Imatinib- and Nilotinib-Induced Lichenoid Eruption in Chronic Myeloid Leukemia: A Rare Case Report.

Imatinib and nilotinib are inhibitors of tyrosine kinases (TKIs) generated from the bcr-abl fusion protein, c-Kit, and platelet-derived growth factor receptors. Cutaneous adverse effects (AEs) of TKI are the most frequent non-hematological sequelae. In our case, the common molecular target raises the possibility that cross-intolerance, in which similar AEs occur with both agents, can arise. We hereby report a rare case report on cross-intolerance of cutaneous AEs of imatinib and nilotinib in chronic myeloid leukemia.

Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry.

OBJECTIVE: To compare long-term effectiveness of Standard (UV intensity: 3 mW/cm2, duration: 30 min) vs Accelerated (UV intensity: 9 mW/cm2, duration: 10 min) corneal cross-linking (CXL) for stabilising keratoconus. METHODS: Data for this observational study were captured through a web-based registry system from the routine clinical practice (15 sites across Australia, New Zealand and Italy). The outcomes were compared using mixed-effects regression models. A total of 100 eyes (75 patients) who had standard CXL and 76 eyes (66 patients) who had accelerated CXL, with a follow-up visit at five-year post-CXL were included. RESULTS: Both CXL protocols were effective and safe in stabilising keratoconus and improving outcomes. The adjusted mean changes (95% CI) in outcomes were better in standard CXL than in accelerated CXL [visual acuity gain, 10.2 (7.9-12.5) vs 4.9 (1.6-8.2) logMAR letters; pinhole visual acuity 5.7 (3.5-7.8) vs 0.2 (-2.2 to 2.5) logMAR letters; Kmax -1.8 (-4.3 to 0.6) vs 1.2 (-1.5 to 3.9)D; K2 -0.9 (-2.2 to 0.3) vs 0.1 (-1.3 to 1.6)D; MCT -3.0 (-13.7 to 7.7) vs -11.8 (-23.9 to 0.4) µm (p values for visual acuity, pinhole visual acuity, Kmax: <0.05; for K2 and MCT: >0.05)]. The frequency of adverse events at the 5-year follow-up visit was low in both groups [standard, 5 (5%; haze 3; scarring 1, epithelial defect 1) and accelerated 3 (3.9%; haze 2, scarring 1)]. CONCLUSIONS: Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term. The standard CXL resulted in greater improvements in visual acuity and keratometry.

Addisonian pigmentation associated with acute lymphoblastic leukemia: A rare paraneoplastic phenomenon.

Addisonian pigmentation usually presents with nonspecific symptoms and signs, which are often ignored or misdiagnosed as a sign of other more common diseases. We present a case of 12-year-old child in whom diffuse Addisonian hyperpigmentation of skin was associated with underlying acute lymphoblastic leukemia (B-type), a rare paraneoplastic phenomenon in hematological malignancies.

Heart Transplantation from COVID-19-Positive Donors: A Word of Caution.

BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.

Normocalcemic Parathyroid Adenoma with Brown's Tumor Maxilla: A Rare Case.

Introduction: Primary hyperparathyroidism due to parathyroid adenoma commonly causes raised serum calcium and focal giant cell lytic lesions in bones known as Brown's tumors. It is more common in females in the post-menopausal age group. Case Report: We report a case of a 29-year-old female patient with Brown's tumor maxilla in a clinical setting of normocalcemic primary hyperparathyroidism. The patient presented to us with facial and palatal swelling for which FNAC was done. Cytology revealed hemosiderin-laden macrophages suspicious for Brown's tumor. On further imaging studies such as CT Neck, Tc99 Sestamibi scan, and other biochemical tests like parathyroid hormone assay and serum calcium level, the diagnosis of a hyperfunctioning parathyroid gland with normal calcium level was made. Parathyroidectomy was performed and parathyroid adenoma came out to be the primary pathology. On post-operative follow up there was regression of the swelling on the face and palate relieving the patient symptomatically. Conclusion: The diagnostic suspicion of primary hyperparathyroidism should be kept in mind whenever a young female presents with suspected Brown's tumor, even with normal serum calcium levels, for appropriate management. Ours was a highly uncommon case that was a diagnostic challenge and had a successful treatment outcome. Very few such cases have been reported in the literature to date to the best of our knowledge.

