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Objective Police officers typically face multiple potentially traumatic events and consequently have a higher conditional probability of developing PTSD. Although most police officers with PTSD benefit from first-line treatment, it is unknown whether recommended intensification of treatment for low responders is effective and which factors contribute to response. This study aimed to examine the treatment response of a day clinic for police officers with PTSD and identify predictors of treatment response. Method Between 2009 and 2019, routine outcome monitoring measurements consisting of PTSD symptom severity and general psychological distress were administered at two timepoints among 102 patients undergoing a day clinic treatment consisting of trauma-focused therapy, sociotherapy, and psychomotor therapy. Hierarchical regression was used to assess whether change in PTSD symptom severity was associated with baseline PTSD and depression severity, gender, age, and eligibility for a recognition procedure. Results Significant improvements in PTSD symptom severity were found over the course of the treatment (d = .59), with 47% of patients showing statistically reliable improvement in their symptoms. The only significant predictor of treatment response was eligibility for a recognition procedure, with the total model explaining approximately 10% of the variation in treatment response. Conclusions Intensifying treatment for police officers with PTSD who do not respond to previous trauma-focused treatment appears beneficial for a substantial number of patients. However, eligibility for a recognition procedure may negatively impact treatment response. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Material and methods In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

BACKGROUND: Epidemiological studies from Europe and North America report an increasing incidence of microscopic colitis (MC) in the late twentieth century followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS: Residents of Olmsted County, Minnesota diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011 and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19–90); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% confidence interval [CI] 22.7–28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4–18.2) and CC 9.9 (95% CI, 8.1–11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (p

Osteoarthritis, the most common degenerative joint disease, occurs more frequently in joints that have sustained injury. Currently, osteoarthritis is diagnosed with imaging that finds radiographic changes after the disease has already progressed to multiple tissues. The primary objective of this study was to compare potential metabolomic biomarkers of joint injury between the synovial fluid and serum in a mouse model of post-traumatic osteoarthritis. The secondary objective was to gain insight into the pathophysiology of osteoarthritis by examining metabolomic profiles after joint injury. 12-week-old adult female C57BL/6 mice (n=12) were randomly assigned to control, day 1 post injury, or day 8 post injury groups. Randomly selected stifle (i.e., knee) joints were placed into a non-invasive injury apparatus and subjected to a single dynamic axial compression causing anterior translation of the tibia relative to the femur to tear the anterior cruciate ligament. At days 1 and 8 post injury, serum was extracted then mice were immediately euthanized prior to synovial fluid collection. Metabolites were extracted and analyzed by liquid chromatography coupled to mass spectrometry. We detected ~2500 metabolites across serum and synovial fluid. Of these metabolites 179 were positively correlated and 51 were negatively correlated between synovial fluid and serum, indicating potential for the development of metabolomic biomarkers. Synovial fluid appeared to capture differences in metabolomic profiles between injured mice at both day 1 and 8 after injury whereas serum did not. However, synovial fluid and serum were distinct at both days 1 and 8 after injury. In the synovial fluid, pathways of interest across different time points mapped to amino acid synthesis and degradation, bupropion degradation, and the tRNA charging pathway. In the serum, notable pathways across time points were amino acid synthesis and degradation, the phospholipase pathway, and nicotine degradation. These results provide a rich picture of the injury response at early time points following traumatic joint injury. Furthermore, the correlations between synovial fluid and serum metabolites suggest that there is potential to gain insight into intra-articular pathophysiology through analysis of serum metabolites.

Background Clinical manifestations of coronavirus disease 2019 (COVID19) can vary from asymptomatic to profusely symptomatic due to many factors. Having data on the clinical characteristics of the affected patients is important for the screening and diagnosis of COVID-19. Main objective of this study is to evaluate the clinical and epidemiological characteristics and outcomes of patients with COVID-19 admitted to six treatment centres in Sri Lanka. Methods For the specific epidemic situation of COVID-19, we chose to conduct a descriptive retrospective study from six treatment centres in the country between March 10, 2020 and May 30, 2020. Results The study included 431 laboratory confirmed patients with COVID-19. Of them, 335 (78.2%) were males and their mean age was 37 years. Most patients (373: 86.5%) had had close contact with COVID-19 positive patients. The majority were asymptomatic (243: 56.3%) and of the symptomatic patients, the most common symptom was sore throat (81, 19%), followed by cough (72, 17%), headache (72, 17%), fever (50, 12%), and nasal discharge (36, 8%). Eight patients required either high dependency care or intensive unit care two of them succumbed to the illness (0.5%). Hydroxychloroquine (HCQ) was used as a treatment in 248 patients and they had a significantly longer (17.6 days) duration of hospital stays compared those who were not treated (13.6 days) with HCQ. When the HCQ was not used as a treatment, asymptomatic individuals had significantly shorter durations of hospital (11.1 days) stays compared to symptomatic individuals (14.3 days). Conclusions The majority of patients remained asymptomatic during the course of illness. The most common symptom was sore throat, seen in one fifth of patients, followed by cough, and headache. Our study also indicated the possibility of reduced viral clearance and hence longer duration of hospital stays with HCQ.

