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Background: Synchronous endometrial and ovarian carcinomas represent up to 10% of all endometrial and ovarian tumors. These are diagnostically challenging cases to determine if they represent dual primary tumors or related metastatic tumors. Case: A 48-year-old was diagnosed with synchronous primary ovarian and endometrial malignancies on pathology based on traditional morphological parameters. However, following next generation sequencing (NGS) of tumors from both the uterus and ovary, the malignancies were unequivocally recognized as primary uterine tumor metastatic to the ovary using mismatch repair protein expression profile and tumor clonality. Conclusion: NGS using FDA-approved commercially available platforms is becoming increasingly utilized to understand the genetic landscape of tumors and select the appropriate targeted therapies for improved outcomes. Simultaneous sequencing of synchronous endometrial and ovarian carcinomas may represent the new gold standard to unequivocally demonstrate tumor clonal relationships, properly classify disease as well as guide the most appropriate adjuvant treatment in these challenging cases.

Background: Treatment of recurrent platinum-resistant high grade serous ovarian cancer (HGSOC) remains a challenge. Novel treatment options for recurrent disease are an unmet need. Case: A 69-year-old with recurrent, metastatic, platinum-resistant HGSOC overexpressing TROP2 experienced a significant response to the antibody-drug conjugate (ADC) sacituzumab govitecan after multiple failed lines of chemotherapy and targeted treatment. Following sacituzumab govitecan treatment she experienced a confirmed partial response as well as a return of CA-125 to baseline. Having now completed 8 cycles (ie, over 6 months of treatment), her disease continues to demonstrate a response to sacituzumab govitecan treatment. The ADC has been well tolerated at a dose of 10 mg/kg with no dose-limiting toxicity or need for dose reductions. Conclusion: Sacituzumab govitecan may represent a treatment option for platinum-resistant/recurrent HGSOC that have previously failed prior lines of chemotherapy. Clinical trials with sacituzumab govitecan in platinum-resistant ovarian cancer patients are currently ongoing (https://classic.clinicaltrials.gov/ct2/show/NCT06028932).

Up to 30 % of COVID-infected patients may develop post-acute sequelae of COVID-19 (PASC), also known as Long COVID (LC), a syndrome characterized by a variety of debilitating symptoms lasting for more than 3 months after the acute infection. While the pathophysiological mechanisms behind PASC/LC are not completely understood, growing evidence suggests that an important component of this syndrome may be related to persistent microvascular inflammation causing clumping/clotting of red blood cells and platelets and thrombotic complications. We retrospectively evaluated the plasma levels of von Willebrand factor (VWF), Factor VIII and D-dimer in 10 gynecologic patients (60 % with an endometrial or ovarian cancer diagnosis) affected by PASC/LC vs 5 control patients (60 % harboring endometrial or ovarian tumors). We found elevated VWF and Factor VIII levels in all 10 PASC/LC patients (means of 254 % and 229 %, respectively) vs none of the 5 randomly selected cancer control patients (means of 108 % and 95 %, respectively), p = 0.0046 and p

Post-acute sequelae of COVID-19 (PASC), also known as Long-Covid (LC), may affect 10–30 % of COVID-infected patients, and is characterized by a variety of debilitating symptoms lasting over 3 months after the acute infection, including but not limited to dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. Vitamin D is an essential nutrient primarily recognized for its role in regulating calcium and bone health but also endowed with potent anti-inflammatory activity affecting a variety of immune cells. We retrospectively evaluated the plasmatic levels of both 1,25-dihydroxyvitamin-D (1,25 OH), and 25-hydroxyvitamin-D (25 OH), the active and storage forms of vitamin-D3, respectively, in the serum of gynecologic cancer patients affected by PASC/LC vs control cancer patients. We found elevated 1,25-dihydroxyvitamin-D levels in 5 out of 5 of the PASC/LC patients (mean ± SD = 97.2 ± 26.9 pg/mL) versus 0 out of 10 of randomly selected cancer control patients (44.9 ± 17.2 pg/mL, p = 0.0005). In contrast, no significant difference was noted in the levels of 25-dihydroxyvitamin-D in PASC/LC (mean ± SD = 48.2 ± 15.8 ng/mL) versus controls (43.0 ± 11.6 ng/mL, p = 0.48). Importantly, abnormal levels of vitamin D were found to persist for at least 2 years in patients with long covid symptoms. The active form (1,25OH) but not the storage form (25 OH) of vitamin-D is significantly elevated in PASC/LC cancer patients. Abnormally and persistently elevated 1,25OH levels, similarly to sarcoidosis patients, may represent the results of extrarenal conversion of vitamin D by activated macrophages, and a novel biomarker of persistent inflammation in gynecologic cancer patients with PASC/LC.

