Τετάρτη 21 Σεπτεμβρίου 2022

Ad5‐nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants

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Abstract

Background

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses.

Methods

Plasma was collected from InV pre-vaccinated Omicron infected patients (OIPs), unvaccinated OIPs between 0-22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay.

Results

InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days post-infection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3- and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35112 and 28186 during 11-22 DPI, about 2.6- and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-, 5.6-, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs.

Conclusion

InV and Ad5-nCoV booster could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

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Less is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-associated Pneumonia

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Abstract
Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data. We highligh t strengths and weaknesses of existing data on this topic and provide recommendations for future avenues of study.
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Incidence of occult cleft palate on prenatal magnetic resonance images obtained for non-cleft indications

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Prenatal diagnosis of craniofacial anomalies has improved family education and preparedness. Isolated cleft palate, however, remains difficult to identify sonographically. The aim of this study was to investigate the rate of incidental cleft palate identified on fetal magnetic resonance imaging (MRI) following the ultrasound detection of non-cleft abnormalities. This was a retrospective study of pregnant women who had fetal MRI performed between 2003 and 2017. To be included, the woman had to have been referred for fetal imaging for a non-cleft indication, with subsequent identification of an isolated cleft palate on MRI. (Source: International Journal of Oral and Maxillofacial Surgery)
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Control of Pre‐phonatory Glottal Shape by Intrinsic Laryngeal Muscles

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Control of Pre-phonatory Glottal Shape by Intrinsic Laryngeal Muscles

Complex interactions between intrinsic laryngeal muscles and their effects on the vocal fold pre-phonatory posture were studied. The thyroarytenoid (TA) was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the lateral cricoarytenoid (LCA). The cricothyroid (CT) contributed minimally to vocal fold medial shape but elongated the glottis.


Objectives

Surgical manipulations to treat glottic insufficiency aim to restore the physiologic pre-phonatory glottal shape. However, the physiologic pre-phonatory glottal shape as a function of interactions between all intrinsic laryngeal muscles (ILMs) has not been described. Vocal fold posture and medial surface shape were investigated across concurrent activation and interactions of thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid/interarytenoid (LCA/IA) muscles.

Study Design

In vivo canine hemilarynx model.

Methods

The ILMs were stimulated across combinations of four graded levels each from low-to-high activation. A total of 64 distinct medial surface postures (4 TA × 4 CT × 4 LCA/IA levels) were captured using high-speed video. Using a custom 3D interpolation algorithm, the medial surface shape was reconstructed.

Results

Combined activation of ILMs yielded a range of unique pre-phonatory postures. Both LCA/IA and TA activation adducted the vocal fold but with greater contribution from TA. The transition from a convergent to a rectangular glottal shape was primarily mediated by TA muscle activation but LCA/IA and TA together resulted in a smooth rectangular glottis compared to TA alone, which caused rectangular glottis with inferomedial bulging. CT activation resulted in a lengthened but slightly abducted glottis.

Conclusions

TA was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the LCA/IA. CT contributed minimally to vocal fold medial shape but elongated the glottis. These findings further refine laryngeal posture goals in surgical correction of glottic insufficiency.

Level of Evidence

N/A, Basic science Laryngoscope, 2022

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Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant

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Abstract

Pediatric and adolescent and young adult (AYA) patients who receive many blood product transfusions, such as individuals with sickle cell disease (SCD), severe aplastic anemia (SAA) or indolent hematologic malignancies, are at high risk for developing donor-specific antibodies (DSA). DSAs with mean fluorescence intensity (MFI) greater than 5000 have been associated with significant graft failure, but lower MFI values between 2000 and 5000 may result in poor graft function after hematopoietic cell transplant (HCT). Desensitization strategies have been developed to reduce the DSA burden in HCT recipients before graft infusion, but the experience with these strategies in the pediatric and AYA populations is not well described in the literature. Here, we describe our experience with successful desensitization by using a combination of treatment strategies in five pediatric and AYA patients, including a novel use of daratumumab in a young adult patient who had refractory DSAs and had s uffered serious side effects from conventional desensitization strategies. The presence of elevated DSAs in pediatric and AYA recipients of a human leukocyte antigen (HLA)-mismatched haploidentical HCT can be overcome by a multipronged treatment strategy.

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Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers

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Abstract

The susceptibility of cells to DNA damage and their DNA repair ability are crucial for cancer therapy. Homologous recombination is one of the major repairing mechanisms for DNA double-strand breaks. Approximately half of ovarian cancer (OvCa) cells harbor homologous recombination deficiency (HRD). Considering that HRD is a major hallmark of OvCas, scholars proposed HRD scoring to evaluate the HRD degree and guide the choice of therapeutic strategies for OvCas. In the last decade, synthetic lethal strategy by targeting poly (ADP-ribose) polymerase (PARP) in HR-deficient OvCas has attracted considerable attention in view of its favorable clinical effort. We therefore suggested that the uses of other DNA damage/repair-targeted drugs in HR-deficient OvCas might also offer better clinical outcome. Here, we reviewed the current small molecule compounds which targeted DNA damage/repair pathways, and discussed the HRD scoring system to guide their clinical uses.

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Neuropathic pain prevalence and risk factors in head and neck cancer survivors

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Abstract

Background

Neuropathic pain (NP) is a debilitating symptom among head and neck cancer (HNC) survivors although few large studies report its prevalence and associated risk factors.

Methods

A cross-sectional survey assessing demographic, behavioral, and clinical risk factors for NP. NP was assessed using the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS).

Results

Forty-five percent (227/505) reported having pain including 13.7% (69/505) who were positive for S-LANSS. Reported pain sites were in the regions of the head and oral cavity (46.2%) and neck and throat (41.5%). Despite a higher self-reported use of analgesic medication (NP+ = 41.2%; NP− = 27.4%; p = 0.020) and alternative pain therapies (NP+ = 19.1%; NP− = 8.4%; p = 0.009), severe pain was more prevalent among those with NP (N+ = 23.2%; NP− = 13.3%; p = 0.004). Adjusted for opioid medications, ethnicity/race, age, surgery, depression, and comorbidities were risk factors for NP.

Conclusion

NP remains prevalent in HNC survivors highlighting the importance of routine pain surveillance.

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

The human frontal cortex of SAD, FAD, and APOEch is characterized by specific astrocyte phenotypes which define the integrity of Gliovascular unit. ApoE3ch mutation in an E280A carrier might be related to the promotion of astrocytic and gliovascular homeostatisis despite the massive load of Aβ. This study provides new insights into the potential relevance of the gliovascular unit in the development and protection of AD.


Abstract

In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.

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