Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

Effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in gastrointestinal, adipose, and liver tissue of Holstein dairy calves.

The objective of this study was to evaluate the effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in Holstein dairy calves. A total of 70 1-d-old calves (38.8 ± 4.4 kg BW ± SD), blocked by sex and birth BW, were randomly assigned to a 2 × 2 factorial arrangement of treatments. The first factor was weaning age, which was either early (6 wk) or late (8 wk). The second factor was weaning pace, which was either abrupt (4 steps down over 3 d; the initial milk replacer was 7.6 L, which was reduced by 1.9 L in each step-down) or gradual (7 steps down over 14 d; the initial milk replacer was 7.6 L, which was reduced by 1.09 L in each step-down), generating early-abrupt (EA), early-gradual (EG), late-abrupt (LA), and late-gradual (LG) treatments. All treatments had 10 female and 8 male calves, except EA that had 1 fewer male calf. Milk replacer (24% CP, 17% fat) was bottle fed, up to 1,200 g/d, twice daily (0600 h and 1800 h). The EA and EG treatment calves received 46.2 kg of milk replacer, and the LA and LG treatment calves received 63 kg of milk replacer. The study had 2 cohorts (2020, n = 40; 2021, n = 31), and each cohort included all treatments. Blood was collected from the jugular vein at 0900 h at 3 and 7 d of age, and a day before starting and a day after weaning completion. Male calves were humanely killed a day after weaning. Rumen, jejunum, large intestine, liver, omental adipose and perirenal adipose tissues were sampled to determine the mRNA abundance of inflammation-related genes. Weaning pace, age, pace × age, birth BW, and sex were included as fixed and cohort was included as random effects in the model. Blood metabolites and cortisol were analyzed as repeated measures, and sampling day, pace × sampling day, and age × sampling day were also included as additional fixed effects. Significance was noted at P ≤ 0.05 and tendencies when 0.05

Prodromes in demyelinating disorders, amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer's dementia.

A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.

Average and statistical properties of coherent radiation from steady-state microbunching.

A promising accelerator light source mechanism called steady-state microbunching (SSMB) is being actively studied. With the combination of strong coherent radiation from microbunching and high repetition rate of a storage ring, high-average-power narrow-band radiation can be anticipated from an SSMB storage ring, with wavelengths ranging from THz to soft X-ray. Such a novel light source could provide new opportunities for accelerator photon science like high-resolution angle-resolved photoemission spectroscopy and industrial applications like extreme ultraviolet (EUV) lithography. In this paper, a theoretical and numerical study of the average and statistical properties of coherent radiation from SSMB are presented. The results show that 1 kW average-power quasi-continuous-wave EUV radiation can be obtained from an SSMB ring provided that an average current of 1 A and a microbunch train with bunch length of 3 nm can be formed at the radiator which is assumed to be an undulator. Together with the narrow-band feature, the EUV photon flux can reach 6 × 1015 photons s-1 within a 0.1 meV energy bandwidth, which is three orders of magnitude higher than that in a conventional synchrotron source and is appealing for fundamental condensed matter physics and other research. In this theoretical investigation, we have generalized the definition and derivation of the transverse form factor of an electron beam which can quantify the impact of its transverse size on coherent radiation. In particular, it has been shown that the narrow-band feature of SSMB radiation is strongly correlated with the finite transverse electron beam size. Considering the pointlike nature of electrons and quantum nature of radiation, the coherent radiation fluctuates from microbunch to microbunch, or for a single microbunch from turn to turn. Some important results concerning the statistical properties of SSMB radiation are presented, with a brief discussion on its potential applications, for example the beam diagnostics. The presented work is of value for the development of SSMB to better serve potential synchrotron radiation users. In addition, this also sheds light on understanding the radiation characteristics of free-electron lasers, coherent harmonic generation, etc.

Hysterectomy and risk of osteoarthritis in women: a nationwide nested case-control study.

OBJECTIVE: Hysterectomy is the most common gynaecological surgery, performed mainly for benign uterine pathologies in women. Studies have suggested that hysterectomy is associated with osteoarthritis (OA); however, the association remains controversial. This study aimed to investigate the association between hysterectomy and the risk of OA. METHOD: We performed a population-based nested case-control study using the National Health Insurance programme database from 2000 to 2016 in Taiwan. All medical conditions for each case and control were categorized using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10. A multiple conditional logistic regression model was applied to analyse the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between hysterectomy and OA. RESULTS: Our analyses included 16 592 patients with OA and 66 368 matched controls. After adjustment for possible confounders, hysterectomy had a significant association with OA (aOR = 1.19, 95% CI = 1.09-1.30), especially knee OA (aOR = 1.25, 95% CI = 1.13-1.38). Furthermore, women who received oestrogen therapy (ET) alone and patients who underwent hysterectomy without ET showed a greater risk of OA development compared to women who did not receive ET (aOR = 1.14, 95% CI = 1.07-1.23, and aOR = 1.19, 95% CI = 1.08-1.31, respectively). CONCLUSION: Our findings indicate that hysterectomy is associated with OA, especially knee OA. We also found that women who received ET alone and patients who underwent hysterectomy without ET had an increased risk of OA.

