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Neutrophils are traditionally considered short‐lived, circulating innate immune cells that are rapidly recruited to sites of inflammation in response to infectious and inflammatory stimuli. Neutrophils efficiently internalize, kill or entrap pathogens, but their effector molecules may cause collateral tissue damage. More recently, it has been appreciated that neutrophils can also influence adaptive immunity. Lymph nodes (LNs) are immune cell‐rich secondary lymphoid organs that provide an ideal platform for cellular interaction and the integration of immunological information collected from local tissues. A variety of peripheral stimuli promote neutrophil migration to draining LNs via blood or lymphatics, utilizing differing molecular cues depending on the site of entry. Within LNs, neutrophils interact with other innate and adaptive cells. Crosstalk with subcapsular sinus macrophages contributes to the control of pathogen spread beyond the LN. Neutrophils can influence antigen presentation indirectly by interacting with DCs or directly by expressing major histocompatibility complex (MHC) and costimulatory molecules for antigen presentation. Interactions between neutrophils and adaptive lymphocytes can alter B‐cell antibody responses. Studies have shown conflicting results on whether neutrophils exert stimulatory or inhibitory effects on other LN immune cells, with stimulus‐specific and temporal differences in the outcome of these interactions. Furthermore, neutrophils have also been shown to traffick to LNs in homeostasis, with a potential role in immune surveillance, antigen capture and in shaping early adaptive responses in LNs. Understanding the mechanisms underpinning the effects of neutrophils on LN immune cells and adaptive immunity could facilitate the development of neutrophil‐targeted therapies in inflammatory diseases., In addition to their role in pathogen defence, neutrophils can also influence adaptive immune responses. Neutrophils can traffick to lymph nodes, at baseline and following inflammatory stimuli, to interact with other lymph node immune cells to shape innate and adaptive immune responses.

Introduction Digital cognitive behavioral therapy for insomnia (dCBTi) has been shown to be efficacious; however, treatment adherence and efficacy are suboptimal compared to CBTi delivered in person. The present study evaluated whether the addition of different types of coaching support (i.e., phone coaching by a therapist trained in CBTi, phone coaching by a research assistant not trained in CBTi, and virtual coaching by a chatbot that simulates human dialogue) would improve treatment adherence to and efficacy of dCBTi. It was hypothesized that the addition of any form of coaching will have beneficial effects, with therapist coaching achieving the best outcomes. Methods A single-blind, parallel, randomized controlled trial was conducted. One-hundred-fifty adults with insomnia, indicated by Insomnia Severity Index (ISI) >=10, were randomly assigned to one of the five conditions: dCBTi with three 20-min therapist phone coaching sessions (C1), dCBTi with three 20-min non-therapist phone coaching sessions (C2), dCBTi with chatbot virtual coaching (C3), dCBTi without any coaching (C4), and the sleep hygiene and sleep diary control (C5). dCBTi is a smartphone application adopting a six-session CBTi with components of sleep hygiene, sleep restriction, stimulus control, relaxation, and cognitive therapy. Participants completed sleep diaries, ISI, dysfunctional beliefs about sleep (DBAS), sleep-related behavior questionnaire (SRBQ), and measures of mood, fatigue, and quality of life at pre-intervention, post-intervention, and 4-week follow-up. Results Mixed modeling analysis showed that participants in C1, C2, C3, and C4 had greater improvements in insomnia symptoms, sleep efficiency, DBAS, SRBQ, mood, and fatigue than C5. Participants in C1 had significantly greater treatment adherence and improvement in DBAS and SRBQ than those in C4; those in conditions with any form of coaching had greater treatment adherence than those in C4. However, improvements in insomnia symptoms were not significantly different between conditions with or without coaching. Conclusion Adding human support, especially therapist phone coaching, improved treatment adherence to dCBTi but not efficacy. Nonetheless, adding therapist coaching led to greater improvements in the mechanisms of change, i.e., reductions in dysfunctional beliefs and behaviors related to insomnia, which may promote greater maintenance of treatment efficacy at longer follow-up. Clinicaltrials.gov registration#: NCT05136638 Support (if any) HKU Fund for Translation Research #104005654

Significance IgG antibodies are a key component of adaptive humoral immunity but can cause organ damage if they bind self-antigen, as occurs in the autoimmune disease systemic lupus erythematosus (SLE). Many of the proinflammatory effects of IgG are mediated by ligating Fcγ receptors (FcγRs) expressed by tissue-resident leukocytes such as macrophages. One of the most serious complications of SLE is kidney inflammation: lupus nephritis. Here we show that IgG ligation of FcγRs on macrophages in the kidney leads to a change in their metabolism, resulting in a switch toward glycolysis. Administration of a glycolysis inhibitor attenuated IgG-associated kidney macrophage activation, proinflammatory cytokine secretion, and kidney inflammation. Therefore, manipulating macrophage metabolism may be a useful therapeutic strategy in lupus nephritis., IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis.

