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Background: Although the incidence of osteochondritis dissecans (OCD) of the knee may be low, an overview and comparison of sports-related outcomes with current surgical management techniques are needed. Purpose: To summarize the available evidence regarding outcomes for different surgical treatment options for unstable OCD of the knee in both skeletally mature and immature patients by calculating the return to sports (RTS) rate, the mean RTS time, and other sports-related postoperative outcome measures. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of studies on RTS after surgical correction of unstable OCD within the knee was conducted utilizing PubMed, Embase, and the Cochrane databases. Included were studies discussing the treatment of unstable OCD with minimum 1-year follow-up outcomes. Multivariate analysis was used to compare studies grouped together based on RTS and skeletal maturity. Results: Of 2229 articles, 6 studies (197 patients; 198 knees) met the inclusion criteria and were included in our analysis. The percentage of patients who returned to the previous level of sport ranged from 52% to 100%; those returning to any level of sport ranged from 87% to 100%. Clinical outcomes did not differ between patients with open versus closed physes. Osteochondral Autograft Transfer System (OATS) procedures had a 100% RTS rate across several studies with skeletally mature and mixed cohorts, and microfracture had the lowest overall RTS rate (52%). For skeletally immature patients, all examined studies that utilized either open or arthroscopic reduction and internal fixation, 77% and 78%, respectively, had acceptable RTS rates. Arthroscopic fixation had a higher rate of revision surgery in both skeletally mature and immature patients. Conclusion: Our analysis indicated that the treatment of unstable OCD lesions using the OATS technique demonstrated high RTS rates across several studies, while microfracture alone exhibited the lowest RTS rate. Both arthroscopic and open internal fixation utilizing bioabsorbable screws yielded satisfactory RTS rates for juvenile patients with OCD.
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BACKGROUND: Despite excellent long-term outcomes, a small proportion of patients who undergo fundoplication with hiatal hernia repair (laparoscopic antireflux surgery [ARS]) for treatment of gastroesophageal reflux disease (GERD) may require reoperation. Esophagogastroduodenoscopy (EGD) assessment in patients presenting with symptom recurrence plays a critical role in surgical planning of redo-ARS by confirming failure of the fundoplication and revealing the pattern of failure. We aimed to compare the findings documented by external endoscopists (i.e., outside physicians) to those documented by internal endoscopists (i.e., operating foregut or thoracic surgeons) before redo-ARS. METHODS: After IRB approval, we conducted a retrospective chart review of patients who underwent redo-ARS at a tertiary surgical center between November 2016 and March 2023. Patients with both external and internal EGD reports were included, and findings from the two reports were compared. RESULTS: Of 197 patients who underwent redo-ARS, both preoperative EGD reports were available for 181 (136 [75.1%] women; median age, 61 years [IQR 53-69]; median BMI, 27.9 kg/m2 [IQR 24.9-31.3]). The median time between primary and redo-ARS was 89 months (IQR 38-153), and the median time between external and internal endoscopic evaluation was 5 months (IQR 2-12). Only 38.9% of external reports mentioned a prior fundoplication. Compared to the operating surgeons, external physicians reported a significantly lower proportion of Barrett's esophagus (52.4%, p < .001), slipped fundoplications (28.8%, p < .001), paraesophageal hernias (20.5%, p < .001), disrupted fundoplications (20%, p < .001), intrathoracic fundoplications (0%, p < .001), and twisted fundoplications (0%, p < .001). CONCLUSIONS: External endoscopists' reports of failed fundoplications are often incomplete and lack relevant details. Discrepancies between nonsurgical endoscopists and experienced surgeons are likely explained by a lack of training and experience to discern and document fundoplication changes accurately. To reduce this gap, we strongly recommend the adoption of standard definitions describing post-fundoplication endoscopic changes and the inclusion of relevant training within educational programs.