Background: Treatment of uterine serous carcinoma (USC) is challenging; effective treatment options for metastatic and recurrent disease are needed. Case: A 68-year-old woman with recurrent, metastatic, USC overexpressing HER2/neu experienced durable response to the antibody drug conjugate (ADC) trastuzumab-deruxtecan (T-DXd), after failing multiple standard and experimental treatments targeting HER2/neu. She experienced a significant reduction in disease burden, disappearance of metastatic back bone pain as well as normalization of CA-125 quickly after starting treatment. Her disease continued to show response to treatment over 5 months and 7 cycles of T-DXd therapy. She did not experience any dose-limiting side effects and tolerated treatment with 5.4 mg/kg T-DXd without issue. Conclusion: T-DXd may present a new treatment option for chemotherapy-resistant uterine serous carcinoma.

Background: Treatment of ovarian clear cell carcinoma (CCC) poses many challenges. Effective treatment options for recurrent and metastatic disease remain limited. Case: A 70-year-old woman with recurrent metastatic ovarian CCC experienced durable response to the combination of pembrolizumab, a PD-1 targeting monoclonal antibody and lenvatinib, an oral multikinase inhibitor, after failing standard and experimental treatments. She experienced a 40.1% reduction of target lesions over 26 weeks of therapy. CA-125 trends confirmed serial CT scan findings of shrinking disease burden. She experienced overall mild side effects from the drug combination, and lenvatinib dosage was decreased from 20 to 10 mg/day over her 10 cycles. Conclusion: The combination of pembrolizumab and lenvatinib may represent a new treatment option for chemotherapy-resistant ovarian CCC.

Carotid plaque instability contributes to large vessel ischemic stroke. Although vascular smooth muscle cells (VSMCs) affect atherosclerotic growth and instability, no treatments aimed at improving VSMC function are available. Large genetic studies investigating atherosclerosis and carotid disease in relation to the risk of stroke have implicated polymorphisms at the HDAC9 locus. The HDAC9 protein has been shown to affect the VSMC phenotype; however, how this might affect carotid disease is unknown. We conducted a pilot investigation using single nuclei RNA sequencing of human carotid tissue to identify cells expressing HDAC9 and specifically investigate the role of the HDAC9 in carotid atherosclerosis. We found that carotid VSMCs express HDAC9 and genes typically associated with immune characteristics. Using cellular assays, we have demonstrated that recruitment of macrophages can be modulated by HDAC9 expression. HDAC9 expression might affect carotid plaque stability and progression through its effects on the VSMC phenotype and recruitment of immune cells.

Research within a gynecologic oncology population has lagged behind the uptake in use of medical cannabis for symptom control. This study seeks to evaluate patient experience with prescribed medical cannabis obtained through licensed dispensaries in women with gynecologic malignancies.A 43-item survey exploring patient experience with medical cannabis was administered to women with gynecologic malignancies who used medical cannabis prescribed by a gynecologic oncologist.Thirty-six eligible patients were approached for consent, and 31 patients returned completed surveys (86%). Ninety-three percent had advanced or recurrent disease; 74% were receiving chemotherapy or immunotherapy. Eighty-three percent reported medical cannabis provided relief from cancer or treatment-related symptoms including decreased appetite (41%), insomnia (41%), neuropathy (41%), anxiety (35%), nausea (29%), joint pain (29%), bone pain (29%), abdominal pain (25%), and depression (19%). Eighty percent of patients reported medical cannabis worked the same or better than other traditional medications for management of their cancer or treatment-related symptoms, and 83% reported medical cannabis had an equivalent or better side effect profile. Of the subset of patients using medical cannabis for pain, 63% reported a reduction in opioid use.Patients perceive that medical cannabis was useful for relief of cancer and treatment-related symptoms, suggesting medical cannabis may be a reasonable alternative or adjunct therapy. Medical cannabis was well tolerated and may have the potential to improve neuropathic pain and decrease opioid use.

Background: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines. Case: We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients. Conclusion: Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.

Purpose: NRG Oncology conducted a phase II trial to assess the antitumor activity and tolerability of copanlisib, a selective inhibitor of PIK3CA, in persistent or recurrent endometrial carcinoma harboring hotspot PIK3CA mutations. Patients and methods: Eligible patients had endometrial cancer with endometrioid, serous or mixed histology, a somatic PIK3CA gene mutation, measurable disease, and GOG performance status ≤2. Treatment consisted of IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle) until disease progression or prohibitive toxicity. The primary endpoints of the study were objective tumor response as assessed by RECIST 1.1 and to determine the nature and degree of toxicity of copanlisib as assessed by CTCAE version 4. The study used a 2-stage group sequential design. Results: Eleven patients were enrolled onto stage I of the treatment trial. Five patients had endometrioid, four serous and two had a tumor of mixed histology. The most common PIK3CA mutation was Q546X (n = 3) in exon 9. The most common grade 3 or 4 AE was hyperglycemia. No grade 5 adverse events were reported. No clinical responses were detected. Six patients had a best overall response of stable disease. Of 11 who initiated treatment, 10 progressed on treatment. One patient with stable disease on copanlisib withdrew from treatment secondary to relocation. The median progression-free survival (PFS) was 2.8 months; at 6 months 27% were alive, progression-free. The median overall survival (OS) was 15.2 months. Due to the lack of CR/PR continuation of accrual to the second stage of accrual was not warranted. Conclusion: Copanlisib is well tolerated but has limited activity as a single agent in this population. Keywords: Endometrial neoplasms, Copanlisib, Pik3ca, Targeted treatment

