Whole slide images as non-fungible tokens: A decentralized approach to secure, scalable data storage and access.

Background: Distributed ledger technology (DLT) enables the creation of tamper-resistant, decentralized, and secure digital ledgers. A non-fungible token (NFT) represents a record on-chain associated with a digital or physical asset, such as a whole-slide image (WSI). The InterPlanetary File System (IPFS) represents an off-chain network, hypermedia, and file sharing peer-to-peer protocol for storing and sharing data in a distributed file system. Today, we need cheaper, more efficient, highly scalable, and transparent solutions for WSI data storage and access of medical records and medical imaging data. Methods: WSIs were created from non-human tissues and H&E-stained sections were scanned on a Philips Ultrafast WSI scanner at 40× magnification objective lens (1 µm/pixel). TIFF images were stored on IPFS, while NFTs were minted on the Ethereum blockchain network in ERC-1155 standard. WSI-NFTs were stored on MetaMask and OpenSea was used to display the WSI-NFT collection. Filebase storage application programing interface (API) were used to create dedicated gateways and content delivery networks (CDN). Results: A total of 10 WSI-NFTs were minted on the Ethereum blockchain network, found on our collection "Whole Slide Images as Non-fungible Tokens Project" on Open Sea: https://opensea.io/collection/untitled-collection-126765644. WSI TIFF files ranged in size from 1.6 to 2.2 GB and were stored on IPFS and pinned on 3 separate nodes. Under optimal conditions, and using a dedicated CDN, WSI reached retrieved at speeds of over 10 mb/s, however, download speeds and WSI retrieval times varied significantly depending on the file and gateway used. Overall, the public IPFS gateway resulted in variably poorer WSI download retrieval performance compared to gateways provided by Filebase storage API. Conclusion: Whole-slide images, as the most complex and substantial data files in healthcare, demand innovative solutions. In this technical report, we identify pitfalls in IPFS, and demonstrate proof-of-concept using a 3-layer architecture for scalable, decentralized storage, and access. Optimized through dedicated gateways and CDNs, which can be effectively applied to all medical data and imaging modalities across the healthcare sector. DLT and off-chain network solutions present numerous opportunities for advancements in clinical care, education, and research. Such approaches uphold the principles of equitable healthcare data ownership, security, and democratization, and are poised to drive significant innovation.

Utility of Wnt family member 9b (Wnt9b) immunohistochemistry in the cytologic diagnosis of metastatic breast carcinoma.

Wnt family member 9b (Wnt9b) has been demonstrated as a valuable marker for breast cancer diagnosis in surgical pathology. In this study, we examined the utility of Wnt9b in diagnosing metastatic breast carcinoma in cytology samples. Cell blocks from fine needle aspirations (FNA) and fluid specimens of 96 metastatic breast carcinomas and 123 primary and metastatic non-breast neoplasms from various organ systems were evaluated by Wnt9b and GATA3 immunohistochemistry (IHC). Wnt9b and GATA3 were positive in 81.3% and 92.7% of metastatic breast carcinomas, respectively. Conversely, 93.5% and 90.0% of non-breast, non-urothelial carcinomas were negative for Wnt9b and GATA3, respectively. Wnt9b expression was positive in rare gastrointestinal, gynecological, lung, pancreas, and salivary gland tumors. All twenty-eight urothelial carcinomas were negative for Wnt9b, while twenty-six (92.9%) were positive for GATA3. Wnt9b was slightly less sensitive but more specific than GATA3 in diagnosing metastatic breast cancer in cytology samples. Particularly, Wnt9b shows higher specificity in differentiating breast and urothelial primaries. The combined use of Wnt9b and GATA3 may increase diagnostic accuracy.

Pronator quadratus musculo-osseous free flap for wide hard palatal defect reconstruction: An anatomical study.

Wide hard palate defects include congenital and acquired defects that are six square centimeters or larger in size. Obturator prostheses and autologous soft tissue transfers have been used to reconstruct palatal defects. This study aims to repair wide, hard palatal defects by using a pronator quadratus musculo-osseous free flap to achieve subtotal reconstruction. Seventeen formalin-fixed cadavers were dissected. Free musculo-osseous pronator quadratus flaps were prepared after a 12 cm curvilinear volar skin incision. Standard 30 × 23 mm (690 ± 52.12 mm2) hard palate defects were made by chisels and saws. A subcutaneous tunnel was created between the mandibular edge cross point of the facial vessels and the retromolar trigone through the subcutaneous to the superficial musculoaponeurotic system by dissection. Area measurements of the pedicle and palate defects were performed by the ImageJ program (National Institutes of Health, Bethesda, MD, USA) on drawings over an acetate layer of materials. Mandibular distances of gonion-facial vessel cross point (a), gonion-gnathion (m), and facial vessels' cross point-retromolar entrance point (h) were measured. Ratios of h/m and a/m were calculated. The mean pronator quadratus area was 2349.39 ± 444.05 mm2, and the arterial pedicle pronator quadratus diameter was 2.32 ± 0.34 mm. The mean pedicle length of the pronator quadratus was 117.13 ± 8.10 mm. Study results showed that musculo-osseous pronator quadratus flaps' bone and muscle parts perfectly fit on the defects in all cadavers. Pronator quadratus musculo-osseous flap is a feasible surgical option for wide, hard palatal defect reconstruction strategies.

