Nevin Manimala

Int Ophthalmol. 2022 Oct 20. doi: 10.1007/s10792-022-02558-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of using Mitomycin-C (MMC) or Ologen implant as an adjunct to combined trabeculotomy-trabeculectomy (CTT) surgery relative to non-augmented CTT surgery in achieving higher success rates in patients with primary congenital glaucoma (PCG).

STUDY DESIGN: A prospective triple-armed randomized controlled clinical trial was conducted in the period between April 2019 and May 2021, targeting 75 eyes of patients with PCG over one year, with patients being followed up for at least one whole year.

PATIENTS AND METHODS: The study included 75 eyes; only 70 fulfilled the inclusion criteria and were randomly assigned to one of the three study groups using a computer program to generate random number list. Eyes were treated by either CTT without augmentation, CTT augmented with MMC, or CTT augmented with Ologen implant. Only 63 eyes completed one year of follow-up and were evenly distributed among the three study groups; with 21 eyes in each group were statistically analyzed.

OUTCOME MEASURES: Our primary outcome measure is to report and compare the percentage of patients who demonstrated complete success with intraocular pressure (IOP) controlled and maintained below 21 mmHg without the use of antiglaucoma medications or additional glaucoma surgery over a one-year follow-up. Secondary outcome measures include reporting failure, intra- and postoperative complications of the three surgical modalities, postoperative corneal diameter, clearance of corneal edema, and postoperative cup/disk (C/D) ratio.

RESULTS: Complete success was achieved in 17 eyes (81.0%) in CTT group, 18 eyes (85.7%) in MMC group, and 17 eyes (81.0%) in Ologen group. Qualified success (IOP < 21 with or without antiglaucoma medications) was achieved in 18 eyes (85.7%) in both the CTT and the Ologen groups, with 19 eyes (90.5%) in the MMC group. Failure was observed in three eyes (14.3%) in both CTT and Ologen groups and two eyes (9.5%) in the MMC group. Based on survival analysis, CTT group had a cumulative success probability of 95.2% at three months, which dropped to 85.7% at six months and remained at that level for the 9th and 12th months of follow-up. With respect to the MMC group, the cumulative success probability at three months was 95.2%, dropped to 90.5% at six months, and remained at that level for the 9th and 12th months of follow-up. While in the Ologen group, the cumulative success probability at three months was 85.7% and remained at the same level during the 6th, 9th, and 12th months of follow-up, with p value = 0.862 using the logrank test.

CONCLUSION: CTT is a safe and effective primary surgical intervention in patients with PCG without the need for augmentation while preserving the augmented procedure’s use for recurrent cases.

PMID:36266601 | DOI:10.1007/s10792-022-02558-1

Mol Imaging Biol. 2022 Oct 20. doi: 10.1007/s11307-022-01781-7. Online ahead of print.

ABSTRACT

PURPOSE: The presence and functional competence of intratumoral CD8⁺ T cells is often a barometer for successful immunotherapeutic responses in cancer. Despite this understanding and the extensive number of clinical-stage immunotherapies focused on potentiation (co-stimulation) or rescue (checkpoint blockade) of CD8⁺ T cell antitumor activity, dynamic biomarker strategies are often lacking. To help fill this gap, immuno-PET nuclear imaging has emerged as a powerful tool for in vivo molecular imaging of antibody targeting. Here, we took advantage of immuno-PET imaging using ⁸⁹Zr-IAB42M1-14, anti-mouse CD8 minibody, to characterize CD8⁺ T-cell tumor infiltration dynamics following ICOS (inducible T-cell co-stimulator) agonist antibody treatment alone and in combination with PD-1 blocking antibody in a model of mammary carcinoma.

PROCEDURES: Female BALB/c mice with established EMT6 tumors received 10 µg, IP of either IgG control antibodies, ICOS agonist monotherapy, or ICOS/PD-1 combination therapy on days 0, 3, 5, 7, 9, 10, or 14. Imaging was performed at 24 and 48 h post IV dose of ⁸⁹Zr IAB42M1-14. In addition to ⁸⁹Zr-IAB42M1-14 uptake in tumor and tumor-draining lymph node (TDLN), 3D radiomic features were extracted from PET/CT images to identify treatment effects. Imaging mass cytometry (IMC) and immunohistochemistry (IHC) was performed at end of study.

