Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong.

PURPOSE: We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre. METHODS: A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD). RESULTS: Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) (p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases (p = 0.01). CONCLUSION: We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.

Effects of syphilis infection among HIV-1-positive individuals on suppressive antiretroviral therapy.

INTRODUCTION: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. METHODS: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. RESULTS: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. CONCLUSIONS: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis.

Peptidylarginine Deiminases 2 Mediates Caspase-1-Associated Lethality in Pseudomonas aeruginosa Pneumonia-Induced Sepsis.

BACKGROUND: Pseudomonas aeruginosa (PA) is a pathogenic bacterium that causes severe pneumonia in critically ill and immunocompromised patients. Peptidylarginine deiminase (PAD) 2, PAD4, and caspase-1 are important enzymes in mediating host response to infection. The goal of this study was to determine the interplay between PAD2, PAD4, and caspase-1 in PA pneumonia-induced sepsis. METHODS: Pneumonia was produced in wild-type, Pad2-/-, and Pad4-/- mice by intranasal inoculation of PA (2.5 × 106 colony-forming units per mouse), and survival (n = 15/group) was monitored for 10 days. Bone marrow-derived macrophages (BMDMs) were isolated for in vitro studies. Samples were collected at specific timepoints for Western blot, bacterial load determination, and flow cytometry analysis. RESULTS: Caspase-1-dependent inflammation was diminished in PA-inoculated Pad2-/- mice, contributing to reduced macrophage death and enhanced bacterial clearance. In addition, Pad2-/- mice exhibited improved survival and attenuated acute lung injury after PA infection. In contrast, Pad4-/- mice did not display diminished caspase-1 activation, altered bacterial loads, or improved survival. CONCLUSIONS: Peptidylarginine deiminase 2 plays an essential role in the pathogenesis of pulmonary sepsis by mediating caspase-1 activation. This goes against previous findings of PAD4 in sepsis. Our study suggests that PAD2 is a potential therapeutic target of PA pneumonia-induced sepsis.

Effects of structural modification of (alkyldiene-imidazolium bromide)-based gemini monomers on the formation of the lyotropic bicontinuous cubic phase.

Seven homologues of an amphiphilic gemini monomer were synthesized and screened for the ability to form a bicontinuous cubic (Q) lyotropic liquid crystal phase. Four of these homologues form a Q phase with glycerol or water that can be cross-linked with retention of the nanoporous structure, with one exhibiting a well-ordered Q phase with a wider phase window than the parent monomer.

mTORC2 Activity Disrupts Lysosome Acidification in Systemic Lupus Erythematosus by Impairing Caspase-1 Cleavage of Rab39a.

Lysosomes maintain immune homeostasis through the degradation of phagocytosed apoptotic debris; however, the signaling events regulating lysosomal maturation remain undefined. In this study, we show that lysosome acidification, key to the maturation process, relies on mTOR complex 2 (mTORC2), activation of caspase-1, and cleavage of Rab39a. Mechanistically, the localization of cofilin to the phagosome recruits caspase-11, which results in the localized activation of caspase-1. Caspase-1 subsequently cleaves Rab39a on the phagosomal membrane, promoting lysosome acidification. Although caspase-1 is critical for lysosome acidification, its activation is independent of inflammasomes and cell death mediated by apoptosis-associated speck-like protein containing a caspase recruitment domain, revealing a role beyond pyroptosis. In lupus-prone murine macrophages, chronic mTORC2 activity decouples the signaling pathway, leaving Rab39a intact. As a result, the lysosome does not acidify, and degradation is impaired, thereby heightening the burden of immune complexes that activate FcγRI and sustain mTORC2 activity. This feedforward loop promotes chronic immune activation, leading to multiple lupus-associated pathologies. In summary, these findings identify the key molecules in a previously unappreciated signaling pathway that promote lysosome acidification. It also shows that this pathway is disrupted in systemic lupus erythematosus.

RiboTag translatomic profiling of Drosophila oenocytes under aging and induced oxidative stress.

