Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.

Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein-like 7 (OSBPL7) modulates the expression and function of ATP-binding cassette subfamily A member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Using mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. Although as expected, the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7 deficiency-related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7 deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study sheds new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthens the role of OSBPL7 as a novel therapeutic target.NEW & NOTEWORTHY OSBPL7 and ER stress comprise a central mechanism in glomerular injury. This study highlights a crucial link between OSBPL7 deficiency and ER stress in CKD. OSBPL7 deficiency causes ER stress, leading to podocyte apoptosis. There is a selective effect on lipid homeostasis in that OSBPL7 deficiency affects lipid homeostasis, altering cellular triglyceride but not cholesterol content. The interaction of ER stress and apoptosis supports that ER stress, not reduced autophagy, is the main driver of apoptosis in OSBPL7-deficient podocytes.

Improved survival with immunotherapy for microsatellite unstable colorectal cancer with peritoneal metastases.

BACKGROUND: KEYNOTE-177 demonstrated that immunotherapy was superior to chemotherapy for microsatellite-instability-high (MSI-high) metastatic colorectal cancer. Colorectal cancer with peritoneal metastases (CRPM) has a poorer prognosis than other metastatic sites, with an unclear role of immunotherapy. We evaluated trends in immunotherapy use and overall survival (OS). METHODS: Patients with CRPM and MSI testing were identified in the National Cancer Database (2016-2020). We evaluated immunotherapy use by year and associated patient/hospital factors. OS was compared for immunotherapy versus chemotherapy, cytoreductive surgery (CRS), and immunotherapy plus CRS. RESULTS: Among 15 322 CRPM patients, 7072 (46.2%) patients had documented MSI testing, with 819 (11.6%) MSI-high. Ninety-eight MSI-high patients received immunotherapy alone (12.3%), increasing from 0% in 2016 to 19.1% in 2020 (p < 0.01). On multivariable analysis, only higher comorbidity was associated with immunotherapy (OR: 2.83 [1.22-6.52]). Two-year OS with immunotherapy versus chemotherapy was 64.2% versus 54.1% (p < 0.05). In patients receiving CRS plus systemic therapy (N = 96), 2-year OS was 68.4%. Among patients who underwent immunotherapy and CRS versus immunotherapy alone, 2-year OS was 80.0% versus 60.0% (p = 0.14). CONCLUSIONS: Immunotherapy was associated with significantly better survival compared to chemotherapy in MSI-high CRPM. Two-year OS with systemic + CRS was 68.4%. Despite its role in guiding treatment, MSI testing remains low for these patients.

Oncologic outcomes and survival of modern surgical approaches for gastric gastrointestinal stromal tumor (GIST).

BACKGROUND: Studies have demonstrated comparable outcomes between laparoscopic and open resection of gastrointestinal stromal tumor (GIST). We sought to compare outcomes among robotic, laparoscopic, and open resection of gastric GIST in the era of expanding minimally invasive surgery. METHODS: A retrospective analysis was performed of adult patients with gastric GIST undergoing definitive surgery using the National Cancer Database from 2010 to 2020, excluding cases converted to open. Patients were stratified into minimally invasive surgery (MIS), (combined robotic (R) and laparoscopic (L)), and open (O). Hospital length of stay (LOS), 30-day mortality, 90-day mortality, and margin status were assessed. Subgroup analysis was performed to evaluate outcomes between R and L cohorts. Entropy balancing was used to adjust for intergroup differences. Kaplan-Meier survival estimates were used to compare unadjusted 5-year survival. RESULTS: Of the 15,022 patients (R = 10.4%, L = 44.3%, O = 45.3%), 63.2% were stage I and 70.6% underwent partial gastrectomy. MIS approach was associated with shorter hospital LOS (ß: - 2.58; 95% CI: - 2.82 to - 2.33) and lower odds of 30-day (OR 0.45; 95% CI: 0.30-0.68) and 90-day mortality (OR 0.54; 95% CI: 0.39-0.74) compared to O. Likelihood of R0 resection similar between groups (OR 1.00; 95% CI: 0.88-1.14). Hospital LOS (ß: + 0.25; 95% CI: - 0.14-0.64), odds of 30-day (OR 0.99; 95% CI: 0.40-2.46) and 90-day mortality (OR 0.89; 95% CI: 0.47-1.70), and rate of R0 resection (OR 1.02; 95% CI: 0.82-1.27) were comparable between R and L cohorts. Compared to O, MIS approach was associated with improved 5-year OS (log rank p < 0.001). Overall survival was not significantly different between R and L (log rank p = 0.44). CONCLUSION: These findings suggest that MIS approach may be considered for resection of gastric GIST in select patients. Among patients receiving an MIS approach, the robotic technique can be considered an oncologically safe alternative to laparoscopic surgery.

