Does the intraoperative 3D-flat panel control of the planned implant position lead to an optimization and increased in safety in the anatomically demanding region C1/2?

BACKGROUND: The aim of this study was to evaluate the applicability and advantages of intraoperative imaging using a 3D flat panel in the treatment of C1/2 instabilities. MATERIALS: Prospective single-centered study including surgeries at the upper cervical spine between 06/2016 and 12/2018. Intraoperatively thin K-wires were placed under 2D fluoroscopic control. Then an intraoperative 3D-scan was carried out. The image quality was assessed based on a numeric analogue scale (NAS) from 0 to 10 (0 = worst quality, 10 = perfect quality) and the time for the 3D-scan was measured. Additionally, the wire positions were evaluated regarding malpositions. RESULTS: A total of 58 patients were included (33f, 25 m, average age 75.2 years, r.:18-95) with pathologies of C2: 45 type II fractures according to Anderson/D'Alonzo with or without arthrosis of C1/2, 2 Unhappy triad of C1/2 (Odontoid fracture Type II, anterior or posterior C1 arch-fracture, Arthrosis C1/2) 4 pathological fractures, 3 pseudarthroses, 3 instabilities of C1/2 because of rheumatoid arthritis, 1 C2 arch fracture). 36 patients were treated from anterior [29 AOTAF (combined anterior odontoid and transarticular C1/2 screw fixation), 6 lag screws, 1 cement augmented lag screw] and 22 patients from posterior (regarding to Goel/Harms). The median image quality was 8.2 (r.: 6-10). In 41 patients (70.7%) the image quality was 8 or higher and in none of the patients below 6. All of those 17 patients the image quality below 8 (NAS 7 = 16; 27.6%, NAS 6 = 1, 1.7%), had dental implants. A total of 148 wires were analyzed. 133 (89.9%) showed a correct positioning. In the other 15 (10.1%) cases a repositioning had to be done (n = 8; 5.4%) or it had to be drawn back (n = 7; 4.7%). A repositioning was possible in all cases. The implementation of an intraoperative 3D-Scan took an average of 267 s (r.: 232-310 s). No technical problems occurred. CONCLUSION: Intraoperative 3D imaging in the upper cervical spine is fast and easy to perform with sufficient image quality in all patients. Potential malposition of the primary screw canal can be detected by initial wire positioning before the Scan. The intraoperative correction was possible in all patients. Trial registration German Trials Register (Registered 10 August 2021, DRKS00026644-Trial registration: German Trials Register (Registered 10 August 2021, DRKS00026644- https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00026644 ).

Cervical spine injury after virtual reality gaming: a case report.

BACKGROUND: We report a patient who fractured the seventh cervical vertebra while playing a virtual reality (VR) game, without any other trauma. This case report aims to describe the spinal trauma incurred during the use of a VR headset in a video game. CASE PRESENTATION: The Caucasian patient presented with pain and swelling in the lower cervical spine at our clinic after playing a video game involving a combination of shoulder, arm and head movements while wearing a VR headset. Preexisting comorbidities were not present in the 31-year-old male. No history of regular medication use or drug abuse was recorded. After performing a clinical examination and radiological diagnostics, we found a dislocated traumatic fracture of the spinous process of the seventh cervical vertebra. After a soft tissue defect was excluded through magnetic resonance imaging (MRI) diagnostics, a conservative therapy regimen with pain therapy and immobilization was started. After hospitalization, outpatient controls were conducted at 4, 6 and 12 weeks. At 6 weeks after hospitalization, the patient had recovered from the injury without complications. CONCLUSIONS: Rapid movements during VR gaming can lead to injuries of the cervical spine. In addition to rapid movements, the additional weight of the VR headset as well as the decoupling of audiovisual stimuli from the perceived proprioceptive information should be considered. Determining whether this is an isolated incident induced by unknown preexisting factors or whether the trauma mechanism alone can lead to severe spinal trauma needs to be studied further with additional cases.

Comparison of three different screw trajectories in osteoporotic vertebrae: a biomechanical investigation.

