Utilidad del injerto de membrana amniótica en el manejo de la exposición del implante XEN® / Usefulness of the amniotic membrane graft in the management of the exposure of the XEN® implant

Se presenta el caso de una mujer de 79 años con glaucoma severo y falta de adherencia al tratamiento, que es sometida a cirugía de catarata e implante XEN® en su ojo izquierdo. Dos semanas después de la intervención se objetiva una erosión conjuntival con exposición del extremo distal del implante, por lo que se realiza una reparación quirúrgica mediante la combinación de una sutura aposicional del tubo, adaptando su trayectoria a la curvatura escleral, y el recubrimiento con injerto de membrana amniótica. Tras 6 meses de seguimiento, presenta una presión intraocular controlada, sin necesidad de tratamiento adicional, y sin mostrar progresión de su enfermedad (AU)

We report a case of a 79-year-old woman with severe glaucoma and absence of therapeutic adherence, who underwent cataract surgery and XEN® implant in her left eye. Two weeks after the intervention, conjunctival erosion was observed with exposure of the distal end of the implant, so a surgical repair was performed by combining an appositional suture of the tube, adapting its trajectory to the scleral curvature, and an amniotic membrane graft. After 6 months of follow-up, the intraocular pressure was controlled, without additional treatment needed, and no disease progression (AU)

Usefulness of the amniotic membrane graft in the management of xen® implant exposure.

We report a case of a 79-year-old woman with severe glaucoma and absence of therapeutic adherence, who undergone cataract surgery and XEN® implant in her left eye. Two weeks after the intervention, conjunctival erosion was observed with exposure of the distal end of the implant, so a surgical repair was performed by combining an appositional suture of the tube, adapting its trajectory to the scleral curvature, and an amniotic membrane graft. After 6 months of follow-up, the intraocular pressure is controlled, without additional treatment needed, and no disease progression.

Macular oedema associated with taxanes: A case report and literature review. / Edema macular asociado a taxanos: presentación de un caso y revisión de la literatura.

BACKGROUND AND PURPOSE: Although taxanes are a frequently used group of chemotherapy agents, they can, rarely, lead to macular oedema. The purpose of this article is to review and communicate, in an integrated way, the data of the cases previously reported in the literature, as well as to present a new case. MATERIAL AND METHODS: Narrative review of reports of cases of macular oedema associated with taxanes, and communication of the clinical case of a 73-year-old woman who, after treatment with paclitaxel for metastatic breast cancer, developed macular oedema that disappeared after discontinuing the drug. RESULTS: The review included 57 cases with data from 109 eyes collected in 52 articles. The large majority (76.79%) of the cases were women, and the mean age was 58.75 years. The cancer that most frequently motivated the treatment was breast cancer (60.72%), and 92.5% of cases had metastases. The most frequently associated drug was paclitaxel (52.63%). The median time to symptom development was 4.25 months. At the initial examination, 92.86% of the cases had bilateral oedema and the mean visual acuity was 0.4 (decimal scale). The mean macular thickness was 509.63 microns, and 97.83% of the eyes had no or minimal angiographic findings. In 90.57% of the cases, the treatment with taxanes was interrupted, and some other treatment was used in 43.86% of the cases, with the most widely used being acetazolamide. The outcome was favourable, to a greater or lesser extent, in 96.23% of cases. CONCLUSIONS: Despite being a rare entity, macular oedema associated with the use of taxanes is a disorder that every oncologist and ophthalmologist should be aware of, taking into account the good outcome of the condition that usually occurs when treatment is suspended.

Neurotensin and dynorphin Bi-Directionally modulate CeA inhibition of oval BNST neurons in male mice.

