Magnetic resonance imaging as a structural refinement to the American College of Rheumathology clinical classification criteria for knee osteoarthritis.

OBJECTIVE: To evaluate if fulfilment of the definition of osteoarthritis (OA) based on the American College of Rheumatology (ACR) clinical criteria corresponds to pathological knee findings evaluated by magnetic resonance imaging (MRI). To evaluate if any such criteria is associated with a specific MRI pattern. METHODS: Forty-six consecutive patients aged 50 years or more referred by their general practitioners (GPs) to a radiology department because of non-traumatic knee pain underwent MRI using a dedicated low field (0.2 T) machine. RESULTS: MRI results were compared against the ACR criteria for knee OA. Patients with knee pain fulfilling the ACR criteria showed more severe synovial fluid effusion (OR 6.2, 95% CI 2.02 to 19.1), cartilage lesions in the medial area (OR 2.4, 95% CI 1.2 to 5) and higher mean number of osteophytes (OR 2.3, 95% CI 1.1 to 4.5). The association between single criteria and MRI features was more difficult to establish. Nonetheless, crepitus at joint movement was associated with synovial fluid effusion (p=0.02); bone enlargement was more frequent in patients with lesions of the posterior cruciate ligament (p=0.0001); no palpable warmth was associated with cartilage lesions (p=0.02), and morning stiffness shorter than 30 minutes was associated with the surface of bone edema (p=0.02). CONCLUSIONS: The ACR clinical criteria identify patients showing the most important features of OA. The association between individual clinical ACR criteria and OA pathology depicted by MRI may be difficult to explain on the basis of anatomical changes and needs further evaluation.

Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae.

OBJECTIVES: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae. METHODS: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally. RESULTS: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae. CONCLUSIONS: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Pseudorabies Virus US3 Protein Kinase Protects Infected Cells from NK Cell-Mediated Lysis via Increased Binding of the Inhibitory NK Cell Receptor CD300a.

UNLABELLED: Several reports have indicated that natural killer (NK) cells are of particular importance in the innate response against herpesvirus infections. As a consequence, herpesviruses have developed diverse mechanisms for evading NK cells, although few such mechanisms have been identified for the largest herpesvirus subfamily, the alphaherpesviruses. The antiviral activity of NK cells is regulated by a complex array of interactions between activating/inhibitory receptors on the NK cell surface and the corresponding ligands on the surfaces of virus-infected cells. Here we report that the US3 protein kinase of the alphaherpesvirus pseudorabies virus (PRV) displays previously uncharacterized immune evasion properties: it triggers the binding of the inhibitory NK cell receptor CD300a to the surface of the infected cell, thereby providing increased CD300a-mediated protection of infected cells against NK cell-mediated lysis. US3-mediated CD300a binding was found to depend on aminophospholipid ligands of CD300a and on group I p21-activated kinases. These data identify a novel alphaherpesvirus strategy for evading NK cells and demonstrate, for the first time, a role for CD300a in regulating NK cell activity upon contact with virus-infected target cells. IMPORTANCE: Herpesviruses have developed fascinating mechanisms to evade elimination by key elements of the host immune system, contributing to their ability to cause lifelong infections with recurrent reactivation events. Natural killer (NK) cells are central in the innate antiviral response. Here we report that the US3 protein kinase of the alphaherpesvirus pseudorabies virus displays a previously uncharacterized capacity for evasion of NK cells. Expression of US3 protects infected cells from NK cell-mediated lysis via increased binding of the inhibitory NK cell receptor CD300a. We show that this US3-mediated increase in CD300a binding depends on aminophospholipids and on cellular p21-activated kinases (PAKs). The identification of this novel NK cell evasion strategy may contribute to the design of improved herpesvirus vaccines and may also have significance for other PAK- and CD300a-modulating viruses and cancer cells.

Placental programmed cell death: insights into the role of aquaporins.

