First-in-human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy.

BACKGROUND: Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL). METHODS: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. RESULTS: No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. CONCLUSIONS: PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

Meibomian Gland Changes in Open-angle Glaucoma Users Treated with Topical Medication.

SIGNIFICANCE: Glaucoma patients treated with topical hypotensive eye drops often experience changes in the ocular surface, including the lid margin and the meibomian glands. In this study, the clinical parameters of the ocular surface have been analyzed to detect the presence of meibomian gland dysfunction-related dry eye disease. PURPOSE: This study aimed to evaluate the meibomian gland dysfunction in glaucoma patients secondary to topical antiglaucomatous treatment. METHODS: A total of 131 eyes from different patients with open-angle glaucoma treated with topical medication and 92 eyes from different patients with untreated ocular hypertension were consecutively and prospectively enrolled. The structure of the meibomian glands was assessed using noncontact meibography (Keratograph 5M; Oculus, Wetzlar, Germany), and their function was evaluated by measurement of meibomian glands expressibility, the duct appearance, and the Marx line location. Moreover, tear osmolarity measurement, corneal staining score (Oxford scale), and ocular symptom assessment (Ocular Surface Disease Index questionnaire) were performed. We also compared these variables in the glaucoma group according to the presence (or not) of preservative in topical treatment. RESULTS: Meibomian gland depletion was higher in glaucoma patients with topical medication (P < .001). Furthermore, the quantity of meibomian glands and expressibility of meibum in these patients were altered compared with the control group (P < .001 in both cases). In addition, the glaucoma group presented a higher degree of corneal staining as measured with the Oxford scale (P < .001). The Marx line location score was higher (P < .001 in central Marx line and P < .003 in temporal Marx line) in patients using drugs containing preservative than in those having preservative-free treatment. Logistical regression found that Marx line central, Marx line temporal, quantity of meibum expression, and quality of meibum expression have predictive ability to detect meibomian gland dysfunction-related dry eye disease. CONCLUSIONS: Glaucoma topical treatments produce meibomian gland dysfunction altering their structure and function, and this condition can be worsened using topical treatments containing preservative.

[Primary stromal cyst of the iris: case report].

Primary stromal cysts of the iris are rare, often asymptomatic, and incidentally found entities. Treatment is usually indicated in cases of enlargement or complications. However, imaging tests are required to determine their cystic nature and make an accurate differential diagnosis with malignant tumors, as well as for long-term follow-up. Ultrasound biomicroscopy is the technique of choice, although in most centers anterior segment optical coherence tomography is a more accessible and available imaging modality. We present a case of primary stromal cyst of the iris with an atypical presentation to illustrate the diagnosis and initial follow-up using anterior segment optical coherence tomography and photographs, and the management of complications. Anterior segment optical coherence tomography may be useful in the initial study and follow-up of anterior non-pigmented lesions where the cyst can be fully seen.

Ru-Ce0.7Zr0.3O2-δ as an Anode Catalyst for the Internal Reforming of Dimethyl Ether in Solid Oxide Fuel Cells.

The development of direct dimethyl ether (DME) solid oxide fuel cells (SOFCs) has several drawbacks, due to the low catalytic activity and carbon deposition of conventional Ni-zirconia-based anodes. In the present study, the insertion of 2.0 wt.% Ru-Ce0.7Zr0.3O2-δ (ruthenium-zirconium-doped ceria, Ru-CZO) as an anode catalyst layer (ACL) is proposed to be a promising solution. For this purpose, the CZO powder was prepared by the sol-gel synthesis method, and subsequently, nanoparticles of Ru (1.0-2.0 wt.%) were synthesized by the impregnation method and calcination. The catalyst powder was characterized by BET-specific surface area, X-ray diffraction (XRD), field emission scanning electron microscopy with an energy-dispersive spectroscopy detector (FESEM-EDS), and transmission electron microscopy (TEM) techniques. Afterward, the catalytic activity of Ru-CZO catalyst was studied using DME partial oxidation. Finally, button anode-supported SOFCs with Ru-CZO ACL were prepared, depositing Ru-CZO onto the anode support and using an annealing process. The effect of ACL on the electrochemical performance of cells was investigated under a DME and air mixture at 750 °C. The results showed a high dispersion of Ru in the CZO solid solution, which provided a complete DME conversion and high yields of H2 and CO at 750 °C. As a result, 2.0 wt.% Ru-CZO ACL enhanced the cell performance by more than 20% at 750 °C. The post-test analysis of cells with ACL proved a remarkable resistance of Ru-CZO ACL to carbon deposition compared to the reference cell, evidencing the potential application of Ru-CZO as a catalyst as well as an ACL for direct DME SOFCs.

