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A bicentric propensity score matching study comparing percutaneous computed tomography-guided radiofrequency Ablation to Magnetic Resonance-guided Focused Ultrasounds for the treatment of osteoid osteoma

J Vasc Interv Radiol. 2021 Mar 25:S1051-0443(21)00932-5. doi: 10.1016/j.jvir.2021.03.528. Online ahead of print.

ABSTRACT

PURPOSE: To assess safety and efficacy of CT-guided radio frequency ablation (RFA) and Magnetic Resonance guided Focused Ultrasounds (MRgFUS) in the treatment of osteoid osteoma with a long-term follow-up study (mean follow-up time longer than 2 years).

MATERIALS AND METHODS: Database research was carried out in two different centres with experience in musculoskeletal interventions. Both centres, one performing RFA, the other MRgFUS, identified 116 patients, who were submitted to either RFA or MRgFUS for the treatment of symptomatic osteoid osteoma and retrospectively evaluated data regarding pain scores (using a visual analogue scale). Complications were recorded according to the CIRSE classification system. Propensity score matching for multiple variables was performed. Pre- and post-therapy pain scores were compared.

RESULTS: Out of the 116 patients treated, 61 underwent RFA and 55 MRgFUS. The mean values of pre-treatment pain in the two groups were 9.1±0.88 (RFA) and 8.7±0.73 (MRgFUS) VAS units. Post- treatment statistically significant (p<0.00001) overall reduction in pain symptomatology was recorded. No statistically significant difference was observed between the post-treatment mean values of both groups (p=0.256). Four cases of relapse (1 RFA; 3 MRgFUS) and one complication (RFA) were observed. The analysis from propensity score matching that identified a matched cohort of 48 patients showed similar results.

CONCLUSIONS: Both techniques for the treatment of osteoid osteoma seem to ensure a similar pain relief. The presence of thick cortical bone over the nidus can of reduce the effectiveness of MRgFUS.

PMID:33775816 | DOI:10.1016/j.jvir.2021.03.528

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Serum ceramide concentrations are associated with depression in patients after ischemic stroke-A two-center case-controlled Study

Clin Chim Acta. 2021 Mar 25:S0009-8981(21)00097-8. doi: 10.1016/j.cca.2021.03.014. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The present study aims to correlate the severity of post-stroke depression (PSD) and serum ceramide concentration.

MATERIALS AND METHODS: In this two-center case-control study, we prospectively collected clinical and demographical information from age and gender-matched 51 PSD patients, 56 non-post-stroke depression (Non-PSD) patients, and 39 patients with major depression (MD) to perform the suitable biochemical analysis to bring a correlation in causing depression in patients soon after the stroke. The ROC curve method was used to evaluate ceramide’s diagnostic efficacy in all three groups of patients. A follow-up analysis was also conducted based on PSD severity to associate serum ceramide levels and neuropsychiatric symptoms. The severity of the patient’s depressive symptoms was assessed by using the self-rating depression scale (SDS).

RESULTS: In comparison between PSD and MD patients, three serum ceramide species were found to be significantly different. Compared with Non-PSD patients, PSD patients had significantly higher levels of all the four serum ceramides, and increasing levels ofC16:0, C18:0(VS MD) and C16: 0(VS Non-PSD) serve as a diagnostic tool and an independent risk factor in all three categories of patients. Moreover, the follow-up analysis results showed that, as the treatment progressed, the differences in the 3 serum ceramide species were statistically significant.

CONCLUSION: There was a stage-specific association between serum ceramides and PSD, and the potential pathophysiological mechanism has to be investigated in future research.

PMID:33775701 | DOI:10.1016/j.cca.2021.03.014

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Association between self-reported signs and symptoms and SARS-CoV-2 antibody detection in UK key workers

J Infect. 2021 Mar 25:S0163-4453(21)00151-1. doi: 10.1016/j.jinf.2021.03.019. Online ahead of print.

ABSTRACT

BACKGROUND: Screening for SARS-CoV-2 antibodies is under way in some key worker groups; how this adds to self-reported COVID-19 illness is unclear. In this study, we investigate the association between self-reported belief of COVID-19 illness and seropositivity.