STUDY HYPOTHESIS: Are the placental aquaporins (AQPs) involved in the apoptosis of human trophoblast? STUDY FINDING: The general blocking of placental AQPs with HgCl2 and, in particular, the blocking of AQP3 activity with CuSO4 abrogated the apoptotic events of human trophoblast cells. WHAT IS KNOWN ALREADY: Although apoptosis of trophoblast cells is a natural event involved in the normal development of the placenta, it is exacerbated in pathological processes, such as pre-eclampsia, where an abnormal expression and functionality of placental AQPs occur without alterations in the feto-maternal water flux. Furthermore, fluctuations in O2 tension are proposed to be a potent inducer of placental apoptotic changes and, in explants exposed to hypoxia/reoxygenation (H/R), transcellular water transport mediated by AQPs was undetectable. This suggests that AQPs might be involved in processes other than water transport, such as apoptosis. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Explants from normal term placentas were maintained in culture under conditions of normoxia, hypoxia and H/R. Cell viability was determined by assessing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide incorporation. For the general or specific inhibition of AQPs, 0.3 mM HgCl2, 5 mM CuSO4, 0.3 mM tetraethylammonium chloride (TEA) or 0.5 mM phloretin were added to the culture medium before explants were exposed to each treatment. Oxidative stress parameters and apoptotic indexes were evaluated in the presence or absence of AQPs blockers. AQP3 expression was confirmed by western blot and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: First, we observed that in H/R treatments cell viability decreased by 20.16 ± 5.73% compared with those explants cultured in normoxia (P = 0.009; n = 7). Hypoxia did not modify cell viability significantly. Both hypoxia and H/R conditions induced oxidative stress. Spontaneous chemiluminescence and thiobarbituric acid reactive substance levels were significantly increased in explants exposed to hypoxia (n = 6 per group, P = 0.0316 and P = 0.0009, respectively) and H/R conditions (n = 6 per group, P = 0.0281 and P = 0.0001, respectively) compared with those cultured in normoxia. Regarding apoptosis, H/R was a more potent inducer of trophoblast apoptosis than hypoxia alone. Bax expression and the number of apoptotic nuclei were significantly higher in explants cultured in H/R compared with normoxia and hypoxia conditions (n = 12, P = 0.0135 and P = 0.001, respectively). DNA fragmentation was only observed in H/R and, compared with normoxia and hypoxia, the activity of caspase-3 was highest in explants cultured in H/R (n = 12, P = 0.0001). In explants exposed to H/R, steric blocking of AQP activity with HgCl2 showed that DNA degradation was undetectable (n = 12, P = 0.001). Bax expression and caspase-3 activity were drastically reduced (n = 12, P = 0.0146 and P = 0.0001, respectively) compared with explants cultured in H/R but not treated with HgCl2. Similar results were observed in explants exposed to H/R when we blocked AQP3 activity with CuSO4. DNA degradation was undetectable and the number of apoptotic nuclei and caspase-3 activity were significantly decreased compared with explants cultured in H/R but not treated with CuSO4 (n = 12, P = 0.001 and P = 0.0001, respectively). However, TEA and phloretin treatments, to block AQP1/4 or AQP9, respectively, failed in abrogate apoptosis. In addition, we confirmed the expression and localization of AQP3 in explants exposed to H/R. LIMITATIONS, REASONS FOR CAUTION: Our studies are limited by the number of experimental conditions tested, which do not fully capture the variability in oxygen levels, duration of exposure and alternating patterns of oxygen seen in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that any alteration in placental AQP expression might disturb the equilibrium of the normal apoptotic events and may be an underlying cause in the pathophysiology of placental gestational disorders such as pre-eclampsia. Furthermore, the dysregulation of placental AQPs may be one of the crucial factors in triggering the clinical manifestations of pre-eclampsia. LARGE SCALE DATA: n/a. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.

Subthreshold grid laser versus intravitreal bevacizumab as second-line therapy for macular edema in branch retinal vein occlusion recurring after conventional grid laser treatment.