BACKGROUND Traditionally, promotion of colorectal cancer (CRC) screening among Black men was delivered by community health workers, patient navigators, and decision aids (printed text or video media) at clinics and in the community setting. A novel approach to increase CRC screening of Black men includes developing and utilizing a patient-centered, tailored message delivered via virtual human technology in the privacy of one’s home. OBJECTIVE The objective of this study was to incorporate the perceptions of Black men in the development of a virtual clinician (VC) designed to deliver precision messages promoting the fecal immunochemical test (FIT) kit for CRC screening among Black men in a future clinical trial. METHODS Focus groups of Black men were recruited to understand their perceptions of a Black male VC. Specifically, these men identified source characteristics that would enhance the credibility of the VC. The modality, agency, interactivity, and navigability (MAIN) model, which examines how interface features affect the user’s psychology through four affordances (modality, agency, interactivity, and navigability), was used to assess the presumed credibility of the VC and likability of the app from the focus group transcripts. Each affordance triggers heuristic cues that stimulate a positive or a negative perception of trustworthiness, believability, and understandability, thereby increasing source credibility. RESULTS In total, 25 Black men were recruited from the community and contributed to the development of 3 iterations of a Black male VC over an 18-month time span. Feedback from the men enhanced the visual appearance of the VC, including its movement, clothing, facial expressions, and environmental surroundings. Heuristics, including social presence, novelty, and authority, were all recognized by the final version of the VC, and creditably was established. The VC was named Agent Leveraging Empathy for eXams (ALEX) and referred to as “brother-doctor,” and participants stated “wanting to interact with ALEX over their regular doctor.” CONCLUSIONS Involving Black men in the development of a digital health care intervention is critical. This population is burdened by cancer health disparities, and incorporating their perceptions in telehealth interventions will create awareness of the need to develop targeted messages for Black men.

Infection or vaccination leads to the development of germinal centers (GCs) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. We followed the migratory pathways of B cells emerging from germinal centers (BEM) and found that many migrated into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From there, B cells may exit the lymph node to enter distant tissues. Some BEM cells interacted with and took up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibited the recycling of BEM cells and resulted in less efficient adaption to antigenic variation. Our findings suggest that the recycling of BEM cells, that transport antigen and that contain the genetic code for B cell receptor variants, may support affinity maturation to antigenic drift.

Neutrophils play an important role in the lung tumour microenvironment. We hypothesised that radiolabelled neutrophils coupled to single-photon emission CT (SPECT) may non-invasively quantify neutrophil uptake in tumours from patients with non-small cell lung cancer. We demonstrated increased uptake of radiolabelled neutrophils from the blood into tumours compared with non-specific uptake using radiolabelled transferrin. Moreover, indium-111-neutrophil activity in the tumour biopsies also correlated with myeloperoxidase (MPO)-positive neutrophils. Our data support the utility of imaging with In-111-labelled neutrophils and SPECT-CT to quantify neutrophil uptake in lung cancer.

Vedolizumab is a humanized monoclonal antibody that binds to the human a4β7 integrin and is approved for use in inflammatory bowel diseases. We describe a patient with severe, refractory erosive gingivostomatitis, which appeared a few days after the first dose of vedolizumab and resolved after discontinuation of the drug. We believe the gingivostomatitis to be a direct side effect of vedolizumab, rather than an extraintestinal manifestation of the underlying inflammatory bowel diseases. The clinicians need to be aware of this adverse event, which could be mistakenly considered as an extraintestinal manifestation of inflammatory bowel diseases.

