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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.

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.

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.

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.

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.

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.

Eosinophils are mediators of allergic inflammation and are implicated in the pathogenesis of numerous conditions including asthma, parasitic infections, neoplasms, hyper-eosinophilic syndromes, vasculitic disorders, and organ-specific conditions. Assessing eosinophilic inflammation is therefore important in establishing a diagnosis, in monitoring and assessing response to treatment, and in testing novel therapeutics. Clinical markers of atopy and eosinophilic inflammation include indirect tests such as lung function, exhaled breath condensate analysis, fractional exhaled nitric oxide, serum immunoglobulin E levels and serum periostin. Direct measures, which quantify but do not anatomically localise inflammation include blood eosinophil counts, serum or plasma eosinophil cationic protein and sputum eosinophil levels. Cytology from bronchoalveolar lavage and histology from endobronchial and transbronchial biopsies are better at localising inflammation but are more invasive. Novel approaches using radiolabelled eosinophils with single-photon emission computed tomography, offer the prospect of non-invasive methods to localise eosinophilic inflammation.

Objectives: To investigate the clinical outcomes of cataract surgery elderly adults. Design: Retrospective cohort study. Setting: Two clustered hospitals. Participants: Two hundred seven individuals aged 90 and older who underwent cataract surgery for primary senile cataracts. Measurements: Best-corrected preoperative and postoperative Snellen visual acuity, type of cataract, surgical techniques, preoperative systemic or ocular comorbidities, and intraoperative and postoperative complications were assessed. Improvement of visual acuity was defined as a decrease in logMAR acuity of 0.1. Factors associated with visual outcome within 6 months after surgery were identified using logistic regression modeling. The duration of postoperative survival was calculated. Results: In the 207 participants (mean age 92.0 ± 2.1), 79.7% achieved visual improvement after cataract surgery. Forty-eight percent (mean age 97.4 ± 2.8) were alive on December 31, 2012. The most common systemic comorbidities were hypertension (66.2%), diabetes mellitus (25.1%), and myocardial infarction (19.8%). Age-related macular degeneration (AMRD) (15.9%), glaucoma (10.6%), and myopic degeneration (5.3%) were the three most common ocular comorbidities. Uncomplicated cataract surgery was performed in 87.0% cases. The most common complications were vitreous loss (8.2%), posterior capsular rupture (7.2%), and zonular rupture (4.8%). Participants with AMRD (P = .001, odds ratio (OR) = 4.77, 95% confidence interval (CI) = 1.86�12.26) and vitreous loss (P = .001, OR = 12.86, 95% CI = 2.71�61.10) were less likely to achieve postoperative visual improvement. Conclusion: Despite a high prevalence of systemic and ocular comorbidities in very elderly adults, good clinical outcomes of cataract surgery were attainable. ARMD and vitreous loss were associated with a lower chance of postoperative visual improvement.

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.

Summary Background Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have been scarcely reported. Objectives To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention-to-treat analysis. Results We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n = 24), adalimumab (n = 7), etanercept (n = 6), ustekinumab (n = 3) or efalizumab (n = 2). A 75% improvement of BSA or Psoriais Area and Severity Index 12–14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events, consisting of bacterial infection in seven of them, were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was administered for up to 48 weeks in 34% of flares. Conclusions Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side-effects is frequently observed on a longer term, with only one-third of patients still receiving the same drug after 1 year. The most significant safety concern consists of severe infections.

