Analyzing genetic diversity in luffa and developing a Fusarium wilt-susceptible linked SNP marker through a single plant genome-wide association (sp-GWAS) study.

BACKGROUND: Luffa (Luffa spp.) is an economically important crop of the Cucurbitaceae family, commonly known as sponge gourd or vegetable gourd. It is an annual cross-pollinated crop primarily found in the subtropical and tropical regions of Asia, Australia, Africa, and the Americas. Luffa serves not only as a vegetable but also exhibits medicinal properties, including anti-inflammatory, antidiabetic, and anticancer effects. Moreover, the fiber derived from luffa finds extensive applications in various fields such as biotechnology and construction. However, luffa Fusarium wilt poses a severe threat to its production, and existing control methods have proven ineffective in terms of cost-effectiveness and environmental considerations. Therefore, there is an urgent need to develop luffa varieties resistant to Fusarium wilt. Single-plant GWAS (sp-GWAS) has been demonstrated as a promising tool for the rapid and efficient identification of quantitative trait loci (QTLs) associated with target traits, as well as closely linked molecular markers. RESULTS: In this study, a collection of 97 individuals from 73 luffa accessions including two major luffa species underwent single-plant GWAS to investigate luffa Fusarium wilt resistance. Utilizing the double digest restriction site associated DNA (ddRAD) method, a total of 8,919 high-quality single nucleotide polymorphisms (SNPs) were identified. The analysis revealed the potential for Fusarium wilt resistance in accessions from both luffa species. There are 6 QTLs identified from 3 traits, including the area under the disease progress curve (AUDPC), a putative disease-resistant QTL, was identified on the second chromosome of luffa. Within the region of linkage disequilibrium, a candidate gene homologous to LOC111009722, which encodes peroxidase 40 and is associated with disease resistance in Cucumis melo, was identified. Furthermore, to validate the applicability of the marker associated with resistance from sp-GWAS, an additional set of 21 individual luffa plants were tested, exhibiting 93.75% accuracy in detecting susceptible of luffa species L. aegyptiaca Mill. CONCLUSION: In summary, these findings give a hint of genome position that may contribute to luffa wild resistance to Fusarium and can be utilized in the future luffa wilt resistant breeding programs aimed at developing wilt-resistant varieties by using the susceptible-linked SNP marker.

Forcefully engaging rods into tulips with gap discrepancy leading to pedicle screw loosening-a biomechanical analysis using long porcine spine segments.

BACKGROUND CONTEXT: Long-segment pedicle screw instrumentation is widely used to treat complex spinal disorders. Rods are routinely precontoured to maximize assistance on the correcting side of the deformity, but there often exists a residual gap discrepancy between the precontoured rods and screw tulips. No previous research has investigated the diminished pullout strength of the most proximal or distal pedicle screw resulting from a mismatched rod in long-segment pedicle screw instrumentation. PURPOSE: The present study aimed to investigate the decreased pullout force of pedicle screws affected by the gap discrepancy when forcefully engaging a mismatched rod into a tulip in a normal-density porcine spine. STUDY DESIGN: The pedicle screw fixation strength under axial pullout force was compared among three different gap discrepancies between rods and tulips using long porcine spine segments. METHODS: Twelve porcine lumbar vertebrae (L3-L6) were implanted with pedicle screws and rods. Screws on one side had no gap between the tulip and rod (0-mm group), while the most proximal screw on the other side had an intentional gap of 3 mm (3-mm group) or 6 mm (6-mm group). Three hours after forcefully engaging the rod into the tulips at room temperature, the set screws in all specimens were loosened, and each specimen was dissected into individual vertebrae for subsequent pullout testing. RESULTS: The control group exhibited significantly greater pullout strength (1987.68 ± 126.80 N) than the groups from different rod-tulip configurations (p<.05), with significantly greater strength in the 3-mm group (945.62 ± 97.43 N) than the 6-mm group (655.30 ± 194.49 N) (p<.05). Only 47.6% and 33.0% of the pullout strength was retained in the 3-mm and 6-mm groups, respectively, compared to the control group. CONCLUSIONS: Gap discrepancies between rods and tulips can significantly reduce pedicle screw pullout strength, with a correlation between decreased strength and increased gaps. Surgeons should avoid forcefully engaging mismatched rods and consider well-fitted contoured rods in spinal surgery to minimize the risk of screw loosening. CLINICAL SIGNIFICANCE: The gap discrepancy between rod and tulip significantly affected pullout strength, with greater gaps leading to reduced strength. Forcefully engaging mismatched rods into tulips in degenerative spinal surgery should be avoided to minimize the risk of early screw pullout.

