Nicole Graf

Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD.

PurposeEvaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an “insufficient anatomic response” to prior anti-VEGF therapy with ranibizumab or bevacizumab.MethodsThe retrospective analysis included 96 eyes that had received at least three intravitreal 0.5xa0mg ranibizumab or 1.25xa0mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2xa0mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4xa0weeks after the third aflibercept injection.ResultsA significant reduction of mean CRT (−39xa0μm; pu2009<u20090.001) and maximum PED height (−46xa0μm; pu2009<u20090.001) as found 4xa0weeks after the third aflibercept injection. Eighty-two out of 96 eyes (85xa0%) had a PED just prior to switching to aflibercept. There was an improvement in BCVA of 1.9 letters 4xa0weeks after the last aflibercept injection; the vision gain, however, did not reach statistical significance (pu2009=u20090.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments.ConclusionRetinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments.

Incidence of presumed endophthalmitis after intravitreal injection performed in the operating room: a retrospective multicenter study.

Purpose: To evaluate the incidence of presumed endophthalmitis (EO) after intravitreal injection (IVI) of anti–vascular endothelial growth factor agents performed in the operating room. Methods: Retrospective study at 2 Swiss eye hospitals between 2004 and 2012. Hospital records were used to identify patients treated with an IVI of an anti–vascular endothelial growth factor agent between 2004 and 2012 and those treated for EO, defined as any intraocular inflammation treated with intravitreal antibiotics. All IVIs were performed using standard sterile technique in a Swiss Class 1 operating room. No patient received preinjection topical antibiotics. Postinjection topical antibiotics were used only in one hospital. Results: A total of 40,011 IVIs were performed at the 2 centers during the study period. Of the IVIs, ranibizumab was injected in 36,398 (91%), bevacizumab in 3,518 (9%), aflibercept in 89 (0.2%), and pegaptanib in 6 (<0.1%). Three cases of post-IVI presumed EO occurred, yielding a combined incidence of 0.0075% per injection (95% confidence interval: 0.0026–0.0220%) or 1 case per 13,337 IVIs. Two of the three cases of EO occurred in patients using post-IVI antibiotics. All three cases followed ranibizumab injection and were culture negative by anterior chamber tap or vitreous biopsy. Conclusion: The risk of EO after IVI performed under the sterile conditions of the operating room was very low.

Determinants of efficacy and safety in epicutaneous allergen immunotherapy: summary of three clinical trials

The results of our third trial on epicutaneous allergen‐specific immunotherapy (EPIT) will be presented and discussed in the context of our previous trials. This monocentric, placebo‐controlled, double‐blind phase I/IIa trial included 98 patients with grass pollen rhinoconjunctivitis. Prior to the pollen season 2009, patients received six patches (allergen extract: n = 48; placebo: n = 50) with weekly intervals, administered onto tape‐stripped skin. Allergen EPIT produced a median symptom improvement of 48% in 2009 and 40% in the treatment‐free follow‐up year 2010 as compared to 10% and 15% improvement after placebo EPIT (P = 0.003). After allergen EPIT but not placebo EPIT, conjunctival allergen reactivity was significantly decreased and allergen‐specific IgG4 responses were significantly elevated (P < 0.001). In conclusion, our three EPIT trials found that allergen EPIT can ameliorate hay fever symptoms. Overall, treatment efficacy appears to be determined by the allergen dose. Local side‐effects are determined by the duration of patch administration, while risk of systemic allergic side‐effects is related to the degree of stratum corneum disruption.

Sclerostin Blood Levels Before and After Kidney Transplantation

Background/Aims: Sclerostin is secreted by osteocytes. As a circulating inhibitor of the Wnt-signaling pathway it inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and end-stage renal disease. Since data for patients after kidney transplantation are scarce, we have prospectively measured sclerostin levels before and during the first year after renal transplantation and have examined the association of sclerostin with parameters of bone mineral metabolism and with bone mineral density. Methods: Sclerostin levels were measured by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year after transplantation. Bone mineral density was measured by dual energy X-ray absorptiometry. Results: Pre-transplant serum sclerostin levels were elevated in all patients (61.8 ± 32.3 pmol/l, normal range 20-30 pmol/l). Within 15 days after transplantation and correlating with the improvement of renal function, sclerostin levels dropped to 21.0 ± 14.7 pmol/l and subsequently increased to 23.8 ± 14.9 and 28.0 ± 16.8 pmol/l after 6 and 12 months, respectively (P<0.001). A linear mixed model indicated that pre-transplant sclerostin levels (P<0.001) and time after transplantation (P<0.001) were the most important predictors for the rise of post-transplant sclerostin levels. No correlation was found between post-transplant sclerostin levels and bone mineral density. Conclusions: The rapid reduction of elevated serum sclerostin levels shortly after kidney transplantation parallels the improvement of renal function, but contrasts with the more delayed improvement of hyperparathyroidism. The normalization of both hormones could contribute to improved bone health after renal transplantation.

Effect of Twice-Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial

We conducted an open‐label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3–5.9%) in 46 patients in the denosumab group and decreased by −0.5% (95% CI −1.8% to 0.9%) in 44 patients in the control group (between‐group difference 5.1% [95% CI 3.1–7.0%], p < 0.0001). Denosumab also increased aBMD at the total hip by 1.9% (95% CI, 0.1–3.7%; p = 0.035) over that in the control group at 12 months. High‐resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C‐terminal telopeptide of type I collagen, procollagen type I N‐terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection.