Timeliness of Multimodal Care for At-Risk Breast Cancer Patients at a Safety Net Institution.

INTRODUCTION: Because limited data exist, we sought to evaluate timeliness of multimodal treatments in a safety net breast cancer population. METHODS: Breast cancer patients treated at a safety net hospital from 2016 to 2020 were analyzed retrospectively. Time intervals were defined as primary time (PT) from diagnosis to initiation of primary intervention, secondary time (ST) from completion of primary to initiation of secondary intervention, and tertiary time (TT) from completion of secondary to initiation of tertiary intervention. Variables included primary language, insurance type, and race. RESULTS: Of 223 patients, 99 (44.4%) primarily spoke Spanish, 29 (13.0%) were of Black race, and 184 (82.5%) had Medicaid or uninsured status. Median (IQR) age at diagnosis was 55 (48-62) years. Primary intervention was surgical in 127/216 (58.8%); secondary intervention was systemic in 38/169 (22.5%); and tertiary intervention was radiation in 67/80 (83.8%). Overall, median days (IQR) for PT were 69 (53, 98), ST were 65 (42, 95), and TT were 69 (43, 88). PT was significantly longer in Black [105 (76, 142) days] patients compared to non-Hispanic White patients [68 (51, 107) days, P = 0.031)] and White Hispanic patients [65 (53,91) days, P = 0.014]. There were no significant differences in PT, ST, or TT by spoken language or insurance type. CONCLUSIONS: Black patients remain at risk due to prolonged time to intervention. Spanish-speaking status was not associated with inferior timeliness or completion of multimodal care at a safety net hospital. Identifying safety net hospital barriers to achieving benchmarks for timely completion of all phases of multimodal care warrants further attention.

Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases.

BACKGROUND: The signaling molecule stimulator of IFN genes (STING) was identified as a crucial regulator of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-STING pathway, and this signaling pathway regulates inflammation and energy homeostasis under conditions of obesity, kidney fibrosis, and AKI. However, the role of STING in causing CKD, including diabetic kidney disease (DKD) and Alport syndrome, is unknown. METHODS: To investigate whether STING activation contributes to the development and progression of glomerular diseases such as DKD and Alport syndrome, immortalized human and murine podocytes were differentiated for 14 days and treated with a STING-specific agonist. We used diabetic db/db mice, mice with experimental Alport syndrome, C57BL/6 mice, and STING knockout mice to assess the role of the STING signaling pathway in kidney failure. RESULTS: In vitro, murine and human podocytes express all of the components of the cGAS-STING pathway. In vivo, activation of STING renders C57BL/6 mice susceptible to albuminuria and podocyte loss. STING is activated at baseline in mice with experimental DKD and Alport syndrome. STING activation occurs in the glomerular but not the tubulointerstitial compartment in association with autophagic podocyte death in Alport syndrome mice and with apoptotic podocyte death in DKD mouse models. Genetic or pharmacologic inhibition of STING protects from progression of kidney disease in mice with DKD and Alport syndrome and increases lifespan in Alport syndrome mice. CONCLUSION: The activation of the STING pathway acts as a mediator of disease progression in DKD and Alport syndrome. Targeting STING may offer a therapeutic option to treat glomerular diseases of metabolic and nonmetabolic origin or prevent their development, progression, or both.