Neuropeptides are often co-expressed in neurons, and may therefore be working together to coordinate proper neural circuit function. However, neurophysiological effects of neuropeptides are commonly studied individually possibly underestimating their modulatory roles. Here, we triggered the release of endogenous neuropeptides in brain slices from male mice to better understand their modulation of central amygdala (CeA) inhibitory inputs onto oval (ov) BNST neurons. We found that locally-released neurotensin (NT) and dynorphin (Dyn) antagonistically regulated CeA inhibitory inputs onto ovBNST neurons. NT and Dyn respectively increased and decreased CeA-toovBNST inhibitory inputs through NT receptor 1 (NTR1) and kappa opioid receptor (KOR). Additionally, NT and Dyn mRNAs were highly co-localized in ovBNST neurons suggesting that they may be released from the same cells. Together, we showed that NT and Dyn are key modulators of CeA inputs to ovBNST, paving the way to determine whether different conditions or states can alter the neuropeptidergic regulation of this particular brain circuit.

Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies.

The incidence of hypocalcemia and bone mineral density (BMD) changes in end-stage renal disease (ESRD) patients on denosumab remains unclear. We performed this meta-analysis to assess the incidence of denosumab-associated hypocalcemia and effects of denosumab on BMD in ESRD patients. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through November 2017 to identify studies evaluating incidence of denosumab-associated hypocalcemia and changes in serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and BMD from baseline to post-treatment course of denosumab in ESRD patients. Study results were pooled and analyzed using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017081074). Six observational studies with a total of 84 ESRD patients were enrolled. The pooled estimated incidence of hypocalcemia during denosumab treatment was 42% (95% CI 29-55%, I2 = 0%). Hypocalcemia occurred approximately 7 to 20 days after the first dose and reached nadir of low calcium levels in the first 2 weeks up to 2 months. However, there were no significant changes in serum calcium or phosphate from baseline to post-treatment course (≥ 3 months after treatment) with mean differences [MDs] of 0.20 mg/dL (95% CI, - 0.30 to 0.69 mg/dL) and - 0.10 mg/dL (95% CI, - 0.70 to 0.49 mg/dL). There were significant reductions in ALP and PTH levels with standardized mean differences (SMDs) of - 0.65 (95% CI - 1.13 to - 0.16) and - 1.89 (95% CI - 3.44 to - 0.34), respectively. There were significant increases in T-scores with MDs of 0.39 (95% CI 0.10 to 0.69) and 0.79 (95% CI 0.60 to 0.98) for lumbar spine and femoral neck, respectively. Our study demonstrates the estimated incidence of denosumab-associated hypocalcemia in dialysis patients of 42%. From baseline to post-treatment course, although there are no differences in serum calcium and phosphate, our findings suggest significant reductions in ALP and PTH and a significant increase in BMD. Currently, denosumab should not be considered as the treatment of choice in ESRD patients until more safety and efficacy data are available.

Lower kidney allograft survival in African-Americans compared to Hispanic-Americans with lupus.

Background and objective African-Americans and Hispanic-Americans with lupus are the two most common minority groups who receive kidney transplants in the USA. It is unknown if African-Americans and Hispanic-Americans with lupus have similar outcomes after kidney transplantation. In this study, we assessed whether African-Americans compared to Hispanic-Americans have worse kidney allograft survival after risk factors of rejection and other prognostic factors were matched between both groups. Methods Out of 1816 African-Americans and 901 Hispanic-Americans with lupus, who received kidney transplants between 1987 and 2006 and had complete records in the UNOS program, 478 pairs were matched in 16 baseline predictors and follow-up time employing a predicted probability of group membership. The primary outcome was kidney allograft survival. Main secondary outcomes were rejection, allograft failure attributed to rejection, and mortality. Results Matched pairs were predominantly women (81%) with the mean age of 36 years. 96% were on dialysis before transplantation. 89% of recipients received kidneys from deceased donors and 15.5% from expanded criteria donors. 12% of recipients had zero HLA mismatch. African-Americans compared to Hispanic-Americans had lower cumulative allograft survival during 12-year follow-up ( p < 0.001). African-Americans compared to Hispanic-Americans had higher rates of rejection (10.4 vs 6.73 events/100 patients-years; p = 0.0002) and allograft failure attributed to rejection (6.31 vs 3.99; p = 0.0023). However, African-Americans and Hispanic-Americans had similar mortality rates (2.71 vs 2.31; p = 0.4269). Conclusions African-Americans compared to Hispanic-Americans with lupus had lower kidney allograft survival when recognized risk factors of rejection were matched between groups.

