Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

The use of autogenous tooth bone graft is an efficient method of alveolar ridge preservation - meta-analysis and systematic review.

BACKGROUND: Ridge resorption following tooth extraction may be reduced by alveolar ridge preservation (ARP). Previous randomized clinical trials and systematic reviews have suggested that autogenous tooth bone graft (ATB) can be an effective alternative material for ARP. However, the results are heterogeneous. Therefore, our research aimed to evaluate the efficacy of ATB in ARP. METHODS: A systematic search was conducted in Cochrane Library, Embase, MEDLINE and Scopus for studies published from inception to 31 November 2021. We searched searched for randomized, non-randomized controlled trials and case series reporting on ATB use for ARP. The primary outcome was the ridge width difference pre- and post-surgery, measured in millimetres (mm) measured on CBCT (cone beam computed tomography). The secondary outcomes were the histological results. We followed the PRISMA2020 recommendations for reporting our systematic review and meta-analysis. RESULTS: The analysis included eight studies for the primary and six for the secondary outcomes. The meta-analysis revealed a positive ridge preservation effect with a pooled mean difference ridge width change of -0.72 mm. The pooled mean residual graft proportion was 11.61%, and the newly formed bone proportion was 40.23%. The pooled mean of newly formed bone proportion was higher in the group where ATB originated from both the root and crown of the tooth. CONCLUSIONS: ATB is an effective particulate graft material in ARP. Complete demineralization of the ATB tends to decrease the proportion of newly formed bone. ATB can be an attractive option for ARP. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD42021287890).

Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Topical pharmacotherapy for ocular surface squamous neoplasia: systematic review and meta-analysis.

Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.

Estimation of the timing of BAP1 mutation in uveal melanoma progression.

Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 µm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.

Comparison of various intraocular lens formulas using a new high-resolution swept-source optical coherence tomographer.

PURPOSE: To compare vergence, artificial intelligence, and combined intraocular lens (IOL) calculation formulas using a new swept-source optical coherence tomographer (SS-OCT) and to analyze their performance based on manifest and estimated refractive outcomes of cataract surgery. SETTING: Department of Ophthalmology, University of Pécs Medical School, Pécs, Hungary. DESIGN: Retrospective data analysis. METHODS: Optical biometry readings of patients who underwent uneventful cataract removal and implantation of a monofocal acrylic IOL were used to predict IOL power with Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, Radial Basis Function (RBF) 2.0, Kane, Ladas Super Formula, and SRK/T. All the implanted IOLs were calculated by using the Haigis formula. The arithmetic prediction error and median and mean absolute refractive errors for all formulas were computed. The percentage of eyes within ±0.25 diopters (D), ±0.50 D, and ±1.0 D of prediction error was calculated. RESULTS: A total of 95 eyes of 95 patients with a mean age of 68.80 ± 7.57 years were included. There was a statistically significant difference in absolute prediction error across the 8 IOL calculation formulas (P < .0001). Haigis showed the lowest mean absolute error, and it differed significantly from the BUII, Hoffer Q, Holladay 1, Ladas, RBF 2.0, and SRK/T formulas (P < .05). In terms of eyes within ±0.25 D, ±0.50 D, and ±1.0 D of prediction error, the Haigis formula showed the overall best performance. CONCLUSIONS: The results indicated that a recently developed SS-OCT provided accurate ocular biometry measurements before cataract surgery, and the Haigis formula incorporated in its software enabled precise calculation of IOL refractive power.

Differential diagnosis and management of melanocytic lesions of the ocular surface / [Pigmentsejt-eredetu szemfelszíni elváltozások differenciáldiagnózisa és kezelése]

Our purpose is to summarize the actual knowledge about melanocytic lesions of the ocular surface (conjunctival nevus, primary acquired melanosis and conjunctival melanoma),especially their clinical appearance, differential diagnosis and treatment. Conjunctival nevus is the most common benign, conjunctival melanocytic lesion. Primary acquired melanosis mainly presents in middle-aged or elderly individuals, characterized by proliferation of melanocytes of the conjunctival epithelial layer. Conjunctival melanoma is a rare tumor, it is the second most common malignant ocular surface tumor after ocular surface squamous neoplasia and the third most common ocular malignancy following choroideal malignant melanoma and ocular surface squamous neoplasia. Early recognition and proper management of conjunctival melanoma is indispensable due to its high malignant and metastatic potential. Due to frequent recurrences, the knowledge and use of intra- and postoperative adjuvant treatment modalities, and regular follow-up are necessary. Orv Hetil. 2020; 161(15): 563­574.

Scleral Thinning after Transscleral Biopsy for Uveal Melanoma Using Lamellar Scleral Flap.