Self-Sorting Governed by Chelate Cooperativity.

Self-sorting phenomena are the basis of manifold relevant (bio)chemical processes where a set of molecules is able to interact with no interference from other sets and are ruled by a number of codes that are programmed in molecular structures. In this work, we study, the relevance of chelate cooperativity as a code for achieving high self-sorting fidelities. In particular, we establish qualitative and quantitative relationships between the cooperativity of a cyclic system and the self-sorting fidelity when combined with other molecules that share identical geometry and/or binding interactions. We demonstrate that only systems displaying sufficiently strong chelate cooperativity can achieve quantitative narcissistic self-sorting fidelities either by dictating the distribution of cyclic species in complex mixtures or by ruling the competition between the intra- and intermolecular versions of a noncovalent interaction.

Spanish-Speaking Status: A Protective Factor in Colorectal Cancer Presentation at a Safety-Net Hospital.

INTRODUCTION: Lower screening rates and poorer outcomes for colorectal cancer have been associated with Hispanic ethnicity and Spanish-speaking status, respectively. METHODS: We reviewed sequential colorectal cancer patients evaluated by the surgical service at a safety-net hospital (SNH) (2016-2019). Insurance type, stage, cancer type, surgery class (elective/urgent), initial surgeon contact setting (outpatient clinic/inpatient consult), operation (resection/diversion), and follow-up were compared by patient-reported primary spoken language. RESULTS: Of 157 patients, 85 (54.1%) were men, 91 (58.0%) had colon cancer, 67 (42.7%) primarily spoke Spanish, and late stage (III or IV) presentations occurred in 83 (52.9%) patients. The median age was 58 y, cancer resection was completed in 48 (30.6%) patients, and 51 (32.5%) patients were initially seen as inpatient consults. On univariate analysis, Spanish-speaking status was significantly associated with female sex, Medicaid insurance, being seen as an outpatient consult, and undergoing elective and resection surgery. On multivariable logistic regression, Spanish-speaking patients had higher odds of having Medicaid insurance (AOR 2.28, P = 0.019), receiving a resection (AOR 3.96, P = 0.006), and undergoing an elective surgery (AOR 3.24, P = 0.025). Spanish-speaking patients also had lower odds of undergoing an initial inpatient consult (AOR 0.34, P = 0.046). CONCLUSIONS: Spanish-speaking status was associated with a lower likelihood of emergent presentation and need for palliative surgery among SNH colorectal cancer patients. Further research is needed to determine if culturally competent infrastructure in the SNH setting translates into Spanish-speaking status as a potentially protective factor.

Adsorption of acrolein and its hydrogenation products on Cu(111).

The adsorption of acrolein and its hydrogenation products propanal, 1-propanol, and 2-propenol on Cu(111) was studied by reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD). The experimental RAIR spectra were obtained by adsorbing multilayers of each molecule at 85 K and then annealing the surface up to 200 K to desorb the multilayer and produce the most stable monolayer structure on the surface. Each of the four molecules adsorbs weakly to the surface and desorbs at temperatures below 225 K. Compared to acrolein and propanal, the two alcohols, 2-propenol and 1-propanol, have notably higher desorption temperatures and broadened and redshifted O-H stretches that reveal strong hydrogen bonding in the multilayers. Upon annealing to 160 K, the OH stretches of both 2-propenol and 1-propanol disappear, indicating the hydrogen bonding in the multilayers is not present in the monolayers. For 2-propenol, the hydrogen bonding in the multilayer correlates with the observation of the CC stretch at 1647 cm-1, which is invisible for the monolayer. This suggests that the CC bond is parallel to the surface for monolayer coverages of 2-propenol. Similarly, for propanal, the CO stretch peak at 1735 cm-1 compared to those at 1671 and 1695 cm-1 is very weak at low coverages but becomes the most prominent peak for the multilayer, indicating a change in molecular orientation. For acrolein, the out-of-plane bending modes are more intense than the CO stretch at submonolayer coverages, indicating that the molecular plane is mainly parallel to the surface. In contrast, the opposite intensity trend was observed for multilayer acrolein, suggesting that the CO bonds are tilted away from the surface.

