Predicting nodal metastases in squamous cell carcinoma of the oral tongue using artificial intelligence.

OBJECTIVE: The presence of occult nodal metastases in patients with squamous cell carcinoma (SCC) of the oral tongue has implications for treatment. Upwards of 30% of patients will have occult nodal metastases, yet a significant number of patients undergo unnecessary neck dissection to confirm nodal status. This study sought to predict the presence of nodal metastases in patients with SCC of the oral tongue using a convolutional neural network (CNN) that analyzed visual histopathology from the primary tumor alone. METHODS: Cases of SCC of the oral tongue were identified from the records of a single institution. Only patients with complete pathology data were included in the study. The primary tumors were randomized into 2 groups for training and testing, which was performed at 2 different levels of supervision. Board-certified pathologists annotated each slide. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic (ROC) curves and the Youden J statistic were used for primary analysis. RESULTS: Eighty-nine cases of SCC of the oral tongue were included in the study. The best performing algorithm had a high level of supervision and a sensitivity of 65% and specificity of 86% when identifying nodal metastases. The area under the curve (AUC) of the ROC curve for this algorithm was 0.729. CONCLUSION: A CNN can produce an algorithm that is able to predict nodal metastases in patients with squamous cell carcinoma of the oral tongue by analyzing the visual histopathology of the primary tumor alone.

Comparison between effects of instrument-assisted soft tissue mobilization and manual myofascial release on pain, range of motion and function in myofascial pain syndrome of upper trapezius - A randomized controlled trial.

Background: Myofascial pain syndrome (MPS) is a muscle pain disorder characterized by the presence of Myofascial Trigger Point (MTrP) within a taut band, local tenderness, referral of pain to a distant site, restricted range of motion, and autonomic phenomena. The upper trapezius is the muscle most often affected by MTrPs. Manual myofascial release (MFR) and Instrument-Assisted Soft Tissue Mobilization (IASTM) are techniques of soft tissue release that are used to resolve MPS. Fifty six percent of physiotherapists complain of pain in multiple areas due to the massage and manual therapy that they have to perform. Objective: The objective of this study is to find whether IASTM is better than manual MFR in treating patients with MPS in upper trapezius. Methods: This study was a single-blinded randomized controlled trial that included 31 participants, both males and females between the age groups of 18-50 years. Participants were randomly divided into two groups. Three sessions were given over a period of one week for both groups. Group A received IASTM along with conventional treatment and Group B received Manual MFR along with the conventional treatment. The outcome measures evaluated were pain, cervical range of motion, pain pressure threshold (PPT) of trigger points, and the neck disability index. Pre- and post-measurements were taken and the analysis was done. Results: Both the treatment methods significantly reduced pain, improved PPT, range of motion, and function. The effects between the groups showed that IASTM was significantly better than manual MFR to reduce pain. The improvement in PPT, range of motion and function were equal in both the groups. Conclusion: IASTM and manual MFR both are effective individually as treatment procedures for pain, PPT, range of motion, and function. Neither of the treatment options can be considered better that the other. The clinician can decide based on the availability of the instrument, training, patient's preference, and his/her comfort whether which of the two treatment methods should be used.

Adjunctive use of saturated solution of potassium iodide (SSKI) with liposomal amphotericin B (L-AMB) in mucormycosis achieves favorable response, shortened dose and duration of amphotericin: A retrospective study from a COVID-19 tertiary care center.

PURPOSE: Second wave of COVID-19 pandemic was associated with an unprecedented rise in cases of mucormycosis, treatment of which has been challenging owing to the availability and side effects associated with amphotericin. METHODS: All patients presenting with rhino-orbital cerebral mucormycosis (ROCM) following COVID-19 infection between April 2021 to June 2021 were included in this retrospective interventional study. Primary objective was to assess the clinical response with combination of intravenous liposomal amphotericin B (4-5 mg/kg/day) and saturated solution of potassium iodide (SSKI) given orally along with surgical debridement. RESULTS: Twenty-five patients of ROCM were treated with the regimen. Mean age and fasting blood sugar levels were 53.48 years and 239.64 mg/dL respectively. All patients had history of intake of steroids with a mean daily dose of 86.39 mg of prednisolone equivalent. 88% of patients had a "proven" diagnosis of mucormycosis. Cultures were positive in 52% of patients with Rhizopus arrhizus as the predominant species. The mean daily dose of amphotericin received was 268 mg/day with a mean duration of 9.52 days. Mean daily dose of SSKI was 2.57 g. 21 patients (84%) had stabilization of disease at week 8 and achieved cure at the end of treatment whereas the mortality rate was 16%. Factors that significantly affected outcome were eye and central nervous system (CNS) involvement on presentation. CONCLUSION: SSKI, with its remarkably low cost and safety profile, makes it a potential adjuvant drug that may help achieve the twin benefits of shortened duration and dose of LAMB.

