A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number

Retinopathy of prematurity like retinopathy in full-term infants

PURPOSE: The purpose of this study is to assess clinical characteristics, risk factors, and management outcomes of retinal changes similar to retinopathy of prematurity (ROP), seen in full-term infants. PATIENTS AND METHODS: This is a retrospective review of 46 eyes of 23 patients, born at full term or near full term and diagnosed to have active ROP-like retinopathy or sequelae of ROP-like retinopathy. RESULTS: Mean birth weight (BW) and gestational age (GA) were 2342 ± 923 g (range, 1200–4160 g) and 38.5 ± 1.85 weeks (range, 37–40 weeks). Mean age at the time of diagnosis was 3.5 ± 8.75 years (range, 1 month–16 years). Stage 1 and 2 of retinopathy was seen in 10 eyes (21.7%), threshold disease with plus disease in 12 eyes (26%) and Stage 4 or 5 in 14 eyes (30.4%). Involutional sequelae were noted in 10 eyes (21.7%). Twenty-one eyes (45.6%) underwent appropriate treatment in the form of laser, cryotherapy, or retinal detachment surgery. Eight eyes (17.4%) with advanced sequelae such as total closed funnel retinal detachment and macular fold were not treated. Mean follow-up was 3 years (range, 1 month to 12 years). At the last follow-up, 29 eyes (63%) had a favorable structural outcome (P < 0.001). Among the patients in whom visual acuity could be assessed (16 eyes), favorable visual outcome was noted in 9 eyes (56.2%). Low BW (P = 0.038), multiple births (P = 0.013), respiratory distress syndrome (RDS) (P = 0.001), phototherapy (P = 0.001), and oxygen administration (P < 0.001) were significantly associated with the development of ROP-like retinopathy in these full-term infants. CONCLUSIONS: ROP-like retinopathy can occur in full-term and near full-term infants and can potentially lead to permanent visual impairment. Screening of infants with risk factors such as oxygen administration, RDS, multiple births, and low BW, regardless of GA, may reduce visual impairment

Brain abscess: Current management

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. Most arise in association with major nerve trunks. Their most common anatomical sites are the proximal portions of the upper and lower extremities and the trunk. MPNSTs have rarely been reported in literature to occur in other unusual body parts. We review all such cases reported till now in terms of site of origin, surgical treatment, adjuvant therapy and outcome and shortly describe our experience with two of these cases. Both of our case presented with lump at unusual sites resembling neurofibroma, one at orbitotemporal area and other in the paraspinal region with characteristic feature of neurofibroma with the exception that both had very short history of progression. They underwent gross total removal of the tumor with adjuvant radiotherapy postoperatively. At 6‑month follow‑up both are doing well with no evidence of recurrence

Comparison of Dexamethasone Implant and Anti-VEGF Agents in the Treatment of Naive Diabetic Macular Oedema: A Prospective Cohort Study

