Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans.

In photoaged human skin, type I collagen fragmentation impairs dermal extracellular matrix (ECM) integrity, resulting in collapsed/contracted fibroblasts with reduced type I procollagen synthesis. Injections of cross-linked hyaluronic acid (CL-HA) reverse these deleterious changes. To investigate the time course and effects of biochemical changes induced by injected CL-HA, particularly whether fibroblast activation leads to accumulation/deposition of dermal collagen, we injected CL-HA into photoaged skin of human participants over 60 years-old and performed biochemical/microscopic analyses of skin samples. Beginning 1 week post-injection and lasting 6-9 months, fibroblasts exhibited activation, including increased immunostaining and gene expression of markers of type I collagen synthesis, such as heat shock protein 47 and components of the transforming growth factor-ß pathway. At 1 week post-injection, multiphoton microscopy revealed elongation/stretching of fibroblasts, indicating enhanced dermal mechanical support. At 4 weeks, second-harmonic generation microscopy revealed thick collagen bundles densely packed around pools of injected CL-HA. At 12 months, accumulation of thick collagen bundles was observed and injected CL-HA remained present in substantial amounts. Thus, by occupying space in the dermal ECM, injected CL-HA rapidly and durably enhances mechanical support, stimulating fibroblast elongation and activation, which results in thick, densely packed type I collagen bundles accumulating as early as 4 weeks post-injection and continuing for at least a year. These observations indicate that early and prolonged clinical improvement following CL-HA injection results from space-filling and collagen deposition. As type I collagen has an estimated half-life of 15 years, our data provide the foundations for optimizing the timing/frequency of repeat CL-HA injections.

Long-term care planning and the influencing factors among sexual minority older women: A qualitative study.

AIMS: The aim of the study was to explore plans, considerations and factors influencing long-term care among older sexual minority (SM) women. DESIGN: Qualitative interview study. METHODS: Semi-structured in-depth interviews were conducted with 37 older Taiwanese SM women between May and September 2019. This study analysed interview data using a socio-ecological model and constant comparative analysis. RESULTS: The most frequently reported long-term care plans were housing and institutions, private medical or long-term care insurance, financial planning and medical decisions. Factors associated with women's long-term care plans were categorized using the socio-ecological model level: (1) intrapersonal factors: current physical and mental health status, ageing signs and women's attitudes towards ageing; (2) interpersonal-level factors: receiving support from partners, child(ren), siblings or significant others, concerns about being a caregiver for parents and worries regarding social isolation; (3) community-level factors: receiving support from lesbian, gay, bisexual and transgender (LGBT) organizations; private lesbian online groups; or religious groups; (4) societal-level factors: concerns about negative social environments, concerns about the healthcare system and healthcare providers, inappropriate policies and insufficient resources. CONCLUSION: This study identified multi-level factors related to long-term care plans and concerns among older Taiwanese SM women. Recommendations for nurses, managers of long-term care and healthcare settings, policymakers, and governments have been provided to diminish health disparities and reduce anxiety among older SM women. IMPACT: This study assists nurses in understanding older SM women's long-term care concerns and worries when accessing long-term care and healthcare services and helps nurses provide SM-sensitive services and care for women. PATIENT OR PUBLIC CONTRIBUTION: SM older women were recruited from LGBT organizations, LGBT-friendly bookstores, restaurants, coffee shops and LGBT online chatrooms using purposive and snowball sampling.

Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

Cutaneous malakoplakia arising on the ankle of a patient with pyoderma gangrenosum.

Malakoplakia is a rare chronic inflammatory condition that most commonly involves the urogenital tract. Cutaneous malakoplakia is extremely rare and many patients diagnosed with skin involvement are immunosuppressed. While the clinical presentation of cutaneous malakoplakia is variable, the histopathologic features are quite distinct and include sheets of closely packed dermal histiocytes with foamy-appearing cytoplasm and Michaelis-Gutmann bodies that are positive with certain immunohistochemical stains. While the exact pathogenesis of malakoplakia is unknown, it has been associated with certain bacterial infections. Treatment generally involves a combination of surgery and antimicrobial agents and/or modulation of immunosuppressant therapy if appropriate. Herein, the authors report a unique case of cutaneous malakoplakia arising in a patient on chronic immunosuppressive therapy for the management of pyoderma gangrenosum.