To study the effect of concurrent psychiatric disorders on health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA).Consecutive Chinese patients who fulfilled the American College of Rheumatology (ACR) criteria for RA were recruited and interviewed by a psychiatrist for psychiatric disorders using the Chinese Bilingual Structured Clinical Interview for DSM-IV Axis I Disorders, Patient version (CB-SCID-I/P). HRQOL was assessed by the validated Chinese version of the 36-item Short Form Health Survey (SF-36). Sociodemographic and clinical data were also collected. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F).Two hundred patients with RA were studied (79% women, mean age 51.4 ± 10.5 years; median RA duration 4.0 years). Forty-seven (23.5%) patients were diagnosed with a psychiatric disorder: depressive disorders in 29 patients and anxiety disorders in 26 patients. Patients with either condition had significantly higher fatigue scores (26 ± 8.8 vs. 16 ± 6.9, p0.001) and were more likely to be unemployed (p = 0.02) and dependent on government subsidy for living (p0.001) than those without. The scores of the eight domains and the physical and mental components of the SF-36 were significantly lower in RA patients with psychiatric disorders (p0.001 in all). In a linear regression model, the presence of either depressive or anxiety disorders (β = -0.23, p0.001), older age (β = -0.16, p = 0.006), self-perceived pain (β = -0.25, p0.001) and fatigue (β = -0.42, p0.001) were independently and inversely associated with the total SF-36 score after adjustment for disease activity and other sociodemographic variables.Concomitant depressive or anxiety disorders in RA patients are associated with significantly poorer HRQOL. Early identification and treatment of psychiatric disorders in RA patients are warranted.

Objective. We previously showed that DU significantly increased global and hand disability with a significant impact on activities of daily living (ADLs) and work disability. This study aims to evaluate the impact of digital ulcer (DU) healing on disability and daily activity limitations in SSc. Methods. From January 2008 and June 2009, we prospectively evaluated 189 SSc patients for DU history, disability, employment and occupational status during meetings of the French SSc Patient Association (n = 86, 45.5%) or during hospitalization (n = 103, 54.5%)1. Among the 60 patients with at least one active DU at baseline (M0), 40 patients were followed longitudinally over 6 (3) months. These patients were evaluated for DU history, global and hand disability, health-related quality of life (HRQoL), daily activity limitation and employment status. Results. The median (IQR) age was 57.5 (43.5-68) years and the median (IQR) disease duration was 8.3 (3-16.5) years. Twenty-two (55%) patients had diffuse SSc and 34 (85%) were females. At baseline, a mean of 2.9 (2.8) DU per patient was reported. Thirty-three (82.5%) patients had ischaemic DU, 7 (17.5%) patients had >1 DU associated with calcinosis and 13 (32.5%) patients had mechanical DU. Thirteen (32.5%) patients had >4 DU at baseline. Among the 40 patients, 16 (40%) patients showed complete ulcer healing. In these patients with DU, the presence of calcinosis was associated with a lower probability of healing (P = 0.03). Comparison between healed and no-healed DU patients showed an improvement of hand disability provided by an improvement of the Cochin Hand Function score (P = 0.05)) and a trend towards HAQ domain dressing and grooming (P = 0.06) between M0 and M6 (3) visit in healed patients but not in no-healed patients. Concerning HRQoL, there were no difference for Mental and Physical component Scores of SF-36 but significant improvement of Bodily Pain score (P = 0.04) and Physical Role score (P = 0.05) between M0 and M6 (3) visit in patients with healed DU. The absence of healing was associated with significantly decreased work productivity (P = 0.05), whereas the performance in ADL was not significantly decreased (P = 0.15). Patients who were on sick-leave and who received some help for household tasks at the time of active DU were more likely to heal. Conclusion. For the first time, we provide prospective data with evidence that DU healing is associated with an improvement in hand function. Sick leave was associated with better healing of DU