Influence of various pilot hole profiles on pedicle screw fixation strength in minimally invasive and traditional spinal surgery: a comparative biomechanical study.

Despite advancements in pedicle screw design and surgical techniques, the standard steps for inserting pedicle screws still need to follow a set of fixed procedures. The first step, known as establishing a pilot hole, also referred to as a pre-drilled hole, is crucial for ensuring screw insertion accuracy. In different surgical approaches, such as minimally invasive or traditional surgery, the method of creating pilot holes varies, resulting in different pilot hole profiles, including variations in size and shape. The aim of this study is to evaluate the biomechanical properties of different pilot hole profiles corresponding to various surgical approaches. Commercially available synthetic L4 vertebrae with a density of 0.16 g/cc were utilized as substitutes for human bone. Four different pilot hole profiles were created using a 3.0 mm cylindrical bone biopsy needle, 3.6 mm cylindrical drill, 3.2-5.0 mm conical drill, and 3.2-5.0 mm conical curette for simulating various minimally invasive and traditional spinal surgeries. Two frequently employed screw shapes, namely, cylindrical and conical, were selected. Following specimen preparation, screw pullout tests were performed using a material test machine, and statistical analysis was applied to compare the mean maximal pullout strength of each configuration. Conical and cylindrical screws in these four pilot hole configurations showed similar trends, with the mean maximal pullout strength ranking from high to low as follows: 3.0 mm cylindrical biopsy needle, 3.6 mm cylindrical drill bit, 3.2-5.0 mm conical curette, and 3.2-5.0 mm conical drill bit. Conical screws generally exhibited a greater mean maximal pullout strength than cylindrical screws in three of the four different pilot hole configurations. In the groups with conical pilot holes, created with a 3.2-5.0 mm drill bit and 3.2-5.0 mm curette, both conical screws exhibited a greater mean maximal pullout strength than did cylindrical screws. The strength of this study lies in its comprehensive comparison of the impact of various pilot hole profiles commonly used in clinical procedures on screw fixation stability, a topic rarely reported in the literature. Our results demonstrated that pilot holes created for minimally invasive surgery using image-guided techniques exhibit superior pullout strength compared to those utilized in traditional surgery. Therefore, we recommend prioritizing minimally invasive surgery when screw implantation is anticipated to be difficult or there is a specific need for stronger screw fixation. When opting for traditional surgery, image-guided methods may help establish smaller pilot holes and increase screw fixation strength.

Finite element analysis of optimized novel additively manufactured non-articulating prostheses for cervical total disc replacement.