Improvement in Breast Reconstruction Disparities following Medicaid Expansion under the Affordable Care Act.

BACKGROUND:  Under the Affordable Care Act, Medicaid expansion effective 1 January 2014 aimed to increase access to health care. We sought to determine the association of Medicaid expansion with disparities in utilization of breast reconstruction. METHODS: Non-Hispanic Black (NHB) and White (NHW) breast cancer patients undergoing mastectomy +/- reconstruction between 2010 and 2017 were selected from the National Cancer Database. Annual trends for utilization of breast reconstruction by race, income, and education were evaluated by Medicaid expansion status using difference-in-differences regression analyses. Medicaid expansion was categorized by expansion date as early (2010-2013), 2014 (1/2014), late (after 1/2014), or no expansion. RESULTS: Of 443,607 patients, 36.3% (n = 161,128) underwent reconstruction, 13.1% (n = 58,249) were NHB, 16.8% (n = 74,430) had median income < $40,227, and 17.1% (n = 75,718) were in the lowest education quartile. In non-expansion states, lower proportions of NHB patients underwent reconstruction than NHW patients in all years, with the smallest disparity (NHB% - NHW%) (- 6.4%) in 2017. Decreases in disparities between NHB and NHW patients were seen with the smallest difference observed in 2014 (- 2.5%) in early-expansion states, in 2017 (- 0.7%) in 1/2014 expansion states, and in 2017 (- 4.5%) in late-expansion states. Similar findings for convergence of reconstruction utilization rates for the lowest two education levels and lowest two income quartiles were found with Medicaid expansion, with no convergence seen in non-expansion states over the study period. CONCLUSIONS: Some improvement in breast reconstruction disparities followed Medicaid expansion. Failure to improve parity without Medicaid expansion should be a consideration with any modifications to Medicaid access.

Dinucleoside-Based Macrocycles Displaying Unusually Large Chelate Cooperativities.

High-fidelity production of a single self-assembled species in competition with others relies on achieving strong chelate cooperativities, which can be quantified by the effective molarity parameter. Therefore, supramolecular systems displaying very high effective molarities are reliably formed in a wide range of experimental conditions and exhibit "all-or-none" phenomena, meaning that the assembly is either fully formed or fully dissociated into the corresponding monomeric components. We summarize here our efforts in the study and characterization of one of these synthetic systems exhibiting record chelate cooperativities: the self-assembly of rod-like dinucleoside molecules into tetrameric macrocycles through hydrogen-bonding Watson-Crick interactions.

The influence of palladium on the hydrogenation of acetylene on Ag(111).

We have used reflection absorption infrared spectroscopy (RAIRS) and temperature programmed reaction (TPR) to study the selective hydrogenation of acetylene on both a clean Ag(111) surface and on a Pd/Ag(111) single-atom-alloy surface. The partial hydrogenation of acetylene to ethylene is an important catalytic process that is often carried out using PdAg alloys. It is challenging to study the reaction with ultrahigh vacuum techniques because H2 does not dissociate on Ag(111), and while H2 will dissociate at Pd sites, H-atom spillover from Pd to Ag sites does not generally occur. We bypassed the H2 dissociation step by exposing the surfaces to atomic hydrogen generated by the hot filament of an ion gauge. We find that hydrogen atoms react with acetylene to produce adsorbed ethylene at 85 K, the lowest temperature studied. This is revealed by the appearance of a RAIRS peak at 950 cm-1 due to the out-of-plane wagging mode of adsorbed ethylene when acetylene is exposed to a surface on which H atoms are pre-adsorbed. The formation of both ethylene and ethane are detected with TPR, but no acetylene coupling products, such as benzene, were found. From quantitative analysis of the TPR results, the percent conversion and selectivities to ethylene and ethane were determined. Low coverages of Pd enhance the conversion but do so mainly by increasing ethane formation.

