IC Group Research Articles

Long-term treatment outcomes of complicated acute diverticulitis in immunocompromised patients

PurposeThe main aim of this study was to determine the short- and long-term outcomes of the non-operative management of acute left-sided complicated diverticulitis (ALCD) in severely immunocompromised patients (IMS group) and compare them with immunocompetent patients (IC group). The secondary aim was to assess the necessity of an elective surgery following a successful prior non-operative management in the IMS group after a non-operative management of the first episode of ALCD.MethodsPatients presented with their first episode of ALCD between 2012 and 2018 were retrospectively reviewed. Only severely immunosuppressed patients were considered for the analysis, including the following: long-term oral or intravenous steroid intake, current malignancy undergoing chemotherapy, chronic kidney disease on hemodialysis, or solid organ transplant with immunosuppressive medication. For each group, demographic data, severity of the episode, management decisions (conservative or operative), and short- and long-term outcomes were recorded and compared. A sub-analysis of patients with ALCD associating and abscess (modified Hinchey classification Ib/II) was performed.ResultsA total of 290 patients were included in the study: 50 among the IMS and 240 among the IC group. The rate of emergent surgery was higher in the IMS group (50.0% vs. 22.5%, p < 0.001) and was associated with increased morbidity (72.4% vs. 50.0%, p = 0.041) and mortality (24.1% vs. 4.3%, p = 0.003). The duration of the hospital stay was significantly longer in the IMS group (15 vs. 8 days, p < 0.001). The final stoma rate was significantly higher in the IMS group (82.1% vs. 22.9, p < 0.001), with a median follow-up of 51.4 months. A total of 141 patients presented ALCD with an abscess; 25 in the IMS and 116 in the IC group. There was a higher rate of surgical intervention among the IMS group as the initial treatment approach (24.0% vs. 5.2%, p = 0.002), even though the conservative treatment had a similar rate of success (81.3% vs. 92.0%, p = 0.178). The recurrence rate following a non-operative approach was similar (IMS: 31.2% vs. 35.4% in the IC group, p = 0.169). Furthermore, 81.2% of non-operatively managed IMS patients (13 out of 16) did not require a surgical intervention at the end of the follow-up, with similar findings in the IC group (78/96, 81.2%, p = 0.148).ConclusionMedical treatment of immunosuppressed patients during their first ALCD episode associated with an abscess is feasible, with a high success rate and results comparable with the IC group. Moreover, taking into account the readmission rates, the need for emergent surgery of the recurrence, and the perioperative mortality and morbidity in the IMS group, conservative management with no differed scheduled surgery seems to be a safe option in this subgroup of patients.

An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension – a comprehensive assessment of patient satisfaction

BackgroundManagement of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop concept. Here, we aimed to evaluate effects of this one-stop concept on subjective patient satisfaction and economic outcome in patients with IIH.MethodsIn a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding subjective patient satisfaction (assessed by the Vienna Patient Inventory). Multivariable binary linear regression models were used to adjust for confounders.ResultsBaseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, management within IC concept was associated with statistically significantly higher subjective patient satisfaction (beta = 0.93; p < 0.001) with the strongest effects observed in satisfaction with treatment accessibility and availability (beta = 2.05; p < 0.001). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of IC in these groups.ConclusionsInterdisciplinary integrated management of IIH statistically significantly and clinically meaningfully improves patient satisfaction – particularly in socioeconomically underprivileged patient groups. Providing structured central coordination to facilitate and improve access to interdisciplinary management provides means to further improve outcome.

