Vaccine development against tuberculosis before and after Covid-19.

Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by Mycobacterium tuberculosis (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities.

The cruciform drain: a technical note on the surgical management of cystic lesions of the sella.

BACKGROUND: The postoperative recurrence of cystic lesions of the sella is frequent and may require further surgery for re-drainage. OBJECTIVE: To tackle this problem, we propose to insert a small cross-shaped drain coursing from the cyst lumen to the suprasellar cistern. At this early stage of innovation, the technique is primarily intended for patients who present with a recurrence. METHODS: The cruciform drain is fashioned from the tip of a ventricular catheter and is inserted under endoscopic vision. We retrospectively reviewed the pre- and postoperative records of patients in whom this technique was implemented. RESULTS: A cruciform drain was placed in five patients since the introduction of the technique into our practice in 2018. The use of the cruciform drain did not impact upon the expected surgical workflow nor was it associated with adverse intraoperative events, but three patients did develop a postoperative CSF leak that was successfully treated in all cases. None of the patients showed re-collection of their cysts on early radiological follow-up. CONCLUSION: The cruciform drain is intended to prevent the renewed build-up of cystic fluid by allowing it to flow through and around the drain into the subarachnoid space. We have modified our repair protocol in response to the observed high CSF leak rate, as a basis for further development of the technique. Studies involving long-term follow-up will also be required to assess its efficacy in reducing cyst recurrence.

Therapeutic Vaccines for Tuberculosis: An Overview.

Tuberculosis (TB), caused by Mycobacterium tuberculosis is the world's deadliest bacterial infection, resulting in more than 1.4 million deaths annually. The emergence of drug-resistance to first-line antibiotic therapy poses a threat to successful treatment, and novel therapeutic options are required, particularly for drug-resistant tuberculosis. One modality emerging for TB treatment is therapeutic vaccination. As opposed to preventative vaccination - the aim of which is to prevent getting infected by M. tuberculosis or developing active tuberculosis, the purpose of therapeutic vaccination is as adjunctive treatment of TB or to prevent relapse following cure. Several candidate therapeutic vaccines, using killed whole-cell or live attenuated mycobacteria, mycobacterial fragments and viral vectored vaccines are in current clinical trials. Other modes of passive immunization, including monoclonal antibodies directed against M. tuberculosis antigens are in various pre-clinical stages of development. Here, we will discuss these various therapeutics and their proposed mechanisms of action. Although the full clinical utility of therapeutic vaccination for the treatment of tuberculosis is yet to be established, they hold potential as useful adjunct therapies.

Identification of the Immune Subtype of Hepatocellular Carcinoma for the Prediction of Disease-Free Survival Time and Prevention of Recurrence by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

Background: The main factors affecting the long-term prognosis of hepatocellular carcinoma (HCC) patients undergoing radical surgery are recurrence and metastasis. However, the methods for predicting disease-free survival (DFS) time and preventing postoperative recurrence of HCC are still very limited. Methods: In this study, immune cell abundances in HCC samples were analyzed by single-sample gene set enrichment analysis (ssGSEA), while the prognostic values of immune cells for DFS time prediction were evaluated by the least absolute shrinkage and selection operator (LASSO) and subsequent univariate and multivariate Cox analyses. Next, a risk score was constructed based on the most prognostic immune cells and their corresponding coefficients. Interactions among prognostic immune cells and the specific targets for the prevention of recurrence were further identified by single-cell RNA (scRNA) sequencing data and CellMiner. Results: A novel efficient T cell risk score (TCRS) was constructed based on data from the three most prognostic immune cell types (effector memory CD8 T cells, regulatory T cells and follicular helper T cells) for identifying an immune subtype of HCC patients with longer DFS times and inflammatory immune characteristics. Functional differences between the high- and low-score groups separated by TCRS were clarified, and the cell-cell communication among these immune cells was elucidated. Finally, fifteen hub genes that may be potential therapeutic targets for the prevention of recurrence were identified. Conclusions: We constructed and verified a useful model for the prediction of DFS time of HCC after surgery. In addition, fifteen hub genes were identified as candidates for the prevention of recurrence, and a preliminarily investigation of potential drugs targeting these hub genes was carried out.