BACKGROUND: Pedicle screw insertion in osteoporotic patients is challenging. Achieving more screw-cortical bone purchase and invasiveness minimization, the cortical bone trajectory and the midline cortical techniques represent alternatives to traditional pedicle screws. This study compares the fatigue behavior and fixation strength of the cement-augmented traditional trajectory (TT), the cortical bone trajectory (CBT), and the midline cortical (MC). METHODS: Ten human cadaveric spine specimens (L1 - L5) were examined. The average age was 86.3 ± 7.2 years. CT scans were provided for preoperative planning. CBT and MC were implanted by using the patient-specific 3D-printed placement guide (MySpine®, Medacta International), TT were implanted freehand. All ten cadaveric specimens were randomized to group A (CBT vs. MC) or group B (MC vs. TT). Each screw was loaded for 10,000 cycles. The failure criterion was doubling of the initial screw displacement resulting from the compressive force (60 N) at the first cycle, the stop criterion was a doubling of the initial screw displacement. After dynamic testing, screws were pulled out axially at 5 mm/min to determine their remaining fixation strength. RESULTS: The mean pull-out forces did not differ significantly. Concerning the fatigue performance, only one out of ten MC of group A failed prematurely due to loosening after 1500 cycles (L3). Five CBT already loosened during the first 500 cycles. The mean displacement was always lower in the MC. In group B, all TT showed no signs of failure or loosening. Three MC failed already after 26 cycles, 1510 cycles or 2144 cycles. The TT showed always a lower mean displacement. In the subsequent pull-out tests, the remaining mean fixation strength of the MC (449.6 ± 298.9 N) was slightly higher compared to the mean pull-out force of the CBT (401.2 ± 261.4 N). However, MC (714.5 ± 488.0 N) were inferior to TT (990.2 ± 451.9 N). CONCLUSION: The current study demonstrated that cement-augmented TT have the best fatigue and pull-out characteristics in osteoporotic lumbar vertebrae, followed by the MC and CBT. MC represent a promising alternative in osteoporotic bone if cement augmentation should be avoided. Using the patient-specific placement guide contributes to the improvement of screws' biomechanical properties.

Chiropractic patients in the Netherlands: a descriptive study.

BACKGROUND: Despite the worldwide popularity of chiropractic, there is still relatively little known about the patients who visit chiropractors in the Netherlands and other European countries. OBJECTIVE: To describe in-depth the patient population of new patients to chiropractors in the Netherlands. DESIGN: Study population consisted of 10 consecutive new patients per participating chiropractor. A retrospective-type questionnaire was used. SETTING: Private practice. OUTCOME MEASURES: Mode of referral, area, and nature of the complaints; related to the chief complaint: previous treatments, examinations, type of referral, days lost at work, level of pain, and treatment expectations. RESULTS: Of the 130 chiropractors registered with the Netherlands Chiropractors'Association, 94 chiropractors(78%) participated. Eight hundred thirty-three patients (89%) returned questionnaires. By far, the greatest reason that patients visit chiropractors in the Netherlands is for neuromusculoskeletal (NMS) complaints. At the time of examination, 86% of the patients had spinal-related complaints, of which 12% involved multiple areas of the spine. Non-NMS complaints are minimal (<2%). Seventy-seven percent of patients with NMS complaints have chronic complaints (>12 weeks). Three-quarters of these patients have undergone previous conservative therapy for their complaint, which includes physical and manual therapy, postural correction, and exercise therapy. Despite the chronic nature of their complaints, patients have high expectations that their treatment will be effective. CONCLUSIONS: Most patients who see chiropractors in the Netherlands have chronic NMS-related complaints. Chiropractors are not a part of the normal referral system in this country, with the result that the patients have rather long histories, including previous evaluations by medical specialists and other previous forms of (conservative) care.

Chiropractic in The Netherlands: a survey of Dutch chiropractors.

BACKGROUND: In the Netherlands, there is increasing public and political interest in chiropractic treatment. There is, however, very little descriptive information available in the Netherlands on the chiropractic profession. Therefore, a survey was conducted among all Dutch chiropractors. METHODS: A questionnaire was sent to all members of the Netherlands' Chiropractors Association (n = 59). It contained questions on (postgraduate) education, practice management, diagnostics (including radiology use), treatment, interprofessional cooperation and referral. RESULTS: The response was 88%. Chiropractic is growing rapidly: the number of chiropractors has doubled in five years. Chiropractors primarily treat back and neck pain, with an average of 8 treatments. Conventional orthopedic and neurological examination along with motion palpation are the cornerstones of physical examination. The respondents stressed the importance of direct access to radiography and specialized (hospital) diagnostics. Fifty-eight percent of the chiropractors have their own X-ray equipment. The most frequent reason for taking new X-rays was the absence of cooperation with radiology departments. Self-referral is the largest source of patients. The referral rate to other health care professionals is low. CONCLUSIONS: The number of chiropractors is growing rapidly. They have an exceptional position in the Dutch health care system. Access to X-ray and more specialized diagnostics are presently the most important political issues.