Influence of gel matrix on the wound healing activity of adhesive dressings filled with silver nanoparticles and humic acid applied on a rat burn model

BACKGROUND: Thermal injuries to the skin (burns) are common household and man-made traumatic injuries in humans. In wartime, thermal injuries are additional damaging factors in combined skin lesions caused by the damaging elements of modern weapons. AIM: This study aimed to evaluate the effectiveness of gels based on silver nanoparticles in combination with humic acid on the healing of thermal skin injuries (burn wounds) in rats. MATERIALS AND METHODS: In the experiments on 57 white nonlinear male rats weighing 218–260 g, the wound healing effects of gels with 10% humic acid modified with nanosilver on various bases, prepared in a pharmacopoeial manner, on a grade IIIB thermal skin burn model were examined. The gel bases used in three experimental groups were as follows: sodium carboxymethylcellulose (group Ia, n = 12), polyacrylamide (group Ib, n = 12), and polyethylene glycol (group Ic, n = 12). The comparison group (group II, n = 12) received Levomekol ointment, whereas the control group (group III, n = 8) did not receive treatment. A grade III thermal burn was made on the proximal part of the back under general anesthesia using a thermal applicator with a circular-shaped flat working part with a diameter of 20 mm. Seventy-two hours after the burn, the wound was freed from scab by complete excision along the border of the intact skin, a splinting ring was applied, and the study drugs were administered. The dynamics of the changes in the burn wound were assessed on days 10, 14, 17, 21, 24, and 28 using the Universal Desktop Ruler program. RESULTS: The average times (median) to reach 75% epithelialization of wounds in groups Ia, Ic, and II were 29.4 ± 0.2, 34 (33–34), and 33.3 ± 0.45 days, respectively, whereas in groups Ib and III, the median time to 75% epithelization was not achieved. The 28-day healing index (%/day) values were 8.6, 4.8, 6.5, 6.1, and 4.4 in groups Ia, Ib, Ic, II, and III, respectively. The dynamics of epithelialization of thermal burns were most pronounced in group Ia, where the sodium carboxymethylcellulose acted as a gel base for humic substances modified with nanosilver. CONCLUSIONS: The results indicated that the gel added with nanosilver-modified humic substances based on sodium carboxymethylcellulose has a wound healing effect on thermal skin injuries, superior to the effect of the reference drug Levomekol in terms of the healing time of burn wounds.

Identification of diagnostic signature and immune infiltration for ischemic cardiomyopathy based on cuproptosis-related genes through bioinformatics analysis and experimental validation

BackgroundIschemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called “cuproptosis” is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. MethodsThe expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. ResultsWe identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. ConclusionIn summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.

Clinical performance of Circulating HBV RNA and iTACT-HBcrAg Assays in HBeAg-negative and HBsAg-cleared Chronic Hepatitis B Patients.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) have been reported to reflect the transcriptional activity of covalently closed circular HBV DNA. We retrospectively investigated the proportions of quantifiable serum HBV RNA and immunoassay for total antigen including complex via pretreatment-hepatitis B core-related antigen (iTACT-HBcrAg) in chronic hepatitis B patients negative for hepatitis B e antigen (HBeAg) and/or with hepatitis B surface antigen (HBsAg) seroclearance. This study included 246 HBeAg-negative HBV-infected patients, who comprised 13 with liver cirrhosis (LC, the LC group), 118 chronic hepatitis (CH, the CH group), and 115 inactive carriers (IC, the IC group), and 44 patients with HBsAg seroclearance. iTACT-HBcrAg and HBV RNA levels were determined using stored serum samples. Higher proportions of the patients had quantifiable iTACT-HBcrAg than HBV RNA in all groups of HBeAg-negative patients (iTACT-HBcrAg: 84.6%, 90.7%, 35.7%, HBV RNA: 23.1%, 26.3%, 14.8%, for the LC, CH, IC groups). With HBsAg seroclearance (HBsAg <0.05 IU/mL), the proportions of quantifiable samples for HBV RNA were also lower than iTACT-HBcrAg (0% for HBV RNA). Thus, iTACT-HBcrAg was more often detectable than circulating HBV RNA in this study population. Further long-term prospective evaluation of iTACT-HBcrAg is desirable for its utilization in clinical practice.

Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

Assessment of the Additive Effect of Remineralizing Agents in Combination With Fluoride Releasing Adhesives in the Prevention of Enamel Decalcification in Orthodontic Patients: An In Vitro Study.

