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Posterior Vitreous Detachment Determines the Clinical Impact of Fibrovascular Membrane Fibrosis After Anti-VEGF Treatment in Proliferative Diabetic Retinopathy: A Real-World Study
No full textMeng Zhao,1 Zhaoyang Wang,1,&ast; Lin Liu,1,&ast; Louise O’Toole,2 Jipeng Li1 1Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland&ast;These authors contributed equally to this workCorrespondence: Jipeng Li, Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email [email protected]: To investigate the relationship between posterior vitreous detachment (PVD) status and fibrovascular membrane (FVM) angio-fibrotic transformation following anti-VEGF therapy in advanced proliferative diabetic retinopathy (PDR), and their combined impact on disease progression and visual outcomes.Methods: This prospective real-world study enrolled 165 treatment-naïve PDR patients with vitreous hemorrhage (VH) and FVM who received intravitreal anti-VEGF injection followed by panretinal photocoagulation(PRP) when possible. PVD status and FVM characteristics were monitored during a median follow-up of 13.0 months. Cox proportional hazards and Kaplan-Meier analyses evaluated factors influencing visual prognosis and timing of surgical intervention.Results: FVM fibrosis occurred in 43% of patients, with distinct PVD-dependent patterns: predominantly in complete PVD cases, moderately in partial PVD, and rarely without PVD. Multivariate analysis identified macular involvement as the strongest risk factor for poor visual outcomes (HR=3.65), while PVD (HR=0.37) and FVM fibrosis (HR=0.023) were strongly protective. Patients with both PVD and FVM fibrosis maintained stable vision longest (median 28.5 months) and demonstrated significantly longer surgery-free survival (28.3 months) compared to those without either condition (3.2 months, p< 0.0001), who frequently presented with vitreoschisis and recurrent VH disproportionate to visible FVM grade.Conclusion: PVD status critically determines the clinical manifestation and prognosis of post-anti-VEGF FVM fibrosis in PDR. This PVD-dependent pattern challenges the conventional view that FVM fibrosis inevitably leads to “Crunch syndrome” and creates a risk stratification framework that can guide individualized surgical timing decisions, potentially improving functional outcomes in advanced PDR.Plain Language Summary: Proliferative diabetic retinopathy (PDR) is a serious complication of diabetes and a leading cause of blindness. It often involves the growth of abnormal blood vessels and membranes inside the eye, which can cause severe vision problems. Doctors frequently treat this condition by injecting medications called anti-VEGF agents, which slow the growth of these harmful vessels. However, sometimes these treatments cause the abnormal vessels and membranes to become fibrotic—meaning they harden and contract, potentially causing further issues.This study aimed to understand how a condition called posterior vitreous detachment (PVD), where the gel-like substance in the eye separates from the retina, influences the outcomes after anti-VEGF treatment. Researchers observed 165 patients with severe PDR who received anti-VEGF injections and monitored how their conditions changed over approximately one year.The study found that nearly half the patients experienced membrane fibrosis after treatment. Importantly, patients with a complete vitreous detachment showed better results, including less tractional damage to the retina and longer periods without needing surgery. Conversely, patients without vitreous detachment faced more severe complications, needed surgery sooner, and had worse vision outcomes.These results indicate that the presence of a vitreous detachment significantly impacts whether fibrosis will be beneficial or harmful after treatment. Understanding this relationship helps doctors predict outcomes more accurately and plan treatments better. Ultimately, this could lead to improved vision preservation and fewer surgical interventions for people with severe diabetic retinopathy.Keywords: proliferative diabetic retinopathy, real world study, posterior vitreous detachment, anti-VEGF, fibrovascular membran
Factors Associated with Patient Treatment Satisfaction in Diabetes Mellitus Care Using the DTSQs: A Nationwide Cross-Sectional Study in Saudi Arabia
