Review of novel therapeutic medicines targeting androgen signaling in castration-resistant prostate cancer

Prostate cancer is the most common male malignant neoplasm.Androgens and the androgen receptor(AR)play a key role in the onset and progression of prostate cancer.The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer(CRPC).CRPC is considered to be induced by the following mechanisms:(1)sustained AR activation by enhancing intracellular conversion of adrenal androgens to dehydrotestosterone via a de novo route;(2)AR hypersensitivity;(3)promiscuous activation of AR signaling;and(4)outlaw pathways.Recent advances in the treatment of CRPC include novel medicinestargeting AR signaling pathways.In addition,functional molecular studies have shown that some of the ARregulated genes and AR coregulators are prognostic markers and potential therapeutic targets for prostate cancer,particularly in the castration-resistant state.Therefore,identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.

美国护理信息的应用与发展趋势

美国的护理人数高达310万人，是健康照护专业人员最多的国家。在照护团队中，护士作为患者与家属之间的沟通枢纽，负责护理、协调与整合工作。医学研究所（Institute of Medicine）的研究报告显示：医护差错及医疗护理质量的差异性已被广泛认可。

Current status in the treatment options for esophageal achalasia

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy(POEM).The first multicenter randomized,controlled,2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy(LHM)was not superior to pneumatic dilations(PD).Publications on the long-term success of laparoscopic surgery continue to emerge.In addition,laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication.The optimal treatment option is an ongoing matter of debate.In this review,we provide an update of the current progress in the treatment of esophageal achalasia.Unless new conclusive data prove otherwise,LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications.However,PD is the first choice for non-surgical treatment and is more costeffective.Repeated PD according to an"on-demand"strategy based on symptom recurrence can achieve long-term remission.Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options.POEM has shown promise but its long-term efficacy and safety need to be assessed further.

Survey of <i>C. difficile</i>-Specific Infection Control Policies in Local Long-Term Care Facilities

Introduction: The incidence and severity of Clostridium difficile infection (CDI) has been increasing and long-term care facility (LTCF) residents are at high risk given their age, co-morbidities, and high antibiotic exposure. Infection control policies are crucial for controlling CDI, but there are currently no regulatory guidelines in the United States. Therefore, we evaluated infection control policies in local LTCFs to define the CDI-specific policies and the administrative and staff understanding of CDI, so as to identify perceived barriers for compliance. Methods: IRB approval was sought and exemption granted, all 8 local LTCFs were asked to participate. Each facility was visited by study personnel who interviewed the administrative Infection Control Practitioner (ICP) and 3-4 Licensed Practical Nurses (LPNs) with distinct survey format. Infection control policies were then compared to the SHEA recommendations for CDI in LTCFs. Results: Of the eligible facilities, 75% (n = 6) participated. ICP (n = 6) and LPNs (n = 21) were interviewed. All facilities accept residents with active CDI and 2 had written CDI-specific infection control policies. All facilities had hand hygiene or glove use policies and 2 had policies for the use of sporicidal environmental cleaning. No facility restricted antibiotic use. Each facility has a policy to instruct their staff through in-services, either annually or upon new hire, but 33% (n = 7) LPNs reported no facility-based CDI training. While 80% (n = 17) of LPNs felt comfortable with the facility CDI policies, only 11 accurately restated it. ICPs felt the most relevant barrier to staff compliance was time constraints (n = 4, 67%), however, LPNs felt it was limited knowledge (n = 10, 48%) and poor communication (n = 2, 10%). Discussion and Conclusions: With the increasing incidence and severity of CDI in LCTF, few of the facilities surveyed had CDI-specific policies. Despite CDI-specific training, there is a perceived knowledge and communication gap for staff caring for residents with CDI.

Combined Effects of Blood Pressure and Aldosterone on Cardiac Left Ventricular Mass Index—Ethnic Differences between Kazakh, Uygur and Han Subjects

Previous Background: Hemodynamic factors, like blood pressure, have been established to be major determinants of cardiac left ventricular structure. However, several factors other than blood pressure to influence cardiac mass have been implicated. When we did medical survey, cardiac left ventricular mass index (LVMI) of one ethnic group that had higher blood pressure was found to be smaller than that of the other ethnic groups with a lower blood pressure. Such contradicted data from the present study were analyzed combining blood pressure, LVMI and chemical parameters obtained from blood and urine. Methods: In a medical survey conducted in Xinjiang, China, 279 people (65 - 70 years old) from three ethnic groups (Kazakh, Uygur and Han) from two separated regions provided blood and urine samples and underwent echocardiography and 24-h ambulatory blood pressure monitoring (ABPM). Results: Systolic and diastolic blood pressure obtained from ABPM and urinary sodium excretion values were significantly higher in Kazakh than that in Uygur and Han. However, LVMI in Kazakh was lower than that in other 2 groups. Plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were significantly lowest in Kazakh. The values of LVMI in all ethnic groups were positively related to both blood pressure and PAC. An inverse correlation was identified between PAC and urinary sodium excretion value. Conclusion: Although higher blood pressure in Kazakh subjects, their LVMI was lower than those of Uygur and Han, whose blood pressure was lower than that in Kazakh. These results suggest that blood pressure is not always a determinant for LVMI value. There is a possibility that relatively lower PAC resulted from higher sodium intake suppressed the rise in LVMI caused by higher blood pressure in Kazakh.

Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors

AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal(GI) organic diseases.METHODS: Participants were 4738(603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms(borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios(ORs) were estimated.RESULTS: In multivariate analysis, constipation [adjusted odds ratio(AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools(AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency(AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation(AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good(mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with Hb A1 c ≥ 8.0%(AOR = 2.11, CI: 1.19-3.73), b o d y m a s s i n d e x( B M I) < 2 5( A O R = 2. 1 1, C I : 1.22-3.66), and insulin use(AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration(AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25(AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25(AOR = 2.60, CI: 1.52-4.43), serum creatinine level(AOR = 1.27, CI: 1.10-1.47), and insulin use(AOR = 1.92, CI: 1.09-3.38).CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.

Daily high-dose aspirin does not lower APRI in the Aspirin-Myocardial Infarction Study

Antiplatelet agents reduce liver fibrosis by inhibiting platelet activation and platelet-derived growth factor production. Previous cross-sectional epidemiological studies suggest that the use of aspirin is related to reduced liver fibrosis. The Aspirin-Myocardial Infarction Study(AMIS) aims to examine this relationship in a multicenter,randomized, double-blind and placebo-controlled trial. The existing clinical trial of aspirin was conducted to study the benefit of one gram aspirin daily among 4 524 individuals who had experienced at least one documented myocardial infarction. The aspartate aminotransferase(AST)-to-Platelet Ratio Index(APRI) was calculated at baseline and annually from the platelet count and AST levels. Participants in the AMIS trial had a mean baseline APRI of 0.34±0.36, and only 1% individuals had APRI scores higher than 1.0, a common cutoff for cirrhosis. The daily use of aspirin was associated with an increase, rather than a reduction of APRI, by 0.007 per year(95% CI0.002-0.015, P=0.12). The use of aspirin did not significantly affect platelet counts. In a sensitivity analysis of individuals with probable significant fibrosis at baseline(APRI≥0.7), the aspirin group had a sustained reduction in APRI over time, although this change was not significant compared to that in the placebo group. In the AMIS trial, the daily use of high-dose aspirin did not significantly affect APRI, a surrogate index of liver fibrosis. This study highlights the need for de novo clinical trials to investigate the potential benefit of antiplatelet agents on liver fibrosis.

Transradial vs transfemoral secondary access outcomes in transcatheter aortic valve implantation:A systematic review and meta-analysis