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As Wolbachia pipientis is more widely being released into field populations of Aedes aegypti for disease control, the ability to select the appropriate strain for differing environments is increasingly important. A previous study revealed that longer-term quiescence in the egg phase reduced the fertility of mosquitoes, especially those harboring the wAlbB Wolbachia strain. This infertility was also associated with a greater biting rate. Here, we attempt to quantify the effect of this heightened biting behavior on the transmission potential of the dengue virus using a combination of assays for fitness, probing behavior, and vector competence, allowing repeat feeding, and incorporate these effects in a model of R0. We show that Wolbachia-infected infertile mosquitoes are more interested in feeding almost immediately after an initial blood meal relative to wild type and Wolbachia-infected fertile mosquitoes and that these differences continue for up to 8 days over the period we measured. As a result, the infertile Wolbachia mosquitoes have higher virus prevalence and loads than Wolbachia-fertile mosquitoes. We saw limited evidence of Wolbachia-mediated blocking in the disseminated tissue (legs) in terms of prevalence but did see reduced viral loads. Using a previously published estimate of the extrinsic incubation period, we demonstrate that the effect of repeat feeding/infertility is insufficient to overcome the effects of Wolbachia-mediated blocking on R0. These estimates are very conservative, however, and we posit that future studies should empirically measure EIP under a repeat feeding model. Our findings echo previous work where periods of extensive egg quiescence affected the reproductive success of Wolbachia-infected Ae. aegypti. Additionally, we show that increased biting behavior in association with this infertility in Wolbachia-infected mosquitoes may drive greater vector competence. These relationships require further exploration, given their ability to affect the success of field releases of Wolbachia for human disease reduction in drier climates where longer egg quiescence periods are expected.
Subject(s)
Aedes , Dengue Virus , Dengue , Feeding Behavior , Mosquito Vectors , Wolbachia , Aedes/microbiology , Aedes/virology , Aedes/physiology , Animals , Wolbachia/physiology , Dengue Virus/physiology , Mosquito Vectors/microbiology , Mosquito Vectors/virology , Mosquito Vectors/physiology , Dengue/transmission , Female , Viral Load , Ovum/virology , Ovum/microbiologyABSTRACT
OBJECTIVES: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. METHODS: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). RESULTS: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. CONCLUSIONS: Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.
Subject(s)
Acetates , Antiviral Agents , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Quinazolines , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Cytomegalovirus Infections/prevention & control , Female , Middle Aged , Quinazolines/therapeutic use , Retrospective Studies , Antiviral Agents/therapeutic use , Adult , Acetates/therapeutic use , Acetates/administration & dosage , Case-Control Studies , Aged , Transplantation, Homologous/adverse effects , Young Adult , Cytomegalovirus , Adolescent , Germany/epidemiology , IncidenceABSTRACT
PURPOSE: The rectus femoris forms the anterior portion of the quadriceps muscle. It has a proximal tendinous complex, which is constituted by a direct tendon, an indirect tendon, and a variable third tendon. Direct and indirect tendons converge into a common tendon. The purposes of this study are to add anatomical knowledge about the proximal tendinous complex and describe anatomical variants of the indirect tendon and, on these basis, categorize different anatomical patterns. METHOD: In this study, 48 hemipelvis from bodies donated to the Universitat Autònoma de Barcelona have been dissected to examine the proximal tendinous complex of the rectus femoris. RESULTS: The following anatomical variants of the indirect tendon were described: inferior aponeurotic expansion in 23/48 cases (47.9%); superior aponeurotic expansion in 21/48 cases (43.7%); and an unusual origin of the myotendinous junction of the rectus femoris in the free portion of the indirect tendon in 19/48 cases (39.6%). On the basis of the aponeurotic expansions, the following anatomical patterns of the indirect tendon were defined: standard (19/48 cases, 39.6%), superior and inferior complex (15/48 cases, 31.2%), inferior complex (8/48 cases, 16.7%), and superior complex (6/48 cases, 12.5%). CONCLUSION: We can categorize four different anatomical patterns of the indirect tendon, three of which are complex. We suggest that complex patterns can cause an increased stiffness of the indirect tendon and so be considered non-modifiable risk factors for rectus femoris injuries. Finally, it would be useful to identify complex patterns and perform injury prevention actions through specific physical preparation programs.