HBME1 and CK19 expression in non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) vs other follicular patterned thyroid lesions.

BACKGROUND: Thyroid neoplasms with follicular architecture can have overlapping morphologic features and pose diagnostic confusion among pathologists. Various immunohistochemical stains have been investigated as potential diagnostic markers for PTC, among which HBME1 and CK19 have gained popularity. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses similar diagnostic challenges with interobserver variability and is often misdiagnosed as adenomatoid nodule or follicular adenoma. This study aims to evaluate expression of HBME1 and CK19 in NIFTPs in comparison to other well-differentiated thyroid neoplasms and benign mimickers. METHOD: Seventy-three thyroid cases diagnosed over a period of 3 years at Methodist University Hospital, Memphis, TN, USA, were included in this study: 9 NIFTP; 18 papillary thyroid carcinoma (PTC); 11 follicular variant of papillary thyroid carcinoma, invasive (I-FVPTC); 24 follicular adenomas (FA); and 11 multinodular goiters/adenomatoid nodules (MNG). A tissue microarray (TMA) was constructed and HBME1 and CK19 immunohistochemistry was performed. RESULTS: 77.8% of NIFTPs, 88.9% of PTCs, 81.8% of I-FVPTCs, 16.7% of FAs, and 18.2% of MNGs showed HBME-1 expression. 66.7% of NIFTPs, 83.3% of PTCs, 81.8% of I-FVPTCs, 33.3% of FAs, and 45.4% of MNGs expressed CK19. Difference in expression of HBME1 and CK19 was statistically significant for NIFTP vs FA (qualitative; p < 0.05) and NIFTP vs MNG (p < 0.05). No statistically significant difference was found for HBME1 in NIFTP vs PTC (conventional and FVPTC), p ≥ 0.2. Sensitivity of HBME1 and CK19 for NIFTP were 78% and 67%, ~ 88% each for PTC, and 89% and 100% for FVPTC, respectively, while specificity of HBME1 and CK19 for NIFTP were 53% each, ~ 62% each for PTC, and ~55% each for FVPTC. CONCLUSION: Our study indicated that HBME1 and CK19 are valuable markers in differentiating NIFTPs from morphologic mimics like follicular adenoma and adenomatoid nodules/multinodular goiter. While HBME1 and CK19 are both sensitive in diagnosing lesions with PTC-like nuclear features, CK19 stains a higher number of benign lesions in comparison to HBME1. No increase in sensitivity or specificity in diagnosis of NIFTP, PTC, or FVPTC was noted on combining the two antibodies.

Vitreoretinal Complications and Outcomes in 92 Eyes Undergoing Surgery for Modified Osteo-Odonto-Keratoprosthesis: A 10-Year Review.

PURPOSE: To analyze vitreoretinal (VR) complications and treatment outcomes in eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery. DESIGN: Retrospective case series. PARTICIPANTS: All patients who underwent modified OOKP (mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013 were included. METHODS: Medical records were reviewed for relevant medical history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound scan, oral examination findings, and VR complications. MAIN OUTCOME MEASURES: The BCVA at the last visit. Optimal anatomic outcome was attached retina with a normal intraocular pressure at the last visit. RESULTS: A total of 92 eyes of 90 patients were included. Indications for OOKP included Stevens-Johnson syndrome (n = 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A total of 41 eyes of 39 patients developed VR complications, including vitritis (n = 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane (RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage (VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median, 41.9 months; range, 0.2-95.5 months). After treatment of VR complication, visual improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1-2.5 logMAR), visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4 logMAR; range, 0.3-1.8 logMAR), and no change in BCVA in 17 eyes (42%). However, BCVA ≥6/60 was retained in 19 eyes and ≥6/18 was retained in 9 eyes after final VR treatment. CONCLUSIONS: Vitreoretinal complications constitute a significant cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging situation to manage. However, appropriate and timely intervention can achieve encouraging results.

Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells.

OBJECTIVE AND DESIGN: We sought to determine the effect of necrosis-induced activation of the complement protein C3 in medulloblastoma. MATERIALS/METHODS: Twelve medulloblastoma surgical specimens were evaluated for complement activation using immunohistochemistry, with H&E stains performed on adjacent tissue sections to determine the relationship of complement activation to necrotic tissue. Flow cytometry and Western blot were performed on three established medulloblastoma lines and one surgically-procured cell culture to determine expression of C3a receptor (C3aR) in medulloblastoma. In vitro proliferation of siRNA C3aR knockdown cells was compared to that of control siRNA cells with cell line Daoy. RESULTS: Three surgical specimens were found to have necrosis on H&E sections. In each case, iC3b staining was identified on adjacent sections, limited to the necrotic region. In no case did necrosis occur without iC3b staining on adjacent sections. C3aR protein was demonstrated on both the three established cell lines and on the surgical culture. Proliferation assays of Daoy cells with siRNA knockdown vs. control siRNA revealed significantly reduced proliferation at 72 h (p = 0.001). CONCLUSIONS: Necrosis is associated with complement activation in medulloblastoma. Medulloblastoma cells express C3aR, and siRNA-mediated knockdown of C3aR inhibits proliferation of these cells in vitro.

Bone augmentation of the osteo-odonto alveolar lamina in MOOKP--will it delay laminar resorption?

PURPOSE: We aimed to describe a new technique and analyse the early outcomes of augmenting the canine tooth using a mandibular bone graft in an attempt to delay or retard the process of laminar resorption following the modified osteo odonto keratoprosthesis (MOOKP) procedure. DESIGN: This was a retrospective case series. PATIENTS AND METHODS: Eyes that underwent the bone augmentation procedure between December 2012 and February 2014 were retrospectively analysed. The procedure, performed by the oromaxillofacial surgeon, involved securing a mandibular bone graft beneath the periosteum on the labial aspect of the canine tooth chosen to be harvested for the MOOKP procedure. This procedure was performed simultaneously with the Stage 1 A of the MOOKP. Three months later, the tooth was harvested and fashioned into the osteo-odonto alveolar lamina similar to the method described in the Rome-Vienna Protocol. RESULTS: The bone augmentation procedure was performed in 11 eyes (five SJS/ six chemical injuries). The mean follow-up after Stage 2 of MOOKP procedure in these eyes was 7.45 months (2 to 20 months). Complications noted were peripheral laminar exposure (three eyes-SJS) and bone graft exposure and necrosis in the mouth (nine-SJS). No evidence of clinical laminar resorption was noted in any of the eyes. CONCLUSION: Laminar resorption in MOOKP can lead to vision and globe threatening complications due to the consequent cylinder instability and chances of extrusion. Augmenting the bone on the labial aspect of the canine tooth might have a role to play in delaying or preventing laminar resorption.

Comprehensive approach to ocular consequences of Stevens Johnson Syndrome - the aftermath of a systemic condition.

BACKGROUND: Stevens Johnson Syndrome (SJS) can lead to end stage corneal blindness. This study describes the comprehensive treatment measures and their outcomes in the management of ocular sequelae and complications of SJS. METHODS: Four hundred sixty-four eyes of 232 patients of SJS who underwent surgical intervention (punctal cautery, mucus membrane grafting for lid margin keratinisation, fornix reconstructive procedures, tectonic procedures, keratoplasty and keratoprosthesis) were studied. It was a non-comparative, retrospective, interventional case series. The primary outcome was the change in the best corrected visual acuity (BCVA). Secondary outcome measures included an improvement in the ocular surface status as indicated by corneal epithelial fluorescein staining and Schirmer's I strip wetting. RESULTS: The BCVA and the ocular surface status improved and/or stabilized in > 70 % of eyes following punctal cautery (n = 160) and > 80 % of eyes following lid margin mucus membrane grafting (n = 238). BCVA improved in 50 % of eyes following fornix reconstructive procedures (n = 24) with COMET (n = 6), in 63.9 % eyes with the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) lens (n = 36), in 81.8 % of eyes after cataract surgery (n = 22). A BCVA of ≥20/200 was achieved in 72.34 % of eyes following keratoprostheses procedures (n = 47). The mean duration of follow up was 53.3 ± 15.2 months. CONCLUSION: The ocular sequelae of Stevens Johnson Syndrome can be blinding. They need to be identified and addressed early to retard the continued deterioration of the ocular surface. Our study aims to highlight the problem as well as the importance of comprehensive measures in the management of this potentially blinding disorder.