Polymicrobial Infections in the Immunocompromised Host: The COVID-19 Realm and Beyond.

Immunosuppression changes both susceptibility to and presentation of infection. Infection with one pathogen can also alter host response to a different, unrelated pathogen. These interactions have been seen across multiple infection domains where bacteria, viruses or fungi act synergistically with a deleterious impact on the host. This phenomenon has been well described with bacterial and fungal infections complicating influenza and is of particular interest in the context of the COVID-19 pandemic. Modulation of the immune system is a crucial part of successful solid organ and hematopoietic stem cell transplantation. Herein, we present three cases of polymicrobial infection in transplant recipients. These case examples highlight complex host-pathogen interactions and the resultant clinical syndromes.

Multiphase computed tomography angiography (mCTA) derived source images in acute ischemic stroke: Beyond collaterals. Can it obviate the need for computed tomography perfusion (CTP)?

BACKGROUND AND PURPOSE: To compare Multiphase CT Angiography derived source images (mCTA-SI) in acute ischemic stroke (AIS) with CT Perfusion (CTP) derived automated color maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) and to assess the comparability of mCTA-SI with CTP in the prediction of final radiological and clinical outcome. METHODS: This prospective single-centre observational study comprised of patients with AIS of the anterior circulation, presenting within 24 h and undergoing neuroimaging under stroke protocol with follow-up. Non-contrast computed tomography (NCCT), mCTA, and CTP were acquired with follow-up NCCT at 24 h and modified Rankin score (mRS) at 3 months. mCTA-SI and CTP color maps were scored by the ASPECTS (Alberta Stroke program early CT score) method and compared amongst each other and with the outcome. ROC (Receiver operating characteristic) curves were plotted considering mRS 0-2 and FIV≤ 28 ml as favourable clinical and radiological outcomes respectively. RESULTS: The study included 55 patients. The 1st and 2nd phase of mCTA-SI correlated significantly with CBF maps (r = 0.845, p < 0.01, r = 0.842, p < 0.01 respectively). 3rd phase of mCTA-SI correlated significantly with CBV maps (r = 0.904, p < 0.01). A favourable functional and radiological outcome was best predicted by the 1st (AUC 0.8, 95%CI 0.671-0.896) and 2nd ( AUC 0.895, 95% CI 0.783-0.962) phase of mCTA-SI respectively. CONCLUSIONS: The 1st and 2nd phases of mCTA-SI produces results congruent to CBF color maps and the 3rd phase of mCTA-SI simulate CBV color maps. In addition to predicting radiological and functional outcomes, mCTA can predict the salvageable and non-salvageable tissue in AIS and is non-inferior to CTP.

Diagnostic yield of candidate genes in an Australian corneal dystrophy cohort.

Corneal dystrophies describe a clinically and genetically heterogeneous group of inherited disorders. The International Classification of Corneal Dystrophies (IC3D) lists 22 types of corneal dystrophy, 17 of which have been demonstrated to result from pathogenic variants in 19 identified genes. In this study, we investigated the diagnostic yield of genetic testing in a well-characterised cohort of 58 individuals from 44 families with different types of corneal dystrophy. Individuals diagnosed solely with Fuchs endothelial corneal dystrophy were excluded. Clinical details were obtained from the treating ophthalmologist. Participants and their family members were tested using a gene candidate and exome sequencing approach. We identified a likely molecular diagnosis in 70.5% families (31/44). The detection rate was significantly higher among probands with a family history of corneal dystrophy (15/16, 93.8%) than those without (16/28, 57.1%, p = .015), and among those who had undergone corneal graft surgery (9/9, 100.0%) compared to those who had not (22/35, 62.9%, p = .041). We identified eight novel variants in five genes and identified five families with syndromes associated with corneal dystrophies. Our findings highlight the genetic heterogeneity of corneal dystrophies and the clinical utility of genetic testing in reaching an accurate clinical diagnosis.

Goserelin Ovarian Ablation Failure in Premenopausal Women With Breast Cancer.

