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Τρίτη 17 Μαΐου 2022

Oral swabs tested with Xpert MTB/RIF Ultra for diagnosis of pulmonary tuberculosis in children: a diagnostic accuracy study

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Abstract
Background
Microbiological diagnosis of childhood tuberculosis may be difficult. Oral swabs are a potential non-invasive alternative to sputum for diagnosis.
Methods
A prospective diagnostic accuracy study of oral swabs (buccal and tongue) for pulmonary tuberculosis (PTB) diagnosis in children (aged ≤15 years) in two South African hospital sites. Children with cough of any duration and either: a positive tuberculin skin test, TB contact, loss of weight or chest X-ray suggestive of PTB were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Ultra) and liquid culture. Oral swabs were taken preceding sputum, frozen and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed TB, Unconfirmed TB (received TB treatment) or unlikely TB according to NIH consensus definitions based on sputum microbiological results.
Results
Among 291 participants (median age 32 [IQR 14-73] months), 57 (20%) were living with HIV and 87 (30%) were malnourished. 90 (31%) had confirmed PTB (six (7%) with rifampicin-resistant TB), 157 (54%) unconfirmed PTB and 44 (15%) unlikely TB. One oral swab was obtained from 126 (43%) participants (96 tongue, 30 buccal) and two swabs from 165 (57%) (110 tongue, 55 buccal). Sensitivity was low; 22% (95% CI 15-32) for all swabs combined (confirmed PTB as reference), but specificity was high (100%, 95% CI 91-100). The highest sensitivity was 33% (15-58) among participants living with HIV. Overall yield was 6.9% with one oral swab, and 7.2% with two.
Conclusions
Ultra on oral swabs provides poor yield for microbiologic PTB confirmation in children.
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Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharynx cancer: a multi-centre study

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Publication date: Available online 17 May 2022

Source: Radiotherapy and Oncology

Author(s): J.M. Price, C.M. West, L.M. Dixon, Z. Iyizoba-Ebozue, K. Garcez, L. Lee, A. McPartlin, F. Slevin, A. Sykes, R.J.D. Prestwich, D.J. Thomson

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The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial

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imageObjective: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. Background: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. Methods: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3–4, N0–2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. Results: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%–81.0%] and 76.2% (95% CI 71.9%–80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800– 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. Conclusion: The present study failed to confirm the superiority of the no touch.
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Δευτέρα 16 Μαΐου 2022

ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice

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Abstract

As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8's function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion,we examined the plasma samples of COVID-19 convalescent patients and found that the patients aged 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in five-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of SARS-CoV-2 infection on the human reproductive system.

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In silico analysis of mutations near S1/S2 cleavage site in SARS‐CoV‐2 spike protein reveals increased propensity of glycosylation in Omicron strain

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Abstract

Cleavage of the Severe Respiratory Syndrome Coronavirus–2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directe d kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. Further experimental work is needed to confirm the effect of mutations and post-translational modifications on SARS-CoV-2 spike protein cleavage sites.

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Radiographic bone volume alteration after jaw cyst enucleation with or without simultaneous bone grafts: A prospective randomized study

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Abstract

Objective

This study was aimed to evaluate bone healing after jaw cyst enucleation with or without bone substitutes by cone beam computed tomography, and to analyze potential influence factors for bone formation as well.

Materials and Methods

Sixty seven jaw cyst patients were randomly assigned to two groups. Thirty three patients in control group accepted cystectomy without any filling material. The rest 34 bone cavities which filled with xenograft (DBBM, Bio-Oss®) and covered by absorbable membrane (Bio-Gide®) were included in the guided bone regeneration (GBR) group. All patients were examined with cone bean computerized tomography before operation, 3 and 6 months after surgery. Linear regression analysis was applied to evaluate the influence factors of bone healing.

Results

There was no significant difference in bone formation rate at 3 months after enucleation, with shrinkage rate (SR) of cystic lesion in control group and GBR group of 26.43 ± 14.98% and 20.78 ± 10.80%, respectively (p > 0.05). Larger shrinkage area in GBR group was detected on postoperative radiographs after 6 months with SR of 60.11 ± 19.23%, when compared to those in patients without filling (6 months SR: 48.63 ± 19.39%, p = 0.018, <0.05). Linear regression analysis showed that cyst size was negatively correlated with bone formation.