Ball-and-socket designs of cervical total disc replacement (TDR) have been popular in recent years despite the disadvantages of polyethylene wear, heterotrophic ossification, increased facet contact force, and implant subsidence. In this study, a non-articulating, additively manufactured hybrid TDR with an ultra-high molecular weight polyethylene core and polycarbonate urethane (PCU) fiber jacket, was designed to mimic the motion of normal discs. A finite element (FE) study was conducted to optimize the lattice structure and assess the biomechanical performance of this new generation TDR with an intact disc and a commercial ball-and-socket Baguera®C TDR (Spineart SA, Geneva, Switzerland) on an intact C5-6 cervical spinal model. The lattice structure of the PCU fiber was constructed using the Tesseract or the Cross structures from the IntraLattice model in the Rhino software (McNeel North America, Seattle, WA) to create the hybrid I and hybrid II groups, respectively. The circumferential area of the PCU fiber was divided into three regions (anterior, lateral and posterior), and the cellular structures were adjusted. Optimal cellular distributions and structures were A2L5P2 in the hybrid I and A2L7P3 in the hybrid II groups. All but one of the maximum von Mises stresses were within the yield strength of the PCU material. The range of motions, facet joint stress, C6 vertebral superior endplate stress and path of instantaneous center of rotation of the hybrid I and II groups were closer to those of the intact group than those of the Baguera®C group under 100 N follower load and pure moment of 1.5 Nm in four different planar motions. Restoration of normal cervical spinal kinematics and prevention of implant subsidence could be observed from the FE analysis results. Superior stress distribution in the PCU fiber and core in the hybrid II group revealed that the Cross lattice structure of a PCU fiber jacket could be a choice for a next-generation TDR. This promising outcome suggests the feasibility of implanting an additively manufactured multi-material artificial disc that allows for better physiological motion than the current ball-and-socket design.

Biomechanical evaluation of pedicle screw stability after 360-degree turnback from full insertion: effects of screw shape, pilot hole profile and bone density.

Intraoperative pedicle screw depth adjustment after initial insertion, including both forward and backward adjustments, is sometimes necessary to facilitate rod application and ensure that the screw is in the correct position, which is determined by intraoperative fluoroscopy. Adjusting the screw with forward turns has no negative influence on the screw fixation stability; however, screw turnback may weaken the fixation stability. The aim of this study is to evaluate the biomechanical properties of screw turnback and demonstrate the reduction in the fixation stability after the screw is turned 360° from its full insertion position. Commercially available synthetic closed-cell polyurethane foams with three different densities simulating various degrees of bone density were utilized as substitutes for human bone. Two different screw shapes (cylindrical and conical) together with two different pilot hole profiles (cylindrical and conical) were tested. Following specimen preparation, screw pullout tests were conducted using a material test machine. The mean maximal pullout strength between full insertion and 360-degree turnback from full insertion in each setting was statistically analyzed. The mean maximal pullout strength after 360-degree turnback from full insertion was generally lower than that at full insertion. The reduced mean maximal pullout strength after turnback increased with decreasing bone density. Conical screws had significantly lower pullout strength after 360-degree turnback than cylindrical screws. The mean maximal pullout strength was reduced by up to approximately 27% after 360-degree turnback when using a conical screw in a low bone density specimen. Additionally, specimens treated with a conical pilot hole presented a less reduction in pullout strength after screw turnback as compared to those with a cylindrical pilot hole. The strength of our study was that we systematically investigated the effects of various bone densities and screw shapes on screw stability after turnback, which has rarely been reported in the literature. Our study suggests that pedicle screw turnback after full insertion should be reduced in spinal surgeries, particularly procedures that use conical screws in osteoporotic bone. Pedicle screw secured with a conical pilot hole might be beneficial for screw adjustment.

Biomechanical evaluation of position and bicortical fixation of anterior lateral vertebral screws in a porcine model.

Although an anterior approach with anterior lateral screw fixation has been developed for stabilizing the thoracolumbar spine clinically, screw loosening still occurs. In this novel in vitro study, we attempted to elucidate the optimal screw position in the lateral lumbar vertebra and the effect of bicortical fixation. A total of 72 fresh-frozen lumbar vertebrae from L1-6 were harvested from 12 mature pigs and randomly assigned to two modalities: bicortical fixation (n = 36) and unicortical fixation (n = 36). Six groups of screw positions in the lateral vertebral body in each modality were designated as central-anterior, central-middle, central-posterior, lower-anterior, lower-middle, and lower- posterior; 6 specimens were used in each group. The correlations between screw fixation modalities, screw positions and axial pullout strength were analyzed. An appropriate screw trajectory and insertional depth were confirmed using axial and sagittal X-ray imaging prior to pullout testing. In both bicortical and unicortical fixation modalities, the screw pullout force was significantly higher in the posterior or middle position than in the anterior position (p < 0.05), and there was no significant differences between the central and lower positions. The maximal pullout forces from the same screw positions in unicortical fixation modalities were all significantly lower, decreases that ranged from 32.7 to 74%, than those in bicortical fixation modalities. Our study using porcine vertebrae showed that screws in the middle or posterior position of the lateral vertebral body had a higher pullout performance than those in the anterior position. Posteriorly positioned lateral vertebral screws with unicortical fixation provided better stability than anteriorly positioned screws with bicortical fixation.