Summary Macrophages play a central role in intestinal immunity, but inappropriate macrophage activation is associated with inflammatory bowel disease (IBD). Here, we identify granulocyte-macrophage colony stimulating factor (GM-CSF) as a critical regulator of intestinal macrophage activation in patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis. We find that GM-CSF drives the maturation and polarization of inflammatory intestinal macrophages, promoting anti-microbial functions while suppressing wound-healing transcriptional programs. Group 3 innate lymphoid cells (ILC3s) are a major source of GM-CSF in intestinal inflammation, with a strong positive correlation observed between ILC or CSF2 transcripts and M1 macrophage signatures in IBD mucosal biopsies. Furthermore, GM-CSF-dependent macrophage polarization results in a positive feedback loop that augmented ILC3 activation and type 17 immunity. Together, our data reveal an important role for GM-CSF-mediated ILC-macrophage crosstalk in calibrating intestinal macrophage phenotype to enhance anti-bacterial responses, while inhibiting pro-repair functions associated with fibrosis and stricturing, with important clinical implications., Graphical Abstract, Highlights • ILCs are a major source of GM-CSF, a critical regulator of gut inflammatory macrophages • GM-CSF promotes ILC-macrophage crosstalk and augments type 17 and barrier immunity • GM-CSF-induced macrophages are protective during infection but drive inflammatory colitis • GM-CSF suppresses wound-healing macrophage response associated with intestinal fibrosis, Castro-Dopico et al. identify GM-CSF as a major upstream regulator of intestinal inflammatory macrophages, with ILC-derived GM-CSF polarizing macrophages toward a glycolytic, anti-microbial phenotype while suppressing wound-healing, pro-fibrotic activity. GM-CSF initiates further ILC-macrophage crosstalk, amplifying ILC3 activation and type 17 immunity.

To describe and evaluate the trends in the incidence of retinopathy of prematurity over a 10-year period in a tertiary hospital in Hong Kong. A retrospective review was performed on all preterm infants screened and/or treated for retinopathy of prematurity from January 2006 to December 2015 at Prince of Wales Hospital, Hong Kong. Preterm infants with incomplete records or transferred-in from other hospitals/region solely for treatment of ROP were excluded. The incidence of any ROP or Type 1 ROP was analysed with gestational age and birth weight over a 10-year period with consecutive 2-year intervals to evaluate the trends. Of all 754 infants included in the study, 234 (31.0%) patients had any ROP and 34 (4.5%) infants developed Type 1 ROP. The incidence of any ROP demonstrated a statistically significant decreasing trend over the five consecutive 2-year intervals (p = 0.016), but the incidence trend of Type 1 ROP is not statistically significant. No infants weighing more than 1250 g developed Type 1 ROP. We observed a decreasing trend in the incidence of any ROP across the 10-year period in a tertiary hospital in Hong Kong, while the incidence of Type 1 ROP remained stable at 4.5%. The factors leading to the trend were unclear. Improved prenatal care, changing proportion of cases with different birth weight and gestational age, oxygenation level practice in neonatal unit may all contribute to the decreasing trend. Revision of screening criteria may be made according to local experience to maximise cost-effectiveness.

Significance The classical view of neutrophils is as circulating phagocytes that are recruited to tissues following infection or injury. Here we show that neutrophils were present in mouse and human lymph nodes in the absence of perturbation. Lymph node neutrophils were phenotypically distinct, with increased expression of major histocompatibility complex II, and predominantly localized to the interfollicular zone, where CD4 T lymphocytes are activated. Neutrophils trafficked into lymph nodes via blood and lymphatic vessels, and were capable of rapidly carrying systemically acquired, IgG antibody-opsonized cargo to lymph nodes. These data support a novel role for neutrophils in homeostatic immune surveillance, sampling circulating antigens and delivering them to lymph nodes, with the potential to activate adaptive immunity., Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.

Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts.This was a retrospective and prospective multicenter study including all drug addicts with CW.We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up.Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.