Objective To evaluate long-term reproductive outcomes in couples who were enrolled in a large randomized controlled trial that studied optimal treatment for unexplained infertility. Design Telephone survey, administered between March 2019 and February 2020. Setting Large urban university-affiliated fertility center. Patient(s) Couples who enrolled in the Fast Track and Standard Treatment Trial (FASTT). Intervention(s) None. Main Outcomes Measure(s) Number of live births, methods of conception, adoption, and satisfaction regarding family size. Result(s) Of the 503 couples enrolled in FASTT, 311 (61.8%) were contacted and 286 (56.9%) consented to participate. The mean age and follicle-stimulating hormone level at the time of enrollment in FASTT were 33.1 ± 3.2 years and 6.8 ± 2.2 mIU/mL, respectively, for those who participated in this study. The mean age at follow-up was 49.5 ± 3.4 years. Of the 286 women, 194 (67.8%) had a live birth during the trial and 225 (78.7%) continued to try to conceive after FASTT. Of those who tried to conceive without treatment, 101 of 157 (64.3%) had a successful live birth, whereas 12 (5.3%) women had a live birth via intrauterine insemination and 82 (36.4%) via autologous oocyte in vitro fertilization. Overall, 182 (80.9%) women achieved a live birth after FASTT. Conclusion(s) The majority of couples were able to achieve a live birth after FASTT. Only 19 (6.6%) never achieved a live birth during their reproductive years. Moving to treatment sooner allows the opportunity to achieve >1 live birth, which is associated with increased satisfaction regarding family size. This further supports access to care and insurance coverage for infertility treatment.

Next-generation sequencing (NGS) of rearranged Ig genes is an effective technology for identifying pathologic clonal cells in multiple myeloma (MM) and tracking minimal residual disease. The clinical effect of implementing NGS in Ig gene clonality analysis was evaluated via a retrospective chart review. A total of 312 patients diagnosed with MM were enrolled in the study. Ig gene clonality was determined by fragment analysis using BIOMED-2 multiplex PCR assays and by NGS using the LymphoTrack IGH FR1 Assay and LymphoTrack IGK Assay. The clonality detection rates in diagnostic samples obtained using fragment analysis and NGS were 96.7% and 95.4%, respectively (statistically nonsignificant difference; P = 0.772). Among samples of patients in complete remission, the clonality detection rates obtained using fragment analysis and NGS were 33.3% and 60.3%, respectively (statistically significant difference; P = 0.034). Progression-free survival was significantly longer in negative than positive patients by NGS analysis (P = 0.03). Clonality detection by NGS-based methods using IGH FR1 and IGK assays in routine clinical practice is feasible, provides good clonality detection rates in diagnostic samples, and allows monitoring of samples in MM patients with significant prognostic value.

Objectives: We examined the use and long-term outcomes of vaginal hysterectomy for women with early-stage endometrial cancer. Methods: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women with stage I-II endometrial cancer treated with primary hysterectomy from 2000-2015. Multivariable models were developed to examine clinical, demographic, and pathologic factors associated with performance of TVH. The association between route of hysterectomy and cancer specific and overall survival was examined using multivariable Cox proportional hazards models. Results: A total of 19,212 patients including 837 (4.6%) who underwent TVH were identified. Performance of vaginal hysterectomy declined from 4.5% in 2000 to 2.2% in 2015 (P 80 years old (aRR=1.60; 95% CI, 1.30-1.97) were more likely to undergo TVH. There was no association between either overall co-morbidity (Charlson index) or any individual comorbidities and performance of TVH. Women with high grade tumors were less likely to undergo TVH. Five-year survival was 78.4% (95% CI: 77.6-79.2) in those who underwent abdominal hysterectomy, 83.3% (95% CI: 82.1-84.4) in those who had a laparoscopic hysterectomy and 80.9% (95% CI: 77.8-83.5) in those who underwent TVH. In multivariable models, there was no adverse impact between TVH and either overall (HR=1.06; 95% CI, 0.94-1.19) or cancer-specific (HR=0.95; 95% CI, 0.70-1.28) survival. Download : Download high-res image (83KB) Download : Download full-size image Conclusions: Use of vaginal hysterectomy for stage I/II endometrial cancer has decreased in the U.S. Chronologic age is the greatest predictor of performance of TVH. Performance of TVH does not negatively impact survival for women with early-stage endometrial cancer.

Purpose: Advances in the diagnosis and treatment of prostate cancer have increased the patients’ stress level and decreased the quality of life. A variety of instruments are currently available to evaluate patients with prostate cancer. However, only a few tools are available to assess Korean patients, and therefore we demonstrated a linguistic validation of Korean Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP).Methods: EPIC-CP was translated into Korean and the linguistic validation was evaluated. The evaluation process includes permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two bilingual translators independently translated the original questionnaire, discussed the feasibility and naturalness of initial translation, followed by revision to the reconciled version. Another translator then performed a backward translation into English. Ten patients with prostate cancer completed the translated questionnaire and performed cognitive debriefing.Results: The original EPIC-CP was translated into 2 Korean versions. The different wording in both versions and the ordinary words in the initial translations were changed considering the nuances and meanings of medical terms. During the backward translation, the panels made slight changes to clarify the meaning and nuances of the translated questionnaire. During cognitive debriefing, 10 patients answered the questionnaire and offered their opinions regarding comprehensibility and naturalness. Most patients agreed that the translation was comprehensible in general.Conclusions: Our study provides a successful linguistic validation of the EPIC-CP questionnaire. The translation is a helpful diagnostic tool to ensure the quality of life of patients with prostate cancer attending crowded clinics.

