Tag: nevin manimala

J Gastrointest Surg. 2024 Apr;28(4):381-388. doi: 10.1016/j.gassur.2024.02.015.

ABSTRACT

BACKGROUND: Among bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide.

METHODS: In 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured.

RESULTS: SG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group.

CONCLUSION: Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

PMID:38583887 | DOI:10.1016/j.gassur.2024.02.015

J Gastrointest Surg. 2024 Apr;28(4):375-380. doi: 10.1016/j.gassur.2024.01.025. Epub 2024 Feb 1.

ABSTRACT

PURPOSE: This study aimed to investigate the correlation between sarcopenia and adverse events (AEs) of postoperative imatinib therapy through computed tomography (CT) quantitative body composition for intermediate- and high-risk gastrointestinal stromal tumors (GISTs).

METHODS: The study retrospectively analyzed the clinical data of 208 patients with intermediate- and high-risk GIST treated surgically and treated with imatinib afterward at the First Affiliated Hospital of Wenzhou Medical University between October 2011 and October 2021. Images of preoperative CT scans within 1 month were used to determine the body composition of the patients. On the basis of the L3 skeletal muscle index, patients were classified into sarcopenia and nonsarcopenia groups. In 2 groups, AEs related to imatinib were analyzed.

RESULTS: The proportion of AEs related to imatinib in the sarcopenia group was higher, and this disparity had a significant statistical significance (P = .013). Sarcopenia was significantly associated with hemoglobin reduction compared with nonsarcopenia (P = .015). There was a significant difference between the sarcopenia group and the nonsarcopenia group in the ratio of severe AEs (grades 3-4). Hemoglobin content (odds ratio [OR], 0.981; 95% CI, 0.963-1.000; P = .045), sex (OR, 0.416; 95% CI, 0.192-0.904; P = .027), and sarcopenia (OR, 5.631; 95% CI, 2.262-14.014; P < .001) were the influential factors of imatinib severe AEs in patients with intermediate- and high-risk GIST within 1 year after imatinib treatment.

CONCLUSION: Patients with preoperative sarcopenia have a higher incidence and severity of AEs during adjuvant imatinib therapy.

PMID:38583886 | DOI:10.1016/j.gassur.2024.01.025

Bone Jt Open. 2024 Apr 8;5(4):277-285. doi: 10.1302/2633-1462.54.BJO-2023-0132.R1.

ABSTRACT

AIMS: The mean age of patients undergoing total knee arthroplasty (TKA) has reduced with time. Younger patients have increased expectations following TKA. Aseptic loosening of the tibial component is the most common cause of failure of TKA in the UK. Interest in cementless TKA has re-emerged due to its encouraging results in the younger patient population. We review a large series of tantalum trabecular metal cementless implants in patients who are at the highest risk of revision surgery.

METHODS: A total of 454 consecutive patients who underwent cementless TKA between August 2004 and December 2021 were reviewed. The mean follow-up was ten years. Plain radiographs were analyzed for radiolucent lines. Patients who underwent revision TKA were recorded, and the cause for revision was determined. Data from the National Joint Registry for England, Wales, Northern Island, the Isle of Man and the States of Guernsey (NJR) were compared with our series.

RESULTS: No patients in our series had evidence of radiolucent lines on their latest radiological assessment. Only eight patients out of 454 required revision arthroplasty, and none of these revisions were indicated for aseptic loosening of the tibial baseplate. When compared to data from the NJR annual report, Kaplan-Meier estimates from our series (2.94 (95% confidence interval (CI) 1.24 to 5.87)) show a significant reduction in cumulative estimates of revision compared to all cemented (4.82 (95% CI 4.69 to 4.96)) or cementless TKA (5.65 (95% CI 5.23 to 6.10)). Our data (2.94 (95% CI 1.24 to 5.87)) also show lower cumulative revision rates compared to the most popular implant (PFC Sigma Cemented Knee implant fixation, 4.03 (95% CI 3.75 to 4.33)). The prosthesis time revision rate (PTIR) estimates for our series (2.07 (95% CI 0.95 to 3.83)) were lower than those of cemented cases (4.53 (95% CI 4.49 to 4.57)) from NJR.

