ABSTRACT
A 45-year-old male with Vogt-Koyanagi-Harada (VKH) syndrome presented with vision loss in his right eye after discontinuing treatment during the COVID-19 pandemic. He was found to have bullous retinal detachment (RD) in the right eye and was started on subcutaneous adalimumab with oral corticosteroid following three doses of pulse corticosteroid. But when RD did not resolve after 4 months of treatment and ultrasound B scan showed bullous RD with retino-retinal adhesion, he was planned for surgical intervention. During surgery, there was retino-retinal adhesions due to long-standing "kissing exudative RD", causing non-settling exudative RD. Following surgery, the vision improved to 2/60, with attached retina. The patient has been under follow-up with us for the last one year now and developed no recurrence of RD till now. This case emphasises the significance of retinoretinal adhesion in long-standing bullous RD that does not respond to conventional aggressive medical therapy.
Subject(s)
Retinal Detachment , Tomography, Optical Coherence , Uveomeningoencephalitic Syndrome , Visual Acuity , Humans , Male , Retinal Detachment/etiology , Retinal Detachment/diagnosis , Retinal Detachment/surgery , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/complications , Uveomeningoencephalitic Syndrome/drug therapy , Middle Aged , Visual Acuity/physiology , COVID-19/complications , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , SARS-CoV-2 , VitrectomyABSTRACT
A 42-year-old male presented initially with conjunctivitis and was treated with topical medical medications without any improvement. He developed ocular pain subsequently and further examination revealed lid edema, conjunctival hyperemia with chemosis, matting of lashes with yellowish discharge, and deeper episcleral congestion which did not blanch with topical vasoconstrictor. Subsequent laboratory investigation revealed positive cytoplasmic-antineutrophil cytoplasmic antibody (Anti-PR 3 antibody). He continued to develop recurrences and finally responded to oral azathioprine. Granulomatosis with polyangitis may rarely present as conjunctivitis and subsequently manifest as scleritis.
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Importance: Co-located bridge clinics aim to facilitate a timely transition to outpatient care for inpatients with opioid use disorder (OUD); however, their effect on hospital length of stay (LOS) and postdischarge outcomes remains unclear. Objective: To evaluate the effect of a co-located bridge clinic on hospital LOS among inpatients with OUD. Design, Setting, and Participants: This parallel-group randomized clinical trial recruited 335 adult inpatients with OUD seen by an addiction consultation service and without an existing outpatient clinician to provide medication for OUD (MOUD) between November 25, 2019, and September 28, 2021, at a tertiary care hospital affiliated with a large academic medical center and its bridge clinic. Intervention: The bridge clinic included enhanced case management before and after hospital discharge, MOUD prescription, and referral to a co-located bridge clinic. Usual care included MOUD prescription and referrals to community health care professionals who provided MOUD. Main Outcomes and Measures: The primary outcome was the index admission LOS. Secondary outcomes, assessed at 16 weeks, were linkage to health care professionals who provided MOUD, MOUD refills, same-center emergency department (ED) and hospital use, recurrent opioid use, quality of life (measured by the Schwartz Outcome Scale-10), overdose, mortality, and cost. Analysis was performed on an intent-to-treat basis. Results: Of 335 participants recruited (167 randomized to the bridge clinic and 168 to usual care), the median age was 38.0 years (IQR, 31.9-45.7 years), and 194 (57.9%) were male. The median LOS did not differ between arms (adjusted odds ratio [AOR], 0.94 [95% CI, 0.65-1.37]; P = .74). At the 16-week follow-up, participants referred to the bridge clinic had fewer hospital-free days (AOR, 0.54 [95% CI, 0.32-0.92]), more readmissions (AOR, 2.17 [95% CI, 1.25-3.76]), and higher care costs (AOR, 2.25 [95% CI, 1.51-3.35]), with no differences in ED visits (AOR, 1.15 [95% CI, 0.68-1.94]) or deaths (AOR, 0.48 [95% CI, 0.08-2.72]) compared with those receiving usual care. Follow-up calls were completed for 88 participants (26.3%). Participants referred to the bridge clinic were more likely to receive linkage to health care professionals who provided MOUD (AOR, 2.37 [95% CI, 1.32-4.26]) and have more MOUD refills (AOR, 6.17 [95% CI, 3.69-10.30]) and less likely to experience an overdose (AOR, 0.11 [95% CI, 0.03-0.41]). Conclusions and Relevance: This randomized clinical trial found that among inpatients with OUD, bridge clinic referrals did not improve hospital LOS. Referrals may improve outpatient metrics but with higher resource use and expenditure. Bending the cost curve may require broader community and regional partnerships. Trial Registration: ClinicalTrials.gov Identifier: NCT04084392.