Enzastaurin cardiotoxicity: QT interval prolongation, negative inotropic responses and negative chronotropic action.

Several clinical trials observed that enzastaurin prolonged QT interval in cancer patients. However, the mechanism of enzastaurin-induced QT interval prolongation is unclear. Therefore, this study aimed to assess the effect and mechanism of enzastaurin on QT interval and cardiac function. The Langendorff and Ion-Optix MyoCam systems were used to assess the effects of enzastaurin on QT interval, cardiac systolic function and intracellular Ca2+ transient in guinea pig hearts and ventricular myocytes. The effects of enzastaurin on the rapid delayed rectifier (IKr), the slow delayed rectifier K+ current (IKs), transient outward potassium current (Ito), action potentials, Ryanodine Receptor 2 (RyR2) and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) expression and activity in HEK 293 cell system and primary cardiomyocytes were investigated using whole-cell recording technique and western blotting. We found that enzastaurin significantly prolonged QT interval in guinea pig hearts and increased the action potential duration (APD) in guinea pig cardiomyocytes in a dose-dependent manner. Enzastaurin potently inhibited IKr by binding to the human Ether-à-go-go-Related gene (hERG) channel in both open and closed states, and hERG mutant channels, including S636A, S631A, and F656V attenuated the inhibitory effect of enzastaurin. Enzastaurin also moderately decreased IKs. Additionally, enzastaurin also induced negative chronotropic action. Moreover, enzastaurin impaired cardiac systolic function and reduced intracellular Ca2+ transient via inhibition of RyR2 phosphorylation. Taken together, we found that enzastaurin prolongs QT, reduces heart rate and impairs cardiac systolic function. Therefore, we recommend that electrocardiogram (ECG) and cardiac function should be continuously monitored when enzastaurin is administered to cancer patients.

The role of counter-torque holders in tightening of pedicle screw-rod constructs: a biomechanical study in a porcine model.

BACKGROUND CONTEXT: Pedicle screw-rod assembly procedures following pedicle screw insertion include contouring and placing rods into screw tulips, introducing set screws into the tulip along the screw thread, applying a counter-torque holder and tightening all the set screws clockwise. Even if an appropriate pedicle screw is implanted, screw dislodgement after tightening of the tulip and set screw is not uncommon. Pedicle wall violation resulting from excessive rotational force due to inadequate use of a counter-torque holder might be the reason. However, the strain change in the pedicle during tulip-set screw tightening and the role of counter-torque have never been investigated. PURPOSE: This study determined differences in the strain change in the outer and inner pedicle walls during tulip-set screw tightening; additionally, the influence of counter-torque on pedicle wall violation was elucidated. STUDY DESIGN: A controlled biomechanical study; the strain values of outer and inner pedicle walls in cadaveric porcine L4-L5 vertebrae during tulip-set screw tightening with or without a counter-torque holder were measured. METHODS: Twelve L4-L5 fresh-frozen porcine lumbar vertebrae were implanted with screw-rod constructs; the set screw was randomly locked into the tulip in the right L5, right L4, left L5 and left L4 testing groups. The maximal values from eight strain gauges (P-R-O: outer cortex of right pedicle in proximal vertebra; P-R-I: inner cortex of right pedicle in proximal vertebra; D-R-O: outer cortex of right pedicle in distal vertebra; D-R-I: inner cortex of right pedicle in distal vertebra; P-L-O: outer cortex of left pedicle in proximal vertebra; P-L-I: inner cortex of left pedicle in proximal vertebra; D-L-O: outer cortex of left pedicle in distal vertebra; D-L-I: outer cortex of left pedicle in proximal vertebra) for each specimen during tightening to 12 Nm were measured. RESULTS: The maximal strain values of the ipsilateral strain gauges in all testing groups were almost significantly higher when a counter-torque holder was not used than when one was used. The strain values in the adjacent pedicle of specimens without a counter-torque holder were significantly increased: P-R-O and P-R-I in the right L5 group; D-R-I in the right L4 group; P-L-I and P-L-O in the left L5 group; D-L-O and D-L-I in the left L4 group. CONCLUSIONS: The constraint effect of counter-torque during tulip-set screw tightening is necessary. Clockwise rotational force with a fragile lateral pedicle wall suggests that caution is required when using a counter-torque holder to tighten the right L5 and left L4 constructs. CLINICAL SIGNIFICANCE: A counter-torque holder is important during tulip-set screw tightening; improper use may lead to adjacent pedicle wall violation, sequentially resulting in pedicle screw loosening.