Background: Uterine serous carcinoma (USC) is a biologically aggressive variant of uterine cancer. Effective treatment options for recurrent, chemotherapy-resistant USC are extremely limited. Case: We describe a 74-year-old woman with recurrent and widespread treatment-resistant disease, who experienced a dramatic response to sacituzumab govitecan, a novel antibody-drug conjugate (ADC) targeting human trophoblast-cell-surface antigen (TROP-2), after failing multiple chemotherapy and immunotherapy. The impressive clinical response (66% reduction of target lesions by RECIST 1.1 with a duration response of over 10 months) was confirmed with serial CT scans in the absence of significant adverse events. Conclusion: Sacituzumab govitecan may present a new treatment option for recurrent USC patients harboring Trop-2+ tumors resistant to chemotherapy. Clinical trials with sacituzumab govitecan are warranted. Keywords: Sacituzumab govitecan, IMMU-132, Uterine serous carcinoma, Recurrent, Treatment-resistant

Background: Management of advanced/recurrent low-grade serous ovarian carcinoma (LGOSC) is often challenging. Effective treatment options remain limited for hormone and chemotherapy-resistant LGSOC.CASE: A 65-year-old woman with recurrent widespread LGSOC harboring the KRAS-G12 V hotspot mutation experienced a dramatic clinical response to Binimetinib (MEK162), a mitogen-activated protein kinase (MEK) inhibitor, after failing multiple chemotherapy and hormonal treatments. An 81% reduction of target lesions by RECIST 1.1 over 31 months of response duration was confirmed with serial CT scans. Episodes of drug-related toxicity (pneumonitis) easily resolved without sequelae with the use of oral steroids. Conclusion: Binimetinib may present a new treatment option for hormone- and chemotherapy-resistant LGSOC harboring KRAS mutations. Keywords: Binimetinib, MEK162, Low-grade ovarian cancer, Serous, Recurrent, Treatment-resistant

Objective: This study sought to evaluate characteristics of cases of free-floating tumor fragments within the lumen of fallopian tubes (‘floaters’) on final pathology for Type I and Type II endometrial adenocarcinoma, including relationships with disease recurrence and mortality. Methods: A single institution experience of 1022 consecutive cases of uterine cancer presenting between 2005 and 2010 was retrospectively reviewed, with data extraction from electronic medical records. Associations of floaters with baseline characteristics were studied with logistic regression, and relationships with disease recurrence and survival were assessed with Cox proportional hazards models. Results: Among 816 included cases of Type I or Type II endometrial adenocarcinoma, floaters were identified on final pathology for 20 patients (2.5%). Patient characteristics of cases with floaters mirrored the overall sample. With adjustment, presence of floaters trended towards association with laparoscopic/robotic approach (OR = 3.84; 95%CI 0.98-15.1), and was significantly associated with lymphovascular invasion (OR = 9.65; 95%CI 2.35-39.6) and higher stage disease. Although floaters were associated with increased risk of recurrence in unadjusted analysis (HR = 3.22; 95%CI 1.41-7.37), after adjustment for disease type, stage, and patient comorbidities, no evidence for impact on disease recurrence or overall survival was found. Conclusions: The presence of floaters is rare. Floaters were generally associated with more extensive disease, but no evidence was found to show any independent prognostic impact on risk of recurrence or death. In agreement with prior research, this study found a trend towards association of floaters with laparoscopic/robotic approach, indicating the possibility of floaters sometimes being the result of trauma from uterine manipulator insertion.

Background: The management of uterine-serous-carcinoma (USC) no longer amenable to treatment with surgery, radiation and/or chemotherapy remains dismal. Alternative therapeutic options are desperately needed. Case: We describe the case of a heavily pretreated 74-year-old patient with a recurrent USC overexpressing HER2/neu at 3+ level by IHC treated with the anti-HER2/neu antibody-drug-conjugate (ADC) trastuzumab-emtansine (TDM-1-Kadcyla-Genentech/Roche). She experienced a remarkable clinical response to TDM-1 with a complete resolution of a large metastatic, radiation/chemotherapy resistant tumor deposit in her abdominal wall muscle confirmed by multiple CAT scans and a prolonged systemic control of her disease. Conclusion: TDM-1 may represent a novel treatment option for recurrent/metastatic HER2/neu-positive USC patients refractory to salvage-treatment.