MMR Deficiency Defines Distinct Molecular Subtype of Breast Cancer with Histone Proteomic Networks.

Mismatch repair (MMR) alterations are important prognostic and predictive biomarkers in a variety of cancer subtypes, including colorectal and endometrial. However, in breast cancer (BC), the distinction and clinical significance of MMR are largely unknown. This may be due in part to the fact that genetic alterations in MMR genes are rare and only seen to occur in around 3% of BCs. In the present study, we analyzed TCGA data using a multi-sample protein-protein interaction (PPI) analysis tool, Proteinarium, and showed a distinct separation between specific MMR-deficient and -intact networks in a cohort of 994 BC patients. In the PPI networks specific to MMR deficiency, highly connected clusters of histone genes were identified. We also found the distribution of MMR-deficient BC to be more prevalent in HER2-enriched and triple-negative (TN) BC subtypes compared to luminal BCs. We recommend defining MMR-deficient BC by next-generation sequencing (NGS) when any somatic mutation is detected in one of the seven MMR genes.

Brucella Species Staining as Gram-Positive Rod and Gram-Positive Cocci in Chains.

Two cases of Brucellosis were identified at a hospital in Rhode Island. In both cases, the organisms were isolated from the blood cultures. The bacteria did not appear as the classical textbook description of Brucella spp. as short, Gram-negative rods; instead, Gram-positive rods and Gram-positive cocci in chains were observed. Due to the atypical Gram stain morphology, Brucella spp. were not initially considered as a possible pathogen. Antimicrobial prophylaxes were offered to the technologists who were exposed to the organisms.

Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient.

OBJECTIVE: Valproic acid (VPA) is an effective first-line anticonvulsant that is associated with several side effects including bone marrow suppression and subsequent cytopenia. However, VPA associated myelodysplasia is not a well described entity that can be seen in patients on VPA treatment. CASE REPORT: Herein, we describe a 9-year-old female patient with a past medical history of seizure disorder who presented with 3-week history of intermittent fevers, fatigue, weakness, and multiple unexplained bruises. Complete blood count (CBC) was remarkable for marked thrombocytopenia. Trephine biopsy showed a normocellular marrow with maturing trilineage hematopoiesis and scattered atypical megakaryocytes including numerous small hypolobated forms with frequent forms showing separated nuclei. Her CBC showed normalization 7 months after VPA was stopped. CONCLUSIONS: The presence of bone marrow suppression and myelodysplasia in patients on VPA treatment should be taken into consideration as it can cause a diagnostic pitfall especially in pediatric and elderly populations. A careful review of past medical history and medications can help make the correct diagnosis.

Malignant Variant of Calcifying Epithelial Odontogenic Tumor with Neuroendocrine Differentiation.

A 60-year-old female presented with asymptomatic failing mandibular dental implants. Computed tomography (CT) showed a partially calcified, hypointense lesion within the soft tissues, measuring 1.3 x 0.8 x 1.0 cm along the buccal cortex. Incisional biopsy demonstrated a basaloid type of tumor composed of sheets of cells with plump ovoid nuclei, distinct nucleoli, and scant eosinophilic cytoplasm. Mitoses were present, averaging about 2 per 10 high power fields with scattered individual apoptotic cells. Numerous laminated calcified bodies (Liesegang rings) were observed with confluence of these bodies to form larger foci of dystrophic mineralization. These features clearly established the malignant nature of this tumor. Immunohistochemically, the tumor was positive for synaptophysin, focally positivity for CAM 5.2 and had a Ki-67 proliferation index of approximately 25%. This is the first report of a tumor with features of a malignant variant of calcifying epithelial odontogenic tumor and neuroendocrine differentiation.

Describing IgA Myeloma: An Immunophenotypic and Molecular Approach.