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. MATERIALS AND METHODS: The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. RESULTS: N = 91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7 ± 7.7% and -3.7 ± 3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3 ± 3.1% vs. -2.9 ± 3.3% per week, p = 0.005) and increased in distance from GTVs over time (+2.7 ± 7.2% per week, p < 1 × 10-5 ). Automatic structure propagations agreed well with manual revisions (Dice = 0.88 ± 0.09 for parotids and 0.80 ± 0.15 for GTVs), but for GTVs the agreement degraded 4-5 weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC = 0.79). CONCLUSION: AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Immunogenicity of the mRNA-1273 and ChAdOx1 nCoV-19 vaccines in Asian patients with autoimmune rheumatic diseases under biologic and/or conventional immunosuppressant treatments.

OBJECTIVE: Nucleic acid-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are effective in the general population. However, it is unknown whether this is true in Asian patients with autoimmune rheumatic diseases (ARDs) who have received various combinations of disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We designed a large prospective observational study recruiting 228 patients with ARDs in a tertiary rheumatology centre in Taiwan. Altogether, 142 received biological or targeted synthetic DMARDs and 86 received only conventional synthetic (cs) DMARDs. Serum levels of immunoglobulin G antibody against SARS-CoV-2 spike proteins were measured 2-6 weeks after COVID-19 vaccination with mRNA-1273 (Moderna®) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca®). The immunomodulatory therapies were not modified before or after vaccination. RESULTS: Overall, 194 patients (85.09%) exhibited antibodies (758.33 ± 808.43 ng/mL) but 34 patients did not (103.24 ± 41.08 ng/mL). Patients with systemic lupus erythematosus or rheumatoid arthritis had significantly lower humoral responses to COVID-19 vaccination than those with other ARDs (p < 0.05). There was no significant difference in immunogenicity among patients on different csDMARD treatments. Compared to patients treated with only csDMARDs, those on rituximab or abatacept therapy had significantly lower immune response to the vaccination (p = 0.008 and p = 0.035, respectively). Patients who were treated with anti-tumour necrosis factor-α or interleukin-6 inhibitor exhibited higher titres of vaccination antibodies than those treated with direct lymphocyte inhibitors. CONCLUSIONS: mRNA-1273 and ChAdOx1 nCoV-19 vaccines were immunogenic in the majority of ARD patients. Rituximab and abatacept were associated with significantly diminished COVID-19 vaccination immunogenicity.

Any day, split halfway: Flexibility in scheduling high-dose cisplatin-A large retrospective review from a high-volume cancer center.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m2 × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m2 × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.

Metastasis-directed therapy for oligometastasis and beyond.

Metastasis-directed therapy (MDT)-local therapy that is intended to eradicate specific metastatic lesions-has hitherto been used with varying degrees of clinical efficacy and acceptance as a meaningful therapy for metastatic disease. Over the past 25 years, however, the momentum for using MDT to manage patients with metastatic solid tumours has increased, driven by several factors. Among these factors is the recognition that patients with limited metastatic burden could potentially derive survival benefits from MDT. Furthermore, although current systemic therapies are increasingly effective, they are infrequently curative. In addition, technological advances have broadened the spectrum of metastatic lesions that can be treated with ablative intent. Here we aim to briefly review the status of evidence for the clinical benefit of MDT based on current data mainly from trials in patients with oligometastatic disease, discuss the myriad of clinical states that might fall under and beyond the definition of oligometastasis, review technological advances in MDT and their applications beyond oligometastasis, and discuss the need for the continued co-evolution of MDT and systemic therapy as we seek to understand which patients with metastatic cancer can achieve durable remission and how to optimally manage those who cannot.

Socioeconomic inequality and omission of adjuvant radiation therapy in high-risk, early-stage endometrial cancer.

OBJECTIVE: Gaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer. METHODS: A retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models. RESULTS: 19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001). CONCLUSION: Adjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome.

Probiotic supplementation containing Bacillus velezensis enhances expression of immune regulatory genes against pigeon circovirus in pigeons (Columba livia).