OBJECTIVES Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Rationale Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with COVID-19 is unknown. The objective of this study was to identify clinically relevant, novel subgroups in COVID-19-related ARDS, and compare them to previously described ARDS subphenotypes. Methods Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis (LCA) was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously-developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect (HTE) for corticosteroid-use in subgroups was tested. Measurements and Main Results From 3/2-4/30/2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class LCA model best fit the population (p=0.0075). Class 2 (23%) had higher pro-inflammatory markers, troponin, creatinine and lactate, lower bicarbonate and lower blood pressure than Class 1 (77%). 90-day mortality was higher in Class 2 versus Class 1 (75% vs 48%; p

PURPOSE Pain is among the most common and consequential symptoms of cancer, particularly in the context of lung cancer. Māori have extremely high rates of lung cancer, and there is evidence that Māori patients with lung cancer are less likely to receive curative treatment and more likely to receive palliative treatment and to wait longer for their treatment than non-Māori New Zealanders. The extent to which Māori patients with lung cancer are also less likely to have access to pain medicines as part of their supportive care remains unclear. METHODS Using national-level Cancer Registry and linked health records, we describe access to subsidized pain medicines among patients with lung cancer diagnosed over the decade spanning 2007-2016 and compare access between Māori and non-Māori patients. Descriptive and logistic regression methods were used to compare access between ethnic groups. RESULTS We observed that the majority of patients with lung cancer are accessing some form of pain medicine and there do not appear to be strong differences between Māori and non-Māori in terms of overall access or the type of pain medicine dispensed. However, Māori patients appeared more likely than non-Māori to first access pain medicines within 2 weeks before their death and commensurately less likely to access them more than 24 weeks before death. CONCLUSION Given the plausibility that there are differences in first access to pain medicines (particularly opioid medicines) among Māori approaching end of life, further investigation of the factors contributing to this disparity is required.

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004&ndash, 2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan&ndash, Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

Long-term cannabis use during adolescence has deleterious effects in brain that are largely ascribed to the activation of cannabinoid-1 receptors (CB1Rs) by delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive compound in marijuana. Systemic administration of ∆9-THC inhibits acetylcholine release in the prelimbic-prefrontal cortex (PL-PFC). In turn, PL-PFC acetylcholine plays a role in executive activities regulated by CB1R-targeting endocannabinoids, which are generated by cholinergic stimulation of muscarinic-1 receptors (M1Rs). However, the long-term effects of chronic administration of increasing doses of ∆9-THC in adolescent males on the distribution and function of M1 and/or CB1 receptors in the PL-PFC remains unresolved. We used C57BL\6J male mice pre-treated with vehicle or escalating daily doses of ∆9-THC to begin filling this gap. Electron microscopic immunolabeling showed M1R-immunogold particles on plasma membranes and in association with cytoplasmic membranes in varying sized dendrites and dendritic spines. These dendritic profiles received synaptic inputs from unlabeled, CB1R- and/or M1R-labeled axon terminals in the PL-PFC of both treatment groups. However, there was a size-dependent decrease in total (plasmalemmal and cytoplasmic) M1R gold particles in small dendrites within the PL-PFC of mice receiving ∆9-THC. Whole cell current-clamp recording in PL-PFC slice preparations further revealed that adolescent pretreatment with ∆9-THC attenuates the hyperpolarization and increases the firing rate produced by local muscarinic stimulation. Repeated administration of ∆9-THC during adolescence also reduced spontaneous alternations in a Y-maze paradigm designed for measures of PFC-dependent memory function in adult mice. Our results provide new information implicating M1Rs in cortical dysfunctions resulting from adolescent abuse of marijuana.

Introduction The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. Methods Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response. Results In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6–18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5–93.5) by investigator and 92.0% (95% CI: 84.1–96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6–88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9–98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1–87.7). Safety data were consistent with the known tolerability profile of alectinib. Conclusions These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.

Cognitive behavioral therapy, first introduced by Beck in the 1950s to treat depression by integrating cognitive and behavioral therapies, is now an established psychotherapy technique used to treat insomnia, chronic pain, and anxiety. Currently, cognitive behavioral therapy is widely used to treat tinnitus in European countries, and the efficacy and safety of the treatment have been proven through randomized clinical trials and meta-analyses. Although interest in cognitive behavioral therapy for tinnitus is increasing in Korea, there are limited reports. Because many studies so far have targeted patients in Western countries, it is difficult to apply the same to domestic patients due to cultural and linguistic differences, the absence of standardized guidelines, and limitations in clinic hours. We experienced various cases in which tinnitus was effectively treated simultaneously with pharmacotherapy and cognitive behavioral therapy, so here we report an introduction to the program along with a literature review. Cognitive behavioral therapy was performed as a 4-week program in our hospital, and progress was evaluated through Visual Analogue Scales (VAS) and tinnitus handicap inventory (THI). After each weekly 20-minute individual counseling session, a take-home writing task was given to the patient. The main goal was to guide the patient to discover and correct automatic thoughts related to their tinnitus symptoms. This paper aimed to introduce a specific scheme on how to perform cognitive behavioral therapy for domestic tinnitus patients.

OBJECTIVE While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses. DESIGN Cost-effectiveness study POPULATION: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management. METHODS The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings. MAIN OUTCOME MEASURES The primary outcome was the cost-effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost-effectiveness ratios (ICERs). RESULTS MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer-related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses. CONCLUSION MIS constitutes a cost-effective management strategy for women with suspicious ovarian masses. TWEETABLE ABSTRACT MIS is a cost-effective management strategy for women with suspicious ovarian masses.

