Staphylococcus lugdunensis Peritoneal Dialysis-Related Peritonitis: A Matched Comparative Analysis.

Rationale & Objective: Staphylococcus lugdunensis (S lugdunensis) is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus (S aureus). No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared with those with S aureus peritonitis. We aim to evaluate the clinical course of peritonitis as caused by these organisms. Study Design: A retrospective matched comparative analysis involving a single tertiary center from July 2000 to July 2020. Setting & Participants: Forty-eight episodes of S aureus peritonitis were matched to 19 cases of S lugdunensis peritonitis. Analytical Approach: The cases were individually matched for year of peritonitis, sex, age (±10 years), and Charlson Comorbidity Index (±3). A comparative analysis was performed between the 2 organisms. The outcome includes responses at day 5 of peritonitis and the rate of complete response. Results: There is a higher predilection of diabetes in those with S aureus peritonitis than in those with S lugdunensis (64.6% vs 31.6%; P = 0.03). Patients with S aureus peritonitis also have a much higher total cell count at presentation (4,463.9 ± 5,479.5 vs 1,807.9 ± 3,322.7; P = 0.05); a higher prevalence of poor response at day 5 (50.0% vs 15.8%; P = 0.03); a lower rate of complete response (64.6% vs 94.7%; P = 0.01) and are more prone to relapse with the same organism (29.2% vs 0%, respectively; P = 0.01) as compared to those with S lugdunensis. Limitations: The result of this small retrospective study involving a single center may not be generalizable to other centers. There is also no data for comparative analysis on other coagulase-negative staphylococci such as Staphylococcus epidermidis, which belongs to the same family as S lugdunensis. Conclusions: Although S aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. This largest case series of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis peritonitis.

Staphylococcus lugdunensis is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus. No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared those with S aureus peritonitis. This largest retrospective matched comparative analysis of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis. Our result suggested that although S. aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. Regardless, S lugdunensis remains susceptible to most antibiotics and penicillin group, penicillin G in particular, can be considered as the first line antibiotic.

Prevalence of oral human papillomavirus infection among the general adult population in Hong Kong.

A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.

Iris depigmentation and cytomegalovirus in aqueous humor as predictors of uveitic activity and recurrence in chronic and recurrent anterior uveitis.

PURPOSE: To examine the clinical outcomes in chronic or recurrent anterior uveitis in the presence or absence of cytomegalovirus (CMV) and investigate the predictive factors for uveitic activity and recurrence. METHODS: Polymerase chain reaction (PCR) was performed in a prospective cohort of immunocompetent adults with recurrent or chronic anterior uveitis to detect CMV in aqueous humor. The clinical outcomes were compared between eyes with and without CMV DNA. Logistic regression was performed to evaluate associations between iris depigmentation, CMV-PCR status, uveitic activity, and recurrence. RESULTS: Thirty-eight eyes of 38 subjects with a mean age of 61.1 ± 11.2 years old were analyzed. Fifteen eyes were positive for CMV. More eyes with CMV developed recurrences and remained actively inflamed at 6, 12, and 24 weeks though the differences were insignificant. The presence of iris depigmentation was predictive of a greater odd of uveitic recurrences by 12 and 24 weeks (Odds ratio (OR) = 9.17 and 5.72, P = 0.007 and 0.034 respectively), whereas positive CMV-PCR predicts a greater odd of uveitic activity at postoperative 12 and 24 weeks (OR = 13.08, 34.30; P = 0.027, 0.007). CONCLUSION: Eye with and without detectable CMV behaved similarly in their clinical course. Our findings suggested that iris depigmentation was predictive of more frequent uveitic recurrence, regardless of the PCR status, whereas the presence of CMV in aqueous humor was associated with persistent uveitic activity. Iris changes may be present during the earlier phase of the disease and precede the detection of virus from the aqueous humor at a later stage of CMV infection.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population.

