Causes of congenital corneal opacities and their management in a tertiary care center.

PURPOSE: To evaluate causes and management of congenital corneal opacities (CCO) diagnosed in a tertiary care eye center and to compare the data with a previous study at the same institution. METHODS: Computerized medical records in all patients with congenital corneal opacities diagnosed in the Cornea Service at Wills Eye Hospital (Philadelphia, PA) between January 1, 2007, and December 31, 2015, were retrospectively reviewed. Children aged 12 years and younger at the first visit were included in the study. Patients\u27 demographics, ocular diagnosis, laterality, associated ocular abnormalities, other ocular surgery performed prior or subsequent to the first visit, and their treatment were extracted from the medical records. RESULTS: A total of 77 eyes in 56 patients were examined. The mean age at presentation was 32.8 ± 44.2 months, with the mean follow-up period of 26.7 ± 30.1 months. The most frequent diagnosis was Peters anomaly (53.2%), followed by limbal dermoid (13.0%), aniridia with glaucoma and microphthalmos (6.5%), sclerocornea and congenital glaucoma (5.2%), idiopathic (3.9%), Axenfeld-Rieger anomaly and Hurler syndrome (2.6%), and microcornea (1.3%). Primary keratoplasty was performed in 26 eyes, with the outcome rate in the clear cornea of 76.0% during the follow-up. CONCLUSION: Peters anomaly is the most common cause of congenital corneal opacities encountered at our institution. Penetrating keratoplasty is the most frequent choice of corneal surgery to treat congenital corneal opacities. Additional interventions during penetrating keratoplasty were moderately positively correlated with graft failure. This study also shows the rates of some etiologies of that changed over the recent decades in our tertiary care Cornea Service. Although Peters anomaly remains the most common presenting reason for congenital corneal opacities, its rate appears to be increasing over the recent decade. Congenital corneal opacities due to birth trauma, which is one of the preventable causes, were observed in a previous study in our clinic; however, no new cases were noted in this study

Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.

Progenics\u27s rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company\u27s Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063]

Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort.

