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

alexandrossfakianakis shared this article with you from Inoreader Virologic failure following low-level viremia and viral blips during antiretroviral therapy: results from a European multicenter cohort via Clinical Infectious Diseases Advance Access 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. View on Web

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DETECTION OF SARS‐COV‐2 RNA AND ANTIBODIES IN BREAST MILK OF INFECTED MOTHERS

alexandrossfakianakis shared this article with you from Inoreader DETECTION OF SARS‐COV‐2 RNA AND ANTIBODIES IN BREAST MILK OF INFECTED MOTHERS via Journal of Medical Virology Abstract The SARS-CoV-2 outbreak in December 2019 brought many challenges to be addressed. One concerns the possible transmission of the virus and protective antibodies against SARS-CoV-2 to newborns through breastfeeding. The aim of this study was the detection of SARS-CoV-2 RNA and antibodies in the milk of SARS-CoV-2 positive mothers. Milk and blood samples were collected from twelve women with SARS-CoV-2 positive nasopharyngeal swabs. Viral RNA was investigated by RT-PCR, and the presence of IgA, IgM, and IgG anti-SARS-CoV-2 was evaluated in both breast milk and maternal blood. All milk samples showed negative results for SARS-CoV-2 RNA. Eight women (66%) had a detectable level of anti -SARS-CoV-2 IgA in their milk. Of this group, only one sample presented simultaneously serum antiviral IgM and IgG while other three samples showed only anti-SARS-CoV-2 IgG. The remaining four mothers with anti-SARS-CoV-2 IgA in their breast milk had no serum antibodies again st SARS-CoV-2. Finally, four mothers (34%) did not have any anti-SARS-CoV-2 antibodies in breast milk and serum, except one mother who had antiviral IgG and IgA in serum. Our results suggest that breastfeeding of SARS-CoV-2 infected mothers is safe and should be encouraged as breast milk transmits maternal antiviral antibodies which protect the infant while its immune system is immature. This article is protected by copyright. All rights reserved. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Antagonistic, synergistic, and additive antibacterial interaction between ciprofloxacin and amoxicillin against Staphylococcus aureus via Fundamental & Clinical Pharmacology 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. View on Web

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The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

alexandrossfakianakis shared this article with you from Inoreader The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review via Journal of Oral Rehabilitation Abstract Background Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD-related pain, which suggests that alterations in autonomic tone may contribute to this pain condition. Objectives This narrative review examines the association between altered autonomic function and pain in TMD. Methods Relevant articles were identified by searching PubMed and through the reference list of those studies. Results TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD-related pain through β2 adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD-related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β2 adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β2 adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α1 adrenergic receptor activation has been found to induce mechanical sensitization. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α2 adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism. Conclusion Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader Opsoclonus‐myoclonus syndrome associated with neuroblastoma: Insights into antitumor immunity via Pediatric Blood & Cancer 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. View on Web

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Human papillomavirus vaccination uptake among childhood cancer survivors

alexandrossfakianakis shared this article with you from Inoreader Human papillomavirus vaccination uptake among childhood cancer survivors in Western New York via Pediatric Blood & Cancer Abstract Introduction The risk of human papillomavirus (HPV)-associated cancers is significantly higher among survivors of a childhood cancer compared to the general population. Despite this, their HPV vaccine uptake rates are lower. We examined factors related to HPV vaccine uptake among childhood cancer survivors from Western New York over 13 years following the introduction of HPV vaccines. Methods Retrospective review of patients diagnosed with invasive or noninvasive cancerous conditions at age 9 or younger treated at Roswell Park Oishei Children's Cancer and Blood Disorder Program. We matched vaccine date information for patients aged 9–26 years between 2006 and 2020 from the New York State Immunization Information System. Demographic and cancer-related information was abstracted from electronic medical records. Cumulative vaccine uptake was assessed by Kaplan–Meier and Cox proportional hazards regression models. Results A total of 284 patients were included in the analyses. Most were non-Hispanic/White (80.3%) and resided in a metropolitan area (81.7%). Approximately half had leukemia or lymphoma (54.9%), and most received chemotherapy. Females were more likely to initiate the HPV vaccine and did so sooner (median = 5.5 years) than males (median = 5.7 years; log-rank p = .301). Patients who were older at vaccine eligibility and males who received blood product transfusions were significantly less likely to initiate the HPV vaccine. Conclusion While rates of HPV vaccine initiation have been increasing with time among childhood cancer survivors, they remain low overall, with differences seen by treatment and diagnosis. Our findings support the need for further research to optimize HPV vaccine delivery in cancer care. View on Web

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Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls

alexandrossfakianakis shared this article with you from Inoreader Failure modes and effects analysis of pediatric I‐131 MIBG therapy: Program design and potential pitfalls via Pediatric Blood & Cancer 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. View on Web

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