Pain Intensity and Misconceptions Among Hospice Patients With Cancer and Their Caregivers: Status After 2 Decades.

There is little evidence about barriers to pain management or their relationships with pain outcomes of hospice patients with cancer. The purpose of the study was to determine the barriers reported by hospice patients with cancer and their caregivers and the relationships with demographic characteristics and the patients' pain. In this cross-sectional study, we used selected baseline data from an ongoing randomized clinical trial of patient and lay caregiver dyads receiving home-level hospice care. Participants used an Internet-enabled tablet to complete the valid, reliable measures of pain intensity, pain management barriers (Barriers Questionnaire 13 items [BQ-13]), and demographic characteristics. The responses indicate that the 2 areas of highest concern (mean scores >3) to both patients and caregivers were "pain means disease progression" and "constipation." Additionally, 3 other areas of highest concern (mean scores >3) to caregivers were "addiction" pain medicine causing "one to do embarrassing things" and "confusion." The mean BQ-13 scores ranged from 0.2 to 4.9 and averaged 2.6 ± 0.9 for the patients and ranged from 0.5 to 4.7 and averaged 2.7 ± 0.9 for the caregivers. Mean barrier scores remain high and were not different between patients and their caregivers or significantly related to the patients' pain intensity. However, there were differences in race, ethnic, and hospice setting in the barrier scores. Patients with Hispanic heritage reported higher barrier scores than non-Hispanic patients. Together, these findings not only support prior research findings but also contribute new insights about pain intensity and pain barriers that are relevant to hospices serving minorities with cancer.

A biological tool to assess flow connectivity in reference temporary streams from the Mediterranean Basin.

Many streams in the Mediterranean Basin have temporary flow regimes. While timing for seasonal drought is predictable, they undergo strong inter-annual variability in flow intensity. This high hydrological variability and associated ecological responses challenge the ecological status assessment of temporary streams, particularly when setting reference conditions. This study examined the effects of flow connectivity in aquatic macroinvertebrates from seven reference temporary streams across the Mediterranean Basin where hydrological variability and flow conditions are well studied. We tested for the effect of flow cessation on two streamflow indices and on community composition, and, by performing random forest and classification tree analyses we identified important biological predictors for classifying the aquatic state either as flowing or disconnected pools. Flow cessation was critical for one of the streamflow indices studied and for community composition. Macroinvertebrate families found to be important for classifying the aquatic state were Hydrophilidae, Simuliidae, Hydropsychidae, Planorbiidae, Heptageniidae and Gerridae. For biological traits, trait categories associated to feeding habits, food, locomotion and substrate relation were the most important and provided more accurate predictions compared to taxonomy. A combination of selected metrics and associated thresholds based on the most important biological predictors (i.e. Bio-AS Tool) were proposed in order to assess the aquatic state in reference temporary streams, especially in the absence of hydrological data. Although further development is needed, the tool can be of particular interest for monitoring, restoration, and conservation purposes, representing an important step towards an adequate management of temporary rivers not only in the Mediterranean Basin but also in other regions vulnerable to the effects of climate change.

Lupus vasculopathy: Diagnostic, pathogenetic and therapeutic considerations.

