Close Mimic Research Articles

Tuberculosis in kidney transplant candidates and recipients.

Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.

Kawasaki Disease Diagnosis and Treatment in over 1000 Patients: A Continuum of Dysregulated Inflammatory Responses.

Kawasaki disease (KD) is a pediatric vasculitis, leading to coronary artery aneurysms (CAAs) in ~4-14%. Attention to the etiology and course of KD was generated by the close mimic of a SARS-CoV-2-induced phenotype, called multisystem inflammatory syndrome in children (MIS-C). A total of 1179 cases were collected from 2012 with ~50% of cases retrospectively included. Clinical characteristics were described and risk factors for CAA (persistence) were investigated. Phenotypic patterns of the prospectively included KD patients were evaluated. These patterns were also compared to the seronegative KD and seropositive MIS-C cases identified during the SARS-CoV-2 pandemic. KD mostly affected boys and children < 5 years. IVIG resistance, CAAs, and giant CAAs occurred in 24.5%, 21.4%, and 6.6%, respectively. Giant CAAs were significantly more likely to normalize to a normal Z score in patients that were younger than 2.5 years old at the time of initial giant CAA (χ2 test p = 0.02). In our prospective (SARS-CoV-2-seronegative) KD series, there was a diminishing male predominance over time, whereas the proportions of incomplete presentations (p < 0.001) and patients with circulatory shock (p = 0.04) increased since the COVID-19 pandemic. Pre- and post-pandemic KD cases presented with different levels of C-reactive protein, thrombocyte counts, and hemoglobin levels over the years. Compared to pandemic KD, SARS-CoV-2-seropositive MIS-C patients were older (p < 0.001), and more often required intensive care admission (p < 0.001), with a gradual decrease over time between 2020 and 2022 (p = 0.04). KD carried a substantial risk of CAA development in contrast to MIS-C. the phenotypic changes seen over the last twelve years of our prospective follow-up study suggest a spectrum of hyperinflammatory states with potentially different triggering events within this clinical entity.

Spectrum of Somatic Malignancy in Testicular Germ Cell Tumors—A Histopathological Review of 25 Cases with Clinical Outcome

Abstract Introduction Germ cell tumors (GCTs) are the commonest testicular malignancy in young males. These tumors are highly chemoresponsive, however become resistant to conventional therapy when a somatic-type malignancy (SM) develops, which happens in ∼3 to 6% of the cases. Methods We reviewed the histologic profile of all cases of testicular/retroperitoneal GCT with SM, diagnosed over a period of 12 years in our institute. Correlation of histologic profile with clinical outcome was done wherever feasible. Results A total of 25 cases of testicular/retroperitoneal GCT with SM were identified for review. The histological spectrum of SMs included carcinoma (n = 9), sarcoma (n = 9), embryonic-type neuroectodermal tumor (ENET) (n = 4), and other rare histological types (n = 3). SMs were frequently seen at the resected metastatic sites (n = 13) and in postchemotherapy setting (n = 12); 14 cases had concurrent GCT and SM at the time of diagnosis/initial resection and 9 cases presented as late relapses (more than 2 years after initial presentation). Four patients were treated with metastasectomy and lymph node dissection, six patients were treated with combined resection and chemotherapy, and nine patients were treated with only adjuvant chemotherapy. The patients with SM confined to testis and those treated with multimodality approach had relatively better outcome. Conclusion GCTs with SM are a highly heterogeneous group of tumors with varying histologic types and management strategies. Strict adherence to histological diagnostic criteria, differentiating these tumors from close mimics such as glandular and sarcomatoid yolk sac tumors, teratomatous overgrowth, and a new second primary somatic tumor are important due to implications in management and prognosis.

Spindle epithelial tumor with thymus-like elements (SETTLE): a diagnostic challenge with distinct therapeutic implication; case report

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity.

Distributable, metabolic PET reporting of tuberculosis

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose – 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) – is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.

Proton Domino Reactions at an Imidazole Relay Control the Oxidation of a TyrZ-His190 Artificial Mimic of Photosystem II.