Conclusion

GBR with bovine xenograft and absorbable membrane showed considerable bone regeneration property in the healing of jaw cystic defects after enucleation of radicular cysts. Cyst size showed a suppressive influence on bone formation.

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Κυριακή 15 Μαΐου 2022

Survival Rate of Ultrawide Diameter Implants Placed Into Molar Postextraction Sockets and in Function for Up to 144 Months

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Abstract

Purpose

Innovations in macroimplant design, specifically ultrawide implants 7.0 mm or greater in diameter, have allowed immediate molar replacement. This is a retrospective study assessing the survival rates of ultrawide diameter implants (7.0, 8.0, 9.0 mm) immediately placed into molar extraction sockets. Implants were followed up to 144 months post-placement.

Materials and methods

A retrospective study was conducted of all patients treated in a private surgical practice between January 1, 2008, and December 31, 2020, who received ultrawide dental implants (7.0, 8,0, 9.0mm.) placed immediately into molar extraction sockets. Wide diameter healing abutments were placed on all implants at the time of surgery. Abutments and crown restorations were fabricated after at least 4 months of unloaded healing. Patient age, gender, implant location and implant diameters were examined for survival. Insertion torque values at the time of placement and time in function were also evaluated. Biometric statistics were computed with P values (<0.05. Descriptive and bivariate statistics were computed; P values were set at .05.

Results

: Five hundred forty-four patients (225 males; 319 females) [average age 62.5 years; range 27 to 95] had 563 implants placed. Five hundred thirty-five of five hundred sixty-three (535/563) implants survived; 28 failed [clinical survival rate (CSR) 95.03%]. Number and time in function were: 0–12 years 100%; 0–9 years 85%; 0–6 years 69%; 0–3 years 35% or 10–12 years 16%; 7–9 years 16%; 4–6 years 34%; 0–3 years 35%. No significant differences were found between gender and implant failures (p = 0.22). Maxillary (266/285; 93.3%) and mandibular (269/278; 96.8%) implant CSRs were not significantly different. Three implant diameters were used: 7.0 mm (206/563) [36.6%]; 8.0 mm (267/563) [47.4%]; 9.0 mm (90/563) [15.9%]. Clinical survival rates were: 7.0 mm (201/206) [97.6%]; 8.0 mm (252/267) [94.4%]; 9.0 mm (82/90) [91.1%]. Mean age for patients with failed implants did not show any significant differences (p = 0.1398). Fifteen of the 28 failed implants failed within 120 da ys of surgical placement (prior to definitive restoration; [53.6%]; 4 implants failed between 4 and 12 months [14.3%]; 9 implants failed at least 1-year post-loading [32.1%].

Conclusions

The results of this long-term retrospective study regarding ultrawide diameter implants suggested that these implants were viable treatment options for immediate molar replacement following tooth extraction in either jaw with an unloaded healing protocol. High clinical survival rates were reported over a 144 month (12 year) timeframe.

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Intranasal Spray Characteristics for Best Drug Delivery in Patients With Chronic Rhinosinusitis

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Objectives

To determine parameter combinations for effective drug delivery of intranasal spray steroids to the ostiomeatal complex (OMC) and maxillary sinus (MS) in patients with chronic rhinosinusitis (CRS).

Methods

Each patient's sinonasal cavity was reconstructed from computed tomography scans. Intranasal airflow and drug particle transport were simulated using computational fluid dynamic modeling. Airflow simulations were performed at 15 Pascal inhalation pressure. Intranasal spray particles of 1–100 μm were simulated at release speeds of 1, 5, and 10 m/s from 6 release locations (Bottom, Center, Top, Lateral, Lateral-Bottom, and Lateral-Top) at a nozzle insertion depth of 15 mm. Drug delivery simulations were performed in the head tilted forward position.

Results

Maximal OMC deposition was 0.78%–12.44%, while maximal MS deposition was 0.02%–1.03% across all simulations. In general, particles between 6 and 10 μm had the best OMC (at 1 m/s particle velocity) and MS (at 10 m/s particle velocity) deposition. Particles ranging from 21 to 30 μm also had superior OMC deposition. The lateral and lateral-top spray release locations produced maximum OMC deposition, but no one release location demonstrated an increase in MS deposition.