Zika virus: what the dermatologist should know. Probably a new vaccine against herpes zoster and postherpetic neuralgia in older adults. Defining moderate, significant and extensive types of pemphigus with ABSIS et PDAI scores. Biologic Therapies and serious infections in patients with psoriasis. We can be cautiously optimistic, in that tuberculosis is rare but still occurs despite adherence to tuberculosis prevention guidelines. Others serious infections are rare, mainly pneumonia and cellulitis. Hidradenitis suppurativa: an unrecognized paradoxical effect of biologic agents. There is an association between Inflammatory Bowel Disease (IBD) and Hidradenitis suppurativa (HS), mostly with Crohn's disease, suggesting the need to look for signs and symptoms of IBD in HS patients. A study of 550 twins found that genetic and environmental factors each contribute to approximately half of the score of rosacea. Telangiectasia Macularis Eruptiva Perstans is a difficult to diagnose type of mastocytosis, often with a delay and which is associated with a systemic involvement in 50% of cases. Vitiligo. Management and development of new scores for the dermatologist and the patient. Livedoid vasculopathy. Anticoagulation with new molecules could prove an efficient means of treatment. Pyoderma Gangrenosum. Don't forget the toxic etiology. Daily practice: Laboratory monitoring for liver function tests and serum lipid profile during isotretinoin therapy for acne is currently recommended at baseline and every 3 months, depending on the results. Daily practice: Mikailov and al., challenge our habits by their medico economic study and propose an empirical treatment with terbinafine for patients with suspected onychomycosis that is cost effective with minimal effect on patient safety as terbinafine-induced liver injury is very rare. It makes think and especially propose studies to update our recommendations.

IntroductionRadionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET).Sources of dataMostly the authors’ own studies, following on from studies of the early pioneers.Areas of controversyFrom early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual.Areas of agreementFollowing refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome.Growing pointsMore recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma.Areas timely for developing researchThese include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.

Zika virus: what the dermatologist should know. Probably a new vaccine against herpes zoster and postherpetic neuralgia in older adults. Defining moderate, significant and extensive types of pemphigus with ABSIS et PDAI scores. Biologic Therapies and serious infections in patients with psoriasis. We can be cautiously optimistic, in that tuberculosis is rare but still occurs despite adherence to tuberculosis prevention guidelines. Others serious infections are rare, mainly pneumonia and cellulitis. Hidradenitis suppurativa: an unrecognized paradoxical effect of biologic agents. There is an association between Inflammatory Bowel Disease (IBD) and Hidradenitis suppurativa (HS), mostly with Crohn's disease, suggesting the need to look for signs and symptoms of IBD in HS patients. A study of 550 twins found that genetic and environmental factors each contribute to approximately half of the score of rosacea. Telangiectasia Macularis Eruptiva Perstans is a difficult to diagnose type of mastocytosis, often with a delay and which is associated with a systemic involvement in 50% of cases. Vitiligo. Management and development of new scores for the dermatologist and the patient. Livedoid vasculopathy. Anticoagulation with new molecules could prove an efficient means of treatment. Pyoderma Gangrenosum. Don't forget the toxic etiology. Daily practice: Laboratory monitoring for liver function tests and serum lipid profile during isotretinoin therapy for acne is currently recommended at baseline and every 3 months, depending on the results. Daily practice: Mikailov and al., challenge our habits by their medico economic study and propose an empirical treatment with terbinafine for patients with suspected onychomycosis that is cost effective with minimal effect on patient safety as terbinafine-induced liver injury is very rare. It makes think and especially propose studies to update our recommendations.

Variations in the clinical and histological presentation of cutaneous T-cell lymphoma (CTCL) can hamper diagnosis. We report two cases of a novel presentation of CTCL characterized by an aberrant immunophenotype with complete loss of pan T-cell antigens including T-cell receptor β chain and showing the clinical and histopathological appearance of erythrodermic and plaque-stage mycosis fungoides.

Background Decreases in circulating neutrophils (polymorphonuclear leukocytes, PMNs) have been reported in patients treated with the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab (TCZ); the mechanism for this is unclear. We hypothesize that TCZ reduces circulating neutrophils by affecting margination and / or bone marrow trafficking without affecting neutrophil function or apoptosis. Materials and methods 18 healthy subjects were randomized to single intravenous dose of TCZ 8 mg/kg (n = 12) or placebo (n = 6) on day 0. On day 4, each subject had autologous indium-111-labeled neutrophils re-injected, and their kinetics quantified with longitudinal profiling in a whole body gamma-counter. TCZ-treated subjects were divided into two groups according to the extent of reduction in neutrophil count. Results Mean day 4 neutrophil counts, as % baseline, were 101.9%, 68.3% and 44.2% in the placebo, TCZ-PMN-’high’ and TCZ-PMN-’low’ groups, respectively (p < 0.001). Following TCZ, neutrophil function, activation and apoptosis ex vivo were all unaffected. In vivo, there were no differences in early blood recovery or margination to liver / spleen and bone marrow; however, later neutrophil re-distribution to bone marrow was markedly reduced in the TCZ-PMN-low group (peak pelvic count as % day 4 count on: day 5, 188% placebo vs 127% TCZ-PMN-low, p < 0.001; day 10, 180% placebo vs 132% TCZ-PMN-low, p < 0.01), with a trend towards higher liver / spleen neutrophil retention. Conclusions We have demonstrated for the first time in humans that IL-6R blockade affects neutrophil trafficking to the bone marrow without influencing neutrophil functional capacity. This article is protected by copyright. All rights reserved.