A close mimic of P680 and the TyrosineZ-Histidine190 pair in photosystem II (PS II) has been synthesized using a ruthenium chromophore and imidazole-phenol ligands. The intramolecular oxidation of the ligands by the photoproduced Ru(III) species is characterized by a small driving force, very similar to PS II where the complexity of kinetics was attributed to the reversibility of electron transfer steps. Laser flash photolysis revealed biphasic kinetics for ligand oxidation. The fast phase (τ<50 ns) corresponds to partial oxidation of the imidazole-phenol ligand, proton transfer within the hydrogen bond, and formation of a neutral phenoxyl radical. The slow phase (5-9 μs) corresponds to full oxidation of the ligand which is kinetically controlled by deprotonation of the distant 1-nitrogen of the imidazolium. These results show that imidazole with its two protonatable sites plays a special role as a proton relay in a 'proton domino' reaction.

An atypical presentation of ulcerative colitis: case report

BackgroundBloody diarrhea in children often indicates a severe gastrointestinal illness. Although infections are the most likely cause, inflammatory bowel disease (IBD) is a close mimic. IBD generally presents with chronic and persistent symptoms requiring long-term treatment. Hence, acute or atypical presentations may mislead the physician leading to delays in diagnosis. We report the case of an atypical presentation of ulcerative colitis.Case presentationWe present the case of a 6-year-old girl with acute symptoms of bloody diarrhea, fever, abdominal pain, and tenesmus for 5 days. The child came to us after the non-resolution of symptoms after treatment from a local practitioner. The child was found to have signs of chronic malnutrition and clubbing on general examination. After ruling out infective causes, the child was evaluated further by colonoscopy, which revealed lesions suggestive of ulcerative colitis, and hence started on topical and oral treatment for the same.ConclusionAwareness about the disease and its atypical presentations like poor growth, anemia, or extraintestinal manifestations is necessary, especially in primary healthcare and resource-poor settings as it can lead to early diagnosis, referral, and treatment initiation.

Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis.

Sarcoidosis is a complex immune-mediated disease characterized by clusters of immune cells called granulomas. Despite major steps in understanding the cause of this disease, many questions remain. In this Review, we perform a mechanistic interrogation of the immune activities that contribute to granuloma formation in sarcoidosis and compare these processes with its closest mimic, tuberculosis, highlighting shared and divergent immune activities. We examine how Mycobacterium tuberculosis is sensed by the immune system; how the granuloma is initiated, formed, and perpetuated in tuberculosis compared with sarcoidosis; and the role of major innate and adaptive immune cells in shaping these processes. Finally, we draw these findings together around several recent high-resolution studies of the granuloma in situ that utilized the latest advances in single-cell technology combined with spatial methods to analyze plausible disease mechanisms. We conclude with an overall view of granuloma formation in sarcoidosis.

Fluorescent carbazole-derived α-amino acids: structural mimics of tryptophan.

Fluorescent tags are commonly used for imaging of proteins and peptides during biological events; however, the large size of dyes can disrupt protein structure and function, and typically require the use of a chemical spacer. Herein, we report the synthesis of a new class of fluorescent unnatural α-amino acid, containing carbazole side-chains designed to mimic l-tryptophan and thus, readily incorporated into peptides. The amino acids were constructed using a Negishi cross-coupling reaction as the key step and exhibited strong fluorescent emission, with high quantum yields in both organic solvents and water. Compatible with solid phase peptide synthesis, the carbazole amino acids were used to replace tryptophan in a β-hairpin model peptide and shown to be a close structural mimic with retention of conformation. They were also found to be effective fluorescent molecular reporters for biological events. Incorporation into a proline-rich ligand of the WW domain protein demonstrated that the fluorescent properties of a carbazole amino acid could be used to measure the protein-protein binding interaction of this important biological signalling process.

Subungal exostosis: Differentiating from the closest mimic with an X‐ray

Subungal exostosis: Differentiating from the closest mimic with an X‐ray

Pulmonary paragonimiasis: Close mimic to pulmonary tuberculosis in endemic regions

We, hereby, report a case of pulmonary paragonimiasis in a patient from an endemic region who was misdiagnosed with pulmonary tuberculosis as the clinical features of both diseases are the same. The subtle clue such as eosinophilia, food habits, and travel history can help us diagnose parasitic infections. Pulmonary paragonimiasis with coughing up rusty brown sputum is the most common presentation of the disease. Praziquantel is mainstay of treatment. Highlight: This case report is to draw the attention of the medical fraternity to the diagnosis of paragonimiasis which is endemic in Asian, African, and South American countries, whose diagnosis is often delayed or missed.