A Drosophila homologue of human Sp1 is a head-specific segmentation gene.

Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.

Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less.

Homeotic genes encode transcription factors that are thought to specify segmental identity by regulating expression of subordinate genes. Limb development is repressed in the abdominal segments of the Drosophila embryo by the hometic genes of the Bithorax complex (BX-C). Localized expression of the homeobox gene Distal-less (DII) is required for leg development in thoracic segments. We have identified a minimal cis-regulatory enhancer element that directs DII expression in the larval leg primordia. We present evidence that the BX-C proteins repress DII expression in abdominal segments by binding to a small number of specific sites in this element. Mutating these sites eliminates BX-C protein binding and renders the element insensitive to BX-C-mediated repression in vivo. Repression of limb development in the abdomen appears to be controlled at the DII enhancer. Thus DII may serve as a downstream target gene through which the homeotic genes control abdominal segment identity in the Drosophila embryo.

apterous, a gene required for imaginal disc development in Drosophila encodes a member of the LIM family of developmental regulatory proteins.

The apterous (ap) gene is required for the normal development of the wing and haltere imaginal discs in Drosophila melanogaster. ap encodes a new member of the LIM family of developmental regulatory genes. The deduced amino acid sequence of ap predicts a homeo domain and a cysteine/histidine-rich domain known as the LIM domain. In these domains ap is highly similar to the mec-3 and lin-11 proteins of Caenorhabditis elegans and to the vertebrate insulin enhancer-binding protein isl-1. ap is presumably required for transcriptional regulation of genes involved in wing and haltere development. The nature of the defects in homozygous null mutant flies is consistent with the pattern of ap expression in the larval imaginal discs. ap is also expressed in a complex pattern in the embryo, including portions of the peripheral nervous system (PNS) and central nervous system (CNS). A requirement for ap expression in the larval and adult CNS may be the underlying cause of the defects in hormone production and vitellogenesis described for ap mutations.

A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo.

Segmentation of the Drosophila embryo depends on a hierarchy of interactions among the maternal and zygotic genes in the early embryo. The anterior region is organized maternally by the bicoid (bcd) gene product, which forms a concentration gradient in the anterior half of the embryo. The gap genes are also involved in establishing the body plan, with hunchback (hb) being expressed both maternally and zygotically. Zygotic expression of hb is directly activated by the bcd gene product, leading to a subdivision of the embryo into an anterior half expressing zygotically provided hb protein and a posterior half that does not. A similar effect on maternally provided hb protein is caused by the gene nanos, which represses the translation of maternally provided transcripts in the posterior half. This regulation of hb protein is a prerequisite for abdomen development, because the presence of hb protein in the posterior half represses posterior segmentation. This repression mechanism suggests that posterior segmentation might not directly depend on maternal positional cues, but be solely organized at the zygotic level. Here we report further evidence to support this hypothesis and show that the hb protein itself is crucially involved in organizing abdominal segmentation. Differential concentrations of hb protein determine the anterior and posterior borders of expression of the gap gene Krüppel (Kr) and the anterior border of the gap gene knirps (kni), thus defining three positional values. These regulatory pathways are controlled in a redundant way, in part by bcd and in part by the maternal hb gene product.

Comparison of the pharmacokinetics of ultrafilterable cisplatin species detectable by derivatization with diethyldithiocarbamate or atomic absorption spectroscopy.