Positive Perceptions Towards Virtual Didactics During The COVID-19 Pandemic: A Survey Assessment of Dermatology Residents.

BACKGROUND: During the COVID-19 pandemic, resident didactics at many institutions, including ours, were transitioned from in-person to virtual. OBJECTIVES: We aimed to assess dermatology residents' satisfaction, impression of effectiveness, and preference for virtual didactics, and factors correlating with these sentiments. METHODS: Questionnaire administered to dermatology residents at our institution 3-6 months following transition to virtual didactics. RESULTS: Response rate was 26/31 residents (83.9%), with 20/26 (76.9%) expressing satisfaction, 15/26 (57.7%) effectiveness, and 12/26 (46.2%) preference towards virtual didactics. Factors associated with satisfaction included feeling that virtual didactics positively impacted learning retention, represented time well spent, and utilized high-quality images. Perception of effectiveness correlated with using high-quality images, baseline preference for online instruction, and feeling engaged. Factors associated with preference for virtual didactics included having opportunities for critical thinking, using high-quality images, and utilizing images applicable to teledermatology care. Advantages to virtual didactics included convenience, decreased commuting, and easily hosting guest lecturers. Disadvantages included distractions/decreased focus, reduced social interaction, and difficulty with communication. CONCLUSIONS: Residents expressed satisfaction, effectiveness, and some preference towards virtual didactics, which correlated with numerous factors. Our findings suggest that it is reasonable to maintain a virtual didactic component as part of dermatology resident education. Furthermore, our data provide insights into strategies that residency program directors and educators may consider when/if integrating virtual didactics into future educational curricula.

A striking presentation of pustular Sweet syndrome induced by trimethoprim-sulfamethoxazole.

We describe a strikingly robust presentation of trimethoprim-sulfamethoxazole (TMP-SMX)-induced pustular Sweet syndrome and discuss how to distinguish it from iododerma and other neutrophil-rich conditions. A review of the literature indicates that TMP-SMX-induced Sweet syndrome (SS) may have higher rates of neutrophilia and greater ocular, mucosal, and musculoskeletal involvement compared to SS from other drugs. Recognizing these features and identifying the offending agent are critical for correctly diagnosing TMP-SMX-induced SS in a timely manner.

Dermatology residency preparation curriculum: a model for initiating new residents into dermatology clinical care.

Entering dermatology residency is an immersive experience requiring new specialty-specific skills. There is no standard Accreditation Council for Graduate Medical Education (ACGME) protocol for orienting new dermatology residents. We aimed to design, develop, and evaluate a curriculum for incoming first-year dermatology residents focusing on practical introduction to dermatologic clinical care emphasizing ACGME dermatology milestones. A concentrated 8-hour residency preparation course for first-year dermatology residents was designed and developed by faculty. The course encompassed clinical competencies, procedural techniques, and professionalism and collegiality principles. Teaching methods included lectures, video demonstrations, simulated patient experiences, and one-on-one practical instruction. Surveys were distributed before, immediately after, and 6-months following the course from 2016-2018 to assess participants' skill-based confidence level and perceived usefulness of the course. A total of 24 first-year dermatology residents participated in the residency preparation course over 3 years from 2016-2018. Residents' confidence levels in performing dermatology-specific skills immediately increased following the course and continued to increase 6 months into training. The majority of first-year residents "agreed" or "strongly agreed" that the course was helpful for improving clinical competence. Our residency preparation course increased first-year residents' confidence and perceived competence in performing clinical skills related to ACGME dermatology milestones.

Cutaneous microsporidiosis in an immunosuppressed patient.

Microsporidia are a group of obligate intracellular parasites that naturally infect domestic and wild animals. Human microsporidiosis is an increasingly recognized multisystem opportunistic infection. The clinical manifestations are diverse with diarrhea being the most common presenting symptom. We present a 52-year-old woman with a history of amyopathic dermatomyositis complicated by interstitial lung disease managed with mycophenolate mofetil and hydroxychloroquine who presented with a 7-month history of recurrent subcutaneous nodules as well as intermittent diarrhea and chronic sinusitis. A punch biopsy showed superficial and deep lymphocytic and granulomatous dermatitis with focal necrosis. Tissue stains for microorganisms revealed oval 1 to 3 µm spores within the necrotic areas in multiple tissue stains. Additional studies at the Centers for Disease Control and Prevention confirmed cutaneous microsporidiosis. This case is one of very few confirmed examples of cutaneous microsporidiosis reported in the literature.