Structural & functional rehabilitation in eyes with lamina resorption following MOOKP--can the lamina be salvaged?

PURPOSE: To describe a new technique and analyze the outcome of procedures performed for anatomic and functional rehabilitation in eyes with lamina resorption following the modified osteo-odonto keratoprosthesis (MOOKP) procedure. DESIGN: Retrospective case series. PATIENTS & METHODS: Eighteen eyes were noted to have lamina resorption of the 85 eyes that underwent the MOOKP surgery over the last 10 years. Further intervention to salvage the globe, and therefore the visual potential, was possible in only 11 eyes, of which two are yet to undergo further intervention. Two patients who had undergone the procedure elsewhere also presented to our centre with evidence of resorption. In all, 11 eyes (nine operated at our centre, two operated elsewhere) were included in this study. Bone morphogenetic protein (BMP) was used alone or along with mandibular cancellous bone within the fibrovascular capsule of the osteo-odonto alveolar lamina, in an effort to prevent further resorption and promote bone generation in areas of resorption in ten eyes. In three of these eyes, there was a continued progression of resorption requiring lamina removal. In these three eyes and another eye with extrusion of the cylinder from the eye, the Lucia Type 2 keratoprosthesis was performed for visual rehabilitation (four eyes). RESULTS: The BMP procedure was performed in ten eyes. Continued resorption with need for further rehabilitative surgery in the form of Lucia Type 2 Kpro was required in three of these eyes. Of the four patients who had the Lucia Type 2 Kpro, visual acuity improved to better than 20/200 in three eyes over a mean follow-up period of 3 months. Of the remaining seven eyes that had the BMP procedure performed, all have remained stable with respect to anatomic integrity of the lamina and globe, with maintenance of or improvement in pre BMP visual acuity over a mean follow-up of 9.2 months. No other complications of the procedure were noted. CONCLUSION: Resorption of the lamina in MOOKP can be addressed by reinforcing the same with BMP in eyes where the cylinder mobility is not significant, as a means to prolong the longevity of the existing lamina. The Lucia Type 2 Kpro might also have a role to play in the functional rehabilitation of eyes with severe lamina resorption or cylinder extrusion if preparation of a new lamina cannot be performed for various reasons.

A Retrospective Cytomorphologic Analysis of Salivary Gland Fine Needle Aspirates Classified as Salivary Gland Neoplasm of Uncertain Malignant Potential: A 6-year Institutional Experience.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology is an effective reporting system for salivary gland fine needle aspirations with well-established risks of malignancy. Salivary gland neoplasm of uncertain malignant potential (SUMP) comprises a heterogenous group of lesions which have features that can be recognized as at least neoplastic but preclude further classification into benign or malignant. In this study, we reviewed the cytomorphologic features of salivary gland fine needle aspirations diagnosed as SUMP at our institution (over the past 6 years) and correlated those with the final diagnosis on surgical follow up. DESIGN: A retrospective search was performed to identify cases classified as SUMP at our institution from January 2018 to February 2024. Cytology slides were reviewed, and cases were subclassified based on key cytomorphologic features into the following categories: (1) basaloid, (2) oncocytic, (3) with clear cell features and (4) mixed features (myoepithelial/oncocytoid/squamoid features). Histologic diagnosis was recorded if available. RESULTS: A total of 36 cases of SUMP were identified; 31/36 had surgical follow up; final diagnosis included 22 benign lesions (2 non-neoplastic and 20 benign neoplasms), and nine malignant lesions. The overall risk of neoplasm and risk of malignancy were 93.5% and 29% respectively, with the oncocytic sub-category recording the highest ROM (42.8%). Mucoepidermoid carcinoma was the most common malignant diagnosis and pleomorphic adenoma the most common benign diagnoses. CONCLUSIONS: Our study supports the subclassification of SUMP lesions based on key cytomorphologic features, thereby aiding in refining this ambiguous entity and providing a precise risk assessment.

Unique cytokine signature in ocular Stevens-Johnson syndrome non-responders.