A rare form of vascular disease in systemic lupus erythematosus (SLE), lupus vasculopathy is characterized by necrosis and accumulation of immunoglobulins (IGs) and complements in the wall of arterioles and small arteries resulting in luminal narrowing. Lupus vasculopathy often accompanies lupus nephritis and portends a poor prognosis. Although there is general agreement on the treatment of lupus nephritis, effective treatment strategies for lupus vasculopathy remain to be defined. We report a 20-year-old woman with SLE who presented with generalized tonic-clonic seizure. Her immunosuppressive regimen consisted of mycophenolate mofetil, prednisone and hydroxychloroquine. On physical examination, she was Cushingoid in appearance and hypertensive. Laboratory tests indicated renal disease. Coagulation studies disclosed de novo lupus anticoagulant. Magnetic resonance imaging of the brain demonstrated acute focal cerebral hemorrhage. Echocardiography revealed reduced ejection fraction and severe mitral regurgitation. Despite high-dose glucocorticoids and mycophenolate mofetil, renal function remained poor. Kidney biopsy demonstrated lupus vasculopathy and glomerulonephritis. Plasma exchange therapy and intravenous cyclophosphamide were administered. Over the ensuing four weeks, renal function improved, complement levels increased, autoantibody titers decreased and lupus anticoagulant disappeared. In conclusion, lupus vasculopathy can occur in SLE despite a heavy immunosuppressive regimen. Antiphospholipid antibodies might be involved in the pathogenesis of lupus vasculopathy. Plasma exchange therapy in conjunction with intravenous cyclophosphamide may represent an effective treatment strategy for lupus vasculopathy.

Effect of age and severity of cognitive dysfunction on two simple tasks in pet dogs.

Dogs exhibit age-dependent losses in learning and memory as well as a progressive accumulation of neuropathology that parallels that observed in normal human aging and early Alzheimer's disease. These deficits have been extensively studied using a number of standard cognitive tasks in the laboratory; however, appropriate tools for their assessment in veterinary clinics are still lacking. The aim of this study was to evaluate the effect of age and the severity of cognitive dysfunction syndrome (CDS) on two simple tests conducted in a clinical setting. A food searching (FS) task and a problem-solving (PS) task were administered to young (1-4 years, n=9), middle-aged (5-8 years, n=10), cognitively unimpaired aged (≥9 years, n=31), and cognitively impaired aged (≥ 9 years, n=37) dogs. Cognitive status was classified using an owner-based questionnaire, and in the impaired group, dogs were categorized as having either mild or severe CDS. During the FS task, younger dogs (<9 years) were able to locate the food more quickly and with more success than the aged groups (≥9 years). Dogs with severe CDS exhibited poorer performance than those with mild CDS or their healthy counterparts. In the PS task, younger dogs performed better than the aged dogs in obtaining food, but there were no differences related to CDS severity. The FS task might help to better characterize cognitively affected dogs in the clinical setting than the PS task. These and similar tasks require further investigations in the field.

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 1: locomotor and exploratory behaviour.

Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs. An open-field (OF) test and a curiosity test were administered at baseline and 6 months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively unimpaired aged (≥ 9 years, n=31), and cognitively impaired aged ( ≥ 9 years, n=36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed. The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6 months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals.

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 2: social responsiveness.

Changes in social interactions with owners and other dogs are frequently observed in dogs with cognitive dysfunction syndrome (CDS). The aim of this work was to assess the effect of age and severity of CDS on social responsiveness. This is the second part of a 2-part report on spontaneous activity in pet dogs. A human interaction test and a mirror test were administered at baseline and 6 months later to assess social responses to humans and conspecifics, respectively, to four groups of privately-owned dogs: young (n=9), middle-aged (n=9), cognitively unimpaired aged (n=31), and cognitively impaired aged (n=36). The severity of cognitive impairment was considered in the last group and dogs were categorised as having either mild or severe CDS. The influence of the person and the mirror on locomotion and exploratory behaviour was also studied. Dogs were recorded in a testing room and the video recordings were subsequently analysed. Young dogs displayed more interactions involving physical contact with a person. Young and middle-aged dogs showed more vocalisations in response to social isolation. In contrast, aged animals spent more time in front of the mirror. Changes in social responsiveness associated with severe CDS included decreased response to social isolation and human interaction and increased time in front of the mirror, suggesting a deficit in habituation. Testing of spontaneous activity might help to characterise CDS in aged dogs, a condition increasingly diagnosed in veterinary clinics and a potentially useful natural model of Alzheimer's disease in humans.

