Nevin Manimala

Ann Surg Oncol. 2021 Jul 24. doi: 10.1245/s10434-021-10443-x. Online ahead of print.

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been the standard of care for clinically node-negative women with invasive breast cancer (IBC); however, there is less agreement on whether to perform SLNB when the risk of metastasis is low or when it does not affect survival or locoregional control.

METHODS: An Institutional Review Board-approved survey was sent to members of the American Society of Breast Surgeons asking in which scenarios surgeons would recommend SLNB. Descriptive statistics and multivariable analysis were performed using SPSS software.

RESULTS: There was a 23% response rate; 68% identified as breast surgical oncologists, 6% as surgical oncologists, 24% as general surgeons, and 2% as other. The majority practiced in a community setting (71%) versus an academic setting (29%). In a healthy female with clinical T1N0 hormone receptor-positive (HR+) IBC, 83% favored SLNB if the patient was 75 years of age, versus 35% if the patient was 85 years of age. Academic surgeons were less likely to perform axillary staging in a healthy 75-year-old (odds ratio [OR] 0.51 [0.32-0.80], p = 0.004) or a healthy 85-year-old (OR 0.48 [0.31-0.74], p = 0.001). For DCIS, 32% endorsed SLNB in women undergoing lumpectomy, with breast surgical oncologists and academic surgeons being less likely to endorse this procedure (OR 0.54 [0.36-0.82], p = 0.028; and OR 0.53 [0.34-0.83], p = 0.005, respectively).

CONCLUSIONS: Despite studies showing that omitting SLNB in older patients with HR+ IBC does not impact regional control or survival, most surgeons are still opting for axillary staging. In addition, one in three are performing SLNB for lumpectomies for DCIS. Breast surgical oncologists and academic surgeons were more likely to be practicing based on recent data and guidelines. Practice patterns are changing but there is still room for improvement.

PMID:34304312 | DOI:10.1245/s10434-021-10443-x

Eur Arch Otorhinolaryngol. 2021 Jul 25. doi: 10.1007/s00405-021-07016-9. Online ahead of print.

ABSTRACT

PURPOSE: Narrow band imaging (NBI) enhances mucosal vasculature and could help in the identification of recurrences. We assessed the effectiveness of NBI with flexible video-endoscope in the early detection of recurrence after treatment of head and neck squamous cell carcinoma, its diagnostic advantage over high-definition white-light (HD WL) endoscopy, also in relation to recurrence site, and the influence of previous radiotherapy (RT) or chemotherapy (CT). Moreover, we investigated the association between index tumor site and the risk of developing recurrence, and the relation between index tumor site and recurrence site.

METHODS: From January 2018 to November 2020, 160 patients previously treated with surgery and/or RT ± CT were evaluated using NBI with flexible video-endoscope. Sensitivity, specificity, positive/negative predictive value, and accuracy were calculated for NBI and HD WL, and compared using the McNemar test. The Fisher exact test was used to compare the other associations investigated.

RESULTS: The difference between NBI and HD WL sensitivity was statistically significant (p < 0.001). The NBI diagnostic advantage was 62.5%, highest in the hypopharynx (p = 0.05), and was not influenced by previous RT or CT (p = 0.49). Index tumor site statistically related with recurrence site (p < 0.001), but not with the risk of developing recurrence (p = 0.81).

CONCLUSION: NBI with flexible video-endoscope could represent a valid option to detect recurrence early during the follow-up, especially in a difficult-to-visualize site such as the hypopharynx.

PMID:34304298 | DOI:10.1007/s00405-021-07016-9

Arch Gynecol Obstet. 2021 Jul 25. doi: 10.1007/s00404-021-06147-y. Online ahead of print.

ABSTRACT

PURPOSE: To investigate and propose a new simple tridimensional (3D) ultrasonographic method to diagnose a T-shaped uterus (Class U1a).