RESULTS: ⁸⁹Zr-IAB42M1-14 uptake in the tumor was observed by day 11 and was preceded by an increase in the TDLN as early as day 4. The spatial distribution of ⁸⁹Zr-IAB42M1-14 was more uniform in the drug treated vs. control tumors, which had spatially distinct tracer uptake in the periphery relative to the core of the tumor. IMC analysis showed an increased percentage of cytotoxic T cells in the ICOS monotherapy and ICOS/PD-1 combination group compared to IgG controls. Additionally, temporal radiomics analysis demonstrated early predictiveness of imaging features.

CONCLUSION: To our knowledge, this is the first detailed description of the use of a novel immune-PET imaging technique to assess the kinetics of CD8⁺ T-cell infiltration into tumor and lymphoid tissues following ICOS agonist and PD-1 blocking antibody therapy. By demonstrating the capacity for increased spatial and temporal resolution of CD8⁺ T-cell infiltration across tumors and lymphoid tissues, these observations underscore the widespread potential clinical utility of non-invasive PET imaging for T-cell-based immunotherapy in cancer.

PMID:36266600 | DOI:10.1007/s11307-022-01781-7

Parasitol Res. 2022 Oct 21. doi: 10.1007/s00436-022-07687-1. Online ahead of print.

ABSTRACT

Cystic echinococcosis (CE) is a neglected helminthic zoonosis in many parts of the world. Some CE cysts in the intermediate host are non-fertile. Considering the function of microRNAs in many biological processes such as embryonic development, cell proliferation, and apoptosis, this study investigated the function and comparison of miR-71 and let-7 in fertile and non-fertile CE cysts. Here, we determined the expression level of the miRNAs for 33 animal cysts and 16 human cysts (Echinococcus granulosus sensu stricto (G1). The quantitative real-time PCR method was conducted for the expression evaluation of miR-71 and let-7. The expression of both miRNAs in all samples was determined using the following formula: [ΔCT = CT (target) – CT (internal control)]. A comparison of Δct of miR-71 and let-7 in fertile and non-fertile cysts did not show a significant difference (P = 0.911 and 0.354). In cattle, sheep, and humans, Δct of miR-71, and let-7 were higher, respectively. Therefore, the mean expression of miR-71 and let-7 indicates an increase in humans compared to other intermediate hosts. Also, statistical results show a significant difference in the expression of these miRNAs in sheep, cattle, and human cysts (P = 0.025 and 0.01). The lower expression of these miRNAs in cattle cysts and their common infertility might be associated with the hypothesis and function of miRNAs in the fertility of CE cysts. So we should not ignore the function and role of miRNAs in this subject due to the importance of infertility in E. granulosus epidemiology.

PMID:36266590 | DOI:10.1007/s00436-022-07687-1

Oral Radiol. 2022 Oct 20. doi: 10.1007/s11282-022-00661-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the potential of maxillary molar dimensions as predictors of the presence of the second mesiobuccal (MB2) canal.

METHODS: Micro-computed tomography scans were obtained from 47 maxillary molars, out of which 26 had the MB2 canal. The distance between root canals, extension of the canals, and thickness of surrounding dentin were obtained from axial images at the furcation level, 3 mm from the apex, and 5 mm from the apex. The association between the measurements and the presence of the MB2 canal was assessed using multiple logistic regression and odds ratio.

RESULTS: At the furcation level, the bucco-palatal extension of the MB1 canal significantly decreased the chance of the presence of the MB2 canal. Regarding the thickness of surrounding dentin measurements, the mesial and distal aspects of the MB1 canal at 3 mm from the apex were statistically significant to decrease and increase the chance of presence of the MB2 canal, respectively. Regarding the extension of the canals, only buccal-palatal extension seems to decrease the chance of the presence of the MB2 canal.

