Tag: pubmed

Neuro Oncol. 2021 May 29:noab133. doi: 10.1093/neuonc/noab133. Online ahead of print.

ABSTRACT

BACKGROUND: Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important.

METHODS: PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M. Immunofluorescence and MALDI-MSI were performed to detect drug levels in the brain. EGFR levels and compensatory pathways were studied using quantitative flow cytometry, Western blots, RNAseq, FISH and phosphoproteomics.

RESULTS: Systemic delivery of Depatux-M was highly effective in nine of 10 EGFR-amplified heterotopic PDXs with survival extending beyond one year in eight PDXs. Acquired resistance in two PDXs (GBM12 and GBM46) was driven by suppression of EGFR expression or emergence of a novel short-variant of EGFR lacking the epitope for the Depatux-M antibody. In contrast to the profound benefit observed in heterotopic tumors, only two of seven intrinsically sensitive PDXs were responsive to Depatux-M as intracranial tumors. Poor efficacy in orthotopic PDXs was associated with limited and heterogeneous distribution of Depatux-M into tumor tissues, and artificial disruption of the BBB or bypass of the BBB by direct intracranial injection of Depatux-M into orthotopic tumors markedly enhanced the efficacy of drug treatment.

CONCLUSIONS: Despite profound intrinsic sensitivity to Depatux-M, limited drug delivery into brain tumor may have been a key contributor to lack of efficacy in recently failed clinical trials.

PMID:34050676 | DOI:10.1093/neuonc/noab133

J Periodontol. 2021 May 29. doi: 10.1002/JPER.20-0842. Online ahead of print.

ABSTRACT

BACKGROUND: This study evaluated the effects of infrared light laser therapy (ILLT) on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT), histology, fibroblast migration, and viability analysis.

METHODS: Forty-eight rats were randomly distributed into three groups: control (no periodontitis), PDC (periodontitis without laser therapy), and PD+L (periodontitis with laser therapy). Periodontitis was induced by ligature placement for four weeks. The 12-week-old rats (baseline) were subjected to laser treatment and euthanized 30 days after. After treatment, the mandibular first molars were prepared for micro-CT scanning, and histological sections were assessed as to the cementoenamel junction, alveolar bone crest, and polymorphonuclear (PMN) cell infiltration. In vitro assays were carried out to examine NIH/3T3 fibroblast viability after laser therapy.

RESULTS: Migration and cell viability assays revealed that the ILLT maintained fibroblast cell viability with 4 J/cm² , reaching 100% healing. The control group (at baseline and 30 days) presented a statistically significant difference from the PDC group at 30 days in terms of distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC). The PD+L group showed a statistically substantial difference from the PDC group at 30 days in terms of trabecular thickness (Tb.Th), degree of anisotropy (DA), and closed porosity percentage (Po%).

CONCLUSION: Infrared light laser therapy seemed to preserve the bone structure in the in vivo periodontitis induction model at 30 days and did not reduce cell viability or increase fibroblast migration in vitro. The ILLT provides positive effects on mandibular bone microstructure. This article is protected by copyright. All rights reserved.

PMID:34050677 | DOI:10.1002/JPER.20-0842

Int J Med Educ. 2021 May 27;12:94-100. doi: 10.5116/ijme.609d.4db0.

ABSTRACT

OBJECTIVES: To explore potential disparities in representation of Racially Minoritised (RM) persons and women in leadership roles in London Medical Schools compared to their RM and female student populations.

METHODS: General Medical Council’s Medical School Annual Return 2017-18 data and official leadership team webpages were used to determine percentages of RM and female students and percentages of RM and women leaders in London medical schools. Student and leadership team percentages were then compared using chi-squared tests to assess statistically significant differences.

RESULTS: The percentage of RM persons filling leadership roles in London medical schools combined was statistically significantly less than the percentage of RM persons that compose the combined student body (8.6% (N=81) versus 60.2% (N=8786, χ²(1, N=8,867)=88.83, p<0.001). There was no statistically significant difference between the percentage of women filling leadership roles and the percentage of women in the combined student body (43.4% (N = 83) versus 52.5% (N=9026, χ²(1, N=9,109) =2.85, p=0.0913).

