1) was carried out. The cytotoxicity of [KL(2)](2)[Pt(2)I(6)] against human tumor cell lines was assessed using the MTT [-3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide] assay. The complex exerted concentration-dependent cytotoxic effects that were comparable or even superior to that of cisplatin. Moreover, the novel complex retained significant activity against CaCo-2 and Neuro-2A cells, which showed primary resistance to cisplatin. As evidenced by the rising level of genomic DNA fragmentation following treatment with [KL(2)](2)[Pt(2)I(6)], the cytotoxic effects are at least partly mediated by induction of apoptosis. The DNA binding of [KL(2)](2)[Pt(2)I(6)] and cisplatin were assessed using a 40-base fragment, whereby the present GG-motif is the recognition sequence of the nuclease BamH1. The DNA platination was determined after BamH1 treatment, 5% PAGE, and ethidium bromide staining. Cisplatin completely inhibited the BamH1-mediated fragmentation of the target DNA molecule. [KL(2)](2)[Pt(2)I(6)] also significantly inhibited the fragmentation of the target DNA sequence. The platination induced by [KL(2)](2)[Pt(2)I(6)] was better repaired by the nucleotide excision repair than the cisplatin lesions. As evidenced by electrophoresis mobility shift assay, the Ad-1-modified DNA was efficiently recognized and bound by the high mobility group box (HMGB)-1 protein, a member of the HMG domain proteins, which implies that the latter are most probably important for the cytotoxicity mode of action of this agent.

In vitro evaluation of a stable monomeric gold(II) complex with hematoporphyrin IX: cytotoxicity against tumor and kidney cells, cellular accumulation, and induction of apoptosis.

The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp(-2H).(H(2)O)(2)], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, with IC(50) values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp(-2H).(H(2)O)(2)] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp(-2H).(H(2)O)(2)] which shows that its putative pharmacological targets are readily accessible after a short incubation period.

Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione.

New platinum(II) and platinum(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione and various halogen ions with general formula [PtL(2)X(2)] and [PtL(2)Cl(4)], where L is the organic ligand and X is Cl(-), Br(-), J(-), were synthesized. The molecular formulae of all the complexes were confirmed by elemental analysis, IR, (1)H, (13)C NMR spectral analyses and molar conductivity. The cytotoxic effects of these complexes were examined on some human tumor cell lines. The newly synthesized cis-[PtL(2)Cl(2)] exerted cytotoxic activity against SKW-3, MCF-7, EJ, U-266 tumor cell lines, while cis-[PtL(2)Br(2)], trans-[PtL(2)I(2)] were less active. The higher oxidation state complex cis-[PtL(2)Cl(4)] was inactive in all cell lines but in SKW-3 some augmentation of the cytotoxicity was seen after co-administration of ascorbic acid but not when treated in combination with reduced glutathione or N-acetylcysteine. A DNA-fragmentation analysis revealed that the cytotoxicity of the dichloro analogue, characterized with superior activity compared to the other complexes, is mediated by induction of apoptotic cell death.

In vitro toxicological evaluation of a dinuclear platinum(II) complex with acetate ligands.

In the present study the toxicological potential of a tumor-inhibiting dinuclear platinum(II) complex (bis(acetato)diammine-bis-micro-acetato diplatinum(II) dihydrate (BAP)) was evaluated, utilizing in vitro models of nephrotoxicity, myelosuppression and neurotoxicity. Regarding the discrepancies between the hallmark toxicity of the clinically utilized platinum drugs, we used three distinct referent compounds as follows cisplatin for the assessment of in vitro nephrotoxicity, carboplatin in case of cultured bone marrow cells and oxaliplatin for the determination of the in vitro neurotoxicty, respectively. The results obtained indicate that the investigated dinuclear complex is endowed by a lower potential to induce detrimental effects upon these typically susceptible platinum toxicity cellular populations as compared to the corresponding referent drugs. These findings, together with the previously encountered profound cytotoxic efficiency of this dinuclear platinum(II) complex against human tumor cell lines, recall for a further detailed evaluation of BAP as potential antineoplastic agent.