Substance use disorders (SUDs) are moderately to highly heritable and are in part cross-transmitted genetically, as observed in twin and family studies. We performed exome-focused genotyping to examine the cross-transmission of four SUDs: alcohol use disorder (AUD, n = 4487); nicotine use disorder (NUD, n = 4394); cannabis use disorder (CUD, n = 954); and nonmedical prescription opioid use disorder (NMPOUD, n = 346) within a large nationally representative sample (n = 36,309), the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). All diagnoses were based on in-person structured psychiatric interview (AUDADIS-5). SUD cases were compared alone and together to 3959 "super controls" who had neither a SUD nor a psychiatric disorder using an exome-focused array assaying 363,496 SNPs, yielding a representative view of within-disorder and cross-disorder genetic influences on SUDs. The 29 top susceptibility genes for one or more SUDs overlapped highly with genes previously implicated by GWAS of SUD. Polygenic scores (PGS) were computed within the European ancestry (EA) component of the sample (n = 12,505) using summary statistics from each of four clinically distinct SUDs compared to the 3959 "super controls" but then used for two distinctly different purposes: to predict SUD severity (mild, moderate, or severe) and to predict each of the other 3 SUDs. Our findings based on PGS highlight shared and unshared genetic contributions to the pathogenesis of SUDs, confirming the strong cross-inheritance of AUD and NUD as well as the distinctiveness of inheritance of opioid use disorder.

Background Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate‐resistant prostate cancer (mCRPC). Methods We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high‐ and moderate‐intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews. Results Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty‐three men (82%) completed the 12‐week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others. Conclusions Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer., We conducted a 3‐arm pilot randomized controlled trial to determine the feasibility, safety, and acceptability of two modes of remotely monitored exercise (resistance or aerobic) over 12 weeks compared to usual care in 25 men with metastatic castrate‐resistant prostate cancer (mCRPC). We report that remotely monitored exercise training is feasible, safe, and acceptable in this patient population, with a high satisfaction rate. Through this research we provide direction and rationale for future studies of exercise and clinical outcomes for people with metastatic cancer.

Over 30% of adults with congenital heart disease (CHD) experience depression.To evaluate the effectiveness of Rational Emotive Behavior Therapy (REBT) in reducing depressive symptoms in adults with CHD.Forty-two adults with CHD were recruited from an outpatient clinic and randomized to a study group (n = 21), which comprised 8-weekly group-based counseling sessions, or a control group (n = 21), which received usual care. REBT effectiveness was examined using the Hamilton Depression Rating Scale, Beck Depression Inventory, Shorten General Attitude and Belief Scale, and salivary cortisol levels before therapy, after the last session, and at follow-up 4 weeks later.Average participant ages were 30.1 ± 7.58 and 33.3 ± 7.1 years in study and control groups, respectively; 52.4% of participants in each group were female. After REBT, depression (p 0.001), irrational beliefs (p 0.001), and salivary cortisol levels (p = 0.006) were significantly lower in the study group than in the control group. Effects of REBT in the study group remained consistent at the 4-week follow-up.REBT may be effective in reducing depression in adults with CHD.

Tyrosine kinase inhibitors (TKIs) have been widely used to treat various malignancies, dramatically improving survival. The use of these treatments has been limited by adverse effects. Ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, has been associated with increased prevalence of atrial fibrillation (AF) in approximately 5%–16% of patients, especially those with prior history of AF,1 and often leads to treatment discontinuation in a significant proportion of patients. Management of AF in this patient population also presents a unique challenge. Current guidelines recommend rate control as the primary strategy,2,3 which can be challenging, since pharmacological management is limited by significant drug interactions with cancer therapies as well as potential side effects. Additionally, the need for anticoagulation in this strategy is challenged by increased risk of bleeding owing to inhibition of collagen-induced platelet aggregation by ibrutinib.4 Recent studies document the long-term benefits of catheter ablation in maintaining sinus rhythm in the general population. We present a case of ibrutinib-associated symptomatic AF, which was successfully treated with ablation therapy, and allowed the patient to return to ibrutinib therapy for adequate management of his cancer (Figure 1). Open in a separate window Figure 1 Timeline showing cardiovascular and hematologic disease and treatment course. AF = atrial fibrillation; CLL = chronic lymphocytic leukemia; AAD = antiarrhythmic drug; OAC = oral anticoagulant. (Figure created with BioRender.com.)

Background To investigate the impact of programmed death‐ligand 1 (PD‐L1) polymorphisms on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with curative radiotherapy. Methods Four single nucleotide polymorphisms (SNPs) (rs822336G>C, rs822337T>A, rs822338C>T, and rs2297136A>G) in the PD‐L1 gene were evaluated in 124 NSCLC patients. Clinical stage was I in 28, II in 17, and III in 79 patients. Fifty‐seven patients received radiotherapy alone, including 28 patients who received stereotactic body radiotherapy. Sixty‐seven patients received sequential or concurrent chemoradiotherapy. Risk factors for survival outcomes were analyzed with the log‐rank test and multivariate Cox proportional hazards models. Results The rs822336GC+CC genotype was associated with better overall survival (OS) (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.97, p = 0.036) and regional failure‐free survival (RFFS) (HR = 0.32, 95% CI = 0.14–0.76, p = 0.009), compared with rs822336GG genotype. The rs822337TA+AA genotype was associated with better OS (HR =0.54, 95% CI = 0.34–0.88, p = 0.014), progression‐free survival (PFS) (HR = 0.64, 95% CI = 0.41–0.99, p = 0.046), and RFFS (HR = 0.38, 95% CI = 0.17–0.81, p = 0.013), compared with rs822337TT genotype. Three SNPs (rs822336, rs822337, and rs822338) were in linkage disequilibrium. Combined GTC and GTT (GT*) haplotype was associated with significantly worse OS (p = 0.018), PFS (p = 0.044), and RFFS (p = 0.038), compared with those with other combined haplotypes. Patients with diplotypes of two GT* haplotypes showed significantly worse OS (p = 0.023) and RFFS (p = 0.014) than those with other diplotypes. Conclusions These findings suggest that PD‐L1 polymorphisms could be predictive markers for NSCLC patients receiving radiotherapy., Genotypes of two SNPs (rs822336G>C and rs822337T>A) and the risk groups of diplotypes of rs822336‐rs822337‐rs822338 haplotypes in the PD‐L1 gene were significantly associated with overall survival. These genotypes were related to regional failure‐free survival in terms of patterns of initial failure.