BACKGROUND Complications of transcatheter aortic valve implantation(TAVI)procedures include bleeding,vascular complications,and strokes.These complications are often associated with the type of access used.The two types of access in TAVI procedures are primary and secondary.The main use of the primary access is for valve delivery,while secondary access is used for angiography and hemodynamic monitoring.While there are many options for primary access,those for secondary access are transfemoral and transradial.AIM To compare outcomes between transradial vs transfemoral secondary access(TFSA).METHODS A systematic search was conducted using major databases(EMBASE,PubMed,Cochrane Central,Google Scholar),which resulted in 5 studies that met the criteria for study selection.Outcomes of interest were 30-d rates each of major/life-threatening bleeding,vascular complications,strokes,and mortality.All 5 studies were observational.Only adjusted or matched data were used when available in this meta-analysis.RESULTS A total of 5065 patients underwent TAVI,with 1453 patients(28.7%)having undergone transradial secondary access(TRSA)and 3612 patients(71.3%)TFSA.Irrespective of the site of primary access,the odds of having major or lifethreatening bleeding were 60%lower in the TRSA group than the TFSA group(P<0.00001).The odds of having major vascular complications were 52%lower in the TRSA group(P<0.0001)with no difference in minor vascular complications between the 2 groups.Similarly,the odds of mortality in 30-d after the procedure were 41%lower(P=0.006)and the odds of stroke were 54%lower(P=0.001)in the TRSA group than the TFSA group.CONCLUSION The transradial secondary approach appears to be a safer alternative to the transfemoral secondary approach in TAVI procedures.

Associations between Pneumococcal Vaccinationand Adverse Outcomes in Patients with Suspected Acute Coronary Syndrome

Background: Although pneumococcal vaccination prevents the most common pneumonia of bacterial etiology, its associations without comes of Acute Coronary Syndrome (ACS) are unknown. Methods: This is a prospective cohort study of 1436 patients hospitalized with suspected ACS/non-ST elevation MI that were eligible for pneumococcal vaccination. Primary outcomes were death and subsequent Myocardial Infarction (MI) within 6-months of the index hospitalization. We used Cox regression to assess associations between pneumococcal vaccination and outcomes, adjusting for influenza vaccination and relevant clinical covariates. We also utilized propensity scores to adjust for potential confounding. Results: Overall, 937 (65.3%) patients received pneumococcal vaccination either prior to or during the index hospitalization. Unvaccinated patients had higher mortality (26.9% vs. 7.9%;p < 0.001) and non-significantly higher frequency of subsequent MI (7.4% vs. 3.5%;p = 0.06).Compared to patients who did not receive either pneumococcal or influenza vaccination, the unadjusted Hazard Ratio (HR) of death was significantly lower for those who received only pneumococcal vaccination (HR = 0.13;95% CI 0.07 - 0.23) or both vaccinations (HR = 0.66, 95% CI 0.47 - 0.92), and significantly higher for patients who received only influenza vaccination (HR = 1.88, 95% CI 1.33 - 2.64). The corresponding HRs and 95% CIs for subsequent MI were 0.58 (95% CI 0.32 - 1.03) for pneumococcal vaccination only, 0.41 (95% CI 0.21 - 0.80) for both vaccinations and 0.97 (95% CI 0.48 - 1.95) for influenza vaccination alone. These remained unchanged after covariate or propensity score adjustment. Conclusions: Among patients hospitalized with suspected ACS, pneumococcal vaccination, with or without influenza vaccination, was associated with significantly lower risk of mortality within 6 months.

男性和女性房颤发生风险与纤维蛋白原及白蛋白水平的关系:哥本哈根市心脏研究

Cross-sectional and limited prospective evidence has suggested that inflammatory markers may predict for the risk of atrial fibrillation(AF). In a prospective cohort study, we studied the risk of incident AF among 8,870 women and men free of cardiovascular disease enrolled in the Copenhagen City Heart Study. We measured plasma fibrinogen and serum albumin levels at a study visit from 1991 to 1994. We identified 286 subsequent cases of AF during a mean of 7.5 years of follow-up by a validated nationwide registry of all hospitalizations. The fibrinogen levels at baseline were associated with a higher risk of AF, with a multivariate-adjusted hazard ratio for the highest versus lowest quartiles of 1.98(95%confidence interval[CI] 0.94 to 4.17) among men and 2.14(95%CI 1.15 to 3.96) among women. The albumin levels were inversely associated with the risk of AF among women(hazard ratio 0.47, 95%CI 0.28 to 0.77) but not among men(hazard ratio 1.01, 95%CI 0.56 to 1.84). Additional adjustment for cases of coronary heart disease, congestive heart failure, and stroke that occurred during follow-up did not attenuate these associations. In conclusion, higher levels of fibrinogen and lower levels of albumin were prospectively associated with a higher risk of AF, even accounting for their relation with the risk of cardiovascular disease. These findings support the hypothesis that inflammation contributes to the etiology of AF.

丙型肝炎患者因乙醇相关问题入院的指标结果

Background/Aims: Alcohol is known to act synergistically with chronic hepatitis C virus (HCV) infection to cause liver disease; however, their combined effect on outcomes in acutely hospitalized patients is less clear. We examined the impact of HCV infection on hospital mortality and length of stay among hospitalized patients with alcohol abuse problems. Methods: We retrospectively identified 6354 admissions to an urban, public hospital between July 1996 and January 2002 with discharge diagnoses related to alcohol dependence or abuse. Hepatitis C diagnosis and other information were extracted from a clinical database and tested for associations with death and length of hospital stay using multivariable regression techniques. Results: The prevalence of diagnosed HCV infection in this sample of patients with alcohol abuse was 15% . Patients with HCV were about twice as likely to die during hospital admission (4.4 vs. 2.4% ; P-value< 0.01), and there appeared to be a trend toward increased mortality even after adjustment for demographics, medical service, homelessness and comorbidities (fully adjusted OR 1.41; 95% CI: 0.97-2.04). Length of stay was significantly longer for patients with HCV (19% longer; 95% CI: 12-27% after adjustment) than those without. Conclusions: Patients admitted to the hospital with alcohol-related diagnoses have longer hospital stays and are more likely to die in hospital if they have a diagnosis of HCV.

与孕妇体重增加过多或不足相关的孕前、妊娠期纤维因素分析

Objective: Gestational weight gain consistent with the Institute of Medicine’s recommendations is associated with better maternal and infant outcomes. The objective was to quantify the effect of pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors on the risks of inadequate and excessive gestational weight gain. Method: A longitudinal cohort of pregnant women (N = 1100) who completed questions about diet and weight gain during pregnancy and delivered a singleton, full-term infant. Results: Gestational weight gain was inadequate for 14%and excessive for 53%. Pre-pregnancy factors contributed 74%to excessive gain, substantially more than pregnancy-related health conditions (15%) and modifiable pregnancy factors (11%). Pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors contributed fairly equally to the risk of inadequate gain. Conclusion: Interventions to prevent excessive gestational gain may need to start before pregnancy. Women at risk for inadequate gain would also benefit from interventions directed toward modifiable factors during pregnancy.

丙型肝炎病毒经抗体阴性供体向器官和组织受体传播

Background: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor. Objective: To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients. Design: Descriptive epidemiologic study; serum testing for HCV infection. Setting: Recipients were located in 16 states and 2 other countries. Participants: Donor and graft recipients. Measurements: Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis. Results: The donor was anti-HCV-negative but was HCV RNA-positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16). Limitations: Post-transplantation serum specimens were unavailable for 5 recipients. Conclusions: An anti-HCV-negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV-negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.

冠状动脉搭桥术患者的饮酒、动脉粥样硬化进展和预后

Background: Although moderate drinking has been associated with lower mortality among patients after myocardial infarction, its relationship with prognosis and graft obstruction among patients with coronary artery bypass grafts is unknown. Methods: We studied 1351 patients enrolled in the Post- CABG trial, who had undergone coronary bypass surgery 1 to 11 years before entry. Participants were randomly assigned to lovastatin in low or high doses and to low- dose warfarin or placebo in a factorial design. Participants underwent coronary angiography at baseline and after a mean follow- up of 4.3 years and were followed up for a composite end point of death, myocardial infarction, stroke, bypass surgery, or angioplasty. We categorized reported weekly alcohol intake as abstention(< 1 drink), light(1- 6 drinks), moderate(7- 13 drinks), and heavier(≥ 14 drinks). Results: During follow- up, 238 participants sustained a clinical event. Moderate drinking was associated with a trend toward both fewer clinical events(hazard ratio 0.7, 95% CI 0.4- 1.1) and less angiographic progression(odds ratio 0.7, 95% CI 0.5- 1.1), although neither of these effects were statistically significant. High- density lipoprotein cholesterol appeared to account for one third of the trend toward lower risk among moderate drinkers. Conclusion: We did not demonstrate statistically significant differences in prognosis according to alcohol intake in this study, although there were inverse trends between moderate drinking and both morbidity and graft progression of a magnitude similar to studies in other populations. Larger studies of alcohol intake among patients with coronary artery bypass grafts are needed.

Pneumoscrotum in a Patient with Pneumocystis jirovecii Pneumonia: A Case Report

Pneumoscrotum is a rare condition described as the accumulation of air within the scrotum. We report the case of a patient with acquired immune deficiency syndrome (AIDS) with Pneumocystis jirovecii pneumonia who developed a secondary pneumoscrotum as a complication of volutrauma from mechanical ventilation.

Trends in characteristics of neurologists who provide stroke consultations in the USA,2008-2021

Introduction Patients with acute ischaemic strokes(AIS),on average,fare better with timely neurologist consultation,and a growing proportion of them receive one.However,little is known about trends in the characteristics of neurologists who treat AIS.Methods We identified AIS and transient ischaemic attack(TIA)episodes with neurologist consults in fee-for service Medicare from January 2008 to September 2021.For each episode,we determined whether the neurologist was a vascular neurologist,was a high-volume provider,whether the patient was transferred between hospitals and the distance between the patient’s home and physician’s practice.Results From 2008 to 2021,the share of AIS/TIA episodes(n=5073294)with neurologist consults increased(52.9%to 61.7%).Among episodes with consults,the fraction conducted by a vascular neurologist(5.2%to 13.7%)or by a high-volume neurologist(13.2%to 14.9%)also increased.The fraction with the patient’s home and neurologist greater than 100 miles apart(4.8%to 9.6%)or in different states(5.1%to 8.1%)increased,as did the fraction with transfers(4.2%to 8.5%).Discussion Over the study period,the proportion of AIS/TIA episodes with consultations from neurologists with either vascular neurology certifications or high volumes increased substantially.

Puncturing the myths of acupuncture

Acupuncture is a widely practiced system of medicine that has been in place for thousands of years. Consumer interest and use of acupuncture are becoming increasingly popular in the United States, as it is used to treat a multitude of symptoms and disease processes as well as to maintain health and prevent illness. A growing body of evidence increasingly validates the practice of acupuncture. Further developing scientific data will play an important role in the future of acupuncture and other complementary and alternative medicines in public health. Acupuncture is commonly used concurrently with conventional medicine. Although acupuncture is embraced by consumers and medical professionals misconceptions abound. We have explored and dispelled ten misconceptions common to the practice of acupuncture, utilizing an evidence-based approach. As the trend of merging conventional medical care with acupuncture treatment grows, it is important to develop a conceptual model of integrative medicine. Using a scientific evidence approach will create a structure from which to begin and grow confidence among conventional medical providers. Acupuncture is a safe and effective modality when performed properly by trained professionals. Educating both the consumer and medical community is important to enable appropriate and evidence-based applications of acupuncture and integration with conventional medicine for high-quality patient care.

食物是良药:将食物和营养融入医疗保健服务的行动

Sarah Downer及其同事探讨在医疗保健服务体系中将食品和营养纳入膳食相关疾病的预防、管理和治疗的新举措。与膳食相关的慢性病的全球流行,促使人们尝试将改善饮食作为患者医疗和护理的正规举措。

Multi-disciplinary clinic models for the management of non-alcoholic fatty liver disease

In recent years,there has been an increasing interest in the implementation of multi-disciplinary clinic(MDC)models in the medical field,in an effort to improve coordination of care due to the increasing complexity of medical practice.It is therefore unsurprising that there is such interest in non-alcoholic fatty liver disease(NAFLD),which is now the most prevalent liver disease worldwide.

术后谵妄：具有远期作用的急性改变

谵妄是一种认知力和注意力的急性改变，包括意识改变和思维涣散。尽管谵妄可以出现于任何年龄组的患者，但是最常见于老年患者，尤其是那些已存在认知功能障碍的老年患者。术后谵妄的患者较无谵妄的患者恢复慢，因此增加了住院时间和医疗费用。术后谵妄的发生率与手术类型、手术紧迫性和谵妄评估方法的类型及敏感性有关。尽管谵妄通常被认为是一种短期病变，其实它可以持续数月并且与术后中期认知功能不良有关。本文中，我们给出了指南对谵妄这一常见的病理状态风险进行术前评估及预防、诊断和治疗。提高诊疗水平，例如术前明确谵妄发生的风险；训练外科医生、麻醉医生和护士诊断谵妄的能力；实行谵妄预防计划以及制定谵妄治疗的标准流程可能有助于减少谵妄及其相关发病率。