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Τετάρτη 14 Σεπτεμβρίου 2022

Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort

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Abstract
Background
It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort.
Methods
People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrate d Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data.
Results
During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM.
Conclusions
Both blips and LLV during ART are associated with increased risk of subsequent VF.
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Comparison of the accuracy between conventional and various digital implant impressions for an implant‐supported mandibular complete arch fixed prosthesis: an in vitro study

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Abstract

Purpose

This in vitro study compared the accuracy between conventional and different intraoral scanner impression methods and stereophotogrammetry term of 3D deviation for a complete mandibular edentulous arch with 5 placed implants.

Materials and methods

An edentulous mandibular model was prepared with three straight and two 17° angled screw-retained abutments screwed on implants. Different impression techniques were compared: 1 conventional impression, CO (Open-tray splint impression coping, Polyether), 3 groups of intraoral scanners, TS (Trios 4), IT (iTero Element 2), and PS (Primescan), and 1 Stereophotogrammetry, PIC (Precise Implants Capture). An extraoral scanner (E4 scanner) was used to digitize the reference model as a control group. Scan body positions were compared with 3D deviation by using a 3D analysis software program (Geomagic ControlX 2020.1.1) with the best fit alignment technique. The accuracy of the scan bodies' position of each impression technique between each group area was analyzed using one-way ANOVA followed by Scheffé's comparison test for trueness and precision. (α = 0.05)

Results

Statistical 3D deviations of the whole scan body were found among the CO, TS, PS, IT, and PIC groups for both trueness (p < 0.05) and precision (p < 0.05). PIC showed the least 3D deviation of trueness (48.74 ± 1.80 μm) and precision (5.46 ± 1.10 μm), followed by TS, PS, IT, and CO. CO had the highest 3D deviation of trueness (141 ± 5.58 μm) and precision (40.4 ± 1.3.39 μm), which was significantly different from PIC, TS, and PS.

Conclusion

For completed-arch digital implant impressions, a stereophotogrammetry has shown better accuracy than other digital and conventional impression techniques, especially in terms of precision. The highest 3D deviation was found in the conventional splint open tray impression technique.

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Antagonistic, synergistic, and additive antibacterial interaction between ciprofloxacin and amoxicillin against Staphylococcus aureus

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Abstract

The aim of this in vitro study was to evaluate the interaction between ciprofloxacin and amoxicillin against beta-lactamase-producing Staphylococcus aureus (S. aureus). Concentration-dependent curves for each individual drug were carried out to obtain the mean inhibitory concentration in the agar well diffusion assay. Then, different ratios of the ciprofloxacin-amoxicillin combination (0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05 and 0.05:0.95) were assessed. Data were analyzed using the isobolographic analysis and interaction index. The isobolographic evaluation show that the 0.9:0.1 and 0.95:0.05 ratios of the ciprofloxacin-amoxicillin combination produced a synergistic antimicrobial interaction, the 0.8:0.2, 0.2:0.8, 0.1:0.9, and 0.05:0.95 proportions showed an additive antibacterial effect, and the 0.5:0.5 proportion induced antagonistic antimicrobial effects. The interaction index showed similar outcomes to the isobolographic analysis. In conclu sion, the data of this study mainly show antimicrobial additive results of the ciprofloxacin-amoxicillin combination against beta-lactamase-producing S. aureus.
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Imaging of pediatric cardiac tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

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Abstract

Cardiac tumors in children are rare and the majority are benign. The most common cardiac tumor in children is rhabdomyoma, usually associated with tuberous sclerosis complex. Other benign cardiac masses include fibromas, myxomas, hemangiomas, and teratomas. Primary malignant cardiac tumors are exceedingly rare, with the most common pathology being soft tissue sarcomas. This paper provides consensus-based imaging recommendations for the evaluation of patients with cardiac tumors at diagnosis and follow-up, including during and after therapy.
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Heritable cancer predisposition testing in pediatric cancer patients excluding retinoblastoma in a middle‐income country

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Abstract

Resource-limited settings often have financial barriers to genetic testing for heritable cancer. This retrospective study investigated the pattern of heritable cancer predisposition testing in a middle-income country over the period 2014–2021, excluding retinoblastoma. After establishing a specific fund in 2019, rate of tests increased from 1.1% to 10.9% of new diagnoses. Most common testing was for constitutional mismatch repair deficiency (CMMRD), rhabdoid predisposition syndrome, TP53 (tumor protein 53) mutation, and hereditary cancer panel. Of 33 patients, 13 (39%) tested positive, 12 (36%) negative, and eight (24%) had variants of unknown significance. Positivity rate was 43% for a clinical phenotype and 44% for a tumor type indication.
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HSPA9 frameshift and loss‐of‐function mutations in a patient manifesting syndromic sideroblastic anemia and congenital anomalies

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Opsoclonus‐myoclonus syndrome associated with neuroblastoma: Insights into antitumor immunity