Conclusion

This preliminary study suggests that it is challenging to determine a common set of intranasal spray parameter combinations for effective drug delivery to the OMC and MSs. Although drug particle size and spray particle velocity seem to impact particle deposition patterns, spray release location appears to vary with anatomical differences between subjects, particularly when the MS is the target location for particle deposition. Laryngoscope, 2022

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Comparison of Adult and Pediatric Cochlear Implant Wound Complications: A Meta‐Analysis

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Comparison of Adult and Pediatric Cochlear Implant Wound Complications: A Meta-Analysis

The objective of this study is to compare age-related differences in wound complications following cochlear implantation (CI). CI wound complication rates reported in the literature are low; however, adults have a higher risk of these complications than pediatric patients. The reported complication rate in elderly adults is low.


Objective

To compare age-related differences in wound complications following cochlear implantation (CI).

Methods

We performed a systematic review of PubMed, Cochrane Database, and Web of Science databases to identify original research evaluating the patient-level factors (demographics and medical history) associated with wound complications following CI. Outcomes were expressed as relative risk (RR) with 95% confidence intervals using the inverse variance method. Studies without comparison groups were described qualitatively.

Results

Thirty-eight studies representing 21,838 cochlear implantations were included. The rate of wound complications ranges from 0% to 22%. Patient age (adult versus pediatric) was the only factor with comparison groups appropriate for meta-analysis. The 10 studies (n = 9547 CI's) included in the meta-analysis demonstrated that adults had a higher incidence of overall wound complications (2.94%) than in children (2.44%) (RR 1.31, 95% CI 1.01–1.69). Adults had a higher incidence of general/unclassified wound complications (2.07%) than in children (1.34%) (RR 1.68, 95% CI 1.12–2.52). There was no difference between adults and children for specific complications such as hematoma, infection, or seroma. Elderly patients (over age 75) have wound complication rates that range from 1% to 4%. No studies contained comparison groups regarding other patient-level factors and CI wound complications.

Conclusion

CI wound complication rates reported in the literature are low; however, adults have a higher risk of these complications than pediatric patients. The reported complication rate in elderly adults is low. There is a gap in CI research in consistently reporting wound complications and rigorous research investigating the impact of patient-level factors and wound complications.

Level of Evidence

Not applicable Laryngoscope, 2022

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Pharmacological and clinical monitoring in children with acute lymphoblastic leukemia treated with a biogeneric PEG‐l‐asparaginase product

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Abstract

Background

l-Asparaginase (ASP) plays a crucial role in the treatment of childhood acute lymphoblastic leukemia (ALL). Currently, different ASP products are available in the market, including both native and pegylated drugs. Several biogeneric Escherichia coli ASP (GEN-ASP) products have been developed in response to shortages and expensiveness of the native E. coli ASP innovator compounds, but some concerns have been raised about their quality. Recently, a number of generic pegylated ASP products (GEN-PEG-ASP) have been marketed to substitute for the innovator product (PEG-ASP).

Methods

Clinical courses and serum asparaginase activity (SAA) levels were monitored in 12 children with ALL, who were treated in our institution with two doses of a GEN-PEG-ASP product, given IV at 2500 IU/m2 during the remission induction phase. Results were compared with those obtained in a reference cohort of 35 patients treated in our institution, who received the innovator PEG-ASP product at same dosage and within the same chemotherapy background.

Results

Compared to the reference cohort treated with PEG-ASP, SAA levels were significantly lower in the 12 patients receiving GEN-PEG-ASP (p < .0001); a higher proportion of ASP-associated hypersensitivity reactions (2/12 vs. 0/35; p = .061) and silent inactivation (3/12 vs. 0/35; p = .014) were observed in comparison with the reference cohort.

Conclusions

Our results highlighted different pharmacological profiles and different rates of hypersensitivity reactions and silent inactivation in the GEN-PEG-ASP cohort compared to those treated with the innovator product. Our findings suggest that a rigorous clinical attention and a thorough pharmacological monitoring are advisable in patients treated with GEN-PEG-ASP products.

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