CONCLUSIONS: Results mirror the underrepresentation of RM persons in leadership positions throughout the National Health Service (NHS) and in higher education but reflect the improved representation of women in leadership positions seen at the NHS board level. Greater effort is necessary to rectify RM representation within London medical school leadership teams. This is especially imperative given that racially similar role models for RM students are an important predictor in determining academic and future success.

PMID:34050640 | DOI:10.5116/ijme.609d.4db0

Int J Pharm Pract. 2021 May 29:riab029. doi: 10.1093/ijpp/riab029. Online ahead of print.

ABSTRACT

OBJECTIVES: The storage, use and disposal of controlled drugs (CDs) in hospitals and other healthcare centres are governed by a combination of government legislation and local policy. In the UK, a running balance must be kept for Schedule 2 CDs and when discrepancies arise, they must be investigated and reconciled. Policies on acceptable discrepancies are varied and based on anecdotal evidence. This study was designed to simulate dosing and stock check procedures for oxycodone oral solution, as a sample CD solution, and evaluate where the volume losses that cause discrepancies could arise from.

METHODS: Hypromellose solutions were formulated to simulate oxycodone commercial solutions. These were used to simulate dosing and stock check practices. Quantification of volume loss during simulated routine dosing and stock check of viscous oral CD formulations were performed in triplicate.

KEY FINDINGS: Dosing with enteral syringes via a fitted rubber bung never resulted in volume loss. Volume loss was always observed during stock checks with no statistical difference between methods used.

CONCLUSIONS: The findings of this study support the following recommendations. Hospital pharmacy departments should provide oxycodone and other CD liquid formulation bottles pre-fitted with a bung and make sure personnel use enteral syringes that are compatible with the chosen adaptor and of the most appropriate size for the intended dose. Stock checks should be limited to the minimum required by law or local policy.

PMID:34050645 | DOI:10.1093/ijpp/riab029

Eur J Cardiothorac Surg. 2021 May 29:ezab232. doi: 10.1093/ejcts/ezab232. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to assess single right ventricular (RV) function in a large cohort of hypoplastic left heart syndrome (HLHS) patients after the completion of total cavopulmonary connection by analysing serial cardiovascular magnetic resonance (CMR) studies.

METHODS: CMR studies from 95 HLHS patients were analysed. RV end-diastolic and end-systolic volumes (RVEDV, RVESV), ejection fraction (RVEF) and long-axis strain (LAS) were measured from cine images.

RESULTS: All 95 patients had at least 2 CMR scans and 35 patients had 3 CMR scans. The median age (first quartile-third quartile) at the 3 examinations was 4.2 (3.3-6.1), 9.4 (6.1-11.4) and 14.6 (11.8-16.8) years. RV indexed volumes (RVEDVi and RVESVi) increased from first to the second and from the first and second examination to the third examination in patients with >10 years of age (P < 0.05). There was a slight decrease in RVEF and LAS throughout the examinations, but this was not statistically significant. Correlations were found between RVEF and LAS (r = -0.23; P < 0.01). Both RVEF and LAS correlated with RVEDVi and RVESVi (r = -0.17 to 0.43; P < 0.05).

CONCLUSIONS: Serial assessment of CMR studies in HLHS patients after total cavopulmonary connection completion demonstrate an increase in indexed RV volumes in older HLHS patients but only mild reduction in RVEF and LAS. The correlation of indexed RV volumes with RVEF and LAS together with the significant increase in RV volumes over time suggests that indexed RV volumes might be superior to RV functional markers to monitor the RV in HLHS patients.

PMID:34050651 | DOI:10.1093/ejcts/ezab232

Hepatol Res. 2021 May 29. doi: 10.1111/hepr.13675. Online ahead of print.