Introduction: Diabetic Retinopathy (DR) is one of the common microvascular complications of diabetes. In patients with DR, the most frequent cause of vision loss is Diabetic Macular oedema (DME). In the present era, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents are the mainstay of treatment for managing DME. A majority of patients show a good response to multiple doses of these agents administered by a pro re nata regimen at regularly spaced fixed intervals. However, the tendency of DME to become chronic and resistant to these agents, as well as the burden of repeated injections, necessitates considering alternative treatment options with similar or better efficacy. As steroids can address these drawbacks of anti-VEGF treatment, the present study compared the efficacy of anti-VEGF agents with dexamethasone implant in the treatment of naïve DME. Aim: To compare the effectiveness of dexamethasone implant with anti-VEGF agents in the treatment of naïve DME. Materials and Methods: A prospective cohort study was conducted in the Department of Ophthalmology at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, Odisha, India from September 2020 to September 2022. A total of 100 eyes with DME, newly diagnosed patients aged 18 years and above, without other macular oedema-causing diseases, were included. A total of 50 eyes in each group were treated with an anti-VEGF agent (Group A) or dexamethasone implant (Group B), and Best Corrected Visual Acuity (BCVA) and Central Foveal Thickness (CFT) were monitored for six months. For statistical analysis, paired t-test and independent t-test were used for within-group and inter-group analysis, respectively. A p-value <0.05 was considered statistically significant. Results: In both groups, post-treatment BCVA showed marked improvement, but there was no significant difference in mean BCVA between the groups (p=0.89) at six months. However, the mean CFT showed significant improvement in Group B at six months. In Group A, the mean CFT reduced from 441.87±54.48 μm to 257.83±25.73 μm, and in Group B, the mean CFT reduced from 464±109.44 μm to 207±22.51 μm at six months (p<0.0001). Adverse events like cataracts and glaucoma were seen in patients treated with the dexamethasone implant and were managed by cataract surgery and topical anti-glaucoma medications, respectively. Conclusion: Dexamethasone implant and anti-VEGF agents are equally effective in improving visual acuity; however, dexamethasone stands superior in reducing macular thickness. Needing fewer injections while treating with a dexamethasone implant improves compliance. The progression of cataract remains a major side-effect with the dexamethasone implant, which is not a concern when treating DME in pseudophakic eye

A case of multiple myeloma presenting as scalp swelling with intracranial extension

Multiple myeloma is a malignant neoplasm of bone marrow affecting plasma cells. It is usually detected in skull bone with characteristic features of multiple punched-out lesions. Its presentation as a solitary scalp swelling with underlying skull bone erosion and intracranial extension is very rare. A 35-year-old female presented to us with complains of rapidly growing left-side scalp swelling with right-side paresis and simple partial seizure of right upper limb. Local examination, X-ray skull, CT scan, and MRI of brain were suggestive of a malignant lesion. Near total excision of lesion was done. Histopathological study was suggestive of plasmacytoma of skull. Bone marrow study further confirmed it as a case of multiple myeloma. Cases presenting with solitary osteolytic skull lesions, possibility of plasmacytoma, or multiple myeloma should be kept in mind

A HOSPITAL-BASED OBSERVATIONAL STUDY ON THE SURVIVAL OUTCOMES OF PATIENTS WITH HIGH-GRADE GLIOMA ABOUT DIVERSE PROGNOSTIC FACTORS.

Background:   Despite the treatment available for tumors in the brain, the prognosis of these tumors has a significant effect on the emotional and cognitive abilities of the patients. Early diagnosis and suitable treatment can prevent the worsening of the tumor. The effect of the tumor on the brain leads to a negative impact on an individual’s social life. This necessitates the requirement for a treatment that is reliable and prevents the worsening of tumors. This study aimed to study the various clinical presentations, various imaging features, Immunohistochemical expression of various tumor markers, and the outcome after surgery and adjuvant chemotherapy and radiotherapy and to analyze various prognostic factors of high-grade glioma. Material & Methods:  This includes 103 cases of High-grade gliomas admitted to the Department of Neurosurgery, SCB Medical College & Hospital, Cuttack between January 20202 to March 2023. Before the resection of the tumor, neurological and radiological examinations were carried out. The extent of removal was determined by running a CT scan after the surgery. Results:  In the present study of 103 cases, males constituted 62.1% as compared to females who constituted 37.9%. 48.5% of all tumors were found in the frontal lobe, followed by the temporal lobe (32%) of cases. Enhancement was seen in 89% of cases, mostly it was seen in Glioblastomas. Hemorrhage was seen in 40.8% of cases mostly seen in grade 4 gliomas. Lipid lactate peak was seen in 71.8% of cases. Conclusion:  KPS score, surgical resection, Adjuvant chemotherapy, and radiotherapy showed statistically significant association with the outcome and survival rate. Recommendation:  Further studies with a larger number of patients, using multiple immunohistochemical markers, and a longer follow-up are needed, which will provide significant data to conclude on the outcome and survival analysis

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10(-109)); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10(-9)) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number