A Diaphragmatic Hernia and Pericardial Rupture Caused by Blunt Injury of the Chest: A Case Review.

Blunt traumatic diaphragmatic hernias are most commonly seen in combination with other injuries. Right diaphragmatic ruptures with serious pericardium ruptures are relatively rare. The diagnosis of diaphragmatic hernias is not difficult; however, prior to surgery, it is difficult to judge whether pericardium damage has occurred, particularly on the right side. This injury may occur in a critical pathological state in which cardiac tissue is outside the pericardium due to the pericardial defect. Severe hemodynamic disorders or even death may occur if the patient's condition is not diagnosed and treated in a timely manner. The transportation of patients with severe trauma must be performed with extreme caution. It is necessary to weigh a wide range of differential diagnoses in a serious and thorough initial investigation.

Does a Higher Cutoff Value of Lymph Node Retrieval Substantially Improve Survival in Patients With Advanced Gastric Cancer?-Time to Embrace a New Digit.

BACKGROUND: The present study assessed the impact of the retrieval of >25 lymph nodes (LNs) on the survival outcome of patients with advanced gastric cancer after curative-intent gastrectomy. PATIENTS AND METHODS: A total of 5,386 patients who had undergone curative gastrectomy for gastric cancer from 1994 to 2011 were enrolled. The clinicopathological parameters and overall survival (OS) were analyzed according to the number of LNs examined (≤15, n = 916; 16-25, n = 1,458; and >25, n = 3,012). RESULTS: The percentage of patients with >25 LNs retrieved increased from 1994 to 2011. Patients in the LN >25 group were more likely to have undergone total gastrectomy and to have a larger tumor size, poorer tumor differentiation, and advanced T and N stages. Hospital mortality among the LN ≤15, LN 16-25, and LN >25 groups was 6.1%, 2.7%, and 1.7%, respectively (p < .0001). The LN >25 group consistently exhibited the most favorable OS, in particular, with stage II disease (p = .011) when OS was stratified according to tumor stage. Similarly, the LN >25 group had significantly better OS in all nodal stages (from N1 to N3b). The discrimination power of the lymph node ratio (LNR) for the LN ≤15, LN 16-25, and LN >25 groups was 483, 766, and 1,560, respectively. Multivariate analysis demonstrated that the LNR was the most important prognostic factor in the LN >25 group. CONCLUSION: Retrieving more than 25 lymph nodes during curative-intent gastrectomy substantially improved survival and survival stratification of advanced gastric cancer without compromising patient safety. The Oncologist 2017;22:97-106Implications for Practice: D2 lymph node (LN) dissection is currently the standard of surgical management of gastric cancer, which is rarely audited by a third party. The present study, one of the largest surgical series worldwide, has shown that the traditionally recognized retrieval of ≥16 LNs during curative-intent gastrectomy might not be adequate in regions in which locally advanced gastric cancers predominate. The presented data show that retrieval of >25 LNs, which more greatly mimics D2 dissection, improves long-term outcomes and survival stratification without compromising patient safety.

Expression profile of microRNA-200 family in cholangiocarcinoma arising from choledochal cyst.