Breast cancer is the most prevalent cancer known worldwide in women. It is a heterogeneous, phenotypically diverse disease composed of several biologic subtypes that have distinct behavior and response to therapy. Hormone receptor-positive (i.e., estrogen [ER] and/or progesterone [PR] receptor-positive) breast cancers comprise the most common types of breast cancer, accounting for 75% of all cases. This makes endocrine therapy the standardized treatment for patients with ER+/PR+ breast cancer. Drugs that block estrogen receptors or that lower estrogen levels are the mainstay of treatment. High-risk patients benefit from the addition of ovarian function suppression (OFS)/ablation to either an aromatase inhibitor (AI) or tamoxifen. This case report discusses a 36-year-old premenopausal female who presented with an abnormal right breast lump in the upper outer quadrant of the right breast. Due to high suspicion of malignancy, a biopsy was performed which showed features of both lobular and ductal carcinoma with ER and PR positivity, HER 2 was negative. The patient underwent mastectomy with axillary lymph node removal due to concern for multifocal disease. No clinically relevant genetic mutations were present. Oncotype DX breast recurrence score was 16 and no chemotherapy was offered. Due to large tumor size, young age OFS with goserelin 3.6mg/28 days and letrozole 2.5 mg once daily was recommended. After 16 months of treatment, the patient developed a failure of goserelin-induced ovarian suppression. This case report highlights the possibility of the development of hormonal resistance after long-term use of goserelin.

The Rarest of the Rare: A Case of BAP1-Mutated Primary Peritoneal Mesothelioma.

Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.

RNA therapeutics in ophthalmology - translation to clinical trials.

The use of RNA interference technology has proven to inhibit the expression of many target genes involved in the underlying pathogenesis of several diseases affecting various systems. First established in in vitro and later in animal studies, small interfering RNA (siRNA) and antisense oligonucleotide (ASO) therapeutics are now entering clinical trials with the potential of clinical translation to patients. Gene-silencing therapies have demonstrated promising responses in ocular disorders, predominantly due to the structure of the eye being a closed and compartmentalised organ. However, although the efficacy of such treatments has been observed in both preclinical studies and clinical trials, there are issues pertaining to the use of these drugs which require more extensive research with regards to the delivery and stability of siRNAs and ASOs. This would improve their use for long-term treatment regimens and alleviate the difficulties experienced by patients with ocular diseases. This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-LRX in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology.

Topical Application of Peptide-Chondroitin Sulfate Nanoparticles Allows Efficient Photoprotection in Skin.

In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous with positive surface charges and stable at physiological and acidic pH under certain conditions. They were able to enter into the human keratinocyte cell line (HaCaT), artificial skin membrane (mimicking the human skin), and mouse skin tissue unlike free chondroitin sulfate. The preapplication of nanoparticles also exhibited reduced levels of oxidative stress, cyclobutane pyrimidine dimer formation, TNF-α, and so on in UV-B-irradiated HaCaT cells. In an acute UV-B irradiation mouse model, their topical application resulted in reduced epidermal thickness and sunburn cells, unlike in the case of free chondroitin sulfate. Thus, a completely noninvasive method was used to deliver a bio-macromolecule into the skin without using injections or abrasive procedures.

Cytopathologic findings in histiocytic sarcoma of thyroid mimicking as anaplastic carcinoma: A report of a rare case with review of literature.

BACKGROUND: Histiocytic sarcoma is an extremely rare malignant hematological histiocytic neoplasm which is a diagnosis of exclusion based on its morphological and predominantly immunohistochemical criteria. CASE DESCRIPTION AND DIAGNOSIS: A 63-year female presented with complaints of a midline neck swelling along with right sided neck swelling. On fine-needle aspiration (FNA) from the thyroid lesion and the right cervical lymph node, the smears showed similar findings and a provisional morphological diagnosis of malignant spindle cell neoplasm was kept. On immunohistochemistry, the tumor cells showed immunoreactivity for vimentin, CD45, CD 68 and fascin and were immunonegative for thyroglobulin, S100, CD21, CD3, CD4 and other markers. Based on the immunohistochemical profile, a diagnosis of histiocytic sarcoma was established. CONCLUSION: Histiocytic sarcoma is a rare malignant neoplasm that can be easily missed in thyroid resembling an anaplastic carcinoma.