Subject(s)
Drug Overdose , Opioid-Related Disorders , Adult , Humans , Male , Female , Length of Stay , Aftercare , Quality of Life , Patient Discharge , Inpatients , Hospitals , Opioid-Related Disorders/therapyABSTRACT
Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF from n = 31 patients with GBM and n = 13 individuals with non-neoplastic conditions (controls), by mass spectrometry. Hierarchical clustering and sparse partial least square-discriminant analysis (sPLS-DA) revealed differences in CSF metabolites between GBM and control CSF, including metabolites associated with fatty acid oxidation and the gut microbiome (i.e., carnitine, 2-methylbutyrylcarnitine, shikimate, aminobutanal, uridine, N-acetylputrescine, and farnesyl diphosphate). In addition, we identified differences in CSF metabolites in GBM patients based on the presence/absence of TP53 or PTEN mutations, consistent with the idea that different mutations have different effects on tumor metabolism. In summary, our results increase the understanding of CSF metabolites in patients with diffuse gliomas and highlight several metabolites that could be informative biomarkers in patients with GBM.
Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Humans , Glioblastoma/genetics , Brain Neoplasms/pathology , Glioma/genetics , Mutation/genetics , Genomics , Biomarkers, Tumor/genetics , Isocitrate Dehydrogenase/geneticsABSTRACT
PURPOSE: Genomic alterations are fundamental for molecular-guided therapy in patients with breast and lung cancer. However, the turn-around time of standard next-generation sequencing assays is a limiting factor in the timely delivery of genomic information for clinical decision-making. METHODS: In this study, we evaluated genomic alterations in 54 cerebrospinal fluid samples from 33 patients with metastatic lung cancer and metastatic breast cancer to the brain using the Oncomine Precision Assay on the Genexus sequencer. There were nine patients with samples collected at multiple time points. RESULTS: Cell-free total nucleic acids (cfTNA) were extracted from CSF (0.1-11.2 ng/µl). Median base coverage was 31,963× with cfDNA input ranging from 2 to 20 ng. Mutations were detected in 30/54 CSF samples. Nineteen (19/24) samples with no mutations detected had suboptimal DNA input (< 20 ng). The EGFR exon-19 deletion and PIK3CA mutations were detected in two patients with increasing mutant allele fraction over time, highlighting the potential of CSF-cfTNA analysis for monitoring patients. Moreover, the EGFR T790M mutation was detected in one patient with prior EGFR inhibitor treatment. Additionally, ESR1 D538G and ESR1::CCDC170 alterations, associated with endocrine therapy resistance, were detected in 2 mBC patients. The average TAT from cfTNA-to-results was < 24 h. CONCLUSION: In summary, our results indicate that CSF-cfTNA analysis with the Genexus-OPA can provide clinically relevant information in patients with brain metastases with short TAT.
Subject(s)
Cell-Free Nucleic Acids , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Cell-Free Nucleic Acids/cerebrospinal fluid , Mutation , ErbB Receptors/genetics , Protein Kinase InhibitorsABSTRACT
Necrotizing scleritis is the most destructive and vision-threatening form of scleritis. Necrotizing scleritis can occur in systemic autoimmune disorders and systemic vasculitis, as well as following microbial infection. Rheumatoid arthritis and granulomatosis with polyangiitis remain the commonest identifiable systemic diseases associated with necrotising scleritis. Pseudomonas species is the most common organism causing infectious necrotizing scleritis, with surgery the most common risk factor. Necrotizing scleritis has the highest rates of complications and is more prone to secondary glaucoma and cataract than other phenotypes of scleritis. The differentiation between non-infectious and infectious necrotizing scleritis is not always easy but is critical in the management of necrotizing scleritis. Non-infectious necrotizing scleritis requires aggressive treatment with combination immunosuppressive therapy. Infectious scleritis is often recalcitrant and difficult to control, requiring long-term antimicrobial therapy and surgical debridement with drainage and patch grafting due to deep-seated infection and the avascularity of the sclera.
