Femto-LASIK after Deep Anterior Lamellar Keratoplasty to Correct Residual Astigmatism: A Long-Term Case Series Study

Purpose: To evaluate the long-term outcomes of femtosecond laser-assisted in situ keratomileusis (Femto-LASIK) to correct residual astigmatism after deep anterior lamellar keratoplasty (DALK). Methods: This retrospective case series study included 10 eyes that underwent Femto-LASIK after a DALK. The refractive error, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, thinnest corneal thickness (TCT), and central corneal thickness (CCT) were registered. The postoperative follow-up ranged between 36 and 60 months. Results: All surgeries were uneventful, with no intra- or postoperative complications. The mean UDVA (Snellen scale) rose from 0.13 ± 0.05 to 0.47 ± 0.15 six months after Femto-LASIK (p < 0.001). All cases experienced a significant improvement in UDVA. None of the eyes lost lines of CDVA, and seven eyes (70%) improved the CDVA compared to preoperative values. The refractive cylinder changed from a preoperative value of −3.88 ± 1.00 D to −0.93 ± 0.39 six months after Femto-LASIK (p < 0.0001). In eight eyes (80%), the UDVA and refractive outcomes remained stable at postoperative follow-up visits. In contrast, one eye experienced a refractive regression over the follow-up. TCT and CCT were stable at the different postoperative follow-up visits. Conclusions: Our findings suggest that Femto-LASIK might safely and effectively corrects residual astigmatism after DALK. Despite these encouraging results, further long-term studies, including a larger number of cases, are required to confirm the safety of the procedure. The refractive stability in eyes with prior RK might be lower than for other DALK indications.Depto. de Optometría y VisiónFac. de Óptica y OptometríaTRUEpu

Three-year follow-up of posterior chamber phakic intraocular lens with a central port design after deep anterior lamellar keratoplasty

Background: To evaluate clinical outcomes of the Visian implantable collamer lens (ICL) with a central port to correct myopia and astigmatism after deep anterior lamellar keratoplasty (DALK) for keratoconus throughout 3 years of follow-up. Methods: This study included 20 eyes of 20 patients that underwent V4c ICL (13 eyes with a spherical ICL and 7 eyes with a toric ICL) implantation after DALK. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, intraocular pressure (IOP), endothelial cell density (ECD), and vault were analyzed. Results: The mean UDVA improved from the preoperative 1.18 ± 0.33 logMAR to 0.25 ± 0.14 logMAR at 6 months after surgery (P < 0.0001) and remained unchanged throughout the whole follow-up (P = 0.4). All eyes gained lines of CDVA compared to preoperative values. At the last follow-up visit, all eyes achieved CDVA of 0.2 logMAR or better and 13 eyes (65%) 0.1 logMAR or better. At 6 months post-surgery, all eyes (100%) had a spherical equivalent within ± 1.50 D, and 19 (95%) within ± 1.00 D. The mean manifest spherical equivalent was stable over the postoperative follow-up (P = 0.25). No significant increase in IOP occurred in any case throughout the 3 years of follow-up. The loss in ECD from the preoperative baseline at the last follow-up visit was 2.27%. Conclusions: The clinical outcomes suggest that the V4c ICL implantation for correction of myopia and regular astigmatism in post-DALK eyes was satisfactory in terms of effectiveness, safety, and stability during 3 years of follow-up.Depto. de Optometría y VisiónFac. de Óptica y OptometríaTRUESTAAR® Surgical (Estados Unidos)pu

A New Pre-descemetic Corneal Ring (Neoring) in Deep Anterior Lamellar Keratoplasty for Moderate-Advanced Keratoconus: A Pilot 2-Year Long-Term Follow-Up Study

Purpose: To assess the outcomes of implanting a new polymethylmethacrylate (PMMA) ring (Neoring; AJL Ophthalmic) in pre-descemet deep anterior lamellar keratoplasty (PD-DALK) procedure for moderate-advanced keratoconus. Methods: This prospective study included 10 eyes of 10 patients with moderate-advanced keratoconus who underwent PD-DALK with Neoring implantation. Neoring was implanted in a pre-descemetic pocket. The post-operative examination included refraction, corrected distance visual acuity (CDVA), corneal tomography, and endothelial cell density (ECD). The root mean squares (RMSs) for coma-like aberrations and spherical aberration were evaluated for a pupil size of 4.5mm. The junctional graft (Tg) and host (Th) thicknesses were measured. The post-operative follow-up was 24 months. Results: Post-operative CDVA was 0.82 ± 0.14 (decimal scale), 100% of the eyes achieved a CDVA of 0.7 (decimal scale). The refractive cylinder was −2.86 ± 1.65 2-years after surgery. No eyes had a post-operative refractive cylinder ≥5.00 D and in five eyes (50%), it was ≤2.50 D. At the last visit, the mean keratometry was 45.64 ± 1.96 D, the RMS for coma-like aberrations was 0.30 ± 0.15μm and spherical aberration was 0.22 ± 0.09. The mean ECD remains without changes over the follow-up (P = 0.07). At the last visit, Tg and Th were 679.9 ± 39.0 and 634.8 ± 41.2μm, respectively. The thickness of the complex (host-Neoring) was 740.6 ± 35.6μm. In all cases, this thickness was thicker than Tg. Conclusion: The results of this study suggest that PD-DALK along Neoring implantation is a viable, effective, and safe option to optimize the post-operative results for moderate-severe keratoconu