Introduction Incorporation of remineralizing agents with fluoride-releasing bracket adhesives may prevent the development of white spot lesions (WSL) or reverse the established WSL in patients undergoing fixed orthodontic treatment. We aimed to find out how effectively casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride varnish (FV) can remineralize teeth when mixed with fluoride-releasing orthodontic adhesive. Materials and methods We randomly assigned a total of 60 premolar teeth, therapeutically extracted for orthodontic purposes, into two equal groups. Group I (n = 30) utilized fluoride-releasing adhesive (FR), and Group II (n = 30) bonded with non-fluoride adhesive (NFR). Based on the applied remineralizing agent, we further divided each of the two groups into three equal subgroups of 10: Group IA (FR+FV), Group IB (FR+CPP-ACP), Group IC (control-only FR), Group IIA (NFR+FV), Group IIB (NFR+CPP-ACP), and Group IIC (control-only NFR). Following bonding procedures, all the samples underwent pH cycling for 28 days, where the enamel samples were immersed in 20 ml of demineralizing solution for three hours, followed by immersion in 30 ml of remineralizing solution for 17 hours. The samples were analyzed for shear bond strength (SBS) on a universal testing machine and hardness values (HV) by the Vickers microhardness test (VMT) using the indentation method. We also evaluated the adhesive remnant index (ARI) scores to determine the site of bracket failure. Statistical analysis The shear bond strength (SBS) and hardness value (HV) were expressed as the mean, standard deviation (SD), and median for each subgroup. We used the non-parametric Kruskal-Wallis test to analyze the SBS and HV, followed by the Dunn-Bonferroni test for intra-pair differences. The ARI score was expressed as the frequency of the percentage distribution, and the difference in the distribution of ARI scores between the groups was assessed by the Cochran chi-square test. The probability (p) value equal to or less than 0.05 was considered statistically significant. Results The results show that Group IB, bonded with a fluoride-releasing adhesive and a CPP-ACP remineralizing agent surface treatment, has the highest HV of300.23 units. Group IIC (only NFR) has the lowest hardness of153.3 units, which is statistically significant (p < 0.001). However, the ARI scores are not statistically significant between the groups tested. Conclusion The bond strength of the adhesive and the surface hardness of the enamel increased with the addition of fluoride varnish and CPP-ACP to both the fluoride-releasing and non-fluoride-releasing adhesives.

PD-(L)1 inhibitors plus bevacizumab and chemotherapy as first-line therapy in PD-L1 negative metastatic lung adenocarcinoma: A real-world data.

e20577 Background: Chemotherapies combined with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC and IBC respectively) are the preferred first-line options for PD-L1 negative and oncogenic driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined. Methods: This retrospective real-world study enrolled PD-L1 negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated. Results: A total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. Patients receiving IBC obtained the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those receiving IC (40.4%, 84.2%) or BC (40.5%, 96.2%). Compared with the IC (6.74m) or BC (8.28m) group, IBC group improved significantly median progression-free survival (mPFS) (9.53m, P = 0.005). However, the difference in overall survival (OS) were not observed among the three groups. When analyzed based on different clinical and molecular information, we found that male gender, ever smoking, wild-type genes, and adrenal metastasis predicts superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment achieved better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups. Conclusions: Combined IBC treatment achieved superior DCR and PFS compared with IC or BC treatment in patients with PD-L1 negative metastatic lung adenocarcinoma, while did not increase the adverse events.

Response to first-line therapies in metastatic lung adenocarcinoma with low PD-L1 expression: A multi-center retrospective study.