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487

Procalcitonin as an Early and Reliable Marker of Neonatal Sepsis

INTRODUCTION: Infection as a prime cause or a complication of other illness is the major cause of mortality and morbidity throughout the world in neonates. Early recognition, diagnosis and treatment of serious infections in the neonates are mandatory because of poor defense; newborn cannot localize the pathogens, which can easily spread to multiple organs. Lack of intervention at an early stage leads to mortality or severe sequelae. Progression from mild symptoms to death occurs more rapidly1. Most neonatal bacterial infections have an early bacteraemic phase preceding the development of full blown septicemia or localization of infection in organs and tissues. During this phase the clinical signs are subtle, but this is when the treatment must be started if there is to be intact survival. Neonatal sepsis is classified into early onset sepsis and late onset sepsis. Early onset sepsis (EOS): It develops within 72hrs of life. Organisms present in genital tract or in labour room and operation theatre are most common causes. Most cases are due to gram negative organisms like E.Coli, Klebsiella and Enterobacter species in our country. Late onset sepsis (LOS): It develops after 72 hrs of life due to community or hospital acquired infection. Two third of LOS is caused by gram negative organisms such as Klebsiella pneumoniae, Enterobacter, E.Coli, Pseudomonas aeruginosa, Alcaligenes faecalis, Salmonella typhimurium, Proteus, Citrobacter and Serratia. Rest is caused by gram positive organisms such as Coagulase negative staphylococcus (CONS) and Staph aureus. OBJECTIVES: Primary objective: Procalcitonin as an early and reliable marker of neonatal sepsis Secondary objective: To compare the effectiveness of CRP and WBC with procalcitonin in predicting the neonatal sepsis at the earliest. DISCUSSION: The major cause of neonatal morbidity and mortality is neonatal sepsis. This study was conducted to show Procalcitonin can be used as an early and reliable marker of neonatal sepsis and to compare its efficacy with that of CRP and WBC count. These two tests are routinely used in our institution for initial sepsis screening. If CRP and WBC count are as efficacious as procalcitonin, they can be substituted for procalcitonin in resource poor setting and cost effective. This study was conducted in 50 neonates who had clinical features of sepsis. Both preterm and term neonates were included. Both early onset sepsis and late onset sepsis were included. Blood samples were drawn for CRP, PCT, WBC count and blood culture before starting antibiotics. Other investigations like CSF analysis, CXR were done in symptomatic infants. Out of 50 neonates blood culture was positive in 27 (54%) neonates. 15 out of remaining 23 infants had other positive investigations like CSF analysis, CXR supporting sepsis and hence grouped as culture negative sepsis. Remaining 8 neonates had only clinical features and hence termed as suspected sepsis. Procalcitonin was positive (≥2ng/dl) in 35 neonates, CRP was positive (≥1mg/dl) in 25 neonates and WBC count was positive ( 20,000) in 22 neonates. Sensitivity, specificity, positive predictive value and negative predictive value are calculated for PCT, CRP and WBC count taking blood culture as gold standard test. The sensitivity, specificity, positive predictive value and negative predictive value for procalcitonin were 92.59%, 56.52%, 71.4% and 86.6% respectively. The sensitivity, specificity, positive predictive value and negative predictive value for CRP were 55.55%, 56.52%, 60% and 52% respectively. The Sensitivity, specificity, positive predictive value and negative predictive value for WBC count were 40.74%, 52.17%, 50% and 42.85%. Procalcitonin had highest sensitivity (92.59%) compared to that of CRP (55.55%) and WBC count (40.74%). The specificity of procalcitonin (56.52%) was almost same as that of CRP, but greater than the specificity of WBC count (52.17%) and lesser than that of platelet count (86.95%). The positive predictive value (71.4%) and negative predictive value (86.6%) of procalcitonin were higher than positive and negative predictive value of CRP and WBC count, which were (60%, 52%) and (50% and 42.85%) respectively. CONCLUSION: 1. Procalcitonin can be used as an early and reliable marker of neonatal sepsis. 2. CRP and WBC count though can be used as initial sepsis screening; it cannot be substituted for procalcitonin. 3. No combined investigation excluding procalcitonin was superior to procalcitonin. 4. Combination of procalcitonin and CRP had highest sensitivity but low specificity. 5. Combination of procalcitonin and platelet had both higher sensitivity and specificity. 6. Sampling interval greatly influence the level of CRP but not procalcitonin level. 7. Klebsiella Pneumoniae is the most common organism causing both early onset and late onset sepsis in our institution

A Study on Cryptococcal Meningitis in patients with Acquired Immunodeficiency Syndrome.

