Refractive predictive errors using Barrett II, Hoffer-Q, and SRKT formulae for pediatric IOL implantation.

PURPOSE: To compare the accuracy of the Barrett II universal (BU II) formula, Hoffer-Q, and SRKT formulae following lensectomy and IOL implantation in a large pediatric cohort. METHODS: Retrospective study of children who underwent lensectomy and IOL implantation between 2015 and 2023 at Hadassah-Hebrew University Medical Center, Jerusalem, Israel. RESULTS: One hundred and fifty-one eyes of 104 children aged 6.0 ± 3.9 years were included. The mean prediction error (PE) was - 0.08 ± 1.54 diopters (D) with BU II, 0.24 ± 1.46 D with Hoffer-Q, and 0.71 ± 1.92 D with SRKT (P = 0.10). In eyes with axial length (AL) < 22 mm, BU II and Hoffer-Q had a smaller PE than SRKT (P = 0.024). In eyes with AL ≥ 22 mm, BU II had a smaller PE than Hoffer-Q (P = 0.048). In children 24 months or older at surgery, BU II had a smaller PE than SRKT and Hoffer-Q (P = 0.012). However, in younger children, no difference was found between the formulae (P = 0.61). For mean k-values ≥ 44.5 D, BU II and Hoffer-Q had a smaller PE than SRKT (P = 0.002). An absolute prediction error < 1.0 D was obtained with BU II in 66% of eyes and SRKT in 35% (P = 0.01). CONCLUSIONS: The BU II formula performed well with a small prediction error. No significant difference in PE was detected overall between the formulae. However, only BU II demonstrated a stable prediction error at varying axial lengths, K-readings, and ages. As the biometric parameters of the developing eye change with growth, the BU II formula offers a reliable and stable option for pediatric IOL calculation.

Cardiovascular Morbidity and Risk Factors in Holocaust Survivors in Israel.

OBJECTIVES: To compare the prevalence of cardiovascular diseases and risk factors in Holocaust survivors with that of Jewish immigrants from Europe and America. DESIGN: Population-based, cross-sectional study. SETTING: Clalit, a large Israeli healthcare provider. PARTICIPANTS: Holocaust survivors (n=83,971) and a comparison group of Jewish individuals born in North or South America or European countries not under Nazi occupation or who immigrated to Israel before 1939 (n=16,058) (mean age 84±7, 61% female) MEASUREMENTS: Univariate and multivariable logistic regression analyses of cardiovascular diseases and risk factors. Matching the comparison group to Holocaust Survivors on propensity scores for exposure. RESULTS: The prevalence of ischemic heart disease (38.7% vs 31.3%), congestive heart failure (10.9% vs 9.1%), past stroke (15.7% vs 13.4%), and peripheral vascular disease (9.5% vs 7.9%) was higher in Holocaust survivors (p<.001 for all comparisons). Similar results were found for cardiovascular risk factors (diabetes mellitus (14.4% vs 13.6%), hypertension (89.3% vs 86.4%), dyslipidemia (75.9% vs 74.0%) (p<.001 for all comparisons). In multivariable analysis, matched on propensity scores and controlled for confounders, odds ratios for men and women were higher for diabetes (1.23, 1.55), dyslipidemia (1.53, 1.51), hypertension (1.56 , 1.94), stroke (1.18, 1.17), and ischemic heart disease (1.18, 1,40), but not congestive heart failure (0.95, 1.02). A Positive association was noted for peripheral vascular disease in males (1.20) but not females (0.96). CONCLUSION: Prevalence of cardiovascular diseases and risk factors was higher in Holocaust survivors. These associations were stronger in women in most cases.

Elevated cancer risk in Holocaust survivors residing in Israel: A retrospective cohort study.

BACKGROUND: The purpose of this study was to examine the incidence of malignant diseases among Holocaust survivors in Israel compared with European and American immigrants who did not experience the Holocaust. METHODS: Study subjects included Holocaust survivors born in European countries under Nazi occupation before 1945, who immigrated to Israel after 1945 and were alive as of the year 2000. Living survivors were identified based on recognition criteria in accordance with the Holocaust Survivor Benefits Law. The comparison group consisted of Clalit enrollees who were born before 1945 in European countries not under Nazi occupation and were alive in 2000 or were born in any European country or America, immigrated to Israel before 1939 and were alive in 2000. The incidence of malignant diseases was compared in univariate and Poisson regression models analyses, controlling for age, smoking, obesity, diabetes and place of residence. RESULTS: The study included 294,543 Holocaust survivors, and the mean age at the beginning of follow-up was 74 ± 8.7 years; 43% males. In multivariable analyses, the rate ratio (RR) values for males and females were 1.9 and 1.3 for colon cancer, 1.9 and 1.4 for lung cancer, 1.6 and 1.4 for bladder cancer and 1.2 and 1.3 for melanoma, respectively. For prostate cancer in males, the RR was 1.4, while for breast cancer in females, it was 1.2. CONCLUSIONS: The incidence of malignant diseases among Holocaust survivors residing in Israel was higher than that among non-Holocaust survivors. These associations remained statistically significant in a multivariable analysis and were stronger for males.