Subject(s)
Anatomic Variation , Cadaver , Quadriceps Muscle , Tendons , Humans , Quadriceps Muscle/anatomy & histology , Tendons/anatomy & histology , Male , Female , Aged , Aged, 80 and over , Dissection , Middle AgedABSTRACT
Regulatory T (Treg) cells in epidydimal visceral adipose tissue (eVAT) of lean mice and humans regulate metabolic homeostasis. We found that constitutive or punctual depletion of eVAT-Treg cells reined in the differentiation of stromal adipocyte precursors. Co-culture of these precursors with conditional medium from eVAT-Treg cells limited their differentiation in vitro, suggesting a direct effect. Transcriptional comparison of adipocyte precursors, matured in the presence or absence of the eVAT-Treg-conditioned medium, identified the oncostatin-M (OSM) signaling pathway as a key distinction. Addition of OSM to in vitro cultures blocked the differentiation of adipocyte precursors, while co-addition of anti-OSM antibodies reversed the ability of the eVAT-Treg-conditioned medium to inhibit in vitro adipogenesis. Genetic depletion of OSM (specifically in Treg) cells or of the OSM receptor (specifically on stromal cells) strongly impaired insulin sensitivity and related metabolic indices. Thus, Treg-cell-mediated control of local progenitor cells maintains adipose tissue and metabolic homeostasis, a regulatory axis seemingly conserved in humans.
Subject(s)
Adipocytes , Cell Differentiation , Homeostasis , Insulin Resistance , T-Lymphocytes, Regulatory , Animals , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Humans , Mice , Adipocytes/metabolism , Cell Differentiation/immunology , Oncostatin M/metabolism , Signal Transduction , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/cytology , Intra-Abdominal Fat/immunology , Stromal Cells/metabolism , Mice, Inbred C57BL , Coculture Techniques , Adipogenesis , Cells, Cultured , Male , Adipose Tissue/metabolism , Adipose Tissue/cytology , Culture Media, Conditioned/pharmacologyABSTRACT
BACKGROUND: Metabolomics plays a critical role in deciphering metabolic alterations within individuals, demanding the use of sophisticated analytical methodologies to navigate its intricate complexity. While many studies focus on single biofluid types, simultaneous analysis of multiple matrices enhances understanding of complex biological mechanisms. Consequently, the development of data fusion methods enabling multiblock analysis becomes essential for comprehensive insights into metabolic dynamics. RESULTS: This study introduces a novel guideline for jointly analyzing diverse metabolomic datasets (serum, urine, metadata) with a focus on metabolic differences between groups within a healthy cohort. The guideline presents two fusion strategies, 'Low-Level data fusion' (LLDF) and 'Mid-Level data fusion' (MLDF), employing a sequential application of Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS), linking the outcomes of successive analyses. MCR-ALS is a versatile method for analyzing mixed data, adaptable at various stages of data processing-encompassing resonance integration, data compression, and exploratory analysis. The LLDF and MLDF strategies were applied to 1H NMR spectral data extracted from urine and serum samples, coupled with biochemical metadata sourced from 145 healthy volunteers. SIGNIFICANCE: Both methodologies effectively integrated and analysed multiblock datasets, unveiling the inherent data structure and variables associated with discernible factors among healthy cohorts. While both approaches successfully detected sex-related differences, the MLDF strategy uniquely revealed components linked to age. By applying this analysis, we aim to enhance the interpretation of intricate biological mechanisms and uncover variations that may not be easily discernible through individual data analysis.
Subject(s)
Metabolomics , Humans , Metabolomics/methods , Male , Female , Multivariate Analysis , Healthy Volunteers , Adult , Proton Magnetic Resonance Spectroscopy , Cohort Studies , Middle Aged , Least-Squares Analysis , Young AdultABSTRACT
Purpose: To assess the difference in perceived readiness to return to sport (RTS) within the first year postoperative period between individuals undergoing anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BTB) autografts or allografts. Methods: This was a prospective cohort study of patients undergoing primary ACL reconstruction done either with BTB autograft or allograft from 2010 to 2018. Skeletally mature patients aged 14 to 25 were eligible for inclusion. Patients completed the Marx Activity Rating Scale (MARS) questionnaire postoperatively evaluating perceived ability to perform various activities to compare subjective ability to RTS. Those patients who were outside outlined cohort age, failed to complete a single post-operative survey, underwent revision procedures, or underwent simultaneous or staged additional ligament surgery were excluded. Results: Fifty-nine patients (20.1 ± 3.19 years, 57.6 % Male) were included in the study. Sixteen patients underwent ACL reconstruction with allograft (19.8 ± 3.43 years) while 43 patients received autograft (20.2 ± 3.13). At 3 months autograft recipients reported higher perceived ability to cut (P = .003). At 6-months, allograft recipients reported higher perceived ability to run (P = .033), cut (P = .048), and decelerate (P = .008) as well as a higher overall perceived ability to RTS (P = .032). At all other times, there was no significant difference between cohorts' subjective readiness to perform activities. Conclusion: The results of this study indicate that at times within the first year of recovery following ACL reconstruction, patients who receive allografts and autografts may have significantly different perceived ability to perform activities or RTS. However, while present at various times throughout the first year of recovery, any difference in perceived ability to perform activities or in overall RTS is no longer present at 12 months. Level of evidence: Level II, Prospective cohort study.