BACKGROUND: Aging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, liver shows age-related dysregulation of lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In the fruit fly, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Compared to fat body, little is known about how oenocytes age and what are their roles in aging regulation. To characterize age- and stress-regulated gene expression in oenocytes, we performed cell-type-specific ribosome profiling (RiboTag) to examine the impacts of aging and oxidative stress on oenocyte translatome in Drosophila. RESULTS: We show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, oxidative phosphorylation, ribosome, proteasome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and immune response pathways were up-regulated. In addition, most of the peroxisomal genes were down-regulated in aged oenocytes, including genes involved in peroxisomal biogenesis factors and fatty acid beta-oxidation. Many age-related mRNA translational changes in oenocytes are similar to aged mammalian liver, such as up-regulation of innate immune response and Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism. Furthermore, oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). CONCLUSIONS: Our oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes were altered in both oenocytes and liver during aging. Thus, our translatome analysis provide important genomic resource for future dissection of oenocyte function and its role in lipid metabolism, stress response and aging regulation.

Cognitive screening in treatment-naïve HIV-infected individuals in Hong Kong - a single center study.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known. METHODS: Between 2013 and 2015, 98 treatment-naïve HIV-1-infected individuals were referred to and screened by the AIDS Clinical Service, Queen Elizabeth Hospital with (1) the International HIV Dementia Scale (IHDS), a screening tool that targets moderate to severe HAND, (2) the Montreal Cognitive Assessment (MoCA), a frequently used cognitive screening test and (3) the Patient Health Questionnare-9 (PHQ-9), a 9-item questionnaire that evaluates depression symptoms. Within the study period, 57 of them completed the second set of IHDS and MoCA at 6 months after baseline assessment. RESULTS: Most participants were male (94%), with a median age of 31 years. At baseline, 38 (39%) and 25 (26%) of them scored below the IHDS (≤10) and MoCA (25/26) cut-offs respectively. Poor IHDS performers also scored lower on MoCA (p = 0.039) but the correlation between IHDS and MoCA performance was weak (r = 0.29, p = 0.004). Up to a third of poor IHDS performers (13/38) showed moderate depression (PHQ-9 > 9). In the multivariable analysis, a lower education level (p = 0.088), a history of prior psychiatric illness (p = 0.091) and the presence of moderate depression (p = 0.079) tended to be significantly associated with poor IHDS performance. At follow-up, 54 out of 57 were on cART, of which 46 (85%) had achieved viral suppression. Their blood CD4+ T-lymphocytes and IHDS scores were higher at follow-up compared to baseline values (both p < 0.001) but their MoCA performance was similar at both assessments. Of note, 17 participants in this subgroup scored below the IHDS cut-off at both assessments. CONCLUSIONS: Poor IHDS performance, and likely cognitive impairment, was frequently observed in treatment-naïve HIV-infected individuals in our locality. A considerable proportion continued to score below the IHDS cut-off at 6 months after cART. Depression was frequently observed in this vulnerable population and was associated with poor IHDS performance.

Total hip arthroplasty in osteonecrosis secondary to sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a multisystem disease, and the predominant articular manifestation is osteonecrosis (ON). Total hip arthroplasty (THA) is technically challenging, and the complication rates are high. In this retrospective study, we have analysed the outcome of THA in a cohort of patients with SCD at our institution. MATERIALS AND METHODS: We identified 34 THAs between 1999 and 2016 in 30 patients (mean age 37 years) from our SCD database. Co-morbidities, both sickle and non-sickle-related, were documented. Complications and indications for revision surgery were analysed. RESULTS: An uncemented prosthesis was predominantly used. The mean follow-up was 10.5 years (range 1-18). Six patients had revision surgery (17.6%), 2 (5.8%) for Prosthetic Joint Infection (PJI), and 4 (11.7%) for osteolysis of the acetabular component. CONCLUSION: Our revision rates were comparable to the published literature. Our combined sickle cell clinic and the coordinated multidisciplinary management have been successful in reducing morbidity.

Highly efficient homology-driven genome editing in human T cells by combining zinc-finger nuclease mRNA and AAV6 donor delivery.

The adoptive transfer of engineered T cells for the treatment of cancer, autoimmunity, and infectious disease is a rapidly growing field that has shown great promise in recent clinical trials. Nuclease-driven genome editing provides a method in which to precisely target genetic changes to further enhance T cell function in vivo. We describe the development of a highly efficient method to genome edit both primary human CD8 and CD4 T cells by homology-directed repair at a pre-defined site of the genome. Two different homology donor templates were evaluated, representing both minor gene editing events (restriction site insertion) to mimic gene correction, or the more significant insertion of a larger gene cassette. By combining zinc finger nuclease mRNA delivery with AAV6 delivery of a homologous donor we could gene correct 41% of CCR5 or 55% of PPP1R12C (AAVS1) alleles in CD8(+) T cells and gene targeting of a GFP transgene cassette in >40% of CD8(+) and CD4(+) T cells at both the CCR5 and AAVS1 safe harbor locus, potentially providing a robust genome editing tool for T cell-based immunotherapy.