PURPOSE: To compare the effects of subthreshold grid laser treatment (SGLT) and intravitreal bevacizumab injection (IVBI) for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) recurring after conventional grid laser photocoagulation. METHODS: Thirty-five eyes were considered in this prospective, randomised, interventional study and treated with micropulse diode laser (SGLT subgroup) or IVBI (IVBI subgroup). SGLT was administered once, whereas IVBI (1.25 mg) was given at baseline and then on a pro re nata regimen according to ME presence on optical coherence tomography (OCT), performed at monthly examinations over a 12-month follow-up. Primary outcome measures were the mean BCVA changes over the follow-up and the decrease in mean central foveal thickness (CFT) on optical coherence tomography (OCT). Secondary outcomes included the proportion of eyes that gained at least 15 letters (approximately three lines) at the 12-month examination. RESULTS: Eighteen and 17 patients were assigned to SGLT and IVBI subgroups, respectively. At baseline, the subgroups were similar with regard to mean ME duration, BCVA, and CFT. At month 12, mean CFT significantly improved from 484 µm to 271 µm in the IVBI subgroup, whereas it was unchanged in the SGLT subgroup. Mean BCVA changed from 0.92 ± 0.3 (LogMAR) to 0.99 ± 0.2 in the SGLT subgroup; in the IVBI subgroup, mean BCVA showed a statistically significant improvement from 0.94 ± 0.3 to 0.72 ± 0.2. Ten patients in the IVBI subgroup (58 %) and no patient in the SGLT subgroup gained at least three lines. CONCLUSION: At the 1-year follow-up, IVBI provided a significant functional and anatomical improvement, whereas SGLT failed to demonstrate any beneficial effects. IVBI might be a useful approach in the treatment of recurrent ME secondary to BRVO already treated with conventional grid laser photocoagulation. UMIN registry, number UMIN000005014, URL: http://www.umin.ac.jp/ctr/index.htm.

Pharmacological approach to diabetic macular edema.

Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a remarkable impact on public health, and on the quality of life of diabetic patients. Even though laser photocoagulation has been the standard of care for decades, a substantial group of patients are unresponsive and fail to improve after laser treatment. Recently, new pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have revolutionized the treatment of DME. The use of intravitreal drugs is supported by the improvement in visual acuity reported by several clinical trials and can limit the potentially destructive effects of the laser treatment. Encouraging results also emerged from studies evaluating the use of a combination therapy, or the association of intravitreal drugs and laser treatment. This review aims at providing a brief synopsis of the main investigations regarding the current pharmacological approach to DME.

Translation and validation of the PVSQ and DHI-PC questionnaires for pediatric dizziness.

AIMS: Validation of the PVSQ self-report questionnaire (diagnosis) and the DHI-PC caregiver report questionnaire (Dizziness Handicap Inventory) aims to improve the management of pediatric vertigo, which is often under-diagnosed. MATERIALS AND METHODS: The PVSQ and DHI-PC questionnaires were translated according to the Forward-Backward method and presented to a group of patients consulting for dizziness in a referral center and to a control group. A retest was performed at 2weeks for both questionnaires. Statistical validation consisted in calculating discriminatory capacity, ROC curve, reproducibility and internal consistency. The main study objective was the translation and validation of the PVSQ and DHI-PC questionnaires in French. The secondary objectives were to compare results in two subgroups according to the vestibular or non-vestibular etiology of dizziness and to assess the correlation between the two questionnaires. RESULTS: In total, 112 children, in two comparable groups (53 cases and 59 controls), were included. Mean PVSQ score was 14.62 for cases and 6.55 for controls (P<0.001). Reproducibility was moderate, and internal consistency and construct validity were satisfactory. A cut-off of 11 corresponded to maximum Younden index. Mean DHI-PC score was 41.6 (cases only). Reproducibility was moderate, and internal consistency and construct validity were satisfactory. CONCLUSION: The validation of the PVSQ and DHI-PC questionnaires offers two new tools in the management of dizziness, for both screening and follow-up.

Paediatric vestibular assessment in French cochlear implant centres: Challenges and improvement areas.