Pathogenic bacteria spectrum of infectious stones and experience of preventing stone recurrence / 中华泌尿外科杂志

Objective:To investigate the pathogenic bacteria profiles in preoperative urine bacterial cultures of patients with infected kidney stones and use antibacterial drugs to prevent recurrence.Methods:The data of 79 cases with infected kidney stones admitted to the Second Affiliated Hospital of Zhengzhou University from January 2017 to July 2021 were retrospectively analyzed, among whom 29 (36.7%) were male and 50 (63.3%) were female. The age ranged from 17-75 years, with a median age of 49.0 (40, 55) years. Fifteen cases (19.0%) combined hypertension, 13 cases (16.5%) combined diabetes mellitus, and 3 cases (3.8%) combined with cardiovascular disease. Fifty-one cases (64.6%) were diagnosed with cast infectious stones. All patients underwent surgical lithotripsy, and postoperative review of the urological computerized tomography (CT) revealed no residual stones defined as complete lithotripsy, and postoperative oral medication was continued to control infection and prevent stone recurrence. According to post-hospitalization compliance, patients were divided into high and low compliance groups. The high compliance group consisted of patients who returned to the hospital regularly for routine urinalysis and urine bacterial culture after discharge, followed the doctor's prescription for standardized antibacterial drug therapy, and complied with urease inhibitor therapy for ≥6 months. The low compliance group included patients who did not take sensitive antimicrobial drugs regularly and/or were unable to adhere to the medication even after the reduction of vinblastine due to adverse events such as tremor, palpitations, headache, anemia, or gastrointestinal discomfort. The recurrence of stones at 3, 6 and 12 months of follow-up was compared between the two groups.Results:Of the 79 cases in this group, 56(70.9%) were completely clear of stone after surgery. Thirty-three cases (41.8%) presented positive in preoperative urine bacterial culture, and the most common causative organism was Aspergillus oddus in 17 cases (21.5%), followed by Escherichia coli in 8 cases (10.1%) and Klebsiella pneumoniae in 3 cases (3.8%). Among the 17 positive cases of A. oddis, six were positive for ultra broad spectrum β-lactamases (ESBLs), 6/6 were resistant to ampicillin, cefazolin, and cotrimoxazole, 1/6 were resistant to amikacin, cefoxitin, and ticarcillin/stick acid, and none were resistant to imipenem, polymyxin, or aminotrans (0/6 cases). Of the cases, 11 were negative for ESBLs. Ten out of eleven cases were resistant to ampicillin. Furthermore, 8/11 cases were resistant to cefazolin, levofloxacin, ciprofloxacin, and cotrimoxazole and 1/11 were resistant to cefoxitin, cefaclor, furantoin, amikacin, and minocycline, and 0/11 were resistant to imipenem, ticarcillin/stick acid, aminotrans. ESBLs positive strains were resistant to 78.6% of the tested drugs (cefaclor, cefazolin, ceftazidime, furantoin, norfloxacin, levofloxacin, ciprofloxacin, cefoxitin, amoxicillin/rod acid, ticarcillin/rod acid, ampicillin, ceftriaxone, cefotaxime, cefuroxime, cefepime, gentamicin, cotrimoxazole, tobramycin, amikacin, tetracycline, chloramphenicol, and minocycline) at a lower rate of resistance than ESBLs positive strains. Of the eight positive cases of E. coli, seven were ESBLs positive, 7/7 were resistant to ampicillin, cefazolin, cefotaxime, cefuroxime, and cefepime, 1/7 were resistant to cefoxitin and minocycline, and 0/7 were resistant to imipenem, furantoin, or amikacin. One case was ESBLs negative and was resistant to all antimicrobial drugs except for ampicillin. Stone recurrence rates at 3, 6, and 12 months after discharge were 9.1%(4/44) and 31.4%(11/35), 13.6%(6/44), respectively, in the high compliance group, and 60.0%(21/35), 36.4%(16/44), and 71.4% (25/35), respectively, in the low compliance group. All differences were statistically significant.Conclusion:The most common pathogenic bacteria isolated from urine bacterial cultures of patients with infectious stones were A. chimaera, E. coli, and K. pneumoniae. The resistance rate of ESBLs-positive strains to antimicrobial drugs was significantly higher than that of ESBL-negative strains, and the resistance rate of antimicrobial drugs such as β-lactamase inhibitors, cefoxitin, amikacin, and imipenem was low. Combination therapy with standardized sensitive antimicrobial drugs and urease inhibitors significantly reduced the recurrence rate of stones among patients.

Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects.

