Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study.

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010-2020 consisting of two nucleos(-t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50-499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non-adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI- (n = 5119; 20.9%), PI- (n = 8935; 36.4%), and NNRTI-use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non-blip VLs were RNAneg (no RV) (n = 15 326; 63.4%), 1-19 cp/mL (n = 6318; 26.1%), 20-49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNAneg in all VLs assessed. RV 1-19 cp/mL and 20-49 cp/mL (vs. RNAneg ) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98-3.58 and 3.41-7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin.

Pneumococcal pericarditis in a patient with newly diagnosed diabetes mellitus: a case report.

BACKGROUND: After the introduction of antibiotics, pneumococcal pericarditis has become a rare finding. However, this severe condition with high mortality and complication rates requires rapid recognition and intervention. Herein, we describe a patient that presents with this rare disease resulting in an unusual, fatal outcome. CASE PRESENTATION: A previously healthy, 68-year-old, Caucasian male presented with progressive fatigue, dyspnea, and appetite loss since 12 days. He was diagnosed with diabetes mellitus 5 days before presentation but had not started treatment. After echocardiography revealed pericardial effusion, pericardiocentesis was performed with immediate drainage of a large volume of purulent fluid suggestive of bacterial pericarditis. On the basis of cultures showing Streptococcus pneumoniae as the causative organism, a regimen of intravenous penicillin was initiated. Additionally, antidiabetic drugs were started as his diabetes also predisposed him to invasive infectious disease. No other primary source of the infection, such as pneumonia, was found. Though the patient was found to be severely ill on admission, his clinical condition improved. A total of 1235 mL of pericardial fluid was drained, and adequate drainage was confirmed by daily, bedside echocardiography. However, 6 days post-admission, the patient suddenly developed intrapericardial bleeding with blood clot formation on the right chamber with subsequent cardiac tamponade. With the blood clot precluding adequate drainage through the catheter, the patient suffered cardiac arrest and died before surgical intervention could be attempted. CONCLUSIONS: Pneumococcal pericarditis is a very rare but life-threatening disease that necessitates immediate intervention with antibiotics and drainage of the pericardial effusion. Thus, although symptoms may be variable and aspecific, early recognition of this condition is critical. The present case illustrates the presentation, diagnosis, and clinical course of a patient presenting with pneumococcal pericarditis in current clinical practice. Through this report, we aimed to increase awareness among clinicians both of the existence of this phenomenon and of its uncertain clinical course. As is highlighted by the case, patients with pneumococcal pericarditis are at high risk for complications and should be closely monitored.

Hepatitis B virus-specific CD4 T cell responses differentiate functional cure from chronic surface antigen+ infection.

BACKGROUND & AIMS: With or without antiviral treatment, few individuals achieve sustained functional cure of chronic hepatitis B virus (HBV) infection. A better definition of what mediates functional cure is essential for improving immunotherapeutic strategies. We aimed to compare HBV-specific T cell responses in patients with different degrees of viral control. METHODS: We obtained blood from 124 HBV-infected individuals, including those with acute self-limiting HBV infection, chronic infection, and chronic infection with functional cure. We screened for HBV-specific T cell specificities by ELISpot, assessed the function of HBV-specific T cells using intracellular cytokine staining, and characterized HBV-specific CD4 T cells using human leukocyte antigen (HLA) class II tetramer staining, all directly ex vivo. RESULTS: ELISpot screening readily identified HBV-specific CD4 and CD8 T cell responses in acute resolving infection compared with more limited reactivity in chronic infection. Applying more sensitive assays revealed higher frequencies of functional HBV-specific CD4 T cells, but not CD8 T cells, in functional cure compared to chronic infection. Function independent analysis using HLA multimers also identified more HBV-specific CD4 T cell responses in functional cure compared to chronic infection, with the emergence of CD4 T cell memory both after acute and chronic infection. CONCLUSIONS: Functional cure is associated with higher frequencies of functional HBV-specific CD4 memory T cell responses. Thus, immunotherapeutic approaches designed to induce HBV functional cure should also aim to improve CD4 T cell responses. LAY SUMMARY: Immunotherapy is a form of treatment that relies on harnessing the power of an individual's immune system to target a specific disease or pathogen. Such approaches are being developed for patients with chronic HBV infection, in an attempt to mimic the immune response in patients who control HBV infection spontaneously, achieving a so-called functional cure. However, what exactly defines protective immune responses remains unclear. Herein, we show that functional cure is associated with robust responses by HBV-specific CD4 T cells (a type of immune cell).