Objective: This 24-month, double-blind, split-mouth randomized equivalence clinical trial compared the clinical performance of a bulk-fill thermoviscous composite resin using two different preheating methods for the restoration of non-carious cervical lesions (NCCLs)., Material and Methods: A total of 120 NCCLs were randomized into two groups (n = 60 each). In one group, a bulk-fill thermoviscous composite resin (VisCalor bulk, Voco GmbH) was preheated using a dispenser heater (DH, VisCalor Caps dispenser/warmer), while in the other group, the same resin was preheated with a bench heater (BH, Caps Warmer). In the BH group, the composite underwent preheating at 68 °C using a heating bench for 3 min while in the DH group, the composite was preheated at the same temperature for 30 s using a dispenser heater. Subsequently, the preheated bulk-fill thermoviscous composite resin was directly applied to the NCCLs. The restorations were evaluated at baseline, and after 6, 12, 18, and 24 months of clinical service using the FDI criteria. The total working time was recorded. The study used TOST-P to assess groups equivalence, Kaplan-Meier analysis for retention/fracture rate, log-rank test for secondary outcomes' survival distributions, and paired t-tests for comparing time per clinical step between groups (α = 0.05)., Results: After 24 months, 106 restorations were evaluated. Four restorations were lost-two from the DH group and two from the BH group-resulting in similar retention rates for both groups (96.1%, 95% CI 86.8 - 98.9, p > 0.05). The hazard ratio was 0.83 (95% CI 0.26 to 2.72), indicating no significant difference between the groups (p > 0.05). All other FDI parameters were deemed clinically acceptable. However, the total working time for the BH group was significantly longer than that for the DH group (p < 0.001)., Conclusions: Both preheating protocols employed for the bulk-fill thermoviscous composite resin demonstrated high and equivalent survival rates after 24 months, the other FDI parameters were deemed clinically acceptable over the same period., Clinical Significance: Clinicians can choose either method for heating the thermoviscous composite resin for restoration of non-carious cervical lesions, as they do not impact important clinical outcomes after 24 months. The total working time for the bench heater is higher than that for the dispenser heater due to the need for preheating of the bench heater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To compare the risk and intensity of tooth sensitivity (TS) and gingival irritation (GI), as well as bleaching efficacy (BE) in the maxillary and mandibular arches after in-office dental bleaching., Materials and Methods: 90 participants were randomly into two groups according to the arch (maxillary or mandibular) in which the patient will first receive a 35 % hydrogen peroxide gel (2 sessions; 1 × 30 min; 1 week apart). TS and GI were recorded immediately after, up to 1 h, 24 h and 48 h after bleaching, using the 0-10 Visual Analogue Scale (VAS). BE was assessed before bleaching and 30 days after the end of the treatment (shade guide units [ΔSGU], CIELab [ΔE ab ], CIEDE2000 [ΔE 00 ] , and Whiteness Index for Dentistry [WI D ]). TS and GI were compared using McNemar's and paired t-test. BE were compared with Wilcoxon Signed Rank Test (ΔSGU) and paired t-test (ΔE ab , ΔE 00, and WI D ) (α = 0.05)., Results: The risk and the intensity of TS was statistically higher for the mandibular arch (p < 0.003). The risk and intensity of GI did not differ between arches (p > 0.38). Both arches demonstrated significant BE (ΔSGU, ΔE ab , ΔE 00 and WI D ), without differences between them (p > 0.08)., Conclusions: In-office dental bleaching induces higher risk and the intensity of TS in the mandibular arch when compared to maxillary arch, without significant differences in gingival irritation, or bleaching efficacy., Clinical Relevance: Most patients experience tooth sensitivity regardless of the dental arch involved. However, when performing in-office dental bleaching, clinicians should consider that the mandibular arch is more likely to experience greater sensitivity compared to the maxillary arch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To assess the Quality of Life (QoL) of participants treated with dental bleaching using different techniques by administering two questionnaires Oral Health Impact Profile (OHIP-14) and Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), as well as the bleaching efficacy and tooth sensitivity (TS)., Materials and Methods: Secondary results for nine randomized clinical trials were included, involving 489 participants who underwent bleaching procedures. The questionnaires were applied at baseline and 30-day post-bleaching. Bleaching efficacy (ΔSGU/ΔE ab ) and TS were also evaluated (VAS/NRS). The effect of bleaching on aesthetic self-perception was evaluated using the Paired t-test. The Kruskal-Wallis test assessed variations by technique. Also, the correlations between questionnaires and outcomes was evaluated (α = 0.05)., Results: After the bleaching treatment, both questionnaire revealed significant differences compared to the baseline, regardless of the factor evaluated (p < 0.05), except for Physical pain in OHIP-14 (p = 0.53). No correlation was found between OHIP-14 and bleaching efficacy (p < 0.008). A significant correlation was found between bleaching efficacy and dental self-confidence, indicating that dental self-confidence increased as the number of SGU (ΔSGU) increased, while social impact (ΔE ab ) and aesthetic concern (ΔSGU) decreased. Additionally, a significant correlation was observed between TS and OHIP-14 (Physical pain). For PIDAC, both dental self-confidence and psychological impact were correlated with TS in the VAS., Conclusion: Subjects who underwent dental bleaching treatment improved their self-perception and dental self-confidence. Dental bleaching, besides enhancing the patient's smile, also improves their self-esteem., Clinical Relevance: Dental bleaching, besides improving the patient's smile, also enhances their self-esteem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Toxoplasma gondii is a globally distributed zoonotic protist, capable of infecting all warm-blooded animals. In Australia, cats (Felis catus) are the only definitive host capable of spreading T. gondii infection via oocysts. Free-roaming cats are widespread in Australia and can play a central role in the ecology of T. gondii. Therefore, understanding the epidemiology of this parasite in stray and feral cats is essential to understanding the potential risk of infection in animals and humans. Due to a lack of easily accessible commercial kits, an in-house modified agglutination test (MAT) was established to test for IgG antibodies against T. gondii, using cell culture-derived T. gondii tachyzoites, and compared with a commercial MAT. A total of 552 serum samples collected during 2018 - 2021 from stray (n = 456) and feral cats (n = 90) (samples with missing data n = 6) from four Australian states, representing different age groups of both sexes, were screened for antibodies against T. gondii. Risk factors for T. gondii infection were assessed using multivariable logistic regression analysis. The in-house MAT had excellent agreement with the commercial MAT and provided a reliable and economical serological tool for T. gondii screening in animals. The overall observed seroprevalence for T. gondii in cats was 40.4 % (223/552). Bodyweight (as a proxy for age), geographical location, season and whether cats were feral or stray, were factors associated with T. gondii seropositivity in cats. Sex was not found to be a risk factor for T. gondii infection in feral and stray cats. This study shows that Australian stray and feral cats have a high T. gondii seroprevalence, which may translate to significant health impacts for wildlife species, livestock and the public., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work stated in this report., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Synchronous endometrial and ovarian carcinomas represent up to 10% of all endometrial and ovarian tumors. These are diagnostically challenging cases to determine if they represent dual primary tumors or related metastatic tumors., Case: A 48-year-old was diagnosed with synchronous primary ovarian and endometrial malignancies on pathology based on traditional morphological parameters. However, following next generation sequencing (NGS) of tumors from both the uterus and ovary, the malignancies were unequivocally recognized as primary uterine tumor metastatic to the ovary using mismatch repair protein expression profile and tumor clonality., Conclusion: NGS using FDA-approved commercially available platforms is becoming increasingly utilized to understand the genetic landscape of tumors and select the appropriate targeted therapies for improved outcomes. Simultaneous sequencing of synchronous endometrial and ovarian carcinomas may represent the new gold standard to unequivocally demonstrate tumor clonal relationships, properly classify disease as well as guide the most appropriate adjuvant treatment in these challenging cases., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A.D.S. reports grants from GILEAD, grants and personal fees from MERCK, grants from BOEHINGER-INGELHEIM, grants and personal fees from 10.13039/501100002973Daiichi-Sankyo and grants and personal fees from EISAI and R-Pharm USA. The other authors declare no conflict of interest]., (© 2024 The Authors.)