METHODS: Cross-sectional study of three key worker streams comprising (A) Police and Fire & Rescue (2 sites) (B) healthcare workers (1 site) and (C) healthcare workers with previously positive PCR result (5 sites). We collected self-reported signs and symptoms of COVID-19 and compared this with serology results from two SARS-CoV-2 immunoassays (Roche Elecsys® and EUROIMMUN).

RESULTS: Between 01 and 26 June, we recruited 2847 individuals (Stream A: 1,247, Stream B: 1,546 and Stream C: 154). Among those without previous positive PCR tests, 687/2,579 (26%) reported belief they had had COVID-19, having experienced compatible symptoms; however, only 208 (30.3%) of these were seropositive on both immunoassays. Both immunoassays had high sensitivities relative to previous PCR positivity (>93%); there was also limited decline in antibody titres up to 110 days post symptom onset. Symptomatic but seronegative individuals had differing symptom profiles and shorter illnesses than seropositive individuals.

CONCLUSION: Non-COVID19 respiratory illness may have been mistaken for COVID-19 during the outbreak; laboratory testing is more specific than self-reported key worker beliefs in ascertaining past COVID-19 disease.

PMID:33775704 | DOI:10.1016/j.jinf.2021.03.019

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Vorinostat combined with brigatinib overcomes acquired resistance in EGFR-C797S-mutated lung cancer

Cancer Lett. 2021 Mar 25:S0304-3835(21)00133-6. doi: 10.1016/j.canlet.2021.03.022. Online ahead of print.

ABSTRACT

The development of a new generation of tyrosine kinase inhibitors (TKIs) has improved the treatment response in lung adenocarcinomas. However, acquired resistance often occurs due to new epidermal growth factor receptor (EGFR) mutations. In particular, the C797S mutation confers drug resistance to T790M-targeting EGFR TKIs. To address C797S resistance, a promising therapeutic avenue is combination therapy that targets both total EGFR and acquired mutations to increase drug efficacy. We showed that combining vorinostat, a histone deacetylase inhibitor (HDACi), with brigatinib, a TKI, enhanced antitumor effects in primary culture and cell lines of lung adenocarcinomas harboring EGFR L858R/T790 M/C797S mutations (EGFR-3M). While EGFR phosphorylation was decreased by brigatinib, vorinostat reduced total EGFR-3M (L858R/T790 M/C797S) proteins through STUB1-mediated ubiquitination and degradation. STUB1 preferably ubiquitinated other EGFR mutants and facilitated protein turnover compared to EGFR-WT. The association between EGFR and STUB1 required the functional chaperone-binding domain of STUB1 and was further enhanced by vorinostat. Finally, STUB1 levels modulated EGFR downstream functions. Low STUB1 expression was associated with significantly poorer overall survival than high STUB1 expression in patients harboring mutant EGFR. Vorinostat combined with brigatinib significantly improved EGFR-TKI sensitivity to EGFR C797S by inducing EGFR-dependent cell death and may be a promising therapy in treating C797S-resistant lung adenocarcinomas.

PMID:33775711 | DOI:10.1016/j.canlet.2021.03.022

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γH2AX foci assay in glioblastoma: surgical specimen versus corresponding stem cell culture

Radiother Oncol. 2021 Mar 25:S0167-8140(21)06160-0. doi: 10.1016/j.radonc.2021.03.023. Online ahead of print.

ABSTRACT

AIM: To assess radiation response using γH2AX assay in surgical specimens from glioblastoma (GB) patients and their corresponding primary gliosphere culture. To test the hypothesis that gliospheres (stem cell enriched) are more resistant than specimens (bulky cell dominated) but that the interpatient heterogeneity is similar.

MATERIAL AND METHODS: Ten pairs of specimens and corresponding gliospheres derived from patients with IDH-wildtype GB were studied. Specimens and gliospheres were irradiated with graded doses and after 24 h the number of residual γH2AX foci was counted.

RESULTS: Gliospheres showed a higher Nestin expression than specimens and exhibited two different phenotypes: free floating (n=7) and attached (n=3). Slope analysis revealed an interpatient heterogeneity with values between 0.15 and 1.30 residual γH2AX foci/ Gy. Free-floating spheres were more resistant than their parental specimens (median slope 0.13 foci/ Gy versus 0.53) as well as than the attached spheres (2.14). The slopes of free floating spheres did not correlate with their corresponding specimens while a trend for a positive correlation was found for the attached spheres and the respective specimens. Association with MGMT did not reach statistical significance.