ABSTRACT

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21,155 newly registered patients and 43,041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from 1 January 2012 to 31 December 2013. Basic statistics compiled for patients newly registered in the 22nd survey was cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world. This article is protected by copyright. All rights reserved.

PMID:34050584 | DOI:10.1111/hepr.13675

Orthop Surg. 2021 May 27. doi: 10.1111/os.12965. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the value of multi-mode neuroelectrophysiological monitoring (MIOM) in evaluating spinal cord and nerve root function in the treatment of thoracic tuberculosis via costal transverse process approach.

METHODS: From December 2017 to September 2019, a retrospective study of thoracic tuberculosis patients in our hospital was conducted. This study included 25 patients (14 men and 11 women). The average age of patients at the time of surgery was 63.3 years (range, 20-83 years). All patients (three cases with the destruction of a single vertebral body, 13 cases with the destruction of two vertebral bodies, and nine cases with the destruction of three or more vertebral bodies) underwent costal transverse process approach with debridement and bone grafting and internal fixation combined with intraoperative multimodal neuroelectrophysiological monitoring. During the operation, somatosensory evoked potential (SEP), transcranial electrical stimulation motor evoked potential (TES-MEP), and spontaneous electromyography (EMG) were used to monitor progress. ESR, visual analogue scale (VAS), Cobb angle, and Oswestry disability index (ODI) were statistically analyzed to evaluate the treatment effects and patient satisfaction.

RESULTS: All 25 patients were successfully monitored. The follow-up time ranged from 12 to 21 months, with an average of 15.3 months. SEP waveform abnormalities occurred in five patients during the operation, the incidence rate was 28%. Of these five patients, three patients changed their instruments and postures, and adjusted the flushing water flow in time; one patient received pressure therapy in time; the operation was suspended for 10 min for one patient. There were seven cases with abnormal TES-MEP waveform, the incidence rate was 28%. Among these seven cases, five cases adjusted the nail path during the operation and adjusted the nail position in time. One case adjusted the inclination angle of the operating table in time; one case completed the contralateral nail stick correction in time; five of them had abnormal TES-MEP waveforms, and EMG burst potential was also detected, the incidence rate was 20%. After prompt treatment, the abnormal waveforms of all patients returned to normal; no abnormal waveforms, recurrence of tuberculosis, loosening of internal fixation, nerve and spinal cord dysfunction, etc. The VAS score, erythrocyte sedimentation rate (ESR), Cobb angle, and ODI scores of the patients 1 year after operation were significantly improved compared with 1 week after operation (P < 0.05).

CONCLUSION: Multi-mode intraoperative electrophysiological detection combined with costal transverse process approach for the treatment of thoracic tuberculosis could avoid intraoperative nerve and blood vessel damage, reduce surgical risk, improve surgical efficiency, and ensure curative effect.

PMID:34050623 | DOI:10.1111/os.12965

Head Neck. 2021 May 29. doi: 10.1002/hed.26764. Online ahead of print.

ABSTRACT

BACKGROUND: Medical litigation is different than it was 20 years ago due to changes in health care. This study provides an updated analysis of oral cavity malpractice litigation from the past two decades (2000-2010 and 2011-2019).

METHODS: Verdict reviews from the Westlaw database were analyzed from January 2000 to August 2019. Data were collected and analyzed with the Statistical Package for the Social Sciences.

RESULTS: Sixty-five lawsuits were evaluated across 24 states. Failure to diagnose was the most common allegation in both decades. Adjusting for inflation, the average amount awarded from 2000 to 2010 was $1 721 068 and $3 925 504 from 2011 to 2019.

CONCLUSIONS: There has been a significant rise in allegations of failure to biopsy and failure to refer (p < 0.05). In addition, while award amounts appear different between decades, the difference is not statistically significant (p = 0.248). Education should focus on early diagnosis, biopsy, and referral to physicians who routinely care for this patient population.

PMID:34050580 | DOI:10.1002/hed.26764

Head Neck. 2021 May 29. doi: 10.1002/hed.26763. Online ahead of print.