Radioguided surgery of mesenchymal tumors with 125I seeds.

INTRODUCTION: Radioguided surgery uses radioactive substances to identify and remove hard-to-locate lesions. Mesenchymal tumors constitute a heterogeneous group of neoplasms derived from the mesoderm, including benign lesions and malignant sarcomas. The aim of this study was to evaluate the ability of 125I radioactive seeds to guide intraoperative localization of mesenchymal tumors, analyzing the complication rates and evaluating the margins of the surgical specimens retrieved. METHODS: Retrospective observational study of all consecutive patients undergoing radioguided surgery of a mesenchymal tumor with a 125I radioactive seed from January 2012 to January 2020 at a tertiary referral center in Spain. The seed was inserted percutaneously guided by ultrasound or computed tomography in an outpatient setting. RESULTS: Fifteen lesions were resected in 11 interventions in 11 patients, recovering all lesions marked (100%) with a 125I seed. The lesions included areas of benign fibrosis (26.7%), cellular angiofibroma (6.7%), desmoid tumor (20%), solitary fibrous tumor (13.3%), chondrosarcoma (6.7%), and pleomorphic sarcoma (26.7%), with a high rate of recurrent tumors (60%). There was only one complication (6.7%) due to the seed falling within the surgical bed. According to the UICC classification of residual tumors, 80% of the lesions resulted in an R0 resection, 6.7% were R1 resections, and 13.3% were R2 resections. CONCLUSION: Radioguided surgery is an accurate technique for the resection of hard-to-locate mesenchymal tumors.

Isolated medial rectus muscle rupture after a traffic accident.

A 30-year-old male suffered an orbital trauma due to a traffic accident. At the Emergency Unit, the patient presented with avulsion of the upper left eyelid in the medial canthus, wounds in the lower eyelid and the inferior canaliculus, conjunctival laceration, proptosis and palpebral hematomas. The patient reported persistent diplopia. During the examination, exotropia and total absence of adduction were observed. Computerized tomography (CT) revealed a discontinuity at the left medial rectus. No orbital fractures were identifiable. The medial rectus was still attached to its anatomic insertion at the globe. The discontinuity was suggestive of laceration or rupture of this muscle at approximately 10-12 mm from its insertion. Surgical exploration revealed total rupture of the medial rectus at approximately 12 mm from its insertion. The posterior edge of the damaged muscle was found and sutured to its anterior edge with 6-0 polyglactin. The following day, the eyes were completely straight and the patient did not mention any signs of diplopia. Botulinum toxin injection into the ipsilateral lateral rectus was not necessary. After six months of follow-up, the patient still reported no diplopia. When muscular laceration is suspected after an orbital trauma, early CT is recommended. The only procedures that assure a significant recovery of the normal function of the eye are early muscle repair and avoidance, if possible, of transposition surgery.

New pathogenic variant in the FGF10 gene in the agenesis of lacrimal and salivary gland syndrome: Ophthalmological and genetic study.