No full textSaleh F Alqifari,1 Palanisamy Amirthalingam,1 Kousalya Prabahar,1 Khulood A Qasem,2 Fawaz E Alanazi,3 Tariq Alrasheed,4 Noura A Al-Ajlan,5 Ahmed Aljabri6 1Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 2College of Medicine, Sulaiman Alrajhi University, Al Bukairiyah, Saudi Arabia; 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 4Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia; 5Department of Pharmacy, Dr. Sulaiman Al Habib Hospital, Riyadh, Saudi Arabia; 6Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Saleh F Alqifari, Email [email protected]: Patient satisfaction is crucial in managing chronic diseases like diabetes mellitus (DM). This study aims to identify the key factors associated with patient satisfaction with DM treatment in the Kingdom of Saudi Arabia.Methods: This cross-sectional study collected data from 709 participants country-wide via an online survey. Participants included patients receiving care from public and private healthcare facilities offering primary or specialized diabetes care. Patient satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQs), with chi-square tests for HbA1c control and Mann–Whitney U-tests for comparisons of means between groups.Results: Governmental healthcare patients had higher satisfaction (Mean = 27.32, SD = 7.62) than private (Mean = 25.5, SD = 8.51) (p = 0.007). Patient treatment satisfaction was also greater in diabetes centers (Mean = 28.93, SD = 6.34), than in primary care (Mean = 25.45, SD = 8.51), (p= < 0.001). Although overall treatment satisfaction scores did not differ significantly between controlled and uncontrolled diabetes (p= 0.784), patients with controlled diabetes experienced significantly fewer hyperglycemic and hypoglycemic episodes, (p= < 0.001), and higher satisfaction with treatment flexibility (p= 0.006), diabetes understanding (p= 0.013) and willingness to recommend their treatment to others (p= < 0.001).Conclusion: Mode of healthcare delivery (public or private hospitals) and choice between primary care or diabetes centers was significantly associated with treatment satisfaction with greater satisfaction in governmental healthcare and specialized diabetes centers. Glycemic control, measured by HbA1c, showed no significant association with overall treatment satisfaction but was associated with specific item scores (including satisfaction with understanding and treatment flexibility). This study is among the first in Saudi Arabia to compare DM treatment satisfaction across different healthcare settings using the DTSQs. Recognizing these associations can provide healthcare professionals with valuable insights for more successful treatment of diabetes patients and ultimately improve patient outcomes.Keywords: treatment satisfaction, diabetes mellitus, healthcare delivery, glycated hemoglobin, HbA1c, diabetes treatmen
Strengthening Health Systems to Overcome Respiratory Infectious Diseases in Indonesia: A Comprehensive Review
No full textRano K Sinuraya,1,2 Auliya A Suwantika,1,2 Irma M Puspitasari1,2 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, IndonesiaCorrespondence: Rano K Sinuraya, Email [email protected]: Respiratory infectious diseases (RIDs) remain a persistent public health challenge in Indonesia, a vast archipelago with complex healthcare delivery and marked regional inequities. The COVID-19 pandemic revealed critical weaknesses in the country’s surveillance systems, diagnostic capacity, and outbreak response, underscoring the urgent need for stronger pandemic preparedness and a transition from a reactive, crisis-driven model to a proactive, prevention-focused health system. This study synthesizes existing literature, policy documents, and recent evaluation reports to assess Indonesia’s health system performance in RID management and to identify evidence-based priorities for reform. The analysis is structured around five health system components: (1) surveillance and early warning, (2) diagnostic and laboratory capacity, (3) healthcare workforce, (4) public health infrastructure and primary care, and (5) governance and financing. Indonesia demonstrates important strengths, including a nationwide network of more than 10,000 Primary Health Centers (Puskesmas) and proven vaccination campaign capacity. However, significant gaps persist: during COVID-19, Early Warning Alert and Response System (EWARS) reporting completeness dropped from 75% to 53%, rural and remote areas remain underserved by diagnostics, and health workforce distribution continues to be inequitable Priority reforms include scaling up point-of-care diagnostics across all Puskesmas, integrating fragmented surveillance platforms through SatuSehat, empowering community health workers with digital tools, and ensuring sustainable financing for preparedness. Medium-term strategies focus on workforce redistribution and the establishment of regional health security centers, while long-term priorities emphasize predictive health intelligence, resilient supply chains, and nationwide facility upgrades. Building a resilient, prevention-oriented system will require sustained political commitment, innovative financing, and cross-sectoral collaboration, positioning Indonesia not only to strengthen domestic health security but also to serve as a regional leader in epidemic preparedness.Keywords: respiratory infectious diseases, health system strengthening, pandemic preparedness, surveillance systems, Indonesi