Angiotensin II modifies the expression of α(1)-adrenoceptors in aorta smooth muscle cells of α(1D)-adrenoceptor knockout mice.

1 The effect of angiotensin II (Ang II) on α(1A)-, α(1B)-, and a(1D)-adrenoceptors (α(1)-AR) expression was analyzed in aorta smooth muscle cells obtained from wild-type (WT) and knock out of α(1D)-AR (α(1D)-AR KO) mice. 2 The relative abundance of mRNA for the three α(1)-ARs was determined in WT and α(1D)-AR KO aortic smooth muscle cells. There were no significant differences between WT and α(1D)-AR KO cells. 3 As early as 1 h Ang II increased α(1B)-AR mRNA in WT cells ≈ 2 fold compared with control; in contrast, in α(1D)-AR KO cells the α(1B)-AR transcript was ≈ 50% of control. 4 Western blot assays showed that Ang II incremented protein content for α(1A)-AR, 86% and 107% in WT and α(1D)-AR KO cells, respectively. 5 Protein for α(1B)- and α(1D)-ARs did not change significantly with Ang II in both WT and a(1D)-AR KO cells. 6 The effect of Ang II on α(1B)-AR mRNA seems to be influenced by the absence of α(1D)-AR in aortic smooth muscle cells, which might be important to understand the interactions among α(1)-ARs.

Anemia control in kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta (mircera): the Anemiatrans Group.

BACKGROUND: Kidney transplant, the gold standard treatment for chronic kidney disease (CKD), is increasingly complicated by anemia. Once-monthly dosing of methoxy polyethylene glycol-epoetin beta provides stable, sustained hemoglobin levels in CKD patients. The present study evaluated anemia control in recipients treated with methoxy polyethylene glycol-epoetin beta to correct or as conversion treatment from other erythropoiesis-stimulating agents (ESAs). PATIENTS AND METHODS: This observational, retrospective study included kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta according to investigators' clinical practice. Information about demographics, CKD, anemia, blood analyses, treatment, and adverse events were collected from patients' medical charts at baseline as well as months 1, 3, and 6. RESULTS: From October 2009 to March 2010, the 285 patients in the study included: an overall mean age of 52.8±13.9 years with 146 females (51.2%) and 152 patients (55.1%) in stage 3 CKD. Forty-five patients (15.8%) were in the immediate posttransplant period; 51, naïve- treatment (17.9%) and 189, converted subjects (66.3%). Eighty-two of the converted patients (48.0%) had previously received darbepoietin; 81 (47.4%), epoetin beta; and 8 (4.7%), epoetin alfa. The mean doses of methoxy polyethylene glycol-epoetin beta at baseline were 75.0±22.4 µg per month, 95.8±45.5 µg per month, and 118.9±58.9 µg per month among naïve, converted, and immediate posttransplant patients, respectively. Mean hemoglobin content varied from baseline to month 6, namely 10.2±0.7 versus 11.8±0.9 g/dL in naïve (P<.001) and 11.4±1.3 versus 12.0±1.2 g/dL in converted patients (P=.001). Patients in the immediate posttransplant period showed mean hemoglobin values maintained between 10.4±1.7 g/dL at baseline and 11.5±1.2 g/dL at month 3. The only study-drug-related adverse event was hypertension. No patient died during the study. CONCLUSION: These preliminary results suggested that hemoglobin stability can be achieved and maintained after correction or conversion to once-monthly methoxy polyethylene glycol-epoetin beta in kidney recipients. It was well tolerated; the safety profile was that expected and comparable with shorter acting ESAs.