e20574 Background: For metastatic lung adenocarcinoma with low PD-L1 expression (tumor proportion score:1-49%), chemotherapy in combination with immune checkpoint inhibitors (IC), with bevacizumab (BC), or with both (IBC) have been established as standard first-line options. However, the optimal scheme is still undetermined. Methods: This retrospective study enrolled 125 metastatic lung adenocarcinoma patients with low PD-L1 expression from four cancer centers. All the patients received IC, BC, or IBC as the first-line therapies. Propensity score matching (PSM) with a ratio of 1:1:1 was used to balance the inter-group clinical characteristics. Efficacy, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), as well as safety were evaluated. Results: 35 of the 125 patients received IBC, 37 received BC, and 53 received IC. After PSM, a total of 35 pairs of patients were enrolled in the analysis. Patients receiving IBC (ORR: 57.1%, DCR:100%) or IC (ORR: 57.1%, DCR: 91.4%) obtained superior ORR and DCR in relative to those receiving BC (ORR: 45.7%, DCR: 82.9%). However, only IBC (median PFS: 20.47m; median OS: not research) rather than IC (median PFS: 10.0m; median OS: 21.36m) treatment generated significantly prolonged PFS and OS compared with BC (median PFS: 9.43m, P = 0.007; median OS: 23.2m, P = 0.048). We further analyzed the survival benefit based on different clinical and molecular features. We found patients with female gender had more significant OS benefit from IBC treatment over IC or BC treatment. In addition, non-smokers benefit more from IBC compared with IC. The occurrence of adverse events (AEs) was more frequent in IBC (74.3%) and IC (85.7%) group in relative to BC group (42.8%). Meanwhile, ≥ grade 3 AEs (22.9%) was markedly higher in IBC group compared with that in BC group (5.7%). However, leukopenia and neutropenia represent the most common ≥ grade 3 AEs, which are easy to be clinically managed. Conclusions: For metastatic lung adenocarcinoma patients with low PD-L1 expression, IBC is the preferred first-line therapy in terms of survival. However, the AEs should be carefully concerned.

Service needs and neurobehavioral functioning following traumatic brain injury in U.S. military personnel.

The purpose of this study was to (a) identify the prevalence and barriers of self-reported service needs in a military sample with and without traumatic brain injury (TBI), (b) evaluate the influence of the number of service needs on overall neurobehavioral functioning, and (c) examine the longitudinal trajectories of service needs over time. Participants were 941 U.S. service members and veterans (SMVs) prospectively enrolled into four groups: uncomplicated mild TBI (MTBI; n = 455); complicated mild, moderate, severe, and penetrating TBI combined (STBI; n = 164); injured controls (IC, n = 138); and noninjured controls (NIC, n = 184). Participants completed a battery of neurobehavioral measures, as well as a self-reported service need interview, 12 or more month's postinjury. In addition, a longitudinal cohort (n = 553) was included using a subset of participants who had completed two or more evaluations. When examining the total number of self-reported service needs, there was a greater proportion of the MTBI and STBI groups that had a higher number of service needs compared to the NIC and IC groups (p < .001). In the MTBI and STBI groups, as the number of service needs increased, worse scores were found on all neurobehavioral measures. In the longitudinal cohort, the STBI group reported the highest number of service needs that persisted or developed over time (six needs), followed by the MTBI (three needs), IC (one need), and NIC (zero need) groups. These findings call for the need to enhance the provision of information given to service members and veterans following TBI regarding available services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms "gender" and "men/women" are used in this article in place of "sex" or "males/females" given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2 = 0.018-0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2 = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n2 = 0.032-0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2 = 0.024-0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

An interdisciplinary integrated specialized one-stop outpatient clinic for idiopathic intracranial hypertension – an assessment of sick leave, presenteeism, and health care utilization

BackgroundManagement of idiopathic intracranial hypertension (IIH) is complex requiring contributions from multiple specialized disciplines. In practice, this creates considerable organizational and communicational challenges. To meet those challenges, we established an interdisciplinary integrated outpatient clinic for IIH with a central coordination and a one-stop- concept. Here, we aimed to evaluate effects of this concept on sick leave, presenteeism, and health care utilization.MethodsIn a retrospective cohort study, we compared the one-stop era with integrated care (IC, 1-JUL-2021 to 31-DEC-2022) to a reference group receiving standard care (SC, 1-JUL-2018 to 31-DEC-2019) regarding economic outcome parameters assessed over 6 months. Multivariate binary logistic regression models were used to adjust for confounders.ResultsBaseline characteristics of the IC group (n = 85) and SC group (n = 81) were comparable (female: 90.6% vs. 90.1%; mean age: 33.6 vs. 32.8 years, educational level: ≥9 years of education 60.0% vs. 59.3%; located in Vienna 75.3% vs. 76.5%). Compared to SC, the IC group showed significantly fewer days with sick leave or presenteeism (-5 days/month), fewer unscheduled contacts for IIH-specific problems (-2.3/month), and fewer physician or hospital contacts in general (-4.1 contacts/month). Subgroup analyses of patients with migration background and language barrier consistently indicated stronger effects of the IC concept in these groups.ConclusionsInterdisciplinary integrated management significantly improves the burden of IIH in terms of sick leave, presenteeism and healthcare consultations – particularly in socioeconomically underprivileged patient groups.