Adsorption properties of acrolein, propanal, 2-propenol, and 1-propanol on Ag(111).

Reflection absorption infrared spectroscopy and temperature programmed desorption were used to study the adsorption of acrolein, its partial hydrogenation products, propanal and 2-propenol, and its full hydrogenation product, 1-propanol on the Ag(111) surface. Each molecule adsorbs weakly to the surface and desorbs without reaction at temperatures below 220 K. For acrolein, the out-of plane bending modes are more intense than the C[double bond, length as m-dash]O stretch at all coverages, indicating that the molecular plane is mainly parallel to the surface. The two alcohols, 2-propenol and 1-propanol, have notably higher desorption temperatures than acrolein and display strong hydrogen bonding in the multilayers as revealed by a broadened and redshifted O-H stretch. For 1-propanol, annealing the surface to 180 K disrupts the hydrogen-bonding to produce unusally narrow peaks, including one at 1015 cm-1 with a full width at half maximum of 1.1 cm-1. This suggests that 1-propanol forms a highly orderded monolayer and adsorbs as a single conformer. For 2-propenol, hydrogen bonding in the multilayer correlates with observation of the C[double bond, length as m-dash]C stretch at 1646 cm-1, which is invisible for the monolayer. This suggests that for monolayer coverages, 2-propenol bonds with the C[double bond, length as m-dash]C bond parallel to the surface. Similarly, the C[double bond, length as m-dash]O stretch of propanal is very weak for low coverages but becomes the largest peak for the multilayer, indicating a change in orientation with coverage.

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces.

Dipeptides self-assemble into supramolecular structures showing plenty of applications in the nanotechnology and biomedical fields. A set of Fmoc-dipeptides with different aminoacid sequences has been synthesized and their self-assembly at fluid interfaces has been assessed. The relevant molecular parameters for achieving an efficient 2D self-assembly process have been established. The self-assembled nanostructures of Fmoc-dipeptides displayed significant chirality and retained the chemical functionality of the aminoacids. The impact of the sequence on the final supramolecular structure has been evaluated in detail using in situ characterization techniques at air/water interfaces. This study provides a general route for the 2D self-assembly of Fmoc-dipeptides.

OSCANN: Technical Characterization of a Novel Gaze Tracking Analyzer.

Eye-movement analysis has grown exponentially in recent decades. The reason is that abnormalities in oculomotor movements are usually symptoms of injuries in the nervous system. This paper presents a novel regulated solution named OSCANN. OSCANN aims at providing an innovative tool for the control, management and visualization of oculomotor neurological examinations. This solution utilizes an eye-tracker sensor based on video electro-oculography (VOG) technology to capture eye movements and store them in video files. Such a sensor can store images at a rate of 100 frames per second. A characterization study was performed using twenty-two volunteers (13 male, 9 female, ages 22-45 years, mean 29.3 years, SD = 6.7) to assess the accuracy and precision specifications of OSCANN during oculomotor movement analysis. The accuracy was evaluated based on the offset, whereas precision was estimated with Root Means Square (RMS). Such a study reported values lower than 0.4 ∘ and 0.03 ∘ of accuracy and precision, respectively. These results suggest that OSCANN can be considered as a powerful tool to measure oculomotor movement alterations involved in some neurological disease progression.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

BACKGROUND: The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. METHODS: A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. RESULTS: Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). CONCLUSION: Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. KEY POINTS: • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

New insights in the analysis of blunt force trauma in human bones. Preliminary results.