More evidence is available for maternal intake, absorption, distribution, tissue specific concentrations, and pregnancy outcomes with folic acid (fortification/supplementation) during preconception - first trimester. This Quality Improvement prevention review used expert guidelines/opinions, systematic reviews, randomized control trials/controlled clinical trials, and observational case control/case series studies, published in English, from 1990 to August 2021. Optimization for an oral maternal folic acid supplementation is difficult because it relies on folic acid dose, type of folate supplement, bio-availability of the folate from foods, timing of supplementation initiation, maternal metabolism/genetic factors, and many other factors. There is continued use of high dose pre-food fortification 'RCT evidenced-based' folic acid supplementation for NTD recurrence pregnancy prevention. Innovation requires preconception and pregnancy use of 'carbon one nutrient' supplements (folic acid, vitamin B12, B6, choline), using the appropriate evidence, need to be considered. The consideration and adoption of directed personalized approaches for maternal complex risk could use serum folate testing for supplementation dosing choice. Routine daily folic acid dosing for low-risk women should consider a multivitamin with 0.4 mg of folic acid starting 3 months prior to conception until completion of breastfeeding. Routine folic acid dosing or preconception measurement of maternal serum folate (after 4-6 weeks of folate supplementation) could be considered for maternal complex risk group with genetic/medical/surgical co-morbidities. These new approaches for folic acid oral supplementation are required to optimize benefit (decreasing folate sensitive congenital anomalies; childhood morbidity) and minimizing potential maternal and childhood risk.

Nursing care for a patient with right frontoparietal inflammatory granuloma complicated with acute pulmonary embolism: a case report.

Intracranial inflammatory granuloma is a common intracranial occupying lesion. Common postoperative complications include intracranial edema, intracranial infection, hydrocephalus, epilepsy, and cerebrospinal fluid leakage. This report aims to summarize the nursing care of a patient with right frontoparietal inflammatory granuloma complicated with acute pulmonary embolism (APE). Acute pulmonary embolism is a clinical syndrome in which endogenous or exogenous emboli block the main trunk or branches of the pulmonary artery, resulting in disorders of pulmonary and respiratory circulation that seriously threatening the lives of patients. The occurrence and report of pulmonary embolism caused by intracranial inflammatory granuloma are rare. The patient had rapid onset, atypical clinical manifestations, and was in critical condition. Pulmonary embolism can easily lead to death. Nursing care after rapid thrombolysis included observation of coagulation function, prevention of complication, control of infection, improvement of intestinal dysfunction, maintenance and monitoring of sedation, prevention and observation of epilepsy, and prevention of the recurrence of embolism. After early intervention, active treatment and meticulous care, the patient's condition improved, mechanical ventilation was successfully withdrawn, and the patient was ultimately discharged and walked out on his own.

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

In Situ Nanoadjuvant-Assembled Tumor Vaccine for Preventing Long-Term Recurrence.

Although immune checkpoint inhibitors have emerged as a breakthrough in cancer therapy, a monotherapy approach is not sufficient. Here, we report an immune checkpoint inhibitor-modified nanoparticle for an in situ-assembled tumor vaccine that can activate immune systems in the tumor microenvironment and prevent the long-term recurrence of tumors. Adjuvant-loaded nanoparticles were prepared by entrapping imiquimod (IQ) in photoresponsive polydopamine nanoparticles (IQ/PNs). The surfaces of IQ/PNs were then modified with anti-PDL1 antibody (PDL1Ab-IQ/PNs) for in situ assembly with inactivated tumor cells and immune checkpoint blocking of PDL1 (programmed cell death 1 ligand 1). The presence of anti-PDL1 antibodies on IQ/PNs increased the binding of nanoparticles to CT26 cancer cells overexpressing PDL1. Subsequent near-infrared (NIR) irradiation induced a greater photothermal anticancer effect against cells treated with PDL1Ab-IQ/PNs than cells treated with plain PNs or unmodified IQ/PNs. To mimic the tumor microenvironment, we cocultured bone marrow-derived dendritic cells with CT26 cells treated with various nanoparticle formulations and NIR irradiated. This coculture study revealed that NIR-inactivated, PDL1Ab-IQ/PN-bound CT26 cells induced maturation of dendritic cells to the greatest extent. Following a single intravenous administration of different nanoparticle formulations in CT26 tumor-bearing mice, PDL1Ab-IQ/PNs showed greater tumor tissue accumulation than unmodified nanoparticles. Subsequent NIR irradiation of mice treated with PDL1Ab-IQ/PNs resulted in tumor ablation. In addition to primary tumor ablation, PDL1Ab-IQ/PNs completely prevented the growth of a secondarily challenged CT26 tumor at a distant site, producing 100% survival for up to 150 days. A long-term protection study revealed that treatment with PDL1Ab-IQ/PNs followed by NIR irradiation inhibited the growth of distant, secondarily challenged CT26 tumors 150 days after the first tumor inoculation. Moreover, increased infiltration of T cells was observed in tumor tissues treated with PDL1Ab-IQ/PNs and NIR-irradiated, and T cells isolated from splenocytes of mice in which tumor recurrence was prevented showed active killing of CT26 cells. These results suggest that PDL1Ab-IQ/PNs in conjunction with NIR irradiation induce a potent, in situ-assembled, all-in-one tumor vaccine with adjuvant-containing nanoparticle-bound, inactivated tumor cells. Such in situ nanoadjuvant-assembled tumor vaccines can be further developed for long-term prevention of tumor recurrence without the need for chemotherapy.

