UNASSIGNED: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP).
UNASSIGNED: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed.
UNASSIGNED: The mean follow-up was 17.6 months. After the 3rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 (p < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR.
UNASSIGNED: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation.

UNASSIGNED: Most neovascular age-related macular degeneration treatments involve long-term follow-up of disease activity. Home monitoring would reduce the burden on patients and those they depend on for transport, and release clinic appointments for other patients. The study aimed to evaluate three home-monitoring tests for patients to use to detect active neovascular age-related macular degeneration compared with diagnosing active neovascular age-related macular degeneration by hospital follow-up.
UNASSIGNED: There were five objectives: Estimate the accuracy of three home-monitoring tests to detect active neovascular age-related macular degeneration. Determine the acceptability of home monitoring to patients and carers and adherence to home monitoring. Explore whether inequalities exist in recruitment, participants\' ability to self-test and their adherence to weekly testing during follow-up. Provide pilot data about the accuracy of home monitoring to detect conversion to neovascular age-related macular degeneration in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Describe challenges experienced when implementing home-monitoring tests.
UNASSIGNED: Diagnostic test accuracy cohort study, stratified by time since starting treatment.
UNASSIGNED: Six United Kingdom Hospital Eye Service macular clinics (Belfast, Liverpool, Moorfields, James Paget, Southampton, Gloucester).
UNASSIGNED: Patients with at least one study eye being monitored by hospital follow-up.
UNASSIGNED: Detection of active neovascular age-related macular degeneration by an ophthalmologist at hospital follow-up.
UNASSIGNED: KeepSight Journal: paper-based near-vision tests presented as word puzzles. MyVisionTrack®: electronic test, viewed on a tablet device. MultiBit: electronic test, viewed on a tablet device. Participants provided test scores weekly. Raw scores between hospital follow-ups were summarised as averages.
UNASSIGNED: Two hundred and ninety-seven patients (mean age 74.9 years) took part. At least one hospital follow-up was available for 317 study eyes, including 9 second eyes that became eligible during follow-up, in 261 participants (1549 complete visits). Median testing frequency was three times/month. Estimated areas under receiver operating curves were < 0.6 for all index tests, and only KeepSight Journal summary score was significantly associated with the lesion activity (odds ratio = 3.48, 95% confidence interval 1.09 to 11.13, p = 0.036). Older age and worse deprivation for home address were associated with lower participation (χ2 = 50.5 and 24.3, respectively, p < 0.001) but not ability or adherence to self-testing. Areas under receiver operating curves appeared higher for conversion of fellow eyes to neovascular age-related macular degeneration (0.85 for KeepSight Journal) but were estimated with less precision. Almost half of participants called a study helpline, most often due to inability to test electronically.
UNASSIGNED: Pre-specified sample size not met; participants\' difficulties using the devices; electronic tests not always available.
UNASSIGNED: No index test provided adequate test accuracy to identify lesion diagnosed as active in follow-up clinics. If used to detect conversion, patients would still need to be monitored at hospital. Associations of older age and worse deprivation with study participation highlight the potential for inequities with such interventions. Provision of reliable electronic testing was challenging.
UNASSIGNED: Future studies evaluating similar technologies should consider: Independent monitoring with clear stopping rules based on test performance. Deployment of apps on patients\' own devices since providing devices did not reduce inequalities in participation and complicated home testing. Alternative methods to summarise multiple scores over the period preceding a follow-up.
UNASSIGNED: This trial is registered as ISRCTN79058224.
UNASSIGNED: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/97/02) and is published in full in Health Technology Assessment; Vol. 28, No. 32. See the NIHR Funding and Awards website for further award information.
Treatment for neovascular age-related macular degeneration, the most common cause of sight loss in those over 50 years, involves regular eye injections and frequent follow-up appointments. This is inconvenient for patients and causes capacity issues in the hospital eye service. Finding tests that could be undertaken at home that could detect if a further injection and hospital appointment was required or not would increase capacity to see those at highest risk of sight loss and also reduce the burden on patients and their carers. We investigated three different visual function tests, one paper-based and two applications on an iPod TouchTM tablet (Apple, Cupertino, CA, USA). We wanted to see if they could detect an increase in disease activity that would require treatment, compared to the decision by a retinal specialist at a traditional hospital eye outpatient visit based on clinical examination and retinal imaging. To encourage those without a smartphone or home internet to participate, we provided both an iPod Touch and Mobile Wireless-Fidelity device with a mobile contract. None of the tests performed well enough to safely monitor patients at home. Those who were willing to participate tended to be younger, had previous experience of using smartphones, sending e-mail and internet access and were more well-off than those who chose not to participate. Some participants also experienced difficulties with the devices provided and successfully uploading the data which were not related to the extent of previous information technology experience. There were also significant technical challenges for the research team. The study helpline was used heavily, considerably more than we anticipated. These tests are not ready to be used in this context. Future studies involving mobile health technology need to carefully consider how to reach those unlikely to participate and provide sufficient technical support to support long-term follow-up.