Plasma cell myeloma (PCM) is defined as a clonal disease of terminally differentiated plasma cells that secrete immunoglobulin. The biologic underpinnings of IgA-type multiple myeloma's (IgAMM) aggressive nature, including its increased morbidity and mortality, have not been elucidated. We describe the clinical, phenotypic, and cytogenetic characteristics of IgA-MM. Flow-cytometry analysis was performed to phenotype clonal plasma cell populations, and interface with fluorescent in situ hybridization (iFISH) to exploit cytogenetics to determine risk stratification; 68.1% of cases were of intermediate or high risk. On flow cytometry, samples from our IgA-PCM cohort revealed less frequent CD56 expression when compared to samples with other PCM subtypes. Our study demonstrated lower frequency of CD56 expression (52.8%). We hypothesize that loss of CD56 may play a significant role in the aggressive behavior of IgA-PCM due to the loss of cell-to-cell adhesion resulting in a higher propensity for extramedullary presentation.

Lung Findings in a Patient with a History of Nicotine Vaping and Cannabis Smoking.

We report a collection of lung findings in a patient with a remote history of cigarette smoking, but now engaged in heavy nicotine vaping with daily edible and combustible cannabis use. Computed tomography (CT) imaging demonstrated numerous, small, and bilateral nodules with ground-glass appearance. The largest nodule is demonstrated in the right upper lung lobe. Clinically the differential diagnosis at this time included hypersensitivity pneumonitis and sarcoidosis. Atypical infection, particularly of a fungal etiology, and metastatic malignancy were also considered. Initial pathology of the right lung needle biopsy revealed alveolar septal thickening with associated atypical pneumocyte proliferation, suggestive of atypical adenomatous hyperplasia (AAH). Subsequently the patient underwent wedge resection of the right upper, middle and lower lobes. Pathology examination revealed pulmonary Langerhans cell histiocytosis (PLCH) in the upper and lower lobes, with CD1a staining highlighting the aggregates of Langerhans cells. Vascular changes were also present including intimal thickening of muscular pulmonary arteries, consistent with pulmonary hypertensive changes. Background lung parenchyma demonstrated respiratory bronchiolitis, smoking-related interstitial fibrosis, an organizing thrombus in muscular artery and associated pneumocyte hyperplasia.

Utility of secretagogin as a marker for the diagnosis of lung neuroendocrine carcinoma.

Small-cell lung cancers (SCLC) and large-cell neuroendocrine carcinomas (LCNEC) are two types of high-grade pulmonary neuroendocrine carcinomas (NECs). Diagnostic neuroendocrine markers commonly include synaptophysin, chromogranin A, CD56, and insulinoma-associated protein 1 (INSM1). In this study, the utility of secretagogin (SCGN) was examined in the context of pulmonary NEC diagnosis. The study included 71 pulmonary NEC cases (18 SCLCs, 13 combined-SCLCs, 23 LCNECs, and 17 combined-LCNECs). Immunohistochemical stains of SCGN, synaptophysin, chromogranin A, CD56, and INSM1 were performed on whole tumor sections. The stains were evaluated based on combined staining intensity and the proportion of positive tumor cells. At least mild staining intensity in at least 1% of the cells was considered positive. Bioinformatic studies showed specific SCGN expression in neuroendocrine cells and NECs. SCGN showed diffuse nuclear and cytoplasmic staining in NECs with intra-tumoral heterogeneity. The non-neuroendocrine components were negative. The sensitivity of SCGN was no better than the other established neuroendocrine markers based on all NECs combined or LCNECs/c-LCNECs only. However, the sensitivity of SCGN (71%) was higher than chromogranin A (68%) for SCLCs/c-SCLCs only. The average proportion of SCGN positive tumor cells was 8% higher than chromogranin A (22% versus 14%, P = 0.0332) in all NECs and 18% higher for SCLC and c-SCLC cases only (32% versus 13%, P = 0.0054). The above data showed that SCGN could be used as a supplemental neuroendocrine marker to diagnose SCLC.

Reliability of patient self-report of cognition, awareness, and consciousness during seizures.