PURPOSE: To clinically define a subset of patients with chronic ocular Stevens-Johnson syndrome non-responders (SJS-NR) and analyze their cytokine profile compared to clinical responders (SJS-CR). METHODS: A total of 32 SJS cases (n = 32, 64 eyes) managed over a period of three years were segregated into clinical responders (n = 24, 48 eyes) and non-responders (n = 8, 16 eyes). Cases were determined as non-responders based on persistent, refractory, and non-mechanical inflammation of the conjunctiva. Age- and sex-matched healthy controls (n = 25, 50 eyes) were recruited. Tear specimens collected using Schirmer's strip were profiled for 27 cytokines using an immunoassay-based 27-bioplex array. RESULTS: Tear cytokine profiling revealed 18 cytokines to be differentially expressed in SJS-NR compared to SJS-CR. While PDGF-BB, IL-4, IL-1ß, VEGF, IL-12p70, IFN-γ, IL-9, and IL-1RA were upregulated, GM-CSF, eotaxin, IP-10, IL-10, MCP-1, G-CSF, IL-6, IL-13, and bFGF were downregulated in SJS-NR compared to SJS-CR. The cytokines IL-13, IL-10, and IP-10 were decreased in both SJS-NR and SJS-CR compared to controls. CONCLUSION: The inflammation in SJS-NR continues to worsen despite the correction of mechanical causes, resulting in progressive deterioration of the cornea. The cytokine profile of SJS-NR was remarkably different from that of SJS-CR, indicating a T helper 2-type protective proliferative response and an impaired migratory potential of the conjunctival epithelium. These factors could possibly lead to poor healing of the corneal epithelium in a markedly pro-inflammatory and pro-angiogenic milieu. The top four differentially expressed cytokines, PDGF-BB, IL-4, IL-10, and IL-6, are proposed as potential biomarkers of SJS-NR.

Unraveling the complexity - Insights and interventions of refractory vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is a chronic severe ocular allergic inflammation mostly observed in children and young adults. The ocular manifestations are the expression of multifactorial immune mechanisms that generally have a good prognosis, however long-term inflammation may remarkably reduce the visual function due to complications and poor therapeutic responses. Lack of responsiveness to a drug or treatment is relatively common in VKC and it is not only due to corneal involvement, which is considered the main sign of severity. The concept of refractory may be relative to multiple factors including the clinical condition, systemic co-morbidities, previous or concomitant drugs or regiments, compliance, patient's psychological condition or expectations, type of exposome and environmental conditions, doctor's experience and expectations, or timing of clinical evaluation. In this narrative review, the authors propose a definition of refractory VKC based on revised literature and clinical experience and consider potential new treatments for refractory patients and surgical management in case of complications.

Depth, size of infiltrate, and the microbe - The trio that prognosticates the outcome of infective keratitis.

PURPOSE: To analyze the influence of infiltrate size, depth, and organism on the outcome of microbial keratitis. DESIGN: Retrospective comparative study. METHODS: Medical records of patients with infective keratitis, who reported from January 2015 to December 2019 to a tertiary eye care center, were analyzed. Size and depth of ulcer at presentation were the factors used to group patients, and the influence on the outcome of the organism causing it was analyzed. Grouping was as follows: group A: ulcer size <6 mm/anterior to midstromal infiltrate, group B: ulcer < 6 mm/full-thickness infiltrate, group C: ulcer >6 mm/anterior to midstromal infiltrate, group D: ulcer > 6 mm/full-thickness infiltrate. Patients with viral keratitis or unidentified organism were excluded. Response to treatment and best-corrected visual acuity (BCVA) at the final follow-up were the outcome measures. RESULTS: In the study, 1117/6276 patients were included, with 60.8% patients in group A. A significant improvement in visual acuity was noted in groups A/B compared to groups C/D. Group A had the best response to medical management, irrespective of the organism. Higher risk for surgery was noted in group C compared to group B, with group A as the reference. Overall resolution with medical treatment was noted in 70% miscellaneous keratitis, 64.8% bacterial keratitis, 64.3% mixed keratitis, 62.5% acanthamoeba keratitis, 52.6% fungal keratitis, and 12.1% Pythium keratitis. Bacteria and acanthamoeba responded better to medical management than fungal keratitis, whereas Pythium had the highest risk for surgery. CONCLUSION: An interplay between virulence of the organism along with depth and size of the infiltrate determines the outcome of microbial keratitis.