Objective: To evaluate the postoperative sensitivity (POS), as well as the clinical performance of posterior restorations using a new chemically-cured bulk-fill composite (Stela Automix and Stela Capsule, SDI) comparing with a light-cured bulk-fill composite after 6 months., Methods: Fifty-five participants with at least three posterior teeth needing restoration were recruited. A total of 165 restorations were performed on Class I or Class II cavities. After the application of Stela primer, the chemically-cured composite (Stela Automix or Stela Capsule) was inserted. For the light-cured composite group, a universal adhesive (Scotchbond Universal) was applied with a bulk-fill composite (Filtek One). Participants were evaluated for spontaneous and stimulated POS in the baseline, after 48 h, 7 days, and 6 months. Additionally, each restoration was assessed using the updated version of FDI criteria after 6 months. The differences in the proportions of the groups were compared by Cochran test statistics (α = 0.05)., Results: Both chemically-cured composites showed a lower risk of POS compared to the light-cured composite at baseline and up to 48 h (p < 0.04). A significantly lower surface luster and texture was observed for the Stela Capsule composite compared to the light-cured bulk-fill composite (baseline and 6 months; p = 0.03). A significant color mismatch was observed for the light-cured bulk-fill composite compared to the chemically-cured composites (baseline and 6 months; p = 0.03). No significant differences were observed in any other item evaluations (p > 0.05)., Conclusion: Chemically-cured composites exhibit lower postoperative sensitivity and less color mismatch compared to a light-cured bulk-fill composite after 6 months of clinical service., Clinical Significance: The chemically-cured composites appear to be an appealing option for restoring posterior teeth, as they exhibit lower postoperative sensitivity compared to a light-cured bulk-fill composite, both at baseline and up to 48 h, and less color mismatch., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the effect of an adhesive loaded with 0.2 % copper (Cu) and 5 % zinc oxide (ZnO) nanoparticles (Nps) on its adhesive properties and enzymatic activity at the hybrid layer ex vivo in a randomized clinical model., Methods: Fifteen patients participated in this study, and a total of 30 third molars were used. Occlusal cavities (4 × 4 × 2 mm) were made in each tooth, and randomly divided into 2 groups: (i) Experimental group: commercial adhesive loaded with 0.2wt % CuNps and 5wt % ZnONps; and (ii) Control Group: non-loaded commercial adhesive. Teeth were restored with resin composite. Thirty days later, extractions were performed. Extracted teeth were longitudinally sectioned. Nps in powder were characterized by field emission scanning electron microscope (FE-SEM) and energy dispersive X-ray (EDX) analysis. Microtensile bond strength (μTBS), degree of conversion (DC), and nanoleakeage (NL) tests were executed. In situ zymography (Zym) was performed to evaluate the gelatinolytic activity at the hybrid layer. Student's t-test (α = 0.05) was applied for all tests., Results: μTBS and DC did not show significant differences (p > 0.05) between both groups. However, NL and gelatinolytic activity at the hybrid layer showed significant values (p < 0.05) for experimental group in comparison with control group., Conclusion: The addition of 0.2 % CuNps and 5 % ZnONps to a universal adhesive decreases NL and gelatinolytic activity at the hybrid layer, without jeopardizing its adhesive properties., Significance: This randomized clinical trial with ex vivo analysis demonstrate that a commercial adhesive modified with 0.2wt % Cu and 5wt % ZnO Nps that does not affect its adhesive properties, reducing gelatinolytic activity and nanoleakage at the hybrid layer, which should contribute to an improvement of long term bonding-dentine clinical performance., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to synthesize, characterize, and assess the penetration of hydrogen peroxide (HP), color change (CC), and surface morphology changes after the application of two distinct nano-hydroxyapatite (nano-HAp)., Methods: Two nano-HAp were previously synthesized by co-precipitation: one with rod-shaped particles (RS) and the other with spherical-shaped particles (SS). The surface charge of the nano-HAp particles was determined at varying pH levels and characterized by X-ray diffraction patterns and Fourier transform infrared spectroscopy. The morphology of the samples was assessed using scanning electron microscopy (SEM). The nano-HAp particles were applied before the dental bleaching procedure. Forty teeth were divided into four groups (n = 10) according to the bleaching treatment: no treatment, bleaching with 35 % HP only, RS application and bleaching with 35 % HP, and SS application and bleaching with 35 % HP. HP concentration (µg mL -1 ) was measured using UV-Vis, while CC was evaluated with a digital spectrophotometer (ΔE ab , ΔE 00 and WI D ). Additionally, four teeth from each group were selected for SEM analysis. Statistical analysis encompassed one-way ANOVA, Tukey's, and Dunnet's tests., Results: RS and SS were successfully synthesized by coprecipitation, primarily differing in pH during synthesis. Both variations of nano-HAp morphology significantly reduced HP diffusion into the pulp chamber (p < 0.001). Regarding enamel morphology, groups analyzed post dental bleaching exhibited greater HAp deposition on the enamel surface. Notably, this deposition did not impede CC., Significance: The utilization of different nano-HAp morphologies prior to dental bleaching appears to be a promising strategy for mitigating adverse effects associated with dental bleaching procedures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Evaluate the penetration of hydrogen peroxide (HP) into the pulp chamber, bleaching efficacy (BE) and amount of gel expended during in-office bleaching using an applicator brush tip and conventional tip from different commercial brands., Materials and Methods: 104 human premolars were randomly distributed into thirteen groups (n = 8) according to the commercial brand: DSP White Clinic 35 % Calcium (DW), Nano White 35 % (NW), Total Blanc One-Step 35 % (TS), Whiteness HP Blue 35 % (WB), Potenza Bianco Pro SS 38 % (PB), Opalescence