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The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.
Subject(s)
Esophagogastric Junction , Lung Transplantation , Manometry , Humans , Male , Female , Esophagogastric Junction/physiopathology , Esophagogastric Junction/surgery , Middle Aged , Aged , Retrospective Studies , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Esophageal Achalasia/surgery , Esophageal Achalasia/physiopathology , Esophageal Motility Disorders/physiopathologyABSTRACT
The domestication process of the common bean gave rise to six different races which come from the two ancestral genetic pools, the Mesoamerican (Durango, Jalisco, and Mesoamerica races) and the Andean (New Granada, Peru, and Chile races). In this study, a collection of 281 common bean landraces from Chile was analyzed using a 12K-SNP microarray. Additionally, 401 accessions representing the rest of the five common bean races were analyzed. A total of 2543 SNPs allowed us to differentiate a genetic group of 165 accessions that corresponds to the race Chile, 90 of which were classified as pure accessions, such as the bean types 'Tórtola', 'Sapito', 'Coscorrón', and 'Frutilla'. Our genetic analysis indicates that the race Chile has a close relationship with accessions from Argentina, suggesting that nomadic ancestral peoples introduced the bean seed to Chile. Previous archaeological and genetic studies support this hypothesis. Additionally, the low genetic diversity (π = 0.053; uHe = 0.53) and the negative value of Tajima' D (D = -1.371) indicate that the race Chile suffered a bottleneck and a selective sweep after its introduction, supporting the hypothesis that a small group of Argentine bean genotypes led to the race Chile. A total of 235 genes were identified within haplotype blocks detected exclusively in the race Chile, most of them involved in signal transduction, supporting the hypothesis that intracellular signaling pathways play a fundamental role in the adaptation of organisms to changes in the environment. To date, our findings are the most complete investigation associated with the origin of the race Chile of common bean.
Subject(s)
Phaseolus , Phaseolus/genetics , Chile , Argentina , Domestication , Gene PoolABSTRACT
Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the clinical efficacy and patient survival of viroimmunotherapy treated animals.
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[This corrects the article DOI: 10.1016/j.omton.2024.200787.].
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The remarkable development of colloidal nanocrystals with controlled dimensions and surface chemistry has resulted in vast optoelectronic applications. But can they also form a platform for quantum materials, in which electronic coherence is key? Here, we use colloidal, two-dimensional Bi2Se3 crystals, with precise and uniform thickness and finite lateral dimensions in the 100 nm range, to study the evolution of a topological insulator from three to two dimensions. For a thickness of 4-6 quintuple layers, scanning tunneling spectroscopy shows an 8 nm wide, nonscattering state encircling the platelet. We discuss the nature of this edge state with a low-energy continuum model and ab initio GW-Tight Binding theory. Our results also provide an indication of the maximum density of such states on a device.
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Common bean (Phaseolus vulgaris L.) is the primary grain legume cultivated worldwide for direct human consumption due to the high nutritional value of its seeds and pods. The high protein content of common beans highlights it as the most promising source of plant-based protein for the food industry. Additionally, landraces of common bean have great variability in nutritional traits, which is necessary to increase the nutritional quality of elite varieties. Therefore, the main objective of this study was to nutritionally characterize 23 Chilean landraces and 5 commercial varieties of common bean to identify genotypes with high nutritional value that are promising for the food industry and for genetic improvement programs. The landrace Phv23 ('Palo') was the most outstanding with high concentrations of minerals such as P (7.53 g/kg), K (19.8 g/kg), Mg (2.43 g/kg), Zn (52.67 mg/kg), and Cu (13.67 mg/kg); essential amino acids (364.8 mg/g protein); and total proteins (30.35 g/100 g seed). Additionally, the landraces Phv9 ('Cimarrón'), Phv17 ('Juanita'), Phv3 ('Araucano'), Phv8 ('Cabrita/Señorita'), and Phv4 ('Arroz') had a high protein content. The landrace Phv24 ('Peumo') stood out for its phenolic compounds (TPC = 218.1 mg GA/100 g seed) and antioxidant activity (ORAC = 22,167.9 µmol eq trolox/100 g extract), but it has moderate to low mineral and protein concentrations. In general, the concentration of nutritional compounds in some Chilean landraces was significantly different from the commercial varieties, highlighting their high nutritional value and their potential use for the food industry and for genetic improvement purposes.