Aplasia/agenesis of lacrimal and salivary glands is a rare congenital defect that has been associated with disturbances in fibroblast growth factor 10 (FGF10). It can present with symptoms of congenital lacrimal obstruction, dry eye, and dry mouth. We report the ophthalmological and genetic study of a 19-year-old woman and her relatives suffering from this syndrome. A new probably pathogenic variant is described in the FGF10 gene.

Early Changes in Visual Quality and Corneal Structure after DMEK: Does DMEK Approach Optical Quality of a Healthy Cornea?

PURPOSE: To evaluate early changes in visual function and visual quality parameters after Descemet membrane endothelial keratoplasty (DMEK) and to compare the outcomes with healthy controls. METHODS: Thirteen patients who underwent DMEK and 14 controls were evaluated. All subjects underwent visual function evaluation, including visual acuity under photopic and mesopic lighting conditions and contrast sensitivity (CSV) tests CSV 1000 and Pelli-Robson. Corneal parameters were assessed with Oculus Pentacam. Corneal mean keratometry (Km), corneal densitometry values, and low and high order aberrations (LOA and HOA) were recorded. In DMEK patients, all tests were performed before surgery and 1 and 6 months after surgery. RESULTS: In patients who underwent DMEK, photopic visual acuity improved from 0.59 to 0.31 at 1 month (p=0.013) and 0.13 at 6 months (p=0.008); mesopic visual acuity and all contrast sensitivity values (both CSV and Pelli-Robson test) improved significantly in the first month (p < 0.005). A significant decrease was observed in corneal density in the 0-2 mm ring (from 43.83 to 35.60, p=0.043) and mean posterior Km (from -5.84 to -6.80, p=0.005) in the first month. Corneal HOAs and all corneal densities improved at 6 months after DMEK (p < 0.05). All visual function parameters and corneal aberrations remained lower and higher, respectively, compared with healthy controls (p < 0.05). Corneal densities were comparable with controls at 6 months after DMEK (p > 0.05). CONCLUSIONS: Patients undergoing DMEK present visual function improvement and a decrease in corneal density at 1 month after surgery. Decrease in corneal posterior HOAs can be observed at 6 months. However, visual function outcomes and corneal aberrations remained worse compared with healthy controls.

Short-term mitomycin C followed by long-term interferon alpha2beta for conjunctiva-cornea intraepithelial neoplasia.

PURPOSE: To report a case of extensive conjunctiva-cornea intraepithelial neoplasia (CIN) treated topically with mitomycin C (MMC) and interferon (INF)-alpha2beta without surgical resection. METHODS: Case report. RESULTS: : An 82-year-old woman showed an extensive gelatinous red mass in the bulbar conjunctiva with invasion into the caruncle, inferior fornix, and tarsal conjunctiva and extending for 270 degrees of the corneal surface. A diagnosis of CIN was made by surgical biopsy. Surgical excision with safety margins carried the risk of limbal stem cell depletion. A conservative treatment strategy was used with 2 cycles of topical MMC (0.02%), followed by INF-alpha2beta eye drops at a dose of 1 million IU/mL, 4 times a day until tumor disappearance. Total resolution was noted after 75 days of treatment with INF, with no clinical evidence of limbal stem cell deficiency. After 1 year of monitoring, no signs of CIN recurrences were observed. CONCLUSION: MMC (0.02%), followed by INF-alpha2beta (1 million IU/mL) 4 times a day, is an effective treatment against highly extensive CIN, in cases where surgical resection with safety margins is unfeasible.

Evaluation of Early Graft Detachment After Descemet Membrane Endothelial Keratoplasty Using New Swept-Source Optical Coherence Tomography.