METHODS: A multicenter non-experimental case-control diagnostic accuracy study was conducted between January 2018 and December 2019, including 50 women (cases) diagnosed with T-shaped uterus (U1a class) and 50 women with a “normal uterus” (controls). All the enrolled women underwent 3D ultrasound, drawing four lines and recording the length of three of them as follow: draw and measure the interostial line (R0); draw from the midpoint of R0 a perpendicular line length 20 mm; draw and measure in the uterine cavity a line parallel to R0 at 10 mm below R0 (R10) and a second line parallel to R0 at 20 mm below R0 (R20). The diagnostic performance of all sonographic parameters statistically significantly different between T-shaped and normal uteri was estimated using the receiver operator characteristic (ROC) curve analysis.

RESULTS: R10 and R20 were statistically significantly shorter in the T-shaped than the normal uterus. R10 reported the highest diagnostic accuracy with an area under the ROC curve of 0.973 (95% CI 0.940-1.000). R10 length maximizing the Youden’s J statistic was 10.5 mm. Assuming R10 length equal to or shorter than 10 mm as the cut off value for defining a woman as having a T-shaped uterus, the new ultrasonographic method following the proposed protocol (R0, R10, and R20) reported sensitivity for T-shaped uterus of 91.1% (95% CI 0.78-0.97%) and a specificity of 100% (95% CI 0.89-100%). The positive likelihood ratio was higher than 30, and the negative likelihood ratio was 0.09 (95% CI 0.04-0.26).

CONCLUSIONS: Measuring the length of the intracavitary line parallel to the interostial line at 10 mm from it and using a length ≤ of 10 mm as cut off value (the “Rule of 10”) appears a simple and accurate 3D ultrasonographic method for the diagnosis of a T-shaped uterus.

PMID:34304295 | DOI:10.1007/s00404-021-06147-y

Eur Biophys J. 2021 Jul 25. doi: 10.1007/s00249-021-01563-z. Online ahead of print.

ABSTRACT

Single-cell adhesion measured with atomic force microscopy (AFM) offers outstanding time and force resolution and allows the investigation of many important phenomena with unmatched precision. However, this technique suffers from serious practical limitations that hinder its effective application to a broader set of situations. Here we propose a different strategy based on the fabrication of large cantilevers and on the culture of the cells directly on them. Cantilevers are fabricated by standard micromachining, with an active area of 300 × 300 µm. A wedged structure is created so that the cantilever surface lies parallel to the substrate when mounted on an AFM system, so that the adhesion measurement probes the whole surface area at the same time. Thanks to the large area, cells can be seeded and grown on the cantilevers the day before the experiment, and let recover to optimal condition for the experiment. We used Human Embryonic Kidney cells, HEK 293A, to demonstrate the measurement of adhesion forces of up to 100 cells in parallel, and obtain a straightforward measurement of the average single cell adhesion energy. Our approach can improve significantly the cell-cell and cell-substrate adhesion statistics, reduce the experiment time and allow the investigation of the adhesion properties of cells that do not grow well in solution or on low adherent substrates, or that develop their characteristic features only after several hours or days of culture on a solid and adherent substrate.

PMID:34304293 | DOI:10.1007/s00249-021-01563-z

Support Care Cancer. 2021 Jul 25. doi: 10.1007/s00520-021-06415-2. Online ahead of print.

ABSTRACT

PURPOSE: Endometrial cancer is strongly linked to obesity and inactivity; however, increased physical activity has important benefits even in the absence of weight loss. Resistance (strength) training can deliver these benefits; yet few women participate in resistance exercise. The purpose of this study was to describe both physiological and functional changes following a home-based strength training intervention.

METHODS: Forty post-treatment endometrial cancer survivors within 5 years of diagnosis were enrolled in a pilot randomized trial, comparing twice-weekly home-based strength exercise to wait list control. Participants conducted the exercises twice per week for 10 supervised weeks with 5 weeks of follow-up. Measures included DXA-measured lean mass, functional fitness assessments, blood biomarkers, and quality of life outcomes.