Epidemiology and clinical outcome of intraocular foreign bodies in Hong Kong: a 13-year review.

The purpose of this study was to describe the epidemiology, visual outcome and prognostic factors of intraocular foreign body (IOFB) injuries in a tertiary centre in Hong Kong. A retrospective review of 21 eyes in 21 patients with IOFB that presented to United Christian Hospital from January 2001 to July 2014 was performed. IOFB represented 16 % of all open-globe traumas. There was a high male predominance (90 %). The mean age was 42. Work-related injuries (86 %) were the main cause, where only 10.5 % had eye protection. Hammering was the commonest mechanism of injury (43 %). Most IOFBs were metallic (67 %). The IOFB was found in the anterior segment in 31 % and posterior segment in 69 %. 57 % presented with an initial visual acuity of ≥0.1, and up to 24 % of patients had an initial visual acuity of better than or equal to 0.5. Most cases (76 %) received prompt surgical intervention within 24 h, and there was a low (0 %) endophthalmitis rate. Forty-eight percent had an improvement in visual acuity, defined as final visual acuity more than or equal to 2 lines of improvement from initial visual acuity, and 48 % attained a final visual acuity of better than or equal to 0.5. One case underwent evisceration. A smaller IOFB size (<5 mm) was associated with a good final visual acuity of better than or equal to 0.5 (p = 0.048). It was also found that a posterior segment IOFB was more likely to give a final VA of less than 0.5 (p = 0.035). IOFB remains a significant complication of work-related injuries in Hong Kong. This is the first local study that explores the epidemiology of IOFB injuries in Hong Kong. The favourable visual outcome and low endophthalmitis rate may be related to early removal of IOFB. Despite legal ordinances for mandatory eye protection, the uptake of eye protection was low.

Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.

HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01_AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoType(TM) HIV-1 and Antivirogram®, respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01_AE strains were highly robust in comparison with the gold-standard PT.

Intracameral cefuroxime in the prevention of postoperative endophthalmitis: an experience from Hong Kong.

PURPOSE: The purpose was to study the effect of introducing intracameral cefuroxime, which was compounded by a hospital pharmacy, on postoperative endophthalmitis in a tertiary eye centre in Hong Kong. METHODS: All cases that underwent cataract surgeries over a 12-year period (January 2004 to December 2015) were included. The routine use of intracameral cefuroxime at the end of cataract surgery was introduced at our centre after April 2010. All cefuroxime aliquots were prepared by the hospital pharmacy using an aseptic compounding technique. The rates of postoperative endophthalmitis before April 2010 (Group 1, no intracameral cefuroxime) and after April 2010 (Group 2, routine use of intracameral cefuroxime) were compared. RESULTS: A total of 30,428 eyes (7,332 in Group 1 and 23,096 in Group 2) were studied. Eight cases developed postoperative endophthalmitis (1.09 in 1000; 0.11 %) in Group 1 whereas no cases developed endophthalmitis (0 %) in Group 2. The rate of reduction was statistically significant (p < 0.0001). Seven out of eight cases of endophthalmitis were confirmed by positive culture. Organisms identified were Group G Streptococcus (two cases), Group B Streptococcus, Staphylococcus aureus, Serratia marcescens, and coagulase-negative Staphylococcus (two cases). Antibiotic susceptibility testing results were available in six cases. Four out of six organisms were susceptible to the penicillin group. No adverse events related to the use of intracameral cefuroxime were encountered. CONCLUSIONS: The use of intracameral cefuroxime could significantly reduce the rate of postoperative endophthalmitis in a tertiary centre in Hong Kong. The use of aseptic compounding to prepare cefuroxime aliquots by hospital pharmacy appeared to be safe and efficacious.

Rib and vertebral bone fibrous dysplasia in a child with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC.

Transmitted drug resistance in recently infected HIV-positive Individuals from four urban locations across Asia (2007-2010) - TASER-S.