Bronchial Reactivity and Lung Function After World Trade Center Exposure.

BACKGROUND: World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, whereas persistence of BHR has not been investigated. METHODS: A total of 173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after September 11, 2001 (9/11) (baseline methacholine challenge test), were reevaluated in 2013 and 2014 (follow-up methacholine challenge test). FEV1 measurements were obtained from the late pre-9/11, early post-9/11, and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded. RESULTS: Bronchial reactivity remained stable (within 1 doubling dilution) for most (n = 101, 58%). Sixteen of 28 (57%) with BHR (provocative concentration of methacholine producing a 20% decline in FEV1 <8 mg/mL) at baseline had BHR at follow-up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR, 6.46) and that BHR at follow-up was associated with an estimated 15.4 mL/y greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use. CONCLUSIONS: Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.

Mineral pitch induces apoptosis and inhibits proliferation via modulating reactive oxygen species in hepatic cancer cells.

BACKGROUND: Mineral Pitch (MP) is a dark brown coloured humic matter originating from high altitude rocks. It is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. METHODS: The Huh-7 cells were treated with different concentrations of MP for 24 h, and both apoptosis and proliferation was determined by the TUNEL and MTT assays respectively. The formation of ROS and nitric oxide was analysed by DCFH-DA and Griess reagent respectively. The expression of miRNA-21 and miRNA-22 were checked by the real time PCR. Effect of miRNA-22 on proliferation and c-myc was studied by over-expressing miRNA-22 premiRs in Huh-7 cells. RESULTS: We found that MP enhanced anti-cancer effects by inducing apoptosis and inhibiting proliferation. MP induced both ROS and NO, upon neutralizing them, there was a partial recovery of apoptosis and proliferation. MP also induced miRNA-22 expression, while miRNA-21 expression was inhibited. Over-expression of miRNA-22 resulted in a significant inhibition of proliferation. miRNA-22 directly targeted c-myc gene, thereby inhibited proliferation. These results clearly show that MP induces its anti-cancer activity by more than one pathway. CONCLUSION: The data clearly indicate that MP induced apoptosis via the production of ROS, and inhibited proliferation by inducing miRNA-22 and inhibiting miRNA-21 in Huh-7 cells.

Acanthomatous ameloblastoma of mandible crossing the midline: a rare case report.

Ameloblastoma is the most common aggressive benign odontogenic tumor of the jaws. Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in the mandible or maxilla or, rarely, in the immediate adjacent soft tissues. A clinical, radiographic and histopathological report is presented of a case of acanthomatous ameloblastoma in relation to molar in the left mandible of a 30-year-old healthy male. The histopathological examination of the removed specimen revealed the histopathological pattern of an acanthomatous ameloblastoma. The radiographic appearance of the lesion showed the presence of multilocular radiolucencies, which were crossing the midline, which is rarely found in ameloblastoma. Due to its rarity and lack of data, we take this opportunity to present a world first case of acanthomatous ameloblastoma which was crossing the midline.

Comparative efficacy of two different dosages of intrathecal magnesium sulphate supplementation in subarachnoid block.

BACKGROUND: Spinal anaesthesia is the primary anaesthetic technique for many types of surgeries. Adjuncts to the local anaesthetics (LA) used in spinal anaesthesia can exhibit undesirable side-effects like respiratory depression, urinary retention, pruritis, haemodynamic instability and nausea and vomiting, limiting their use. Magnesium when used in therapeutic doses avoids all of these side-effects. MATERIALS AND METHODS: We conducted a randomized double blind study on 90 patients, 30 in each group, scheduled for orthopaedic lower limb surgery under subarachnoid block. Group I: received bupivacaine (0.5%), 12.5 mg + 0.5 ml of preservative free 0.9% normal saline, Group II received bupivacaine (0.5%), 12.5 mg + 0.2 ml (50 mg) of preservative free 25 % magnesium sulphate + 0.3 ml of preservative free 0.9% normal saline Group III: received bupivacaine (0.5%) 12.5 mg + 0.3 ml (75 mg) of 25 % magnesium sulphate + 0.2 ml of preservative free 0.9% normal saline for subarachnoid block. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. STATISTICAL ANALYSIS: ANOVA was applied to determine the significance of difference between different groups. If p-value was significant then Turkey's Post Hoc Multicomparison test was applied. Values of p<0.05 were considered to be statistically significant. RESULTS: The time of maximum sensory block, time of onset of motor block, duration of sensory block, duration of motor block and time of analgesia request were prolonged in patients given magnesium 50mg and 75mg along with local anaesthetic intrathecally. CONCLUSION: N-methyl-D-aspartate (NMDA) receptor antagonist, magnesium when administered intrathecally along with local anaesthetics prolongs the duration of spinal analgesia without adverse effects.