CONCLUSION: Consistent with the clinical phenotype and our previous experiments, GB specimens show low radiation sensitivity. Stem-cell enriched free-floating gliospheres were more resistant than specimens supporting the concept of radioresistance in stem cell-like cells. The lack of correlation between specimens and their respective gliosphere cultures needs validation and may have a profound impact on future translational studies using γH2AX as a potential biomarker for personalized radiation therapy.

PMID:33775712 | DOI:10.1016/j.radonc.2021.03.023

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COVID-19 vaccine response in pregnant and lactating women: a cohort study

Am J Obstet Gynecol. 2021 Mar 24:S0002-9378(21)00187-3. doi: 10.1016/j.ajog.2021.03.023. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.

STUDY DESIGN: 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.

RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups.

CONCLUSIONS: COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

PMID:33775692 | DOI:10.1016/j.ajog.2021.03.023

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Effectiveness Of Sofosbuvir And Ribavirin In Hepatitis C Genotype 3 Relapsers

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):49-53.

ABSTRACT

BACKGROUND: Combination of DAAs, Sofosbuvir and Ribavirin has been known as an effective treatment for HCV genotype 3. The aim of our study is to assess the efficacy of Sofosbuvir and Ribavirin in relapsed HCV genotype 3 patients.

METHODS: A cross-sectional retrospective analysis of hospital records between January 2015 and December 2016. Data was taken of only those patients who were followed for one year. A total of 193 cases were included in this study who were HCV genotype 3 relapsers and out of these 28 patients failed to be followed. Data was entered and analysed in IBM SPSS software package 23.

RESULTS: Out of the total 193 cases, 74.1% of cases achieved RVR at 4 weeks of therapy. ETR was achieved by 91.2% cases, while 8.8% of cases were non-responders. There was statistical significance in gender achieving ETR with a p-value of .008. 84.5% of cases achieved SVR-12. Statistical significance was noted between haemoglobin levels at presentation and 4 weeks follow-up with a p-value <0.005, and also between 4 weeks and 12 weeks follow-up with a p-value <0.005. Statistical significance was also found between age and PCR at 4 weeks (p-value of .002), age and PCR at 24 weeks (p-value of .051) and between ALT levels and PCR at 4, 12 and 24 weeks follow up (p-value <0.005). At 1-year follow-up, 79.3% of cases achieved a negative PCR, 28 patients failed to be followed, 6.2% of cases had a positive PCR. 5.5% of cases of the total 163 SVR cases had a relapse at 1 year.

CONCLUSIONS: HCV genotype 3 patients can benefit from Sofosbuvir and Ribavirin. With the SVR of more than 80%, this combination is cost-effective and safe. Treatment duration should be dependent on RVR and viral load at 4 weeks follow-up.

PMID:33774954

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Variations In Spectrum Of Covid-19 Ct Findings And Its Severity Scoring In A Tertiary Care Hospital Of Bahawalpur, Southern Punjab Pakistan

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):54-59.

ABSTRACT

BACKGROUND: Recently the Coronavirus pandemic presented with different manifestations in different parts of the world, both on clinical examinations and on imaging. CT Scanning (CT Scan) chest is used for detailed evaluation of the different characteristic patterns determining the depth of disease. The study is aimed to assess the variations in spectrum of Covid-19 CT findings and relating severity (CT Severity Score) with the Clinical Symptoms in Bahawal Victoria Hospital, Bahawalpur.

METHODS: In this cross-sectional study, patients referred to radiology department from outdoor for COVID screening were included from 1st May to 30th June 2020. Mean age range of patients was calculated, while presenting complaints and co-morbidities were tabulated in frequencies and percentages after analysis. Severity of symptoms and CT findings were correlated with biochemical and haematological tests.

RESULTS: Patients’ age range from 25 to 85 years with 62% males and 38% females. Statistically no significant difference was observed in CTSS on gender basis. As sensitivity of RT PCR is about 70%, negative cases cannot be considered disease free and this is seen in this study as CT findings suggestive of COVID are seen in these patients. Using 40-point CT-SS, 11 patients had a score of >19 with severe diseases, while 14 patients had common disease with a score range of 11-18 and 35 patients had <10 score with mild or no symptoms.