Success of salvage treatment: a critical appraisal of salvage rates for different subsites of HNSCC.

Objective Despite advances in interdisciplinary treatment protocols, the chance of cure for recurrent head and neck squamous cell carcinoma (HNSCC) following failed primary therapy is poor and often entails a high morbidity. Recurrence rates vary widely in the literature depending on tumor localization, primary tumor stage, and treatment modality, and only a minority of patients can be salvaged. Study Design Historical cohort study. Setting This study valuates the outcomes of patients treated for recurrent squamous cell carcinoma of the larynx, pharynx, and oral cavity in the largest tertiary referral center of Switzerland to find predictors for survival in salvage surgery with curative intent. Subjects and Methods Included were 176 consecutive patients with recurrent disease after primary curative treatment of HNSCC, in locations mentioned previously. Kaplan-Meier survival analyses with log-rank testing were performed depending on T and N stage, gender, treatment, and location of first relapse to evaluate the impact on overall survival, disease specific survival, and recurrence free survival. Results Overall successful salvage rates were 49.2% for laryngeal recurrence, 35.1% for oral cavity, 32.7% for oropharyngeal, and a mere 17.4% for hypopharyngeal recurrences. Predictive factors for better outcome were location of recurrence, female gender, lymph node status, and extent of salvage treatment. Conclusion In case of recurrent disease, laryngeal cancers showed the best salvage rates, whereas in hypopharyngeal relapses, very few patients could be successfully salvaged. Patients therefore should be carefully selected and counseled for salvage treatment according to patient motivation, age, type of previous treatment, surgical resectability, and exclusion of distant recurrence.

Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease

Objective Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. Methods To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes. Results The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3±10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (ru200a=u200a0.222) and higher TKV (ru200a=u200a0.134). Conclusions This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

Abductor tendon tears are associated with hypertrophy of the tensor fasciae latae muscle.

ObjectiveTo evaluate the association between hypertrophy of the tensor fasciae latae muscle and abductor tendon tears.Materials and methodsThirty-five patients who underwent MRI of the abductor tendons of the hip were included in this retrospective study. A subgroup of 18 patients was examined bilaterally. The area of the tensor fasciae latae muscle and the area of the sartorius muscle (size reference) were quantified at the level of the femoral head, and a ratio was calculated. Two radiologists assessed the integrity of the gluteus medius and minimus tendon in consensus. Data were analyzed with a Mann–Whitney U test.ResultsSixteen out of 35 patients (46xa0%) had a tear of the gluteus medius or minimus tendon. The ratio of the area of the tensor fasciae latae to the sartorius muscle was significantly higher (pu2009=u2009.028) in the group with an abductor tendon tear (median 2.25; Interquartile Range [IQR] = 1.97–3.21) compared to the group without any tears (median 1.91; IQRu2009=u20091.52–2.26). The bilateral subanalysis showed that in patients without a tear, the ratio of the two areas did not differ between each side (pu2009=u2009.966), with a median of 1.54 (primary side) and 1.76 (contralateral side). In patients with an abductor tendon tear the ratio was significantly higher (pu2009=u2009.031) on the side with a tear (median 2.81) compared to the contralateral healthy side (1.67).ConclusionPatients with abductor tendon tears showed hypertrophy of the tensor fasciae latae muscle when compared to the contralateral healthy side and to patients without a tear.

Feasibility and safety of vascular closure devices in an antegrade approach to either the common femoral artery or the superficial femoral artery.

IntroductionThe purpose of the present study was to analyze complications following antegrade puncture of the common femoral artery (CFA) and the superficial femoral artery (SFA) using vascular closure systems (VCS).MethodsA single-center, retrospective study was performed after obtaining approval from the institutional review board and informed consent from all patients. At our center, the CFA or SFA are used for arterial access. All patients were evaluated clinically on the same day. If there was any suspicion of an access site problem, Duplex ultrasound was performed.ResultsAccess location was the CFA in 50 patients and the SFA in 130 patients. The sheath size ranged from 4F to 10F. Two patients had to be excluded because of lack of follow-up. Successful hemostasis was achieved in 162 of 178 cases (91xa0%). The following complications were observed in 16 patients (8.9xa0%): 4 pseudoaneurysms (2.2xa0%), 11 hematomas (6.2xa0%), and 1 vascular occlusion (0.5xa0%). The two pseudoaneurysms healed spontaneously, in one case an ultrasound-guided thrombin injection was performed, and one aneurysm was compressed manually. No further medical therapy was needed for the hematomas. The one vascular occlusion was treated immediately with angioplasty using a contralateral approach. No significant difference was noted between the CFA and the SFA group with respect to complications (pxa0=xa01.000).ConclusionsThe use of closure devices for an antegrade approach up to 10F is feasible and safe. No differences in low complication rates were observed between CFA and SFA.

SYSTEMIC INTERLEUKIN 1β INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY: A Prospective Open-Label Study Using Canakinumab.

In a prospective, open-label interventional pilot study, repeated systemic canakinumab showed no change in retinal neovascularizations in proliferative diabetic retinopathy over 24 weeks. Promising effects were seen on diabetic macular edema requiring further study.