INTRODUCTION : Cryptococcus neoformans is an encapsulated heterobasidiomycetous fungus that has progressed from being a rare human pathogen to become a common worldwide opportunistic pathogen in immunocompromised hosts. Although the name Cryptococcus Literally means “hidden seed”, the hitherto less known pathogen came into limelight with The advent of the AIDS pandemic. The genus Cryptococcus comprises of over 70 species But human infection is seldom caused by species other than C.neoformans and C.gattii. Occasional cases of infections due to C.laurentii (Lynch et al, 1981), C.albidus (Horowitz et al, 1993) and C.adeliensis (Rimek et al, 2004) have been reported but Isolation of other cryptococcal species from clinical specimens requires both culture and histological proof of invasion before attributing disease to them. In general, C.neoformans Is associated with infection in immunocompromised hosts while C.gattii is associated with Infections in immunocompetent hosts. C.gattii which has long been considered to infect only immunocompetent hosts has Started to cause infections in AIDS patients adding to the burden of cryptococcal infection in this cohort . Since neurological complications are more with C.gattii, identification of this species needs to be prioritized. An additional concern is the emergence of drug Resistance in Cryptococcus to antifungal agents in recent years. Though the reports are sparse, routine testing for antifungal susceptibility testing of clinical isolates is necessary To obtain baseline data and observe any shift in sensitivity pattern. AIMS AND OBJECTIVES : 1. Rapid identification of Cryptococcus as the etiologic agent of meningitis in HIV positive patients using microscopic techniques and latex agglutination test. 2. Isolation of Cryptococcus in culture from the CSF of the affected patients and also from other sites (in cases of disseminated infection). 3. Speciation of the cryptococcal isolates using phenotypic methods. 4. Determination of susceptibility pattern of cryptococcal isolates to antifungal agents and comparison of MIC values obtained by E- test with those of microbroth dilution method. MATERIALS AND METHODS : All patients satisfying the inclusion criteria were included in the study. Informed consent was obtained from the patients/ relatives (in case of patients with altered sensorium) and a structured questionnaire was used to obtain details of the patient. The study was conducted on HIV positive patients admitted to the medicine wards of either of the two hospitals : Rajiv Gandhi Government General Hospital, Chennai and Government Hospital of Thoracic Medicine, Tambaram, Chennai.Inclusion Criteria- Patients infected with HIV and presenting with symptoms suggestive of meningitis like 1. Fever, 2. Diffuse headache, 3. Nausea/vomiting, 4. Drowsiness/ altered sensorium, 5. Visual disturbances: blurring/ diplopia (or) photophobia. Exclusion Criteria - HIV negative patients presenting with features suggestive of meningitis. CONCLUSION : There is a decline in the number of cases of cryptococcal meningitis due to better diagnostic facilities for early detection of HIV infection and wider accessibility to ART. Male patients are more often affected and the symptoms of CM overlap with those due to other pathogens. Microscopic examination of CSF by India ink preparation is cost effective in the diagnosis of CM in HIV positive patients. LAT is highly sensitive in detecting cryptococcal polysaccharide in laboratories where the facility is available. Culture of CSF is the gold standard test in the diagnosis of CM and must be performed on all suspected cases of meningitis. C.neoformans is more often the etiologic agent of CM in HIV positive patients when compared to C.gattii. Treatment of patients with CM using amphotericin-B at the earliest is needed to reduce the mortality which is still unacceptably high. Secondary fluconazole prophylaxis must be started in all patients with CM to reduce/prevent the occurrence of relapse. Institution of HAART must be done after treatment of the primary episode as the benefits outweigh the risk of development of IRIS in these patients. CM often occurs when CD4 count falls below 100cells/μl. So, initiation of ART at CD4 count of 350cells/μl as recommended by the recent NACO guidelines can go a long way in further reduction of incidence of CM. Although resistance of C.neoformans to antifungal agents is rare, periodic monitoring of MIC by microbroth dilution tests is essential to notice any shifts in sensitivity pattern of clinical isolates

Anterior Chamber Characteristics, Endothelial Parameters, and Corneal Densitometry After Descemet Stripping Automated Endothelial Keratoplasty in Patients With Fuchs Dystrophy

Purpose: To compare anterior segment parameters in patients with Fuchs endothelial dystrophy (FED) who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) in one eye and no corneal surgery in the fellow eye. Methods: This prospective study was conducted on 28 eyes of 14 patients with FED who underwent DSAEK in one eye at least one year prior (DSAEK group) and no corneal surgery in the fellow eye (control group). Each eye was analyzed with the anterior segment optical coherence tomography, specular microscopy, and Scheimpflug imaging systems. Data were compared between the two groups. Results: The mean age of the patients was 76.9 ± 7.0 years. There were no statistically significant differences in the mean central corneal thickness (CCT), central anterior chamber depth, anterior chamber angle parameters, cylinder and keratometry values between two groups (all P-values > 0.05). The paracentral corneal thickness, corneal volume, endothelial cell density, and hexagonal cell ratio measurements were statistically significantly higher in the DSAEK group than the control (all P-values < 0.05), and anterior chamber volume in the DSAEK group was significantly less than the control (P = 0.046). While posterior and total corneal densitometry values in the DSAEK group were statistically significantly lower than the control (P < 0.001 and P = 0.011, respectively), there were no statistically significant differences in the anterior or middle corneal densities (P = 0.108 and P = 0.134, respectively). Conclusion: We found that total corneal densitometry value decreased in DSAEK group. Although DSAEK surgery did not affect the anterior chamber angle parameters, it reduced the anterior chamber volume and increased the corneal volume and paracentral corneal thickness due to the addition of the DSAEK graft