Biomechanical comparison of pedicle screw fixation strength among three different screw trajectories using single vertebrae and one-level functional spinal unit.

Three key factors are responsible for the biomechanical performance of pedicle screw fixation: screw mechanical characteristics, bone quality and insertion techniques. To the best of the authors' knowledge, no study has directly compared the biomechanical performance among three trajectories, i.e., the traditional trajectory (TT), modified trajectory (MT) and cortical bone trajectory (CBT), in a porcine model. This study compared the pullout strength and insertion torque of three trajectory methods in single vertebrae, the pullout strength and fixation stiffness including flexion, extension, and lateral bending in a one-level instrumented functional spinal unit (FSU) that mimics the in vivo configuration were clarified. A total of 18 single vertebrae and 18 FSUs were randomly assigned into three screw insertion methods (n = 6 in each trajectory group). In the TT group, the screw converged from its entry point, passed completely inside the pedicle, was parallel to the superior endplate, was located in the superior third of the vertebral body and reached to at least the anterior third of the vertebral body. In the MT group, the convergent angle was similar to that of the TT method but directed caudally to the anterior inferior margin of the vertebral body. The results of insertion torque and pullout strength in single vertebrae were analyzed; in addition, the stiffness and pullout strength in the one-level FSU were also investigated. This study demonstrated that, in single vertebrae, the insertion torque was significantly higher in CBT groups than in TT and MT groups (p < 0.05). The maximal pullout strength was significantly higher in MT groups than in TT and CBT groups (p < 0.05). There was no significant difference in stiffness in the three motions among all groups. The maximal pullout strength in FSUs of MT and CBT groups were significantly higher than the TT groups (p < 0.05). We concluded that either MT or CBT provides better biomechanical performance than TT in single vertebrae or FSUs. The lack of significance of stiffness in FSUs among three methods suggested that MT or CBT could be a reasonable alternative to TT if the traditional trajectory was not feasible.

Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy.

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of ß-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.

Percutaneous Endoscopic Interbody Debridement and Fusion (PEIDF) Decreases Risk of Sepsis and Mortality in Treating Infectious Spondylodiscitis for Patients with Poor Physical Status, a Retrospective Cohort Study.

Background: Postoperative immunosuppression is associated with blood loss and surgical trauma during surgery and subsequently predisposes patients to increased morbidity. Spine endoscopic surgery has been accepted as an effective surgical technique with less surgical trauma and less blood loss for the complication of infectious spondylodiscitis. Therefore, the aim of this study was to investigate whether PEIDF could reduce the morbidity rates for patients with infectious spondylodiscitis. Methods: We launched a retrospective cohort study on the comparison of the perioperative prognosis between PEIDF and conventional open surgery for single-level lumbar infectious spondylodiscitis in patients with poor physical health (ASA ≥ 4) from 2014 to 2019. Results: Forty-four patients were included in this study. Fifteen of them underwent PEIDF, and the rest of the 29 patients were treated with open surgery. Less surgical blood loss (p < 0.001) and intraoperative transfusions (p < 0.001) with a better decline of CRP (p = 0.017) were statistically significant in patients receiving PEIDF. Patients undergoing conventional open surgery encountered more postoperative sepsis (p = 0.030), a higher qSOFA score (p = 0.044), and prolonged-time for CRP normalization (p = 0.001). Conclusions: PEIDF minimizes a poor postoperative outcome due to less surgical trauma, intraoperative blood loss, and the need for a blood transfusion.