AIMS: In this study, we aimed to isolate and evaluate the efficacy of Bacillus velezensis as a probiotic and to assess its activity towards pigeons infected with pigeon circovirus (PiCV). METHODS AND RESULTS: Bacillus velezensis, isolated from pigeon faeces, was orally administered to pigeons for 60 days. After pigeons were challenged with PiCV, the PiCV viral load and expression of indicator genes for innate immunity were detected in spleen tissue and faeces of pigeons. Bacillus velezensis significantly reduced the PiCV viral load in the faeces and spleen of pigeons 5 days post-challenge (dpc). The mRNA expression levels of treated pigeons showed that interferon-gamma (IFN-γ), myxovirus resistance 1 (Mx1), and signal transducers and activators of transcription 1 (STAT1) genes were upregulated, whereas no expression of interleukin-4 (IL-4) was detected. Moreover, toll-like receptor 2 (TLR2) and 4 (TLR4) were significantly upregulated in probiotic-treated pigeons (P < 0·05). CONCLUSIONS: This is the first report showing that probiotic supplementation can effectively enhance the T-helper type 1 immune response and decrease the PiCV viral loads in pigeons. SIGNIFICANCE AND IMPACT OF THE STUDY: This study proposes that the administration of a probiotic strain, B. velezensis, to pigeons can protect against PiCV infection.

Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer.

For patients ineligible for cisplatin with definitive radiotherapy (CP-CRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), concurrent cetuximab (C225-RT) is a popular substitute. Carboplatin-based chemoradiation (CB-CRT) is another option; however, relative efficacies of CP-CRT, CB-CRT and C225-RT are unclear, particularly in the human papillomavirus (HPV)-unrelated population. We identified 316 patients with stage III-IVB cancers of the oropharynx (24.7%), larynx (58.2%) and hypopharynx (17.1%) undergoing definitive C225-RT (N = 61), CB-CRT (N = 74) or CP-CRT (N = 181). Kaplan-Meier and cumulative incidence functions were generated to estimate overall survival (OS), locoregional failure (LRF) and distant metastasis (DM). Cox proportional hazards were used to determine the association of survival endpoints with clinical characteristics. Respectively, 3-year cumulative incidences for CP-CRT, CB-CRT and C225-RT were: LRF (0.19, 0.18 and 0.48, p ≤ 0.001), DM (0.17, 0.12 and 0.25, p = 0.32). Kaplan-Meier estimates for 3 year OS were: CP-CRT: 71%; CB-CRT: 59% and C225-RT: 54%; p = 0.0094. CP-CRT (hazard ratio [HR] 0.336; 95% confidence interval [CI] 0.203-0.557, p < 0.01) and CB-CRT (HR 0.279; 95% CI 0.141-0.551, p < 0.01) were associated with reduced hazard for LRF on multivariable analysis. CP-CRT (HR 0.548; 95% CI 0.355-0.845, p < 0.01) and CB-CRT (HR 0.549; 95% CI 0.334-0.904, p = 0.02) were associated with a reduced hazard for death on multivariable analysis. Propensity matching confirmed reduced hazards with a combined CP/CB-CRT group compared to C225-RT for LRF: HR 0.384 (p = 0.018) and OS: HR 0.557 (p = 0.045) and CB-CRT group compared to C225-RT for LRF: HR 0.427 (p = 0.023). In conclusion, CB-CRT is an effective alternative to CP-CRT in HPV-unrelated LA-HNSCC with superior locoregional control and OS compared to C225-RT.

Outcomes of multimodal therapy in a large series of patients with anaplastic thyroid cancer.

BACKGROUND: The role of radiotherapy (RT) in the treatment of patients with anaplastic thyroid cancer (ATC) for local tumor control is critical because mortality often is secondary to complications of tumor volume rather than metastatic disease. Herein, the authors report the long-term outcomes of RT for patients with ATC. METHODS: A total of 104 patients with histologically confirmed ATC were identified who presented to the study institution between 1984 and 2017 and who received curative-intent or postoperative RT. Locoregional progression-free survival (LPFS), overall survival (OS), and distant metastasis-free survival were assessed. RESULTS: The median age of the patients was 63.5 years. The median follow-up was 5.9 months (interquartile range, 2.7-17.0 months) for the entire cohort and 10.6 months (interquartile range, 5.3-40.0 months) for surviving patients. Thirty-one patients (29.8%) had metastatic disease prior to the initiation of RT. Concurrent chemoradiation was administered in 99 patients (95.2%) and 53 patients (51.0%) received trimodal therapy. Systemic therapy included doxorubicin (73.7%), paclitaxel with or without pazopanib (24.3%), and other systemic agents (2.0%). The 1-year OS and LPFS rates were 34.4% and 74.4%, respectively. On multivariate analysis, RT ≥60 Gy was associated with improved LPFS (hazard ratio [HR], 0.135; P = .001) and improved OS (HR, 0.487; P = .004), and trimodal therapy was associated with improved LPFS (HR, 0.060; P = .017). The most commonly observed acute grade 3 adverse events included dermatitis (20%) and mucositis (13%), with no grade 4 subacute or late adverse events noted (adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). CONCLUSIONS: RT appears to demonstrate a dose-dependent, persistent LPFS and OS benefit in patients with locally advanced ATC with an acceptable toxicity profile. Aggressive RT should be strongly considered for the treatment of patients with ATC as part of a trimodal treatment approach.