CONCLUSION: The presence of the MB2 canal in the mesiobuccal root of maxillary molars is associated with the bucco-palatal extension and surrounding dentin thickness of the first mesiobuccal canal, and seems to be unrelated to the dimensions of the distobuccal and palatal roots.

PMID:36266556 | DOI:10.1007/s11282-022-00661-8

J Immigr Minor Health. 2022 Oct 20. doi: 10.1007/s10903-022-01418-5. Online ahead of print.

ABSTRACT

Community outreach and engagement has been a regular activity of the National Cancer Institute at its designated Cancer Centers. However, in 2016, community outreach and engagement became a required activity for all cancer centers. Yet there is a gap in the literature that provides guidelines for developing materials that resonate with communities. We developed the PEARL rubric to fulfill that gap from our work developing culturally sensitive breast cancer education materials for African American and Immigrant African women. We conducted a targeted literature review to understand the approaches that have been used for developing education materials for communities. We reviewed the literature and distilled key elements into our PEARL guide for creating culturally appropriate education materials. PEARL consists of five elements: Plain language and understandability, Explicit data, statistics, and graphs, Affirmative framing, Representative content, and Local connection. PEARL is a modern comprehensive guide that researchers can use for creating culturally sensitive materials. It is designed to guide researchers develop educational materials who have little to no experience in community engagement.

PMID:36266493 | DOI:10.1007/s10903-022-01418-5

Sci Rep. 2022 Oct 20;12(1):17561. doi: 10.1038/s41598-022-22431-6.

ABSTRACT

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70-80% reduction in relative risk; absolute reduction of 35-40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.

PMID:36266486 | DOI:10.1038/s41598-022-22431-6

Surg Endosc. 2022 Oct 20. doi: 10.1007/s00464-022-09707-8. Online ahead of print.

ABSTRACT

BACKGROUND: Degree of resident participation in a case is often used as a surrogate marker for operative autonomy, an essential element of surgical resident training. Previous studies have demonstrated a considerable disagreement between the perceptions of attending surgeons and trainees when it comes to estimating operative participation. The Da Vinci Surgical System dual console interface allows machine generated measurements of trainee’s active participation, which has the potential to obviate the need for labor intensive direct observation of surgical procedures. However, the robotic metrics require validation. We present a comparison of operative participation as perceived by the resident, faculty, trained research staff observer (gold standard), and robotic machine generated data.

METHODS: A total of 28 consecutive robotic inguinal hernia repair procedures were observed by research staff. Operative time, percent active time for the resident, and number of handoffs between the resident and attending were recorded by trained research staff in the operating room and the Da Vinci Surgical System. Attending and resident evaluations of operative performance and perceptions of percent active time for the resident were collected using standardized forms and compared with the research staff observed values and the robot-generated console data. Wilcoxon two-sample tests and Pearson Correlation coefficients statistical analysis were performed.

RESULTS: Robotic inguinal hernia repair cases had a mean operative time of 91.3 (30) minutes and an attending-rated mean difficulty of 3.1 (1.26) out of 5. Residents were recorded to be the active surgeon 71.8% (17.7) of the total case time by research staff. There was a strong correlation (r = 0.77) in number of handoffs between faculty and trainee as recorded by the research staff and robot (4.28 (2.01) vs. 5.8 (3.04) respectively). The robotic machine generated data demonstrated the highest degree of association when compared to the gold standard (research staff observed data), with r = 0.98, p < 0.0001. Lower levels of association were seen with resident reported (r = 0.66) perceptions and faculty-reported (r = 0.55) perceptions of resident active operative time.

CONCLUSIONS: Our findings suggest that robot-generated performance metrics are an extremely accurate and reliable measure of intraoperative resident participation indicated by a very strong correlation with the data recorded by research staff’s direct observation of the case. Residents demonstrated a more accurate awareness of their degree of participation compared with faculty surgeons. With high accuracy and ease of use, robotic surgical system performance metrics have the potential to be a valuable tool in surgical training and skill assessment.

PMID:36266482 | DOI:10.1007/s00464-022-09707-8

Surg Endosc. 2022 Oct 20. doi: 10.1007/s00464-022-09697-7. Online ahead of print.