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Abstract

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder. Half of these cases occur in children with neuroblastoma. Neuroblastoma patients with OMS usually have better oncological outcomes than those without OMS even after stratification by tumor stage and age, indicating that factors mediating OMS may also inhibit tumor cell proliferation. Although the mechanisms underlying OMS remain undefined, the cytokines and lymphocytes alterations in the cerebrospinal fluid support the concept that it is a pattern of neuroinflammation due to an autoimmune effect. The presence of lymphoid follicles consisting of follicular dendritic cells, CD20+ B lymphocytes, CD3+ T lymphocytes, and CD68+ macrophages in the tumor microenvironment in OMS-associated neuroblastoma support the autoimmune nature of this disorder. This review focuses on the clinical and genetic features of OMS-associated neuroblastoma, and we update readers on immune features of neurobl astoma with or without OMS to gain insights into antitumor immunity as it relates to tumor biology and prognosis.
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Imaging of pediatric liver tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

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Abstract

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%–2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy.
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Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls

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Abstract

Background

There is growing interest among pediatric institutions for implementing iodine-131 (I-131) meta-iodobenzylguanidine (MIBG) therapy for treating children with high-risk neuroblastoma. Due to regulations on the medical use of radioactive material (RAM), and the complexity and safety risks associated with the procedure, a multidisciplinary team involving radiation therapy/safety experts is required. Here, we describe methods for implementing pediatric I-131 MIBG therapy and evaluate our program's robustness via failure modes and effects analysis (FMEA).

Methods

We formed a multidisciplinary team, involving pediatric oncology, radiation oncology, and radiation safety staff. To evaluate the robustness of the therapy workflow and quantitatively assess potential safety risks, an FMEA was performed. Failure modes were scored (1–10) for their risk of occurrence (O), severity (S), and being undetected (D). Risk priority number (RPN) was calculated from a product of these scores and used to identify high-risk failure modes.

Results

A total of 176 failure modes were identified and scored. The majority (94%) of failure modes scored low (RPN <100). The highest risk failure modes were related to training and to drug-infusion procedures, with the highest S scores being (a) caregivers did not understand radiation safety training (O = 5.5, S = 7, D = 5.5, RPN = 212); (b) infusion training of staff was inadequate (O = 5, S = 8, D = 5, RPN = 200); and (c) air in intravenous lines/not monitoring for air in lines (O = 4.5, S = 8, D = 5, RPN = 180).

Conclusion

Through use of FMEA methodology, we successfully identified multiple potential points of failure that have allowed us to proactively mitigate risks when implementing a pediatric MIBG program.
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Examining multi‐level immune response to determine prevalence of COVID‐19 in pediatric tonsillectomy

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Examining multi-level immune response to determine prevalence of COVID-19 in pediatric tonsillectomy


Objective

To determine the prevalence of COVID-19 in a cohort of children undergoing tonsillectomy through assessment of B cell immune responses to SARS-CoV-2 in both peripheral blood and tonsil tissue.

Methods

In this cohort study at a tertiary pediatric hospital (Children's National Hospital) in Washington, DC, we recruited 100 children undergoing tonsillectomy from late September 2020 to January 2021. Serum, peripheral blood cells, and tonsil tissue were collected and examined for immune reactivity to SARS-CoV-2. Parent-reported clinical histories were compared to antibody and B-cell responses.

Results

Among 100 children undergoing tonsillectomy, 19% had evidence of immune responses to SARS-CoV-2 (CoV2+), indicating prior COVID-19. In all seropositive participants, we detected SARS-CoV-2 specific B cells in both peripheral blood mononuclear cells and tonsils, providing evidence for tissue-specific immunity in these children. Of the 19, 63% reported no known history of COVID-19, and an additional 3 were asymptomatic or unaware of an acute infection when detected on pre-surgery screen. Hispanic children represented 74% of CoV2+ subjects compared to 37% of the full cohort. 100% of CoV2+ children lived in a zip code with poverty level >10%.

Conclusions

Nearly one-fifth of children undergoing tonsillectomy at an urban U.S. hospital had evidence of prior COVID-19 during the early pandemic, with the majority unaware of prior infection. Our results underscore the ethnic and socio-economic disparities of COVID-19. We found concordant evidence of humoral immune responses in children in both blood and tonsil tissue, providing evidence of local immune responses in the upper respiratory tract.

Level of Evidence

3 Laryngoscope, 2022
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Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study

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Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study

This serves as the seminal work from the prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity Surgery (POUCHS) Collaborative. Of the 250 persons enrolled, 85% had a Zenker diverticula (ZD), 9% had evidence of cricopharyngeus muscle dysfunction (CPMD) without diverticula and 4% had a Killian Jamieson diverticula (KJD). Patients with isolated CPMD appear to be more symptomatic than persons with ZD or KJD.


Objective

To describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula.

Methodology

Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient-reported outcome measures (e.g., Eating Assessment Tool [EAT-10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance.

Results

A total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty-two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction-type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT-10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT-10 scores compared to the other diagnostic groups (p = 0.03).

Conclusion

ZD is the most common, followed by CPMD without diverticula, KJD, and traction-type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD.

Level of Evidence

Level 4 Laryngoscope, 2022
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