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Pembrolizumab, a programmed death 1 ligand (PD-1) checkpoint inhibitor, has elicited responses in mismatch repair (MMR)–deficient advanced solid tumors, leading to its agnostic approval by the US Food and Drug Administration in 2017 when no other therapeutic options are available. However, there are still insufficient data on the response to checkpoint inhibitors in advanced endometrial cancer related to Lynch syndrome (LS) and, specifically, in uterine serous carcinoma, which is uncommon in LS. Here we report a case of metastatic uterine serous carcinoma due to a germline MSH6 mutation (Lynch syndrome) that was discovered because of a patient's tumor MMR deficiency. The patient was started on first-line pembrolizumab in 2018 and sustained a partial response. She remains asymptomatic and progression free for more than 2 years. Tumor sequencing showed a high mutational burden and an upstream somatic mutation in the same gene, p.F1088fs. Immunohistochemical staining was negative for PD-L1 expression. We discuss clinical characteristics of the patient, molecular features of her tumor, and the mechanism of her tumor response. We also discuss the duration of immunotherapy in her case. Our case demonstrated a partial response and a long-term remission from the frontline single-agent pembrolizumab in a woman with metastatic uterine serous carcinoma and Lynch syndrome due to a germline MSH6 gene mutation. Our experience suggests a potential significant clinical benefit of checkpoint inhibitors used as single agents early on in the treatment of MMR-deficient/high microsatellite instability/hypermutated uterine cancers in women with Lynch syndrome. Key Points Even though checkpoint inhibitors are effective in mismatch repair-deficient endometrial cancer, it is unknown whether the response to them differs between women with endometrial cancer due to germline mutations in a mismatch repair gene (Lynch syndrome) and women with sporadic endometrial cancer. In our case, a patient with Lynch syndrome and recurrent mismatch repair-deficient serous endometrial cancer achieved a durable remission on the first-line therapy with the checkpoint inhibitor pembrolizumab and remains progression free after more than 2 years. Based on our observation and the data, suggesting the stronger immune activation in women with Lynch syndrome–associated endometrial cancer, we propose to use checkpoint inhibitor monotherapy early in the course of their treatment and stratify patients for the presence of Lynch syndrome in clinical trials.

Purpose To determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy. Materials and methods We undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined. Results Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34–0.56) and for overall survival was 0.65 (CI 0.45–0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence. Conclusion This retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association.

Background: $^{40}\mathrm{K}$ plays a significant role in the radiogenic heating of Earth-like exoplanets, which can affect the development of a habitable environment on their surfaces. The initial amount of $^{40}\mathrm{K}$ in the interior of these planets depends on the composition of the interstellar clouds from which they formed. Within this context, nuclear reactions that regulate the production of $^{40}\mathrm{K}$ during stellar evolution can play a critical role.Purpose: In this study, we constrain for the first time the astrophysical reaction rate of $^{40}\mathrm{K}(n,p)^{40}\mathrm{Ar}$, which is responsible for the destruction of $^{40}\mathrm{K}$ during stellar nucleosynthesis. We provide to the nuclear physics community high-resolution data on the cross section and angular distribution of the $^{40}\mathrm{Ar}(p,n)^{40}\mathrm{K}$ reaction. These are important to various applications involving $^{40}\mathrm{Ar}$. The associated reaction rate of the $^{40}\mathrm{Ar}(p,n)^{40}\mathrm{K}$ process addresses a reaction rate gap in the Joint Institute for Nuclear Astrophysics REACLIB database in the region of intermediate-mass isotopes.Methods: We performed differential cross-section measurements on the $^{40}\mathrm{Ar}(p,n)^{40}\mathrm{K}$ reaction, for six energies in the center-of-mass system between 3.2 and 4.0 MeV and various angles between ${0}^{\ensuremath{\circ}}$ and ${135}^{\ensuremath{\circ}}$. The experiment took place at the Edwards Accelerator Laboratory at Ohio University using the beam swinger target location and a standard neutron time-of-flight technique. We extracted total and partial cross sections by integrating the double differential cross sections we measured.Results: The total and partial cross sections varied with energy due to the contribution from isobaric analog states and Ericson type fluctuations. The energy-averaged neutron angular distributions were symmetrical relative to ${90}^{\ensuremath{\circ}}$. Based on the experimental data, local transmission coefficients were extracted and were used to calculate the astrophysical reaction rates of $^{40}\mathrm{Ar}(p,n)^{40}\mathrm{K}$ and $^{40}\mathrm{K}(n,p)^{40}\mathrm{Ar}$ reactions. The new rates were found to vary significantly from the theoretical rates in the REACLIB library. We implemented the new rates in network calculations to study nucleosynthesis via the slow neutron capture process, and we found that the produced abundance of $^{40}\mathrm{K}$ is reduced by up to 10% compared to calculations with the library rates. At the same time, the above result removes a significant portion of the previous theoretical uncertainty on the $^{40}\mathrm{K}$ yields from stellar evolution calculations.Conclusions: Our results support a destruction rate of $^{40}\mathrm{K}$ in massive stars via the $^{40}\mathrm{K}(n,p)^{40}\mathrm{Ar}$ reaction that is larger compared to previous estimates. The rate of $^{40}\mathrm{K}$ destruction via the $^{40}\mathrm{K}(n,p)^{40}\mathrm{Ar}$ reaction now has a dramatically reduced uncertainty based on our measurement. This result directly affects the predicted stellar yields of $^{40}\mathrm{K}$ from nucleosynthesis, which is a critical input parameter for the galactic chemical evolution models that are currently employed for the study of significant properties of exoplanets.