CONCLUSION: The NexGen trabecular (tantalum) cementless implant has lower revision rates in our series compared to all cemented implants and other types of cementless implants, and its use in younger patients should be encouraged.

PMID:38583872 | DOI:10.1302/2633-1462.54.BJO-2023-0132.R1

Chem Biol Interact. 2024 Apr 5:110986. doi: 10.1016/j.cbi.2024.110986. Online ahead of print.

ABSTRACT

Snake venom metalloproteases (SVMPs) are hydrolytic enzymes dependent on metal binding, primarily zinc (Zn²⁺), at their catalytic site. They are classified into three classes (P-I to P-III). BjussuMP-II, a P-I SVMP isolated from Bothrops jararacussu snake venom, has a molecular mass of 24 kDa. It exhibits inhibitory activity on platelet aggregation and hydrolyzes fibrinogen. TNF-α upregulates the expression of adhesion molecules on endothelial cell surfaces, promoting leukocyte adhesion and migration during inflammation. Literature indicates that SVMPs may cleave the TNF-α precursor, possibly due to significant homology between metalloproteases from mammalian extracellular matrix and SVMPs. This study aimed to investigate BjussuMP-II’s effects on human umbilical vein endothelial cells (HUVEC), focusing on viability, detachment, adhesion, release, and cleavage of TNF-α, IL-1β, IL-6, IL-8, and IL-10. HUVEC were incubated with BjussuMP-II (1.5-50 μg/mL) for 3-24 h. Viability was determined using LDH release, MTT metabolization, and 7AAD for membrane integrity. Adhesion and detachment were assessed by incubating cells with BjussuMP-II and staining with Giemsa. Cytokines were quantified in HUVEC supernatants using EIA. TNF-α cleavage was evaluated using supernatants from PMA-stimulated cells or recombinant TNF-α. Results demonstrated BjussuMP-II’s proteolytic activity on casein. It was not toxic to HUVEC at any concentration or duration studied but interfered with adhesion and promoted detachment. PMA induced TNF-α release by HUVEC, but this effect was not observed with BjussuMP-II, which cleaved TNF-α. Additionally, BjussuMP-II cleaved IL-1β, IL-6, and IL-10. These findings suggest that the zinc metalloprotease BjussuMP-II could be a valuable biotechnological tool for treating inflammatory disorders involving cytokine deregulation.

PMID:38583853 | DOI:10.1016/j.cbi.2024.110986

Int J Biol Macromol. 2024 Apr 5:131441. doi: 10.1016/j.ijbiomac.2024.131441. Online ahead of print.

ABSTRACT

The thermal stability of polyurethanes, known for its limitations, was addressed in this research by seeking improvement through the introduction of carbohydrate-based chain extenders. In this research paper, we systematically sought to improve the thermal resistance of polyurethanes by incorporating carboxymethyl cellulose and chitosan, representing a pioneering application of the mixture design approach in their preparation. In this synthesis, hydroxyl-terminated polybutadiene and isophorone diisocyanate (IPDI) were reacted to prepare -NCO terminated prepolymer, which was subsequently reacted with varying mole ratios of CMC and CSN to develop a series of five PU samples. The prepared PU samples were characterized using the Fourier-transformed infrared spectroscopic technique. Thermal pyrolysis of PU samples was examined using thermal gravimetric analysis (TGA). It was observed that, among all the samples, PUS-3 showed remarkable thermal stability over a wide temperature range. A comprehensive statistical analysis was conducted to substantiate the experimental findings. It was estimated that CMC and CSN significantly enhance the thermal stability of the samples when involved in an interaction fashion. The ANOVA Table for the mixture design demonstrates that over 90 % of the total variation in thermal stability is explained by the mixture model across a wide temperature range. Moreover, PSU-3 exhibited 4 % more thermal stability over a wide range of temperatures on average, as compared to contemporary samples.