The pharmacokinetics of the cisplatin (DDP) species detected by measurement of diethyldithiocarbamate (DDTC)-reactive species (DDTC-DDP) were compared to the pharmacokinetics of the species detected by measurement of total ultrafilterable platinum in patients receiving DDP alone or in combination with the nephroprotective agent sodium thiosulfate. The doses of DDP studied were 100 mg/m2 (11 courses given to eight patients) and 202.5 mg/m2 (five courses given to four patients) given as 2 h i.v. infusions, the latter with concurrent thiosulfate. When DDP was given alone (100 mg/m2) the two assays yielded the same area under the curve (AUC) values for DDTC-DDP and total ultrafilterable platinum during the first 4 h after the start of infusion; however, beyond 4 h post-infusion, the AUC for total ultrafilterable platinum was consistently greater than that for DDTC-DDP. When DDP was given with thiosulfate (202.5 mg/m2), the AUC for total ultrafilterable platinum was significantly greater than that of DDTC-DDP during the whole sampling period. The ratio of the AUC for total ultrafilterable platinum to DDTC-DDP, when DDP was given with thiosulfate, was barely significantly greater than that when DDP was given alone. These data indicate that during and immediately following a short infusion of DDP the major platinum-containing species present in plasma ultrafiltrate are still capable of reacting with nucleophilic sites on molecules such as DDTC; however, as the reactive species are eliminated, longer half-lived non-reactive ultrafilterable platinum species begin to predominate. They also indicate that although thiosulfate does neutralize a measurable amount of DDP in the plasma on the schedule employed, this degree of neutralization is not sufficient to explain the protection against DDP-induced nephrotoxicity produced by thiosulfate.

A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback.

We have developed a non-radioactive in situ hybridization technique for the localization of RNA in whole mount Drosophila embryos. After fixation, whole embryos are hybridized in situ with a DNA probe which has been labeled with digoxygenin. The hybridization products are detected by using a phosphatase-coupled antibody against digoxygenin. In parallel experiments, embryos can be treated with an antibody directed against the corresponding protein product to allow the detection of its distribution using standard immunochemical techniques. We have used this approach to compare the spatial and temporal distribution patterns of the RNA and protein products of the segmentation gene hunchback (hb) during the early stages of embryogenesis. This comparison revealed translational control of the maternally derived hb mRNA, which was difficult to detect by conventional techniques. The non-radioactive in situ hybridization method is as sensitive as conventional methods, but is faster and easier to perform. This may make it a useful tool for a variety of other systems.

Comparison of the gap segmentation gene hunchback between Drosophila melanogaster and Drosophila virilis reveals novel modes of evolutionary change.

We have cloned and sequenced a large portion of the hunchback (hb) locus from Drosophila virilis. Comparison with the Drosophila melanogaster hb sequence shows multiple strong homologies in the upstream and downstream regions of the gene, including most of the known functional parts. The coding sequence is highly conserved within the presumptive DNA-binding finger regions, but more diverged outside of them. The regions of high divergence are correlated with regions which are rich in short direct repeats (regions of high 'cryptic simplicity'), suggesting a significant influence of slippage-like mechanisms in the evolutionary divergence of the two genes. Staining of early D.virilis embryos with an hb antibody reveals conserved and divergent features of the spatial expression pattern at blastoderm stage. It appears that the basic expression pattern, which serves as the gap gene function of hb, is conserved, while certain secondary expression patterns, which have separate functions for the segmentation process, are partly diverged. Thus, both slippage driven mutations in the coding region, which are likely to occur at higher rates than point mutations and the evolutionary divergence of secondary expression patterns may contribute to the evolution of regulatory genes.

Posterior segmentation of the Drosophila embryo in the absence of a maternal posterior organizer gene.

Maternal hunchback activity suppresses the genetic pathway for abdomen formation in the Drosophila embryo. The active component of the posterior group of maternal genes, nanos, acts as a specific repressor of hunchback in the posterior region. Absence of both repressors results in normal embryos, indicating that posterior segmentation may not directly require maternal determinants.

Uridine pharmacokinetics in cancer patients.

