Phototherapy and DNA Damage: A Systematic Review.

Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.

Delayed hypersensitivity reaction from microneedling twenty years after silicone fillers.

Skin rejuvenation procedures have increasingly flooded the aesthetic market, one of which includes microneedling. In microneedling, multiple fine punctures of the skin are performed with a needle to induce neocollagenesis. Microneedling has increasingly been used to treat inflammatory acne, acne scarring, photodamaged skin, and even radiation dermatitis. We present a patient with a stable history of liquid injectable silicone (LIS) given 20 years prior who developed chronic periocular and facial hypersensitivity after undergoing microneedling at a medi-spa. Long-term steroids and immunosuppressants were needed for control. The patient's severe reaction and resistance to treatment highlights the potential complications of microneedling administered by a non-medical professional in the setting of prior injectable silicone.

The Risk of COVID-19 Infection in Individuals with Alopecia Areata.

Objective: We sought to determine the risk of contracting coronavirus disease (COVID-19) in individuals with alopecia areata (AA) compared to individuals without AA. Methods: We queried the Symphony Health-derived data from the COVID-19 Research Database, and individuals with a diagnosis of AA from 2019 to 2020 were included in the AA cohort. Subjects with no record of AA diagnosis from 2019 to 2020 were randomly placed in the control group in a 4:1 size ratio compared with the AA group. Laboratory-confirmed cases of COVID-19 between January 1, 2020, and September 1, 2021, were identified. Results: The AA and non-AA cohorts included 73,784 and 280,991 subjects, respectively. The COVID-19 incidence rate ratio (IRR) for adults with AA was 0.72 (95% CI 0.68, 0.76) compared with adults without AA (p<0.001). Within the AA cohort, moderate-severe AA showed a similar decreased risk in COVID-19 infection compared to mild AA. Limitations: This study is limited by its retrospective nature and the use of ICD-10 codes for the identification of individuals with AA and COVID-19, which may underestimate the true burden of disease. Conclusion: Individuals with AA have a slightly decreased risk of contracting COVID-19. Notably, it has been demonstrated that interferon-gamma (IFN- γ) leads to the downregulation of the angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor.1 Thus, it is possible that increased levels of IFN- γ seen in individuals with AA confer some protection against this viral infection.

Association Between Primary Care Use Prior to Cancer Diagnosis and Subsequent Cancer Mortality in the Veterans Affairs Health System.

Importance: Primary care physicians (PCPs) are significant contributors of early cancer detection, yet few studies have investigated whether consistent primary care translates to improved downstream outcomes. Objective: To evaluate the association of prediagnostic primary care use with metastatic disease at diagnosis and cancer-specific mortality (CSM). Design, Setting, and Participants: This cohort study used databases with primary care and referral linkage from multiple Veterans' Affairs centers from 2004 to 2017 and had a 68-month median follow-up. Analysis was completed between July 2021 and September 2022. Participants included veterans older than 39 years who had been diagnosed with 1 of 12 cancers. Inclusion criteria included known clinical staging, survival follow-up, cause of death, and receiving care at the Veterans Affairs health system (VA). Exposures: Prediagnostic PCP use, measured in the 5 years prior to diagnosis. PCP visits were binned into none (0 visits), some (1-4 visits), and annual (5 visits). Main Outcomes and Measures: Metastatic disease at diagnosis, cancer-specific mortality (CSM) for entire cohort and stratified by tumor subtype. Results: Among 245 425 patients representing 12 tumor subtypes, mean age was 65.8 (9.3) years, and the cohort skewed male (97.6%), and White (76.1%), with higher levels of comorbidity (58.6% with Charlson Comorbidity Index scores ≥2). Compared with no prior visit, some PCP use was associated with 26% decreased odds of metastatic disease at diagnosis (odds ratio [OR], 0.74; 95% CI, 0.71-0.76; P < .001) and 12% reduced risk of CSM (subdistribution hazard ratio [SHR], 0.88; 95% CI, 0.86-0.89; P < .001). Annual PCP use was associated with 39% decreased odds of metastatic disease (OR, 0.61; 95% CI, 0.59-0.63; P < .001) and 21% reduced risk of CSM (SHR, 0.79; 95% CI, 0.77-0.81; P < .001). Among tumor subtypes, prostate cancer had the largest effect size for prior PCP use on metastatic disease at diagnosis (OR for annual use, 0.32; 95% CI, 0.30-0.35; P < .001) and CSM (SHRfor annual use, 0.51; 95% CI, 0.48-0.55; P < .001). Conclusions and Relevance: In this cohort study, increased primary care use before cancer diagnosis was associated with significant decreases in metastatic disease at diagnosis and cancer-related death, with potentially the greatest difference from annual use. PCPs play a vital role in cancer prevention, and additional resources should be allocated to assist these physicians.

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).