OBJECTIVE: Survey of paediatric vestibular activity in all 30 French paediatric cochlear implant (CI) centres to identify challenges and areas of improvement. METHOD: All 30 French CI centres answered a 29-question questionnaire about their paediatric vestibular activity, equipment, and management in different clinical situations (e.g. vestibular assessment before a cochlear implantation or in cases of vertigo) at different ages. RESULTS: Eighteen CI centres had dedicated paediatric vestibular clinics and 12 did not. Minimum age required for vestibular testing was 3 years in eight centres. Four vestibular tests stood out: caloric tests, video Head Impulse Test (vHIT), rotating chair, vestibular evoked myogenic potentials (VEMP). Depending on the centre's experience, the use of vestibular tests in clinical routine was very heterogeneous. Expert centres mostly used vHIT and cervical VEMP (in bone conduction) for assessments before the first cochlear implantation in 1-year-old children. Dizziness assessment in 4-year children was based on the use of vHIT, cervical VEMP on bone conduction, rotatory test, and caloric test. Ocular VEMP was rarely used. CONCLUSIONS: Paediatric vestibular assessment requires specific expertise compared to adults. Due to a lack of specialised human resources, some centres may be unable to follow French paediatric CI guidelines. International recommendations could help standardise paediatric vestibular management and public health policies should be discussed to improve training and access for children.

Has the clinical spectrum of gout changed over the last decades?

OBJECTIVES: To evaluate if the clinical spectrum of gout has changed over the last decades, a cohort of 107 patients was studied in relation to the date of disease onset and of presentation to our Institution. METHODS: The structured questionnaires of 107 consecutive patients with gout seen between 1989 and 2009 were retrospectively reviewed. Patients were divided into two subgroups according to the year of the first acute arthritis attack: (a) patients with gout onset dating back to 1967-2001, and (b) patients with gout of later (2002-2009) onset. The patients were also subdivided according to the date of their first admission to our Institution: 1989-2006 and 2007-2009 admissions. RESULTS: The male to female ratio changed from 11.3 in the patients who had the first attack before 2002 to 2.4 in the second onset group (p=0.02). A family history of gout was slightly more frequent in the second subgroup (22.7% vs. 6.4%, p=0.05). The mean number of acute attacks was higher in patients seen before 2002 (p=0.01). Synovial fluid was examined more frequently in the subgroup visited for the first time after 2006 (p=0.001). CONCLUSIONS: Our data indicating that the patients' sex ratio has changed over time, with women more frequently affected, could be of importance to clinicians who often believe that gout is a disease affecting males only. The increased utilisation of synovial fluid analysis suggests a closer attention to the disease in recent years. Clinicians should be aware that gout is increasingly affecting women.

Evidence for anti-VEGF treatment of diabetic macular edema.

Diabetic macular edema (DME) is the most important cause of vision loss in patients with diabetes mellitus. Diabetic retinopathy has a remarkable impact on public health and on the quality of life of diabetic patients and thus requires special consideration. The first line of treatment remains the management of systemic risk factors but is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new strategies in the treatment of DME have been studied, in particular the use of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that acts as a vasopermeability factor and an endothelial cell mitogen. For this reason, it represents an interesting candidate as a therapeutic target for the treatment of DME. The aim of this article is to review the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Imaging of tophi with an extremity-dedicated MRI system.

OBJECTIVES: To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. METHODS: Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. RESULTS: At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. CONCLUSIONS: The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.

The simplified French Matrix. A tool for evaluation of speech intelligibility in noise.

INTRODUCTION: In audiology, the usual tests of speech perception in silence are non-predictive of intelligibility in noise. The French Matrix was developed to assess intelligibility in noise in adults with normal cognitive capacity. A simplified adaptive version, FRA-SIMAT, was derived for use with children and elderly persons with diminished memory span. The aim of the present study was to apply this adaptive procedure to determine signal-to-noise ratio (SNR) according to percentage intelligibility. METHODS: Twenty normal-hearing adults and 60 normal-hearing children aged 5-6 years (G1), 7-8 years (G2) and 9-10 years (G3) were included. FRA-SIMAT uses groups of 3 words, to limit memory demand. RESULTS: In adults, SNR for 50% (SNR-50) and 80% intelligibility (SNR-80) was respectively -7.1±1.4dB and -3.7±1.6dB. In children, SNR-50 was -4.2±1.3dB in G1, -4.6±1.2dB in G2, and -5.5±1.5dB in G3. CONCLUSION: The FRA-SIMAT test of speech perception in noise was validated in adults and children of different ages, and can be implemented as a diagnostic and rehabilitation tool in clinical practice.