Summary Objective To explore how systemic factors that modify knee osteoarthritis risk are connected to ‘whole-joint’ structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. Methods Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9–13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. Results High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. Conclusion Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

PURPOSE: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36–1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29–2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11–1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41–1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19–5.96) and number of cancerous biopsy cores (3 vs 1–2 cores aHR 1.59, 95% CI 1.37–1.84; ≥4 vs 1–2 cores aHR 3.29, 95% CI 2.94–3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93–0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

In this work, we demonstrate that t-tubule remodeling occurs in the atrophied left ventricle as well as the overloaded right ventricle after right-side heart failure. Moreover, we identify that t-tubule remodeling in both ventricles is linked to sarcoplasmic reticulum remodeling as indicated by decreased labeling periodicity of both the Ca2+ release channel, RyR2, and the cardiac junction-forming protein, JPH2, that forms a link between the sarcoplasmic reticulum and sarcolemma. Studies developing treatments for right-sided heart failure should consider effects on both the right and left ventricle.

Despite the expanding clinical application of hydroxychloroquine in dermatology, the overall data on hydroxychloroquine use among dermatologists are limited. With retrospective review of the medical records of the 790 patients who were prescribed hydroxychloroquine, we classified the diagnoses into 12 disease categories, the lupus erythematosus group being the largest. The lupus erythematosus group had the longest prescription duration (median, 6.2 months), whereas the photodermatitis group had a significantly shorter prescription duration (median, 0.5 months). The overall good response rate was 77.1%. The photodermatitis group had the best response (88.7%), followed by the lupus panniculitis (85.1%) and lichen planus (84.4%). In conclusion, hydroxychloroquine has proven utility for various inflammatory skin diseases, including but not limited to cutaneous lupus erythematosus.

The majority of cases of Shiga toxin-producing Escherichia coli are self-limited; however, the infection can occasionally be complicated by more severe phenomena, such as thrombotic microangiopathy, with resultant end-organ damage to the kidneys, colon, nervous system, and various other tissues. Shiga toxin-induced hemolytic uremic syndrome (ST-HUS)-the constellation of thrombocytopenia, hemolysis, and renal failure resulting from thrombotic microangiopathy in a subset of infections producing the Shiga toxin-is classically observed in the pediatric population. Nevertheless, the diagnosis should be considered in adults with this presentation, and especially in those with colonic findings suggestive of ischemia. ST-HUS must also be distinguished from other thrombotic microangiopathies and related conditions, such as disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and complement-mediated HUS, as these diagnoses prompt alternate management strategies. Here, we present a case of ST-HUS in a gentleman following pericardiectomy who was infected with non-O157:H7 E. coli producing Shiga toxin 2.

Background and Objectives Fat myringoplasty is a simple, fast, and effective procedure for repairing tympanic membrane (TM) perforations. The aim of this study is to evaluate the surgical outcomes of pure-fat myringoplasty for small TM perforations at our hospital and review the current knowledge regarding fat myringoplasty, with consideration of the effectiveness of additional substances used in the treatment of small TM perforations.Subjects and Method We retrospectively studied 41 patients who underwent pure-fat myringoplasty at our hospital from March 2008 through April 2019 and were followed up for at least 2 months thereafter.Results Of 41 patients, 16 were males and 25 were females, with the mean age of 48 (male, 9-75 years; female, 16-65 years). All perforations were classified as small perforations, ranging from 1% to 17% of the TM. The overall success rate was 92.7%, with the TMs of 3 patients (7.3%) failing to close. Air-bone gap (ABG) decreased in 19 out of 24 patients who underwent both preoperative and postoperative pure tone audiometric examinations. The mean ABG was 4.42 dB (n=24; paired-t test, p=0.001; 95% confidence interval, 1.77-7.07). The literature review revealed that TM closure success rate of over 80% was associated with pure-fat myringoplasty, while the TM closure success rate for fat myringoplasty with additional substances was 85% to 100%.Conclusion Our study revealed a high TM closure success rate and good hearing outcomes are associated with pure-fat myringoplasty. Pure-fat myringoplasty seems to be sufficient for repairing small TM perforations.

BACKGROUND Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative. OBJECTIVE To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation). METHODS Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment. RESULTS Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n = 3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment. CONCLUSION HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease.

A modified Delphi study was conducted to (1) identify intervention elements that are considered by geriatricians to be important in optimizing prescribing for older adults with multimorbidity, and (2) to select the accompanying behavior change techniques to be incorporated into a context-relevant intervention to support prescribing. Intervention elements such as medication review identified by the Delphi panel mirrored results from a previous scoping review. Statements involving roles of pharmacists selected by the panel validated findings in the literature that pharmacists play important collaborative roles to help reduce potentially inappropriate prescribing among older adults with multimorbidity. We identified relevant intervention elements and their accompanying behavior change techniques to aid in the development of a context-specific intervention. Potentially inappropriate prescribing among older adults is a rising concern, attributed mainly by polypharmacy and multimorbidity. We aimed to identify key components and strategies for construction of a context-relevant intervention to facilitate appropriate prescribing in outpatient clinics in Singapore. The modified Delphi study was conducted in two rounds with 20 geriatricians from seven public hospitals in Singapore. Round one survey presented 69 statements formulated from a scoping review, while round two presented 23 statements with some modifications based on round one comments. The statements were rated against a 7-point Likert scale on their importance and impact on prescribing for older adults with multimorbidty. Consensus were achieved for 90% of the statements. Seven intervention elements were identified as being important: medication review, training, medication therapy management, shared decision making, patient interview, medication reconciliation, comprehensive geriatric assessment. In addition, some commonly identified behavior change techniques included goal setting (behavior), goal setting (outcome) and problem solving. This study identified important intervention elements and their potential strategies that could be adopted in an intervention to optimize appropriate prescribing for older adults with multimorbidity.