ABSTRACT

BACKGROUND: In this study, we aimed to investigate the relationships between histopathological and intraoral ultrasonographic (IUS) findings in patients with tongue cancer.

METHODS: IUS and histopathological findings in 46 patients with tongue cancer were considered for this study. We assessed the relationships between IUS findings regarding tumor thickness, margin type, border type, and internal echo intensity; internal/peripheral Doppler findings; and muscle invasion and histopathological findings regarding tumor thickness, differentiation, Yamamoto-Kohama (YK)-classification grade, blood vessel invasion, lymphatic invasion, perineural invasion, and muscle invasion.

RESULTS: Statistical associations were found between the following findings: between thickness determined through IUS measurement and that determined through histopathological measurement, between the IUS findings regarding tumor margin and border types and the histopathologically determined YK-classifications grades, and between a Doppler image of the internal area of tongue lesions and lymphatic invasion.

CONCLUSIONS: IUS findings may be used to predict histopathological findings about tumor thickness and YK-classification grades.

PMID:34050571 | DOI:10.1002/hed.26763

J Magn Reson Imaging. 2021 May 28. doi: 10.1002/jmri.27746. Online ahead of print.

ABSTRACT

BACKGROUND: There is a clinical need for imaging-derived biomarkers for the management of chronic obstructive pulmonary disease (COPD). Observed pulmonary T₁ (T₁ (TE)) depends on the echo-time (TE) and reflects regional pulmonary function.

PURPOSE: To investigate the potential diagnostic value of T₁ (TE) for the assessment of lung disease in COPD patients by determining correlations with clinical parameters and quantitative CT.

STUDY TYPE: Prospective non-randomized diagnostic study.

POPULATION: Thirty COPD patients (67.7 ± 6.6 years). Data from a previous study (15 healthy volunteers [26.2 ± 3.9 years) were used as reference.

FIELD STRENGTH/SEQUENCE: Study participants were examined at 1.5 T using dynamic contrast-enhanced three-dimensional gradient echo keyhole perfusion sequence and a multi-echo inversion recovery two-dimensional UTE (ultra-short TE) sequence for T₁ (TE) mapping at TE_1-5 = 70 μsec, 500 μsec, 1200 μsec, 1650 μsec, and 2300 μsec.

ASSESSMENT: Perfusion images were scored by three radiologists. T₁ (TE) was automatically quantified. Computed tomography (CT) images were quantified in software (qCT). Clinical parameters including pulmonary function testing were also acquired.

STATISTICAL TESTS: Spearman rank correlation coefficients (ρ) were calculated between T₁ (TE) and perfusion scores, clinical parameters and qCT. A P-value <0.05 was considered statistically significant.

RESULTS: Median values were T₁ (TE_1-5 ) = 644 ± 78 msec, 835 ± 92 msec, 835 ± 87 msec, 831 ± 131 msec, 893 ± 220 msec, all significantly shorter than previously reported in healthy subjects. A significant increase of T₁ was observed from TE₁ to TE₂ , with no changes from TE₂ to TE₃ (P = 0.48), TE₃ to TE₄ (P = 0.94) or TE₄ to TE₅ (P = 0.02) which demonstrates an increase at shorter TEs than in healthy subjects. Moderate to strong Spearman’s correlations between T₁ and parameters including the predicted diffusing capacity for carbon monoxide (DLCO, ρ < 0.70), mean lung density (MLD, ρ < 0.72) and the perfusion score (ρ > -0.69) were found. Overall, correlations were strongest at TE₂ , weaker at TE₁ and rarely significant at TE₄ -TE₅ .

DATA CONCLUSION: In COPD patients, the increase of T₁ (TE) with TE occurred at shorter TEs than previously found in healthy subjects. Together with the lack of correlation between T₁ and clinical parameters of disease at longer TEs, this suggests that T₁ (TE) quantification in COPD patients requires shorter TEs. The TE-dependence of correlations implies that T₁ (TE) mapping might be developed further to provide diagnostic information beyond T₁ at a single TE.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

PMID:34050576 | DOI:10.1002/jmri.27746