BACKGROUND: The availability of HIV antiretroviral therapy (ART) has been associated with the development of transmitted drug resistance-associated mutations (TDRM). TDRM can compromise treatment effectiveness in patients initiating ART and the prevalence can vary in different clinical settings. In this study, we investigated the proportion of TDRM in treatment-naïve, recently infected HIV-positive individuals sampled from four urban locations across Asia between 2007-2010. METHODS: Patients enrolled in the TREAT Asia Studies to Evaluate Resistance - Surveillance Study (TASER-S) were genotyped prior to ART initiation, with resulting resistance mutations analysed according to the WHO 2009 list. RESULTS: Proportions of TDRM from recently infected individuals from TASER-S ranged from 0% to 8.7% - Hong Kong: 3/88 (3.4%, 95% CI (0.71%-9.64%)); Thailand: Bangkok: 13/277 (4.7%, 95% CI (2.5%-7.9%)), Chiang Mai: 0/17 (0%, 97.5% CI (0%-19.5%)); and the Philippines: 6/69 (8.7%, 95% CI (3.3%-18.0%)). There was no significant increase in TDRM over time across all four clinical settings. CONCLUSIONS: The observed proportion of TDRM in TASER-S patients from Hong Kong, Thailand and the Philippines was low to moderate during the study period. Regular monitoring of TDRM should be encouraged, especially with the scale-up of ART at higher CD4 levels.

hnRNPL and nucleolin bind LINE-1 RNA and function as host factors to modulate retrotransposition.

Long INterspersed Element one (LINE-1, or L1), is a widely distributed, autonomous retrotransposon in mammalian genomes. During retrotransposition, L1 RNA functions first as a dicistronic mRNA and then as a template for cDNA synthesis. Previously, we defined internal ribosome entry sequences (IRESs) upstream of both ORFs (ORF1 and ORF2) in the dicistronic mRNA encoded by mouse L1. Here, RNA affinity chromatography was used to isolate cellular proteins that bind these regions of L1 RNA. Four proteins, the heterogeneous nuclear ribonucleoproteins (hnRNPs) R, Q and L, and nucleolin (NCL), appeared to interact specifically with the ORF2 IRES. These were depleted from HeLa cells to examine their effects on L1 IRES-mediated translation and L1 retrotransposition. NCL knockdown specifically reduced the ORF2 IRES activity, L1 and L1-assisted Alu retrotransposition without altering L1 RNA or protein abundance. These findings are consistent with NCL acting as an IRES trans-acting factor (ITAF) for ORF2 translation and hence a positive host factor for L1 retrotransposition. In contrast, hnRNPL knockdown dramatically increased L1 retrotransposition as well as L1 RNA and ORF1 protein, indicating that this cellular protein normally interferes with retrotransposition. Thus, hnRNPL joins a small, but growing list of cellular proteins that are potent negative regulators of L1 retrotransposition.

Telephone and Teleradiology-Guided Thrombolysis Can Achieve Similar Outcome as Thrombolysis by Neurologist On-site.

BACKGROUND: Because of the limitation of on-site neurology workforce, telestroke was implemented to overcome this barrier. We explored the efficacy and safety of intravenous (IV) stroke thrombolysis service by telestroke when neurologist was not available on-site. METHODS: From January 2009 to December 2012, we compared patients treated with IV stroke thrombolysis by telestroke in the form of telephone consultation with teleradiology, to patients treated after in-person assessment by the same team of neurologists in a regional hospital. Door-to-needle time, symptomatic intracranial hemorrhage, and functional outcome at 3 months were prospectively collected and compared between the groups. RESULTS: In all, 152 patients were treated with IV thrombolysis; 102 patients were treated with neurologist on-site; whereas 50 patients were treated by internists with telestroke. Fifty-two percent of the telemedical group achieved excellent outcome compared to 43% of the neurologist on-site group (P = .30). Symptomatic intracranial hemorrhage rate (4.0% versus 4.9%, P = 1.0) and mortality (8.3% versus 11.9%, P = .49) were comparable. Using the multiple logistic regression analysis, age, baseline stroke severity, and extent of early ischemic change on brain computed tomography scan, are independent predictors for excellent outcome, whereas the presence of neurologist on-site is not correlated with the outcome. CONCLUSIONS: Patients treated without neurologist on-site achieved similar outcome. Telephone consultation and teleradiology-guided IV stroke thrombolysis, with the support of on-site internist appeared safe and efficacious.

Immunogenicity of intradermal trivalent influenza vaccine with topical imiquimod: a double blind randomized controlled trial.