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We report an unusual case of sympathetic ophthalmia (SO) in an elderly gentleman following multiple eye surgeries. He presented with diffuse granulomatous panuveitis resembling leopard retinopathy in the left eye. There was a delay in the initiation of effective treatment of his intraocular inflammation, but he responded to corticosteroid and azathioprine. The pigmentary changes in his fundus were highly unusual, and he was investigated extensively to rule out other possible causes including a search for occult malignancy. The delay in initiation of effective treatment or suboptimal therapy in SO, can lead to variable clinical picture in elderly patients. A proper screening to exclude any malignancy along with aggressive immunosuppressive therapy can achieve optimum results.
Subject(s)
Ophthalmia, Sympathetic , Retinal Diseases , Male , Humans , Aged , Ophthalmia, Sympathetic/diagnosis , Ophthalmia, Sympathetic/drug therapy , Ophthalmia, Sympathetic/etiology , Retinal Diseases/diagnosis , Retinal Diseases/drug therapy , Retinal Diseases/etiology , Azathioprine/therapeutic use , Ophthalmologic Surgical Procedures/adverse effects , EyeSubject(s)
Acetaminophen , Drug Eruptions , Male , Humans , Adolescent , Acetaminophen/adverse effects , Drug Eruptions/etiology , SkinABSTRACT
PURPOSE: To report the management and outcome of VKH disease in a 4-year-old boy with a review of literature on VKH in preschool children (3 to 5 years). METHOD: Retrospective chart and literature review. RESULT: A 4-year-old boy presented with visual acuity of light perception in both eyes with panuveitis, secondary cataracts and intraocular pressure (IOP) of ≥40 mmHg in both eyes. He was started on oral corticosteroid, immunosuppressive and underwent glaucoma filtering surgery and lensectomy with vitrectomy after adequate control of intraocular inflammation. Over time his IOP was again uncontrolled even with maximum anti-glaucoma medications, and he underwent Ahmed glaucoma valve (AGV) implantation, and he gained a visual acuity of 20/60 in both eyes with aphakic correction at the last visit. CONCLUSION: Paediatric VKH follows an aggressive disease phase and requires a comprehensive multispeciality management approach.
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PURPOSE: To report the use of tofacitinib in ten patients with scleritis where the traditional immunomodulation was not successful or could not be used. METHOD: A retrospective chart review. RESULT: Tofacitinib was successful in the treatment of scleritis in patients either recalcitrant to or intolerant to conventional therapy in 9 out of 10 cases reported here. Two patients had developed reactivation of herpetic infection after 1 month of starting tofacitinib. The duration from diagnosis of scleritis to the institution of tofacitinib therapy varied from 1 month to 60 months. Duration of follow-up varies from 2 months to 11 months. CONCLUSION: Tofacitinib can be used as an important future option for managing recurrent and recalcitrant cases of scleritis.
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INTRODUCTION: We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas. METHODS: CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatography-mass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images. RESULTS: The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. ctDNA was detected in 7 of the 9 samples from patients with IDH-mutant glioma, and IDH1 p.R132H mutation was detected in 5 of the 7 samples. The MAF ranged from 0.3 to 39.95%. Total 2HG level, D-2HG level, and D/L-2HG ratio in CSF were significantly higher in patients with IDH-mutant gliomas than in patients with IDH-wildtype gliomas. D-2HG level and D/L-2HG ratio correlated with total tumor volume in patients with IDH-mutant gliomas but not in patients with IDH-wildtype gliomas. CONCLUSION: Our results suggest that detection of IDH1 p.R132H mutation by ddPCR and increased D-2HG level in CSF may help identify IDH-mutant gliomas. Our results also suggest that D-2HG level and D/L-2HG ratio correlate with tumor volume in patients with IDH-mutant gliomas. Further prospective studies with larger cohorts are needed to validate these findings.