ABSTRACT

PURPOSE: While it is widely accepted that laparoscopic total extraperitoneal (TEP) inguinal herniorrhaphy has decreased post-operative pain, there are conflicting data as to whether instillation of local anesthetic into the preperitoneal space improves post-operative pain in these patients. We designed a prospective study to evaluate this. Secondary outcomes include time spent in the PACU, need for narcotic pain medication, and total amount of narcotics required postoperatively.

METHODS: Prospective, randomized, double-blind, placebo-controlled study which enrolled 70 patients with unilateral non-recurrent inguinal hernia from 09/2013 to 03/2019 and included immediate and 2-week post-operative follow-up. All patients received unilateral laparoscopic TEP inguinal hernia repair with control patients receiving 10 ml of 0.9% saline instilled into preperitoneal space while treatment group received 10-ml 0.5% bupivacaine without epinephrine.

RESULTS: A total of 70 patients [67 (96%) men and 3 women; mean age (SD), 57 years (13.8)] were enrolled, 35 randomized into each group. Demographics between the two groups were similar. No differences were found in post-operative pain between the control and test groups at 1 h [mean (SD) of 3.15(2.5) vs 3.21(2.9); P = 0.92], 2 h [3.39 (1.55) vs 2.74 (1.85) P = 0.18], or 1 day [4.79 (2.19) vs 4.39 (2.37); P = 0.13] postoperatively. Likewise, no significant differences were observed in usage of narcotic pain medication postoperatively, as 17 control patients (50%) and 16 (46%) study patients required narcotics within 2 h of surgery (P = 0.72).

CONCLUSION: Instilling local anesthetic into the preperitoneal space during laparoscopic TEP inguinal hernia repair did not result in statistically significant difference in post-operative pain (Rade et al. in NESS Annual Meeting, 2021). Trial registry ClinicalTrials.gov Identifier: NCT02055053.

PMID:36266481 | DOI:10.1007/s00464-022-09697-7

Eur J Trauma Emerg Surg. 2022 Oct 20. doi: 10.1007/s00068-022-02141-4. Online ahead of print.

ABSTRACT

PURPOSE: In the last decades, total elbow arthroplasty, elbow osteosynthesis and revision surgery have been more popularized. The study aimed to assess the course of the anconeus branch of the radial nerve in relation to two variations of the lateral para-olecranon approach, considering iatrogenic nerve injuries.

METHODS: The study consisted of 120 upper extremities from 60 Thiel-embalmed human specimens. Two randomized versions of the lateral para-olecranon approach (centrally orientated: P1 and laterally orientated: P2) were performed. The olecranon and the intersection points to the anconeus branch of the radial nerve were determined as anatomical landmarks. The measurements were assessed by two independent observers. Differences were analyzed using the Student’s t test; associations were computed with the Pearson correlation (r). An alpha of 0.05 (p) and a confidence interval of 95% were set.

RESULTS: The intersection points averaged 12.3 cm (SD 1.8, range 8.2-16.8) for P1 versus 5.5 cm (SD 1.4, range 3.0-9.2) for P2 (p ≤ 0.001). Statistically significantly higher values for male and longer humeral specimens were revealed (all values: p < 0.05). Comparison of left and right sides yielded no difference. Excellent inter-rater agreements were found (ICC = 0.902, range 0.860-0.921). A correlation was evaluated between the humeral length and the distances in both approaches (P1: r = 0.550, p < 0.001, P2: r = 0.669, p < 0.001).

CONCLUSION: The data presented here allow preservation of the anconeus branch. The P1 forms a potential advantage by owing a broader safe zone. Using the centrally orientated approach seems to provide adequate nerve protection during surgery for one of the motor branches for extension of the elbow joint and might result in improved postoperative benefits.

PMID:36266477 | DOI:10.1007/s00068-022-02141-4

Nat Ecol Evol. 2022 Oct 20. doi: 10.1038/s41559-022-01902-z. Online ahead of print.

NO ABSTRACT

PMID:36266457 | DOI:10.1038/s41559-022-01902-z