The availability of uridine can alter the sensitivity of tumor cells to antimetabolites such as N-phosphonacetyl-L-aspartic acid (PALA) and acivicin by virtue of the cell's ability to salvage preformed metabolites from its environment. We investigated the pharmacokinetics of physiologically relevant amounts of uridine in cancer patients in a pilot study to further our understanding of uridine metabolism in the human body. Four cancer patients, two males and two females, were given an i.v. bolus of a trace amount of radiolabeled uridine. The nucleoside disappeared from the plasma in a triphasic manner, with initial half-lives of 0.57 +/- 0.28 and 1.79 +/- 0.62 min and a terminal half-life of 17.5 +/- 7.3 min. The volume of distribution was 481 +/- 70 ml/kg, and the plasma uridine clearance was calculated to be 1.70 +/- 0.42 l/min. Simultaneous plasma and bone marrow uridine concentrations were measured in a separate group of seven healthy volunteers. The uridine concentration in plasma was 2.32 +/- 0.58 microM, and that in the bone marrow plasma was 10.44 +/- 5.06 microM. These results suggest a very rapid turnover of uridine in the plasma when the nucleoside is present at physiologic concentrations, and that there is a locally high concentration of uridine available for salvage in the bone marrow.

Cisplatin administered by the intracavitary route as treatment for malignant mesothelioma.

Twenty-one patients with malignant mesothelioma were treated with an experimental intracavitary chemotherapy regimen of weekly intraperitoneal or intrapleural cisplatin (90-100 mg/m2) with simultaneous intravenous sodium thiosulfate delivered to protect against cisplatin-induced nephrotoxicity. One of eight patients (12.5%) receiving intrapleural therapy and nine of 13 patients receiving intraperitoneal therapy demonstrated objective evidence of a clinical response, including three surgically defined major tumor regressions (23%). Patients receiving intrapleural treatment had more advanced disease prior to therapy than those receiving intraperitoneal therapy. It was concluded that intraperitoneal cisplatin is an active treatment program for intra-abdominally localized mesothelioma. Additional investigation of intrapleural cisplatin should be undertaken in a patient population with less advanced disease or following surgical debulking.

Pharmacologic studies of intra-hepatic artery chemotherapy with degradable starch microspheres.

The effect of degradable starch microspheres (DSM) on the pharmacokinetics of 4 drugs administered via the hepatic artery was studied in 5 patients with colon carcinoma metastatic to the liver. The 4 drugs were 99m-technetium diethylenetriamine pentaacetic acid (99mTc-DTPA), an agent which is not metabolized in the liver, and floxuridine, doxorubicin, and mitomycin, agents which undergo hepatic metabolism to varying extents. DSM transiently decreased arterial blood flow to normal liver an average of 64% and to hepatic tumor an average of 78%. DSM increased tumor exposure to DTPA by a mean of 1.71-fold, and increased hepatic exposure by 1.46-fold, but did not affect total plasma exposure. In contrast, DSM did reduce total plasma exposure to floxuridine by a mean of 34%, and to mitomycin by 20%. No information was available on the effect of DSM on plasma doxorubicin levels which never exceeded the limits of detection. Variation in the injection rate of DSM did not appear to influence the relative advantages produced in tumor or plasma AUCs. The estimated increase in tumor exposure produced by DSM was 3.8-fold for floxuridine, and 3.0-fold for mitomycin. These results reflect the differences in extent of hepatic metabolism of these agents, and agree closely with predictions made from mathematical models. Although DSM improved the therapeutic index, the increase in tumor exposure was insufficient to produce significant tumor regression.

Peritoneal access for intracavitary chemotherapy.

Direct intraperitoneal instillation of many chemotherapeutic agents can markedly increase total peritoneal drug exposure and may be useful for the treatment of ovarian carcinoma and mesothelioma. The use of a totally implanted access system (Port-a-CathTM) reduces the risk of inadvertent bowel damage, and infection associated with repeated intraperitoneal instillation of drugs. In addition, patient acceptance is better in comparison to catheters that protrude through the skin. Catheter failure due to the formation of adhesions around the outside of the catheter remains a major problem.

High-dose intracavitary cisplatin with intravenous thiosulfate. Low incidence of serious neurotoxicity.

Recent published reports have suggested that cisplatin administered in high doses or in certain combination chemotherapy can cause serious neurotoxicity in a large percentage of patients treated. In several high-dose cisplatin-based intracavitary chemotherapy trials with the simultaneous intravenous administration of sodium thiosulfate, the incidence of clinically relevant neurotoxicity has been extremely low. In addition, several patients with serious preexisting cisplatin-induced neurologic dysfunction were treated without worsening of their clinical condition. It is suggested that thiosulfate might have been responsible for the low incidence of neurotoxicity in this patient population. Further experimental and clinical investigation of the potential of this agent to protect against cisplatin-induced neuropathy appears warranted.