The 3 Bs of cancer care amid the COVID-19 pandemic crisis: "Be safe, be smart, be kind"-A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis.

Underestimated fracture risk in postmenopausal women-application of the hybrid intervention threshold.

This study evaluated the fragility fracture risk of Taiwanese postmenopausal women with osteopenia. With the incorporation of FRAX and hybrid intervention threshold (HIT), 25% of the participants had high fracture risk. We suggest intervention for fragility fracture for postmenopausal women should be guided by FRAX and HIT instead of bone mineral density alone. INTRODUCTION: To explore the risk of fragility fracture in Taiwanese postmenopausal women with osteopenia using the hybrid intervention threshold (HIT) and Fracture Risk Assessment tool (FRAX). METHODS: The Taiwan Osteoporosis Association (TOA) conducted a nationwide bone mineral density (BMD) survey between 2008 and 2011 using a bus equipped with a dual-energy X-ray absorptiometry (DXA) machine. All participants completed a structured questionnaire, which included the elements in the FRAX. Based on the results, the group made up of postmenopausal women with osteopenia was identified. In order to explore the risk of fragility fracture by HIT and FRAX among Taiwan postmenopausal women with osteopenia, the 10-year probability of fracture (FRAX score) and individual intervention threshold (IIT) in this group were calculated. If the FRAX score of a participant was higher than or equal to the IIT or fixed intervention threshold (FIT), the participant was considered as above the HIT (HIT could be reached by being over a threshold at either major osteoporotic fracture or hip fracture) and categorized as having a high FRAX fracture risk. RESULTS: A total of 13,068 postmenopausal women were enrolled in the program. A total of 5743 (43.9%) participants had osteopenia, of which 1434 (25.0%) had high FRAX fracture risk. CONCLUSIONS: One quarter of Taiwanese postmenopausal women with osteopenia had high fragility fracture risk evaluated by FRAX and HIT. Due to the poor sensitivity of BMD for fragility fracture, we suggest that intervention for fragility fracture for postmenopausal women should also be guided by FRAX and HIT instead of BMD alone.

Long-term survival in patients with metastatic head and neck squamous cell carcinoma treated with metastasis-directed therapy.

BACKGROUND: Our objective was to evaluate the outcomes of metastatic head and neck squamous cell carcinoma (HNSCC) by disease burden with an emphasis on metastasis-directed therapy (MDT) in patients with limited metastatic disease burden. METHODS: In total, 186 patients who developed metastatic disease after definitive therapy for HNSCC were included. Clinically and radiographically apparent metastases were enumerated. Kaplan-Meier methods were used to estimate survival. Cox regression was used to assess the association between clinical variables. RESULTS: Patients with a single metastasis had a 5-year overall survival (OS) of 35% (95% CI 16-54%) in contrast to patients with multiple metastases with a 5-year OS of 4% (95% CI 2-9%). Thirty patients (16.1%) underwent MDT. On multivariable analysis, oral cavity or sinonasal primary (HR 2.22 95% CI 1.16-4.25, p = 0.015; HR 4.88, 95% CI 1.10-21.70, p = 0.037, respectively) were associated with higher risk of death, whereas receipt of MDT (HR 0.36, 95% CI 0.17-0.74, p = 0.006) was associated with lower hazard of death. Median subsequent metastasis-free survival and 5-year survival after MDT (n = 30) were estimated at 26.4 months (95% CI: 9.8-54.0) and 31%, (95% CI: 15-48%). CONCLUSIONS: HNSCC patients with limited metastatic disease may derive significant benefit from MDT. Prospective trials evaluating MDT in HNSCC are warranted.

Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Incidence and risk factors of osteomyelitis in adult and pediatric systemic lupus erythematosus: a nationwide, population-based cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. RESULTS: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. CONCLUSIONS: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.