3D interconnected porous PMMA scaffold integrating with advanced nanostructured CaP-based biomaterials for rapid bone repair and regeneration

Bioactive scaffolds with polymer and nanostructured bioactive glass-based composites are promising materials for regenerative applications in consequence of close mimics of natural bone composition. Poly methyl methacrylate (PMMA) is a highly preferred thermoplastic polymer for orthopedic applications as it has good biocompatibility. Different kinds of bioactive, biodegradable as well as biocompatible biomaterial composites such as Bioglass (BG), Hydroxyapatite (Hap), and Tricalcium phosphate (TCP) can be integrated with PMMA, so as to augment the bioactivity, porosity as well as regeneration of hard tissues in human body. Among the bioactive glass, 60S BG (Bioactive glass with 60 percentage of Silica without Sodium ions) is better materials among aforementioned systems owning to mechanical stability as well as controlled bioactive material. In this work, the fabrication of PMMA-CaP (calcium phosphate)-based scaffolds were carried out by Thermal Induced Phase Separation method (TIPS). X-ray diffractogram analysis (XRD) is used to examine the physiochemical properties of the scaffolds that evidently reveal the presence of calcium phosphate besides calcium phosphate silicate phases. The Field Emission Scanning Electron Microscopy (FESEM) studies obviously exhibited the microstructure of the scaffolds as well as their interconnected porous morphology. The PMMA/60S BG/TCP (C50) scaffold has the maximum pore size, measuring 77 ± 23 μm, while the average pore size ranges from 50 ± 20 to 80 ± 23 μm. By performing a liquid displacement method, the C50 scaffold is found to have the largest porosity of 50%, high hydrophilicity of 118.16°, and a compression test reveals the scaffolds to have a maximum compressive strength of 0.16 MPa. The emergence of bone-like apatite on the scaffold surface after 1st and 21st days of SBF immersion is further supported by in vitro bioactivity studies. Cytocompatibility and hemocompatibility analyses undoubtedly confirmed the biocompatibility behavior of PMMA-based bioactive scaffolds. Nano-CT investigation demonstrates that PMMA-CaP scaffolds provide more or less alike morphologies of composites that resemble the natural bone. Therefore, this combination of scaffolds could be considered as potential biomaterials for bone regeneration application. This detailed study promisingly demonstrates the eminence of the unique scaffolds in the direction of regenerative medicines.

Two-Dimensional NMR Spectroscopy of the G Protein-Coupled Receptor A2AAR in Lipid Nanodiscs.

Eight hundred and twenty-six human G protein-coupled receptors (GPCRs) mediate the actions of two-thirds of the human hormones and neurotransmitters and over one-third of clinically used drugs. Studying the structure and dynamics of human GPCRs in lipid bilayer environments resembling the native cell membrane milieu is of great interest as a basis for understanding structure-function relationships and thus benefits continued drug development. Here, we incorporate the human A2A adenosine receptor (A2AAR) into lipid nanodiscs, which represent a detergent-free environment for structural studies using nuclear magnetic resonance (NMR) in solution. The [15N,1H]-TROSY correlation spectra confirmed that the complex of [u-15N, ~70% 2H]-A2AAR with an inverse agonist adopts its global fold in lipid nanodiscs in solution at physiological temperature. The global assessment led to two observations of practical interest. First, A2AAR in nanodiscs can be stored for at least one month at 4 °C in an aqueous solvent. Second, LMNG/CHS micelles are a very close mimic of the environment of A2AAR in nanodiscs. The NMR signal of five individually assigned tryptophan indole 15N-1H moieties located in different regions of the receptor structure further enabled a detailed assessment of the impact of nanodiscs and LMNG/CHS micelles on the local structure and dynamics of A2AAR. As expected, the largest effects were observed near the lipid-water interface along the intra- and extracellular surfaces, indicating possible roles of tryptophan side chains in stabilizing GPCRs in lipid bilayer membranes.

Atypical presentation of a cystic parathyroid adenoma: Acute airway compromise secondary to intratumoral apoplexy - A case report

Spontaneous hemorrhage into cystic parathyroid lesion is a very rare and life-threatening complication which poses diagnostic challenge to the clinician as well as the radiologist due to various close mimics. Prompt identification, diagnosis, and emergent treatment are imperative to save the life of the patient. We report a case of a 56-year-old female who presented with acute airway compromise due to a giant cystic parathyroid adenoma with spontaneous hemorrhage. Magnetic resonance imaging was performed, and the patient underwent surgical exploration.