XTra Boost 40 % (OB), no bleaching (negative control), and application method: applicator brush tip and conventional tip for all groups. Initial HP concentration (%) was determined via titration and pH was measured with digital pH meter. Concentration (µg/mL) of HP into the pulp chamber was measured using UV-Vis spectrophotometry, the BE (ΔE* ab , ΔE 00 and ΔWI D ) was evaluated with a digital spectrophotometer, and the amount of gel expended was evaluated using a precision analytical digital balance. Statistical analysis included two-way ANOVA, Tukey's, and Dunnett's test. Comparison between HP into the pulp chamber vs BE was performed with Person's correlation (α = 0.05)., Results: Brush tip demonstrated a low amount of HP in the pulp chamber compared to the conventional method for all bleaching gels (p < 0.0003), as well as lower amount of gel expended (p < 0.002). The brush tip did not result in a significant difference in BE compared to the conventional (p > 0.05). No correlations were found between both factors (p > 0.05)., Conclusion: Brush tip showed lower penetration of HP in the pulp chamber and a reduced volume of spent gel when compared to the conventional tip, for all commercial brands., Clinical Relevance: Brush tip is recommended for bleaching gels in an attachable syringe due to its ability to reduce the penetration of HP into the pulp chamber and minimize the amount of bleaching gel used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might have seemed to influence the findings presented in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To evaluate the influence of dentin moisture on the clinical behavior of a universal adhesive on posterior teeth after 36 months of follow-up., Methods: Forty-five patients participated in this study. Following a split-mouth design, three operators placed 90 Class I/Class II restorations over moist dentin (MD) or dry (DD) (n = 45) with resin composite (Filtek Bulk Fill) and a universal adhesive used in the etch-and-rinse mode (Single Bond Universal). Each restoration was evaluated according to the FDI and USPHS criteria (postoperative sensitivity, fracture and retention, marginal staining, marginal adaptation, and recurrence of caries) at baseline and after 6-, 12-, and 36 months. For statistical analysis, Kruskal Wallis analysis of variance rank (α = 0.05) and Kaplan-Meier survival analysis were used., Results: No significant difference between groups was observed in each FDI criterion after 36 months of clinical evaluation (p > 0.05). The retention rates (confidence interval 95 %) were 97.37 % (86.5 - 99.5) for both MD and DD without significant difference between them (p > 0.05). Eight restorations (MD = 4; DD = 4) showed minimal marginal staining defects (p > 0.05). Two restorations were lost (MD = 1; DD = 1). Fifteen restorations (MD = 8; DD = 7) presented minor marginal discrepancies according to the FDI criteria (p > 0.05)., Conclusion: The clinical performance of the universal adhesive when applied in etch-and-rinse mode was not influenced by dentin moisture in posterior bulk-fill composite restorations., Clinical Significance: The level of dentin moisture appears not to influence the clinical efficacy of a universal adhesive when applied using the etch-and-rinse technique in posterior composite resin restorations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Treatment of recurrent platinum-resistant high grade serous ovarian cancer (HGSOC) remains a challenge. Novel treatment options for recurrent disease are an unmet need., Case: A 69-year-old with recurrent, metastatic, platinum-resistant HGSOC overexpressing TROP2 experienced a significant response to the antibody-drug conjugate (ADC) sacituzumab govitecan after multiple failed lines of chemotherapy and targeted treatment. Following sacituzumab govitecan treatment she experienced a confirmed partial response as well as a return of CA-125 to baseline. Having now completed 8 cycles (ie, over 6 months of treatment), her disease continues to demonstrate a response to sacituzumab govitecan treatment. The ADC has been well tolerated at a dose of 10 mg/kg with no dose-limiting toxicity or need for dose reductions., Conclusion: Sacituzumab govitecan may represent a treatment option for platinum-resistant/recurrent HGSOC that have previously failed prior lines of chemotherapy. Clinical trials with sacituzumab govitecan in platinum-resistant ovarian cancer patients are currently ongoing (https://classic.clinicaltrials.gov/ct2/show/NCT06028932)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.D.S. reports grants from GILEAD, grants and personal fees from MERCK, grants from BOEHINGER-INGELHEIM, grants and personal fees from Daiichi-Sankyo and grants and personal fees from EISAI and R-Pharm USA. The other authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized., Methods: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression., Results: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation., Conclusions: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the efficacy of simulated brushing with toothpastes containing different concentrations of hydrogen peroxide (HP) in pulp chamber penetration and color change. Also, physical-chemical properties (concentration, pH and viscosity) were evaluated., Methods: Forty-nine premolars were divided into seven groups (n = 7): untreated (control); whitening gel (White Class 6 %, 6 %BG) with one 90  min application (6 %BG 90  min) and 14 applications of 90  min (6 %BG 14×90 min); toothpastes (Colgate Luminous White Glow 3 %, 3 %TP; Crest 3D White Brilliance 4 %, 4 %TP; Colgate Optic White Pro-Series 5 %, 5 %TP) and 6 %BG toothbrushing for 14 applications of 90 s. HP penetration into the pulp chamber was measured through UV-Vis spectrophotometry and color change with a spectrophotometer (ΔE ab , ΔE 00 , and ΔWI D ). Initial concentration, pH, and viscosity were measured through Titration, Digital pH-meter, and Rheometer, respectively. Statistical analysis used one-way ANOVA and Tukey's test (α = 0.05)., Results: 6 %BG (14×90 min) and 4 %TP groups showed acidic pH and higher concentrations of HP in the pulp chamber compared to the other groups (p < 0.05). On the other side, 3 %TP and 5 %TP groups showed alkaline pH, higher viscosity between the toothpastes and lower HP penetration (p < 0.05). The 6 %BG AH (14×90 