We recorded side effects and other complications of 813 plasma exchanges used in early treatment of polyarteritis nodosa and Churg-Strauss angiitis in a prospective study of 72 patients (22-75 years old). All the patients were also treated with a corticosteroid (1 mg/kg/day), and half were included in a randomized trial of cyclophosphamide (2 mg/kg/day during 1 year). Centrifugation was used in 678 plasma exchange sessions (83.4%) and filtration in 128 (15.7%) (no data were available about the technique used in seven cases). The replacement fluid in 745 sessions was 4% albumin and in 115 was fresh-frozen plasma; eight patients received both (47 sessions). Two hundred and fifty-one complications were reported in 60 patients during 206 (25.3%) of the 813 completed exchanges; 47 sessions (5.8%) were temporarily stopped as a result of complications. The most common problems were technical difficulties (in 90 sessions), moderate or severe hypotension (in 52), and allergy to the replacement fluid (in 51). Hepatitis B antigen appeared in one patient. In four patients, plasma exchange was stopped permanently because of the severe side effects. No patient died during a session. Twelve of the 72 patients died during the study, six in each of the two groups. In the group treated by a combination of corticosteroid and plasma exchange, deaths were related to the deleterious effects of the disease itself and occurred after 12.8 +/- 11.1 months (1-26 months). In the group treated by the same combination plus cyclophosphamide, four of the six deaths were due to severe infections, which were related to leukopenia in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Resume La maladie de Lhermitte-Duclos, appelee encore « gangliocytome dysplasique cerebelleux », est une entite rare, caracterisee par une lesion hamartomateuse en fosse posterieure. Le syndrome de Cowden, ou « syndrome des neoplasies-hamartomes », rare et sous-diagnostique, est une genodermatose autosomique dominante, avec haute incidence de tumeurs malignes. Plusieurs cas cliniques recents montrent que la maladie de Lhermitte-Duclos peut s’integrer dans le cadre d’un syndrome de Cowden. Les auteurs rapportent deux cas de maladie de Lhermite-Duclos avec syndrome de Cowden chez des patients adultes. Le premier cas est celui d’une femme de 40 ans, qui presentait une hypertension intracrânienne avec macrocephalie, une dysplasie fibrokystique de sein ainsi qu’un goitre thyroidien ; l’examen clinique montrait des lesions cutaneo-muqueuses ; sa mere, son pere et un oncle avaient des manifestations de syndrome de Cowden. Le second cas est celui d’un homme de 38 ans, qui avait un œdeme papillaire en relation avec une tumeur cerebelleuse ; il avait des antecedents entrant dans le cadre d’un syndrome de Cowden et son histoire familiale confirmait cette hypothese. Le premier patient etait opere pour sa maladie de Lhermitte-Duclos. Une attitude de surveillance etait envisagee pour le second, avec un recul clinique et radiologique tout a fait stables de plus de 7 ans. Nous pensons que la maladie de Lhermitte-Duclos et le syndrome de Cowden constituent un type de phacomatose. Une attitude expectative peut etre envisageable en raison du faible potentiel evolutif de croissance tumorale. Cependant, ces patients doivent etre examines avec attention en raison du risque de degenerescence tumorale maligne.

Post-transplant cutaneous lymphomas are rare. Cutaneous T-cell lymphomas account for 30% of these lymphomas. The clinical appearance of the skin lesions is identical to cutaneous lymphomas observed in non-immunosuppressed patients, with infiltrated plaques, nodular and ulcerated tumors, but with an increased frequency of erythroderma. Standard histology and immunohistochemistry are also consistent with the features of mycosis fungoides and CD30+ cutaneous lymphomas observed in the general population. However, the pronostic differs from the usually favourable outcome of cutaneous T-cell lymphomas, as 8 out of the 13 patients of our series died, in less than 1 year for 6 of them. This unfavourable course appears to be the same as that observed for systemic T-cell lymphoma in transplant recipients. In contrast to post-transplant B-cell lymphomas (systemic and primary cutaneous), the link to a virus has not been demonstrated. The prognosis is also less favourable for post-transplant cutaneous T-cell lymphomas than for post-transplant cutaneous B-cell lymphomas.

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

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Summary Background Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies. Objectives To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24). Methods A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up. Results In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36·8 ± 55·5 cm2 and 24·8 ± 45·7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0·001), adherence to compression therapy at W4 (P = 0·03) and W24 (P = 0·01), ankle-joint ankylosis (P = 0·01) and mean percentage of VLU area reduction at W4 (P = 0·04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8·4, 95% confidence interval (CI) 1·9–48·2] and percentage reduction of the VLU area at W4 (OR 1·6, 95% CI 1·0–2·14) as being independently associated with healing. Conclusions These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment.