Isolated extramedullary relapse (EMR) without bone marrow relapse (BMR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a rare condition in patients with acute lymphoblastic leukemia (ALL), and the role of immunotherapeutic agents for these patients remains unclear. We analyzed treatment outcomes of blinatumomab or inotuzumab ozogamicin (INO) as first- or second-line salvage therapy in nine patients with Philadelphia chromosome-negative B-cell precursor ALL presenting with isolated EMR after previous allo-HCT. In seven patients receiving blinatumomab as first-line salvage therapy, 4 (57.1%) achieved complete remission (CR). Among the three patients without remission after blinatumomab, two switched to INO and subsequently showed responses {one CR and one partial response [PR]}, and one switched to multiagent chemotherapy that led to CR. In the two patients receiving first-line salvage therapy with INO, one showed PR and the other achieved CR. Overall, 6 (66.7%) of nine patients achieved CR, and five of them proceeded to allo-HCT in CR. The median overall survival after relapse was 27.8 months. In conclusion, both blinatumomab and INO showed good response rates and a safe bridging role to second allo-HCT in patients with isolated EMR. However, clinical differences between isolated EMR and EMR with BMR remain to be elucidated.

Background Although nonmass enhancement (NME) extension to the nipple at preoperative MRI frequently leads to sacrifice of the nipple-areolar complex (NAC), its correlation with pathologically confirmed NAC involvement is unclear. Purpose To evaluate the diagnostic accuracy of using NME extension to the subareolar region at breast MRI to predict pathologic nipple involvement and the eligibility for nipple-sparing mastectomy. Materials and Methods From November 2017 to November 2019, the authors prospectively enrolled participants with breast cancer and NME within 2 cm of the nipple at breast MRI who underwent surgery that included removal of the NAC. The authors evaluated NME extensions that were ipsilateral and contiguous with the biopsy-proven tumor lesions on images acquired during the early contrast phases. Pathologic nipple involvement and the distance from the nipple to the nearest cancer cell were evaluated by using serial vertical sectioning of the area extending from the entire NAC to the tumor. The primary end point was the positive predictive value (PPV) of NME, which was calculated as follows: (number with pathologic nipple invasion and NME extension to the nipple at breast MRI/number with NME extension to the nipple at breast MRI) × 100. Results Of 64 women (mean age, 52 years ± 9.8 [standard deviation]), 49 (77%) had NME extension to the nipple at breast MRI. The PPV of NME extension to the nipple was 86% (42 of 49 women; 95% CI: 73, 94). Among the 15 participants without NME extension to the nipple, only one (7%) had pathologic nipple involvement. The diagnostic accuracy of using NME extension to the nipple was 88% (56 of 64 women; 95% CI: 77, 95). The radiologic distance correlated well with the pathologic distance (Spearman correlation coefficient = 0.71, P = .003). Conclusion Nonmass enhancement extension to the nipple base at preoperative MRI has a high positive predictive value for identifying tumor involvement of the nipple, a contraindication to nipple-sparing mastectomy. © RSNA, 2021 Online supplemental material is available for this article.

Immune checkpoint inhibitors (ICI) have demonstrated efficacy in the treatment of solid cancers. However, there is no unified predictive biomarker available for ICIs. We aimed to compare the prognostic impact of using three PD-L1 antibodies (SP142, SP263, and 22C3) for immunohistochemical (IHC) analysis. We retrospectively investigated tumor tissues derived from 316 breast cancer cases, by constructing tissue microarrays and by performing IHC staining. The immune-cell expression rate (for SP142 and SP263) and combined proportional score (for 22C3) were evaluated, and survival outcomes were analyzed. Prediction models were developed, and values of Harrel’s c-index and areas under curves were calculated to compare the discriminatory power. Negative PD-L1 expression based on the 22C3-IHC assay was determined to be an independent prognostic marker for recurrence-free survival (RFS, P = 0.0337) and distant metastasis-free survival (DMFS, P = 0.0131). However, PD-L1 expression based on SP142- and SP263-IHC assays did not reveal a prognostic impact. Among the three antibodies, adding PD-L1 expression data obtained via 22C3-IHC assay to the null model led to a significant improvement in the discriminatory power of RFS and DMFS. We suggest that PD-L1 expression based on the 22C3-IHC assay is a superior prognostic marker than that based on SP142- and SP263-IHC assays.

Background: Heart rate (HR) monitored by a wearable device (WD) has demonstrated its clinical feasibility for thyrotoxicosis subjects. However, the association of HR monitored by wearables with hypothyroidism has not been examined. We assessed the association between serum thyroid hormone concentration and three WD-HR parameters in hypothyroid subjects.Methods: Forty-four subjects scheduled for radioactive iodine therapy (RAI Tx) after thyroid cancer surgery were included. Thirty subjects were prepared for RAI Tx by thyroid hormone withdrawal (hypothyroidism group) and 14 subjects by recombinant human thyrotropin (control group). Three WD-HR parameters were calculated from the HR data collected during rest, during sleep, and from 2:00 AM to 6:00 AM, respectively. We analyzed the changes in conventionally measured resting HR (On-site rHR) and WDHR parameters relative to thyroid hormone levels.Results: Serum free thyroxine (T4) levels, On-site rHR, and WD-HR parameters were lower in the hypothyroid group than in the control group at the time of RAI Tx. WD-HR parameters also reflected minute changes in free T4 levels. A decrease in On-site rHR and WD-HR parameters by one standard deviation (On-site rHR, approximately 12 bpm; WD-HR parameters, approximately 8 bpm) was associated with a 0.2 ng/dL decrease in free T4 levels (P