Subject(s)
Circulating Tumor DNA , Glioma , Isocitrate Dehydrogenase , Biomarkers , Brain Neoplasms/cerebrospinal fluid , Brain Neoplasms/diagnosis , Circulating Tumor DNA/cerebrospinal fluid , Glioma/diagnosis , Glutarates , Humans , Isocitrate Dehydrogenase/cerebrospinal fluid , Isocitrate Dehydrogenase/genetics , Mutation , Prospective StudiesSubject(s)
Sarcoidosis , Uveitis , Humans , India/epidemiology , Sarcoidosis/diagnosis , Uveitis/diagnosis , Uveitis/epidemiologyABSTRACT
A 33-year-old male presented with history of blurring of vision in the left eye for two months. He was seen by the local ophthalmologist and diagnosed as nongranulomatous anterior uveitis in the left eye with normal fundus. He had history of fever 20 days back and was diagnosed positive for COVID-19 by RT-PCR. He presented with acute anterior uveitis in the left eye. Fundus examination revealed a cotton wool spot close to the fovea, which was confirmed by swept-source optical coherence tomography (SS-OCT) of the macula. The patient after two months' follow-up showed resolution of the cotton wool spot, which was confirmed by SS-OCT. Our case indicates that cotton wool spot can be an ocular manifestation of COVID-19 infection, and swept-source optical coherence tomography can precisely document the resolution of the lesion.
Subject(s)
COVID-19 , Tomography, Optical Coherence , Adult , Fluorescein Angiography , Fundus Oculi , Humans , Male , SARS-CoV-2ABSTRACT
BACKGROUND: Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes. METHODS: We reviewed characteristics of GBM IDH-WT (2009-2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Progression-free survival (PFS) and overall survival (OS) were evaluated with the log-rank test and Cox regression models. We validated our results utilizing data from cBioPortal (MSK-IMPACT dataset). RESULTS: Multivariable analysis of GBM IDH-WT revealed that treatment with chemoradiation and RB1-mutant status correlated with improved PFS (hazard ratio [HR] 0.25, P < .001 and HR 0.47, P = .002) and OS (HR 0.24, P < .001 and HR 0.49, P = .016). In addition, younger age (<55 years) was associated with improved OS. Karnofsky performance status less than 80 (HR 1.44, P = .024) and KDR amplification (HR 2.51, P = .008) were predictors of worse OS. KDR-amplified patients harbored coexisting PDGFRA and KIT amplification (P < .001) and TP53 mutations (P = .04). RB1-mutant patients had less frequent CDKN2A/B and EGFR alterations (P < .001). Conversely, RB1-mutant patients had more frequent TP53 (P < .001) and SETD2 (P = .006) mutations. Analysis of the MSK-IMPACT dataset (n = 551) validated the association between RB1 mutations and improved PFS (11.0 vs 8.7 months, P = .009) and OS (34.7 vs 21.7 months, P = .016). CONCLUSIONS: RB1-mutant GBM IDH-WT is a molecular subgroup with improved PFS and OS. Meanwhile, 4q12 amplification (KDR/PDGFRA/KIT) denoted patients with worse OS. Identifying subgroups of GBM IDH-WT with distinct survival is important for optimal clinical trial design, incorporation of targeted therapies, and personalized neuro-oncological care.