PURPOSE: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). MATERIALS AND METHODS: In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). RESULTS: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). CONCLUSION: The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Characterization of the diffusion signal of breast tissues using multi-exponential models.

PURPOSE: Restriction spectrum imaging (RSI) decomposes the diffusion-weighted MRI signal into separate components of known apparent diffusion coefficients (ADCs). The number of diffusion components and optimal ADCs for RSI are organ-specific and determined empirically. The purpose of this work was to determine the RSI model for breast tissues. METHODS: The diffusion-weighted MRI signal was described using a linear combination of multiple exponential components. A set of ADC values was estimated to fit voxels in cancer and control ROIs. Later, the signal contributions of each diffusion component were estimated using these fixed ADC values. Relative-fitting residuals and Bayesian information criterion were assessed. Contrast-to-noise ratio between cancer and fibroglandular tissue in RSI-derived signal contribution maps was compared to DCE imaging. RESULTS: A total of 74 women with breast cancer were scanned at 3.0 Tesla MRI. The fitting residuals of conventional ADC and Bayesian information criterion suggest that a 3-component model improves the characterization of the diffusion signal over a biexponential model. Estimated ADCs of triexponential model were D1,3 = 0, D2,3 = 1.5 × 10-3 , and D3,3 = 10.8 × 10-3 mm2 /s. The RSI-derived signal contributions of the slower diffusion components were larger in tumors than in fibroglandular tissues. Further, the contrast-to-noise and specificity at 80% sensitivity of DCE and a subset of RSI-derived maps were equivalent. CONCLUSION: Breast diffusion-weighted MRI signal was best described using a triexponential model. Tumor conspicuity in breast RSI model is comparable to that of DCE without the use of exogenous contrast. These data may be used as differential features between healthy and malignant breast tissues.

Care for critically and terminally ill patients and moral distress of physicians and nurses in tertiary hospitals in South Korea: A qualitative study.

Physicians and nurses working in acute care settings, such as tertiary hospitals, are involved in various stages of critical and terminal care, ranging from diagnosis of life-threatening diseases to care for the dying. It is well known that critical and terminal care causes moral distress to healthcare professionals. This study aimed to explore moral distress in critical and terminal care in acute hospital settings by analyzing the experiences of physicians and nurses from various departments. Semi-structured in-depth interviews were conducted in two tertiary hospitals in South Korea. The collected data were analyzed using grounded theory. A total of 22 physicians and nurses who had experienced moral difficulties regarding critical and terminal care were recruited via purposive maximum variation sampling, and 21 reported moral distress. The following points were what participants believed to be right for the patients: minimizing meaningless interventions during the terminal stage, letting patients know of their poor prognosis, saving lives, offering palliative care, and providing care with compassion. However, family dominance, hierarchy, the clinical culture of avoiding the discussion of death, lack of support for the surviving patients, and intensive workload challenged what the participants were pursuing and frustrated them. As a result, the participants experienced stress, lack of enthusiasm, guilt, depression, and skepticism. This study revealed that healthcare professionals working in tertiary hospitals in South Korea experienced moral distress when taking care of critically and terminally ill patients, in similar ways to the medical staff working in other settings. On the other hand, the present study uniquely identified that the aspects of saving lives and the necessity of palliative care were reported as those valued by healthcare professionals. This study contributes to the literature by adding data collected from two tertiary hospitals in South Korea.

Update on Biologics for Psoriasis in Clinical Practice.

Biologics have impacted the clinical management of moderate to severe psoriasis. This review article highlights new data findings from phase 3 clinical trials (N=8) published between May 2020 and February 2021. Data on the efficacy of US Food and Drug Administration-approved biologics for treating psoriasis affirms durable skin clearance in the presence of comorbidities and after treatment gaps. This article aims to provide clinicians with up-to-date knowledge on biologic performance focusing on skin disease clearance, time to skin disease clearance, loss of response and relapse, and treatment-emergent adverse events (TEAEs). Recent trial data in this review focus on treatment with IL-17A inhibitors and IL-23 inhibitors.

Hypofractionated radiation therapy as palliative management for symptomatic and local control of advanced thoracic malignancies.