PURPOSE: To evaluate the ability of Swept-source optical coherence tomography (SS-OCT) in detecting early endothelial graft detachment after Descemet membrane endothelial keratoplasty (DMEK) and to determine the possible causes of graft detachment using 2 different protocols for anterior segment (AS) imaging. METHODS: Eight eyes from 8 consecutive DMEK surgeries were evaluated. High-resolution images were captured with SS-OCT using 2 different radial protocols for AS imaging (16- and 6-mm radial protocols). Central and peripheral corneal changes were evaluated. RESULTS: All eyes developed early graft detachment detectable with the SS-OCT. The 16-mm radial protocol scanned the cornea detecting early graft detachment in 6 out of 8 cases. The 6-mm radial protocol provided detailed images of the cornea, detecting early detachment in all cases. Stromal irregularities and small remnants only detectable using SS-OCT were the possible cause of detachment in 3 cases. One of the 8 eyes had air reinjection. The detachment in that eye was apparent by slit-lamp examination. The detachments spontaneously resolved in the other 7 eyes. AS SS-OCT evaluation was found to have added diagnostic value to biomicroscopy in 5 of these eyes (64.5%). CONCLUSIONS: AS SS-OCT is sensitive in detecting early graft detachment after DMEK. The 16-mm radial protocol of Triton SS-OCT is superior regarding quick scan of the entire cornea providing a general visualization of the DMEK graft. The 6-mm radial protocol provides detailed corneal imaging of a selected area, which is useful for evaluating structural alterations that are not detectable with larger scans and may affect the adherence of the endothelial graft.

Incidence Patterns and Trends of non-Central Nervous System Solid Tumours in Children and Adolescents. A Collaborative Study of the Spanish Population Based Cancer Registries.

OBJECTIVE: To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. METHODS: Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. RESULTS: The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95%CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95%CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. CONCLUSIONS: Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence in adolescents increased significantly over the whole period 1983-2007. Several specific tumour groups showed significant rises or decrements in childhood or adolescence, although the small number of cases precludes showing significant trends or inflexion points.

Treatment of Acanthamoeba neurotrophic corneal ulcer with topical matrix therapy.

BACKGROUND: This study was done to evaluate the visual and anatomical outcomes of topical regenerating agents as a novel therapy for neutrophic corneal ulcer (NCU) secondary to acanthamoeba infection. FINDINGS: A 20-year-old woman with a history of contact lens wear was referred to our hospital for keratitis after responding poorly to conventional treatment. In vivo confocal microscopy images suggested acanthamoeba keratitis with double-walled cysts in the anterior corneal stroma. Acanthamoeba infection was confirmed by laboratory findings. She was started on 0.1 % propamidine and 0.02 % chlorhexidine drops every hour. The antibiotic and antifungal drops were stopped when bacterial and fungal cultures proved negative. A central neurotrophic corneal ulcers (NCU) appeared, and despite treatment with artificial tears, bandage contact lens, and autologous serum, the ulcer worsened and she was treated with topical CACICOL20 (1 drop every 2 days) for 8 weeks. The corneal defect was completely repaired in 3 weeks. The treatment was well tolerated, and no local or systemic side effects were noted. Visual acuity remained 20/400. Two months later, the defect was still closed and the patient continued with 0.1 % propamidine and 0.02 % chlorhexidine drops, bandage contact lens, artificial tears, and autologous serum. CONCLUSIONS: Topical regenerating agents interact with components of the extracellular matrix, binding matrix proteins and protecting them from proteolysis, restoring the matrix environment, and improving tissue healing. In this case, CALCICOL20 was effective for vision stabilization, wound healing, and was well tolerated for NCU secondary to acanthamoeba infection.

Predictive value of brain natriuretic peptide in the diagnosis of heart transplant rejection.