RETENTIVE STRENGTH OF CEMENTRETAINED IMPLANT-SUPPORTED FIXED DENTAL PROSTHESES ACCORDING TO DIFFERENT CEMENT TYPES AND CEMENTATION PROTOCOLS: AN IN VITRO STUDY.

To develop the most compatible cementation protocol for ensuring minimal residual cement and optimal retention of cement-retained implant-supported fixed dental prostheses. A total of 30 custom implant abutments and zirconia crowns with bilateral wings were prepared. Three cement types were used for cementation: noneugenol resin cement (Premier Implant Cement; Group IC), dual-polymerizing self-adhesive resin cement (SmartCem2; Group SC), and zinc oxide eugenol cement (Temp-Bond; Group TB; n &#61; 30 per group). Three cementation methods were applied for each cement type, and the samples were divided into subgroups: (1) cement was injected using a graduated syringe (ICN, SC-N, and TB-N); (2) a cementa/on jig made with a silicone impression material and temporary resin material was used (IC-CJ, SC-CJ, and TB-CJ); (3) 3D-printed abutments were used as replicas for cementation (IC-3DP, SC-3DP, and TB-3DP). The amount of cement injected, surface area of the residual cement, and retentive strength were measured. Kruskal- Wallis and post-hoc Mann-Whitney tests were used for statistical analyses. Excess cement was not observed when cementa/on jig or 3D-printed replicas were used. For IC and SC subgroups, non-use of these auxiliary tools resulted in significantly higher amounts of injected cement. The retentive strength differed significantly among the IC subgroups but not among the SC subgroups. The retentive strength of subgroups TB-N and TB-CJ was significantly higher than that of subgroup TB-3DP. To prolong the main purpose of each cement type, a cementation jig or 3D-printed replica is highly recommended regardless of the cement type.

Regional analgesia using ultrasound-guided intermediate cervical plexus block versus cervical erector spinae block for anterior cervical spine surgery: a randomized trial.

Regional analgesia techniques are crucial for pain management after cervical spine surgeries. Anesthesiologists strive to select the most effective and least hazardous regional analgesia technique for the cervical region. Our hypothesis is that an intermediate cervical plexus (IC) block can provide adequate postoperative analgesia compared to a cervical erector spinae (ES) block in patients undergoing anterior cervical spine surgery. In this double-blind prospective trial, 58 patients were randomly assigned into two equal groups prior to the administration of general anesthesia. Patients in the IC group (n = 29) underwent ultrasound-guided bilateral intermediate cervical plexus block with 15ml of bupivacaine 0.25% administered to each side. The ES group (n = 29) underwent ultrasound-guided bilateral cervical erector spinae plane blocks with 15ml of 0.25% bupivacaine administered to each side at the C6 level. The primary outcome was to record the time to the first call for rescue analgesia (nalbuphine), and the secondary outcomes were to measure the performance time, the onset of the sensory block, the intraoperative fentanyl consumption, postoperative pain intensity using VAS, the postoperative total nalbuphine consumption, and postoperative complications such as nausea, vomiting, hypotension, and bradycardia. The performance and onset of sensory block times were significantly shorter in the IC group compared to the ES group. The time to first call for nalbuphine was significantly shorter in the IC group (7.31 ± 1.34h) compared to the ES group (11.10 ± 1.82h). The mean postoperative VAS scores were comparable between the two groups at the measured time points, except at 8h, where it was significantly higher in the IC group, and at 12h, where it was significantly higher in the ES group. The total nalbuphine consumption was significantly higher in the IC group (33.1 ± 10.13mg) compared to the ES group (22.76 ± 8.62mg). For patients undergoing anterior cervical spine surgery, the intermediate cervical plexus block does not provide better postoperative regional analgesia compared to the cervical erector spinae block. Performance time and onset time were shorter in the IC group, whereas nalbuphine consumption was lower in the ES group. The trial was registered at clinicaltrials.gov. (NCT05577559, and the date of registration: 13-10-2022).