PURPOSE: The purpose of the study is to describe the clinical history and histopathologic findings of three cases of scleral thinning after lamellar scleral flap, including one case with confirmed extraocular tumor extension. METHODS: The medical records and pathology specimens of three patients with scleral thinning after biopsy and plaque brachytherapy and lamellar scleral flap performed during a transscleral biopsy were reviewed. RESULTS: The first two patients developed scleral thinning and visible pigmentation, but had tumors that were regressing in size on ultrasound. The two patients were followed by serial observation. The third patient exhibited scleral thinning and evidence of tumor growth on ultrasound, raising the suspicion for extraocular tumor extension. Histopathologic examination of the enucleated eye confirmed extrascleral tumor extension and showed necrotic and intact melanoma with associated pigmented macrophages. CONCLUSIONS: Patients with scleral flaps created for biopsy of uveal melanoma are at risk for scleral thinning and extrascleral extension of tumor recurrence through the flap.

Association of Uveal Melanoma Metastatic Rate With Stochastic Mutation Rate and Type of Mutation.

Importance: It is necessary to understand the mechanisms of metastasis of uveal melanoma to advise patients and develop treatments for this tumor. Objective: To examine the stochastic properties of primary uveal melanoma including the mutation rate as a function of tumor size and metastatic rate relative to the type of mutation. Design, Setting, and Participants: We computed the mutation rate in different sized uveal melanomas using previously published large data sets. Tumor volume was estimated using the spherical cap method. We also calculated the metastatic rate using an updated data set of patients with uveal melanoma with known mutations in BAP1, SF3B1, and EIF1AX provided by the Rotterdam Ocular Melanoma Study Group. Data were analyzed from 2 studies, one taking place from August 25, 1970, to August 27, 2008, and the other taking place between 1993 and 2013. Data were analyzed between 2016 and 2017. Main Outcomes and Measures: Mutation rates and metastic rates. Results: Based on the 5-year metastatic rates, mutation rates ranged from 1.09 × 10-8 to 7.86 × 10-7 per cell division, using our calculation algorithm. A higher mutation rate was found for tumors with smaller thicknesses. EIF1AX mutations were not exclusive of other mutations because 2 cases with EIF1AX mutations and metastasis also had BAP1 mutations. None of the tumors with only an EIF1AX mutation metastasized. After plotting the yearly metastatic rate vs time after treatment, we observed a small peak at 1 year and a large peak at 3.5 years after treatment for BAP1 mutations, with peaks between 2 and 3 years and at 7 years for SF3B1 mutations. Conclusions and Relevance: We observed a higher mutation rate for smaller tumors, which may be explained by a greater number of cell divisions occurring during the expansion phase of smaller uveal melanomas. Regarding time to clinically detected metastases, the first 2 peaks appear to be associated with BAP1-mutated tumors and the late peak to SF3B1-mutated tumors.

[Femtosecond laser-assisted keratoplasty]. / Femtoszekundumlézeres keratoplasztika.

INTRODUCTION AND AIM: To present our results on femtosecond laser-assisted penetrating keratoplasty. PATIENTS AND METHOD: Twenty-five eyes of 25 patients underwent surgery with the following indications: pseudophakic bullous keratopathy (n = 10), keratoconus (n = 4), corneal dystrophy (n = 5), corneal scar (n = 4), band keratopathy (n = 2). Trephination of both the donor and recipient corneas were performed with VisuMax femtosecond laser device (Carl Zeiss Meditec AG, Jena, Germany). In each case, trephinaton of the donor tissue was performed first with an artificial anterior chamber (Moria, Antony, France). For the surgical plan and in the postoperative period we obtained different corneal imaging modalities. The corneal power was measured with corneal topography (TMS-4, Tomey, Nürnberg, Germany) and Scheimpflug tomography (Pentacam HR, Oculus, Wetzlar, Germany). The central corneal thickness was evaluated with Pentacam and corneal endothelial cell density was measured with specular microscopy (SP3000P, Topcon, Tokyo, Japan). The corneal structure was imaged with anterior segment optical coherence tomography (Visante, Carl Zeiss Meditec AG). All measurements were performed every 3 months in the first year and yearly thereafter. The follow-up period was 3 years in every case. RESULTS: The corrected decimal visual acuity showed an improvement from a preoperative 0.1 ± 0.1 to a postoperative 0.71 ± 0.18 value at the end of the follow-up period (p = 0.03). All corneal grafts maintained their transparency, there were no immunological rejection during the follow-up. Topographical astigmatism was 4.5 ± 3.1 D in the first month; it showed a decreasing tendency, but there was no significant change in the 3-year period. The mean central corneal thickness changed with 60 µm during the follow-up; there was no significant difference between the first month (564 ± 52 µm) and the third year (596 ± 64 µm) mean pachymetry values (p = 0.1). The mean endothelial cell density decreased first, then remained stable, but did not change significantly from the first (1641 ± 433 cells/mm2) to the last postoperative visit (1220 ± 391 cells/mm2, p = 0.1). CONCLUSIONS: In the case of femtosecond laser-assisted penetrating keratoplasty, trephination of the donor and recipient cornea is performed automatically in a highly precise fashion. The accurate cutting surface provides excellent wound apposition and healing. Both anatomical and functional rehabilitation of patients undergoing surgery are favourable and fast. Orv Hetil. 2018; 159(17): 671-676.