BACKGROUND AND AIM: The risk of cholangiocarcinoma (cCC) arising from choledochal cyst (CC-CC) is imminent, if the latter not treated appropriately in time. Epithelial-to-mesenchymal transition (EMT) is considered a critical step for various solid cancers, which is regulated by the microRNA-200 (miR-200) family. The aim of this study was to assess the role of miR-200 family in the pathogenesis of CC-CC. METHODS: Sixteen patients with CC-CC were enrolled and 254 patients with conventional cCC served as clinicopathologic controls. Fifty-four cCC were selected to compare the miR-200 family expression and immunohistochemical characteristics. Gain-and loss-of-function studies of miR-200 family were conducted using the cCC cell lines. RESULTS: CC-CC were younger (P < 0.01), more female- predominated (P < 0.01), and rarely associated with lithiasis (P < 0.01) compared with those of cCC. miR-200 family was down-regulated in CC-CC, while miR-200 family was paradoxically up-regulated in cCC (P < 0.01). CC-CC exhibited overt overexpression of mesenchymal markers including ZEB1, Twist, Snail, and vimentin as well an aberrant E-cadherin expression in comparison with cCC. In vitro migration assay showed that cCC cells bearing lower miR-200 s levels exhibited stronger migration ability. Invasive ability of cCC cells was increased after miR-200 s knockdown, accompanied by up-regulation of mesenchymal markers. CONCLUSIONS: CC-CC was characterized by distinct demographics, precipitating factors, and down-regulation of miR-200 family, compared with those of cCC. The pathogenesis of CC-CC might partly link to the silencing of miR-200 family, acting via ZEB1-directed EMT activation.

Gamma deficits as a neural signature of cognitive impairment in children treated for brain tumors.

Cognitive impairment is consistently reported in children treated for brain tumors, particularly in the categories of processing speed, memory, and attention. Although tumor site, hydrocephalus, chemotherapy, and cranial radiation therapy (CRT) are all associated with poorer function, CRT predicts the greatest deficits. There is a particularly high correlation between CRT and slowed information-processing speed. Cortical gamma-band oscillations have been associated with processing behaviorally relevant information; however, their role in the maintenance of cognition in individuals with processing deficits is unclear. We examined gamma oscillations using magnetoencephalography (MEG) in children undergoing CRT to test whether gamma characteristics can be a signature of cognitive impairment in this population. We collected resting-state data as well as data from baseline and active periods during two visual-motor reaction time tasks of varying cognitive loads from 18 healthy children and 20 patients. We found that only high-gamma oscillations (60-100 Hz), and not low-gamma oscillations (30-59 Hz), showed significant group differences in absolute power levels. Overall, compared with healthy children, patients showed the following: (1) lower total high-gamma (60-100 Hz) power during the resting state, as well as during task-related baseline and performance measures; (2) no change in gamma reactivity to increases in cognitive load; and (3) slower processing speeds both inside and outside MEG. Our findings show that high-gamma oscillations are disrupted in children after treatment for a brain tumor. The temporal dynamic of the high-gamma response during information processing may index cognitive impairment in humans with neurological injury.

Endovascular stenting of mesenterico-portal vein stenosis to reduce blood flow through venous collaterals prior to pancreatoduodenectomy.

BACKGROUND: When the mesenterico-portal vein is stenosed due to tumor related compression, venous collaterals develop and flow occurs antegrade towards the portal vein through the collateral tributaries. Undertaking pancreatoduodenectomy for pancreatic cancer in this setting may result in significant blood loss during the process of ligation of these tributaries. DESCRIPTION OF TECHNIQUE: We describe the technique of endovascular stenting of the mesenterico-portal vein to reduce flow within these collateral tributaries and hence blood loss, to facilitate extended pancreatoduodenectomy and vein resection. CONCLUSION: Percutaneous transhepatic placement of endovascular stent into a stenotic mesentero-portal vein facilitates pancreatoduodenectomy by reducing operative time, which would otherwise be required in dealing with the extensive venous collaterals and hence also reducing blood loss.

Expression profile of microRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombus.