Designing tuberculosis vaccine efficacy trials - lessons from recent studies.

INTRODUCTION: Tuberculosis (TB) is the leading infectious killer globally and new TB vaccines will be crucial to ending the epidemic. Since the introduction in 1921 of the only currently licensed TB vaccine, BCG, very few novel vaccine candidates or strategies have advanced into clinical efficacy trials. Areas covered: Recently, however, two TB vaccine efficacy trials with novel designs have reported positive results and are now driving new momentum in the field. They are the first Prevention of Infection trial, evaluating the H4:IC31 candidate or BCG revaccination in high-risk adolescents and a Prevention of Disease trial evaluating the M72/AS01E candidate in M.tuberculosis-infected, healthy adults. These trials are briefly reviewed, and lessons learned are proposed to help inform the design of future efficacy trials. The references cited were chosen by the author based on PubMed searches to provide context for the opinions expressed in this Perspective article. Expert opinion: The opportunities created by these two trials for gaining critically important knowledge are game-changing for TB vaccine development. Their results clearly establish feasibility in the relatively near term of developing novel, effective vaccines that could be crucial to ending the TB epidemic.

Treatment and Prevention of Recurrent Clostridium difficile Infection with Functionalized Bovine Antibody-Enriched Whey in a Hamster Primary Infection Model.

Toxin-induced Clostridium difficile infection (CDI) is a major disease characterized by severe diarrhea and high morbidity rates. The aim with this study was to develop an alternative drug for the treatment of CDI. Cows were repeatedly immunized to establish specific immunoglobulin G and A titers against toxins A (TcdA) and B (TcdB) and against C. difficile cells in mature milk or colostrum. The effect of three different concentrations of anti-C. difficile whey protein isolates (anti-CD-WPI) and the standard of care antibiotic vancomycin were investigated in an animal model of CD infected hamsters (6 groups, with 10 hamsters each). WPI obtained from the milk of exactly the same cows pre-immunization and a vehicle group served as negative controls. The survival of hamsters receiving anti-CD-WPI was 50, 80 and 100% compared to 10 and 0% for the control groups, respectively. Vancomycin suppressed the growth of C. difficile and thus protected the hamsters at the time of administration, but 90% of these hamsters nevertheless died shortly after discontinuation of treatment. In contrast, the surviving hamsters of the anti-CD-WPI groups survived the entire study period, although they were treated for only 75 h. The specific antibodies not only inactivated the toxins for initial suppression of CDI, but also provoked the inhibition of C. difficile growth after discontinuation, thus preventing recurrence. Oral administration of anti-CD-WPI is a functional therapy of CDI in infected hamsters for both primary treatment and prevention of recurrence. Thus, anti-CD-WPI could address the urgent unmet medical need for treating and preventing recurrent CDI in humans.