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Metastasis arises from cancer cell-intrinsic adaptations and permissive tumor microenvironments (TME) that are distinct across different organs. Deciphering the mechanisms underpinning organotropism could provide novel preventive and therapeutic strategies for patients with cancer. Rogava and colleagues identified Pip4k2c as a driver of liver metastasis, acting by sensitizing cancer cells to insulin-dependent PI3K/AKT signaling, which could be reversed by dual pharmacologic inhibition of PI3K and SGLT2 or a ketogenic diet. The study highlights the importance of tumor microenvironment communication in the context of systemic physiology and points toward potential combination therapies.
Subject(s)
Liver Neoplasms , Signal Transduction , Tumor Microenvironment , Humans , Liver Neoplasms/secondary , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Animals , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Wild emmer (Triticum turgidum ssp. dicoccoides) genotypes were studied for their high-nutritional value and good tolerance to various types of stress; for this reason, several QTL (quantitative trait loci) studies have been conducted to find favorable alleles to be introgressed into modern wheat cultivars. Given the complexity of the QTL nature, their interaction with the environment, and other QTLs, a small number of genotypes have been used in wheat breeding programs. Meta-QTL (MQTL) analysis helps to simplify the existing QTL information, identifying stable genomic regions and possible candidate genes for further allele introgression. The study aimed to identify stable QTL regions across different environmental conditions and genetic backgrounds using the QTL information of the past 14 years for different traits in wild emmer based upon 17 independent studies. A total of 41 traits were classified as quality traits (16), mineral composition traits (11), abiotic-related traits (13), and disease-related traits (1). The analysis revealed 852 QTLs distributed across all 14 chromosomes of wild emmer, with an average of 61 QTLs per chromosome. Quality traits had the highest number of QTLs (35%), followed by mineral content (33%), abiotic-related traits (28%), and disease-related traits (4%). Grain protein content (GPC) and thousand kernel weight (TKW) were associated with most of the QTLs detected. A total of 43 MQTLs were identified, simplifying the information, and reducing the average confidence interval (CI) from 22.6 to 4.78 cM. These MQTLs were associated with multiple traits across different categories. Nine candidate genes were identified for several stable MQTLs, potentially contributing to traits such as quality, mineral content, and abiotic stress resistance. These genes play essential roles in various plant processes, such as carbohydrate metabolism, nitrogen assimilation, cell wall biogenesis, and cell wall extensibility. Overall, this study underscores the importance of considering MQTL analysis in wheat breeding programs, as it identifies stable genomic regions associated with multiple traits, offering potential solutions for improving wheat varieties under diverse environmental conditions.
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BACKGROUND: Improved outcomes with the use of non-absorbable mesh (NAM) for inguinal hernia repairs led to its rapid adoption for hiatal hernia (HH) repairs; however, feared complications occurred, and the trend shifted toward using absorbable mesh (AM). We aimed to analyze the literature assessing objective HH recurrence rates after primary laparoscopic cruroplasty with or without the use of different mesh types. METHODS: A systematic literature review with both pairwise and time-organized proportion meta-analyses of articles published between January 1993 and September 2022 was performed using the MEDLINE, EMBASE, and Taylor & Francis databases to identify relevant studies comparing groups undergoing cruroplasty with suture repair (SR) alone, AM, NAM, or partially absorbable mesh (PAM). Studies documenting an objective follow-up ≥ 6 months were included. The primary outcome was the HH recurrence rate confirmed by barium esophagram or upper GI endoscopy. RESULTS: A total of 34 studies met the inclusion criteria, including 6 randomized clinical trials, 25 retrospectives studies, and 3 prospective cohort studies. A total of 2170 subjects underwent laparoscopic HH repair and completed an objective follow-up ≥ 6 months after surgery; the objective recurrence rate was 20.8% (99/477) at a mean follow-up of 25.8 ± 16.4 months for the SR group, 20.6% (244/1187) at 28.1 ± 13.8 months for the AM group, 13.7% (65/475) at 30.8 ± 15.3 months for the NAM group, and 0% (0/31) at 32.5 ± 13.5 months for the PAM group. However, the pairwise meta-analysis revealed that overall mesh use was not superior to SR in preventing long-term HH recurrence. CONCLUSION: The use of AM does not appear to reduce HH recurrence compared to SR alone. Although the data favors NAM to decrease objective HH recurrence in the mid-term, the long-term (≥ 48 months) recurrence rate was similar with or without any type of mesh.
