The Longitudinal Effects of Posterior Spinal Fusion with Derotation on Axial Deformity in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the change in angle of trunk rotation (ATR), axial vertebral rotation (AVR), and body surface rotation (BSR) in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with en-bloc derotation across multiple postoperative visits. SUMMARY OF BACKGROUND DATA: Previous research has documented ATR, AVR, and BSR correction for AIS patients after surgery. However, there is a lack of evidence on the sustainability of this correction over time. METHODS: This was a retrospective study from a single-center prospective surface topographic registry of patients with AIS, age 11-20 at time of surgery, who underwent PSF with en-bloc derotation. Patients with previous spine surgery were excluded. ATR was measured with a scoliometer, AVR through EOS radiographic imaging, and BSR via surface topographic scanning, Data collection occurred at: preoperative, six-week, three-month, six-month, one-year, and two-year postoperative visits. BSR and AVR were tracked at the preoperative apical vertebral level, and the level with maximum deformity, at each respective timepoint. Generalized estimating equations models were used for statistical analysis. Covariates included age, sex, and body mass index. RESULTS: 49 patients (73.4% female, mean age 14.6±2.2 years, mean preoperative coronal curve angle 57.9°±8.5, and 67% major thoracic) were evaluated. ATR correction was significantly improved at all postoperative timepoints and there was no significant loss of correction. AVR Max and AVR Apex were significantly improved at all timepoints but there was a significant loss of correction for AVR Apex between the six-week and one-year visit (P=0.032). BSR Max achieved significant improvement at the three-month visit. BSR Apex was significantly improved at the three-month and one-year visit. CONCLUSION: ATR and AVR demonstrated significant axial plane correction at two-years postoperative in patients undergoing PSF for AIS. BSR did not maintain significant improvement by the two-year visit.

Analysis of 5,070 consecutive pedicle screws placed utilizing robotically assisted surgical navigation in 334 patients by experienced pediatric spine deformity surgeons: surgical safety and early perioperative complications in pediatric posterior spinal fusion.

PURPOSE: This study evaluates the intraoperative and short-term complications associated with robotically assisted pedicle screw placement in pediatric posterior spinal fusion (PSF) from three surgeons at two different institutions. METHODS: We retrospectively reviewed 334 pediatric patients who underwent PSF with robotic-assisted navigation at 2 institutions over 3 years (2020-2022). Five thousand seventy robotically placed screws were evaluated. Data collection focused on intraoperative and early postoperative complications with minimum 30-day follow-up. Patients undergoing revision procedures were excluded. RESULTS: Intraoperative complications included 1 durotomy, 6 patients with neuromonitoring alerts not related to screw placement, and 62 screws (1.2%) with documented pedicle breaches, all of which were revised at time of surgery. By quartile, pedicle breaches statistically declined from first quartile to fourth quartile (1.8% vs. 0.56%, p < 0.05). No breach was associated with neuromonitoring changes or neurological sequelae. No spinal cord or vascular injuries occurred. Seventeen postoperative complications occurred in eleven (3.3%) of patients. There were five (1.5%) patients with unplanned return to the operating room. CONCLUSION: Robotically assisted pedicle screw placement was safely and reliably performed on pediatric spinal deformity by three surgeons across two centers, demonstrating an acceptable safety profile and low incidence of unplanned return to the operating room.

α-Sheet secondary structure in amyloid ß-peptide drives aggregation and toxicity in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the deposition of ß-sheet-rich, insoluble amyloid ß-peptide (Aß) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aß oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aß-associated cytotoxicity peaks, en route to forming nontoxic ß-sheet fibrils. De novo-designed α-sheet peptides specifically and tightly bind the toxic oligomers over monomeric and fibrillar forms of Aß, leading to inhibition of aggregation in vitro and neurotoxicity in neuroblastoma cells. Based on this specific binding, a soluble oligomer-binding assay (SOBA) was developed as an indirect probe of α-sheet content. Combined SOBA and toxicity experiments demonstrate a strong correlation between α-sheet content and toxicity. The designed α-sheet peptides are also active in vivo where they inhibit Aß-induced paralysis in a transgenic Aß Caenorhabditis elegans model and specifically target and clear soluble, toxic oligomers in a transgenic APPsw mouse model. The α-sheet hypothesis has profound implications for further understanding the mechanism behind AD pathogenesis.

Giant mimiviruses escape many canonical criteria of the virus definition.

