Local Cutaneous Scrotal Involvement of Paratesticular Mesothelioma.

ABSTRACT: Paratesticular mesothelioma (malignant mesothelioma arising from the tunica vaginalis of the testis) represents a small proportion of mesothelial neoplasms, and cutaneous involvement by paratesticular mesothelioma is very rare. Cutaneous involvement can manifest as scrotal subcutaneous nodules from regional spread, distant metastasis, or direct extension through surgical scars. Mesothelioma has 3 histopathologic classifications that include epithelioid, biphasic, and sarcomatoid, which is rarely seen in paratesticular mesothelioma. Given the rarity of this condition, cutaneous mesothelioma may be misdiagnosed as histologic mimics, such as metastatic adenocarcinoma or adnexal neoplasms; thus, appropriate immunohistochemical workup and clinical correlation are required to make an accurate diagnosis. In this case, a 75-year-old man with a history of paratesticular mesothelioma, status postorchiectomy, presented with right-sided scrotal swelling, erythema, and subcutaneous nodules. These nodules were identified as local recurrence with cutaneous involvement by paratesticular mesothelioma on histopathologic examination. This case highlights the clinical and histopathologic features of this diagnosis and underscores the importance of dermatopathologists being aware of this condition to ensure accurate diagnosis.

A rare case report of bilateral Purtscher-like retinopathy in juvenile dermatomyositis.

Purpose: To report a rare case of bilateral Purtscher-like retinopathy (PLR) in a young adult diagnosed with dermatomyositis. Method: A case report with multi-modal imaging. Result: A 17-year-old male presented with subacute marked diminution of vision along with arthralgia, weakness of all four limbs and development of multiple rashes around body. Fundus examination revealed bilateral multiple Purtscher flecken, pseudo-cherry red spot, and intra-retinal haemorrhages with cotton wool spots. Systemic and laboratory examinations, magnetic resonance imaging (MRI) and biopsy of tissue confirmed the diagnosis of juvenile dermatomyositis with PLR. Conclusion: Dermatomyositis, being a rare cause of PLR, should essentially be considered as one of the differentials as timely intervention can alter the course of disease and prove life-saving for the patient.

Cerebral autoregulation in paediatric and neonatal intensive care: A scoping review.

Deranged cerebral autoregulation (CA) is associated with worse outcome in adult brain injury. Strategies for monitoring CA and maintaining the brain at its 'best CA status' have been implemented, however, this approach has not yet developed for the paediatric population. This scoping review aims to find up-to-date evidence on CA assessment in children and neonates with a view to identify patient categories in which CA has been measured so far, CA monitoring methods and its relationship with clinical outcome if any. A literature search was conducted for studies published within 31st December 2022 in 3 bibliographic databases. Out of 494 papers screened, this review includes 135 studies. Our literature search reveals evidence for CA measurement in the paediatric population across different diagnostic categories and age groups. The techniques adopted, indices and thresholds used to assess and define CA are heterogeneous. We discuss the relevance of available evidence for CA assessment in the paediatric population. However, due to small number of studies and heterogeneity of methods used, there is no conclusive evidence to support universal adoption of CA monitoring, technique, and methodology. This calls for further work to understand the clinical impact of CA monitoring in paediatric and neonatal intensive care.

ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

AIMS: The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). METHODS AND RESULTS: We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). CONCLUSION: We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.

Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.

Green energy innovation initiatives for environmental sustainability: current state and future research directions.

Worldwide, all countries have been facing the crisis of climate change problem. They have been addressing this issue by focusing on implementing green energy innovation initiatives and promoting a sustainable future through environmental sustainability. In this research study, we focus on examining the role of green finance through green energy innovations, which are taking place in several sectors across different regions to promote environmental sustainability. The study has analysed 152 articles on this research domain through a systematic literature review to understand the present state of existing knowledge. The current study examines the Scopus-indexed research articles from the time period 2002 to 2023. Six emerging themes have been examined to understand their development and the potential impact of green initiatives for environmental sustainability. Various institutional theories have been explored to understand their association with the investigated research area. The paper has discussed multiple challenges that need to be addressed for the speedy implementation of green innovations. Finally, future research questions have been proposed based on the findings from the extant literature and the existing research gaps.

Cutaneous crystal storing histiocytosis: A case series with review of literature.

Crystal-storing histiocytosis (CSH) is a rare condition in which crystals accumulate in the cytoplasm of histiocytes and is usually associated with a lymphoplasmacytic neoplasm. Cutaneous CSH is extraordinarily rare and limited to case reports in the literature. We report two cases of this disease with cutaneous involvement. Case 1 was a 65-year-old male with a 4-month history of a pruritic eruption that started as a solitary pink to skin-colored indurated plaque on the anterior neck before progressing to involve the whole neck, chest wall, and face. Case 2 was a 54-year-old woman with a history of unspecified "lymphoma" who presented with a soft nodule on the forearm. Biopsies from both cases had similar findings and showed a proliferation of epithelioid cells with pink cytoplasm and intracellular crystalline structures infiltrating the dermis and subcutaneous fat. In the first case, the cells were positive for CD43, CD45, CD68, and IgG kappa, and in the second case, the crystals were positive for IgG lambda. Based on these findings, the patients were diagnosed with cutaneous CSH. We highlight this rare diagnosis and the importance of investigating an underlying lymphoplasmacytic neoplasm.