Cat-scratch disease: ocular manifestations and treatment outcome.

PURPOSE: To characterize cat-scratch disease (CSD) ocular manifestations and visual outcome and evaluate the effect of systemic antibiotics and corticosteroids on final visual acuity (VA). METHODS: Multicentre retrospective cohort study. Medical records of 86 patients with ocular disease (107 eyes) of 3222 patients identified in a national CSD surveillance study were reviewed. RESULTS: Mean age was 35.1 ± 14.2 years. Median follow-up was 20 weeks (range 1-806 weeks). Of 94/107 (88%) eyes with swollen disc, 60 (64%) had neuroretinitis at presentation, 14 (15%) developed neuroretinitis during follow-up, and 20 (21%) were diagnosed with inflammatory disc oedema. Optic nerve head lesion, uveitis, optic neuropathy and retinal vessel occlusion were found in 43 (40%), 38 (36%), 34 (33%) and 8 (7%) eyes, respectively. Good VA (better than 20/40), moderate vision loss (20/40-20/200) and severe vision loss (worse than 20/200) were found in 26/79 (33%), 35/79 (44%) and 18/79 (23%) eyes at baseline and in 63/79 (80%), 11/79 (14%) and 5/79 (6%) eyes at final follow-up, respectively (p < 0.001). Significant VA improvement (defined as improvement of ≥3 Snellen lines at final follow-up compared to baseline) occurred in 12/24 (50%) eyes treated with antibiotics compared with 14/16 (88%) eyes treated with antibiotics and corticosteroids (p = 0.02). Multivariate logistic regression was suggestive of the same association (odds ratio 7.0; 95% CI 1.3-37.7; p = 0.024). CONCLUSION: Optic nerve head lesion is a common and unique manifestation of ocular CSD. Most patients improved and had final good VA. Combined antibiotics and corticosteroid treatment was associated with a better visual outcome.

[Bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse in T-cell acute lymphoblastic leukemia].

T-cell acute lymphoblastic leukemia is a hematologic malignancy with propensity to involve extramedullary organs including the eyes. Optic nerve infiltration is relatively rare. This is the case study of a 25-year-old- man who was in full remission following treatment for T-cell acute lymphoblastic leukemia and presented with bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse. The patient was treated with urgent radiotherapy and systemic dexamethasone. Over the following period, gradual resolution of optic disc swelling was noted in both eyes with marked improvement in vision in the right eye. Unfortunately, a few weeks later, a full blown hematological relapse was diagnosed. Salvage chemotherapy was instituted but was complicated by tumor lysis syndrome and septicemia that proved to be fatal. Ophthalmic assessment is essential in patients with hematological malignancies in order to diagnose ocular involvement as a result of malignant infiltration, hematological disturbances or as a complication of systemic therapy.

Toward salivary gland stem cell regeneration.

Head and neck cancer is the sixth most common cancer worldwide, resulting in ~ 640,000 cases. Most of these patients have irreversible damage to their salivary glands due to irradiation therapy, which typically leads to significant decrease in quality of life. In the last 2 decades, several strategies have been suggested to overcome this problem; however, no biologically based treatments are available. In the past few years, the authors of the present article and other researchers have focused on a new strategy of re-implantation of autologous salivary gland cells into the residual irradiated salivary glands. This article reviews the current prospective of the irradiation-induced salivary gland impairment mechanisms and the envisioned therapeutic modalities based on stem cell therapy.

Effect of irradiation on cell transcriptome and proteome of rat submandibular salivary glands.

Salivary glands (SGs) are irreversibly damaged by irradiation (IR) treatment in head and neck cancer patients. Here, we used an animal irradiation model to investigate and define the molecular mechanisms affecting SGs following IR, focusing on saliva proteome and global transcription profile of submandibular salivary gland (SSG) tissue.We show that saliva secretion was gradually reduced to 50% of its initial level 12 weeks post-IR. Saliva protein composition was further examined by proteomic analysis following mass spectrometry (MS) analysis that revealed proteins with reduced expression originating from SSGs and proteins with increased expression derived from the serum, both indicating salivary tissue damage. To examine alterations in mRNA expression levels microarray analysis was performed. We found significant alterations in 95 genes, including cell-cycle arrest genes, SG functional genes and a DNA repair gene.Tissue damage was seen by confocal immunofluorescence of α-amylase and c-Kit that showed an increase and decrease, respectively, in protein expression. This was coherent with real-time PCR results.This data indicates that IR damages the SSG cells' ability to produce and secrete saliva and proteins, and maintain the physiological barrier between serum and saliva. The damage does not heal due to cell-cycle arrest, which prevents tissue regeneration. Taken together, our results reveal a new insight into IR pathobiology.

Long-term cryopreservation model of rat salivary gland stem cells for future therapy in irradiated head and neck cancer patients.