PMID:38583848 | DOI:10.1016/j.ijbiomac.2024.131441

Am J Infect Control. 2024 Apr 5:S0196-6553(24)00161-5. doi: 10.1016/j.ajic.2024.04.004. Online ahead of print.

ABSTRACT

BACKGROUND: Repeat departmental-wide surveys are commonly employed for infection-control. There remains debate concerning their cost-effectiveness.

AIM OF THE STUDY: To measure the impact of repeat departmental-wide surveys in major in-patient departments (IPD) and ambulatory facilities (AF) in a tertiary care hospital.

DESIGN: Retrospective study of 138 surveys conducted in 96 departments over a five-year period.

METHODS: Two itemized questionnaires were designed to assess the most frequently inadequately-adhered-to infection control measures: one for IPD (with 21 items), the other for AF (with 17 items).

RESULTS: A total of 72 surveys were conducted in 49 IPDs, of which 39 (54%) were repeat surveys, and 66 surveys in 47 AFs, of which 33 (50%) were repeat surveys. The baseline rate of adherence/department was 71%±14 for the IPD, with an increase from the first to the last survey to 82%±13 (p=0.037). In 15/21 measured infection control items, adherence improved. Adherence to infection control items was lower at baseline in the AFs than in the IPDs (63±27), with an increase to 76±20 (NS). Although adherence improved for nine items, it deteriorated in another eight, producing an overall statistically unchanged outcome.

CONCLUSION: Repeat whole-department surveys contribute moderately to increased adherence to infection control guidelines. Ambulatory facilities demonstrate lower rates of adherence to infection control guidelines and are less receptive to educational measures.

PMID:38583776 | DOI:10.1016/j.ajic.2024.04.004

Photodiagnosis Photodyn Ther. 2024 Apr 5:104074. doi: 10.1016/j.pdpdt.2024.104074. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate retinal thickness changes by optical coherence tomography in preobese and obese patients without hyperglycemia.

METHODS: This comparative cross-sectional study was conducted on 55 normal (18.5-24.9 kg/m2), 42 preobese (25-29.9 kg/m2), 34 obese (>30 kg/m2), a total of 131, according to body mass index (BMI) value at the time of examination. All participants were examined in the internal medicine department and fasting serological biochemical and lipid tests were performed, and those with hyperglycemia were excluded from the study. All participants underwent a full ophthalmological examination and sectoral examination of the retina with optical coherence tomography.

RESULTS: The study included 55 right eyes of 55 normal, 42 of 42 preobese, and 34 of 34 obese, age- and sex-matched participants, without hyperglycemia. The mean BMI of the normal group was 22.3 ± 1.3, 26.8 ± 1.3 in the preobese group, and 33.2 ± 4.2 in the obese group. Central foveal thickness (normal 229.8 ± 20.1 µm, preobese 234.7 ± 18.8 µm and obese 222.0 ± 23.4 µm, P:0.031) and mean inferior (normal 280.7 ± 55.8 µm, preobese 296.7 ± 11.1 µm and obese 285.3 ± 9.9 µm) thickness in the 3 mm The Early Treatment Diabetic Retinopathy Study (ETDRS) circle was significantly higher in the preobese group and significantly lower in the obese group. Mean nasal, temporal, and superior thickness in the 3 mm ETDRS circle and peripapillary retinal nerve fiber layer was higher in the preobese group and lower in the obese group but this difference was statistically not significant.

CONCLUSION: The fact that preobesity, which is not accompanied by hyperglycemia, causes an increase in the thickness of the central macular regions and obesity causes thinning of the retina, supports that lipid metabolism in the body alone can affect retinal thickness changes and retinal neurodegeneration.