Cover Image

The cover image is based on the Original Article Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics by Woo Cheal Cho et al., https://doi.org/10.1111/cup.14414. image

Perfusion Computed Tomography May Help in Discriminating Gastrointestinal Tuberculosis and Crohn’s Disease

Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimics. This prospective study aimed to evaluate the diagnostic performance of perfusion computed tomography (CT) in differentiating GITB from CD. Consecutive patients with ileocaecal thickening underwent perfusion CT of the ileocaecal region between January 2019 and July 2020. Two radiologists (blinded to the final diagnosis) independently assessed blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability at perfusion CT. These parameters were compared among the patients with GITB as well as active and inactive CD. Receiver operating characteristic curves were utilized for determining the diagnostic performance of perfusion CT. Interclass correlation coefficient and Bland-Altman analysis were performed to compare the observations of the two radiologists. During the study period, 34 patients underwent perfusion CT. Eight patients had diagnoses other than intestinal tuberculosis or CD. Thus, 26 patients (mean age 36 ± 14 years, 18 males) with GITB (n = 11), active CD (n = 6), and inactive CD (n = 9) were evaluated. BF, MTT, and permeability showed significant differences among the groups, while BV did not differ significantly among the groups. BF and permeability had 100% sensitivity and 100% specificity, while MTT had 61.5-100% sensitivity and 70-100% specificity for differentiating GITB from active CD and active from inactive CD. The interclass correlation coefficient for perfusion CT parameters was 0.88-1. Perfusion CT is a novel imaging technique that can improve the diagnostic performance of differentiating tuberculosis from CD.

Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics.

Trichorhinophalangeal syndrome type 1 (TPRS1) expression has been found to be highly sensitive and specific for breast carcinomas. The frequency of TRPS1 expression in cutaneous neoplasms such as mammary Paget disease (MPD) and extramammary PD (EMPD) is currently unknown. We assessed the utility of TRPS1 immunohistochemistry (IHC) in the evaluation of MPD, EMPD, and their histopathologic mimics, squamous cell carcinoma in situ (SCCIS) and melanoma in situ (MIS). Twenty-four MPDs, 19 EMPDs, 13 SCCISs, and 9 MISs were subjected to immunohistochemical analysis using anti-TRPS1 antibody. The intensity (none, 0; weak, 1+ ; moderate, 2+ ; strong, 3+ ) and proportion (<1%, absent; 1%-25%, focal; 26%-75%, patchy; >75%, diffuse) of TRPS1 expression were recorded. Relevant clinical data were documented. TPRS1 expression was present in 100% (24/24) of MPDs, with 88% (21/24) of MPDs exhibiting strong, diffuse immunoreactivity. Sixty-eight percent (13/19) of EMPDs showed TRPS1 expression. Intriguingly, EMPDs lacking TRPS1 expression were consistently of perianal origin. TRPS1 expression was seen in 92% (12/13) of SCCISs but was absent in all MISs. TRPS1 may be useful to distinguish MPDs/EMPDs from MISs, but its utility is limited in distinguishing them from other pagetoid intraepidermal neoplasms such as SCCISs.

Evidence-based approach to diagnosis and management of abdominal tuberculosis.

Abdominal tuberculosis is an ancient problem with modern nuances in diagnosis and management. The two major forms are tuberculous peritonitis and gastrointestinal tuberculosis (GITB), while the less frequent forms are esophageal, gastroduodenal, pancreatic, hepatic, gallbladder and biliary tuberculosis. The clinicians need to discriminate the disease from the close mimics: peritoneal carcinomatosis closely mimics peritoneal tuberculosis, while Crohn's disease closely mimics intestinal tuberculosis. Imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and occasionally positron emission tomography) guide the line of evaluation. Research in diagnostics (imaging and endoscopy) has helped in the better acquisition of tissue for histological and microbiological tests. Although point-of-care polymerase chain reaction-based tests (e.g. Xpert Mtb/Rif) may provide a quick diagnosis, these have low sensitivity. In such situations, ancillary investigations such as ascitic adenosine deaminase and histological clues (granulomas, caseating necrosis, ulcers lined by histiocytes) may provide some specificity to the diagnosis. A diagnostic trial of antitubercular therapy (ATT) may be considered if all diagnostic armamentaria fail to clinch the diagnosis, especially in TB-endemic regions. Objective evaluation with clear endpoints of response is mandatory in such situations. Early mucosal response (healing of ulcers at twomonths) and resolution of ascites are objective criteria for early response assessment and should be sought at twomonths. Biomarkers, especially fecal calprotectin for intestinal tuberculosis, have also shown promise. For most forms of abdominal tuberculosis, sixmonths of ATT is sufficient. Sequelae of GITB may require endoscopic balloon dilatation for intestinal strictures or surgical intervention for recurrent intestinal obstruction, perforation or massive bleeding.