The Critical Role of Follow-Up in Fracture Liaison Services for Geriatric Hip Fracture Patients: A Retrospective Cohort Study
No full textPurpose Fracture Liaison Services (FLS) have been developed as a coordinated, multidisciplinary programs designed to improve the identification and management of patients with fragility fractures, including hip fractures. This study aims to evaluate the impact of coordinator based FLS on medical treatment compliance and mortality in patients following hip fracture. Specifically, it seeks to evaluate the impact of routine follow-up post discharge on these outcomes. Methods Comparative retrospective cohort of following hip fracture patients for one year after surgery. First group with the complete FLS treatment and protocol and second group with partial FLS protocol without the routine clinical follow-up after discharge. Main clinical outcomes were osteoporosis medication compliance and morality rates. Results 347 participants, 182 (52.4%) without a coordinator follow-up and 165 (47.6%) with a coordinator follow-up. Patients with coordinator follow-up had better medication compliance 1 year following hip fracture (77% vs 39%). First year mortality rate was 11% and 13% accordingly without statistical significance. Conclusion This study found that patients in an FLS with coordinator follow-up had better clinical outcomes, receiving more timely medication recommendations and showing higher treatment adherence, highlighting the value of coordinated follow-up in long-term care
Effects of Kangaroo care during retinopathy screening examination: a randomised clinical trial
No full textObjective Providing Kangaroo care (K-care) helps comfort infants through painful and stressful procedures including retinopathy screening examination (RSE) for retinopathy of prematurity. We examined the early pain-related and delayed inflammatory effects of K-care during the first RSE in preterm infants.Design Randomised clinical trial.Setting In a family-centred neonatal intensive care unit between 1 March 2023 and 31 August 2024.Patients Preterm infants (gestation <34+0 weeks and/or birth weight <2000 g) who required RSEs.Interventions Patients were randomly assigned to K-care provided by mother or father during RSE or control group on an examination table (n=50/group).Main outcome measures The Premature Infant Pain Profile (PIPP) score within the first minute of RSE was measured. Salivary samples (>110 uL) were collected before, at 1 and 6–8 hours after RSE for assays of cortisol, interleukin-1β, interleukin-6 and tumour necrosis factor-alpha (TNF-α) levels by ELISA methods in a blinded fashion.Results 100 infants (mean±SD gestational age: 31.1±2.4 weeks; birth weight: 1496±452 g, 58% males) were enrolled. Compared with controls (n=50), infants of the K-care group (n=50) had significantly lower PIPP score (11.0 vs 12.9; p=0.002); salivary cortisol levels (4.9 vs 6.9 ng/mL; p=0.001) at 1 hour after RSE, interleukin-6 (31.9 vs 34.7 pg/mL; p=0.01) and TNF-α (53.9 vs 58.6 pg/mL; p=0.02), but not interleukin-1β (50.4 vs 53.0 pg/mL; p=0.46), levels at 6–8 hour after RSE.Conclusions Providing K-care during RSE in preterm infants may potentially reduce pain-related stress, cortisol and inflammatory responses
The expansion of culturable opportunistic pathogens and antibiotic resistance in mouse gut following antibiotic exposure
No full textABSTRACT Antibiotics significantly change gut microbiota, leading to dysbiosis and changes in bacterial community composition, which further results in a series of dysfunctions with severe health consequences. This work employed both culture-dependent and -independent methods to examine antibiotic-induced changes in gut microbiota at higher resolution using mouse models. By following bacterial changes and antibiotic resistance daily before antibiotic exposure, after antibiotic exposure, and during recovery, several significant novel findings were made. Ampicillin (AMP) and imipenem (IPM) treatment led to an acute, exponential, but temporary bloom in absolute abundances of live opportunistic pathogens Enterobacteriaceae and Enterococcus, while not affecting potentially beneficial Lactobacillus. The absolute abundances of antibiotic-resistant