Outcome for bilateral cochlear implantation in patients with congenital Cytomegalovirus infection.

OBJECTIVES: To analyze the impact of bilateral cochlear implantation (CI) on perceptual and linguistic development in hearing-impaired children with congenital Cytomegalovirus (CMV) infection. PATIENTS AND METHOD: A retrospective study was performed for the period 1991-2016 in a pediatric CI reference center. Closed Set Word (CSW) recognition scores, Categories of Auditory Performance (CAP) and linguistic level on the MT Lenormand scale (MTL) were compared between bilateral (Bi) and unilateral (Uni) groups 12, 24 and 36 months after first CI (CI-1). RESULTS: 84 patients with congenital CMV infection who underwent CI were included, in 2 groups: sequential or simultaneous bilateral CI (Bi) (N=20), and unilateral CI (Uni) (N=64). Twelve, 24 and 36 months after CI-1, CSW scores were 35.56%, 64.52% and 82.93% in Uni and 60.3%, 85% (P=0.0084*), and 100% (P=0.00085*) in Bi. CAP scores 12, 24 and 36 months after CI-1 were 2.57, 3.85 and 4.3 in Uni and 3.91 (P=0.0068*), 5.00 (p=0.029*) and 5.50 (P=0.051*) in Bi. MTL linguistic level scores at 12, 24 and 36 months were 0.72, 1.25 and 1.65 in Uni, and 1.72, 3 (P=0.033) and 3.11 (P=0.045) in Bi. These significantly better scores in Bi at 24 and 36 months after CI-1 were also found on analysis of subgroups with no associated neurologic disorder (P=0.046* and P=0.032*), no associated psychiatric pathology (P=0.0055* and P=0.0073*), and no other associated disorder (P=0.0018* and P=0.035*), and for all subgroups together (P=0.0036 and P=0.037). CONCLUSION: Bilateral CI is a faster way than unilateral CI for patients with congenital CMV infection to achieve structured fluent oral language. 50% of the series showed cerebral abnormalities on MRI, without difference between groups. This was not in itself predictive of poor progression of oral communication, unless associated with major neurologic disorder. Some children made little or no use of their CI in the medium term.

Prognostic value of estrogen receptor and Ki-67 index after neoadjuvant chemotherapy in locally advanced breast cancer expressing high levels of proliferation at diagnosis.

PURPOSE: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. PATIENTS AND METHODS: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≥ 15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. RESULTS: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. CONCLUSIONS: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.

Steroids as part of combination treatment: the future for the management of macular edema?

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, plays a major role in vision loss related to diabetic retinopathy. This article presents an in-depth analysis of therapeutic perspectives on DME by means of an approach based on combination therapy with steroids. Corticosteroid drugs have been demonstrated to both inhibit the expression of vascular endothelial growth factor (VEGF) and the VEGF gene, and to have antiinflammatory properties. A treatment algorithm is provided regarding the management of DME. While grid laser photocoagulation remains the first-line therapy for focal vasogenic DME, diffuse DME can be effectively treated by means of intravitreal injections of corticosteroids. Recalcitrant DME can also be managed beneficially with intravitreal steroids. The management of DME is complex, and often multiple treatment approaches are needed. Each form of DME should be properly classified and specifically treated. The combination treatment has still an important role in the combined treatment options for DME.

Outcome and management of newborns with congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of hearing loss and neurological disorder in children. Its overall prevalence is approximately 0.5% in Europe. In France, systematic screening during pregnancy is not recommended; screening is performed only if there are maternal or fetal symptoms suggestive of this infection. Approximately 90% of infected newborns are asymptomatic at birth, and among them the risk of neurosensory sequelae is 5-15%. By contrast, the prevalence of neurosensory impairment in symptomatic newborns at birth varies from 17% to 60%. Congenital CMV infection must be confirmed at birth before the 21st day of life by polymerase chain reaction (PCR) on saliva or urine samples. A complete clinical examination, blood tests (blood count, liver function test, CMV PCR), hearing tests, brain ultrasound and eye fundus examination should be performed. Neurological and auditory follow-up must be extended well beyond the neonatal period because the occurrence of neurosensory sequelae may be delayed. Oral valganciclovir is the recommended treatment in moderate or severe congenital CMV infections for a period of 6 weeks to 6 months; such treatment requires regular monitoring because of its possible side effects.