The cellular origin and malignant transformation of Waldenström macroglobulinemia

Although information about the molecular pathogenesis of Waldenström macroglobulinemia (WM) has significantly advanced, the precise cell of origin and the mechanisms behind WM transformation from immunoglobulin-M (IgM) monoclonal gammopathy of undetermined significance (MGUS) remain undetermined. Here, we undertook an integrative phenotypic, molecular, and genomic approach to study clonal B cells from newly diagnosed patients with IgM MGUS (n = 22), smoldering (n = 16), and symptomatic WM (n = 11). Through principal component analysis of multidimensional flow cytometry data, we demonstrated highly overlapping phenotypic profiles for clonal B cells from IgM MGUS, smoldering, and symptomatic WM patients. Similarly, virtually no genes were significantly deregulated between fluorescence-activated cell sorter-sorted clonal B cells from the 3 disease groups. Interestingly, the transcriptome of the Waldenström B-cell clone was highly different than that of normal CD25-CD22+ B cells, whereas significantly less genes were differentially expressed and specific WM pathways normalized once the transcriptome of the Waldenström B-cell clone was compared with its normal phenotypic (CD25+CD22+low) B-cell counterpart. The frequency of specific copy number abnormalities [+4, del(6q23.3-6q25.3), +12, and +18q11-18q23] progressively increased from IgM MGUS and smoldering WM vs symptomatic WM (18% vs 20% and 73%, respectively; P = .008), suggesting a multistep transformation of clonal B cells that, albeit benign (ie, IgM MGUS and smoldering WM), already harbor the phenotypic and molecular signatures of the malignant Waldenström clone.This study was supported by Cooperative Research Thematic Network grants RD12/0036/0058 and RD12/0036/0048 of the Red de Cancer (Cancer Network of Excellence), Consejería de Sanidad, Junta de Castilla y Leon, Valladolid, Spain (557/A/10).Peer Reviewe

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia

For PETHEMA Programa para el Estudio de la Terapéutica en Hemopatías Malignas Cooperative Study Group.The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥0.1%; ≥0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p = 0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p = 0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.This work was supported in part by Spanish grants from Fondo de Investigación Sanitaria-ISCIII (FIS 00/0023-03, PI12/02321), DGCYT (SAF 94- 0308, SAF2001-1687), Conserjería de Educación de Castilla y León (HUS416A12), and Red Temática de Investigación Cooperativa en Cáncer (RTICC-ISCIII) (RD12/0036/0069).Peer Reviewe

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)

© The Author(s) 2018.Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative and the EuroFlow Consortium; Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00369, CB16/12/00489 and CB16/12/00233; grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain. Acuerdo de colaboración con Fundación de Hemoterapia y Hemodonación de Castilla y León, Valladolid, Spain. This study was also supported by the Qatar National Research Fund (QNRF) Award No. 7-916-3-237, the AACR-Millennium Fellowship in Multiple Myeloma Research (15-40-38-PAIV), ERA-NET TRANSCAN-2 (iMMunocell), by a 2017 Leonardo Grant (BZG10931) for Researchers and Cultural Creators, BBVA Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT)

The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

Isolation, Characterization and Lipid-Binding Properties of the Recalcitrant FtsA Division Protein from Escherichia coli

We have obtained milligram amounts of highly pure Escherichia coli division protein FtsA from inclusion bodies with an optimized purification method that, by overcoming the reluctance of FtsA to be purified, surmounts a bottleneck for the analysis of the molecular basis of FtsA function. Purified FtsA is folded, mostly monomeric and interacts with lipids. The apparent affinity of FtsA binding to the inner membrane is ten-fold higher than to phospholipids, suggesting that inner membrane proteins could modulate FtsA-membrane interactions. Binding of FtsA to lipids and membranes is insensitive to ionic strength, indicating that a net contribution of hydrophobic interactions is involved in the association of FtsA to lipid/membrane structures

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy

BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA). RESULTS: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. CONCLUSIONS: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy