The potential of integrating stereotactic ablative radiotherapy techniques with hyperfractionation for lung cancer.

BACKGROUND: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. METHODS: We utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test. RESULTS: The transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/ß in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). CONCLUSIONS: The hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation.

Machine learning-based comparison of factors influencing estimated glomerular filtration rate in Chinese women with or without non-alcoholic fatty liver.

BACKGROUND: The prevalence of non-alcoholic fatty liver (NAFLD) has increased recently. Subjects with NAFLD are known to have higher chance for renal function impairment. Many past studies used traditional multiple linear regression (MLR) to identify risk factors for decreased estimated glomerular filtration rate (eGFR). However, medical research is increasingly relying on emerging machine learning (Mach-L) methods. The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD (NAFLD+, NAFLD-) and to rank their importance. AIM: To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD. METHODS: A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort, accounting for 32 independent variables including demographic, biochemistry and lifestyle parameters (independent variables), while eGFR was used as the dependent variable. Aside from MLR, three Mach-L methods were applied, including stochastic gradient boosting, eXtreme gradient boosting and elastic net. Errors of estimation were used to define method accuracy, where smaller degree of error indicated better model performance. RESULTS: Income, albumin, eGFR, High density lipoprotein-Cholesterol, phosphorus, forced expiratory volume in one second (FEV1), and sleep time were all lower in the NAFLD+ group, while other factors were all significantly higher except for smoking area. Mach-L had lower estimation errors, thus outperforming MLR. In Model 1, age, uric acid (UA), FEV1, plasma calcium level (Ca), plasma albumin level (Alb) and T-bilirubin were the most important factors in the NAFLD+ group, as opposed to age, UA, FEV1, Alb, lactic dehydrogenase (LDH) and Ca for the NAFLD- group. Given the importance percentage was much higher than the 2nd important factor, we built Model 2 by removing age. CONCLUSION: The eGFR were lower in the NAFLD+ group compared to the NAFLD- group, with age being was the most important impact factor in both groups of healthy Chinese women, followed by LDH, UA, FEV1 and Alb. However, for the NAFLD- group, TSH and SBP were the 5th and 6th most important factors, as opposed to Ca and BF in the NAFLD+ group.

Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study.

Background: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort. Methods: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff's method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS. Results: Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors. Conclusions: Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Repeat left ventricular-assisted device exchange and upgrade from second- to third-generation devices in a high-volume single center.

BACKGROUND: Pump exchange is an established strategy to treat LVAD-related complications such as thrombosis, infection, and driveline failure. Pump upgrades with an exchange to newer generation devices are being performed to the advantage of the patient on long-term support. The safety and efficacy of a repeat LVAD exchange with a concomitant upgrade to a third-generation pump have not been reported. METHODS: We performed a retrospective analysis of all consecutive patients who underwent a repeat LVAD device exchange and upgrade to HeartMate III (HMIII) at Houston Methodist Hospital between December 2018 and December 2020. RESULTS: Five patients underwent exchange and upgrade to HMIII within the specified timeframe. Four patients had already had two prior exchanges (all HMII to HMII), and one patient had one prior exchange (HVAD to HVAD). In all cases, implantation was performed as destination therapy. The surgical exchange was performed via redo median sternotomy on full cardiopulmonary bypass. No unplanned redo surgery of the device component was required. In-hospital mortality was 20% in this very high-risk population. At 1-, 3-, and 6-month follow-up, all discharged patients were on HMIII support, with no major LVAD-related adverse events reported. CONCLUSION: We report the feasibility and safety of a repeat pump exchange with an upgrade to HMIII in a high-volume center. The decision for medical therapy versus surgical exchange has to be tailored to individual cases based on risk factors and clinical stability but in expert hands, even a re-redo surgical approach grants options for good medium-term outcomes.

Real-world outcomes of 18,186 metastatic solid tumor outpatients: Baseline blood cell counts correlate with survival after immune checkpoint inhibitor therapy.

BACKGROUND: Patient survival in advanced/metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) has improved with immune checkpoint inhibitors (ICI). Biomarkers' role in prognosis and treatment has been limited by conflicting trial results. METHODS: This retrospective, observational study analyzed baseline demographic, clinical, laboratory, and treatment data versus outcomes of The US Oncology Network adult outpatients. Patients with advanced/metastatic melanoma, NSCLC, or RCC treated between January 1, 2015 and November 30, 2020 were given ICI monotherapy or combination therapy with ipilimumab, pembrolizumab, nivolumab, or atezolizumab. Treatment outcomes (overall survival [OS], time to treatment discontinuation, time to next treatment) were followed longitudinally until May 31, 2021, last patient record, or date of death. Baseline blood cell counts, including absolute monocyte count (AMC), absolute lymphocyte count (ALC), monocyte-to-lymphocyte ratio (MLR), absolute neutrophil count (ANC), and eosinophil count, were subdivided into quintiles for univariate and multivariable Cox regression analyses. RESULTS: Data from 18,186 patients with advanced/metastatic melanoma (n = 3314), NSCLC (n = 12,416), and RCC (n = 2456) were analyzed. Better OS correlated with increased baseline serum albumin concentration, increased eosinophil and lymphocyte counts, and Western United States physician practice location. Decreased OS correlated with increased AMC, MLR, ANC, age, and worse Eastern Cooperative Oncology Group performance status. CONCLUSIONS: To our knowledge, this study is the largest to date to associate baseline survival indicators and outcomes in outpatients with advanced/metastatic melanoma, NSCLC, or RCC and receiving ICIs. Results may inform disease-specific prognostic models and help providers identify patients most likely to benefit from ICI therapy.

Developing an AI-assisted planning pipeline for hippocampal avoidance whole brain radiotherapy.

BACKGROUND AND PURPOSE: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) is effective for controlling disease and preserving neuro-cognitive function for brain metastases. However, contouring and planning of HA-WBRT is complex and time-consuming. We designed and evaluated a pipeline using deep learning tools for a fully automated treatment planning workflow to generate HA-WBRT radiotherapy plans. MATERIALS AND METHODS: We retrospectively collected 50 adult patients who received HA-WBRT. Using RTOG- 0933 clinical trial protocol guidelines, all organs-at-risk (OARs) and the clinical target volume (CTV) were contoured by experienced radiation oncologists. A deep-learning segmentation model was designed and trained. Next, we developed a volumetric-modulated arc therapy (VMAT) auto-planning algorithm for 30 Gy in 10 fractions. Automated segmentations were evaluated using the Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95 % HD). Auto-plans were evaluated by the percentage of PTV volume that receives 30 Gy (V30Gy), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) and the minimum dose (D100%) and maximum dose (Dmax) for the hippocampus, Dmax for the lens, eyes, optic nerve, brain stem, and chiasm. RESULTS: We developed a deep-learning segmentation model and an auto-planning script. For the 10 cases in the independent test set, the overall average DSC and 95 % HD of contours were greater than 0.8 and less than 7 mm, respectively. All auto-plans met the RTOG- 0933 criteria. The HA-WBRT plan automatically created time was about 10 min. CONCLUSIONS: An artificial intelligence (AI)-assisted pipeline using deep learning tools can rapidly and accurately generate clinically acceptable HA-WBRT plans with minimal manual intervention and increase efficiency of this treatment for brain metastases.

Signal Detection of Adverse Events Associated with Trastuzumab in a Cohort of Elderly Patients with Breast Cancer.

AIM: Utilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset. METHODS: Using data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 1:2 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2- patients treated with standard chemotherapy. Inpatient and outpatient encounters up to 6 months from start of therapy were used to identify adverse events. RESULTS: A total of 4191 patients were included in the study. Across all methods, use of trastuzumab generated signals on 9 distinct body systems. Cardiomyopathy and heart valve disease were the most consistently detected signals. Clinical review determined that most signals represented known ADEs. CONCLUSIONS: We showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex.

BACKGROUND: Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.k.a. Agrobacterium biovar 1), a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes. RESULTS: We utilized 35 genome assemblies, including 14 newly generated ones, to achieve a phylogenetically balanced sampling of A. tumefaciens. Our genomic analysis suggested that the 10 genomospecies described previously are distinct biological species and supported a quantitative guideline for species delineation. Furthermore, our inference of gene content and core-genome phylogeny allowed for investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins. CONCLUSIONS: We demonstrate that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. We show that the T6SS VgrG proteins involved in specific effector binding and delivery can be classified into distinct types based on domain organization. The co-occurrence patterns of VgrG-associated domains and the neighboring genes that encode different chaperones/effectors can be used to infer possible interacting partners. Similarly, the associations between plant host preference and the pTi type among these strains can be used to infer phenotype-genotype correspondence. Our strategies for multi-level investigations at scales that range from whole genomes to intragenic domains and phylogenetic depths from between- to within-species are applicable to other bacteria. Furthermore, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.

Opioid Prescribing Trends in Women Following Mastectomy or Breast-Conserving Surgery Before and After the 2014 Federal Reclassification of Hydrocodone.

BACKGROUND: Given concerns about suboptimal pain management for actively treated cancer patients following the 2014 federal reclassification of hydrocodone, we examined changes in patterns of opioid prescribing among surgical breast cancer patients. MATERIALS AND METHODS: Data from a large nationally representative commercial health insurance program from 2009 to 2017 were used to identify women aged 18 years and older who were diagnosed with carcinoma in-situ or malignant breast cancer and received breast-conserving surgery or mastectomy from 2010 to 2016. Generalized linear mixed models were used to estimate the adjusted odds ratio (aOR) for receipt of ≥1-day, >30-day, or ≥ 90-day supply of opioids in the 12 months following surgery adjusting for demographics, cancer treatment-related characteristics, and preoperative opioid use. RESULTS: A total of 60,080 patients were included in the study. Surgically treated breast cancer patients in 2015 (aOR = 0.90, 0.84-0.97) and 2016 (aOR = 0.80, 0.74-0.86) were less likely to receive ≥1-day supply of opioid prescriptions when compared with patients in 2013. Patients who had surgery in 2015 (aOR = 0.89, 0.81-0.98) and 2016 (aOR = 0.80, 0.73-0.87) were also less likely to receive >30-day supply of prescription opioids in the 12 months following surgery. However, only surgical breast cancer patients in 2016 were less likely to receive ≥90-day supply (aOR = 0.86, 0.76-0.98). CONCLUSION: Surgically treated breast cancer patients are less likely to receive short- and long-term opioid prescriptions following the implementation of hydrocodone rescheduling. Further studies on the potential impact of federal policy on cancer patient pain management are needed. IMPLICATIONS FOR PRACTICE: Clinicians and researchers with diverse perspectives should be included as stakeholders during policy development for restricting opioid prescriptions. Stakeholders can identify potential unintended consequences early and help identify methods to mitigate concerns, specifically as it relates to policy that influences how providers manage pain for actively treated cancer patients. This work shows how federal policy may have led to declines in opioid prescribing for breast cancer patients who underwent mastectomy or breast-conserving surgery.

Esthetic Occipital Augmentation With Computer-Aided Design-Computer-Aided Manufacturing Prefabricated Customized Polymethyl Methacrylate Implant: Comparison of Planned and Final Results.

PURPOSE: Augmentation of the occiput is an esthetic procedure that is gaining more popularity but is not well reported in the literature. The aim of this retrospective study on a case series of patients was to describe the use of computer-aided design-computer-aided manufacturing prefabricated polymethyl methacrylate (PMMA) implants in esthetic occipital augmentation. Furthermore, comparison between the surgical outcome and the digital planning was carried out to ascertain the replicability of the surgical planning. MATERIALS AND METHODS: We performed a retrospective study of a case series of patients who underwent occipital augmentation with computer-aided design-computer-aided manufacturing prefabricated implants. Customized PMMA occipital implants were fabricated and were inserted via a bicoronal approach with patients under general anesthesia. The patients' 1-week postoperative cone-beam computed tomography image was superimposed onto the preoperative virtual planning images, and the positions of the actual implant and virtual implant were compared. RESULTS: A total of 15 patients who were treated at Charm Clinic, Taipei, Taiwan, and received occipital implants for esthetic purposes were included in this study. The percentage overlap of the occipital implant ranged from 87.8% to 99.99% (mean, 95.71%). One patient experienced partial wound dehiscence, which recovered after wound revision and suturing. In another patient, mild hematoma developed, which resolved spontaneously. Although no formal questionnaire was administered, all patients expressed satisfaction with the cosmetic outcome. CONCLUSIONS: The use of prefabricated PMMA posterior calvarial implants showed a rate of replicability of 87.8% to 99.99% (mean, 95.71%) compared with the preoperative virtual planning, and we recommend it as a feasible method for esthetic occipital augmentation.

Opioid Prescribing to Medicare Part D Enrollees, 2013-2017: Shifting Responsibility to Pain Management Providers.

OBJECTIVE: To examine opioid prescribing frequency and trends to Medicare Part D enrollees from 2013 to 2017 by medical specialty and provider type. METHODS: We conducted a retrospective, cross-sectional, specialty- and provider-level analysis of Medicare Part D prescriber data for opioid claims from 2013 to 2017. We analyzed opioid claims and prescribing trends for specialties accounting for ≥1% of all opioid claims. RESULTS: From 2013 to 2017, pain management providers increased Medicare Part D opioid claims by 27.3% to 1,140 mean claims per provider in 2017; physical medicine and rehabilitation providers increased opioid claims 16.9% to 511 mean claims per provider in 2017. Every other medical specialty decreased opioid claims over this period, with emergency medicine (-19.9%) and orthopedic surgery (-16.0%) dropping opioid claims more than any specialty. Physicians overall decreased opioid claims per provider by -5.2%. Meanwhile, opioid claims among both dentists (+5.6%) and nonphysician providers (+10.2%) increased during this period. CONCLUSIONS: From 2013 to 2017, pain management and PMR increased opioid claims to Medicare Part D enrollees, whereas physicians in every other specialty decreased opioid prescribing. Dentists and nonphysician providers also increased opioid prescribing. Overall, opioid claims to Medicare Part D enrollees decreased and continue to drop at faster rates.

Long-Term Opioid Therapy in Older Cancer Survivors: A Retrospective Cohort Study.

OBJECTIVES: To examine the rates and predictors of long-term opioid therapy in older cancer survivors. DESIGN: Retrospective cohort study. SETTING: Texas, United States. PARTICIPANTS: Cancer survivors (5 years or more postcancer diagnosis) diagnosed from 1995 to 2008 and who were also Medicare Parts A, B, and D beneficiaries. MEASUREMENTS: We used Medicare Part D event data to calculate the proportion of cancer survivors with a prolonged opioid prescription (90-day or more supply of opioids/year). Adjusted odds ratios were calculated to identify predictors of prolonged opioid prescribing. All analyses were repeated with a subcohort of opioid-naïve cancer survivors. RESULTS: The rate of prolonged opioid therapy for cancer patients diagnosed in 2008 was 7.1% prior to cancer diagnosis; it rose to 9.8% within a year of cancer treatments, and to 13.3% at 5 years postdiagnosis. The rate at the sixth year varied by cancer sites: 19.4% in lung cancer and 9.6% in prostate cancer. Among opioid-naïve survivors, the rate increased from 1.4% to 7.1%, from 5 to 18 years postcancer diagnosis. Cancer survivors diagnosed in 2004 to 2008 had higher rates of opioid prescribing compared to those diagnosed in 1995 to 1998 and 1999 to 2003. Years since diagnosis, a later year of diagnosis, female sex, urban location, lung cancer diagnosis, disability as reason for Medicare entitlement, Medicaid eligibility, one or more comorbidity, and history of depression or drug abuse were predictors of prolonged opioid therapy. Among opioid-naïve cancer survivors, diagnosis in 2004 to 2008 was the strongest predictor, while a history of drug abuse was the strongest predictor for all the survivors. CONCLUSION: The rates of prolonged opioid prescribing for older cancer survivors remained high at 5 or more years after cancer diagnosis. Our findings have potential to inform the development of clinical guidelines and public policy to ensure safer and more effective pain treatment in older cancer survivors. J Am Geriatr Soc 67:945-952, 2019.

Factors Associated With Prolonged Survival in Left Ventricular Assist Device Recipients.

BACKGROUND: Limited data exist on factors predicting prolonged survival in left ventricular assist device (LVAD) recipients. We sought to identify patient characteristics and complications associated with prolonged survival. METHODS: We conducted retrospective review of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database, including primary continuous-flow LVAD recipients, between May 2012 and March 2013. Patients were identified as having survived with a device in place after 3 years or not, conditional on having initially survived 6 months. Patients who received a transplant, underwent explant due to recovery, or were lost to follow-up before 3 years were excluded. Multivariate logistic regression evaluated perioperative factors and adverse events within 6 months associated with long survival. RESULTS: Of 1,116 patients who survived past the initial 6 months, 725 (65%) survived beyond 3 years. On univariate analysis, long-term survivors were significantly younger, were less likely to be white, supported for destination therapy, have diabetes, solid-organ cancer, or take amiodarone. On multivariate analysis, factors associated with increased odds of death at 3 years included diabetes, amiodarone use, and developing stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis within 6 months of implantation. CONCLUSIONS: Preoperative diabetes and amiodarone use were associated with poor long-term survival in LVAD recipients. Development of early complications of stroke, gastrointestinal bleeding, hemolysis, or pump thrombosis was also associated with poor long-term survival. Early diagnosis and treatment of these complications may improve survival in LVAD recipients.