RESULTS: On average, participants were 60.9 years old (SD = 8.7) with BMI of 39.9 kg/m² (SD = 15.2). At baseline, participants had 51.2% (SD = 6.0) body fat, which was not different between groups. Improvements were seen in the 30-s chair sit to stand (d = .99), the 30-s arm curl (d = .91), and the 8-ft up-and-go test (d = .63). No changes were measured for HbA1c or C-reactive protein. No changes were observed for flexibility (chair sit and reach, back scratch tests), 6-min walk test, maximum handgrip test, anxiety, depression, fatigue, or self-efficacy for exercise.

CONCLUSIONS: Home-based muscle-strengthening exercise led to favorable and clinically relevant improvements in 3 of 7 physical function assessments. Physical function, body composition, blood biomarkers, and patient-reported outcomes were feasible to measure. These fitness improvements were observed over a relatively short time frame of 10 weeks.

PMID:34304292 | DOI:10.1007/s00520-021-06415-2

Abdom Radiol (NY). 2021 Jul 25. doi: 10.1007/s00261-021-03225-2. Online ahead of print.

ABSTRACT

PURPOSE: To assess chronic liver disease (CLD) using multiparametric US in a private practice setting in a cohort of patients with increased skin-to-liver distance.

METHODS: 110 consecutive patients with increased skin-to-liver distance scheduled for US assessment of CLD were reviewed for study completion time, liver stiffness values (LS), attenuation imaging, and shear wave dispersion slope. The ROI was placed 2 cm below the liver capsule. The study included patients with NAFLD/NASH (68), hepatitis C (30), prior Fontan surgery (1), elevated liver function tests (5), alcohol abuse (3), hepatitis B (2), and primary biliary cirrhosis (1). IQR/M values were obtained. Comparison of less experienced sonographers (LES) and more experienced sonographers (MES) were evaluated through Student’s t test for independent data. Pearson coefficient r of correlation among quantitative variables was calculated.

RESULTS: The mean time to perform the exam was 129.7 ± 62.1 s. There was a statistically significant difference between LES and MES. The mean IQR/M for LS was 12.3 ± 5.5% m/s. Overall, in a cohort of difficult patients, 4.5% of LS values were not reliable. Fat quantification using attenuation imaging had a mean value of 0.60 ± 0.15 dB/cm/MHz (range 0.35-0.98 cm/dB/MHz) with an IQR/M of 14.7 ± 9.2%. Less reliable measurements of steatosis were obtained in 4.5% of patients. The mean shear wave dispersion slope was 12.74 ± 4.05 (m/s)/kHz (range 7.7-27.5 (m/s)/kHz) with an IQR/M of 38.7 ± 20.2% (range 3-131%). 20.9% of patients had values suggestive of compensated advanced chronic liver disease (cACLD).

CONCLUSION: Multiparametric US can provide assessment of CLD in less than 3 min in most patients and identify patients at risk for cACLD.

PMID:34304291 | DOI:10.1007/s00261-021-03225-2

Ann Hematol. 2021 Jul 24. doi: 10.1007/s00277-021-04558-0. Online ahead of print.

ABSTRACT

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.

PMID:34304287 | DOI:10.1007/s00277-021-04558-0

Anal Bioanal Chem. 2021 Jul 25. doi: 10.1007/s00216-021-03536-9. Online ahead of print.

ABSTRACT

Immuno-mass spectrometry imaging (iMSI) uses laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to determine the spatial expression of biomolecules in tissue sections following immunolabelling with antibodies conjugated to a metal reporter. As with all immunolabelling techniques, the binding efficiency of multiplexed staining can be affected by a number of factors including epitope blocking and other forms of steric hindrance. To date, the effects on the binding of metal-conjugated antibodies to their epitopes in a multiplexed analysis have yet to be quantitatively explored by iMSI. Here we describe a protocol to investigate the effects of multiplexing on reproducible binding using the muscle proteins, dystrophin, sarcospan, and myosin as a model, with antibodies conjugated with Maxpar® reagents before histological application to murine quadriceps sections using standard immunolabelling protocols and imaging with LA-ICP-MS. The antibodies were each individually applied to eight sections, and multiplexed to another eight sections. The average concentrations of the lanthanide analytes were determined, before statistical analyses found there was no significant difference between the individual and multiplexed application of the antibodies. These analyses provide a framework for ensuring reproducibility of antibody binding during multiplexed iMSI, which will allow quantitative exploration of protein-protein interactions and provide a greater understanding of fundamental biological processes during healthy and diseased states.