min) group exhibited the most significant color change (ΔE ab , ΔE 00 , and ΔWI D ) (p < 0.05)., Conclusions: Brushing with whitening toothpaste with an acidic pH leads to greater HP penetration into pulp chamber; but, even when a high concentrated HP whitening toothpaste was used, a lower whitening effect was observed when compared to a two-week at-home bleaching., Clinical Significance: Whitening toothpastes containing up to 5 % HP produced lower whitening effect than two-week at-home bleaching. Additionally, HP was detected within the pulp chamber which can potentially impact in tooth sensitivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This 24-month, double-blind, split-mouth randomized clinical trial aimed to compare the retention rates of a preheated thermoviscous composite resin (PHT) compared to a non-heated composite resin (NHT) in non-carious cervical lesions (NCCLs)., Methods: A total of 120 restorations were restored on NCCLs using a preheated (VisCalor bulk, Voco GmbH) and a non-heated (Admira Fusion, Voco GmbH) composite resins with 60 restorations per group. A universal adhesive in the selective enamel conditioning was applied. In the PHT group, composite was heated at 68 °C for using a bench heater. In the NHT group, no heating was employed. Both restorative materials were dispensed into caps and inserted into the NCCLs. The restorations were evaluated at baseline, 6, 12, 18, and after 24 months of clinical service using the FDI criteria. Statistical analysis was performed with Kaplan-Meier estimation analysis for retention/fracture rate and Chi-square test for the other FDI parameters (α=0.05)., Results: After 24 months 108 restorations were assessed. Seven restorations were lost (two for PHT group and five for NHT group), and the retention rates (95 % confidence interval [CI]) were 96.7 % (81.5-99.9) for PHT group and 90.8 % (81.1-96.0) for NHT group, with no statistical differences between them (p > 0.05). The hazard ratio (95 % CI) was 0.52 (0.27 to 1.01), with no significant difference within groups. In terms of all other FDI parameters that were assessed, all restorations were deemed clinically acceptable., Conclusions: Both composites showed high rates of retention rates after 24 months., Clinical Significance: The clinical performance of the new preheated thermoviscous was found to be as good as the non-heated composite after 24-month of clinical evaluation in non-carious cervical lesions., Registration of Clinical Trials: RBR-6d6gxxz., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The prevalence of end-stage heart failure and patients who could benefit from heart transplantation requires an expansion of the donor pool, relying on the transplant community to continually re-evaluate and expand the use of extended criteria donor organs. Introduction of new technologies such as the Paragonix SherpaPak Cardiac Transport System aids in this shift. We seek to analyze the impact of the SherpaPak system on recipient outcomes who receive extended criteria organs in the GUARDIAN-Heart Registry., Methods: Between October 2015 and December 2022, 1,113 adults from 15 US centers receiving donor hearts utilizing either SherpaPak (n = 560) or conventional ice storage (ice, n = 453) were analyzed from the GUARDIAN-Heart Registry using summary statistics. A previously published set of criteria was used to identify extended criteria donors, which included 193 SherpaPak and 137 ice., Results: There were a few baseline differences among recipients in the 2 cohorts; most notably, IMPACT scores, distance traveled, and total ischemic time were significantly greater in SherpaPak, and significantly more donor hearts in the SherpaPak cohort had >4 hours total ischemia time. Posttransplant mechanical circulatory support utilization (SherpaPak 22.3% vs ice 35.0%, p = 0.012) and new extracorporeal membrane oxygenation/ventricular assist device (SherpaPak 7.8% vs ice 15.3%, p = 0.033) was significantly reduced, and the rate of severe primary graft dysfunction (SherpaPak 6.2% vs ice 13.9%, p = 0.022) was significantly reduced by over 50% in hearts preserved using SherpaPak. One-year survival between cohorts was similar (SherpaPak 92.9% vs ice 89.6%, p = 0.27)., Conclusions: This subgroup analysis demonstrates that SherpaPak can be safely used to utilize extended criteria donors with low severe PGD rates., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of prolonged (P) polymerization time of a universal adhesive system applied in etch-and-rinse (ER) or self-etch (SE) strategies on the clinical performance of restorations in non-carious cervical lesions (NCCLs), after 36 months of clinical service., Methods: A total of 140 restorations were randomly placed in 35 subjects according to the polymerization time groups: ER (10 s); ER-P (40 s); SE (10 s); and SE-P (40 s) at 1,200 mW/cm 2 . Composite resin was placed incrementally. The restorations were evaluated immediately and after 6, 12, 18, and 36 months using the FDI criteria. Data were analyzed using the Kaplan-Meier survival test for retention loss, and the Kruskal-Wallis' test for secondary outcomes (α = 0.05)., Results: After 36 months, 19 restorations were lost: ER 6, ER-P 2, SE 9, SE-P 2. The retention rates were 82.3% for ER; 94.1 % for ER-P; 73.5 % for SE; and 94.1 % for SE-P, with a significant difference between ER vs. ER-P and SE vs. SE-P, as well as ER vs. SE-P and ER-P vs. SE (p < 0.0001). Minor defects were observed in 18 restorations for the marginal staining criteria: ER 5, ER-P 2, SE 8, SE-P 3; and in 33 restorations for the marginal adaptation criteria: ER 11, ER-P 4, SE 12, and SE-P 6 (p > 0.05). No restorations showed recurrence of caries or postoperative sensitivity., Conclusions: A prolonged polymerization time of 40 s improves the clinical performance of the universal adhesive for both adhesive strategies evaluated, even after 36 months., Clinical Significance: Prolonging the polymerization time of a universal adhesive from 10 to 40 s has been shown to improve its clinical performance when used in NCCLs., Competing Interests: Declaration of competing interest Declarations of interest: The authors of the article entitled “Prolonged Polymerization of a Universal Adhesive in Non-Carious Cervical Lesions: 36-month Double-Blind Randomized Clinical Trial” certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)