Central Giant Cell Granuloma: Negotiating the Diagnostic and Management Dilemmas.

Introduction: Giant cell lesions of orofacial region although rare in presentation, have diagnostic and treatment challenges due to overlapping clinical, radiological, and histopathological signs. Background: We happened to come across a case, which presented to us with an aggressive jaw lesion of nonodontogenic origin, mimicking a malignancy and putting us in a conundrum with regard to work up and treatment. The sequential work up not only helped us reach a definitive diagnosis but also led us the draw algorithms for diagnosis of Giant cell lesions and management of Central giant cell granuloma. Conclusion: Meticulous planning along with molecular studies helps in better delineating one giant cell lesion from other.

Atypical Squamous Verrucous Lesions of the Oral Cavity: Challenges in Interpretation of Small Incisional Biopsies.

BACKGROUND: Squamous verrucous proliferative lesions of oral cavity can pose a diagnostic challenge for the general pathologist, especially on small biopsies. The superficial nature of incisional biopsies and inconsistent histologic terminologies used for these lesions contribute to often-discrepant clinical diagnosis, resulting in delayed treatment. This study aims to explore the proliferative squamous lesions of oral cavity, correlate biopsy & resection diagnoses, and evaluate possible reasons for discrepant diagnosis (if any). DESIGN: A retrospective review of oral verrucous squamous lesions was undertaken. Pathology database was searched for oral cavity biopsies from January2018 through August2022 with the keywords: atypical, verrucous, squamous, and proliferative. Cases with follow-up were included in this study. A blinded review of the biopsy slides was performed and documented by a single head and neck pathologist. Demographic data, biopsy and final diagnosis were recorded. RESULTS: Twenty-three cases met criteria for inclusion. The mean patient age was 61.1 years with a male: female ratio of 1.09. Most frequent site was lateral border of tongue (36%) followed by buccal mucosa and retromolar trigone. The most common biopsy diagnosis was "Atypical squamoproliferative lesion, excision recommended" (n = 16/23, 69%) with 13/16 showing conventional squamous cell carcinoma (SCC) on follow-up resection. 2/16 atypical cases underwent repeat biopsy for confirmation of diagnosis. Overall, conventional SCC was the most prevalent final diagnosis (73%, n = 17), followed by verrucous carcinoma (17%, n = 4). On slide review, six initial biopsies were reclassified as SCC, while one final diagnosis was reclassified as a hybrid carcinoma (on resection specimen). Diagnostic concordance (biopsy and resection) was observed in three cases, all three were recurrences. The primary reasons for discrepant diagnosis on initial biopsies were found to be 1. Obscuring inflammation, 2. Superficial biopsies, and 3. Under recognition of morphologic features (e.g., tear shaped rete, loss of polarity, dyskeratotic cells, paradoxical maturation) that help differentiate dysplasia from reactive atypia. CONCLUSION: This study highlights the rampant interobserver variability in diagnosis of oral cavity squamous lesions and emphasizes importance of identifying morphologic clues that can aid in correct diagnosis, thereby helping in adequate clinical management.

Salivary Duct Carcinoma Arising in a Warthin Tumor of the Parotid Gland: A Rare Case Report with Review of Literature and PD-L1 Expression.

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary duct carcinoma. He subsequently underwent left parotidectomy along with left level II-IV lymph node dissection. Histology revealed both in situ as well as invasive salivary duct carcinoma arising from Warthin tumor. Immunohistochemistry showed tumor cells positive for CK7, AR, and GATA3, while p63 highlighted the myoepithelial cell layer in the in situ component. Her2 was 2+ by immunohistochemistry. In addition, PD-L1 IHC revealed positive expression with a combined positive score of 20%.

E-PIX: An enhanced grading for acute ocular burns.