Clinical Results of Subtotal Fasciectomy for Treatment of Dupuytren Contracture / 대한정형외과학회잡지

PURPOSE: In the treatment of Dupuytren's contracture, the aim of optical treatment is to lower the recurrence rate and reduce complications. This paper reports the results of subtotal fasciectomy in Dupuytren's contracture, extending the excision of palmar fascial structures from the diseased to normal appearing adjacent fascial structure. MATERIALS AND METHODS: From 2007 to 2017, 45 patients with Dupuytren's contracture treated by subtotal fasciectomy were reviewed retrospectively. The mean follow-up period was 45.9 months. Ninety-two digits were involved (index: 2, middle: 10, ring: 44, little: 36). The predisposing factors and affected joint were reviewed and the preoperative and postoperative contracture was measured. For clinical results, quick disabilities of the arm, shoulder, and hand (quick DASH) were used. Complications, including wound or skin problems, nerve injuries, hematoma, and complex regional pain syndrome, were assessed. RESULTS: Preoperative flexion contracture was 43.2° in the proximal interphalangeal joint and 32.9° in the metacarpophalangeal joint. In nine cases, patients had residual contracture of 9.7° (range, 5°–20°) on average and if the total number of cases were included, the mean residual contracture was 2.3° on average. The quick DASH score at the 12 months follow-up was 12.4. The overall complication rate was 26.6%. CONCLUSION: Subtotal fasciectomy can be a good surgical treatment option for Dupuytren's contracture with a low recurrence and low complication rate compared to other open procedures.

MEDIACONNEX: a multicenter randomised trial based on short message service to reduce suicide attempt recurrence in adolescents.

BACKGROUND: Suicide attempt among adolescents is a public health problem around the world. The risk of recurrence is high: about 30 % of adolescents. New ways to prevent suicide attempt recurrence being developed for adult suicide attempters include maintaining contact with them, and results are encouraging. METHODS/DESIGN: The MEDIACONNEX study will be a simple blinded, parallel-group, multicenter randomised controlled trial. It will compare usual care alone to a program based on usual care plus short message service (SMS) provided to adolescents who attempt suicide and who receive treatment in pediatric and adolescent psychiatry units at hospitals in eastern France. Adolescents will be recruited over an 18-month period. The intervention will be based on the SMS, involving personalized and evolving text messages, sent on days 7 to 14 and months 1, 2, 4 and 6 after the SA. The primary endpoint will be the recurrence of an SA, with an assessment during 12 months. Secondary endpoints will be the evolution of 1) social networks, 2) depression and 3) health-related quality of life, with an assessment at inclusion and at 6 months. DISCUSSION: This paper describes the design of MEDIACONNEX, which will assess the effectiveness of an SMS program for adolescent suicide attempters on SA recurrence. This program will be easy to reproduce and inexpensive. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (no. NCT02762734 ) on March 2016.

Metabolic risk-evaluation and prevention of recurrence in stone disease: does it make sense?

In this review, aspects on the importance of information on urine composition and selection of the most appropriate regimen for prevention of recurrence are discussed. For patients with urolithiasis the treatment is facilitated by urine analysis with estimates of supersaturation levels. Despite lack of strong scientific evidence for the benefit of selective versus non-selective prevention of recurrence in patients with calcium stone disease, there is currently both convincing and logical information in support of tailored/selective treatment regimens aiming at correction of abnormal target variables. Such an approach is also recommended in the EAU and AUA guidelines. It is important, however, that every preventive regimen is balanced between the effects on urine composition and patients' tolerance to the treatment in order to achieve satisfactory compliance. It is possible that future improved understanding of the causes of calcium stone formation might provide a different therapeutic approach.

Innovative clinical trial designs to rationalize TB vaccine development.

A recent trial of a leading tuberculosis (TB) vaccine candidate in 3000 South African infants failed to show protection over that from BCG alone, and highlights the difficulties in clinical development of TB vaccines. Progression of vaccine candidates to efficacy trials against TB disease rests on demonstration of safety and immunogenicity in target populations and protection against challenge in preclinical models, but immunologic correlates of protection are unknown, and animal models may not be predictive of results in humans. Even in populations most heavily affected by TB the sample sizes required for Phase 2b efficacy trials using TB disease as an endpoint are in the thousands. Novel clinical trial models have been developed to evaluate candidate TB vaccines in selected populations using biologically relevant outcomes and innovative statistical approaches. Such proof of concept studies can be used to more rationally select vaccine candidates for advancement to large scale trials against TB disease.

Baseline feature of a randomized trial assessing the effects of disease management programs for the prevention of recurrent ischemic stroke.