Risk factors for gouty dactylitis.

OBJECTIVE: To investigate the risk factors associated with dactylitis in gout. METHODS: The questionnaires of 73 consecutive gouty patients, diagnosed according to the ACR criteria, were reviewed. They were consecutively screened for the presence of dactylitis. RESULTS: Seven out of 73 (9.6%) patients showed dactylitis. They had (1) longer disease duration, (2) a higher number of involved joints, (3) higher serum uric acid concentration, (4) more tophi, (5) higher ESR, and (6) a higher number of ACR criteria besides crystal identification, than the others. By logistic regression, renal stones (OR 13.3, 95% CI 1.1-158.3), upper extremity involvement (OR 4.9, 95% CI 1.4-16.6), number of ACR criteria (OR 1.9, 95% CI 1.1-3.3), and ESR (OR 1.02, 95% CI 1-1.04), significantly predicted dactylitis. CONCLUSIONS: Dactylitis is a feature of gout representing an indicator of disease severity.

[Clinical features of gout in a cohort of Italian patients]. / Caratteristiche cliniche della gotta in una coorte di pazienti Italiani.

OBJECTIVE: To assess the clinical characteristics of gout and its diagnostic approach in a group of Italian patients. METHODS: In a retrospective analysis, we evaluated 72 consecutive gouty patients examined in the years 2000-2007. We recorded demographic data, family history, comorbidities and disease characteristics (seasonality of the attacks, joints affected, serum uric acid concentration, and treatment). RESULT: 63/72 (87.5%) patients were men and 9 women, with mean age 61.9+/-13.7 years. 8/72 (11.1%) patients reported a familial history of gout. The first attack occurred mainly in the months of June, July and December. The first metatarsophalangeal joint was affected in 59.7% of patients and the hand in 25%. Treatment changed over the follow-up period, with a decreased use of NSAIDs (p<0.0001) and an increased use of colchicine (p=0.015) and allopurinol (p<0.0001). In 9 (12.5%) patients, joint aspiration was performed and monosodium urate crystals were found in synovial fluid or tophi. 42/72 (58.3%) patients fulfilled a minimum of 6 clinical criteria of the American College of Rheumatology, necessary for gout diagnosis. 47/72 (65.3%) patients, met the EULAR recommendations and had an 82% probability of being affected by gout. CONCLUSIONS: The diagnosis of gout is not always easy because of its changing clinical spectrum. Identification of MSU crystals in joint aspirates was obtained only in a minority of patients. In this setting the diagnosis with gout was often based on the observation of an acute intermittent monoarthritis involving mainly the first metatarsophlangeal joint, associated with hyperuricaemia and responsive to colchicine.

Hearing impairment and osteogenesis imperfecta: Literature review.

The goal is to clarify the epidemiology of hearing loss in patients with osteogenesis imperfecta (OI), so as to improve management. A literature review analyzed data from 15 patient series. Hearing loss prevalence in OI varied widely, from 2% to 94.1%. Typically, hearing loss was conductive in young patients and sensorineural in older patients. Prevalence increased with age, but after 50 years the increase was slight, and seldom became total. Hearing loss was usually bilateral, but not necessarily symmetrical. There were no correlations between type of mutation (COL1A1 or COL1A2), prevalence, type or severity of hearing loss, or age of symptom onset; there was intra-familial variability. There was also no correlation between mutated gene, type of mutation and auditory phenotype. Frequency, type and severity of hearing loss were unrelated to other clinical parameters. Hearing loss prevalence depended on type of OI: higher in type I and lower in type IV. Incidence of otitis media was higher in children with OI, related to the associated craniofacial dysmorphia. Hearing screening before 5 years of age with long-term follow-up are recommended.