Determining the time of injury is an important but still a challenging task in forensic anthropology. In literature, many descriptions can be found to make a distinction between perimortem and postmortem fractures. Characteristics that are more related to fractures in fresh conditions, however, are not extensively investigated. This study compared 28 perimortem fractures from autopsies and 21 both fresh and dry experimentally reproduced human bone fractures. Preliminary results showed the following five distinct traits that might be related to perimortem conditions: layered breakage, bone scales, crushed margins, wave lines and flakes with matching flake defect. These distinct traits might not only be good estimators of perimortem trauma but also may be an indicator of trauma in intra vitam conditions, especially related with muscular reaction to injury. Furthermore, layered breakage seems to be a good trait to infer the biomechanics of trauma.

[Pedestrian head injury biomechanics and damage mechanism. Pedestrian protection automotive regulation assessment]. / Biomecánica y mecanismo de producción del traumatismo cráneo-encefálico en el peatón atropellado. Evaluación de la normativa actual en la automoción.

INTRODUCTION: Pedestrian-vehicle collisions are a leading cause of death among motor vehicle accidents. Recently, pedestrian injury research has been increased, mostly due to the implementation of European and Japanese regulations. This research presents an analysis of the main head injury vehicle sources and injury mechanisms observed in the field, posteriorly the data are compared with the current pedestrian regulations. METHODS: The analysis has been performed through an epidemiologic transversal and descriptive study, using the Pedestrian Crash Data Study (PCDS) involving 552 pedestrians, sustaining a total of 4.500 documented injuries. RESULTS: According to this research, the hood surface is responsible for only 15,1% of all the head injuries. On the other hand, the windshield glazing is responsible for 41,8%. In case of sedan vehicles the head impact location exceeds what is expected in the current regulation, and therefore no countermeasures are applied. From all the head injuries sustained by the pedestrians just 20% have the linear acceleration as isolated injury mechanism, 40% of the injuries are due to rotational acceleration. CONCLUSIONS: In this research, the importance of the rotational acceleration as injury mechanism, in case of pedestrian-vehicle collision is highlighted. In the current pedestrian regulation just the linear acceleration is addressed in the main injury criteria used for head injury prediction.

Perforating elastic fibers ('elastic fiber trapping') in the differentiation of keratoacanthoma, conventional squamous cell carcinoma and pseudocarcinomatous epithelial hyperplasia.

Keratoacanthoma (KA), an epithelial neoplasm occurring in sun-exposed skin of the elderly, is considered a well-differentiated form of conventional squamous cell carcinoma (SCC) that often follows a course of spontaneous regression. Distinguishing KA from conventional SCC or pseudocarcinomatous epithelial hyperplasia ensures proper diagnosis, treatment and management. For some time, perforating elastic fibers have been utilized in differentiating KA from SCC. This phenomenon may also occur in association with scars and hypertrophic lupus erythematosus (LE). To assess the diagnostic utility of perforating elastic fibers, we compared their incidence in KA, SCC, scars with overlying pseudocarcinomatous hyperplasia, hypertrophic LE, hypertrophic lichen planus (LP) and lichen simplex chronicus (LSC). A retrospective case search identified 359 lesions and the presence of perforating elastic fibers was evaluated using routinely stained sections. This phenomenon was documented in all studied groups except hypertrophic LP. The incidence was found to be 71% in KA, 37% in SCC, and was lowest in inflammatory conditions with associated pseudocarcinomatous hyperplasia (hypertrophic LP 0%, hypertrophic LE 5.9% and LSC 28.2%). The observed frequency in pseudocarcinomatous hyperplasia overlying scars (57.8%) vs. KA (71%) was not statistically different. Although elastic fiber trapping has potential value as a diagnostic criterion for KA, dermatopathologists should consider its limitations. Its diagnostic utility was greatest in distinguishing KA from hypertrophic LE and hypertrophic LP. Conversely, elastic trapping is not helpful differentiating pseudocarcinomatous hyperplasia from recurrent/persistent KA following surgery.

