METHODS: The clinical records of five patients exhibiting ocular manifestations and testing positive for serum MPO-ANCA were retrospectively reviewed.
RESULTS: Three out of five patients were female. The youngest patient was aged 26, whereas the eldest was 83 years old. 80% (n = 4) of them had purely anterior segment involvement, with the commonest manifestation being peripheral ulcerative keratitis and scleritis. Only one patient had posterior segment involvement, specifically posterior ischemic optic neuropathy. Two patients demonstrated unilateral involvement. There was only one patient diagnosed with systemic involvement, presenting as mixed nephrotic and nephritic syndrome, who required a course of intravenous methylprednisolone during the active stage. Three patients required second-line immunosuppressants throughout the course due to frequent relapse.
CONCLUSION: Anterior segment ocular manifestations are not uncommon and can be the initial presentation of p-ANCA-associated vasculitis (AAV). Therefore, its evaluation should be considered in establishing the diagnosis of AAV, a life-threatening disease.
OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence.
STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up.
RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure.
CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.
METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis.
RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC
MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.
CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
MATERIALS AND METHODS: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs).
RESULTS: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09-17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81-15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39-25.89]; p<0.01).
CONCLUSIONS: This SRMA indicates that ASA positivity is significantly higher among men with varicocele when tested by direct method (MAR) or indirect method (ELISA). This data suggests an immunological pathology in infertile men with varicocele and may have implications for the management of these patients.
OBJECTIVE: To develop a diagnostic approach that combines measurements of cellular and serologic autoimmunity.
METHODS: We recruited 71 controls and 101 pediatric patients with PIRD with autoimmunity. Flow cytometry was used to measure CD4+CXCR5+ T cells expressing the chemokine receptors CXCR3 and/or CCR6. IgG and IgA autoantibodies were quantified in 56 patients and 20 controls using a microarray featuring 1616 full-length, conformationally intact protein antigens. The 97.5th percentile in the controls serves as the upper limit of normal for percentages of cTfh cells, CD4+CXCR5+ T cells expressing CXCR3 and/or CCR6, and autoantibody intensity and number.
RESULTS: We found that 27.7% of patients had increased percentages of CD4+CXCR5+PD1+ cTfh cells and 42.5% had increased percentages of CD4+CXCR5+ cells expressing CXCR3 and/or CCR6. Patients had significantly more diverse IgG and IgA autoantibodies than controls and 37.5% had increased numbers of high-titer autoantibodies. Integrating measurements of cTfh cells, CD4+CXCR5+ T cells with CXCR3 and/or CCR6, and numbers of high-titer autoantibodies had 71.4% sensitivity (95% CI: 0.5852 - 0.8158) and 85% specificity (95% CI: 0.6396 - 0.9476) for patients with PIRD compared to controls.
CONCLUSION: By integrating CD4+ T cell phenotyping and total burden of autoantibodies, this approach provides additional tools for the diagnosis of PIRD lacking clinical diagnostic criteria.
DESIGN: An online survey was disseminated through the British Academy of Audiology and ENT UK.
STUDY SAMPLE: A total of 191 hearing healthcare professionals responded to the survey.
RESULTS: Overall, while 63% of the respondents considered themselves to be adequately informed about APD, only 4% viewed themselves as very informed on the topic. Fewer than half of the respondents report screening (31%), diagnosing (14%), or managing (36%) cases of APD. For screening APD, professionals most commonly use auditory processing tests in adults and take case histories in children, whereas routine audiological procedures are the primary method for diagnosing APD in both adults and children. Although modifying the listening environment is a widely recommended management strategy for APD, half of the respondents indicated that a diagnosis of APD has no implications for patient management.
CONCLUSIONS: There is a critical need to promote APD-related training to ensure they can provide appropriate referrals and management.
METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs.
RESULTS: Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97-0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24-2.64, and HR = 3.79, 95% CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09-11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03-6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%).
CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.
OBJECTIVES: To explore the experiences and preferences of Malaysian patients with advanced cancer.
DESIGN: Qualitative study of semi-structured interviews with thematic analysis.
SETTING/SUBJECTS: Purposive sampling of 19 patients with Stage 4 cancer recruited from inpatient and outpatient settings in National Cancer Institute Malaysia.
RESULTS: Three major themes emerged in the exploration of patients' experiences and care preferences in facing advanced cancer namely: 1) Dealing with poor prognosis 2) Spirituality as a source of strength and 3) Enablers of advance care planning.
CONCLUSION: This study highlighted the preference for healthcare providers to be culturally sensitive during end-of-life care discussion and the need for improved spiritual care for Malaysian patients with advanced cancer. Further studies exploring the role of spiritual and cultural factors in advance care planning among Malaysians would be helpful in guiding these efforts.
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AIM OF REVIEW: The review encapsulates the transformative trajectory of green CDs as future anticancer nanomedicine, poised to redefine the strategies employed in the ongoing fight against cancer.