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INTRODUCTION: Optimal treatment for recurrent glioblastoma isocitrate dehydrogenase 1 and 2 wild-type (rGBM IDH-WT) is not standardized, resulting in multiple therapeutic approaches. A phase III clinical trial showed that tumor treating fields (TTFields) monotherapy provided comparable survival benefits to physician's chemotherapy choice in rGBM. However, patients did not equally benefit from TTFields, highlighting the importance of identifying predictive biomarkers of TTFields efficacy. METHODS: A retrospective review of an institutional database with 530 patients with infiltrating gliomas was performed. Patients with IDH-WT rGBM receiving TTFields at first recurrence were included. Tumors were evaluated by next-generation sequencing for mutations in 205 cancer-related genes. Post-progression survival (PPS) was examined using the log-rank test and multivariate Cox-regression analysis. RESULTS: 149 rGBM patients were identified of which 29 (19%) were treated with TTFields. No significant difference in median PPS was observed between rGBM patients who received versus did not receive TTFields (13.9 versus 10.9 months, p = 0.068). However, within the TTFields-treated group (n = 29), PPS was improved in PTEN-mutant (n = 14) versus PTEN-WT (n = 15) rGBM, (22.2 versus 11.6 months, p = 0.017). Within the PTEN-mutant group (n = 70, 47%), patients treated with TTFields (n = 14) had longer median PPS (22.2 versus 9.3 months, p = 0.005). No PPS benefit was observed in PTEN-WT patients receiving TTFields (n = 79, 53%). CONCLUSIONS: TTFields therapy conferred a significant PPS benefit in PTEN-mutant rGBM. Understanding the molecular mechanisms underpinning the differences in response to TTFields therapy could help elucidate the mechanism of action of TTFields and identify the rGBM patients most likely to benefit from this therapeutic option.
Subject(s)
Brain Neoplasms , Glioblastoma , PTEN Phosphohydrolase/genetics , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Chronic Disease , Glioblastoma/genetics , Glioblastoma/therapy , Humans , Mutation , Recurrence , Retrospective StudiesABSTRACT
Available tools to evaluate patients with central nervous system (CNS) tumors such as magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology, and brain biopsies, have significant limitations. MRI and CSF cytology have poor specificity and sensitivity, respectively, and brain biopsies are invasive. Circulating tumor DNA in CSF (CSF-ctDNA) could be used as a biomarker in patients with CNS tumors, but studies in this area are limited. We evaluated four CSF-ctDNA extraction methods and analyzed mutations in CSF-ctDNA with the Oncomine Pan-Cancer cell-free assay. CSF-ctDNA was extracted from 38 patients with primary or metastatic CNS tumors and 10 patients without CNS malignancy. Commercial ctDNA controls were used for assay evaluation. CSF-ctDNA yields ranged from 3.65 to 3120 ng. Mutations were detected in 39.5% of samples. TP53 was the most commonly mutated gene and copy number alterations were detected in CCND1, MYC, and ERBB2/HER2. Twenty-five percent of CSF-cytology-negative samples showed mutations in CSF-ctDNA. There was good concordance between mutations in CSF-ctDNA and matching tumors. The QIAamp Circulating Nucleic Acid Kit was the optimal method for extraction of CSF-ctDNA and the Oncomine cell-free DNA assay is suitable for detection of mutations in CSF-ctDNA. Analysis of CSF-ctDNA is more sensitive than CSF-cytology and has the potential to improve the diagnosis and monitoring of patients with CNS tumors.
Subject(s)
Biological Assay , Central Nervous System Neoplasms/cerebrospinal fluid , Circulating Tumor DNA/cerebrospinal fluid , Adult , Aged , Cell-Free System , Circulating Tumor DNA/genetics , DNA Copy Number Variations/genetics , Female , Genome, Human , Humans , Male , Middle Aged , Mutation/genetics , Young AdultABSTRACT
Brainstem infarction typically presents with vague symptoms, including headache, nausea, vomiting, and vertigo. Rarely do patients present with complete unilateral facial paralysis, mimicking Bell's palsy. Here we report the case of a 40-year-old woman who presented to the emergency department with intractable nausea, vomiting, and vertigo upon waking along with left-sided upper and lower extremity numbness and right-sided facial paralysis. Her atypical presentation of unilateral facial nerve paralysis in the context of nausea, vomiting, and vertigo prompted neurological studies, which were significant for a small punctate infarct in the pons involving the right facial colliculus. âHistory, physical examination, and clinical suspicion are important to prevent anchoring bias. Physicians rely on history and physical examination to help distinguish true Bell's palsy from other causes of facial nerve paralysis. Stroke and other clinically emergent etiologies should be considered high on the differential diagnosis when patients have neurological signs and symptoms in addition to facial nerve palsy.