OBJECTIVE: The aim of this study was to assess the role of the miR-200 family in the pathogenesis of hepatocellular carcinoma with bile duct tumor thrombus (HCC-BDTT). BACKGROUND: Hepatocellular carcinoma with bile duct tumor thrombus is a challenging condition because of its rarity and dismal prognosis. Epithelial-to-mesenchymal transition (EMT) is considered a critical step in the progression and metastasis of HCC and is regulated by the microRNA-200 (miR-200) family. METHODS: Thirty patients with HCC-BDTT were enrolled and 1240 patients with conventional HCC (cHCC) served as clinicopathologic controls. Sixty age- and sex-matched cHCC patients were selected to compare the miR-200 family expression profile and immunohistochemical characteristics. Gain- and loss-of-function studies of the miR-200 family were conducted using the hepatoma cell lines. RESULTS: Although the mean size of HCC-BDTT was smaller than that of cHCC, the former had a higher incidence of vascular invasion and a poorer long-term survival. The expressions of miR-200c and miR-141 were downregulated in HCC-BDTT (4.5- and 4.8-fold decrease, respectively). Downregulation of both miR-200c and miR-141 independently predicted disease-free survival. The HCC-BDTT, but not cHCC, exhibited overexpression of ZEB1, Twist, transforming growth factor-ß receptor type II, and vimentin, and aberrant E-cadherin expression, indicating EMT. The HCC-BDTT demonstrated increased expression in IL-6 and stemness factor Bmi1, but reduced level of metastasis-suppressive protein, insulin-like growth factor-binding protein 4. The invasive ability of the highly aggressive Mahlavu cell was attenuated by pre-miR-200c+141, whereas the invasive ability of the less aggressive Huh7 cell was enhanced by anti-miR-200c+141. CONCLUSIONS: Simultaneous silencing of miR-200c and miR-141 was likely to be responsible for the development of HCC-BDTT via ZEB1-directed EMT activation and Sec23a-mediated secretome.

Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy.

Typical childhood development is characterized by the emergence of intrinsic connectivity networks (ICNs) by way of internetwork segregation and intranetwork integration. The impact of childhood epilepsy on the maturation of ICNs is, however, poorly understood. The developmental trajectory of ICNs in 26 children (8-17 years) with localization-related epilepsy and 28 propensity-score matched controls was evaluated using graph theoretical analysis of whole brain connectomes from resting-state functional magnetic resonance imaging (fMRI) data. Children with epilepsy demonstrated impaired development of regional hubs in nodes of the salience and default mode networks (DMN). Seed-based connectivity and hierarchical clustering analysis revealed significantly decreased intranetwork connections, and greater internetwork connectivity in children with epilepsy compared to controls. Significant interactions were identified between epilepsy duration and the expected developmental trajectory of ICNs, indicating that prolonged epilepsy may cause progressive alternations in large-scale networks throughout childhood. DMN integration was also associated with better working memory, whereas internetwork segregation was associated with higher full-scale intelligence quotient scores. Furthermore, subgroup analyses revealed the thalamus, hippocampus, and caudate were weaker hubs in children with secondarily generalized seizures, relative to other patient subgroups. Our findings underscore that epilepsy interferes with the developmental trajectory of brain networks underlying cognition, providing evidence supporting the early treatment of affected children.

Changes to memory structures in children treated for posterior fossa tumors.

Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma.

Limited health insurance coverage of injectable neurotoxins and fillers for gender affirmation: a cross-sectional study of Affordable Care Act silver and Medicaid plans.

Background: Injectable neurotoxins and fillers are potential options for facial gender affirmation for transgender/nonbinary patients. However, the largest barrier to access is cost/insurance coverage. Objective: The purpose of this article is to assess the extent to which Affordable Care Act (ACA) silver plans and Medicaid policies cover gender-affirming injectable neurotoxin and filler procedures. Methods: A cross-sectional study of all ACA silver plans and Medicaid policies was performed from June 22 to August 15, 2021. Plan-specific certificates of coverage, clinical policies of insurance providers, and Medicaid documents were evaluated. Results: A total of 915 plans were reviewed (864 ACA silver plans and all 51 Medicaid policies). None potentially covered neurotoxins. Only 72 (71 ACA and 1 Medicaid) potentially covered fillers, specifically collagen injections and lipofilling. Coverage required demonstration of medical necessity or significant variation of physical appearance from the patient's experienced gender. However, of the 71 ACA plans, 69 outlined cosmetic exclusions, possibly nullifying this coverage. Limitations: Data were sourced from publicly available online information in 2021. Additionally, we were unable to confirm explicit coverage of these procedures with insurance companies. Conclusion: The majority of ACA silver and Medicaid plans did not cover gender-affirming neurotoxin or filler procedures, limiting access to this gender-affirming care.

Clinical significance of cefazolin inoculum effect in serious MSSA infections: a systematic review.

Background: The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates? Methods: Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions. Results: Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders. Conclusions: The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature.

CONTEXT.­: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. OBJECTIVE.­: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. DESIGN.­: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. RESULTS.­: The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. CONCLUSIONS.­: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.