Risk of stroke among patients with cerebral palsy: a population-based cohort study.

AIM: The aim of the study was to investigate the risk of stroke in patients with cerebral palsy (CP), based on nationwide data in Taiwan. METHOD: This prospective cohort study was comprised of patients recorded on the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005) who had a diagnosis of CP (n=1975) in records between 1 January 2004 and 31 December 2007. A comparison group (1:5) drawn from the same database was matched for age and sex (n=9875). Each patient was tracked by data until the development of stroke or the end of 2008. Cox proportional-hazards regression analysis was used to evaluate the hazard ratios after adjusting for potential confounding factors. RESULTS: Patients with CP were more likely to suffer stroke than the comparison population, after adjusting for potential confounding factors (adjusted hazard ratio: 2.17; 95% confidence interval [CI]: 1.74-2.69). The hazard ratio of stroke was 4.78 (95% CI: 3.18-7.17) and 1.57 (95% CI: 1.20-2.05) for patients with CP aged 50 years and under, and over 50 years respectively. INTERPRETATION: Cerebral palsy is a risk factor or marker for stroke that is independent of traditional stroke risk factors. Further research in this area is warranted.

Diabetes mellitus increases the risk of rotator cuff tear repair surgery: A population-based cohort study.

BACKGROUND: Rotator cuff tears are the most common cause of shoulder disability in people older than 50years, and surgical intervention is usually required for restoring functioning. However, in patients undergoing rotator cuff repair surgery, patients with DM had poorer functional outcomes than those without DM, and hence, DM is one of the possible risks factor for rotator cut off tear. The aim of this population-based study was to investigate the relationship between DM and the risk of rotator cuff tear in patients receiving rotator cuff repair surgery. METHODS: In this retrospective longitudinal population-based 7-year cohort study, we investigated the risk of rotator cuff repair surgery in patients with DM. We performed a case-control matched analysis by using data from the Taiwan Longitudinal Health Insurance Database 2005. Patients were enrolled on the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for DM between January 1, 2004, and December 31, 2007. The prevalence and the adjusted hazard ratios (HRs) of a rotator cuff repair surgery in patients with and without DM were estimated according to the Cox proportional hazard regression analysis using the frailty model. RESULTS: The DM and non-DM cohorts comprised 58,652 patients with DM and 117,304 (1:2) patients without DM after matching for age and sex. The incidence of rotator cuff repair surgery was 41 per 100,000 and 26 per 100,000 person-years in the DM and non-DM cohorts, respectively. The HR of rotator cuff repair surgery during the follow-up period was 1.56 (95% confidence interval [CI] 1.25-1.93, p<0.001) for patients with DM. After adjustment for covariates, the adjusted HR of rotator cuff repair surgery was 1.33 (95% CI, 1.05-1.68, p<0.001) in the DM cohort. CONCLUSION: DM is an independent risk factor for rotator cuff tear repair surgery.

Construction and functional analysis of an anti-human cervical carcinoma/anti-human CD3 single-chain bispecific antibody.

The aim of the present study was to construct a single-chain bispecific antibody (scBsAb) against cervical carcinoma and to investigate its biological activities. The scBsAb was constructed using a genetic cloning technique and antigen binding activities were detected by ELISA. The iodogen method was used to analyze the pharmacokinetics. The Rosette formation test was used to detect the binding ability between peripheral blood lymphocytes (PBLs) and Cs1213 cervical cancer cells. In addition, the MTT method was performed to detect the killing effect of PBLs. The molecular weight of the scBsAb was ~60 kDa. The antigen binding activities of scBsAbs were compared with the anti­human cervical carcinoma antibody single­chain Fv fragment (CSAs­1 scFv) and anti­cluster of differentiation (CD)3 scFv (P>0.05). In addition, a pharmacokinetics assay demonstrated that compared with the two corresponding scFvs, scBsAbs exhibited a significantly prolonged retention time in the body (P<0.01). In addition, the number of rosettes formed by PBLs and Cs1213 cells in the scBsAb group was markedly greater than that in the scFv groups or the RPMI­1640 group (P<0.05 and P<0.01, respectively). The killing activity of PBLs against scBsAb­mediated Cs1213 cells was significantly greater than that mediated by the other antibodies (P<0.05). When the concentration of scBsAb was 40 µg/ml, the killing rate was 64.5%. Thus, anti­human cervical carcinoma/anti­CD3 scBsAbs may possess two types of antigen binding activity, prolong the duration in vivo and improve the killing activity of PBLs against cancer cells.