Subject(s)
Hernia, Hiatal , Laparoscopy , Humans , Treatment Outcome , Hernia, Hiatal/surgery , Prospective Studies , Surgical Mesh , Recurrence , HerniorrhaphyABSTRACT
Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.
Subject(s)
Brain Neoplasms , Glioma , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Animals , Mice , Adenoviridae/genetics , Antibodies, Neutralizing , Glioma/therapy , Glioma/pathology , Brain Neoplasms/pathology , Oncolytic Viruses/genetics , Antibodies, Viral , Oligopeptides/therapeutic useABSTRACT
Immobilization of enzymes on aminated supports using the glutaraldehyde chemistry may involve three different interactions, cationic, hydrophobic, and covalent interactions. To try to understand the impact this heterofunctionality, we study the physical adsorption of the beta-galactosidase from Aspergillus niger, on aminated supports (MANAE) and aminated supports with one (MANAE-GLU) or two molecules of glutaraldehyde (MANAE-GLU-GLU). To eliminate the chemical reactivity of the glutaraldehyde, the supports were reduced using sodium borohydride. After enzyme adsorption, the release of the enzyme from the supports using different NaCl concentrations, Triton X100, ionic detergents (SDS and CTAB), or different temperatures (4 °C to 55 °C) was studied. Using MANAE support, at 0.3 M NaCl almost all the immobilized enzyme was released. Using MANAE-GLU, 0.3 M, and 0.6 M NaCl similar results were obtained. However, incubation at 1 M or 2 M NaCl, many enzyme molecules were not released from the support. For the MANAE-GLU-GLU support, none of the tested concentrations of NaCl was sufficient to release all enzyme bound to the support. Only using high temperatures, 0.6 M NaCl, and 1 % CTAB or SDS, could the totality of the proteins be released from the support. The results shown in this paper confirm the heterofunctional character of aminated supports modified with glutaraldehyde.
Subject(s)
Enzymes, Immobilized , Sodium Chloride , Glutaral/chemistry , Enzyme Stability , Adsorption , Cetrimonium , Enzymes, Immobilized/chemistryABSTRACT
The rotarod test, a sensorimotor assessment that allows for quantitative evaluation of motor coordination in rodents, has extensive application in many research fields. The test results exhibit extreme between-study variability, sometimes making it challenging to conclude the validity of certain disease models and related therapeutic effects. Although the variation in test paradigms may account for this disparity, some features of rotarod apparatus including rod diameter make differences. However, it is unknown whether the width of animal compartment has a role in rotarod performance. Here we comprehensively evaluated the active rotarod performance and adverse incidents in multiple strains of mice on an 11-cm- or a 5-cm-wide compartment apparatus. We found that mouse behaviors on these apparatuses were surprisingly different. It took a markedly longer time to train mice on the narrow- than wide-compartment rotarod. Further, non-transgenic B6129S and tau knockout mice aged 11 months and beyond showed different levels of improvement based on the compartment width. These mice had no overt improvements on accelerating rotarod over 4-5 training sessions on the narrow compartment, contrary to marked progress on the wide counterpart. The incidents of mice passively somersaulting round and fragmented running occurred significantly more on the wide than narrow compartment during accelerating rotarod sessions. Mice fell off rod more frequently on narrow than wide compartments upon attempt to turn around and when moving backward on rod. The pros and cons of narrow versus wide compartments are informative as to how to choose a rotarod apparatus that best fits the animal models used.