PMID:38583748 | DOI:10.1016/j.pdpdt.2024.104074

Radiother Oncol. 2024 Apr 5:110270. doi: 10.1016/j.radonc.2024.110270. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Patients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS.

MATERIALS AND METHODS: Forty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6-55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT.

RESULTS: The 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively).

CONCLUSION: In conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes.

PMID:38583721 | DOI:10.1016/j.radonc.2024.110270

Am J Pharm Educ. 2024 Apr 5:100695. doi: 10.1016/j.ajpe.2024.100695. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the perception of students, faculty, and previous lab coaches on a near-peer teaching model integrated into a skills-based laboratory.

METHODS: As part of a longitudinal near-peer teaching experience, third professional year students are utilized as lab coaches in a skills-based laboratory course. Lab coaches deliver lectures, provide feedback, facilitate activities, and assist with class preparation spanning two semesters for first and second professional year students. Students enrolled in the courses received an anonymous 12 question survey to assess comfort and helpfulness of feedback when working with a lab coach and faculty during the 2021-2022 academic year. Statistical analysis was conducted using descriptive and inferential statistics for survey questions, and thematic analysis for open-ended responses. Semi-structured interviews of previous lab coaches and faculty were conducted, and thematic analysis was utilized for the responses.

RESULTS: The student survey had an 81.4% response rate (n=114). Students were significantly more comfortable working with and asking questions to a lab coach than a faculty instructor (mean [SD] of 4.78 [0.66] vs 4.44 [0.75]). Nine (75%) previous lab coaches, and six (43%) faculty members were also interviewed. A total of six themes regarding perceptions of the lab coach position emerged: positive impact on personal and professional development; relationship building; rewarding experience recommended to others; robust teaching experience; struggles and challenges faced by both faculty and lab coaches; appreciation of the position by faculty.

CONCLUSION: Implementing near-peer teachers into a pharmacy skills-based laboratory was very well received by students, previous lab coaches, and faculty.

PMID:38583718 | DOI:10.1016/j.ajpe.2024.100695

J Thromb Haemost. 2024 Apr 5:S1538-7836(24)00181-8. doi: 10.1016/j.jtha.2024.03.022. Online ahead of print.

ABSTRACT

BACKGROUND: Emicizumab has been approved for the prophylaxis of patients with hemophilia A with or without inhibitors. However, spontaneous and trauma-induced breakthrough bleeds have been reported in patients on emicizumab prophylaxis and no laboratory assay is validated to evaluate the hemostatic activity of emicizumab .

OBJECTIVES: The thrombin generation assay (TGA) could be a surrogate marker of the hemostatic efficacy of emicizumab. The correlation between TGA and the methods used to measure emicizumab blood concentration was evaluated in this study.

METHODS: TGA was modified by the use of a trigger reagent combining a very low concentration of tissue factor (TF) and activated factor XI (FXIa). Emicizumab quantification was performed by three methods, the modified one-step factor VIII (FVIII) assay, and two methods based on liquid chromatography and mass spectrometry (LC-MS).

RESULTS: Using TF/FXIa-triggered TGA and platelet-poor plasma, a relationship was observed between the area under the thrombin generation curve (ETP) and the clinical response of patients to emicizumab. The ultrastructure of fibrin clots was consistent with ETP results and showed that emicizumab had a hemostatic activity equivalent to 20-30 IU/dL of factor VIII. Finally, pharmacokinetic/pharmacodynamic analyses showed no correlation between ETP and LC-MS nor with modified one-stage FVIII assay, but a statistically significant correlation between the LC-MS methods and the time to peak results of TGA.

CONCLUSION: Using a modified TGA, this study showed that patients who experienced breakthrough bleeds while on emicizumab had a lower thrombin generating capacity compared to others with good clinical response to emicizumab.

PMID:38583717 | DOI:10.1016/j.jtha.2024.03.022