OBJECTIVE: Assess real-world effectiveness of vaccines against COVID-19. METHODS: A test-negative study was conducted in January-May 2022 during an Omicron BA.2 wave in Hong Kong. COVID-19 was identified by RT-PCR. 1-1 case-control matching was based on propensity score with vaccine effectiveness adjusted for confounders. RESULTS: Altogether, 1781 cases and 1737 controls aged 3-105 years were analysed. The mean lag time from the last dose of vaccination to testing for SARS-CoV-2 was 133.9 (SD: 84.4) days. Two doses of either vaccine within 180 days offered a low effectiveness against COVID-19 of all severity combined (VEadj [95% CI] for BNT162b2: 27.0% [4.2-44.5], CoronaVac: 22.9% [1.3-39.7]), and further decreased after 180 days. Two doses of CoronaVac were poorly protective 39.5% [4.9-62.5] against severe diseases for age ≥ 60 years, but the effectiveness increased substantially after the third dose (79.1% [25.7-96.7]). Two doses of BNT162b2 protected age ≥ 60 years against severe diseases (79.3% [47.2, 93.9]); however, the uptake was not high enough to assess three doses. CONCLUSIONS: The current real-world analysis indicates a high vaccine effectiveness of three doses of inactivated virus (CoronaVac) vaccines against Omicron variant, whereas the effectiveness of two doses is suboptimal.

Iris Depigmentation in the Prediction of Cytomegalovirus Anterior Uveitis.

PURPOSE: We hypothesize that the presence of iris depigmentation is associated with the prediction of cytomegalovirus (CMV) as the etiology of chronic or recurrent anterior uveitis. METHODS: A prospective cohort study on patients with recurrent or chronic anterior uveitis. Pre-operative data on iris depigmentation and corneal endothelial cell densities were compared between eyes with and without CMV. RESULTS: Forty-one eyes of 38 subjects with a mean age of 61.1 ± 11.2 years old were recruited. Seventeen eyes were positive for CMV. A greater proportion of eyes with CMV showed severe or diffuse iris depigmentation than eyes without CMV, and possessed larger corneal endothelial cells (p = .028). When severe iris depigmentation was present with a reduced endothelial cell density, the positive and negative predictive values were raised to 100.0% and 64.9% from 41.5% and 58.5%, respectively. CONCLUSION: Iris depigmentation is a potential clinical biomarker in predicting CMV in chronic or recurrent anterior uveitis.

Prevalence and Epidemiologic Profile of Oral Infection with Alpha, Beta, and Gamma Papillomaviruses in an Asian Chinese Population.

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Uhrf1 and Dnmt1 are required for development and maintenance of the zebrafish lens.

DNA methylation is one of the key mechanisms underlying the epigenetic regulation of gene expression. During DNA replication, the methylation pattern of the parent strand is maintained on the replicated strand through the action of Dnmt1 (DNA Methyltransferase 1). In mammals, Dnmt1 is recruited to hemimethylated replication foci by Uhrf1 (Ubiquitin-like, Containing PHD and RING Finger Domains 1). Here we show that Uhrf1 is required for DNA methylation in vivo during zebrafish embryogenesis. Due in part to the early embryonic lethality of Dnmt1 and Uhrf1 knockout mice, roles for these proteins during lens development have yet to be reported. We show that zebrafish mutants in uhrf1 and dnmt1 have defects in lens development and maintenance. uhrf1 and dnmt1 are expressed in the lens epithelium, and in the absence of Uhrf1 or of catalytically active Dnmt1, lens epithelial cells have altered gene expression and reduced proliferation in both mutant backgrounds. This is correlated with a wave of apoptosis in the epithelial layer, which is followed by apoptosis and unraveling of secondary lens fibers. Despite these disruptions in the lens fiber region, lens fibers express appropriate differentiation markers. The results of lens transplant experiments demonstrate that Uhrf1 and Dnmt1 functions are required lens-autonomously, but perhaps not cell-autonomously, during lens development in zebrafish. These data provide the first evidence that Uhrf1 and Dnmt1 function is required for vertebrate lens development and maintenance.