PD-(L)1 inhibitors plus bevacizumab and chemotherapy as first-line therapy in PD-L1-negative metastatic lung adenocarcinoma: a real-world data

BackgroundChemotherapy combined with immune checkpoint inhibitors (IC), bevacizumab (BC), or both (IBC) is the preferred first-line therapy for PD-L1-negative and oncogenic-driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined.MethodsThis retrospective study enrolled PD-L1-negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated.ResultsA total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. The baseline characteristics among three groups were well balanced. Patients treated with IBC had the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those treated with IC (40.4%, 84.2%) or BC (40.5%, 96.2%) (ORR: P = 0.919, DCR: P < 0.01). Compared with the IC (6.74 m) or BC (8.28 m), IBC treatment significantly improved median progression-free survival (mPFS) (9.53 m, P = 0.005). However, no difference in overall survival (OS) was observed. When stratified by different clinical and molecular information, we found that male gender, ever smoking, wild-type genes mutations, and adrenal metastasis predict superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment displayed better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups.ConclusionCombined IBC treatment achieved superior DCR and PFS compared with IC or BC in patients with PD-L1-negative metastatic lung adenocarcinoma, while did not increase the adverse events.

Plasma from patients undergoing allogeneic hematopoietic stem cell transplantation promotes NETOSIS in vitro and correlates with inflammatory parameters and clinical severity.

NETosis, the mechanism by which neutrophils release extracellular traps (NETs), is closely related to inflammation. During the allogeneic hematopoietic stem cell transplantation (allo-HSCT), different stimuli can induce NETs formation. Inflammation and endothelial injury have been associated with acute graft-versus-host disease (aGVHD) and complications after allo-HSCT. We focus on the study of NETosis and its relation with cytokines, hematological and biochemical parameters and clinical outcomes before, during and after allo-HSCT. We evaluate the capacity of plasma samples from allo-HSCT patients to induce NETosis, in a cell culture model. Plasma samples from patients undergoing allo-HSCT had a stronger higher NETs induction capacity (NETsIC) than plasma from healthy donors throughout the transplantation process. An optimal cut-off value by ROC analysis was established to discriminate between patients whose plasma triggered NETosis (NETs+IC group) and those who did not (NETs-IC group). Prior to conditioning treatment, the capacity of plasma samples to trigger NETosis was significantly correlated with the Endothelial Activation and Stress Index (EASIX) score. At day 5 after transplant, patients with a positive NETsIC had higher interleukin (IL)-6 and C-reactive protein (CRP) levels and also a higher Modified EASIX score (M-EASIX) than patients with a negative NETsIC. EASIX and M-EASIX scores seek to determine inflammation and endothelium damage, therefore it could indicate a heightened immune response and inflammation in the group of patients with a positive NETsIC. Cytokine levels, specifically IL-8 and IL-6, significantly increased after allo-HSCT with peak levels reached on day 10 after graft infusion. Only, IL-10 and IL-6 levels were significantly higher in patients with a positive NETsIC. In our small cohort, higher IL-6 and IL-8 levels were related to early severe complications (before day 15 after transplant). Although early complications were not related to NETosis by itself, NETosis could predict overall non-specific but clinically significant complications during the full patient admission. In summary, NETosis can be directly induced by plasma from allo-HSCT patients and NETsIC was associated with clinical indicators of disease severity, cytokines levels and inflammatory markers.

Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy.

To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups. OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Evaluation of Salivary Immunoglobulin A Level and Its Correlation with Severity of Early Childhood Caries: An Original Research.