Background The treatment of stage I Merkel cell carcinoma (MCC) usually includes wide local excision (WLE) combined with irradiation of the tumor bed (ITB). No randomized study has ever been conducted in MCC. The purpose of this study was to assess the efficacy and safety of prophylactic adjuvant radiotherapy on the regional nodes. Patients and methods In this randomized open controlled study, patients for a stage I MCC treated by WLE and ITB were randomly assigned to regional adjuvant radiotherapy versus observation. Overall survival (OS) and probability of regional recurrence (PRR) were primary end points. Progression-free survival (PFS) and tolerance of irradiation were secondary end points. Results Eighty-three patients were included before premature interruption of the trial, due to a drop in the recruitment mainly due to the introduction of the sentinel node dissection in the management of MCC. No significant improvement in OS (P = 0.989) or PFS (P = 0.4) could be demonstrated after regional irradiation, which, however, significantly reduced the PRR (P = 0.007) with 16.7% regional recurrence rate in the observation arm versus 0% in the treatment arm. The treatment was well tolerated. Conclusion The adjuvant regional irradiation significantly decreased the PRR in MCC, but benefit in survival could not be demonstrated.

Bioreducible poly(amido amine)s (SS-PAAs) with different groups in the side chain were evaluated for gene delivery to ovarian cancer cells, both in vitro and in vivo after intraperitoneal administration in mice bearing an ovarian cancer xenograft. Polyplexes of SS-PAAs with e.g. hydroxybutyl or hydroxypentyl side groups induce much higher transfection in vitro than polyplexes of branched pEI (25 kDa) as a positive control. The in vivo transfection efficiency of polyplexes of SS-PAA with hydroxybutyl side groups is similar to that of linear pEI (22 kDa).

Summary Background Some cases of dermatofibrosarcoma protuberans (DFSP) do not protrude above the skin. Objectives To assess the prevalence of these DFSPs and further to describe their presentation and course. Methods One hundred and forty-three patients were retrospectively collected. They were asked to complete a standardized questionnaire indicating the history and appearance of the DFSP from the first skin changes identified to the time of diagnosis. Results Eighty-one DFSPs were described as protuberant ab initio, and 62 as initially nonprotuberant (npDFSP). The latter remained at this stage for a mean period of 7·6 years. Twenty-nine per cent of npDFSPs were ‘morphoea-like’, 19% were ‘atrophoderma-like’ and 42% were ‘angioma-like’. Age at diagnosis was similar for both initial presentations. npDFSPs were most often misdiagnosed by physicians. Conclusions Nearly half the patients first identified their early DFSP-related skin changes as patches. Both this frequency and the long duration at this preprotuberant stage should prompt dermatologists to consider the diagnosis of DFSP earlier, in order to make surgical treatment easier.

Introduction and objectives Tuberculosis (TB) has re-emerged as an important public health problem in the UK. Subsequent to the publication of ‘Stopping Tuberculosis in England: An Action Plan from the Chief Medical Officer’ in 2004, the London TB Metrics was produced, against which the performance of local TB services can be measured. This audit recorded relevant aspects of diagnosis and management of all adult TB patients in a local district hospital TB clinic, and compared them against the Metric targets. Methods Eight of the nine Metric indices were selected (neonatal BCG vaccination coverage excluded). Data were collected on all adult patients seen in an outpatient TB clinic in 2008 and compared against targets set in the London TB Metrics. Results 73 adults (35 males, 38 females) were diagnosed, of which 38 (49.4%) were pulmonary cases. 69 patients (94.5%) were offered an HIV test; 63 patients attended for testing, with two patients testing positive for HIV. Abstract P57 Table 1 summarises results achieved. Discussion We have audited performance of a local TB clinic against targets set in the London TB Metrics. Achieving a microbiological diagnosis in 65% is difficult as patients are often already on treatment before referred into the service. Changes were instituted in laboratory workflow patterns to improve sputum smear result availability within one working day, increasing to 93.8% in the first 2 months of 2010. Conclusion The London TB Metrics targets are achievable (seven of eight targets met) and provide an audit tool that may facilitate improvements in the standard of TB care.