Anastomotic leak after colorectal surgery can result in serious morbidity for certain patients. The rate of clinically significant anastomotic leak after colon resection ranges from 1.8% to 11.9%. Risk factors include male sex, steroids, smoking, perioperative blood transfusion, malnutrition, and a low anastomosis. However, the effect of pre-operative chemoradiation therapy (CRT) on rates of anastomotic leak is controversial. Specifically, late leaks, which are defined as those that occur greater than 30 days after surgery, are sparsely described in current literature. Recent evidence suggests that CRT may contribute to the presentation of late anastomotic leaks. In this case series, we report our experience with three patients who received CRT and developed varying presentations of a late anastomotic leak. Therefore, our experience supports the consideration of late anastomotic leaks as a separate entity in colorectal surgery. While pre-operative CRT may increase risk for postoperative anastomotic leak overall, further exploration into the relationship between preoperative CRT and late anastomotic leaks is warranted.

Background Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS). Methods A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort. A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort. Results In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17< score ≤0.4), high-risk (0.4< score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P

Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p

Background and Objectives The pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL), an otologic emergency disease, remains unclear. Several studies have attempted to illustrate the association between cytokines and ISSNHL. The purpose of this study was to evaluate the prognostic significance of various cytokines in patients with ISSNHL. Subjects and Method In this case-control study, a total of 55 patients with ISSNHL underwent treatment with oral prednisolone for 2 weeks. Serum cytokine levels, including interleukins (ILs) (IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12), and tumor necrosis factors (TNF-α and TNF-β), were measured using human cytokine panels at first visit. Patient characteristics such as age, gender, the status of hypertension, diabetes mellitus, vertigo, time from onset to visit, and initial hearing levels were also evaluated. Results Serum levels of cytokines were correlated with the prognosis of ISSNHL patients. IL-4 ≥0.225 (pg/mL) and TNF-α ≥5.155 (pg/mL) were significantly associated with poor therapeutic outcomes (OR=44.317, p=0.015 and OR=269.465, p=0.006, respectively). In addition, age and initial hearing levels were also significant prognostic factors. Conclusion Patients’ age, initial hearing levels, and serum levels of IL-4 and TNF-α prior to treatment are associated with hearing recovery and can be used as prognostic factors for patients with ISSNHL.

Purpose: To report a satisfactory clinical outcome of hemorrhagic retinal macrocyst with retinal detachment after pars plana vitrectomy and silicone oil injection. Case summary: A 33-year-old man visited our clinic with a 1-week history of visual disturbance in his left eye. His ocular and medical history were unremarkable, and best-corrected visual acuity (BCVA) in the left eye was 20/40. Fundoscopic examination of the left eye showed a hemorrhagic retinal macrocyst that was well-demarcated, semi-transparent, dome-shaped, and larger than 8 disc diameters at the superonasal location, with macular-off retinal detachment. B-scan ultrasonography also confirmed the presence of an intra-retinal cystic lesion with internal mobile echogenic signals representing blood. The patient underwent 23-gauge pars plana vitrectomy, barrier laser photocoagulation around the retinal tear and boundary of the cyst, and silicone oil injection, without any other additional procedures for the hemorrhagic retinal macrocyst. After the surgery, the patient stayed in the face down position for two weeks. Three months postoperatively, a completely collapsed hemorrhagic retinal macrocyst with successful retinal reattachment was observed. Six months later, the BCVA in the left eye had improved to 20/30. One year later, even after silicon oil removal, the collapsed hemorrhagic retinal macrocyst and reattached retina remained stable.Conclusions: A hemorrhagic retinal macrocyst with retinal detachment was successfully treated with pars plana vitrectomy and silicone oil tamponade.

Purpose: To compare differences between the original criteria for diagnosis of ocular sarcoidosis (OS) (first International Workshop for OS [IWOS] 2009) and the revised criteria (sixth IWOS 2017), and their clinical usefulness when assessing OS in Korean patients. Methods: We analyzed patients with suspected OS who visited our tertiary referral ophthalmological and pulmonary clinic from 2007 to 2018. We diagnosed patients using both sets of criteria. Blood test and biopsy data (collected by physicians) and slit-lamp, fundus, and fluorescein angiography data (collected by ophthalmologists) were reviewed. Results: Thirty-four patients were diagnosed using both criteria. Of 32 patients who underwent biopsies, 31 had OS (96.87%). Using either set of criteria, 31 patients were diagnosed with definite OS and two with presumed OS. One patient diagnosed with possible OS using the previous criteria was diagnosed with presumed OS using the revised criteria. The new criteria add the lysozyme level, the CD4/CD8 ratio, and positron emission tomography imaging data to the old criteria and add the descriptors “presumed OS” and “probable OS”. There is no need to use the revised criteria in Korea; the biopsy and imaging data are adequately diagnostic. Conclusions: IWOS revised the OS diagnostic criteria by adding new parameters. However, this was unnecessary for Korea, where the biopsy and imaging data are adequately diagnostic.