Neuromonitoring in Children with Traumatic Brain Injury.

Traumatic brain injury remains a major cause of mortality and morbidity in children across the world. Current management based on international guidelines focuses on a fixed therapeutic target of less than 20 mm Hg for managing intracranial pressure and 40-50 mm Hg for cerebral perfusion pressure across the pediatric age group. To improve outcome from this complex disease, it is essential to understand the pathophysiological mechanisms responsible for disease evolution by using different monitoring tools. In this narrative review, we discuss the neuromonitoring tools available for use to help guide management of severe traumatic brain injury in children and some of the techniques that can in future help with individualizing treatment targets based on advanced cerebral physiology monitoring.

Comparison of Patient's Procedural Tolerance of EBUS-TBNA Performed Through Nasal Versus Oral Route: The NO-EBUS Randomized Clinical Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly performed procedure by the bronchoscopist for the evaluation of mediastinal lesions. However, evidence directly comparing the nasal and oral routes to guide the choice of an optimal insertion approach is scanty. METHODS: In this prospective, parallel-group, open-label randomized clinical trial, adults posted for a linear EBUS-TBNA examination under conscious sedation were randomized to undergo the procedure via the nasal or oral route. The primary objective was to assess the equivalence of subject-rated tolerance of EBUS-TBNA procedure in the 2 groups. Key secondary objectives were to assess the equivalence of subject-rated overall experience, willingness for a repeat procedure, operator-rated subject's tolerance, and operator-rated ease of performing the procedure. RESULTS: One hundred and eighty subjects were randomized in a 1:1 ratio to the nasal (n=98) or oral (n=82) group. Outcome measures were assessed by both per-protocol (PP) and intention-to-treat (ITT) analysis. Subject-rated procedural tolerance, overall satisfaction and operator's ease of performing the procedure were found to be equivalent in the 2 groups ( P <0.05 in all cases for PP and ITT analysis). The operator-rated subject's tolerance was, however, nonequivalent ( P =0.0596, 0.1286 for PP and ITT, respectively). Subject's willingness to undergo a repeat procedure was similar in both groups [90% CI of difference in proportions: (-0.023, 0.121) in PP and (-0.028, 0.115) in ITT analysis]. CONCLUSION: Nasal route for EBUS-TBNA could be considered where it is feasible and preferable for the patient as well as the operator.

Novel Advances in the Role of Selective Estrogen Receptor Modulators in Hormonal Replacement Therapy: A Paradigm Shift.

Estrogen is a key regulatory hormone in the functioning of a female reproductive system. Estrogen hormone regulates many complex physiological processes, which has its role in reproduction and skeletal and cardiovascular systems by acting on estrogen receptors alpha (ERα) and beta (ERß), which are nuclear transcription factors. Selective estrogen receptor modulators (SERMs) are now being used to treat bone loss, breast carcinoma, and menopausal symptoms, metabolic neurodegenerative because of their characteristics that allow them to function as both estrogen agonists and antagonists, depending on the target tissue. First-generation SERMs, such as Tamoxifen, are used in the management protocol for breast cancer, which is estrogen receptor (ER-positive). Raloxifene is a second-generation SERM that is a valuable adjunct used to treat and prevent osteoporosis in postmenopausal women and prevent compression fractures of the vertebral column. Novel SERM molecules are on the horizon, proven more potent and efficacious in preventing and treating osteoporosis. These include Ospemifene, lasofoxifene, bazedoxifene and arzoxifene. The benefits of Raloxifene versus that of Bazedoxifene are under trial. Despite their therapeutic benefits and actions, these medications are not without adverse effects, such as thromboembolic disorders. Increased risk of uterine cancer has been linked to Tamoxifen. This article delves into the world of SERMs, including their development and discovery. The newer SERMs in late development, ospemifene, lasofoxifene, bazedoxifene, and arzoxifene, are described in detail.

Deep reinforcement learning for forecasting fish survival in open aquaculture ecosystem.