PMID:34304281 | DOI:10.1007/s00216-021-03536-9

Rom J Intern Med. 2021 Jul 23. doi: 10.2478/rjim-2021-0028. Online ahead of print.

ABSTRACT

INTRODUCTION: Thyroid hormones affect the cardiovascular system, but the precise mechanisms of their effects on the development of atherosclerosis are not entirely clear. The relationship between subclinical hypothyroidism, dyslipidemia and carotid atherosclerosis has been widely investigated, but the findings were controversial. The aim of the present study was to determine whether female subjects with subclinical hypothyroidism (SHypo) have increased carotid intima-media thickness (IMT) compared with euthyroid subjects, as well as to examine the association of SHypo, carotid atherosclerosis and dyslipidemia.

METHODS: This research included 100 women aged 30 to 70 years who were divided into two groups: the SHypo group including subjects with signs of subclinical hypothyroidism and the control group of euthyroid subjects. Carotid IMT thickness using B mode ultrasound was determined and its correlation with serum concentrations of fT4, TSH, CRP, and lipid profile including small dense LDL (sdLDL) was analysed.

RESULTS: Subjects with SHypo had significantly increased carotid IMT (IMT ≥ 75th centile) in all three measured segments of the right (p <0.001) and the left (p = 0.001) carotid artery compared to the control group, with a significantly more frequent appearance of plaque (25% vs. 9%; p = 0.05). Significant positive correlations were found between higher TSH and higher IMT values. Increased age, LDL cholesterol, and TSH predicted thickening of the carotid artery IMT.

CONCLUSIONS: It is important to screen people showing early, subclinical signs of thyroid gland dysfunction due to its impact on carotid atherosclerosis development.

PMID:34303321 | DOI:10.2478/rjim-2021-0028

Horm Mol Biol Clin Investig. 2021 Jul 26. doi: 10.1515/hmbci-2021-0012. Online ahead of print.

ABSTRACT

OBJECTIVES: As a systemic inflammatory disease, rheumatoid arthritis (RA) is the most common inflammatory arthritis in the population and there is no specific diagnostic marker in laboratory tests. The purpose of the study was to determine whether serum neopterin and pentraxin 3 (PTX3) levels may be a marker of increased inflammation in RA patients.

MATERIALS AND METHODS: The study were consist of 30 RA patients and 30 healthy controls who were admitted to the department of rheumatology. Blood specimens were taken from both group, and the levels of neopterin were analyzed by chromatography method (HPLC) and the PTX 3 levels were measured by enzyme-linked immunosorbent assay (ELISA). All data and demographic characteristics of participants were also recorded.

RESULTS: Serum neopterin and PTX 3 levels of the patient group (25.99 ± 7.24 ng/mL and 4.19 ± 1.01 ng/dL, respectively) was higher than the control group (9.55 ± 0.74 ng/mL and 2.23 ± 0.39 ng/dL, respectively). These results were remarkable significant (p<0.01). No statistically significant correlation was found between age-PTX 3, age-neopterin and PTX 3-neopterin parameters in the patient group. In the control group, a significant negative correlation was found between age and PTX 3 (p<0.05), and a positive correlation between neopterin and PTX 3.

CONCLUSIONS: Consequently, the serum neopterin and PTX 3 levels were higher in RA patients as compared to the healthy individuals. Our study suggest that there is a relation between neopterin and PTX 3 levels with RA patients. These findings suggest that neopterin and PTX 3 are important markers in the monitoring of RA disease.

PMID:34303320 | DOI:10.1515/hmbci-2021-0012