SUMMARY Objective: Cracks in amalgam-filled teeth may be related to amalgam expansion. This study measured cuspal flexure and used finite element analysis to assess associated stress levels in amalgam-filled teeth. Methods and Materials: External surfaces of 18 extracted molars were scanned in three dimensions. Nine molars were restored with mesio-occluso-distal amalgam fillings; the other teeth were left intact as controls. All teeth were stored in saline and scanned after two, four, and eight weeks. Cuspal flexure and restoration expansion were determined by calculating the difference between scanned surfaces. Stresses in a flexed tooth were calculated using finite element analysis. Results: Cusps of amalgam-filled teeth flexed outward approximately 3 μm, and restoration surfaces expanded 4 to 8 μm during storage. Cuspal flexure was significantly higher in the amalgam group (multivariate tests, p0.05). Expansion caused stress concentrations at the cavity line angles. These stress concentrations increased stresses due to mastication 44% to 178%. Conclusions: Amalgam expansion pushed cavity walls outward, which created stress concentrations at the cavity line angles. Expansion stresses can raise stresses in amalgam-filled teeth and contribute to incidentally observed cracks.

The objective of our study is to estimate the radiation exposure to pediatric patients with sarcoma getting required (or highly recommended) ionizing radiation scans during initial chemotherapy and to determine how often distant progressive disease was discovered. Data from the last 25 years from the Children's Oncology Group open phase III protocols were reviewed for the most common pediatric sarcomas: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. The number of required/recommended ionizing radiation scans, including chest radiographs, chest computed tomography, positron emission tomography scans, and bone scans during induction, consolidation, and maintenance chemotherapy, were recorded and the total radiation dose per patient was calculated. In addition, the number of patients who were removed from protocol during chemotherapy because of new or distant progressive disease was documented. In our analysis of 5845 patients, the average pediatric patient with sarcoma on protocol was exposed to an ionizing radiation dose of 37.1 mGy, equivalent to the lifetime dose of nuclear power plant workers, whereas the progression of disease was detected at most in 5.4% of the patients. Our study is meant to inform pediatric oncologists more precisely of the actual risks and benefits of mandated surveillance scans during chemotherapy in patients with sarcoma.

A 4-month-old boy with a history of muscular ventricular septal defect and atopic dermatitis presented with decreased oral intake, loose stools, stuffy nose, mild cough and diaphoresis. The patient had an in-home exposure to COVID-19. The initial respiratory pathogen panel was positive for adenovirus, consistent with his symptoms. The following day, the COVID-19 PCR was also positive. The patient was treated with supportive care, isolation precautions were implemented and the patient was discharged on day 4. This case demonstrates the importance of testing for COVID-19 even if a patient tests positive for another virus due to the possibility of coinfection, especially in children, in order to limit spread of COVID-19 to others.