Irradiated head and neck cancer patients suffer from irreversible loss of salivary gland (SG) function, along with significant morbidity and compromised quality of life. To date there is no biologically-based treatment for this distress. Adult salivary gland stem cells are promising candidates for autologous transplantation therapy in the context of tissue-engineered artificial SGs or direct cell therapy. The major restrictions in handling such cells are their limited lifespan during in vitro cultivation, resulting in a narrow time-window for implantation and a risk of tumorigenic changes during culture. To overcome these difficulties, we tested in a rat model the possibility of establishing a personal/autologous SG stem cell bank. SG's integrin-α6ß1-expressing cells were shown to hold a subpopulation of SG-specific progenitor-cells. Explanted and cultured single cell-originated clones were cryopreserved for up to 3 years and shown to exhibit genetic and functional stability similar to noncryopreserved cells, as was emphasized by soft agar assay, division potential assessment, flow cytometric analysis, real-time reverse transcriptase-polymerase chain reaction, in vitro three-dimensional differentiation assay, and immunofluorescence confocal microscopy. Future integration of the novel strategies presented herein to a clinical therapeutic model will allow safe preservation until transplantation and repeated transplantation if needed. These tools open a new venue for adult autologous stem-cell transplantation-based SG regeneration.

High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6ß1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function.

Establishment of immortal multipotent rat salivary progenitor cell line toward salivary gland regeneration.

Adult salivary gland stem cells are promising candidates for cell therapy and tissue regeneration in cases of irreversible damage to salivary glands in head and neck cancer patients undergoing irradiation therapy. At present, the major restriction in handling such cells is their relatively limited life span during in vitro cultivation, resulting in an inadequate experimental platform to explore the salivary gland-originated stem cells as candidates for future clinical application in therapy. We established a spontaneous immortal integrin α6ß1-expressing cell line of adult salivary progenitor cells from rats (rat salivary clone [RSC]) and investigated their ability to sustain cellular properties. This line was able to propagate for more than 400 doublings without loss of differentiation potential. RSC could differentiate in vitro to both acinar- and ductal-like structures and could be further manipulated upon culturing on a 3D scaffolds with different media supplements. Moreover, RSC expressed salivary-specific mRNAs and proteins as well as epithelial stem cell markers, and upon differentiation process their expression was changed. These results suggest RSC as a good model for further studies exploring cellular senescence, differentiation, and in vitro tissue engineering features as a crucial step toward reengineering irradiation-impaired salivary glands.

Isolation and cultivation of integrin alpha(6)beta(1)-expressing salivary gland graft cells: a model for use with an artificial salivary gland.

Regeneration of the salivary glands' (SGs) normal function for patients with cancer of the head and neck treated with irradiation would be a major contribution to their quality of life. This could be accomplished by re-implantation of autologous SG cells into the residual irradiated tissue or by implantation of tissue-engineered artificial SGs. Both methods depend on the isolation of cells able to propagate and differentiate into SG epithelial cells. Recently, it has been shown that SG integrin alpha(6)beta(1)-expressing (SGIE) cells have stem cell capabilities, but these cells could be isolated only after duct ligation insult requiring surgical intervention. Because such an invasive procedure is not clinically acceptable for these patients, our aim in the present study was to explore the use of immuno-magnetic separation of untreated and short heat stress-conditioned rats as a less-insulting methodology for enhancement of these cells. Our results show that submandibular SGIE cells could be isolated and cultivated from untreated animals. However, short heat stress (HS) increased the number of isolated SGIE cells 4.7-fold and their proliferation and clonal capability 4.6-fold and 3 fold, respectively. We believe that SGIE graft cells may be suitable candidates for future tissue-engineered SGs that have been damaged by irradiation in patients with head and neck cancer.

Reengineering salivary gland cells to enhance protein secretion for use in developing artificial salivary gland device.

Salivary glands (SGs) are considered exocrine glands, which mainly secrete water into the oral cavity. Nevertheless, they also exhibit a smaller endocrine secretory pathway toward the bloodstream. The concept of an artificial SG device for exocrine fluid secretion into the oral region in xerostomic patients has been previously studied. The purpose of the current study was to examine the potential of such a device for enhancing bioactive protein secretion. We engineered a plasmid encoding a SG-specific signal peptide sequence adjacent to a normally nonsecreted encoded reporter gene creating a chimera protein, and examined if this construct can enhance secretion from salivary epithelial cells. An N-terminal encoding epidermal growth factor (EGF) sequence was synthesized and inserted into a pGL3 control vector 5' of a firefly luciferase gene, creating a pGL3-EGF signal peptide (pGL3-EGFSP) fused vector. This vector was cotransfected with a pRL-CMV vector containing a Renilla luciferase gene, in 293 cells (serving as controls), and human submandibular gland ductal epithelial (HSG), rat submandibular gland acinar epithelial (SMIE), and rat submandibular gland ductal epithelial (A5) salivary cell lines. The transfected 293, SMIE, and HSG cells showed 8-, 18-, and 40-fold higher luciferase activity, respectively. These observations lead to the concept of an envisioned secretory device, which can serve as a potential biological pump for bioactive proteins.