CONCLUSIONS: In this study, a spectrum of patchy ground glass opacities, bilateral peripheral predominantly lower lung consolidations were observed. Quantitative analysis of inflammatory process as occurring in lungs in Coronavirus Disease 2019, using 40-point CTSS scoring on Imaging could provide a timely and objective approach towards identifying patients requiring intensive care and hospitalisation.

PMID:33774955

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Undergraduate Dental Students’ And Instructors’ Perceptions About The Quality Of Clinical Feedback

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):82-88.

ABSTRACT

BACKGROUND: Feedback is an essential component of the clinical skills development of dental students. The clinical training is a complex integration of knowledge, psychomotor skills, behaviour and clinical communication skills under stress for both instructor and student. This study aimed to investigate the perceptions of undergraduate dental students and their instructors on the quality of clinical feedback.

METHODS: The current cross-sectional observational study was conducted at the Department of Operative Dentistry and Endodontics, Riphah International University, Islamabad from August to December 2019. A self-administered questionnaire was used to collect responses from final year undergraduate dental students and faculty. The questionnaire comprised of 13 items, subdivided into six categories, targeting the various aspects of clinical feedback. SPSS 23 was utilized to analyse the data. Descriptive statistics were tabulated and data was analysed using the Mann-Whitney test (p<0.05) for differences between the two cohorts.

RESULTS: The mean age of the 64 students who responded was 24±0.8 years. Students’ male to female ratio was 1:1.56, while for the 18 instructors the ratio was 1:1. Good agreement between the students and instructors was shown for items related to personal dignity and empathy. Moderate agreement was found for items covering the domains of time, understanding, comfort level, professionalism, and self-assessment. The disagreement was observed for the items associated with conflicting feedback, conflict satisfaction, and effective communication.

CONCLUSIONS: Incongruousness existed between the dental students and instructors, about the quality of clinical feedback provided to the dental students. Communication between the instructors and learners must be promoted to increase the level of understanding of the feedback given by the clinical instructors.

PMID:33774960

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Frequency Of Double Expressor Lymphoma In A Tertiary Care Hospital

J Ayub Med Coll Abbottabad. 2021 Jan-Mar;33(1):44-48.

ABSTRACT

BACKGROUND: Accounting for 30% cases of all lymphoid neoplasms, Diffuse large B cell lymphoma (DLBCL) is the commonest lymphoma worldwide. It occurs over a wide age range and has diverse morphology, immunophenotype and clinical outcome. Objectives of the study were to determine the frequency of Double expressor lymphoma (DEL) in a tertiary care hospital.

METHODS: This descriptive cross-sectional study was carried out in the Department of Histopathology, Rehman Medical Institute Peshawar from June 1st to December 1st, 2018. A total of 88 newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL); diagnosed on incisional or excisional biopsies were included in the study by non-probability consecutive sampling. Statistical analysis was carried out using SPSS-23. Quantitative variables were calculated as mean±SD. Qualitative variables were computed as frequency and percentages. Post stratification chi-square test was applied keeping p value equal or less than 0.05 as significance.

RESULTS: In our 88 cases of DLBCL, 56 (63.6%) were males and 32 (36.4%) were females. Age of patients ranged from 15yrs to 84yrs. Mean age was 50.8±15.2SD. Activated B-cell like (ABC) subtype of DLBCL constitute 51 cases (58%) while 37 cases (42%) were of germinal centre B-cell like (GCB) subtype. Nineteen cases (21.6%) were of DEL. Cervical node was the commonest site of involvement (n=17, 19.3%) followed by stomach (n=10, 11.4%) and tonsil (n=6, 6.8%). Out of 19 cases of DEL, 17 cases (89.5%) were of ABC type. DEL was found to have significant correlation with ABC subtype of DLBCL (p=0.002). DEL had no correlation with gender (p=0.6), age (p=0.27), Mib-1 (p=0.36) and tumour site (p=0.42).

CONCLUSIONS: The frequency of DEL in our study was 21.6% which is comparable to other studies who used similar cut-offs for c-Myc and BCL2 and similar criteria of inclusion as in our study. Significant association was found between DEL and ABC subtype of DLBCL.

PMID:33774953