OBJECTIVE: To assess the risk of developing pulmonary tuberculosis (TB) in accordance with prior history of COVID-19 infection.
BACKGROUND: Since the advent of the COVID-19 pandemic much discussion has been had on the possible role it might play on global efforts to combat TB; most, focusing on the pandemic\'s impact on health care systems\' capabilities to manage TB cases. Mechanisms have also been proposed by which the COVID-19 infection may directly affect individuals\' chance of developing TB infection. Cases have been reported with a history of COVID-19 infection preceding a diagnosis of TB, evidencing its possible role as a risk factor for the disease.
METHODS: A case-control study was conducted enrolling patients diagnosed with pulmonary TB in the absence of major risk factors previous history of TB, (HIV) human immunodeficiency virus infection), end-stage renal disease, organ transplants, and use of immunosuppressive agents) for developing TB. Each patient was age and sex matched with one healthy control. Data regarding prior COVID-19 infection, diabetes, and smoking status as well as the use of corticosteroids and Tocilizumab for the treatment of COVID-19 infection was obtained. Bivariate analysis was conducted and variables with a likely association with TB status were entered in a multivariate model.
RESULTS: Bivariate analysis demonstrated a significant relationship between prior COVID-19 infection and TB (95% confidence interval = 1.1-22.8, odds ratio [OR] = 5). Among other variables the severity of COVID-19 infection was found to have a likely association with TB status (p = .125). In a multivariate model, prior COVID-19 infection per se, was not found to be significantly associated with TB (p = .12, OR = 4.5).
CONCLUSIONS: There seems to be an association between prior history of COVID-19 and a future diagnosis of TB partially linked to the severity of disease. The findings of the current study may serve as a basis for further studies to determine the need for and efficacy of measures to follow-up COVID-19 patients at an increased risk for developing TB.

暂无摘要。

Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM).
We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM.
The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death.
Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.

Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.
We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.
Thirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.
Our study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.
https://clinicaltrials.gov, identifier NCT02227641.

The most favorable targets for retrospectively determining human exposure to organophosphorus pesticides, insecticides, retardants, and other industrial organophosphates (OPs) are adducts of OPs with blood plasma butyrylcholinesterase (BChE) and human serum albumin (HSA). One of the methods for determining OP exposure is the reactivation of modified BChE using a concentrated solution of KF in an acidic medium. It is known that under the action of fluoride ion, OPs or their fluoroanhydrides can be released not only from BChE adducts but also from the adducts with albumin; however, the contribution of albumin to the total pool of released OPs after plasma treatment with KF has not yet been studied. The efficiency of OP release can be affected by many factors associated with the experimental technique, but first, the structure of the adduct must be taken into account. We report a comparative analysis of the structure and conformation of organophosphorus adducts on HSA and BChE using molecular modeling methods and the mechanism of OP release after fluoride ion exposure. The conformational analysis of the organophosphorus adducts on HSA and BChE was performed, and the interaction of fluoride ions with modified proteins was studied by molecular dynamics simulation. The geometric and energy characteristics of the studied adducts and their complexes with fluoride ion were calculated using molecular mechanics and semiempirical approaches. The structural features of modified HSA and BChE that can affect the efficiency of OP release after fluoride ion exposure were revealed. Using the proposed approach, the expediency of using KF for establishing exposure to different OPs, depending on their structure, can be assessed.

BACKGROUND: Prospective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis.
METHODS: HEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+).
RESULTS: From August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0-609). Median follow-up was 3.1 years (2.1-4.0). Median number of cycles of anti-CD20 antibodies was 6 (3-7), with a cumulative dose of 8.5 g (5.8-11.2) of rituximab and 3 g (1.8-3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies.
CONCLUSIONS: In this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.

BACKGROUND: Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab.
METHODS: A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin\'s lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups.
RESULTS: In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41-12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4-16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99-26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4-33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999).
CONCLUSIONS: Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.
BACKGROUND: ClinicalTrials.gov Identifier: NCT02585947.

To assess the clinical relevance of varicella zoster virus (VZV) lung detection among patients hospitalized in intensive care unit (ICU).
We present a monocentric retrospective cohort study from 2012 to 2020. VZV genome was detected in bronchoalveolar lavage (BAL) fluid by real-time PCR.
Twelve of 1389 (0.8%) patients exhibited VZV lung detection, corresponding to an incidence of 13.4 (95% confidence interval [CI] 5.8-21.0) per 100 person-years. Immunosuppression and prolonged ICU stay constituted the main risks factors. VZV detection was not associated with pulmonary deterioration but associated with a risk of shingles occurrence during the following days.
VZV lung detection is a rare event among ICU patients, occurring mostly in immunocompromised patients with prolonged ICU stay. Due to its scarcity and the lack of association with pulmonary failure, a targeted approach to the VZV lung detection diagnosis may allow a significant cost saving without affecting the quality of patients care.