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis.

PURPOSE: To examine the BRCA1-associated protein-1 (BAP1) expression of primary uveal melanomas without and with metastasis, and to analyze the correlation between the BAP1 immunoreactivity of primary uveal melanoma and other clinicopathologic features. DESIGN: Retrospective case series. PARTICIPANTS: Forty patients with uveal melanoma (mean age, 57.98±14.75 years) were included in this analysis, of whom 20 had no metastatic disease and 20 had metastasis. METHODS: Medical records and histology slides of patients with primary uveal melanoma treated by enucleation were reviewed. BAP1 expression was evaluated by immunohistochemical staining of formalin-fixed, paraffin-embedded sections. Immunoreactivity in the nucleus and cytoplasm were graded by estimating the percentage of primary tumor cells showing a positive staining of their nucleus or cytoplasm per 1 high-power field 200× (grades 0-3). MAIN OUTCOME MEASURES: Tumor size, histologic features, nuclear and cytoplasmic BAP1 immunoreactivity grade, and patient outcome, including development of metastasis. RESULTS: Significantly lower (P = 0.025) nuclear BAP1 immunoreactivity was observed in the metastatic melanoma group. Greater tumor thickness, basal diameter, and more advanced TNM stage were associated with an increased odds ratio of developing metastasis (P < 0.05). In addition, tumors with a higher proportion of cells expressing nuclear BAP1 had decreased odds of developing metastatic disease in a multivariate model (P = 0.042). Metastasis-free survival was significantly longer in patients with uveal melanoma with high nuclear BAP1 stain (P = 0.004). CONCLUSIONS: Time to metastasis differs in patients with primary uveal melanoma with different grades of nuclear BAP1 immunoreactivity. Nuclear BAP1 stain is the only significant independent predictor of metastatic disease in this study. Our data support the role of BAP1 immunohistochemical staining of primary uveal melanoma to evaluate metastatic risk.

Radiologic and Histopathologic Correlation of Different Growth Patterns of Metastatic Uveal Melanoma to the Liver.

PURPOSE: The purpose of this study was to correlate magnetic resonance imaging (MRI) radiographic results with histopathologic growth patterns of metastatic uveal melanoma (UM) to the liver. DESIGN: Clinicopathologic correlation. PARTICIPANTS: Patients with metastatic UM to the liver. METHODS: A retrospective review of MRI images of patients with metastatic UM to the liver at a single institution between 2004 and 2016 was performed. The MRI growth patterns were classified as nodular or diffuse. The histopathologic findings of core liver biopsies of liver metastases identified by needle localization in a subset of these patients were reviewed. The core samples were evaluated by routine light microscopy, including immunohistochemical/immunofluorescent staining for CD31, CD105, and HMB45, and classified as exhibiting an infiltrative or nodular growth pattern. MAIN OUTCOME MEASURES: Magnetic resonance images and core biopsy findings. RESULTS: A total of 32 patients were identified with metastatic UM to the liver that was imaged by MRI, and 127 lesions were identified. A total of 46 lesions were classified by MRI as infiltrative and 81 as nodular. There were 9 needle-localized core biopsies that corresponded to MRI of metastatic lesions. Of these 9 lesions, 3 that were classified as infiltrative on MRI exhibited stage I infiltrative histologic growth patterns; of the remaining 6 that were classified as nodular by MRI, 5 histologically demonstrated stage II or stage III infiltrative growth patterns and 1 histologically demonstrated a nodular growth pattern. CONCLUSIONS: Magnetic resonance imaging of hepatic infiltrative growth patterns of metastatic UM corresponded to stage I histologic infiltrative growth in the sinusoidal spaces, whereas MRI nodular growth patterns corresponded to stage II/III histologic infiltrative growth that replaced the hepatic lobule or histologic nodular growth in the portal triad that effaced adjacent hepatic parenchyma.

Ring-Shaped Leiomyoma of the Ciliary Body.