Diffuse cystic lung diseases: Imaging spectrum and diagnostic approach using high-resolution computed tomography.

The lung cyst is an air-containing lucent area surrounded by thin imperceptible walls. Other lucent lung lesions like centrilobular emphysema, cavity, cystic bronchiectasis, honeycomb cyst, and pneumatoceles are close mimics of a lung cyst on high-resolution computed tomography (HRCT). Various diseases with multiple lung cysts throughout both the lungs are classified as diffuse cystic lung diseases (DCLDs). HRCT is considered the imaging of choice for diagnosis of such diffuse cystic lung diseases. Common DCLDs like lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome (BHS), Langerhans cell histiocytosis (LCH), lymphocytic interstitial pneumonia (LIP), and desquamative interstitial pneumonia (DIP) can be confidently diagnosed on HRCT without further requirement of histopathological confirmation. The imaging also helps in differentiation of uncommon DCLDs and exclusion of the mimics. This review describes a simple algorithmic approach for DCLDs on HRCT based on scrutinizing the cyst's distribution, size, and shape, background parenchymal changes, and its correlation with clinical features and extrapulmonary imaging findings.

A clinicoepidemiological study on topical steroid misuse in a tertiary-care hospital in North India and the role of dermoscopy as a non-invasive diagnostic modality

Background: Topical corticosteroids (TCs) are one of the most frequently prescribed medications by dermatologists, yet may lead to an array of side effects due to prolonged and improper use. Because of the easy availability of topical corticosteroids as over-the-counter medications in India, these drugs are misused and abused. Objective: The objective was to determine the extent and the side effect profile of topical corticosteroid misuse/abuse in patients attending the OPD, to determine the demographic data and the reason and source of procuring TCs, and to characterize the dermoscopic findings of TSDF. Materials and Methods: This was a prospective, cross-sectional, clinical study conducted over a period of two years in which a predesigned, questionnaire-based proforma was employed. Patients above the age of fifteen reporting to the OPD giving a history of the application of a steroid cream continuously or intermittently for the minimum duration of four weeks were included in the study. A total of two hundred patients who met the clinical criteria were subjected to dermoscopic examination with a handheld dermoscope (DermLite DL4; 3Gen, U.S.; 10×). Results: A total of 2400 patients (fifteen-year-old or older) were enrolled in the study, in which 65% of the patients were females while 35% were males. Mostly, the patients procured these medicines from the pharmacist or paramedic, followed by general practitioners. The most common indications for which topical preparations were used included acne, followed by photodermatoses and ephelides. Most of the patients used combination creams, followed by potent steroids such as clobetasol propionate and betamethasone valerate. The most common side effects were erythema (74%), followed by photosensitivity (49%), hypertrichosis (47%), telangiectasia (42%), acneiform eruption (33%), contact dermatitis (21%), wrinkles (23.50%), etc. The main findings noticed on dermoscopy were irregularly dilated, branching, tortuous vessels almost interconnecting with each other in 79.78%, followed by hypertrichosis in 56.34%, white structureless areas representing atrophy in 42.33%, red dots in 7.22%, and a reddish background in 92.20%. Conclusion: The rampant use of TCs by patients for a prolonged period of time leads to a variety of side effects. Due to the topographical location, the climate of the valley, and the lighter skin type of the local population, the indications for which TCs were employed in our study group and the side effect profile were unique from the rest of the country. Dermoscopy may play a vital role in improving the diagnostic accuracy of TSDF and help us to differentiate it from close mimics.