AIM: To evaluate the pattern of brain natriuretic peptide (BNP) concentration in heart transplant (HT) recipients and its relation to the degree of graft rejection determined by endomyocardial biopsy specimen. METHODS: We studied 71 consecutive HT recipients (62 men, 53 +/- 11 years). The patients underwent 383 biopsies. Creatinine and BNP concentrations and hemodynamic parameters were determined along with the degree of graft rejection using endomyocardial biopsy specimens. We considered treatable rejection as International Society for Heart and Lung Transplantation Grade >or=2 in the first 90 days and >or=3A thereafter. We included a control group of 36 healthy individuals. RESULTS: Brain natriuretic peptide concentration was significantly greater among HT recipients (264 +/- 318 pg/ml) than in controls (17 +/- 16 pg/ml). In the first 90 days, BNP concentration was significantly greater among the patients with graft rejection (510 +/- 470, n = 84, vs 278 +/- 255, n = 87; p < 0.0001), although the corresponding discriminatory capacity was small. After the first 90 days, BNP values were similar in patients with and without graft rejection (170 +/- 297, n = 17, vs 142 +/- 203, n = 195; p = not significant). Creatinine concentration increased with time after transplantation and did not correlate with BNP concentration. We observed significant positive correlation between BNP concentration and hemodynamic parameters. CONCLUSIONS: Brain natriuretic peptide concentration remains increased after HT, with stabilization after the 4th month. Brain natriuretic peptide concentrations are slightly greater among patients with treatable rejection, particularly in the first 90 days, although BNP concentration lacks discriminatory capacity to serve as a guide to performing biopsy.

Cleavage of corneal basement membrane components by ethanol exposure in laser-assisted subepithelial keratectomy.

PURPOSE: To determine the anatomic cleavage plane after exposure to 20% ethanol for approximately 20 to 25 seconds to create an epithelial flap in laser-assisted subepithelial keratectomy (LASEK). SETTING: Ocular Surface Research & Education Foundation, Miami, Florida, and Hermann Eye Center Refractive Surgery Center, Houston, Texas, USA. METHODS: Immunofluorescence staining using monoclonal antibodies against laminin 5, collagen VII, and integrins beta(1) and beta(4) was performed to determine the anatomic location of the cleavage plane in an epithelial flap created by 20-second exposure to 20% ethanol in cadaver eyes and in epithelial flaps obtained from LASEK patients. RESULTS: Immunofluorescence staining to laminin 5 and integrin beta(4) was patchy in the lifted flap and the remaining corneal basement membrane. Immunostaining to collagen VII, the main component of anchoring fibrils, remained exclusively in the corneal bed. Immunostaining to integrin beta(1), present in the pericellular location of all epithelial cell layers, remained exclusively in the epithelial flap. This finding was consistent in cadaver corneas and LASEK epithelial flaps. CONCLUSIONS: The cleavage plane of the ethanol-induced corneal epithelial flap is located between the lamina lucida and the lamina densa of the basement membrane, where integrin beta(4) interacts with laminin 5 to form hemidesmosomes.

[Brain natriuretic peptide. Diagnostic value in heart failure]. / Péptido cerebral natriurético. Valor diagnóstico en la insuficiencia cardíaca.

BACKGROUND: Nowadays a number of diverse biochemical markers have been identified in patients with heart failure (HF) that could indicate the severity of the patients' illness. Among them, probably the most useful is brain natriuretic peptide (BNP) because it is easily obtained and because of its diagnostic and prognostic information. Our objective was to assess the association between BNP and other different associated variables previously known to be related to the evolution of HF, as well as its utility to distinguish systolic from diastolic HF. PATIENTS AND METHOD: We studied 114 patients admitted consecutively for symptomatic HF for all causes (age: 66 years, male: 60%). In all patients plasma BNP was measured, from the third day of admission, with a specific radioinmunoassay. Echocardiography was performed in 101 patients. RESULTS: BNP plasma levels increased in proportion to functional class (p = 0.01) and the degree of left ventricular dysfunction (p = 0.0001, r = 0.44). There was also an association between BNP and male sex (p = 0.008), higher plasmatic creatinine (p = 0.01, r = 0.25), Iarger ventricular diameters (p = 0.0001) and higher pulmonary systolic pressure (p = 0.001, r = 0.44). In the multivariate analysis, BNP was independently related to the rest of variables with left systolic ventricular function (p = 0.0001). Despite this association, we did not find a satisfactory cut-off value in BNP, with a good sensitivity and specificity value from the total number of patients, of which specifically systolic dysfunction as a cause of HF was detected. CONCLUSIONS: a) BNP increases proportionately to the left ventricular dysfunction and HF severity, and b) BNP is not a useful tool to distinguish systolic from diastolic HF.