Anti-β2-glycoprotein I antibodies are considered as a specific marker for the antiphospholipid syndrome. In contrast to lupus circulating anticoagulant and anticardiolipin (aCL) antibodies, they are usually not found at significant levels in infections. We report a case of pulmonary embolism in an adult with varicella. Transient significant levels of aCL antibodies and of IgM anti-b2-GPI antibodies were observed. No other prothrombotic factor, including free protein S antigen deficiency, was found. The direct pathogenic role of these transient antibodies on the thrombotic event may then be suspected. They are probably associated with VZV acute infection and are absent two months after varicella.

Purpose: A tumor control probability (TCP) model incorporating a generalized linear‐quadratic (gLQ) model was investigated to predict clinical outcome after radiation therapy for patients. The clinical utility of the model incorporating the following individually measured radiobiology parameters: intrinsic radiosensitivity, proliferation and number of clonogenic cells, was evaluated. The hypothesis in the study was that the incorporation of individually measured tumor parameters into the TCP model would increase its reliability in predicting treatment outcome compared with the use of average population derived data. Methods: 46 patients with head and neck tumors were included and most of them received both external beam radiotherapy and brachytherapy (as published in Acta Oncologica, 2009; 48:584–590). Primary tumor size was drawn from case records and pre‐treatment CT scans or MRI using two or three dimensional measurements to calculate tumor volume. Surviving fraction after 2 Gy (SF2), reflecting intrinsic radiosensitivity, was estimated by a soft‐agar clonogenic assay (as published in Int J Radiat Oncol Bio Phys, 2000; 46:13–19). Eighteen patients receiving external beam treatment alone were used to perform statistical analyses. Local control was determined by follow‐up records. Results: SF2 correlated significantly with tumor response (p=0.04, Mann‐Whitney test), but initial tumor volume did not (p=0.6). Eight of the 18 patients had a >95% calculated tumor control probability and none developed a local recurrence, yielding a negative predictive value of 100%, compared with 67% for population‐derived data. There was a statistically significant difference in local control levels between the patient group with >95% vs.

The records of 41 courses of plasma exchange (PE) performed in the treatment of 37 patients with dermatomyositis (21) or polymyositis (16) were retrospectively reviewed. In nearly all cases, PE was added to a previously ineffective therapeutic regimen of corticosteroids plus cytotoxic drugs. An improvement in muscle strength was obtained during the PE course in 26 cases (63.4%), especially in diseases with an acute course. Despite their uncontrolled nature, these results confirm the previous publications of P. Dau, suggesting that PE may be of therapeutic value in dermatomyositis and polymyositis.

Objective. To assess the effect of oral treatment with micronized purified flavonoid fraction (MPFF) on leg ulcer healing. Design. Meta-analysis of randomised prospective studies using MPFF in addition to conventional treatment. Materials and methods. Five prospective, randomised, controlled studies in which 723 patients with venous ulcers were treated between 1996 and 2001 were identified. Conventional treatment (compression and local care) in addition to MPFF was compared to conventional treatment plus placebo in two studies (NZ309), or with conventional treatment alone in three studies (NZ414). The primary end point was complete ulcer healing at 6 months. Results. At 6 months, the chance of healing ulcer was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone (RRR: 32%; CI, 3‐70%). This difference was present from month 2 (RRR: 44%; CI, 7‐94%), and was associated with a shorter time to healing (16 versus 21 weeks; PZ0.0034). The main benefit of MPFF was present in the subgroup of ulcers between 5 and 10 cm 2 in area (RRR: 40%; CI, 6‐87%), and those present for 6‐12 months duration (RRR: 44%; CI, 6‐97%). Conclusion. These results confirm that venous ulcer healing is accelerated by MPFF treatment. MPFF might be a useful adjunct to conventional therapy in large and long standing ulcers.