Lower Incidence of HIV-1 Blips Observed During Integrase Inhibitor-Based Combination Antiretroviral Therapy.

BACKGROUND: As the nature of viral blips remains unclear, their occurrence often leads to uncertainty. This study compares blip incidence rates during treatment with different combination antiretroviral therapy anchors. SETTING: Retrospective cohort study in a tertiary hospital. METHODS: All antiretroviral regimens between 2010 and 2020 containing 2 nucleos(-t)ide reverse transcriptase inhibitors and 1 anchor in virologically suppressed people living with HIV (PLWH) from our center were evaluated for the occurrence of blips [isolated viral loads (VLs) 50-499 copies/mL between measurements <50 copies/mL]. Factors associated with blips were identified using multivariable generalized estimating equation-based negative binomial models. The relationship between blips and either persistent low-level viremia (consecutive VLs ≥ 50 copies/mL not classified as failure) or virologic failure (consecutive VLs ≥ 200 or 1 VL ≥ 500 copies/mL) was also evaluated. RESULTS: In total, 308 blips occurred during 3405 treatment courses in 1661 PLWH. Compared with a non-nucleoside reverse transcriptase inhibitor anchor, blip incidence was higher for protease inhibitors (incidence rate ratio 1.37; 95% confidence interval 1.05 to 1.78) and lower for integrase inhibitors (INSTIs) (incidence rate ratio 0.64; 95% confidence interval: 0.43 to 0.96). In addition, blips were associated with higher zenith VL, higher VL test frequency, and shorter time since antiretroviral therapy initiation. PLWH experiencing blips were more likely to demonstrate persistent low-level viremia but not virologic failure. Blips led to extra consultations and measurements. CONCLUSIONS: INSTI-based regimens display a low number of blips. Although we found no correlation with virologic failure, the occurrence of blips led to an increased clinical burden. Further research is needed to elucidate the implications and underlying mechanisms of these findings.

Use of quality indicators in neuroblastoma treatment: A feasibility assessment.

BACKGROUND: Quality indicators (QIs) may be used to monitor the quality of neuroblastoma (NBL) care during treatment, in addition to survival and treatment toxicity, which can only be evaluated in the years after treatment. The present study aimed to assess the feasibility of a new set of indicators for the quality of NBL therapy. PROCEDURE: Seven QIs have been proposed based on literature and consensus of experts: (a) duration of complete diagnostic work-up, (b) prescription of thyroid prophylaxis before metaiodobenzylguanidine imaging, (c) treatment intensity, (d) use of tumor board meetings, (e) number of outpatient visits and sedation procedures during follow-up, (f) protocolled follow-up, and (g) required apheresis sessions. A retrospective data analysis from October 2014 to November 2017 including all patients with NBL in the centralized Princess Máxima Center in the Netherlands was performed to assess these parameters and determine practicality of measurement. RESULTS: A total number of 72 patients (aged between 2 weeks and 15 years) were analyzed. Adherence to all QIs could be determined for all eligible patients using their electronic medical records. Three indicators were compared over time, and an increase in adherence was observed. CONCLUSIONS: Assessment of QIs in neuroblastoma treatment is feasible. Seven new QIs were found to be feasible to measure and showed improvement over time for three indicators. Monitoring of these QIs during treatment may provide tools for quality improvement activities and comparisons of treatment quality over time or between centers. Further study is required to investigate their association with long-term outcomes.