Early childhood caries (ECC) remains one of the most prevalent diseases mutilating the primary dentition. It is a multifactorial disease that severely affects the quality of life of affected children. One of the risk indicators reported in the literature is the presence of viable mutans streptococci (MS) and protective factors such as salivary immunoglobulin A (SIgA). Hence, it is important to identify such risks and protective factors associated with ECC using simple yet reliable methods supported by advanced technology and a fully automated platform to improve the results. A retrospective analysis was done on 40 children who were divided into two groups: group I (experimental) and group II (control). Group I comprised 30 healthy children who were further divided into three subgroups of 10 children each. Group IA with decayed, missing, filled teeth/decayed, extracted, filled teeth (dmft/deft) = 1-2, group IB with dmft/deft = 3-4, group IC with dmft/deft ≥5, and group II, comprising 10 healthy children having no caries by using World Health Organization (WHO) 2013 Oral Health Survey criteria. Unstimulated saliva was collected by drooling saliva into a sterile container. The samples were transported to the central research laboratory for SIgA by the immunoturbidimetry method by a fully automated Abbott Architect c system. The data obtained was subjected to statistical analysis. On comparison of SIgA in between varying severities of dental caries and caries-free children between age-group of 3 and 6 years, it was found to be below the grand median 0.20 mg/mL for subgroups IA and control group II. A significant negative statistical correlation (r = -0.948) was present between the SIgA and varying severities of ECC and the control group. The low dmft/deft group was found to be relatively closer to the caries-free groups as their mean dmft was 1.50, standard deviation (SD) ± 0.53. A slight change in dmft/deft score and SIgA could be used as a potential biomarker for assessing the severity of ECC in children between age-group of 3 and 6 years. Sharma V, Bagchi A, Dutta B, et al. Evaluation of Salivary Immunoglobulin A Level and Its Correlation with Severity of Early Childhood Caries: An Original Research. Int J Clin Pediatr Dent 2024;17(3):316-320.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study

BackgroundFor patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC.MethodsThis study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM).ResultsA total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325–0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236–0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280–0.858], P = 0.011; HR 0.454 [95%CI 0.246–0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis.ConclusionsOur results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

Dietary monoglyceride supplementation to support intestinal integrity and host defenses in health-challenged weanling pigs.

Frequent incidence of postweaning enterotoxigenic Escherichia coli (ETEC) diarrhea in the swine industry contributes to high mortality rates and associated economic losses. In this study, a combination of butyric, caprylic, and capric fatty acid monoglycerides was investigated to promote intestinal integrity and host defenses in weanling pigs infected with ETEC. A total of 160 pigs were allotted to treatment groups based on weight and sex. Throughout the 17-d study, three treatment groups were maintained: sham-inoculated pigs fed a control diet (uninfected control [UC], n = 40), ETEC-inoculated pigs fed the same control diet (infected control [IC], n = 60), and ETEC-inoculated pigs fed the control diet supplemented with monoglycerides included at 0.3% of the diet (infected supplemented [MG], n = 60). After a 7-d acclimation period, pigs were orally inoculated on each of three consecutive days with either 3mL of a sham-control (saline) or live ETEC culture (3 × 109 colony-forming units/mL). The first day of inoculations was designated as 0 d postinoculation (DPI), and all study outcomes reference this time point. Fecal, tissue, and blood samples were collected from 48 individual pigs (UC, n = 12; IC, n = 18; MG, n = 18) on 5 and 10 DPI for analysis of dry matter (DM), bacterial enumeration, inflammatory markers, and intestinal permeability. ETEC-inoculated pigs in both the IC and MG groups exhibited clear signs of infection including lower (P < 0.05) gain:feed and fecal DM, indicative of excess water in the feces, and elevated (P < 0.05) rectal temperatures, total bacteria, total E. coli, and total F18 ETEC during the peak-infection period (5 DPI). Reduced (P < 0.05) expression of the occludin, tumor necrosis factor α, and vascular endothelial growth factor A genes was observed in both ETEC-inoculated groups at the 5 DPI time point. There were no meaningful differences between treatments for any of the outcomes measured at 10 DPI. Overall, all significant changes were the result of the ETEC infection, not monoglyceride supplementation.