BACKGROUND: Radiation therapy plays an important role for symptom palliation for intrathoracic malignancies ineligible for curative-intent therapy. Limited data exists regarding the role of stereotactic body radiation therapy (SBRT) versus conformal radiation in intrathoracic tumors for palliation. We report the efficacy of hypofractionated RT (or palliative SBRT) in the symptom management and durable control of lung and non-lung intrathoracic tumors. METHODS: We performed a retrospective review of ninety-two thoracic lesions across 76 patients who completed palliative SBRT with doses ranging 25-50 Gy in 5-10 fractions between 2009 and 2019. Symptoms (cough, chest pain, hemoptysis, shortness of breath) were assessed at consult and 1-6 months follow-up. Local control was evaluated using follow-up CT imaging via RECIST criteria. Descriptive statistics were used to evaluate symptom palliation and Kaplan-Meier method to analyze local control. RESULTS: Of primary lung (Cohort P) lesions, 40% showed stable symptoms, 30% never developed symptoms, and 19% showed symptom relief. CT imaging 1-6 months post-SBRT showed 91% with partial response (PR) or stable disease (SD) in Cohort P and 87% with PR or SD in metastatic (Cohort M) lesions. In patients with initial PR/SD, local control until death was achieved in 71% of Cohort P and 84% of Cohort M. Of our symptomatic patients (Cohort S), 98% showed no symptom progression post-radiotherapy. All patients with hemoptysis at presentation achieved hemostasis post-radiotherapy. CONCLUSIONS: Palliative SBRT has the advantage of higher biologic dose without protracted course for patients with limited prognosis. Patients showed significant symptom palliation and long-term local control. Palliative SBRT represents a reasonable treatment modality for incurable thoracic malignancies.

18F-Fluciclovine PET/CT in Therapeutic Decision Making for Prostate Cancer: A Large Single-Center Practice-Based Analysis.

METHODS: We carried out a retrospective cohort study of patients with BR after primary treatment of PC who received imaging with 18F-fluciclovine PET/CT at our institution between January 2010 and January 2019. PET/CT results were compared with biopsy, conventional imaging results, and/or response to PC therapy. 18F-Fluciclovine PET/CT performance statistics and effects on treatment planning were calculated. RESULTS: A total of 328 patients with a median age of 71 years (range, 47-90 years) and median serum prostate-specific antigen level of 1.6 ng/mL (0.02-186.7 ng/mL) were included. Three hundred thirty-six 18F-fluciclovine PET/CT scans were analyzed and classified as positive (65%), negative (25%), or equivocal (10%) based on radiology reports. Sensitivity was 93% (95% confidence interval, 86%-96%) and specificity was 63% (95% confidence interval, 45%-77%). Of patients with known management recommendations post-PET/CT, scan results changed or influenced pre-PET/CT management plans in 73%, and 58% of recommendations involved treatment modality decisions. Overall, 82% of patients' actual management was concordant with post-PET/CT recommendations. Of evaluable patients, 116 (35%) had some form of post-PET radiotherapy included in their care plans, with 95% receiving radiotherapy at a PET-avid target. CONCLUSIONS: In the largest single-institutional cohort to date, 18F-fluciclovine PET/CT showed value in the workup of PC in the setting of BR, with noteworthy influence over clinical management decisions. Further studies are needed to evaluate whether PET/CT-based changes in management are associated with improved outcomes.

Discrimination of Breast Cancer from Healthy Breast Tissue Using a Three-component Diffusion-weighted MRI Model.

PURPOSE: Diffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model. EXPERIMENTAL DESIGN: Patients with pathology-proven breast cancer from two datasets (n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C 1 and C 2 and their product, C 1 C 2, and signal fractions F 1, F 2, and F 1 F 2 were compared with the image defined on maximum b-value (DWI max), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (K app). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR80) and ROC AUC. RESULTS: Mean FPR80 for both datasets was 0.016 [95% confidence interval (CI), 0.008-0.024] for C 1 C 2, 0.136 (95% CI, 0.092-0.180) for C 1, 0.068 (95% CI, 0.049-0.087) for C 2, 0.462 (95% CI, 0.425-0.499) for F 1 F 2, 0.832 (95% CI, 0.797-0.868) for F 1, 0.176 (95% CI, 0.150-0.203) for F 2, 0.159 (95% CI, 0.114-0.204) for DWI max, 0.731 (95% CI, 0.692-0.770) for ADC, and 0.684 (95% CI, 0.660-0.709) for K app. Mean ROC AUC for C 1 C 2 was 0.984 (95% CI, 0.977-0.991). CONCLUSIONS: The C 1 C 2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI.

18F-Fluciclovine Uptake in Acute Appendicitis.

An 85-year-old man with biochemical recurrence of prostate cancer after prostatectomy was imaged with F-fluciclovine PET/CT. Images incidentally revealed F-fluciclovine uptake in a dilated appendix with associated fat stranding, suggestive of acute appendicitis. The patient was then questioned about abdominal symptoms, and he reported severe right lower quadrant pain. He then underwent laparoscopic appendectomy with pathology confirming acute appendicitis.

Symptom burden and characteristics of patients who die in the acute palliative care unit of a tertiary cancer center.