Objective During theCOVID-19 pandemic, many clinicians increased provision of telemedicine services. This study describes patient experiences with telemedicine for contraceptive counseling during the COVID-19 pandemic in New York City. Study design This is a mixed-methods study which includes a web-based or phone survey and in-depth phone interviews with patients who had telemedicine visits for contraception. Results A total of 169 patients had eligible telemedicine visits between April 1 and June 30, 2020. Of these, 86 (51%) responded to the survey, and 23 (14%) participated in the interviews. We found that 86% of survey respondents were very satisfied with the telemedicine visit, and 63% said it completely met their needs. A majority (73%) strongly agreed that these visits should be maintained after the COVID-19 pandemic, and half (51%) would be very likely to choose them over in-person visits. In-depth interviews highlighted the convenience of telemedicine, especially for those with work or parenting responsibilities. Although some patients had in-person visits after telehealth, many appreciated the counseling they received remotely, and found the subsequent in-person visits more efficient. Patients identified visits that do not require physical exams as ideal visits for telehealth, and some hoped that all or most of their future visits would be telehealth visits. Many patients (43%) expressed a preference for phone over video visits. Conclusions Patients reported an overall positive experience with telemedicine visits for contraceptive counseling during the COVID-19 pandemic. They appreciated the convenience of telemedicine visits and valued the virtual counseling experience. Implications Health care providers who initiated or expanded telemedicine services for contraceptive counseling during the COVID-19 pandemic should consider continuing to offer them after the pandemic. At the policy level, these findings favor expanding access to telemedicine and providing reimbursement for virtual visits, including telephone visits.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Objective The relation between female emotional laborers’ sleep quality and autonomic nervous system activity was investigated.Methods Thirty-three subjects’ heart rate variability (HRV) data and results of self-reported scale on sleep, depression, anxiety and suicidality, were collected. Subjects were classified into good sleeper (GS) and poor sleeper (PS) groups relying on sleep quality. Changes of HRV between working time and resting time in each group were compared.Results The PS group showed significantly lower difference in root mean square of successive differences (RMSSD), percentage of successive normal-to-normal intervals that differ by more than 50 ms (pNN50), and natural logarithm high-frequency (LnHF) when they were working as compared to when they were resting, which means decreased function of the parasympathetic nervous system (PNS). Repeated measures analysis of covariance showed that the group effect was significant only for LnHF, with score of depression scale as a covariate.Conclusion Female emotional laborers who complain of sleep difficulty may have decreased function of the PNS. Therefore, good sleep quality is essential for maintaining and promoting mental and physical health of women engage in emotional labor.

Microscopic colitis (MC) is a common cause of chronic watery diarrhea, with the highest incidence in women over age 50.1 Cross-sectional studies have suggested that patients with MC have a lower incidence of adenomatous colon polyps compared with those without MC.2-4 The existing literature is limited by cross-sectional design, small sample sizes, lack of longitudinal follow-up, and the use of average-risk patients, rather than those with chronic diarrhea, as controls. We aimed to explore the association between MC and colon adenomas.

Background In advanced cancer patients, pelvic bone metastasis often causes pain and gait disturbance. The use of percutaneous bone cement [polymethylmethacrylate (PMMA)] injection for pain management and strengthening in pelvic bone metastasis has rarely been reported. To evaluate this method, we aimed to determine surgical outcomes and complications over a long-term follow-up period using a large patient group. Patients and Methods We retrospectively collected data from 178 patients who underwent percutaneous cementoplasty for pelvic metastatic lesions, 201 in total. Surgical outcomes evaluated included pain reduction and improvement of ambulation. Mortality within 1 month after procedure and pulmonary embolism caused by thrombus, fat, tumor emboli, or bone cement were investigated as surgical complications. For long-term survivors, pain relapse and mechanical failure were analyzed. The mean follow-up period was 12.6 months, and there were 159 fatalities at last follow-up. Results The mean regional pain numerical rating scale scores decreased from 6.1 preoperatively to 2.4 1 month after procedure (p < 0.01). Gait function was maintained, worsened, and uncheckable in 68%, 24%, and 8% of patients, respectively, 1 month after procedure. Of long-term survivors followed up for > 12 months (n = 53), there were no significant changes in serial plain radiographs, and regional pain aggravation was observed in 9%. Pulmonary cement embolism and bone cement implantation syndrome was observed in 11% and 10%, respectively. However, all patients with these complications were asymptomatic. Conclusions Percutaneous cement injection into the pelvis is a feasible and safe palliative surgical option for patients with advanced malignancy in terms of pain reduction and maintenance of ambulatory function under regional anesthesia.

Vancomycin serum levels (VSL) were measured to prevent dose-dependent side effects. However, the cost of VSL is high, therefore in some cases alternative antibacterial treatments, such as linezolid, can be used. The aim of this study was to perform an economic analysis of the cost of linezolid compared to vancomycin plus therapeutic drug monitoring. This is an ecological, retrospective, quantitative study, conducted in a Brazilian public university hospital. The study period was from January 2018 to January 2019. First part from January/18 - July/18 based on pre-linezolid data (T1) and another after the introduction of linezolid from August/18 - January/19 (T2). A breakeven analysis to vancomycin substitution was performed following 3 scenarios: (i) in all patients, (ii) in critically ill patients with renal failure or (iii) only in patients in hemodialysis. The DDD/1000-patients day, MRSA incidence, costs with VSL, as well as the costs of drugs (vancomycin and linezolid) and infusion kits were evaluated. Vancomycin was substituted in critically ill patients with renal failure from T1 to T2. The incidence of MRSA infections did not vary between T1 and T2. Vancomycin consume maintained constant (p=0.157); while linezolid consuming increased (0 DDD/1000PD versus 33.4 DDD/1000PD; p=0.002). Vancomycin and linezolid costs was lower in T1 than T2 (USD 9202,00 versus 11331,00; p=0.015). Linezolid implementation as a strategy to avoid vancomycin plus VSL was not cost-effective in critically ill patients with renal failure. More studies are needed to understand if linezolid implementation may be cost-effective in different scenarios.