BACKGROUND: The discovery of mimivirus in 2003 prompted the quest for other giant viruses of amoebae. Mimiviruses and their relatives were found to differ considerably from other viruses. Their study led to major advances in virology and evolutionary biology. AIMS: We summarized the widening gap between mimiviruses and other viruses. SOURCES: We collected data from articles retrieved from PubMed using as keywords 'giant virus', 'mimivirus' and 'virophage', as well as quoted references from these articles. CONTENT: Data accumulated during the last 15 years on mimiviruses and other giant viruses highlight that there is a quantum leap between these infectious agents, the complexity of which is similar to that of intracellular microorganisms, and classical viruses. Notably, in addition to their giant structures and genomes, giant viruses have abundant gene repertoires with genes unique in the virosphere, including a tremendous set of translation components. The viruses contain hundreds of proteins and many transcripts. They share a core of central and ancient proteins but their genome sequences display a substantial level of mosaicism. Finally, mimiviruses have a specific mobilome, including virophages that can integrate into their genomes, and against which they can defend themselves through integration of short fragments of the DNA of these invaders. IMPLICATIONS: Mimiviruses and subsequently discovered giant viruses have changed the virus paradigm and contradict many virus definition criteria delineated for classical viruses. The major cellular hallmark that is still lacking in giant viruses is the ribosome, including both ribosomal protein and RNA encoding genes, which makes them bona fide microbes without ribosomes.

Recombinant expression of Mimivirus L725 ORFan gene product.

Mimivirus was the first discovered amoebal giant virus. The Mimivirus virions are covered by a dense layer of approximately 130 nm-long fibers, the length and shape of which diverge from those of other viruses. Here, we aimed at expressing the L725 protein to further confirm and study its role as a fiber-associated protein. We report Escherichia coli expression of the L725 protein, which is encoded by a Mimivirus ORFan, was previously identified by proteomics in purified viral fibers and demonstrated to be a fiber-associated protein by RNA-silencing experiments. The expressed protein was recognized by anti-Mimivirus fiber or anti-Mimivirus L725 polyclonal antibodies. This study is the only expression, to our knowledge, of a product from a Mimiviral ORFan gene.

'Bedside assessment' of acute hantavirus infections and their possible classification into the spectrum of haemophagocytic syndromes.

Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant (p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly (p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower (p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link with the novel clinical entity of haemophagocytic syndromes, also characterised by manifest hypertriglyceridaemia, is discussed.

HIV infection en route to endogenization: two cases.

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3-100% per gene) and 24% overall (0-50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication.

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies-positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer.

We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.

[A new case of systemic contact eczema to nickel in a peripheral venous catheter]. / Eczéma de contact systémique au nickel d'un cathéter périphérique : un nouveau cas.

BACKGROUND: Nickel-elicited systemic contact dermatitis is a rare event seen in previously skin sensitized patients. We report a case of systemic contact dermatitis due to nickel released into the bloodstream from a metal section of a catheter during infusion. CASE REPORT: A 39-year-old woman presented papular and vesicular flexural dermatitis and pompholyx 72h after cervical spine surgery. She received numerous treatments during the perioperative period. A challenge test with one of the suspected treatments, cefazolin, was performed by intravenous infusion over a six-hour period using the same Optiva) peripheral catheter (Johnson & Johnson, USA). Six hours after withdrawal of the catheter, an eruption occurred. A further cefazolin challenge test performed later under identical conditions but using a different type of catheter (nickel-free) was negative. Nickel-elicited systemic contact dermatitis due to nickel release from a catheter was diagnosed. The patient's medical history was notable for contact dermatitis with jewellery. Patch tests confirmed marked nickel sensitization. DISCUSSION: A little-known way of systemic nickel absorption is through insertion of a venous catheter with a metal section containing nickel and a metallic eyelet containing nickel can in fact remain in place after catheter placement. Nickel can thus be released into the circulation during infusion and an eruption may occur during the postoperative period. This diagnosis is noteworthy as such eruptions can easily be mistakenly diagnosed as cutaneous drug eruptions.

A porcine model of systemic and renal haemodynamic responses to infrarenal aortic cross-clamping.

OBJECTIVES: cross-clamping of the infrarenal aorta is associated with complex haemodynamic disturbances. Several experimental models of aortic cross-clamping (AXC) have been described with heterogeneous results. The main purpose of this study was to establish an animal model in which infrarenal AXC could reproduce similar systemic and renal haemodynamic changes to those observed in humans. METHODS: eleven anaesthetised pigs underwent AXC just below the renal arteries. Renal blood flow was measured using clearance of (131)I hippuran. Systemic and renal parameters were collected at 3 consecutive 30-min periods. RESULTS: AXC did not alter the extraction fraction of (131)I hippuran but was accompanied by significant (13%) decrease in cardiac index (p = 0.005) and a 23% increase in mean arterial pressure (p = 0.005). AXC induced significant 135% increase in renal vascular resistance (p = 0.012) and a 35% decrease in renal blood flow (p = 0.016). This worsened after removal of the aortic clamp, whereas systemic variables returned to baseline levels. CONCLUSIONS: this AXC animal model reproduces the changes observed in humans. It provides a reliable animal model which allows to investigate the underlying mechanisms of renal vasoconstriction and the effect of new drugs.

Patient-controlled epidural analgesia after abdominal surgery: ropivacaine versus bupivacaine.