BACKGROUND: Acute palliative care unit (APCU) is a novel inpatient program in a tertiary cancer center that provides aggressive symptom management and assists with the transition to hospice. However, patients often die in the APCU before successfully transferring to hospice. The aim of this study was to evaluate the symptom burden and characteristics of advanced cancer patients who died in the APCU. METHODS: We retrospectively reviewed the medical records of all advanced cancer patients admitted to the APCU between April 2015 and March 2016 at a tertiary cancer center in Korea. Basic characteristics and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS) were retrieved. Statistical analyses were conducted to compare patients who died in the APCU with those who were discharged alive. RESULTS: Of the 267 patients, 87 patients (33%) died in the APCU. The median age of the patients was 66 years (range, 23-97 years). The most common primary cancer types were lung (21%), stomach (17%), and colorectal cancer (15%). Patients who died in the APCU had higher ESAS scores for drowsiness (6 vs. 5, P=0.002), dyspnea (4 vs. 2, P=0.001), anorexia (8 vs. 6, P=0.014) and insomnia (6 vs. 4, P=0.002) compared to patients who were discharged alive. The total symptom distress score (SDS) was also significantly higher (47 vs. 40, P=0.001) in patients who died in the APCU. In the multivariate analysis, patients who died in the APCU were more likely to be male [odds ratio (OR) 2.63, 95% confidence interval (CI): 1.49-4.64, P=0.001] and have higher ESAS scores for drowsiness (OR 2.08, 95% CI: 1.08-3.99, P=0.029) and dyspnea (OR 2.19, 95% CI: 1.26-3.80, P=0.005). Patients who died in the APCU showed significantly shorter survival after APCU admission (7 vs. 31 days, P<0.001). CONCLUSIONS: Advanced cancer patients who die in the APCU were more likely to be male and have significantly higher symptom burden including drowsiness and dyspnea. These patients showed rapid clinical deterioration after APCU admission. More proactive and timely end-of-life care is needed for these patients.

Delirium and its consequences in the specialized palliative care unit: Validation of the Korean version of Memorial Delirium Assessment Scale.

OBJECTIVES: Delirium is highly prevalent in patients with advanced cancer. This study aimed to investigate delirium rates and potential associated factors such as mortality in patients admitted to an acute palliative care unit (APCU). Our second aim was to validate the Korean version of the Memorial Delirium Assessment Scale (K-MDAS). METHODS: A total of 102 patients with advanced cancer, and who were admitted to the APCU, were assessed. Demographic data were collected alongside clinical diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, clinical symptoms according to the Edmonton Symptom Assessment System, history of smoking, alcohol use, hypnotic use, and daily dose of morphine were collected. The Confusion Assessment Method, the Delirium Rating Scale-Revised 98, and the K-MDAS were measured at admission and 1 week later. RESULTS: Twenty-four patients (23.52%) were diagnosed with delirium, and associated factors were old age (P = 0.007), higher ECOG (P = 0.011), and drowsiness (P < 0.001). The presence of delirium was an independent predictor of 1-month mortality; male gender, higher body mass index, and hypnotic use were also related to 1-month mortality. The K-MDAS had reliable internal consistency (α = 0.942) and showed sensitivity of 0.958 and specificity of 0.921 at the optimal cutoff score for diagnosing delirium of 9. CONCLUSIONS: Delirium was prevalent in patients admitted to the APCU and was associated with 1-month mortality. The K-MDAS showed acceptable reliability and validity and can be used to screen for delirium in a palliative care setting.

Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells.

Chromosomal instability (CIN) is a hallmark of many cancers and a major contributor to tumorigenesis. Centromere and kinetochore associated proteins such as the evolutionarily conserved centromeric histone H3 variant CENP-A, associate with centromeric DNA for centromere function and chromosomal stability. Stringent regulation of cellular CENP-A levels prevents its mislocalization in yeast and flies to maintain genome stability. CENP-A overexpression and mislocalization are observed in several cancers and reported to be associated with increased invasiveness and poor prognosis. We examined whether there is a direct relationship between mislocalization of overexpressed CENP-A and CIN using HeLa and chromosomally stable diploid RPE1 cell lines as model systems. Our results show that mislocalization of overexpressed CENP-A to chromosome arms leads to chromosome congression defects, lagging chromosomes, micronuclei formation and a delay in mitotic exit. CENP-A overexpressing cells showed altered localization of centromere and kinetochore associated proteins such as CENP-C, CENP-T and Nuf2 leading to weakened native kinetochores as shown by reduced interkinetochore distance and CIN. Importantly, our results show that mislocalization of CENP-A to chromosome arms is one of the major contributors for CIN as depletion of histone chaperone DAXX prevents CENP-A mislocalization and rescues the reduced interkinetochore distance and CIN phenotype in CENP-A overexpressing cells. In summary, our results establish that CENP-A overexpression and mislocalization result in a CIN phenotype in human cells. This study provides insights into how overexpression of CENP-A may contribute to CIN in cancers and underscore the importance of understanding the pathways that prevent CENP-A mislocalization for genome stability.