Monilethrix is a rare genodermatosis characterized by a hair shaft dysplasia responsible for hypotrichosis. We report the case of a child with monilethrix with no associated cases in the family. Trichoscopy facilitated the diagnosis. A 2-year-old boy presented with diffuse alopecia and persistent fragile hair for several months. Clinical examination revealed alopecia with hairs broken several millimeters from the scalp. Trichoscopy revealed zones of dystrophic constriction of the hair shaft, separated at regular intervals by elliptical nodes of normal thickness, giving a "necklace" appearance. The diagnosis of monilethrix was made on the basis of these specific features. The diagnosis of monilethrix was more difficult to establish in our patient owing to the absence of any familial cases.

Actinomycosis is a chronic and extensive granulomatous, bacterial infection. Revelation by oral ulceration is rare.A 76-year-old patient with diabetes was treated with dabrafenib for stage IV melanoma. A follow-up visit revealed two ulcerated, infiltrated and hyperalgesic lesions of the palate and gingiva. There were no associated signs. The laboratory findings were normal. The possibility of squamous cell carcinoma occurring with BRAF inhibitors was discussed, despite the rarity of such cases in the literature. Histological examination showed an actinomycotic grain. A scan of the facial mass showed no osteitis. Antimicrobial therapy was initiated with amoxicillin for four months, with a favorable outcome.Actinomycetes are Gram-positive filamentous saprophytic bacteria of the oral cavity and the gastrointestinal tract. They can become pathogenic under the influence of several factors. Cervicofacial involvement in the form of a peri-mandibular inflammatory nodule with secondary fistulation on the skin or in the mouth is the classic presentation. To our knowledge, no cases of opportunistic infection under BRAF inhibitors have been described. Only two cases of tuberculosis have been reported with sorafenib. The initial presentation led to suspicion of squamous cell carcinoma. In our patient, poor oral hygiene and diabetes were the two key factors considered. Moreover, this is the first case reported under dabrafenib, which does not appear to be a favoring factor. We would stress the importance of mucosal examination in patients treated with BRAF inhibitors.

Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater, which may cause a compressive effect or vascular compromise. We report on a 28-year-old Chinese woman with a history of granulomatous mastitis 7 years previously and oligomenorrhoea, headache, blurred vision, and raised prolactin level 2 years previously, that was diagnosed as prolactinoma and treated conservatively with bromocriptine. However, she had recurrent bilateral vision loss when the bromocriptine was stopped. Her symptoms were resolved by high-dose steroid injection but remained steroid-dependent. Serial magnetic resonance imaging scan showed progressive diffuse thickening of the pachymeningitis with disappearance of pituitary apoplexy. Lumbar puncture showed lymphocytosis with no organisms. Open biopsy of the meninges was performed and histology showed features of inflammatory infiltrates and vasculitis. This is an unusual presentation of a rare condition in this age-group, with co-existing granulomatous mastitis and chronic otitis media, and is a diagnostic challenge mimicking pituitary macroadenoma and meningioma in initial magnetic resonance imaging scans.

To report the visual outcome and refractive status in first 3 years of age in preterm infants suffered from laser-treated Type 1 retinopathy of prematurity (ROP): a 6-year review in Hong Kong DESIGN: Retrospective case series METHODOLOGY: Clinical records of all infants suffered from Type 1 ROP who had undergone laser therapy between 2007 and 2012 were retrospectively reviewed. Basic demographic data, serial changes of refractive error, visual acuity, severity of ROP and laser were analyzed. Correlation with myopia and astigmatism progression, body weight, height, growth and gestational age were also analyzed.Among 494 babies screened, 14 Chinese babies (26 eyes) recruited with 1:1 male-to-female ratio in this study. All eyes showed gradual progression of myopia in first 3 years of age but no significant change of astigmatism. Further correlation analysis showed no correlation with laser energy consumed, birth weight (p = 0.14), head circumference growth (p = 0.57) and body weight growth (p = 0.71). However, severity of myopia was related to the post-conceptual age when receiving laser therapy (p 0.005), gestation age (p = 0.02) and possibly body height growth with age (p = 0.05).Myopia in early life is one of the most common ocular sequelae in Type 1 ROP survivors. Early detection of refractive error is important for prompt correction and visual rehabilitation to prevent amblyopia.