Ensuring the classification of water bodies suitable for fish habitat is essential for animal preservation and commercial fish farming. However, existing supervised machine learning models for predicting water quality lack specificity regarding fish survival. This study addresses this limitation and presents a novel model for forecasting fish viability in open aquaculture ecosystems. The proposed model combines reinforcement learning through Q-learning and deep feed-forward neural networks, enabling it to capture intricate patterns and relationships in complex aquatic environments. Moreover, the model's reinforcement learning capability reduces the reliance on labeled data and offers potential for continuous improvement over time. By accurately classifying water bodies based on fish suitability, the proposed model provides valuable insights for sustainable aquaculture management and environmental conservation. Experimental results show a significantly improved accuracy of 96% for the proposed DQN-based model, outperforming existing Gaussian Naive Bayes (78%), Random Forest (86%), and K-Nearest Neighbors (92%) classifiers on the same dataset. These findings highlight the effectiveness of the proposed approach in forecasting fish viability and its potential to address the limitations of existing models.

Detecting Human Epidermal Growth Factor Receptor 2 (HER2) Amplification: Proof of Concept of an Alternative Approach.

BACKGROUND: There are multiple genes that are co-amplified along with human epidermal growth factor receptor 2 (HER2) in chromosome 17. GRB7 and PGAP3 are two such genes. We hypothesize that the protein products of these genes may serve as immunohistochemistry (IHC) markers for detecting HER2 amplification in breast cancer. METHODS: Tissue sections from one hundred and thirty-five primary breast carcinoma cases were subjected to immunohistochemical staining for antibodies against HER2, GRB7, and PGAP3 and graded on a scale of 1 to 3. Both membranous staining and cytoplasmic staining were assessed for GRB7 and PGAP3. For equivocal HER2 IHC positivity, fluorescent in situ hybridization was performed to get the final HER2 status. RESULTS: IHC staining for GRB7 and PGAP 3 was a moderate to strong predictor for HER2 status (area under the curve (AUC) of 0.768, 0.868,0.754, and 0.790 for GRB7 membranous staining, GRB7 cytoplasmic staining, PGAP3 membranous staining, and PGAP3 cytoplasmic staining respectively). A combination of GRB7 cytoplasmic and PGAP3 membranous staining resulted in an AUC of 0.905 (95% CI 0.855-0.954), while a combination of GRB7 and PGAP3 cytoplasmic staining resulted in an AUC of 0.902 (95% CI 0.851-0.953). CONCLUSION: The point estimates for the AUC of GRB7 and combined GRB7 and PGAP3 in predicting the AUC suggest a strong predictive ability of these markers to predict HER2. With further refinement in technique, cytoplasmic staining and membranous IHC staining for GRB7 and PGAP3 have potential to serve as surrogate markers for HER2 status. The strategy of using protein products of co-amplified genes of HER2 is likely to be successful in technical validation.

Case of split notochord syndrome: a neonate with thoracic neuroenteric cyst, abdominal duodenal duplication cyst, malrotation and vertebral anomalies.

The authors describe a case of a male neonate with split notochord syndrome presenting with cervico-thoracic deformity, thoracic neuroenteric cyst, separate abdominal duodenal duplication cyst and concurrent intestinal malrotation. This combination of abnormalities is very rare. When these lesions are suspected, patients must be investigated carefully.This case is presented not only to recount an infrequent combination of structural abnormalities but also to raise awareness of the signs that should point to clinical suspicion and prompt diagnosis.Following surgical excision of the thoracic neuroenteric cyst, the patient has made a good recovery.

Can green finance facilitate Industry 5.0 transition to achieve sustainability? A systematic review with future research directions.

Most of the world's rising carbon emission results from industrial activities. Previous industrial revolutions did not put much thought into safeguarding the natural world. Governments worldwide have been continuously implementing regulations and policies for the mitigation of climate change to promote sustainable development. To achieve decarbonization, the climate change discussion is merged with Industry 5.0 (I5.0) where green finance (GF) plays a crucial role. This technological metamorphosis of transition from Industry 4.0 (I4.0) to I5.0 will affect humans and their society. I5.0 forms a symbiotic relationship with different aspects of Society 5.0 (S5.0) such as social (human‒machine centricity), ecological (zero emissions), and technological (green innovations). Thus, the I5.0 transition prioritizes greening the economy in pursuit of achieving S5.0. Through a systematic review of 196 articles, this research study concisely summarizes the rapidly expanding body of information. The research domain gave six major themes: Green Innovations (GI), Green Manufacturing Practices (GMP), Circular Economy (CE), Green Supply Chain Management (GSCM), Emerging Economies, and Net Zero Economy (NZE). Finally, a framework has been provided that illustrates the supporting role of GF for the I5.0 transition eventually followed by S5.0. This study provides an overview of these themes with their propositions and future research directions. The present study addresses the knowledge gap by providing valuable contributions to the burgeoning research domain of I5.0 and GF. Moreover, it aims to garner the attention of different stakeholders to integrate these two concepts of research to attain the goal of sustainable development.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases.

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcoma and myxoid malignant fibrous histiocytoma arising in patients aged ≤40 years with clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34 cm (median 4.1 cm). Anatomic sites included proximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P = .025, P = .005), while tumor depth was also associated with worse EFS (P = <.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis.

A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era.

Background: In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods: An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results: Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions: Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration: Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00008-z.