KEY SCIENTIFIC CONCEPTS OF REVIEW: The versatility of CDs was rooted in their various synthesis approaches and sustainable strategies, enabling their adaptability for diverse therapeutic uses. In vitro studies had showcased CDs' selective cytotoxicity against cancer cells while sparing healthy counterparts, forming the basis for targeted therapeutic potential. This selectivity had been attributed to the reactive oxygen species (ROS) generation, which opened avenues for targeted interventions. The role of CDs in combination therapies, synergizing with chemotherapy, radiotherapy, and targeted approaches was then investigated to heighten their anticancer efficacy. Notably, in vivo studies highlight CDs' remarkable biocompatibility and minimal side effects, endorsing their translational promise. Integration with conventional cancer treatments such as chemotherapy, radiotherapy, and immunotherapy amplified the versatility and effectiveness of CDs. The exploration of CDs' applications in photo-induced treatments further solidified their significance, positioning them as photosensitizers (PS) in photodynamic therapy (PDT) and photothermal agents (PA) in photothermal therapy (PTT). In PDT, CDs triggered the generation of ROS upon light exposure, facilitating cancer cell elimination, while in PTT, they induced localized hyperthermia within cancer cells, enhancing therapeutic outcomes. In vitro and in vivo investigations validated CDs' efficacy in PDT and PTT, affirming their potential for integration into combination therapies. Looking ahead, the future of CDs in anticancer treatment encompasses bioavailability, biocompatibility, synergistic treatments, tumor targeting, artificial intelligence (AI) and robotics integration, personalized medicine, and clinical translation. This transformative odyssey of CDs as future anticancer agents is poised to redefine the paradigm of cancer treatment strategies.
MATERIALS AND METHODS: Using a thematic review framework, a systematic literature search was conducted in two electronic databases (Scopus and WoS) using established criteria. Thematic analysis was done using ATLAS.ti 23 to identify prominent themes, patterns and trends.
RESULTS: A total of 180 documents were found. Twenty-five articles met the inclusion criteria. A thematic review of these 25 articles identified 13 initial codes, which were been clustered into four themes: detection and evaluation; intervention; toy/game category; and design characteristics. The word "Cognitive" appears most frequently in documents according to word cloud.
CONCLUSIONS: Therapeutic toys and games are used to detect and as an intervention for AD. Most of the current studies focused on specific cognitive functions. More research is needed about play therapy for neuropsychiatric symptoms. This thematic review also proposed a conceptual framework for designing toys and games tailored to the needs of the elderly with AD, offering valuable insights to future researchers focusing on this domain.
METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated.
RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 μg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 μg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 μg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity.
CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.
METHODS: It was a retrospective cohort study of prospectively submitted data by 44 Malaysian NICUs participating in the Malaysian National Neonatal Registry. All VLBW neonates of gestation <32 wk born in 2015-2020 and survived to discharge were included.
RESULTS: Of 11768 survivors, 90.5% (n = 10436) had ROP screening; 16.1% (1685/10436) had ROP. ROP was significantly more common in neonates <28 wk gestation (extremely preterm, EPT) than ≥28 wk gestation (37.7% vs. 9.7%; p <0.001), and more common in those with birthweight <1000 g (extremely low birthweight, ELBW) than ≥1000 g (32.9% vs. 9.1%; p <0.001). Multiple logistic regression analysis showed that the significant independent factors associated with increased risk of ROP were ELBW, EPT, Indian ethnic group, vaginal delivery, mechanical ventilation >5 d, high frequency ventilation, total parenteral nutrition, late-onset sepsis, bronchopulmonary dysplasia, and intraventricular hemorrhage. Receiving oxygen therapy at birth was associated with significantly lower risk of ROP.
CONCLUSIONS: The incidence and severity of ROP increased with decreasing gestation and birthweight. Prolonged duration of oxygen therapy, infection, invasive respiratory support, and conditions commonly causing fluctuations of oxygenation were significant factors associated with increased risk of ROP. Receiving oxygen at birth did not increase risk.
METHODS: RPE, heart rate (HR), and oxygen uptake (V˙O2) data were retrospectively extracted from 3 lab-based crossover studies, with a pooled sample size of 45 adolescents, performing either cycling-based or running-based HIIE sessions. Within-participant correlations were calculated for RPE-HR and RPE-V˙O2, and receiver operator characteristic curve analysis was used to establish RPE cut points.
RESULTS: The results showed that RPE-HR demonstrated acceptable criterion validity (r = .53-.74, P < .01), while RPE-V˙O2 had poor validity (r = .40-.48, P < .01), except for HIIE at 100% peak power (r = .59, P < .01). RPE cut points of 4 and 5 were established in corresponding to HR/V˙O2 based thresholds.
CONCLUSION: RPE has some utility in evaluating intensity during lab-based running or cycling HIIE in adolescents. Future studies should expand the validation and calibration of RPE for prescribing and monitoring HIIE in children and adolescents in field-based contexts.
METHODS: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations.
RESULTS: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs.
CONCLUSION: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.