Propranolol use in patients with cirrhosis and refractory ascites: A nationwide study.

Background: The impact of propranolol on patients with cirrhosis and refractory ascites is controversial. We conducted a nationwide longitudinal cohort study to compare the survival between patients with cirrhosis and refractory ascites, with and without using propranolol. Methods: Data of patients with cirrhosis and refractory ascites using propranolol, and controls matched by age and gender, were extracted from The National Health Insurance Research Database of Taiwan. The baseline demographic characteristics were compared between groups. Cox regression analysis was used to examine the predictors of mortality. Results: In this study, 1788 patients were enrolled in each group; 1304 patients (72.9%) in the propranolol group and 1445 patients (80.8%) in the control group died (P < 0.001). The mean survival was 34.3 ± 31.2 months in the propranolol group and 20.8 ± 26.6 months in the control group (P < 0.001). Propranolol (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.55-0.64, P < 0.001), statins (HR: 0.43, 95% CI: 0.34-0.56, P < 0.001), age (HR: 1.02, 95% CI: 1.01-1.02, P < 0.001), and diabetes mellitus (HR: 1.14, 95% CI: 1.05-1.24, P = 0.002) were the independent predictors for mortality. Conclusions: Use of propanolol was associated with reduced mortality, compared with controls, in this nationwide cohort of patients with cirrhosis and refractory ascites.

Improved fixation stability for repairing pedicle screw loosening using a modified cement filling technique in porcine vertebrae.

Polymethylmethacrylate (PMMA) has been applied clinically and biomechanically repair loose pedicle screws. Controversies have arisen over data due to uncontrolled cement properties, various locations and sizes of fenestrated holes in repair screws, irregular holes and different bone densities of specimens. In this study, the pullout strength was compared for two techniques, the modified technique to use PMMA to augment a threaded hole and the traditional technique with retrograde injection of a PMMA filling, for standard loose screws in porcine vertebrae. Both techniques provided statistically significant results for sufficiently randomized specimens and experimental procedures. The difference in the pullout strength between conical and cylindrical screws for the aforementioned cement augmentation techniques was also investigated. Twenty-four single-level fresh-frozen lumbar vertebrae from L1 to L6 were harvested from four mature pigs. A total of 0.8 ml of PMMA was retrograde injected into screw holes with a 5.5 mm diameter, followed by insertion of a 5.0 mm diameter repair screw in the traditional group (n = 12). A stiff threaded PMMA hole was created with a 4.5 mm tapping screw before insertion of repair screws in the modified group (n = 12). Two screw geometries were randomly assigned as cylindrical (n = 6) and conical (n = 6) in each group. The correlations between filling techniques, screw geometries and axial pullout strength were analyzed. An appropriate screw trajectory and insertion depth were confirmed using X-ray imaging prior to pullout testing in both groups. For a given screw geometry (cylindrical or conical), the pullout force of the modified group was significantly higher than that of the traditional group. There was no significant difference in the pullout force between the screw geometries for a given filling technique. The cement augmentation technique is far more influential than the screw outer geometry. The modified PMMA technique created a greater anchor force than the traditional method and could be an alternative for revision of pedicle screw loosening.

Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B.

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) has the advantages of low price, quick onset, good efficacy, and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks, followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM-TDF groups died or received liver transplantation (P = 0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24, and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE. (This study has been registered at ClinicalTrials.gov under identifier NCT01848743).

Risk Factors of Coexisting Septic Spondylitis and Arthritis: A Case-Control Study in a Tertiary Referral Hospital.