BACKGROUND: Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human. METHODS: We performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate. RESULTS: Ninety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P < .001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤ .001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P < .05). All adverse reactions were self-limited. CONCLUSIONS: Pretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population.

Predicting the underestimation of the femoral offset in anteroposterior radiographs of the pelvis using 'lesser trochanter index': a 3D CT derived simulated radiographic analysis.

We developed 'lesser trochanter index' (LTI) and estimated its accuracy in predicting the underestimation of offset in the anteroposterior (AP) pelvic radiographs. We reconstructed 320 simulated radiographs from the CT scans of 40 adult hips at different rotational projections of 10° increments from 30° internal rotation to 40° external rotation. Underestimation of femoral offset as a percentage was derived from the neck profile angle for all radiographs. Radiographs with an LTI value above 35 were 94% (95% CI, 89%-97%) likely to underestimate femoral offset by more than 5%. Radiographs with LTI between 0 and 30 demonstrated femoral offset within 5% of the true offset (predictive value 100%, CI 87%-100%). LTI could be a useful guide in preoperative templating of hip arthroplasty.

The benefit of prothrombin complex concentrate in decreasing neurological deterioration in patients with warfarin-associated intracerebral haemorrhage.

OBJECTIVE: To compare the outcomes of patients with warfarin-associated intracerebral haemorrhage given different treatments to reverse the effect of anticoagulation. DESIGN: Historical cohort study. SETTING: A regional hospital in Hong Kong. PATIENTS: Patients on warfarin who developed intracerebral haemorrhage. INTERVENTIONS: Prothrombin complex concentrate versus fresh frozen plasma treatment. MAIN OUTCOME MEASURES: The primary outcome measures included the international normalised ratio before and after prothrombin complex concentrate treatment and the neurological deterioration in patients with Glasgow Coma Scale score of more than 8/not intubated/not planned for immediate surgery (target group). Secondary outcome measures were haematoma expansion, 7-day and 30-day mortality rates, and 3-month functional outcome. Safety outcome was the occurrence of a thrombotic event after prothrombin complex concentrate treatment within the index admission. RESULTS: Among 33 patients with clearly documented time of infusion of prothrombin complex concentrate, and whose international normalised ratio was checked before and after prothrombin complex concentrate treatment, the mean international normalised ratio was reduced from 2.81 to 1.21 within 24 hours. Within the target group of patients, there was a significantly lower rate of neurological deterioration in the prothrombin complex concentrate group (17.4% of 23 patients) versus fresh frozen plasma group (45.5% of 33 patients) [P=0.027]. In terms of the 7-day mortality, 30-day mortality, and 3-month functional outcome, prothrombin complex concentrate-treated group showed a favourable trend although the difference did not reach a statistical significance. No patient developed thrombotic complications after prothrombin complex concentrate treatment. CONCLUSIONS: Prothrombin complex concentrates can reverse the warfarin effect of prolonged international normalised ratio in a timely manner. It might better improve the outcome of warfarin-associated intracerebral haemorrhage compared with fresh frozen plasma treatment by reduction in neurological deterioration.

"What if that's your last sleep?" A qualitative exploration of the trauma of incarceration and sleep.

Study Background/Objectives: Sleep is an underexplored factor in the health of people involved in the criminal legal system. This study addresses the paucity of research on how individual, social, and physical environmental factors impact sleep health during and after incarceration by highlighting the voices of people involved in the criminal legal system through a community-engaged qualitative research approach. Methods: We conducted 20 semi-structured interviews with men recently released from prison for a study on trauma and healthcare during incarceration and after release. Interviews were coded and analyzed using reflexive thematic analysis and a critical realist framework. Our research team included people with a history of incarceration who performed central roles in the research process. Results: Three themes emerged from participants' descriptions of sleep during and after incarceration: (1) concerns about health contributing to sleep problems, (2) lack of access to treatment for sleep disorders leading to ongoing sleep problems, and (3) issues of safety contributing to sleep problems during incarceration and after release. Conclusions: This study identifies factors and domains influencing sleep during and after incarceration. By identifying which interpersonal, environmental, and structural factors impact sleep quality, medical and carceral staff are better equipped to ameliorate sleep health disparities within populations with a history of incarceration and those actively bound by the criminal legal system. Future research should examine other factors impacting sleep in incarcerated and recently released populations and develop multi-level interventions to improve sleep health. This paper is part of the Sleep and Circadian Health in the Justice System Collection.