Objective To analyse the incidence, application and compliance to Royal College of Ophthalmologists retinopathy of prematurity (ROP) screening recommendations and subsequent treatment of ROP in a neonatal intensive care unit of a large tertiary referral centre in Hong Kong. Design A retrospective review was performed for all eligible premature neonates screened for ROP over a 7-year period from June 2008 to December 2015 in our local tertiary neonatal intensive care unit in Prince of Wales Hospital, Hong Kong, using the Royal College of Ophthalmologists ROP screening guideline (2008). Comparison between established UK and American screening guidelines were analysed for their applicability in our locality. Results A total of 602 infants were screened, with the incidence of ROP in 28.2% and type 1 ROP in 3.8%, and indirect diode laser performed in all type 1 ROP cases. Overall, adherence for screening criteria was 99.7%, with the average time to commence first screening at 4 weeks postnatal age. Of the 602 cases, 94 (15.6%) were early and 35 (5.8%) were later than the guidelines, of which only 5 (0.8%) of late-screened cases developed ROP requiring treatment. Subsequent treatment of ROP for all the late-screened cases was not delayed. Conclusions Current ROP screening using the UK guidelines (2008) is applicable, effective and safe to our predominantly Asian population in Hong Kong, with a low rate of delayed screening.

Objective: To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). Methods: In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results: Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion: This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. © 2016, American College of Rheumatology

In contrast with bone metastasis, acrometastases are uncommon and are associated with advanced cancer. We report the cases of two patients with atypical lesions of the fingers in a context of cancer, in which biopsies confirmed a metastasis. Patients died rapidly before treatment was initiated. We discuss the characteristics of these atypical metastatic sites, associated with a generally poor prognosis.

OBJECTIVES: To determine the mechanism and epidemiology of paediatric finger injuries in Hong Kong during 2003-2005 and 2010-2012. DESIGN: Comparison of two case series. SETTING: University-affiliated teaching hospital, Hong Kong. PATIENTS: A retrospective study of two cohorts of children (age, 0 to 16 years) admitted to Prince of Wales Hospital with finger injuries during two 3-year periods. Comparisons were made between the two groups for age, involved finger(s), mechanism of injury, treatment, and outcome. Telephone interviews were conducted for parents of children who sustained a crushing injury of finger(s) by door. RESULTS: A total of 137 children (group A) were admitted from 1 January 2003 to 31 December 2005, and 109 children (group B) were admitted from 1 January 2010 to 31 December 2012. Overall, the mechanisms and epidemiology of paediatric finger injuries were similar between groups A and B. Most finger injuries occurred in children younger than 5 years (group A, 55%; group B, 75%) and in their home (group A, 67%; group B, 69%). The most common mechanism was crushing injury of finger by door (group A, 33%; group B, 41%) on the hinge side (group A, 63%; group B, 64%). The right hand was most commonly involved. The door was often closed by another child (group A, 37%; group B, 23%) and the injury often occurred in the presence of adults (group A, 60%; group B, 56%). Nailbed injury was the commonest type of injury (group A, 31%; group B, 49%). Fractures occurred in 24% and 49% in groups A and B, respectively. Traumatic finger amputation requiring replantation or revascularisation occurred in 12% and 10% in groups A and B, respectively. CONCLUSIONS: Crushing injury of finger by door is the most common mechanism of injury among younger children and accounts for a large number of hospital admissions. Serious injuries, such as amputations leading to considerable morbidity, can result. Crushing injury of finger by door occurs even in the presence of adults. There has been no significant decrease in the number of crushing injuries of finger by door in the 5 years between the two studies despite easily available and affordable preventive measures. It is the authors' view that measures aimed at promoting public awareness and education, and safety precautions are needed. Language: en

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814