Examining the Potential Relationship Between Multidisciplinary Team Meetings and Patient Survival in Pediatric Oncology Settings: A Systematic Review.

The organization of multidisciplinary team meetings (MTMs) has become standard practice in pediatric oncology and is widely felt to improve communication, knowledge, and patient care. Although the impact of MTMs on survival in adult oncology has been extensively researched, the potential benefits of survival for pediatric cancer patients are still unclear. This systematic review aimed to examine the impact of MTMs on survival in pediatric oncology settings. Relevant studies were identified by searching MEDLINE/PubMed, EMBASE, and the Cochrane Library databases up to January 2020, resulting in 325 unique records. After the title/abstract and full-text screening, 5 studies were included. All of the included studies (one prospective and 4 retrospective cohort studies) described a difference in overall or event-free survival when comparing patients who were discussed in MTMs with non-MTM patients. This association was statistically significant in 3 studies. The quality of the studies was strongly affected by their design. Because of the small number of studies in combination with high clinical and methodological heterogeneity, this review was unable to definitively assert a causal relationship between MTMs and survival in pediatric cancer patients. Further research is needed to explore this relationship and allow cost-benefit analyses, so that time and resources are optimally spent to deliver the best possible care to childhood cancer patients.

Translational Medicine in the Era of Social Media: A Survey of Scientific and Clinical Communities.

Background: The integration of new scientific discoveries into clinical practice costs considerable time and resources. With the increased use of social media for scientific communication, new opportunities arise to "bridge the gap" in translational medicine. The present study aimed to investigate how medical professionals access scientific information and understand their view on the role of social media in translational medicine. Methods: A questionnaire regarding (i) the use of social media for scientific updates, (ii) the opportunities and challenges of social media for translational medicine, (iii) social media function Chatbot, and (iv) participant demographics was developed. The survey link was posted online from February, 2018, until April, 2018. Results: A total of 555 professionals responded to the survey. Respondents identified themselves predominantly as researcher/scientists (27%) or medical/biomedical students (15%). The majority of participants was employed at a university or research institute (59%), and most practiced either in Europe (48%) or in Asia (37%). Seventy-eight percent of respondents reported receiving most of scientific news and updates via non-social media options, such as journal websites and newspapers. Fifty-one percent of respondents believed that social media could contribute to closing the gap between scientific discovery and translation to medical application. The most crucial opportunity created by social media was found to be "connecting the right scientist to the right clinician." Participants rated "the translation of scientific finding to clinical practice is too fast before the safety is properly demonstrated" as the most crucial challenge. Half of the respondents were aware of their institutions policy on the professional use of social media. Only 2% of respondents had previously used Chatbot. Conclusions: Overall, medical professionals were positive about the idea that social media could contribute to the progress of translational medicine. However, it is clear that they are still being cautious about using social media for professional purposes. To fully harness the potential of social media on translational medicine, the medical community needs to be provided with educational programs, guidelines, and support infrastructure within social media.

Possibilities and Pitfalls of Social Media for Translational Medicine.

We live in an age where the sharing of scientific findings and ideas is no longer confined to people with access to academic libraries or scientific journals. Social media have permitted for knowledge and ideas to be shared with an unprecedented speed and magnitude. This has made it possible for research findings to have a greater impact and to be rapidly implemented in society. However, the spread of unfiltered, unreferenced, and non-peer-reviewed articles through social media comes with dangers as well. In this perspective article, we aim to address both the possibilities and pitfalls of social media for translational medicine. We describe how social media can be used for patient engagement, publicity, transparency, sharing of knowledge, and implementing findings in society. Moreover, we warn about the potential pitfalls of social media, which can cause research to be misinterpreted and false beliefs to be spread. We conclude by giving advice on how social media can be harnessed to combat the pitfalls and provide a new avenue for community engagement in translational medicine.