INTRODUCTION: In patients under immunosuppression or severe sepsis, it is sometimes manifested as coexisting septic arthritis and spondylitis. The aim of this study is to evaluate and investigate the risk factors of infectious spondylitis associated with septic arthritis. METHODS: The study retrospectively reviewed the patients diagnosed with infectious spondylitis between January 2010 and September 2018 for risk factors of coexisting major joint septic arthritis. RESULTS: A total of 10 patients with infectious spondylitis and coexisting septic arthritis comprised the study group. Fifty matched patients with solely infectious spondylitis were selected as the control group. Major risk factors include preoperative C-reactive protein (p = 0.001), hypoalbuminemia (p = 0.011), history of total joint replacement (p < 0.001), duration of preoperative antibiotics treatment (p = 0.038) and psoas muscle abscess (p < 0.001). CONCLUSION: Infectious spondylitis and septic arthritis are thought of as medical emergencies due to their high mortality and morbidity. Our study evaluated 5 risk factors as significant major findings: hypoalbuminemia (<3.4 g/dL), higher preoperative CRP (>130 mg/L), psoas muscle abscess, longer preoperative antibiotics treatment (>8 days) and history of total joint replacement. Clinicians should pay attention to the patients with those five factors to detect the coexisting infections as early as possible.

Minimally Invasive Percutaneous Vertebroplasty for Thoracolumbar Instrumented Vertebral Fracture in Patients With Posterior Instrumentation.

BACKGROUND: The traditional treatment for an instrumented vertebral fracture involves removing the loosened pedicle screws and extending the posterior instrumentation cephaladly or caudally. There has been a recent trend of performing minimally invasive fluoroscopy-guided percutaneous vertebroplasty as a salvage procedure. OBJECTIVE: The aim of this study was to compare the outcomes of surgical interventions for instrumented vertebral fracture. STUDY DESIGN: Retrospective assessment. SETTING: All data came from Chang Gung Memorial Hospital, Taiwan. METHODS: We retrospectively reviewed 35 patients with an instrumented vertebral fracture who underwent fluoroscopy-guided percutaneous vertebroplasty (Group I, n = 16) or extension of the posterior instrumentation (Group II, n = 19). Demographic data were recorded. The operating time, amount of intraoperative blood loss, time to postoperative ambulation, and duration of hospital stay were also evaluated. The visual analog scale (VAS) score, kyphotic angle on radiological images, Kirkaldy-Willis functional score, complications, and revision surgery were evaluated at one week and one, 3, 6, and 12 months postoperatively. RESULTS: Group I had a shorter operating time (P < 0.001), less intraoperative blood loss (P < 0.001), earlier postoperative ambulation (P < 0.001), and a shorter hospital stay (P < 0.001). The mean VAS score improved significantly after surgery in both groups (P = 0.001). The postoperative kyphotic angle was better in Group II (P < 0.05). There was no significant between-group difference in the Kirkaldy-Willis functional score at the last follow-up (P = 0.91). There was no significant between-group difference in the need for revision surgery (Group I, n = 4; Group II, n = 5; P = 0.93). LIMITATION: This study is a retrospective cohort. CONCLUSIONS: Minimally invasive fluoroscopy-guided percutaneous vertebroplasty can be used as an alternative to extension of posterior instrumentation for instrumented vertebral fracture. It has several advantages, including a shorter operating time, earlier postoperative ambulation, less blood loss, and a shorter hospital stay. The clinical outcomes of these 2 treatment approaches were similar.

Mechanisms of gefitinib-induced QT prolongation.