Functional outcomes of outpatient balance training following total knee replacement in patients with knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate whether balance training after total knee replacement surgery improves functional outcomes and to determine whether postoperative balance is associated with mobility. DESIGN: A prospective intervention study and randomized controlled trial with an intention-to-treat analysis. SETTING: The rehabilitation center of a university-based teaching hospital. PARTICIPANTS: A total of 130 patients with knee osteoarthritis who had undergone total knee replacement surgery were recruited to attend an outpatient rehabilitation program. They were randomly allocated to additional balance rehabilitation and functional rehabilitation groups. INTERVENTIONS: During the eight-week outpatient rehabilitation program, both groups received general functional training. Patients in the balance rehabilitation group received an additional balance-based rehabilitation program. PRIMARY OUTCOME MEASURES: The functional reach test, single-leg stance test, 10-m walk test, Timed Up and Go Test, timed chair-stand test, stair-climb test, and Western Ontario and McMaster Universities Osteoarthritis Index were measured at baseline, eight weeks (T(1)), and 32 weeks (T(2)). RESULTS: The balance rehabilitation group patients demonstrated significant improvement in the results of the functional reach test at T(1) (37.6 ±7.8 cm) and T(2) (39.3 ±9.7 cm) compared with the baseline assessment (11.5 ±2.9 cm) and Timed Up and Go Test at T(1) (8.9 ±1.2 seconds) and T(2) (8.0 ±1.9 seconds) compared with the baseline assessment (12.5 ±1.8 seconds). Moreover, the balance rehabilitation group patients exhibited significantly greater improvements in balance and mobility than did the functional rehabilitation group patients (all P < 0.001). Furthermore, improved balance was significantly associated with improved mobility at T(2). CONCLUSION: Postoperative outpatient rehabilitation with balance training improves the balance, mobility, and functional outcomes in patients with knee osteoarthritis after total knee replacement.

Monitoring Tumor Response After Histone Deacetylase Inhibitor Treatment Using 3'-Deoxy-3'-[18F]-fluorothymidine PET.

PURPOSE: This study employed 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatoma mouse model. PROCEDURES: The in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections. RESULTS: ISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [(18)F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining. CONCLUSIONS: ISAHA can suppress tumor cell proliferation both in vitro and in vivo. [(18)F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.

Pharmacokinetics of sevoflurane elimination from respiratory gas and blood after coronary artery bypass grafting surgery.

PURPOSE: Sevoflurane, with a relative low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. This study will determine the profiles of four concentration-time curves to characterize the pharmacokinetics of sevoflurane elimination. METHODS: Eight patients (aged 54-76 years) undergoing coronary arterial bypass grafting surgery were enrolled in this study. At the end of surgery, anesthetic gas and blood were sampled 20 min before and after stopping sevoflurane administration, with prior maintenance of a fixed 5% inspired sevoflurane (CIsev) in 6 L/min oxygen flow for 60 min before the cessation of sevoflurane administration for the subsequent 20 min elimination. An infrared analyzer was used to determine both CIsev and end-tidal sevoflurane (CEsev). The sevoflurane concentrations in the internal jugular-bulb (Jsev), arterial (Asev) and pulmonary arterial blood (PAsev) were analyzed by gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: A bi-exponential decay function was the best fit for the CEsev,Jsev, Asev, and PAsev time curves. There were two distinct components, the initial 5-min fast or distribution phase and the subsequent 15-min slow or elimination phase. Before cessation of the sevoflurane supplement, the step-down concentration of sevoflurane was listed in the following order: CIsev > CEsev > Asev ≧ Jsev > PAsev. During the elimination phase, the fastest decay occurred in CEsev, followed by Jsev, Asev and PAsev. Therefore, a reverse step-down pattern was observed (PAsev > Asev ≧ Jsev > CEsev) after 20 min. The ratio of Asev to CEsev was 89% at baseline before stopping sevoflurane administration, but the ratio of Asev to CEsev increased to 128% at the twentieth min of the sevoflurane elimination phase. CONCLUSIONS: During elimination, the initial washout of sevoflurane from the functional residual capacity of the lungs was reflected in the fast component of the CEsev, Jsev, Asev, and PAsev time curves. In contrast, the slow component was dominated by the tangible effects of the physiological membrane barriers, such as the alveoli-pulmonary capillary and blood-brain barriers.