Autonomic nervous system dysfunction in advanced systolic heart failure.

BACKGROUND: An alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients. METHODS: We analyzed 23 patients with advanced HF (NYHA III-IV/IV and IV/IV) and EF<35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of (123)I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined. RESULTS: In the study of the SNS, HMR values were 1.32 ± 0.12, and WR 0.36 ± 0.1. Higher creatinine levels were associated with a lower WR (r=-0.604; p=0.02). In the study of the SNP, TO was higher the lower the LVEF (r=-0.410; p=0.052), and age was associated with a lower TS (r=-0.4; p=0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r=-0.399; p=0.059) and WR with TS (r=-0.447; p=0.033). CONCLUSIONS: In stable patients with advanced HF (NYHA III-IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation.

Keratitis after Implantation of Intrastromal Corneal Rings with Spontaneous Extrusion of the Segment.

PURPOSE: To report a case of bacterial keratitis in a patient with a history of intrastromal corneal ring segments (INTACS®) implantation to correct keratoconus. METHODS: The patient's history, clinical presentation, pathological analysis and therapeutic management were reviewed. RESULTS: A 36-year-old-man was referred to our department due to decreased vision and intense pain in his left eye, 40 days after INTACS® implantation for keratoconus. Slit-lamp examination revealed epithelial defects and stromal infiltrates in the lower channel without evidence of the inferior ring. The anterior chamber also showed a significant fibrin reaction to hypopyon. A low-tension suture was removed at the site of the incision. Microbiological study of the conjunctival swab was positive for Staphylococcus epidermidis, but the corneal culture was sterile. The patient was treated with topical fortified and systemic antibiotics. The infection slowly resolved, leaving opacity at the inferior segment site. CONCLUSIONS: Infectious keratitis following INTACS implantation is an infrequent complication that can have important consequences without suitable and early therapeutic management.

Prognostic relationship between two serial determinations of B-type natriuretic peptide and medium-long-term events in heart transplantation.

BACKGROUND: Persistent elevation of B-type natriuretic peptide (BNP) levels in the first year after transplant appears to be associated with an adverse prognosis. However, there are no data on the prognostic value of two serial determinations of BNP at the end of the first year after transplant in clinically stable patients. OBJECTIVES: The purpose of this study was to analyze the association between the increase in two serial determinations of BNP at the end of the first year and the subsequent development of events in medium-long-term follow-up. METHODS: An observational study was conducted in a consecutive series of 71 patients transplanted between January 1999 and January 2001. Patients who were "unstable" or had other conditions that could elevate BNP levels (rejection, elevated pulmonary pressures, renal dysfunction, depressed ventricular function or severe graft vascular disease) were also excluded. The final number of patients included was 51. BNP determinations were performed at 9 and 12 months post-transplant at the same time as biopsies. Three groups were formed depending on the relationship between the two determinations: Group 1 (20 patients), decrease >20%; Group 2 (16 patients), change <20%; and Group 3 (15 patients), increase >20%. The following were considered events: death; late rejection; and ventricular dysfunction associated or not with graft vascular disease. RESULTS: The baseline clinical profile was similar in the three groups. There was a significant difference in the rate of events (Group 1, 10%; Group 2, 32%; Group 3, 53%; p < 0.017). Event-free survival was statistically different between the groups (p = 0.017), mainly because of the large difference between Groups 1 and 3 (p = 0.003). Thus, cumulative event-free survival at 3,000 days was 89.4% for Group 1, 68.3% for Group 2 and 48.2% for Group 3. CONCLUSIONS: The increase between two serial determinations of BNP levels at the end of the first year post-transplant could identify a subgroup of patients with poor outcome.