Gefitinib, a tyrosine kinase inhibitor, was the first targeted therapy for non-small cell lung cancer (NSCLC). Gefitinib could block human Ether-à-go-go-Related Gene (hERG) channel, an important target in drug-induced long QT syndrome. However, it is unclear whether gefitinib could induce QT interval prolongation. Here, whole-cell patch-clamp technique was used for evaluating the effect of gefitinib on rapidly-activating delayed rectifier K+ current (IKr), slowly-activating delayed rectifier K+ current (IKs), transient outward potassium current (Ito), inward rectifier K+ current (IK1) and on action potentials in guinea pig ventricular myocytes. The Langendorff heart perfusion technique was used to determine drug effect on the ECG. Gefitinib depressed IKr by binding to open and closed hERG channels in a concentration-dependent way (IC50: 1.91 µM). The inhibitory effect of gefitinib on wildtype hERG channels was reduced at the hERG mutants Y652A, S636A, F656V and S631A (IC50: 8.51, 13.97, 18.86, 32.99 µM), indicating that gefitinib is a pore inhibitor of hERG channels. In addition, gefitinib accelerated hERG channel inactivation and decreased channel steady-state inactivation. Gefitinib also decreased IKs with IC50 of 23.8 µM. Moreover, gefitinib increased action potential duration (APD) in guinea pig ventricular myocytes and the corrected QT interval (QTc) in isolated perfused guinea pig hearts in a concentration-dependent way (1-30 µM). These findings indicate that gefitinib could prolong QTc interval by potently blocking hERG channel, modulating kinetic properties of hERG channel. Partial block of KCNQ1/KCNE1 could also contribute to delayed repolarization and prolonged QT interval. Thus, caution should be taken when gefitinib is used for NSCLC treatment.

The comparison between anterior and posterior approaches for removal of infected lumbar interbody cages and a proposal regarding the use of endoscope-assisted technique.

BACKGROUND: In cases of postoperative deep wound infection after interbody fusion with cages, it is often difficult to decide whether to preserve or remove the cages, and there is no consensus on the optimal approach for removing cages. The aim of this study was to investigate the surgical management of cage infection after lumbar interbody fusion. METHODS: A retrospective study was conducted between January 2012 and August 2018. Patients were included if they had postoperative deep wound infection and required cage removal. Clinical outcomes, including operative parameters, visual analog scale, neurologic status, and fusion status, were assessed and compared between anterior and posterior approaches for cage removal. RESULTS: Of 130 patients who developed postoperative infection and required surgical debridement, 25 (27 levels) were diagnosed with cage infection. Twelve underwent an anterior approach, while 13 underwent cage removal with a posterior approach. Significant differences were observed between the anterior and posterior approaches in elapsed time to the diagnosis of cage infection, operative time, and hospital stay. All patients had better or stationary American Spinal Injury Association impairment scale, but one case of recurrence in adjacent disc 3 months after the surgery. CONCLUSIONS: Both anterior and posterior approaches for cage removal, followed by interbody debridement and fusion with bone grafts, were feasible methods and offered promising results. An anterior approach often requires an additional extension of posterior instrumentation due to the high incidence of concurrent pedicle screw loosening. The use of an endoscope-assisted technique is suggested to facilitate safe removal of cages.

Comparison of outcomes between indirect decompression of oblique lumbar interbody fusion and MIS-TLIF in one single-level lumbar spondylosis.

Minimal invasive spinal fusion has become popular in the last decade. Oblique lumbar interbody fusion (OLIF) is a relatively new surgical technique and could avoid back muscle stripping and posterior complex destruction as in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Between December 2016 and September 2018, patients with single level degenerative spondylosis were selected to enroll in this retrospective study. A total of 21 patients that underwent OLIF and 41 patients that received MIS-TLIF were enrolled. OLIF showed significantly less blood loss and shorter surgery time compared to MIS-TLIF (p < 0.05). The improvement in segmental lordosis and coronal balance was significantly more in OLIF group than MIS-TLIF group (p < 0.05). When comparing with MIS-TLIF, OLIF was significantly better in Oswestry Disability Index (ODI) and visual analogue scale for back pain improvement at post-operative 6 months (p < 0.05). Both OLIF and MIS-TLIF are becoming mainstream procedures for lumbar degenerative-related disease, especially for spondylolisthesis. However, the indirect decompression of OLIF has shown to have less perioperative blood loss and shorter surgery time than that of MIS-TLIF. In addition, OLIF gives superior outcome in restoring segmental lordosis and coronal imbalance. While both OLIF and MIS-TLIF provide optimal clinical outcomes, upon comparison between the two techniques, the indirect decompression of OLIF seems to be a superior option in modern days.