opportunistic pathogens followed a similar pattern. Impact on antibiotic resistance, on the other hand, is significant and persistent. Nearly, all Enterobacteriaceae performed AMP-resistant at the end of treatment with AMP, and almost 10% of Enterococcus became IPM-resistant following treatment with IPM. Further analysis of the genomes of isolated bacteria suggested that the former was due to replacement of Enterobacteriaceae strains while the latter is not. These studies show that antibiotic exposure led to expansion of gastrointestinal pathogens and their resistance to antibiotics, increasing risks for bacterial infections, contrary to the traditional anti-infection functions of antibiotics.IMPORTANCEThe antibiotic therapy is the primary method for treating and preventing bacterial infections. However, the consumption of antibiotics may also cause collateral damage in the normal microbial flora in human body, leading to dysbiosis with unwanted consequences. This impact was previously studied mostly with sequencing-based methods, which did not distinguish between live and dead cells, and did not provide absolute quantitative data, limiting the physiological relevance of discoveries. This work expands the methods in studying the side effects of antibiotic therapy by including culturing methods that measure absolute quantities of live bacteria. Surprising findings were made that antibiotic uptake can lead to temporary exponential bloom of opportunistic pathogens in mouse gut, and a permanent change of antimicrobial resistance in these pathogens. These findings expand our knowledge on how antibiotic therapy can affect our health and urges caution on casual antibiotic usage
SodA promotes immune evasion of Streptococcus suis by suppressing ROS accumulation and GSDMD-mediated mitochondrial disruption in neutrophils
No full textABSTRACT Streptococcus suis is a major swine pathogen that poses a serious threat to pig health. Resistance to oxidative stress and modulation of host immune responses are both critical for the survival of S. suis serotype 2 (SS2) strains during infection. In this study, we investigated the role of the sodA gene in SS2 survival, neutrophil responses, and mitochondrial function, focusing particularly on neutrophil extracellular trap (NET) formation. Using a murine peritoneal infection model, we found that sodA deletion significantly reduced neutrophil recruitment. In vitro assays with primary mouse neutrophils further demonstrated that the sodA mutant exhibited reduced intracellular survival and elevated levels of reactive oxygen species (ROS) in neutrophils. The mutant also triggered more robust NET formation, as indicated by significantly increased levels of cell-free DNA and MPO–DNA complexes. Importantly, the inclusion of a complemented strain confirmed restoration of ROS clearance and normalization of NETs-associated markers, supporting the specificity of the sodA-dependent phenotype. Moreover, sodA deficiency exacerbated SS2-induced mitochondrial membrane depolarization and ROS accumulation in neutrophils. Notably, it also enhanced the expression of cleaved gasdermin D (GSDMD-N), which colocalized with mitochondria and likely contributed to mitochondrial damage and NET induction. Collectively, these findings suggest that sodA facilitates SS2 immune evasion by suppressing host ROS accumulation and GSDMD-N-mediated mitochondrial disruption, thereby limiting NET formation and promoting bacterial survival.IMPORTANCEStreptococcus suis is a major swine pathogen with significant economic and zoonotic implications. Neutrophil extracellular traps (NETs) are essential for host defense, but their regulation by bacterial factors remains poorly understood. This study identifies the superoxide dismutase gene sodA as a key factor in immune evasion by S. suis. We demonstrate that sodA deletion enhances reactive oxygen species accumulation, mitochondrial damage, and NETs formation in neutrophils, impairing bacterial survival. These findings reveal a novel mechanism by which S. suis modulates host innate immunity and highlight sodA as a potential target for enhancing host defense against S. suis serotype 2 infection
Molecular detection of respiratory pathogens in tonsillar tissue from asymptomatic children: implications for result interpretation among the asymptomatic and symptomatic