BACKGROUND: Comprehensive and long-term patient education programs designed to improve self-management can help patients better manage their medical condition. Using disease management programs (DMPs) that were created for each of the risk factor according to clinical practice guidelines, we evaluate their influence on the prevention of stroke recurrence. METHODS: This is a randomized study conducted with ischemic stroke patients within 1 year from their onset. Subjects in the intervention group received a 6-month DMPs that included self-management education provided by a nurse along with support in collaboration with the primary care physician. Those in the usual care group received ordinary outpatient care. The primary end point is a difference of the Framingham risk score-general cardiovascular disease 10-year risk [corrected]. Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6-month education period (total of 30 months). RESULTS: A total of 321 eligible subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects (6.5%) with transient ischemic attack, were enrolled in this study. Regarding risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney disease. There were no significant differences between the 2 groups with respect to subject characteristics. CONCLUSIONS: This article describes the rationale, design, and baseline features of a randomized controlled trial that aimed to assess the effects of DMPs for the secondary prevention of stroke. Subject follow-up is in progress and will end in 2015.

Management of multijoint stiffness of bilateral upper limbs secondary to heterotopic ossification: case report and literature review.

The management of heterotopic ossification (HO) is controversial. Although some reports have investigated assessment and surgical resection techniques for HO affecting one or more joints, the cases of multijoint stiffness secondary to HO are rare. This article describes a rare case of HO affecting both upper limbs of a 32-year-old man that severely interfered with activities of daily living. We present the rehabilitation management of this case and the functional outcome 1 to 2 yr after excision of the ossific masses.

Cancer and acupuncture & Moxibustion 3 / 全日本鍼灸学会雑誌

This is the third symposium on 'cancer and acupuncture and moxibustion'. Many physicians and intellectuals are skeptical of the use of Western medicine for cancer patients, which often lead to serious adverse events. Acupuncture and moxibustion, which is capable of improving quality of life (QOL) and activating immunity with minimal side effects is also expected to have beneficial effects on various stages of cancer patients, such as prevention of development or recurrence of cancer and palliative care. In fact, evidence has recently accumulated in the field. Dr. Fukuda, Associate Professor of Meiji University of Integrative Medicine, who reported the usefulness of acupuncture and moxibustion in palliative care in the first symposium and bibliographical information in the second has reported this time on the topic of safety and effectiveness of acupuncture on chemotherapy-induced peripheral neuropathy. Dr. Kurokawa from the National Defense Medical College reported the effectiveness of acupuncture on physical and psychological symptoms, QOL, prevention of adverse events, and pre-and post-operative disorders in cancer patients. Dr. Kouchi from Saitama Medical School reported on the usefulness of acupuncture in the university hospital and factors which influence the effect. Dr. Nakamura from Morinomiya University presented a case with chemotherapy-related symptoms who had been cared for with a long-term application of moxibustion. In contrast to these reports on the efficacy of the acupuncture for chemotherapy-and radiotherapy-induced side effects, Dr. Magara from Somon Hachipuji Clinic, who had consistently reported a preventive effect of autonomic immune therapy that involves acupuncture without Western clinical treatment from the first symposium, this time presented topics regarding improvement in the immunity by increasing various cytokines, the possibility of reduction of a tumor even in a case of advanced cancer that cannot be treated with a surgical approach, reduction of the recurrence rate among cases who were treated with his approach as compared with those under conventional approaches. He insisted we should concentrate our efforts on research on preventing the recurrence of cancer with approaches that activates the natural healing process of human beings.<BR>We concluded that clinical trials with a larger sample are needed to clearly identify the usefulness of acupuncture and moxibustion for cancer patients.

The treatment of deep vein thrombosis in the pelvis and leg.

INTRODUCTION: Deep vein thrombosis is associated with a risk of pulmonary embolism and post thrombotic syndrome (PTS). METHODS: Selective literature review with special reference to the American College of Chest Physicians' current guidelines and the German S2 interdisciplinary guideline. RESULTS AND DISCUSSION: The most important therapeutic measure is prompt and adequate anticoagulation with heparin or fondaparinux. Thrombolysis or thrombectomy is only indicated in highly selected severe cases. The risk of PTS can be reduced by immediate ongoing treatment with compression stockings. Prevention of relapse is achieved using vitamin K antagonists with a target INR of 2.0 to 3.0. The duration of anticoagulation should be tailored to the localisation and etiology of the thrombosis, from at least three months to indefinite treatment. The ongoing risk of bleeding secondary to anticoagulation should be reevaluated at regular intervals as a cost-benefit analysis. New anticoagulants for acute and long term treatment will soon be available for clinical use.