Comparison of 2 high-throughput spectral techniques to predict differences in diet composition of grazing sheep and cattle

Diet composition can be estimated in free-ranging animals by the use of n-alkane and long-chain fatty alcohol concentrations in feces. However, this technique involves relatively laborious and costly analytical techniques. Two spectroscopy techniques were investigated as a way of determining whether dietary differences are likely, thus indicating whether the more expensive and labor-intensive techniques for more detailed analysis are justified. Fourier-transform infrared spectroscopy (FTIR) and front-face fluorescence emission spectroscopy (lambda(excitation) = 380 nm, lambda(emission) = 600 to 760 nm) were used to analyze fecal samples collected from 2 different breeds of cattle and sheep (4 groups in total, n = 6 per group) grazing moorland plants in 2 grazing sessions. These fecal samples were also analyzed for alkane and alcohol concentrations. Fourier-transform infrared spectra, particularly in the alkane regions, demonstrated clear separation between animal species. Fluorescence emission spectra showed similar separation; fluorophores were most likely chlorophylls and their derivatives. Multivariate analysis of all 3 data sets showed similar variation within and between groups of cattle and sheep, indicating differences in diet selection particularly between species, but also between breed and grazing session. Both spectroscopy methods showed utility in suggesting differences in diet composition that would be worth investigating using more detailed chemical analyses. Of the 2 techniques, the FTIR spectroscopy gave the better comparative results, being able to detect differences in sampling months that were detected with alkanes and alcohols that the fluorescence emission spectroscopy did not detect

Histopathological study of pancreatobiliary tumors in a tertiary care center: a 7 year study

Background: The aim of this study was to comprehensively analyse the histopathological spectrum of pancreatobiliary tumors with special reference to ampulla of Vater.Methods: The retrospective study was done for 5 years and a prospective study was carried out for 2 years in the Department of Pathology.Results: A total of 110 cases were included; 103 underwent a standard Whipple procedure and 7 underwent localised resection (partial pancreatectomy). The average age was 52.64 years (16-80 years) and males outnumbered females (3:2). Malignant (93.63%) lesions outweighed benign lesions (6.36%). Among malignant lesions, 71 (68.93%) were peri-ampullary, 15 (14.56%) were pancreatic, 11 (10.67%) were duodenal and only 6 (5.825%) were cholangiocarcinoma. The most common presenting feature was jaundice followed by pain in the abdomen. The mean tumor size was 2.38 cm (0.5-15cm). The pathological stage of most of the tumors was T2 (58.2%), followed by T3 (22.7%), T1 (11.8%) and T4 was only 1.8%. Proximal duodenal resection margin was free in 90.9%, distal duodenal resection margin was free in all cases, CBD resection margin was involved in only 2 cases (1.8%), while the pancreatic duct resection margin was involved in 2.7%. The nodal status was N0 in 61.8%, N1 in 23.6% and Nx in 9.1%.Conclusions: Adenocarcinoma (well differentiated-47.3%) is the most common histological variant of pancreatobiliary region

Pediatric High Risk Leukemia — Molecular Insights

Acute leukemia comprises of 31% of all cancers in children making it the most common childhood malignancy. Significant strides have been made in treatment, partly through risk stratification and intensified therapy. A number of subtypes remain at high risk for relapse and poor outcome, despite current therapies. Here we describe risk stratification and molecular diagnosis used to identify high risk leukemias and guide treatment. Specific cytogenetic alterations that contribute to high risk B and T cell acute lymphoblastic leukemia (ALL), as well as infant leukemia are discussed. Particular attention is given to genetic alterations in IKZF1, CRLF2, and JAK, that have been identified by whole genome sequencing and recently associated with Ph-like ALL. Ongoing studies of disease mechanisms and challenges in developing pre-clinical patient-derived xenograft models to evaluate therapies are discussed