No full textABSTRACT The diagnosis of upper respiratory infections is commonly made using nucleic acid amplification technologies (NAAT). The impact of asymptomatic carriage is not often appreciated. We aimed to detect respiratory pathogens present in tonsil tissues from children without acute infection. Remnant tonsil tissues were obtained from children undergoing tonsillectomy procedures. Nucleic acids of respiratory pathogens were detected using laboratory-developed PCR assays. The most frequently detected virus was Enterovirus, followed by Adenovirus and Rhinovirus. Among 522 enrolled children, 41.0% had at least one pathogen detected, and co-detections with more than one pathogen were found in 5.6%. Younger children were more likely to have a virus detected, and co-detection was more frequent. Results of standard of care testing for children with suspected respiratory infection during the same study period were also analyzed. Our data demonstrate that a wide array of pathogens can be detected in the tonsil tissues from children absent of acute respiratory symptoms. It emphasizes the need for careful interpretation of test results, particularly in the era of widespread multiplex NAAT usage.IMPORTANCEThe diagnosis of upper respiratory infections is now commonly made using nucleic acid amplification technologies (NAATs). One potential limitation of NAATs is the increased detection of the nucleic acids of pathogens in healthy individuals in the absence of symptoms. The findings from this study highlight the critical importance of understanding asymptomatic carriage of respiratory pathogens, particularly in pediatric populations. The detection of pathogens in asymptomatic individuals, especially younger children, calls for cautious interpretation of test results to avoid misdiagnosis and unnecessary treatment. It emphasizes the need for careful interpretation of test results, particularly in the era of widespread multiplex NAAT usage
Comparison of the diagnostic performance of Enterosystem 18R and the BD Phoenix automated identification and susceptibility testing system for identifying gram-negative Enterobacteria: a preliminary study
No full textPstSCAB and SapBCDF are putrescine exporters in Proteus mirabilis
No full textABSTRACT Proteus mirabilis is a cause of urinary tract infection. Putrescine, an aliphatic amine, acts as a messenger molecule during P. mirabilis urothelial invasion. Inhibition of putrescine-mediated cell-cell communication in P. mirabilis may be an effective method for control of urinary tract infection. PlaP is a primary putrescine importer in P. mirabilis PM7002. However, no putrescine exporters have been identified to date. In this study, we screened the putrescine exporter gene from P. mirabilis PM7002 transposon mutant library using a previously developed high-throughput putrescine quantification method and revealed that PstSCAB is a novel putrescine exporter. SapBCDF and PotE have been reported as a putrescine exporter and putrescine-ornithine antiporter, respectively, in Escherichia coli. Although P. mirabilis possesses the SapBCDF and PotE homologs, the effects of these homologs on the putrescine export are unclear. We investigated the contributions of SapBCDF and PotE homologs on putrescine export in P. mirabilis using gene deletion and found that SapBCDF is a putrescine exporter. P. mirabilis exhibits unique and highly coordinated multicellular migration called swarming. Putrescine mediates cell-cell communication during swarming. Therefore, we evaluated the effects of PstSCAB and SapBCDF on swarming. As a result, the swarming diameters of P. mirabilis ΔpstSCAB and ΔsapBCDF were significantly lower than that of the wild type. This revealed that PstSCAB and SapBCDF are putrescine exporters that mediate cell-cell communication during swarming. Inhibition of PstSCAB and SapBCDF is a possible target for treating P. mirabilis-related urinary tract infection.IMPORTANCEAntibiotics are the primary treatment for bacterial urinary tract infections (UTIs). However, overuse of antibiotics promotes the emergence of antibiotic-resistant bacteria; therefore, it is desirable to develop drugs that specifically inhibit virulence without promoting the emergence of antibiotic resistance. Proteus mirabilis causes UTI and uniquely uses putrescine for cell-cell communication during urinary tract invasion. Inhibition of putrescine-mediated cell-cell communication in P. mirabilis impairs its invasion of urothelial cells. Therefore, proteins responsible for putrescine-mediated cell-cell communication are a potential target for treating P. mirabilis UTIs. However, the putrescine exporter of P. mirabilis has yet to be identified. Here, we identified two putrescine exporters of P. mirabilis, PstSCAB and SapBCDF. Furthermore, P. mirabilis ΔpstSCAB and ΔsapBCDF strains showed a lack of swarming activity. This study indicates PstSCAB and SapBCDF as potential targets for treating UTIs caused by P. mirabilis
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