UNLABELLED: In this randomized, double-blinded study we sought to assess the analgesic efficacy of ropivacaine and bupivacaine in combination with sufentanil and the efficacy of ropivacaine alone after major abdominal surgery. Sixty patients undergoing major abdominal surgery received standardized general anesthesia combined with epidural thoracic analgesia. They were allocated to one of three groups: the BS group received postoperative patient-controlled epidural analgesia with 0.125% bupivacaine plus 0.5 microg/mL sufentanil; the RS group received 0.125% ropivacaine plus 0.5 microg/mL sufentanil; and the R group received 0.2% ropivacaine, with the patient-controlled epidural analgesia device set at bolus 2-3 mL and background infusion 3-5 mL/h. Visual analog scale scores were significantly lower during coughing in the BS group compared with the RS and R groups and in the RS group compared with the R group. The BS group required significantly less local anesthetic (milligrams per day) during the first three postoperative days compared with the RS and R groups, and the RS group, significantly less than the R group. No major side effects were noted in any group. We conclude that, after major abdominal surgery, thoracic epidural analgesia was more effective with bupivacaine than with ropivacaine when these two local anesthetics are used in a mixture with sufentanil. Ropivacaine alone was less effective than ropivacaine in combination with sufentanil. IMPLICATIONS: After major abdominal surgery, thoracic epidural analgesia was more effective with 0.125% bupivacaine than with 0.125% ropivacaine when these two local anesthetics were used in a mixture with 0.5 microg/mL sufentanil. Ropivacaine 0.2% alone was less effective than 0.125% ropivacaine combined with sufentanil.

DNA interaction and cytotoxicity of a new series of indolo[2,3-b]quinoxaline and pyridopyrazino[2,3-b]indole derivatives.

Absorption, melting temperature and linear dichroism measurements were performed to investigate the interaction with DNA of a series of 16 tricyclic and tetracyclic compounds related to the antiviral agent B-220. The relative DNA affinity of the test compounds containing an indolo[2,3-b]quinoxaline, pyridopyrazino[2,3-b]indoles or pyrazino[2,3-b]indole planar chromophore varies significantly depending on the nature of the side chain grafted onto the indole nitrogen. Compounds with a dimethylaminoethyl chain strongly bind to DNA and exhibit a preference for GC-rich DNA sequences, as revealed by DNase I footprinting. Weaker DNA interactions were detected with those bearing a morpholinoethyl side chain. The incorporation of a 2,3-dihydroxypropyl side chain does not reinforce the DNA interaction compared with the unsubstituted analogues. Both the DNA relaxation assay and cytotoxicity study using two human leukemia cell lines sensitive (HL-60) or resistant (HL-60/MX2) to the antitumor drug mitoxantrone, indicate that topoisomerase II is not a privileged target for the test compounds which only weakly interfere with the catalytic activity of the DNA cleaving enzyme. Cytometry studies showed that the most cytotoxic compounds induce a massive accumulation of cells in the G2/M phase of the cell cycle. Collectively, the data show a relationship between DNA binding and cytotoxicity in the indolo[2,3-b]quinoxaline series.

Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction.

Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role. Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft (CABG) surgery were allocated to a treatment group [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group, n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass (CPB) (P<0.05) and on postoperative day 2 (P<0.05). The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB (P<0.05). Renal plasma flow, measured as [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the control group before CPB, as was endogenous creatinine clearance after CPB (P<0.05). On post-operative day 7, ClH was significantly higher in the ACEI group than in the control group (P<0.05). Plasma renin activity and vasopressin concentration increased in both groups during CPB (P<0.05). The study demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction. Moreover, renal perfusion was better maintained during surgery, and this effect was sustained up to post-operative day 7.

Synthesis, cytotoxicity, DNA interaction and topoisomerase II inhibition properties of tetrahydropyrrolo[3,4-a]carbazole-1,3-dione and tetrahydropyrido-[3,2-b]pyrrolo[3,4-g]indole-1,3-dione derivatives.

Three tetrahydropyrrolo[3,4-a]carbazole-1,3-diones (6--8) and two tetrahydropyrido[3,2-b]pyrrolo[3,4-g]indole-1,3-diones (11--12) have been synthesized. Their interaction with DNA was probed by absorption and thermal melting studies. Compounds 8 and 12 both equipped with a hydroxyethyl-aminoethyl side-chain demonstrated higher affinities for poly(dA-dT)(2) than compounds 6, 7 and 11 bearing a dimethylaminoethyl side-chain. Circular and electric linear dichroism measurements showed that all five drugs behave as typical DNA intercalating agents. A plasmid cleavage assay was used to evaluate the capacity of the drugs to inhibit human topoisomerase II. Compounds 8 and 12 which bind strongly to DNA were found to stabilize DNA-topoisomerase II covalent complexes but their topoisomerase II inhibitory properties do not correlate with their cytotoxic potential. Compounds 6 and 7 are essentially inactive whereas compounds 8, 11 and 12 exhibit a high toxicity to P388 murine leukemia cells and provoke a marked accumulation in the G2/M phase of the cell cycle. These compounds form a new class of DNA-targeted antitumor agents.