An enhanced online and manual grading system, based on the I's and E's, for acute ocular chemical injuries is being proposed. E-PIX is designed to be an online/manual grading system that includes all the parameters that adversely affect the outcome of acute chemical injuries. The importance of addressing the I's and E's in chemical burns cannot be underestimated. These include the need for the documentation and management of epithelial defect (E), intraocular pressure (P) (IOP), ischemia (scleral) (I), and exposure (X) (acronym - E-PIX). Epithelial defect includes that involving the limbus (L), along with conjunctival (C), corneal (K), and tarsal (T). These additional parameters are graded and represented as an annotation along with the limbal grade providing a comprehensive grading for the injury. A manual entry sheet and a freely accessible online grade generator are a part of the system. The proposed enhanced grading offers a final annotation that provides a clear understanding of all factors that can lead to vision-threatening complications ensuring their assessment and hence subsequently their addressal to improve outcomes, if abnormal. The prognostication continues to be based on the grade of limbal involvement. The additional annotations impact prognosis and outcome if not addressed. Including the laterality of injury provides, in addition, a futuristic understanding of available options. The grade generator retains the flexibility to be dynamic with changes reflecting upon the healing process in the acute stage. The proposed system aims to provide primary and tertiary caregivers alike with a uniform grading system.

Possible Synergistic Role of Cryo-Alcohol Therapy in Infectious Scleritis-Scope and Rationale for Expanding Indications and Review of the Literature.

PURPOSE: The purpose of this study was to highlight the use of topical ethanol as an adjunct to cryotherapy, termed cryo-alcohol therapy, in the management of fungal/acanthamoeba scleritis along with a review of the literature. METHOD: Retrospective interventional case reports of fungal and acanthamoeba scleritis along with a review of the literature. RESULTS: The patient with circumferential necrotic fungal scleritis resolved in 6 weeks achieving a best-corrected visual acuity (BCVA) of 20/20, and the patient with acanthamoeba scleritis is awaiting optical keratoplasty after complete resolution in 8 weeks. The literature review from January 1990 to December 2020 revealed BCVA >20/200 in 50% of the eyes with a mean time to resolution being 4.16 ± 2.13 months in fungal scleritis, with 27.02% and 75% of the eyes requiring evisceration in fungal and acanthamoeba scleritis, respectively. CONCLUSIONS: Cryotherapy is a useful adjunct in managing refractory infectious scleritis, and its efficacy can be enhanced by combining the use of topical ethanol to aid in faster recovery and reduce visual morbidity.

Dry eye module - An application intelligence platform for diagnosing and monitoring dry eye disease.

Dry Eye Module (DEM), a software application, was developed to facilitate the streamlining of dry eye evaluation and documentation, to unify diagnostic jargon, and to analyze data input to generate a dry eye diagnostic report. This diagnostic report generated is based on the current understanding of dry eye diagnostic algorithms (Dry Eye Workshop 2 [DEWS2]/Asia Dry Eye Society [ADES]). Apart from its plausible role in aiding unprecedented multicentric dry eye demographic data collection, the application software can generate a customized referral letter to the rheumatologist, highlighting the salient ophthalmic features to be shared. DEM uses schematic illustrations to depict eyelid, conjunctival, and corneal parameters that impact the ocular surface in dry eyes that can be captured and compared during serial visits. Furthermore, DEM displays a symptom sign trend chart that graphically represents improvement/stability or worsening of the subjective and objective dry eye status. DEM can generate a curated prescription using preloaded advice templates. DEM includes facility for state-of-the-art advanced dry eye diagnostic reporting for super specialty use. The addition of DEM to the dry eye diagnostic armamentarium would help bridge the current unmet needs of dry eye evaluation. These are lack of uniform reporting, lack of multicentric data on a unified platform, the inability to ensure complete evaluation, inability to avoid lacunae during follow-up visits, and the lack of a simple patient-ophthalmologist and an ophthalmologist-rheumatologist interface.

Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis.

BACKGROUND: The etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease. METHODS: Active VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells. RESULTS: Significantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (p<0.001) and S1P(d17:1) (p<0.01) specifically in severe/very severe VKC compared with both mild/moderate VKC and control. Cer(d18:/17:0) (p<0.001), ceramide-1-phosphate (C1P)(d18:1/8:0) (p<0.01) and C1P(d18:1/2.0 (p<0.05) were lowered in severe/very severe VKC compared with mild/moderate VKC. Cultured mast cells treated with IgE revealed significantly increased gene expression of S1P1 and 3 receptors and the protein expression of histone deacetylases (1, 6). CONCLUSION: Altered sphingolipid metabolism in the ocular surface results in low tear ceramide and sphingosine levels in severe/very severe VKC compared with the mild/moderate cases. The novel finding opens up fresh targets for intervention in these refractory cases.