Laparoscopic Conversion to Open Cholecystectomy: Is Incidental Gallbladder Cancer Any Different?

BACKGROUND: A majority of gallbladder cancers present incidentally. Operative risk factors and outcomes for laparoscopic converted to open cholecystectomy in incidental gallbladder cancer are not well characterized. METHODS: Patients with incidental gallbladder cancer and acute cholecystitis undergoing laparoscopic cholecystectomy and conversion to open cholecystectomy in the National Surgical Quality Improvement Program (NSQIP) database of the American College of Surgeons (ACS) from 2010-2019 were reviewed. The primary endpoint was risk factors for conversion to open cholecystectomy in incidental gallbladder cancer. Chi-squared test or Fisher's exact test was used for categorical variables. Continuous variables were compared using the Mann-Whitney U test. RESULTS: A total of 5,789 patients undergoing laparoscopic cholecystectomy were identified, of which, 50 (0.9%) had incidental gallbladder cancer. For incidental gallbladder cancer patients, there were no differences in preoperative profile and risk factors between laparoscopic and converted to open cholecystectomy groups. Incidental carcinoma patients undergoing conversion to open cholecystectomy had lower preoperative sodium levels than the laparoscopic cholecystectomy group (P=0.007). Hospital length of stay (days) was longer for those with a conversion to open cholecystectomy for incidental carcinoma compared to non-conversion, 14 (10.8, 18.8) vs 2 (0.3, 5) (P=0.004). The patients converted to open cholecystectomy also had higher rates of postoperative sepsis (50% vs 0%, P<0.001) and reoperation than the laparoscopic cohort (50% vs 2.2%, P<0.001). Readmission and mortality rates, among other complications, were not significantly different between both surgical approaches in incidental gallbladder cancer patients. CONCLUSIONS:  Patients with conversion to open cholecystectomy had worse outcomes including longer hospital stays and higher rates of sepsis and reoperation. It remains difficult to predict which incidental gallbladder patients will require a conversion to open surgery. Further study examining whether more complicated recovery results in worse oncologic outcomes is warranted.

Small non-coding RNAs and pancreatic ductal adenocarcinoma: Linking diagnosis, pathogenesis, drug resistance, and therapeutic potential.

This review comprehensively investigates the intricate interplay between small non-coding RNAs (sncRNAs) and pancreatic ductal adenocarcinoma (PDAC), a devastating malignancy with limited therapeutic options. Our analysis reveals the pivotal roles of sncRNAs in various facets of PDAC biology, spanning diagnosis, pathogenesis, drug resistance, and therapeutic strategies. sncRNAs have emerged as promising biomarkers for PDAC, demonstrating distinct expression profiles in diseased tissues. sncRNA differential expression patterns, often detectable in bodily fluids, hold potential for early and minimally invasive diagnostic approaches. Furthermore, sncRNAs exhibit intricate involvement in PDAC pathogenesis, regulating critical cellular processes such as proliferation, apoptosis, and metastasis. Additionally, mechanistic insights into sncRNA-mediated pathogenic pathways illuminate novel therapeutic targets and interventions. A significant focus of this review is dedicated to unraveling sncRNA mechanisms underlying drug resistance in PDAC. Understanding these mechanisms at the molecular level is imperative for devising strategies to overcome drug resistance. Exploring the therapeutic landscape, we discuss the potential of sncRNAs as therapeutic agents themselves as their ability to modulate gene expression with high specificity renders them attractive candidates for targeted therapy. In summary, this review integrates current knowledge on sncRNAs in PDAC, offering a holistic perspective on their diagnostic, pathogenic, and therapeutic relevance. By elucidating the roles of sncRNAs in PDAC biology, this review provides valuable insights for the development of novel diagnostic tools and targeted therapeutic approaches, crucial for improving the prognosis of PDAC patients.