OBJECTIVE: Clinicians rely on patient self-report of impairment during seizures for decisions including driving eligibility. However, the reliability of patient reports on cognitive and behavioral functions during seizures remains unknown. METHODS: We administered a daily questionnaire to epilepsy patients undergoing continuous video-EEG monitoring, asking about responsiveness, speech, memory, awareness, and consciousness during seizures in the preceding 24 hours. We also administered a questionnaire upon admission about responsiveness, speech, and awareness during seizures. Subjective questionnaire answers were compared with objective behavioral ratings on video review. Criteria for agreement were Cohen's kappa >0.60 and proportions of positive and negative agreement both >0.75. RESULTS: We analyzed 86 epileptic seizures in 39 patients. Memory report on the daily questionnaire met criteria for agreement with video review (κ = 0.674 for early, 0.743 for late recall). Subjective report of awareness also met agreement criteria with video ratings of memory (κ = 0.673 early, 0.774 late). Concordance for speech was relatively good (κ = 0.679) but did not meet agreement criteria, nor did responsiveness or consciousness. On the admission questionnaire, agreement criteria were met for subjective report of awareness versus video ratings of memory (κ = 0.814 early, 0.806 late), but not for other comparisons. INTERPRETATION: Patient self-report of memory or awareness showed the best concordance with objective memory impairment during seizures. Self-report of impairment in other categories was less reliable. These findings suggest that patient reports about impaired memory during seizures may be most reliable, and otherwise determining functional impairments should be based on objective observations.

Pasteurella Multocida Urinary Tract Infection in a Susceptible Patient with Non-Traumatic Feline Contact.

Pasteurella multocida is a part of the normal oral flora of domestic animals. Humans can develop skin and soft tissue infections from P. multocida after traumatic animal contact, usually through bites and scratches from domestic animals. Although rare, there have been documented case reports where P. multocida has been isolated from patients even after minimal casual animal contact. Even rarer, is the isolation of P. multocida from urine. The few documented cases of urine isolation have been described in patients who have underlying medical conditions, particularly those with urologic abnormalities. Here we present a 34-year-old female patient with known congenital neurological and urological anomalies who developed a P. multocida urinary tract infection from casual contact with a household feline, a previously unrecognized risk factor for P. multocida UTI in anatomically susceptible individuals.

Comparison of Three Surgical Approaches for Frontobasal Meningiomas: Purely Endoscopic Endonasal, Purely Microscopic Bifrontal Transcranial, and Combined Endoscopic and Microscopic Supraorbital Transciliary Approaches.

ABSTRACT: Surgical removal of frontobasal meningiomas (FBMs) can be achieved using different techniques, including endoscopic, transcranial, and combined approaches. The advantages and disadvantages of the outcomes of these approaches should be compared to provide the most convenient surgical treatment to the patient. This study aimed to compare 3 surgical approaches for FBMsin terms of outcomes and determine the superiority of each on the basis of anatomical, surgical, and clinical efficacy. Systematic review was performed to identify studies comparing techniques for the surgical removal of FBMs. Each group included 13 patients; 39 patients with FBMshad undergone surgery. These groups were endoscopic endonasal approach (EEA), microscopic bifrontal transcranial approach (MTA), and endoscopic plus microscopic combined supraorbital transciliary approach (STA) groups. Data on the demographics of patient population, pre- and post-operative neurological examination, tumor properties, imaging studies, and surgical complications were extracted. The mean age at the time of surgery for the patient population was 53.2 years. Among the groups, no statistically significant differences were observed with regard to sex (P = 0.582). The mean follow-up time was 56.7 months. A statistically significant difference was observed in the mean tumor volume among the groups; the MTA group showed the highest mean tumor volume. However, no significant difference was found in the mean tumor volume between EEA and STA groups. Regarding operation duration, the STA group had the shortest operation time (mean = 281.5 minutes), whereas the average surgical duration in MTA group was the longest (mean = 443.8 minutes). The average bleeding volume was highest in the MTA group (mean = 746.2 ml) and lowest in the EEA group (mean = 320.8 ml). Tumor removal was incomplete in three patients (two in the EEA group and one in the MTA group). Recurrence was detected in two cases. One patient with recurrence was operated using the endoscopic surgical approach, whereas the other patient underwent the microscopic bifrontal approach. Post-operative hyposmia/anosmia or decreased olfactory function was the most common complication observed in 5 patients, 2 patients each in the EEA and MTA groups and one in the STA group. The second most common complication was wound infection in one patient in the MTA group and two patients in the STA group (7.7%). Both cerebrospinal fluid (CSF) leakage and meningitis were present in two patients (5.1%), one patient each from the EEA and STA groups. Pre-operative visual disturbances were reported in 13 patients (33.3%), all of which resolved post-operatively No statistical differences were found among the groups. Mortality occurred in a patient in the MTA group (2.6%) caused by cardiac arrest on post-operative day 1. This is the first study comparing the surgical outcomes of three surgical approaches for FBMs. Although recent literature suggests that both endoscopic and transcranial approaches have their own advantages and disadvantages, the authors showed that none of the surgical approaches have obvious superiority over the others with regard to outcomes. Thus, the selection of the ideal surgical approach should be based on surgical experience and tumor characteristics.