PURPOSE: Ciliary body mesectodermal leiomyoma is a rare, benign smooth muscle tumor that typically presents in women in the second to fourth decade of life. The diagnosis is typically based on clinical color, funduscopic appearance, transillumination properties, and B-scan ultrasonography. METHODS: We present a patient with a 360° ciliary body mass with transillumination and ultrasonographic properties consistent with a ring melanoma. RESULTS: This case emphasizes the difficulty in differentiating the benign leiomyoma from similar appearing malignant tumors such as melanoma. CONCLUSION: The eye was enucleated and the diagnosis was ring-shaped leiomyoma.

Mechanisms of Optic Nerve Invasion in Primary Choroidal Melanoma.

AIM: The aim of this study was to assess morphological risk factors associated with optic nerve invasion of choroidal melanoma and to identify possible mechanisms of optic nerve invasion. METHODS: Medical charts and histology slides of patients with primary choroidal melanoma who were treated by enucleation/exenteration and whose pathology showed optic nerve invasion were reviewed. RESULTS: Twenty-one patients (mean age: 65.67 ± 14.72 years) with primary uveal melanoma arising from the choroid were included in this analysis. A peripapillary location was present in 86% of the cases. Four types of optic nerve invasion were identified: transvitreal invasion (10%); retinal invasion (23%); direct peripapillary invasion (57%); and a combined mechanism (10%). Optic nerve invasion was prelaminar in 67%, laminar in 10%, and retrolaminar in 23% of the cases. Significantly higher largest basal diameter (p = 0.021) and tumor thickness values (p = 0.017) and higher rates of vortex vein (p = 0.022) and retinal invasion (p = 0.007) were observed in the transvitreal/retinal invasion groups when compared to the direct peripapillary invasion group. CONCLUSIONS: A peripapillary tumor location was the most common mechanism of optic nerve invasion of choroidal melanoma. In 43% of the cases, other mechanisms including transvitreal and retinal invasion resulted in optic nerve invasion.

Retinoinvasive Uveal Melanoma: Report of 2 Cases and Review of the Literature.

PURPOSE: To describe the clinical history and histopathologic findings of 2 cases of retinoinvasive uveal melanoma. METHODS: The medical records and pathology specimens of 2 patients with retinoinvasive uveal melanoma were reviewed. RESULTS: The first patient had an iris/ciliary body melanoma that was treated and the second patient had suspected iridocorneal endothelial syndrome. Both patients developed a blind, painful eye; the first patient's right eye was enucleated and the left eye of the second patient underwent evisceration. Histopathologic examination of the enucleated eye showed a tumor composed of minimally pigmented spindle-shaped cells with fusiform nuclei and prominent nucleoli and round cells with prominent nucleoli. The tumor cells invaded into the retina where they formed perivascular aggregates. Examination of the evisceration specimen showed a proliferation of pigmented tumor cells within the stroma of one iris leaflet. The tumor cells extended onto the ciliary body and vitreous base and invaded the retina. The pathologic diagnosis in both patients was retinoinvasive uveal melanoma. CONCLUSIONS: Careful funduscopic and imaging examination should be performed in eyes with unilateral glaucoma with iris/ciliary body lesions, and enucleation, rather than evisceration, should be performed, as retinoinvasive melanoma is in the differential diagnosis.

Corneal endothelial morphology and function after torsional and longitudinal ultrasound mode phacoemulsification.

PURPOSE: To study the endothelial cell morphology and corneal thickness changes after phacoemulsification by using the OZil torsional and longitudinal ultrasound techniques (Infiniti Vision System, Alcon Laboratories). SETTING: Department of Ophthalmology, Clinical Center, University of Debrecen, Debrecen, Hungary. METHODS: 52 patients with cataract were randomly assigned to longitudinal ultrasound and torsional mode group. All surgeries were performed through a 2.2 mm clear corneal incision, the method employed being divide and conquer. The endothelial morphometry such as cell density (ECD), mean cell area, coefficient of variation of cell area, and central corneal thickness were examined with specular microscopy (EM-1000, Tomey) preoperatively and 4, 8 weeks postoperatively. RESULTS: ECD values decreased significantly in both surgical groups (P < .001, repeated- mesures ANOVA), the postoperative endothelial cell loss was higher in the longitudinal ultrasound mode group (3.5% and 6.5%, at 4 and 8 weeks after surgery) than in the torsional group (3.3% and 5.5%, at 4 and 8 weeks after surgery), the difference not being significant between the two groups (P = .164 and P = .479, at 4 and 8 weeks after surgery, Mann-Whitney test). There was no statistically significant difference in any of the assessed parameters between the two surgical groups (P > .05). No significant correlation was found between the endothelial cell loss and the nucleus density. CONCLUSIONS: Both phacoemulsification techniques were safe and effective. The torsional handpiece performs oscillatory movements and delivers less energy into the eye than the longitudinal ultrasound technique, therefore providing more favorable energy and thermal safety profile.