Modification of the Miyake-Apple technique for simultaneous anterior and posterior video imaging of wet laboratory-based corneal surgery.

PURPOSE: The aim of this study was to describe a modification of the Miyake-Apple posterior video analysis for the simultaneous visualization of the anterior and posterior corneal surfaces during wet laboratory-based deep anterior lamellar keratoplasty (DALK). METHODS: A human donor corneoscleral button was affixed to a microscope slide and placed onto a custom-made mounting box. A big bubble DALK was performed on the cornea in the wet laboratory. An 11-diopter intraocular lens was positioned over the aperture of the back camera of an iPhone. This served to video record the posterior view of the corneoscleral button during the big bubble formation. An overhead operating microscope with an attached video camcorder recorded the anterior view during the surgery. RESULTS: The anterior and posterior views of the wet laboratory-based DALK surgery were simultaneously captured and edited using video editing software. The formation of the big bubble can be studied. CONCLUSIONS: This video recording camera system has the potential to act as a valuable research and teaching tool in corneal lamellar surgery, especially in the behavior of the big bubble formation in DALK.

Orbital cavernous haemangiomas: immunohistochemical study of proliferative capacity, vascular differentiation and hormonal receptor status.

BACKGROUND/AIMS: Immunohistochemical characterisation of orbital cavernous haemangiomas (CHs) with respect to proliferative capacity, hormone receptor status and vascular differentiation. METHODS: Eleven cases of orbital CHs were reviewed. Immunohistochemical stains for Mib-1, proliferating cell nuclear antigen (PCNA), Bcl-2, estrogen and progesterone receptors (ER & PR), CD31, D2-40, and VEGF were investigated in 11 specimens. RESULTS: Immunohistochemical staining revealed positivity for PCNA in ten of the 11 cases (91%). Bcl-2 was positive in 8 cases (73%). VEGF and PR were each weakly positive in 3 cases. All cases were negative for Mib-1, ER and D2-40. The staining was localized around the endothelium. CONCLUSION: This is the first study to characterise in detail the immunohistochemical features of orbital CHs. The proliferative markers PCNA and Mib-1 show discordant expression in these lesions and the expression of PCNA and Bcl-2 in the absence of Mib-1 is indicative of low proliferative potential. Small subsets of these tumors express PR and VEGF, which may partly explain the proliferative capacity of some orbital CHs.

Characterization of lacrimal sac histology: an immunohistochemical study.

BACKGROUND: A prospective observational study in a university hospital setting to study the immunohistochemical (IHC) characteristics of non-neoplastic human lacrimal sac epithelium. METHODS: Twenty paraffin-embedded specimens of human lacrimal sac were studied using monospecific monoclonal antibodies to 34 beta E12, cell adhesion molecule (CAM 5.2), epithelial membrane antigen (EMA), cytokeratins (CK) 7 and 20, estrogen receptor and progesterone receptor. The distribution and histologic location of IHC staining were examined qualitatively, and the IHC stains scored as positive (+) or negative (-). RESULTS: The haematoxylin-eosin stains were reviewed for tissue morphology. All 20 specimens were positive for 34 beta E12, CAM 5.2, EMA and CK 7 and negative for CK 20, estrogen receptor and progesterone receptor. CONCLUSION: To our knowledge, this is the first study to characterize the IHC properties of human lacrimal sac epithelium. This epithelium appears to possess consistent IHC properties as it stains for 34 beta E12, CAM 5.2, EMA and CK 7 and this information would be potentially useful in differentiating tumours arising in the region of the lacrimal sac.